cardiovascular-agents and Diabetes-Mellitus--Type-2

In the current paper, we review recently published studies that are helping us to understand how the treatment landscape for glucagon-like peptiide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors is moving forward. We have also included relevant articles related to cardiovascular disease prevention in the setting of obesity, atherogenic dyslipidaemia and chronic kidney disease.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors

Prevention of cardiovascular events and regression of atherosclerotic changes are the primary aims of preventive cardiovascular medicine. Arterial thrombosis is caused by endothelial dysfunction, which disrupts vascular haemostasis. Glucagon-like peptide 1 (GLP-1) receptor agonists have been initially used as glucose lowering agents, but over time have been used for other indications due to their cardiorenal benefit, as well as their benefit in the regression of atherosclerosis process. The aim of this paper is to present the benefits of GLP-1 receptor agonists in the prevention of atherosclerotic changes, in the preservation of brain vascular function, and to show the possible role in the treatment of neurodegenerative diseases.

Topics: Atherosclerosis; Brain; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans

Heart failure (HF) and diabetes mellitus (DM) confer considerable burden on the health care system. Although these often occur together, DM can increase risk of HF, whereas HF can accelerate complications of DM. HF is a clinical syndrome resulting from systolic or diastolic impairment caused by ischemic, nonischemic (eg, DM), or other etiologies. HF exists along a spectrum from stage A (ie, persons at risk of DM) to stage D (ie, refractory HF from end-stage DM cardiomyopathy [DMCM]). HF is further categorized by reduced, midrange, and preserved ejection fraction (EF). In type 2 DM, the most prevalent form of DM, several pathophysiological mechanisms (eg, insulin resistance and hyperglycemia) can contribute to myocardial damage, leading to DMCM. Management of HF and DM and patient outcomes are guided by EF and drug efficacy. In this review, we focus on the interplay between HF and DM on disease pathophysiology, management, and patient outcomes. Specifically, we highlight the role of novel antihyperglycemic (eg, sodium glucose cotransporter 2 inhibitors) and HF therapies (eg, renin-angiotensin-aldosterone system inhibitors) on HF outcomes in patients with DM and HF.

Topics: Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Health Behavior; Heart Failure; Humans; Hypoglycemic Agents; Insulin Resistance; Life Style; Phenotype; Risk Factors; Ventricular Remodeling

Cardiovascular and renal complications are a major burden for individuals with type 2 diabetes mellitus (T2DM). Besides lifestyle interventions, current guidelines recommend combination drug therapy to prevent or delay the incidence and progression of comorbidities. However, non-adherence to pharmacotherapy is common in chronic conditions such as T2DM and a barrier to successful disease management. Numerous studies have associated medication non-adherence with worse outcome as well as higher health care costs. This narrative review provides (i) an overview on adherence measures used within and outside research settings, (ii) an estimate on the prevalence of non-adherence to antidiabetic and cardiovascular drugs in T2DM, and (iii) specifically focuses on the association of non-adherence to these drugs with renal and cardiovascular outcomes.

Topics: Cardiovascular Agents; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Health Care Costs; Humans; Hypoglycemic Agents; Medication Adherence

Cardiovascular disease (CVD), the main macro vascular complication of type 2 diabetes (T2D), increases the risk of death significantly in patients with T2D.. Most of the patients with T2D do not have obvious CVD symptoms. Due to the paucity of data, CVD screening in asymptomatic patients with T2D remains highly controversial.. This has driven a panel of experts to establish a novel consensus on how to approach patients with T2D at high CVD risk. The panel formulated a stepwise algorithm by which patients with T2D undergo initial risk stratification into low, intermediate and high risk using the ASCVD calculator. In patients with intermediate risk, coronary artery calcium measurement is used to further stratify those patients into new low and high-risk categories.. The panel recommends using standard diabetes care in low risk patients and using SGLT2 inhibitors and GLP1 agonists with cardio protective effect, on top of standard care, in high risk individuals.

Topics: Algorithms; Calcium; Cardiovascular Agents; Cardiovascular Diseases; Consensus; Coronary Vessels; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Mass Screening; Patient Selection; Protective Agents; Risk Assessment; Sodium-Glucose Transporter 2 Inhibitors; Tomography, X-Ray Computed

We thought to delve deeper into seven meta-analyses of major clinical trials focusing on Glucagon-Like Peptide-One Receptor Agonist (GLP-1 RA) cardioprotective effect.. We explored the role of GLP-1 RA in cardiovascular risk protection as the primary outcome in subjects with type 2 diabetes mellitus.. The current review has explored and critically appraised seven meta-analyses of placebo- controlled randomized clinical trials (RCT-s) involving GLP-1 RA used in diabetes that has exhibited major cardiovascular events as the primary outcome.. Based on the participants-intervention-comparison and outcomes (PICO), the total number of the participants in this review were (138750), the intervention was conducted with GLP-1 RA, the comparator was a placebo and the outcome was major cardiovascular events. The overall evidence for the cardioprotective effect of GLP-1 RA in diabetes was very clear in subjects with the cardiovascular risk of varying degrees. Most of the currently reviewed meta-analyses have not shown cardioprotection with GLP-1 RA in subjects with diabetes exhibiting high cardiovascular risk or medical history of cardiovascular diseases. Patient variability, in addition to potency parameters, will be the key to a successful member of the class. There will be avenues for selection of a candidate based on the suitability to patient preferences and characteristics.. The RCT-s for GLP-1 RA should characterize cardiovascular risk in subjects with diabetes such that disparities between established cardiovascular risk (high, moderate and low) or medical history of cardiovascular disease have been accounted for in subgroup analysis.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Protective Agents; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors

The incidence and prevalence of type 2 diabetes mellitus are increasing in the United States and worldwide. The individual-level risk of atherosclerotic cardiovascular disease events in primary prevention populations with type 2 diabetes mellitus is highly heterogeneous. Accurate risk stratification in this group is paramount to optimize the use of preventive therapies. Herein, we review the use of the coronary artery calcium score as a decision aid in individuals with type 2 diabetes mellitus without clinical atherosclerotic cardiovascular disease to guide the use of preventive pharmacotherapies, such as aspirin, lipid-lowering mediations, and cardiometabolic agents. The magnitude of expected risk reduction for each of these therapies must be weighed against its cost and potential adverse events. Coronary artery calcium has the potential to improve risk stratification in select individuals beyond clinical and laboratory risk factors, thus providing a more granular assessment of the expected net benefit with each therapy. In patients with diabetes mellitus and stable chest pain, coronary computed tomography angiography increases the sensitivity for coronary artery disease diagnoses compared with functional studies because of the detection of nonobstructive atherosclerosis. Most importantly, this anatomic approach may improve cardiovascular outcomes by increasing the use of evidence-based preventive therapies informed by plaque burden. We therefore provide an updated discussion of the pivotal role of coronary computed tomography angiography in the workup of stable chest pain in patients with diabetes mellitus in the context of recent landmark trials, such as PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), SCOT-HEART trial (Scottish Computed Tomography of the Heart), and ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches). Finally, we also outline the current role of coronary computed tomography angiography in acute chest pain presentations.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clinical Decision-Making; Computed Tomography Angiography; Coronary Angiography; Diabetes Mellitus, Type 2; Heart Disease Risk Factors; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Patient-Centered Care; Predictive Value of Tests; Primary Prevention; Prognosis; Risk Assessment

Type 2 diabetes mellitus and cardiovascular diseases (CVD) have become the main cause of morbidity and death worldwide. In addition, current anti-diabetic and cardiovascular therapy is based on conventional drugs that have limited effectiveness and adverse side effects. In this regard, the role of medicinal herbs as a complementary or an alternative medicine is of great interest. Urtica dioica L. (Urticaceae), which is the focus of this review, has been widely used in traditional medicine to treat a variety of ailments, including, diabetes, hypertension and prostate cancer. The aim of this article is to review current knowledge related to the anti-diabetic and cardiovascular properties of U. dioica, with particular emphasis on the bioactive compounds, the plant parts used, and the action mechanism behind lowering blood glucose level and reducing risk of CVD. We also discuss the chemical composition and toxicological properties of the plant. From this review, it was suggested that the anti-diabetic and the cardiovascular effects of U. dioica are attributed to different classes of compounds, such as polyphenols, triterpens, sterols, flavonoids, and lectin which reduce the blood glucose level and the risk of CVD by their antihypertensive, antioxidant and anti-inflammatory properties and/or by interfering with different cellular signalization pathways, including increase of NO, inhibition of α-amylase and α-glycosidase, modulation of GLUT4 and protection of pancreatic β-cells, among others. The identification of the plant constituents and the understanding of their exact action mechanisms are necessary to prove the efficacy of the plant and develop it as pharmacological drug.

Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Phytochemicals; Phytotherapy; Urtica dioica

Type 2 diabetes mellitus is a major risk factor for cardiovascular disease. However, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to sex. In recent years, large meta-analyses have confirmed that women with type 2 diabetes have a higher relative risk of incident coronary heart disease, fatal coronary heart disease, and stroke compared with their male counterparts. The reasons for these disparities are not completely elucidated. A greater burden of cardiometabolic risk in women was proposed as a partial explanation. Indeed, several studies suggest that women experience a larger deterioration in major cardiovascular risk factors and put on more weight than do men during their transition from normoglycemia to overt type 2 diabetes. This excess weight is associated with higher levels of biomarkers of endothelial dysfunction, inflammation, and procoagulant state. Moreover, sex differences in the prescription and use of some cardiovascular drugs may compound an "existing" disparity. We searched PubMed for articles published in English and French, by using the following terms: ("cardiovascular diseases") AND ("diabetes mellitus") AND ("sex disparity" OR "sex differences" OR "sex related differences" OR "sex-related differences" OR "sex disparities"). In this article, we review the available literature on the sex aspects of primary and secondary prevention of cardiovascular disease in people with type 2 diabetes, in the predisposition to cardiovascular disease in those people, and in the control of diabetes and associated cardiovascular risk factors.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Global Health; Healthy Lifestyle; Humans; Incidence; Primary Prevention; Risk Factors; Secondary Prevention; Sex Factors

This review will serve to highlight the clinical rationale used in the selection of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) or glucagon-like peptide 1 receptor agonists (GLP1-ra).. SGLT2-i and GLP1-ra are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit in multiple cardiovascular outcomes trials (CVOTs), with benefits that are consistent across class of medication. Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and glucagon-like peptide 1 receptor agonists (GLP1-ra) are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit. Given the unique side effect and benefit profiles, appropriate consideration of these agents with a focus on cardiovascular risk reduction requires an individualized approach.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Patient Selection; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

The antianginal drug ranolazine, because of its unique mechanism of action, has been shown to have antihyperglycemic effects. Here, we review the reports on the antihyperglycemic and metabolic effects of ranolazine. MEDLINE was searched from 2000 to October 1, 2016 using the terms ranolazine, antihyperglycemic, diabetes, cardiology, and antianginal. Studies and reviews were included if they were in English and provided relevant data to inform practicing clinicians. Ranolazine has been shown to be effective as an antihyperglycemic while utilized as monotherapy or in combination with traditional diabetic regimens. A total of 6 studies were included in this review, with 5 being randomized controlled trials and 1 being a retrospective study. Of the 6 studies, 4 directly measured differences between baseline hemoglobin A1c (HbA1c), another measured endothelium function, and lastly the retrospective study evaluated outpatient clinic visit utilization, all-cause emergency department visits, inpatient admissions, and length of stay in a cohort of patients with angina and diabetes. In conclusion, ranolazine, because of its unique mechanism of action, may have a niche in therapy for patients with chronic stable angina pectoris and diabetes mellitus. Ranolazine has been shown to have positive antihyperglycemic and metabolic effects in patients with uncontrolled HbA1c.

Topics: Adolescent; Cardiovascular Agents; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Ranolazine

The aim of this study is to examine the cardioprotective properties of Glucagon-like peptide-1 receptor agonist, a class of antihyperglycemic therapy, via meta-analysis of four recently published cardiovascular outcomes trials.. Meta-analysis was performed pooling data from the ELIXA, LEADER, SUSTAIN-6 and EXSCEL trials. A random effects model was used to generate risk ratio with 95% confidence interval for cardiovascular and safety outcomes.. A total of 33,457 patients were included in the meta-analysis. Based on the study, GLP-1R agonists significantly reduced all-cause mortality (RR 0.89; 95% CI 0.82 to 0.96) and cardiovascular mortality (RR 0.88; 95% CI 0.80 to 0.97) when compared to placebo. When long-acting agents were analyzed alone, reduction in major adverse cardiac events (RR 0.88; 95% CI 0.81 to 0.97) and non-fatal strokes (RR 0.87; 95% CI 0.76 to 0.99) also showed significance.. Overall, GLP-1R agonists appear to have cardioprotective properties likely via modification of metabolic parameters such as glycemic control, weight loss, and improvement in blood pressure. Additional studies are warranted to compare cardiovascular outcomes among the different agents.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Randomized Controlled Trials as Topic; Risk Factors; Signal Transduction; Treatment Outcome

Diabetes and heart failure (HF) are both global epidemics with tremendous costs on society with increased rates of HF hospitalizations and worsened prognosis when co-existing, making it a significant "deadly duo." The evidence for pharmacological treatment of HF in patients with type 2 diabetes mellitus (T2DM) stems typically from either subgroup analyses of patients that were recruited to randomized controlled trials of HF interventions, usually in patients with reduced ejection fraction (EF), or from subgroup analyses of HF patients recruited to cardiovascular (CV) outcome trials (CVOT) of glucose lowering agents involving patients with T2DM. Studies in patients with HF with preserved EF are sparse. This review summarizes the literature on pathophysiology and interventions aiming to reduce the HF burden in T2DM and includes HF trials of ACEi, digoxin, β-blocker, ARB, I

Topics: Cardiovascular Agents; Comorbidity; Diabetes Mellitus, Type 2; Global Health; Heart Failure; Humans; Hypoglycemic Agents; Prevalence; Prognosis; Risk Factors; Stroke Volume

Topics: Biomarkers; Blood Glucose; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Kidney; Protective Factors; Renal Agents; Risk Factors; Treatment Outcome

Excess visceral adipose tissue is associated with increased risk of high blood pressure, lipid disorders, type 2 diabetes, and cardiovascular disease. Adipose tissue is an endocrine organ with multiple humoral and metabolic roles in regulating whole-body physiology. However, perivascular adipose tissue (PVAT) also plays a functional role in regulating the contractile state of the underlying smooth muscle cell layer. Work during the past decade has shown that this adipose-vascular coupling is achieved by production of numerous substances released from PVAT. Animal disease models have been instrumental in identifying biological and pathophysiological functions of this regulation. These studies have produced strong evidence that alterations in the paracrine control of PVAT in the regulation of arterial tone contribute to vascular dysfunction in obesity, hypertension, and cardiometabolic disease. Perivascular relaxing factors, or perhaps their putative targets, might represent exciting new targets for the prevention and treatment of cardiovascular and metabolic diseases.

Topics: Adipokines; Adipose Tissue; Animals; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Hypertension; Hypoglycemic Agents; Muscle, Smooth, Vascular; Obesity

Vascular calcification (VC), a disorder that causes blood vessel hardening and dysfunction, is a significant risk factor for type-2 diabetes mellitus (T2DM), which invariably manifests associated cardiovascular complications. Although the clinical effects of VC have been well-documented, the precise cellular events underlying the manifestation and progression of VC are only now coming to light. Current research models indicate that VC likely involves signalling pathways traditionally associated with bone remodelling, such as the OPG/RANKL/TRAIL signalling system. In this respect, receptor activator of NF-κB ligand (RANKL) promotes VC whilst osteoprotegerin (OPG) acts as a RANKL decoy receptor to block this effect, events that contrast with the known functional influence of these proteins during bone metabolism. Moreover, evidence suggests that tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), an alternative decoy ligand for OPG, may exert an anti-calcific influence within the vasculature. In the current review, we conduct a timely examination of this complex VC pathology from both mechanistic and therapeutic perspectives. Our objectives are twofold: (i) to critically assess our current understanding of both osteogenic and vascular calcification pathways, with particular focus on the co-interactive roles of OPG, RANKL, and TRAIL. Extensive in vitro, in vivo, and clinical studies will therefore be reviewed and critical findings highlighted; and (ii) to examine a range of therapeutic approaches of potential relevance to VC pathology. In this regard, a clear focus on VC as it applies to T2DM and cardiovascular disease (and particularly atherosclerosis) will be maintained.

Topics: Animals; Arteries; Atherosclerosis; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Osteoblasts; Osteoclasts; Osteogenesis; Osteoprotegerin; Plaque, Atherosclerotic; RANK Ligand; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Vascular Calcification

Chemokines are critical components in pathology. The roles of chemokine CC motif ligand 4 (CCL4) and its receptor are associated with diabetes mellitus (DM) and atherosclerosis cardiovascular diseases. However, due to the complexity of these diseases, the specific effects of CCL4 remain unclear, although recent reports have suggested that multiple pathways are related to CCL4. In this review, we provide an overview of the role and potential mechanisms of CCL4 and one of its major receptors, fifth CC chemokine receptor (CCR5), in DM and cardiovascular diseases. CCL4-related mechanisms, including CCL4 and CCR5, might provide potential therapeutic targets in DM and/or atherosclerosis cardiovascular diseases.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Chemokine CCL4; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Ligands; Receptors, CCR5; Signal Transduction

Type 2 diabetes mellitus escalates the risk of heart failure partly via its ability to induce a cardiomyopathic state that is independent of coronary artery disease and hypertension. Although the pathogenesis of diabetic cardiomyopathy has yet to be fully elucidated, aberrations in cardiac substrate metabolism and energetics are thought to be key drivers. These aberrations include excessive fatty acid utilisation and storage, suppressed glucose oxidation and impaired mitochondrial oxidative phosphorylation. An appreciation of how these abnormalities arise and synergise to promote adverse cardiac remodelling is critical to their effective amelioration. This review focuses on disturbances in myocardial fuel (fatty acids and glucose) flux and energetics in type 2 diabetes, how these disturbances relate to the development of diabetic cardiomyopathy and the potential therapeutic agents that could be used to correct them.

Topics: Antioxidants; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Energy Metabolism; Fatty Acids; Glucose; Humans; Mitochondria, Heart; Myocardium; Organophosphorus Compounds; Oxidative Phosphorylation; Oxidative Stress; Perhexiline; Ranolazine; Trimetazidine; Ubiquinone

Type 2 diabetes (T2D) is a well-established risk factor for patients with coronary artery disease (CAD). Patients with CAD and comorbid T2D also have a higher risk of cardiovascular complications, such as silent ischemia and stable angina. In treating the symptoms of stable angina in patients with CAD and comorbid T2D, it is vital to utilize therapies that reduce symptoms and improve outcomes. At the same time, there is significant concern about the preservation of glycometabolic parameters, such as glycosylated hemoglobin (HbA1c), particularly because some antianginal therapies, such as β-blockers and calcium channel blockers-although effective at improving the symptoms of stable angina and reducing ischemia-may also worsen glycemic control by increasing HbA1c levels. Available trial data on the efficacy of antianginal agents in patients with stable angina and comorbid T2D are limited. Therefore, in patients with stable angina and T2D, a tailored approach to treatment of stable angina by selecting therapies with a neutral or positive glycometabolic profile may improve outcomes and increase treatment compliance. Additionally, patients with a dual diagnosis may benefit from therapies that have beneficial effects on both stable angina and T2D, thereby reducing polypharmacy. Prospective studies in patients with stable angina and T2D are needed to guide therapy decisions.

Topics: Angina, Stable; Biomarkers; Blood Glucose; Cardiovascular Agents; Comorbidity; Diabetes Mellitus, Type 2; Drug Interactions; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Polypharmacy; Risk Factors; Treatment Outcome

Dipeptidyl-peptidase-IV (DPP-IV) inhibitors are a new class of oral hypoglycaemic agents recently approved for the management of type 2 diabetes mellitus. Early data suggested that they had a positive impact on the cardiovascular system: treatment appeared to result in improvements in cardiac performance, blood pressure and lipid levels. However, recent clinical findings bring this into question. Our understanding of the physiological actions of these agents is complicated by the fact that DPP-IV has a wide range of substrates in addition to glucagon-like peptide 1. Indeed, DPP-IV inhibition alters concentrations of a wide variety of cytokines and neuropeptides. A deeper understanding of the physiological effects of these drugs as well as their true impact on cardiovascular risk is needed before consideration can be given to extending their use beyond the treatment of diabetes.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Signal Transduction; Treatment Outcome

Different intervention strategies can prevent type 2 diabetes (T2DM). Aim of the present systematic review and meta-analysis was to evaluate the effectiveness of different strategies.. Studies were grouped into 15 different strategies: 1: diet plus physical activity; 2: physical activity; 3-6: anti-diabetic drugs [glitazones, metformin, beta-cell stimulating drugs (sulphanylureas, glinides), alfa-glucosidase inhibitors]; 7-8: cardiovascular drugs (ACE inhibitors, ARB, calcium antagonists); 9-14 [diets, lipid-affecting drugs (orlistat, bezafibrate), vitamins, micronutrients, estrogens, alcohol, coffee]; 15: bariatric surgery. Only controlled studies were included in the analysis, whether randomized, non-randomized, observational studies, whether primarily designed to assess incident cases of diabetes, or performed with other purposes, such as control of hypertension, of ischemic heart disease or prevention of cardiovascular events. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement] was used. Seventy-one studies (490 813 subjects), published as full papers, were analysed to identify predictors of new cases of T2DM, and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95% confidence intervals (C.I.s). Publication bias was formally assessed.. Body mass index was in the overweight range for 13 groups, obese or morbidly obese in lipid-affecting drugs and in bariatric surgery. Non-surgical strategies, except for beta-cell stimulating drugs, estrogens and vitamins, were able to prevent T2DM, with different effectiveness, from 0.37 (C.I. 0.26-0.52) to 0.85 (C.I. 0.77-0.93); the most effective strategy was bariatric surgery in morbidly obese subjects [0.16 (C.I. 0.11,0.24)]. At meta-regression analysis, age of subjects and amount of weight lost were associated with effectiveness of intervention.. These data indicate that several strategies prevent T2DM, making it possible to make a choice for the individual subject.

Topics: Anti-Obesity Agents; Bariatric Surgery; Cardiovascular Agents; Combined Modality Therapy; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diet, Reducing; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Life Style; Motor Activity; Obesity; Obesity, Morbid; Overweight; Weight Loss

The prevalence of type 2 diabetes is increasing worldwide, and diabetes is a strong adverse prognostic factor among patients with cardiovascular (CV) disease. Four classes of drugs that are commonly used for CV risk reduction, statins, niacin, thiazide diuretics, and ß-blockers, have been shown to increase the risk of new-onset diabetes (NOD) by 9% to 43% in meta-analyses or large-scale clinical trials. Clinical predictors for drug-related NOD appear to be similar to the predictors that have been described for NOD unrelated to drugs: fasting blood glucose >100 mg/dL and features of the metabolic syndrome such as body mass index >30 kg/m(2), serum triglycerides >150 mg/dL, and elevated blood pressure, among others. The mechanisms whereby these drugs increase the risk of NOD are incompletely understood, although different hypotheses have been suggested. Lifestyle intervention consisting of diet and exercise has been shown in multiple studies to reduce the risk of NOD by approximately 50%, with persistent benefit during long-term follow-up. In patients at high risk for NOD, niacin should be avoided, and for hypertension, an angiotensin-converting enzyme inhibitor or even a ß1-selective blocker might be a better choice than a standard ß-blocker. For thiazide diuretics and particularly statins, benefit in terms of CV event reduction outweighs the risk of NOD.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Global Health; Humans; Prevalence; Risk Factors

Rural residents face numerous barriers to healthcare access and studies suggest poorer health outcomes for rural patients. Therefore we undertook a systematic review to determine if cardiovascular medication utilization and adherence patterns differ for rural versus urban patients.. A comprehensive search of major electronic datasets was undertaken for controlled clinical trials and observational studies comparing utilization or adherence to cardiovascular medications in rural versus urban adults with cardiovascular disease or diabetes. Two reviewers independently identified citations, extracted data, and evaluated quality using the STROBE checklist. Risk estimates were abstracted and pooled where appropriate using random effects models. Methods and reporting were in accordance with MOOSE guidelines.. Fifty-one studies were included of fair to good quality (median STROBE score 17.5). Although pooled unadjusted analyses suggested that patients in rural areas were less likely to receive evidence-based cardiovascular medications (23 studies, OR 0.88, 95% CI 0.79, 0.98), pooled data from 21 studies adjusted for potential confounders indicated no rural-urban differences (adjusted OR 1.02, 95% CI 0.91, 1.13). The high heterogeneity observed (I(2) = 97%) was partially explained by treatment setting (hospital, ambulatory care, or community-based sample), age, and disease. Adherence did not differ between urban versus rural patients (3 studies, OR 0.94, 95% CI 0.39, 2.27, I(2) = 91%).. We found no consistent differences in rates of cardiovascular medication utilization or adherence among adults with cardiovascular disease or diabetes living in rural versus urban settings. Higher quality evidence is needed to determine if differences truly exist between urban and rural patients in the use of, and adherence to, evidence-based medications.

Topics: Adult; Aged; Aged, 80 and over; Australia; Canada; Cardiovascular Agents; Cardiovascular Diseases; Databases, Factual; Diabetes Mellitus, Type 2; Europe; Female; Humans; Middle Aged; Patient Compliance; Risk Factors; Rural Population; United States; Urban Population

Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance and inflammation. Central obesity accompanied by insulin resistance is a key factor in the development of metabolic syndrome (MS) and future macrovascular complications. Moreover, the remarkable correlation between coronary artery disease (CAD) and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes mellitus (T2DM) may share a common biological background. We summarize here the current knowledge about the influence of adiponectin on insulin sensitivity and endothelial function, discussing its forthcoming prospects and potential role as a therapeutic target for MS, T2DM, and cardiovascular disease. Adiponectin is present in the circulation as a dimer, trimer or protein complex of high molecular weight hexamers, >400 kDa. AdipoR1 and AdipoR2 are its major receptors in vivo mediating the metabolic actions. Adiponectin stimulates phosphorylation and AMP (adenosin mono phosphate) kinase activation, exerting direct effects on vascular endothelium, diminishing the inflammatory response to mechanical injury and enhancing endothelium protection in cases of apolipoprotein E deficiency. Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis, CAD, T2DM. Lifestyle correction helps to favorably modify plasma adiponectin levels. Low adiponectinemia in obese patients is raised via continued weight loss programs in both diabetic and nondiabetic individuals and is also accompanied by reductions in pro-inflammatory factors. Diet modifications, like intake of fish, omega-3 supplementation, adherence to a Mediterranean dietary pattern and coffee consumption also increase adiponectin levels. Antidiabetic and cardiovascular pharmacological agents, like glitazones, glimepiride, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are also able to improve adiponectin concentration. Fibric acid derivatives, like bezafibrate and fenofibrate, have been reported to enhance adiponectin levels as well. T-cadherin, a membrane-associated adiponectin-binding protein lacking intracellular domain seems to be a main mediator of the antiatherogenic adiponectin actions. The finding of novel pharmacologic agents proficient to improve adiponectin plasma levels should be target of exhaustive research. Interesting future approaches could be the developmen

Topics: Adiponectin; Animals; Biomarkers; Cardiovascular Agents; Coronary Disease; Diabetes Mellitus, Type 2; Drug Delivery Systems; Humans; Hypoglycemic Agents; Metabolic Syndrome; Obesity; Signal Transduction

The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO) synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells' count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Female; Glucose Tolerance Test; Humans; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Obesity; Polycystic Ovary Syndrome; Renal Dialysis; Risk Factors; Signal Transduction; Stem Cells; Vascular Diseases

Cardiovascular complications, including cardiomegaly, myocardial ischemia and left ventricular hypertrophy, are some of the major determinants of the mortality rate in patients with Cushing's syndrome. We herein report the case of a patient with Cushing's syndrome caused by an adrenal adenoma who presented with congestive heart failure secondary to dilated cardiomyopathy. Follow-up echocardiography showed a marked improvement in the left ventricular cardiac function, and the plasma B-type natriuretic peptide (BNP) levels regressed after successful treatment. "Reversible" dilated cardiomyopathy is rarely associated with Cushing's syndrome; however, it should be recognized. Administering appropriate treatment in a timely manner can reverse this cardiomyopathy along with the other symptoms of Cushing's syndrome.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenalectomy; Aged; Biomarkers; Cardiomyopathy, Dilated; Cardiovascular Agents; Circadian Rhythm; Cushing Syndrome; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Heart Failure; Humans; Hydrocortisone; Natriuretic Peptide, Brain; Remission Induction

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents

Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data and mechanistic studies have indicated a possible beneficial action on blood vessels and the heart, via both glucagon-like peptide 1 (GLP-1)-dependent and GLP-1-independent effects. DPP-4 inhibition increases the concentration of many peptides with potential vasoactive and cardioprotective effects. Clinically, DPP-4 inhibitors improve several risk factors in patients with T2DM. They improve blood glucose control (mainly by reducing postprandial glycaemia), are weight neutral (or even induce modest weight loss), lower blood pressure, improve postprandial lipaemia, reduce inflammatory markers, diminish oxidative stress, and improve endothelial function. Some positive effects on the heart have also been described in patients with ischaemic heart disease or congestive heart failure, although their clinical relevance requires further investigation. Post-hoc analyses of phase II-III, controlled trials suggest a possible cardioprotective effect with a trend for a lower incidence of major cardiovascular events with gliptins than with placebo or active agents. However, the actual relationship between DPP-4 inhibition and cardiovascular outcomes remains to be proven. Major prospective clinical trials with predefined cardiovascular outcomes and involving various DPP-4 inhibitors are now underway in patients with T2DM and a high-risk cardiovascular profile.

Topics: Animals; Biomarkers; Blood Glucose; Blood Pressure; Cardiovascular Agents; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Endothelium, Vascular; Heart Failure; Humans; Inflammation Mediators; Lipids; Myocardial Ischemia; Oxidative Stress; Risk Factors; Treatment Outcome

Cardiovascular complications are the leading cause of death and morbidity in patients with diabetes; accounting for around 7 out of 10 of all causes of death in this population. Returning patients to normoglycaemia alone has been shown to have little effect on cardiovascular end points, therefore new therapies and strategies are required in order to reduce the incidence and improve outcomes of cardiovascular disease in diabetic individuals. The metabolic enzyme AMP-activated protein kinase (AMPK) has emerged in recent years as an attractive potential therapeutic target for diabetic vascular disease, and studies have shown improved endothelial and smooth muscle cell function following AMPK activation. Additionally, improved lipid profiles, reduced hypertrophic cardiomyocyte growth and protection from cardiac ischaemia-reperfusion injury have also been observed as beneficial outcomes of AMPK therapy. In this review we will discuss in detail the potential downstream targets of AMPK activation in the cardiovascular system. We will also provide an overview of long-known and newly discovered direct and indirect AMPK activators, as well as novel synthesised AMPK-activating compounds, which will highlight the potential for further exploiting AMPK in a therapeutic context for cardiovascular disease in diabetes.

Topics: AMP-Activated Protein Kinases; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Delivery Systems; Enzyme Activation; Humans; Hypoglycemic Agents; Up-Regulation

To review the relationship between health literacy and adherence to cardiovascular/diabetes medication.. We searched EMBASE (1974-February 2012) and MEDLINE (1948-February 2012). Search terms included health literacy, numeracy, health education and related terms, health literacy measurement tools, and medication adherence.. English-language articles of all study designs were considered. Articles were included if they had a measurement of health literacy and medication adherence and if participants were older adults taking drugs for cardiovascular illness or diabetes mellitus.. A total of 1310 citations were reviewed, including 9 articles that reported on 7 research studies. Most studies were retrospective, and all were based in the US. Because there was considerable diversity in measurements, participant characteristics, and outcome measures, we conducted a narrative synthesis rather than a meta-analysis. In assessing study validity, we looked at participant selection, method of measuring health literacy and medication adherence, missing data or losses, and adjustment for confounders. Of the 7 included studies, only 1 found a demonstrable association between health literacy and refill adherence. One clinical trial failed to show significant improvements in medication adherence after an intervention to improve health literacy.. The current evidence does not show a definite association between health literacy and medication adherence in older adults with cardiovascular disease or diabetes mellitus. In the absence of a definite link, efforts to develop interventions to improve health literacy would not necessarily improve adherence to cardiovascular medications. There is an urgent need for robust studies outside of the US, with wider, generalized recruitment of participants.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Health Literacy; Humans; Hypoglycemic Agents; Medication Adherence; Self Administration

Despite obvious progress in management of diabetes mellitus, the DM-related complications rate remains inadmissibly high. Macroangiopathy is known to rank first amongst complications of diabetes mellitus, and coronary artery disease remains to be the major cause of death. Analysed herein are peculiarities of the clinical course in diabetic patients presenting with coronary artery disease and lower limb critical ischaemia, followed by discussing the issues concerning drug therapy, preoperative examination, and methods of diagnosis in this cohort of patients prior to vascular operations, assessment of the preoperative risk, indications for coronarography and myocardial revascularization. Also presented are the results of the main clinical trials dedicated to preoperative myocardial revascularization, including those in diabetic patients with limb critical ischaemia, and finally highlighting current importance of optimizing approaches to managing and working out algorithms of treatment policy for diabetic patients with a combination of coronary artery disease, diabetes mellitus, and critical limb ischaemia.

Topics: Algorithms; Cardiovascular Agents; Clinical Protocols; Clinical Trials as Topic; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Foot; Disease Management; Humans; Ischemia; Limb Salvage; Myocardial Revascularization; Preoperative Care; Risk Assessment; Severity of Illness Index; Survival Analysis

This paper provides an update on the mechanisms of vascular impairment associated with insulin resistance and the pathogenesis of diabetic nephropathy and peripheral artery disease (PAD). It also considers the optimal treatment strategies for systemic vascular protection in light of recent findings. This area is of major clinical importance given the ongoing global epidemic of type 2 diabetes and the pivotal role played by insulin resistance in the mechanism of vascular impairment that manifests as macroangiopathy and microangiopathy. Timely diagnosis and intervention is critical in patients with systemic arteriosclerotic disease. Therefore, treatment strategies are aimed not only at targeting the presenting pathology, but also at reducing the risk of cardiovascular events. These efforts can help reduce the risk of both cardiovascular events and mortality. Treatment for PAD includes pharmacotherapy, endovascular treatment, and vascular reconstruction, along with exercise therapy. Because PAD can cause ischemia in the lower extremities, typical drug approaches include use of vasodilators and antiplatelet agents. Beraprost sodium and cilostazol are common choices in Japan, and their risks and benefits are discussed. Of note, beraprost has several therapeutic properties, including vascular endothelial protection, and antiplatelet and anti-inflammatory effects, in addition to vasodilatory activity. In patients with PAD, these activities improve the pathological process in the lower extremities and reduce the incidence of systemic vascular events. Recent preclinical findings indicate that beraprost improves not only ischemic extremities through its vasodilatory properties, but also reduces the insulin resistance which affects vascular endothelium. In this way, beraprost may contribute to an overall systemic vascular protective action. The use of agents, such as beraprost, which are capable of improving insulin resistance and resulting vascular endothelial function at an earlier disease stage, may ultimately contribute to increasing the life expectancy of patients with PAD.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endovascular Procedures; Exercise Therapy; Humans; Hypoglycemic Agents; Insulin Resistance; Peripheral Arterial Disease; Treatment Outcome

The decision whether to treat individuals not previously known to have cardiovascular disease is based on a new risk table in which Dutch research data on morbidity have been incorporated. An explanation of the roles of additional risk factors ignored in the cardiovascular risk function, such as a sedentary lifestyle and a high BMI, is provided. A method for estimating the cardiovascular risk in patients with diabetes mellitus and rheumatoid arthritis has been developed. New recommendations concerning the measurement of blood pressure at home and in the ambulatory setting have been formulated. The recommendations for the choice of antihypertensive drugs have been revised. The recommendations on handling therapy-resistant hypertension are provided. Recommendations for choosing statins based on a current cost-effectiveness analysis are provided.

Topics: Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Humans; Hypertension; Hypolipidemic Agents; Netherlands; Practice Guidelines as Topic; Risk Assessment; Risk Management

Correction of diabetic dyslipidaemia in diabetic patients is the most important factor in reducing cardiac risk. Diabetic dyslipidaemia is characterized by elevated triglycerides, low total high-density lipoprotein (HDL) and small dense low-density lipoprotein (LDL) particles. The most important therapeutic goal in diabetic dyslipidaemia is correction of the non-HDL-cholesterol (HDL-C) level. Glycaemic control with particular attention to postprandial glucose control plays a role not only in improving dyslipidaemia but also in lowering cardiac events. Pioglitazone is particularly effective for improving the manifestations of diabetic dyslipidaemia, in addition to its favorable effects on systemic inflammation and hyperglycaemia. Use of statins in addition to lifestyle change is recommended in most if not all type 2 diabetic patients and the goal should be to lower the LDL to a level recommended for the patient with existing cardiovascular disease (CVD) (non-HDL-C level <100 mg/dl). In addition, therapies for normalization of HDL and triglyceride levels should be deployed. Most patients with type 2 diabetes (T2D) will require combining a lipid-lowering therapy with therapeutic lifestyle changes to achieve optimal lipid levels. Combinations usually include two or more of the following: a statin, nicotinic acid, omega-3 fats and bile acid sequestrants (BASs). Fibrates may also be of use in diabetic patients with persistently elevated triglycerides and depressed HDL-C levels, although their role in lowering adverse CV events is questionable.

Topics: Cardiovascular Agents; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Male; Risk Reduction Behavior

Acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) are two naturally occurring carnitine derivates formed by carnitine acetyltransferase. The beneficial cardiovascular effects of ALC and PLC have been extensively evaluated in animals and humans during the last 20 years. For instance, many clinical trials have suggested ALC and PLC as potential strategies in the management of peripheral arterial disease, heart and cerebral ischemia, and congestive heart failure. As a result, several experts have already aimed to revise the clinical evidence supporting the therapeutic use of ALC and PLC. On the basis of their conclusions, our aim was a critical review of the effectiveness of ALC and PLC in the treatment of cardiovascular diseases. Type 2 diabetes mellitus is an independent risk factor for the development of cardiovascular disease. Therefore we also describe recent studies that have addressed the emerging use of ALC and PLC amelioration of the insulin resistant state and its related morbidities.

Topics: Acetylcarnitine; Animals; Cardiovascular Agents; Cardiovascular Diseases; Carnitine; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Insulin Resistance; Treatment Outcome

Glucose-lowering treatment in patients with type 2 diabetes and heart failure is controversial. Metformin is clearly contraindicated when such diseases coexist. Conversely, no contraindications have been established for insulin in this subset of patients, even though several observational and retrospective studies have shown increased mortality and worsening heart failure. Data from the literature have demonstrated that in this patient population, which accounts for one third of all cases of heart failure, metformin reduces mortality by 14-35%. In patients with a glomerular filtration rate >30 ml/min who do not show dehydration, shock, sepsis, severe liver disease or hypoxemia, the administration of metformin doses <2 g/day was associated with a null risk of lactic acidosis. The positive effects of metformin are correlated with the reduction in insulin resistance, which is responsible for both the onset and development of heart failure in diabetic patients. Insulin can provoke severe hypoglycemia and fluid retention, resulting in negative effects. Further randomized and prospective studies are warranted to address these controversial issues in such a large population with high mortality and morbidity rates. Longitudinal studies would be crucial to the understanding of the optimal therapy and for stratification of patients according to the severity of heart failure.

Topics: Acidosis, Lactic; Cardiovascular Agents; Clinical Trials as Topic; Contraindications; Diabetes Mellitus, Type 2; Heart Failure; Hospitalization; Humans; Hypoglycemic Agents; Insulin; Kidney Diseases; Metformin; Multicenter Studies as Topic; Prospective Studies; Retrospective Studies; Risk Factors

GLP-1-modulating therapies are a class of anti-diabetic drugs that improve glycemic control by stimulating glucose-dependent insulin secretion from pancreatic beta-cells. In addition, GLP-1-based therapies have a variety of extrapancreatic effects, including satiety induction and gastric mobility reduction, which extend to distinct cardiovascular actions. GLP-1 was found to reduce infarct size in the context of acute myocardial ischemia which depends on the activation of prosurvival pathways including PI3-kinase, Akt, and ERK1/2. Also, GLP-1 augments the left ventricular function in dilative and metabolic cardiomyopathy, possibly by increasing insulin independent cardiomyocyte glucose uptake. Furthermore, experimental and preliminary clinical evidence suggest vasoprotective efficacy of GLP-1 mediated by improved endothelial function and anti-inflammatory capacities leading to atheroprotection. Mechanistically, the GLP-1 receptor is relevant for glucose lowering efficacy of GLP-1. However, many of its vasoprotective actions have also been described for the GLP-1 metabolite (9-37), which does not activate the GLP-1 receptor, suggesting the presence of an additional, yet unknown, signaling pathway. Ongoing research investigates the relevance of these observations in human disease and underlying mechanisms, which are reviewed in the present article.

Topics: Animals; Cardiovascular Agents; Cardiovascular System; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Incretins

This review outlines the evolving role of percutaneous coronary intervention (PCI) for stable angina in the context of the widely discussed Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials. Factors outlined include defining the appropriate patient population, the clinical circumstances, and the technical aspects of the procedure to optimize clinical outcomes and minimize risk. The COURAGE Trial, as others reported earlier, reported no difference in death or myocardial infarction with PCI compared with medical therapy for stable angina. In patients with type 2 diabetes mellitus in the BARI 2D Trial, a strategy of revascularization with coronary artery bypass graft surgery (CABG) or PCI resulted in no difference in mortality compared with optimal medical therapy. However, PCI for stable angina was associated with reduced angina and improved quality of life. Procedural aspects of PCI that support its continuing role in the management of patients with stable angina include the frequent advancements in PCI technology that have further enhanced both acute and long-term success. In conclusion, the implications of these findings for clinical practice include evaluating the use of PCI for stable angina in addition to optimal medical therapy to reduce angina and improve quality of life, but individualizing care for higher risk patients with more complex coronary artery disease who were not enrolled in the COURAGE and BARI 2D trials.

Topics: Angina Pectoris; Angioplasty; Cardiovascular Agents; Case Management; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Quality of Life; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Treatment Outcome

Treatment of diabetic patients with multivessel coronary artery disease is controversial. This paper reviews pertinent literature on surgical revascularization with emphasis on which patients benefit from therapy. Recent studies of medical, percutaneous, and surgical therapies have added greatly to our understanding of the treatment of diabetic patients with coronary artery disease. Randomized trials show no advantage with prophylactic percutaneous coronary intervention over medical therapy. However, in patients with more severe three-vessel disease, coronary artery bypass graft surgery (CABG) improved outcomes with respect to reduced myocardial infarction events and cardiac death as compared with medical therapy. In addition, rates of late myocardial infarction and mortality were significantly lower in patients treated with CABG compared with those who received drug-eluting stents. Although the need for subsequent revascularization with drug-eluting stents is reduced compared with angioplasty and bare-metal stents, the rate is still higher than that associated with CABG. CABG reduces risks of myocardial infarction, cardiac death, and need for repeat revascularization in diabetic patients with severe, multivessel coronary artery disease.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Treatment Outcome

The increasing prevalence of metabolic diseases is alarming and highlights the need for more effective and safer therapies to treat these diseases. Recent evidence from several animal studies indicates that FGF21 induces numerous beneficial metabolic changes without apparent adverse effects. These results suggest that FGF21 could be a novel and attractive drug candidate for the treatment of cardiovascular disease, obesity and type 2 diabetes. The pharmacology of FGF21, molecular mechanisms contributing to the actions of this compound, and knowledge gaps to be addressed to allow further exploration of the therapeutic potential of this molecule are discussed in this review.

Topics: Animals; Anti-Obesity Agents; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fibroblast Growth Factors; Genetic Therapy; Humans; Hypoglycemic Agents; Obesity; Signal Transduction

Coronary stent thrombosis is a serious problem in the drug-eluting stent era. Despite aggressive antiplatelet therapy during and after percutaneous coronary intervention (PCI), the incidence of sub-acute stent thrombosis remains approximately 0.5%-2%, which may represent a catastrophic clinical situation. Both procedural factors and discontinuation of antiplatelet therapy are normally associated with this event. We report on simultaneous stent thromboses of two drug-eluting stents implanted in two different vessels, which resulted in a life-threatening clinical condition. Possible contributing factors that led to synergistic thrombotic effects are discussed.

Topics: Angioplasty, Balloon, Coronary; Aspirin; Cardiovascular Agents; Clopidogrel; Coronary Angiography; Coronary Stenosis; Coronary Thrombosis; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Humans; Medication Adherence; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Sirolimus; Ticlopidine; Treatment Outcome

Various systemic pharmacological approaches have been evaluated to reduce the risk of restenosis after coronary angioplasty, with or without stent, in the general population and in diabetic patients who are at increased risk for such complication. The aim of the present paper is to describe the effects of the main pharmacological classes on the risk of restenosis, the need for new revascularisation procedures and the incidence of major clinical events (MACE: death, myocardial infarction, revascularisation). We will analyse the role of antiplatelet agents, omega-3 fatty acids, statins, anti-inflammatory compounds, immunomodulators, anti-oxidants, glitazones and, finally, classical antidiabetic drugs such as metformin and insulin. Whenever possible, we will focus our attention on the results obtained in the diabetic population.

Topics: Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents; Antioxidants; Belgium; Cardiovascular Agents; Coronary Restenosis; Coronary Thrombosis; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Evidence-Based Medicine; Fatty Acids, Omega-3; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Immunologic Factors; Incidence; Meta-Analysis as Topic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stents

Paralleling the rise in obesity, the cardiometabolic syndrome is a rapidly growing health problem in the United States. There is a 3-fold increase in the prevalence of coronary heart disease, myocardial infarction, and stroke due to the coagulation, hemodynamic, and metabolic abnormalities seen in these individuals. The use of aspirin for secondary prevention and, to a lesser degree, primary prevention of cardiovascular events is a well-established standard of care. However, in patients with diabetes or the cardiometabolic syndrome, the role of aspirin in prevention of cardiovascular events remains controversial. In this review, the authors examine the clinical trial data on the use of aspirin in diabetes and the cardiometabolic syndrome for cardiovascular protection. They also explore, in addition to aspirin's effects on platelet aggregation, some of the mechanisms by which aspirin may favorably alter the course of atherosclerosis, effects on endothelial function, and glycemia.

Topics: Aspirin; Blood Coagulation; Blood Glucose; Blood Platelets; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Metabolic Syndrome; Treatment Outcome

Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM) comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1), the dipeptidyl peptidase 4 (DPP-4) inhibitors, dual peroxisome proliferator-activated receptors (PPAR) agonists (glitazars) and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patients. Metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as recent myocardial infarction, heart or renal failure. Sulfonylureas exert their effect by closing the ATP-dependent potassium channels. This prevents the opening of these channels during myocardial ischemia, impeding the necessary hyperpolarization that protects the cell. The combined sulfonylurea/metformin therapy reveals additive effects on mortality in patients with coronary artery disease (CAD). Meglitinides effects are similar to those of sulfonylureas, due to their almost analogous mechanism of action. Glitazones lower leptin levels, leading to weight gain and are unsafe in NYHA class III or IV. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates is yet unknown. The incretin GLP-1 is associated with reductions in body weight and appears to present positive inotropic effects. DPP-4 inhibitors influences on the cardiovascular system seem to be neutral and patients do not gain weight. The future of glitazars is presently uncertain following concerns about their safety. The amylin mimetic drug paramlintide, while a satisfactory adjuvant medication in insulin-dependent diabetes, is unlikely to play a major role in the management of T2DM. Summarizing the present information it can be stated that 1. Four out the five classical oral antidiabetic drug groups present proven or potential cardiac hazards; 2. These hazards are not mere 'side effects', but biochemical phenomena which are deeply rooted in the drugs' mechanism of action; 3. Current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of T2DM with proven CAD; 4. Glitazones should be avoided in patients with overt he

Topics: Animals; Cardiovascular Agents; Diabetes Mellitus, Type 2; Heart Diseases; Humans; Hypoglycemic Agents; Insulin; Survival Rate

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide-ranging effects on glucose metabolism, including stimulation of insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP-1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP-1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP-1 receptors (GLP-1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP-1R agonists have wide-ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP-1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP-1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP-1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP-1 as a novel treatment for CVD.

Topics: Animals; Blood Glucose; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Insulin; Insulin Secretion; Receptors, Glucagon

Diabetes mellitus and heart failure show a high coincidence, promote pathogenesis and worsen prognosis of each other. Currently, there are no prospective studies evaluating a specific antidiabetic or cardiologic therapy in diabetic patients with heart failure. Furthermore, a favorable effect of optimized glycemic control on the progression of heart failure has not been proven yet. Retrospective analyses indicate a rather positive effect of the insulin sensitizers metformin and glitazones and a neutral or rather negative effect of insulin and sulfonylureas in diabetic patients with heart failure. Up to now, due to missing prospective, controlled trials no evidence-based antidiabetic therapy can be recommended in diabetic heart failure patients.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Heart Failure; Humans; Hypoglycemic Agents

Statins lower cardiovascular risk in patients with diabetes; however, as these patients are at higher risk than other cardiovascular patients, statins merely decrease coronary event rates to the level seen in untreated nondiabetic individuals at risk for cardiovascular disease, indicating the existence of substantial residual risk. One reasonable explanation resides in the fact that statins have only limited effectiveness on hypertriglyceridemia and low HDL cholesterol, and they do not normalize the LDL size-distribution pattern. Peroxisome proliferator-activated receptor (PPAR)alpha agonists, which include fibrates, normalize this atherogenic lipid profile, as well as several cardiovascular risk markers associated with the metabolic syndrome and type 2 diabetes. In particular, hypertriglyceridemia and the ratio of small dense:large buoyant LDL particles are significantly improved. Outcome trials of PPARalpha agonists have demonstrated reductions in cardiovascular morbidity in patients with diabetes and in those with the metabolic syndrome; plaque progression is diminished, diabetic nephropathy and retinopathy are counteracted and amputation-risk decreased. The combination of fibrates with statins improves overall lipoprotein profile further. PPARalpha agonists seem particularly indicated in patients with diabetes who have residual dyslipidemia (high triglyceride and/or low HDL) despite receiving statin therapy, and patients who are nondiabetic, overweight, insulin-resistant and who have hypertriglyceridemia and/or low HDL cholesterol and chronic inflammation.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Clofibric Acid; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Lipids; PPAR alpha; Risk Assessment; Risk Factors; Treatment Outcome

Metformin is now established as a first-line antidiabetic therapy for the management of type 2 diabetes. Its early use in treatment algorithms is supported by lack of weight gain, low risk of hypoglycaemia and its mode of action to counter insulin resistance. The drug's anti-atherosclerotic and cardioprotective effects have recently been confirmed in prospective and retrospective studies, and appear to reflect a collection of glucose-independent effects on the vascular endothelium, suppressant effects on glycation, oxidative stress and formation of adhesion molecules, stimulation of fibrinolysis and favourable effects on the lipid profile. Although avoidance of troublesome gastrointestinal tolerability issues requires careful dose titration, the risk of serious adverse events is considered low provided that contra-indications (especially with respect to renal function) are observed. As many of its actions go beyond glucose lowering, emerging evidence indicates potential benefits in other insulin-resistant states and possibly tumour suppression.

Topics: Administration, Oral; Blood Glucose; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Patient Selection; Practice Guidelines as Topic; Treatment Outcome

The prevalence of type 2 diabetes is rising at an alarming rate worldwide. Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the diabetic population. Future CAD risk should be routinely assessed in patients with diabetes as specific subgroups might benefit from information derived from cardiac stress testing and other diagnostic procedures. Risk factor control is of paramount importance in all cases and it usually requires sustained lifestyle modifications, coupled with pharmacological interventions. Statins and angiotensin-converting enzyme (ACE) inhibitors are the first-line agents for the treatment of dyslipidaemia and hypertension, respectively. Microvascular, but not macrovascular, complications of diabetes are effectively prevented by good glycaemic control. Metformin is considered the first-choice agent in overweight diabetic subjects, while the role of thiazolidinediones is currently the focus of medical research. The diagnosis of acute coronary events in patients with diabetes is often challenging because of the high prevalence of silent ischaemia in these subjects. All acute cardiac events need to be promptly treated and myocardial reperfusion attempted without delay. Maintaining glucose levels as close to normal as possible, during and shortly after an acute event, improves prognosis in patients with diabetes. Risk factor control remains the cornerstone of secondary prevention; beta-blockers, ACE-inhibitors and antiplatelet agents confer additional symptomatic and survival benefit. Similar therapeutic principles also apply to patients with type 1 diabetes. This article addresses the complex problem of managing patients with diabetes and coronary artery disease.

Topics: Animals; Cardiovascular Agents; Coronary Artery Disease; Diabetes Mellitus, Type 2; Disease Management; Humans; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Risk Factors

Diabetes mellitus (DM) is a worldwide epidemic. Its prevalence is rapidly increasing in both developing and developed countries. Coronary heart disease (CHD) is highly prevalent and is the major cause of morbidity and mortality in diabetic patients. The purpose of this review is to assess the clinical impact of recent advances in the epidemiology, prevention, and management of CHD in diabetic patients. A systematic review of publications in this area, referenced in MEDLINE in the past 5 years (2000 to 2005), was undertaken. Patients with CHD and prediabetic states should undergo lifestyle modifications aimed at preventing DM. Pharmacological prevention of DM is also promising but requires further study. In patients with CHD and DM, routine use of aspirin and an angiotensin-converting enzyme inhibitor (ACE-I)--unless contraindicated or not tolerated-and strict glycemic, blood pressure, and lipid control are strongly recommended. The targets for secondary prevention in these patients are relatively well defined, but the strategies to achieve them vary and must be individualized. Intense insulin therapy might be needed for glycemic control, and high-dose statin therapy might be needed for lipid control. For blood pressure control, ACE-Is and angiotensin receptor blockers are considered as first-line therapy. Noncompliance, particularly with lifestyle measures, and underprescription of evidence-based therapies remain important unsolved problems.

Topics: Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Coronary Disease; Diabetes Mellitus, Type 2; Dyslipidemias; Health Behavior; Humans; Hyperglycemia; Hypertension; Insulin Resistance; Life Style; Metabolic Syndrome; Treatment Refusal

Diabetes mellitus is a major risk factor for restenosis in patients undergoing percutaneous coronary intervention. Randomized controlled trials comparing drug-eluting stents (DESs) with bare metal stents (BMSs) showed a marked decrease in in-stent restenosis and target lesion revascularization with DESs in the total patient population enrolled in the studies, including patients with diabetes. However, it remains unclear whether the antirestenotic benefit of DESs is preserved in the high-risk diabetic subgroup. MEDLINE, EMBASE, ISI Web of Knowledge, Current Contents, International Pharmaceutical Abstracts, and recent Scientific Sessions databases were searched to identify relevant clinical trials comparing DESs with BMSs. A randomized controlled trial was included if it provided outcome data for patients with diabetes for > or =1 of the following: late lumen loss, in-stent restenosis, or target lesion revascularization. Data were combined using fixed-effects models, and standard tests for heterogeneity were performed. Eight studies with 1,520 patients with diabetes were identified that reported > or =1 outcome of interest. Mean late lumen losses (7 studies) were 0.93 mm (95% confidence interval [CI] 0.510 to 1.348) with BMSs and 0.18 mm (95% CI -0.088 to +0.446) with DESs. For patients receiving a DES, this translated into a marked decrease in in-stent restenosis (7 studies, RR 0.14, 95% CI 0.10 to 0.22, p <0.001) and target lesion revascularization (8 studies, RR 0.34, 95% CI 0.26 to 0.45, p <0.001). DES use is associated with a marked decrease in in-stent restenosis and target lesion revascularization in patients with diabetes. In conclusion, the analysis supports the current widespread use of DESs in these high-risk patients.

Topics: Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Databases, Factual; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Paclitaxel; Prosthesis Design; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Acute coronary syndromes (ACS) present a major health challenge in modern medicine. With new clinical trials being conducted, our knowledge of latest therapies for ACS continually evolves. In this article, we review currently available medical therapies and provide evidence-based rationale for current pharmacologic therapies. Among the antiplatelet therapies, aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors demonstrate significant efficacy in reducing morbidity and mortality. Among the anticoagulants, unfractionated heparin and low molecular weight heparin, particularly enoxaparin sodium, remain the hallmarks of therapy against which newer anticoagulants are often compared. Bivalirudin has recently showed significant efficacy in decreasing cardiovascular events and mortality, but with potentially less risk of bleeding than heparin. Results of trials evaluating warfarin remain inconsistent regarding potential benefits. Finally, fondaparinux sodium, recently tested, shows promise as a powerful yet safe anticoagulant. Fibrinolysis is an acceptable modality for reperfusion if facilities equipped for primary percutaneous revascularization are not available. Regarding anti-ischemic therapy, beta-adrenoceptor antagonists and nitrates remain critical in the early management of ACS. Inhibitors of the renin-angiotensin-aldosterone system have also shown significant reductions in the morbidity and mortality of patients presenting with ACS, particularly in patients with left ventricular dysfunction and clinical heart failure, with ACE inhibitors being first-line agents and angiotensin receptor antagonists being a reasonable substitute if ACE inhibitors are not tolerated. Among the lipid-lowering therapies, statins (HMG-CoA reductase inhibitors) have been documented as being the most well tolerated and most efficacious therapies for ACS patients and data exist that they should be administered early in ACS management. Studies evaluating combination therapy (antiplatelet drugs, beta-adrenoceptor antagonists, ACE inhibitors, and lipid-lowering agents) show a clear benefit in mortality in patients with known coronary artery disease. Efforts to improve these key evidence-based medical therapies are numerous and include such programs as the American College of Cardiology's Guidelines Applied in Practice, international patient registries such as the Global Registry of Acute Coronary Events, and studies such as CRUSADE. Finally, patients with diabetes mellitus pose

Topics: Acute Disease; Angina, Unstable; Anticoagulants; Cardiovascular Agents; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Humans; Hypolipidemic Agents; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic

Endothelial dysfunction is universal in diabetes, being intimately involved with the development of cardiovascular disease. The pathogenesis of endothelial dysfunction in diabetes is complex. It is initially related to the effects of fatty acids and insulin resistance on 'uncoupling' of both endothelial nitric oxide synthase activity and mitochondrial function. Oxidative stress activates protein kinase C (PKC), polyol, hexosamine and nuclear factor kappa B pathways, thereby aggravating endothelial dysfunction. Improvements in endothelial function in the peripheral circulation in diabetes have been demonstrated with monotherapies, including statins, fibrates, angiotensin-converting enzyme (ACE) inhibitors, metformin and fish oils. These observations are supported by large clinical end point trials. Other studies show benefits with certain antioxidants, L-arginine, folate, PKC-inhibitors, peroxisome proliferator activated receptor (PPAR)-alpha and -gamma agonists and phosphodiesterase (PDE-5) inhibitors. However, the benefits of these agents remain to be shown in clinical end point trials. Combination treatments, for example, statins plus ACE inhibitors and statins plus fibrates, have also been demonstrated to have additive benefits on endothelial function in diabetes, but there are no clinical outcome data to date. Measurement of endothelial dysfunction in cardiovascular research can provide fresh opportunities for exploring the mechanism of benefit of new therapeutic regimens and for planning and designing large clinical trials.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hypoglycemic Agents; Signal Transduction; Treatment Outcome

The prevalence of diabetes mellitus is increasing worldwide. Among other complications, diabetes is associated with the risk of coronary heart disease (CHD) that is thought to be equal to the risk of CHD in subjects without diabetes with previous myocardial infarction. Studies have shown that CHD risk factors start to increase long before the onset of clinical diabetes. Furthermore, the risk factors that are present in prediabetic individuals are also components of the highly prevalent metabolic syndrome. This suggests that treatment of CHD risk factors may effectively reduce the incidence of type 2 diabetes. Lifestyle interventions have proved effective in preventing the onset of type 2 diabetes in subjects with impaired glucose tolerance. A number of post hoc studies have reported consistent reductions in the incidence of type 2 diabetes in hypertensive patients treated with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). As a result of these positive data, ongoing prospective studies are investigating whether antihypertensive agents prevent or delay the onset of diabetes in patients at risk. Telmisartan, a selective oral ARB that is indicated for first-line therapy of essential hypertension, may provide improved tolerability compared with ACE inhibitors. Therefore, the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program is investigating the effectiveness of telmisartan in the prevention or delay of type 2 diabetes. The program comprises ONTARGET and the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND).

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Humans; Life Style; Male; Metabolic Syndrome; Risk Assessment; Risk Factors

Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) control the development and homeostasis of multiple tissue types in many organisms, from humans to invertebrates. These morphogens are expressed in a tissue-specific manner and they signal by binding to serine-threonine kinase receptors, resulting in coordinated changes in gene expression that regulate the differentiation and development of multiple tissue types. In addition, these proteins are regulated post-transcriptionally through binding to several soluble proteins. In this review we focus on a subset of BMPs and GDFs that have been implicated in the pathophysiology of type 2 diabetes and cardiovascular disease.

Topics: Animals; Atherosclerosis; Bone Morphogenetic Protein 7; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Growth Differentiation Factor 3; Humans; Hypertension, Pulmonary; Hypoglycemic Agents; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Metabolic Diseases; Signal Transduction; Transforming Growth Factor beta

More than 70% of patients with Type 2 diabetes mellitus (T2DM) die because of cardiovascular diseases. Current therapeutic strategies are based on separate treatment of insulin resistance and dyslipidaemia. Development of drugs with multimodal activities should improve management of the global cardiovascular risk of T2DM patients and result in better patient compliance. New therapeutic strategies are aimed at targeting the entire spectrum of dysfunctioning organs, cells and regulatory pathways implicated in the pathogenesis of T2DM, dyslipidaemia and atherosclerosis. PPAR family members play major roles in the regulation of lipid metabolism, glucose homeostasis and inflammatory processes, making these transcription factors ideal targets for therapeutic strategies against these diseases. This review discusses why PPARs and development of novel selective PPAR modulators, dual and pan PPAR agonists constitute promising approaches for the treatment of diabetes, dyslipidaemia and atherosclerosis.

Topics: Animals; Atherosclerosis; Cardiovascular Agents; Combined Modality Therapy; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Peroxisome Proliferator-Activated Receptors

Peroxisome proliferator-activated receptor (PPAR)gamma regulates a number of cellular processes that affect glucose homeostasis, endothelial function and vessel wall inflammation, as well as protecting against cardiovascular complications that occur in diabetes. Thiazolidinediones are PPARgamma agonists that are in clinical use for the treatment of type 2 diabetes. Accumulating evidence indicates that thiazolidinediones may exert cardioprotective effects at each stage of atherogenesis.. This paper reviews preclinical and clinical evidence (identified from a search of MEDLINE databases) supporting a beneficial cardiovascular effect of thiazolidinediones and discusses the implications of these data for the optimal use of thiazolidinediones in clinical practice.. In vitro animal model and clinical studies indicate that thiazolidinediones correct endothelial dys function, suppress chronic inflammatory processes, reduce fatty streak formation, delay plaque evolution and vessel wall thickening and enhance plaque stabilization and regression.. Thus, thiazolidinediones show potential as potent anti-inflammatory, antithrombotic agents that could both improve glucose levels and the long-term cardio vascular risk related to atherosclerosis in patients with type 2 diabetes.

Topics: Animals; Arteriosclerosis; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fibrinolytic Agents; Humans; Models, Animal; PPAR gamma; Thiazolidinediones

People with type 2 diabetes generally carry an array of risk factors for cardiovascular disease (CVD), including hyperglycaemia, dyslipidaemia, alterations in inflammatory mediators and coagulation/thrombolytic parameters, as well as other 'non-traditional' risk factors, many of which may be closely associated with insulin resistance. Consequently, rates of CVD mortality and morbidity are particularly high in this population. Targeting hyperglycaemia alone does not reduce the excess risk in diabetes, highlighting the need for aggressive treatment of other risk factors.. This is a review of cardiovascular risk markers in diabetes, based on MEDLINE and EMBASE literature searches (1994-2004).. Although, the current use of statin therapy is effective at reducing low-density lipoprotein (LDL)-cholesterol, residual risk remains from other independent lipid and non-lipid factors. The peroxisome proliferator-activated receptor-gamma(PPARgamma) appears to be intimately involved in regulating risk markers at multiple levels. Ligands that activate PPARgamma, which include the thiazolidinedione (TZD) insulin-sensitizing agents used to manage type 2 diabetes, display a number of potential anti-atherogenic properties, including effects on high-density lipoprotein (HDL) cholesterol and triglycerides, as well as other beneficial non-lipid effects, such as regulating levels of mediators involved in inflammation and endothelial dysfunction. Data from several sources suggest that simple strategies combining TZDs and statins could have complementary effects on CVD risk factors profiles in diabetes, alongside the ability to control glycaemia.. It is hoped that studies currently underway will provide insights into the value of such treatment approaches in terms of reducing the excess CVD risk, morbidity and mortality associated with type 2 diabetes.

Topics: Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin Resistance; PPAR gamma; Risk; Thiazolidinediones

Lipid abnormalities in people with diabetes are likely to play an important role in the development of atherogenesis. These lipid disorders include potentially atherogenic quantitative (increased triglyceride levels and decreased high-density lipoprotein-cholesterol [HDL-C] levels) and qualitative abnormalities of lipoproteins (changes in lipoprotein size, increase in triglyceride content of low-density lipoprotein (LDL) and HDL, glycation of apoproteins and increased susceptibility of LDL to oxidation). Guidelines from the two main diabetes organizations, the International Diabetes Federation and the American Diabetes Association, recommend the aggressive management of diabetic dyslipidaemia to reduce the risk of cardiovascular disease (CVD). Statins are the first choice pharmacological therapy to address diabetic dyslipidaemia due to their effectiveness at lowering LDL-C levels in patients with diabetes. Fibrates (peroxisome proliferator-activated receptor [PPAR]alpha ligands) target another aspect of dyslipidaemia by lower ing triglycerides (to a greater extent than statins) and raising HDL-C levels, especially when baseline levels are low. The PPARgamma agonist, pioglitazone appears to affect lipid metabolism by decreasing plasma triglycerides, increasing HDL-C and decreasing the number of small, dense atherogenic LDL particles.. This paper provides a review of the current literature (based on searches of MEDLINE and EMBASE from 1985 to 2005, inclusive) supporting the recommendations for the management of dyslipidaemia among patients with type 2 diabetes, including new strategies involving drug combinations that achieve good glycaemic and lipidaemic control that could potentially reduce the morbidity and mortality associated with type 2 diabetes.

Topics: Arteriosclerosis; Cardiovascular Agents; Clofibric Acid; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; PPAR gamma; Risk Reduction Behavior

Outcome studies are used to measure clinically meaningful primary end points, such as mortality and cardiovascular morbidity. However, few outcome trials have been conducted exclusively in people with diabetes; the majority of conventional diabetes trials use surrogate end points that may or may not translate into clinical benefits. Our current knowledge of the effects of pharmacotherapies on cardiovascular risk in patients with diabetes has been gained from subgroups included in large-scale studies. Several trials with lipid-modifying, antiplatelet and/or antihypertensive therapy, for example the recent Collaborative AtoRvastatin Diabetes Study, have included sufficient numbers of patients with diabetes to indicate that effective management can reduce cardio vascular risk in this patient population. The United Kingdom Diabetes Study and the Diabetes Control and Complications Trial provide important, but inconclusive data on the impact of glucose-lowering therapy on the incidence of cardiovascular complications in diabetes. Thiazolidinediones have only become available during the past few years, thus their effects were not assessed in these landmark trials. Ongoing studies in diabetic populations at high risk for further macrovascular events, such as the PROspective pioglitAzone Clinical Trial In macroVascular Events, have been designed to assess the effect of thiazolidinediones on cardiovascular outcome in patients with diabetes and should help to reinforce the importance of broad-based treatment of the multiple metabolic risk factors for cardiovascular disease in people with diabetes.. This paper (based upon MEDLINE and EMBASE literature searches in the year range 1990-2005) reviews what we have learned from outcome studies up to the end of 2004 and looks at what we hope to learn from ongoing studies.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Clofibric Acid; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Risk Reduction Behavior; Thiazolidinediones

To review the antihypertensive, cardiovascular and pleiotropic effects of angiotensin-receptor blockers (ARBs).. ARBs are the most recently approved class of antihypertensive agents. They selectively block the angiotensin II type 1 receptor, thus inhibiting most of the deleterious effects of angiotensin II. In addition to blood-pressure control, other benefits may be gained using ARBs. This is because the renin-angiotensin system plays a crucial role in circulatory homoeostasis, and in patients with atherosclerosis, diabetes or hypertension, angiotensin II contributes to the pathophysiology of disease. Evidence-based medicine includes well-controlled studies with mortality and morbidity endpoints in patients with a variety of conditions including hypertension, type 2 diabetes, stroke, renal disease, heart failure, left-ventricular hypertrophy and coronary heart diseases. In addition to these hard endpoints, it has been shown that treatment with ARBs prevents the development of type 2 diabetes, ameliorates coronary and peripheral vascular endothelial dysfunction and decreases plasma levels of several markers of vascular inflammation.. ARBs are first-line agents for the treatment of hypertension and cardiovascular diseases. Blocking the renin-angiotensin system with these agents has special advantages due to specific vascular and antiatherosclerotic effects, which contribute to a better cardiovascular and renal protection in patients at risk from or with cardiovascular disease.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus, Type 2; Endothelium, Vascular; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases

In the UGDP study, published in the 1970s, a high incidence of cardiovascular mortality was found in patients treated with the sulfonylurea agent tolbutamide. Impaired ischaemic preconditioning is presumed to be the most important mechanism for the excess cardiovascular mortality observed. However, as tolbutamide has only a low affinity for cardiac sulfonylurea receptors, interference with ischaemic preconditioning seems unlikely to account for this excess mortality. Several smaller studies also failed to establish a definite link between sulfonylurea treatment before acute myocardial infarction and in-hospital mortality. However, when the myocardium becomes exposed to repeated or prolonged periods of ischaemia, ischaemic preconditioning may become clinically important. Myocardial ischaemia can also develop during emergency or elective angioplasty and during coronary bypass surgery. Therefore discontinuation of sulfonylurea treatment should be considered in these circumstances.

Topics: Animals; Cardiovascular Agents; Catheterization; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Ischemic Preconditioning, Myocardial; Models, Biological; Myocardial Ischemia; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Tolbutamide

Diabetic cardiomyopathy is characterized by a prominent interstitial fibrosis. Postulated etiologies include microangiopathy, autonomic neuropathy, and metabolic factors. A common root of these pathologies is hyperglycemia or hyperinsulinemia, both of which are prominent in type 2 diabetes mellitus, which has the highest incidence of cardiovascular morbidity and mortality. The relative importance of each factor is a matter of debate; it is likely that both of these factors in addition to the concomitant risk factors seen in diabetics (dyslipidemias, hypertension, obesity, coagulation abnormalities) contribute to the spectrum of myocardial disease in diabetes. A discussion of these contributive pathologies and the hyperglycemia and hyperinsulinemia that underlie them is the subject of this review. Treatment methodologies to control the development of such pathology also are discussed.

Topics: Albuminuria; Blood Coagulation Disorders; Cardiovascular Agents; Cause of Death; Coronary Disease; Diabetes Mellitus, Type 2; Female; Global Health; Heart Failure; Humans; Hyperinsulinism; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Incidence; Insulin Resistance; Male; Obesity; Oxidative Stress; Prognosis; Risk Factors; Sex Characteristics; United States

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticholesteremic Agents; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Agents; Diabetes Mellitus, Type 2; Humans; Practice Guidelines as Topic

Topics: Arteriosclerosis; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hypoglycemic Agents; Inflammation; Insulin Resistance

Angiotensin-receptor blockers have been part of the antihypertensive treatment armamentarium since the mid-1990s. During this period, the number of agents has increased greatly, as has the number of indications for which these drugs are being tested in randomized controlled clinical trials. Beginning as efficacious and very well tolerated antihypertensives, angiotensin-receptor blockers have been shown to have benefits in patients with diabetes and heart failure that are not only attributable to the reduced blood pressure, as supported by recently concluded trials. The expanding treatment areas with these agents widen the interest in their applicability across the entire cardiovascular continuum. A number of large-scale studies set to report within the next few years will further determine the effects of angiotensin-receptor blockers in a range of cardiovascular indications beyond hypertension.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Failure; Humans; Myocardial Infarction; Renin-Angiotensin System

Type 2 diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in type 2 diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with type 2 diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with type 2 diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clofibric Acid; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Lipids; Lipoproteins

The coronary morbi-mortality is particularly high in type 2 diabetes, which represents the vast majority of all diabetes. Hyperglycemia is an independent vascular risk factor in the short and long-term. The relationship between the degree of hyperglycemia and vascular risk is linear with no threshold effect. The occurrence of a first coronary event is an occasion, though late, to review the management of all risk factors in diabetic patients. In these patients, intensive insulin therapy administered in the acute phase of infarction reduces cardiovascular mortality by 30% at 1 and 3 years. There are no specific studies of secondary prevention by optimal therapy of diabetes, but, in the UKPDS, the treatment of hyperglycemia with sulfonylurea or insulin only marginally reduced the number of cardiovascular events. On the other hand, treatment of obese patients with metformin significantly reduced the incidence of myocardial infarction and of mortality diabetes related. These results, though observed with the same level of glycemic control as in the other treatment groups, suggest a cardio-protective effect of metformin itself. These beneficial effects should be weighed up against the potential risk of lactic acidosis which still limits the widespread use of metformin in with coronary heart disease patients. Follow-up studies show that diabetic with coronary heart disease patients do not receive all effective therapeutic inventions in secondary prevention and that the treatment of hyperglycemia is often neglected. Close collaboration between cardiologists and diabetologists is necessary to improve the management of type 2 diabetes.

Topics: Acidosis, Lactic; Acute Disease; Adrenergic beta-Antagonists; Blood Glucose; Cardiovascular Agents; Case Management; Cohort Studies; Controlled Clinical Trials as Topic; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incidence; Insulin; Metformin; Myocardial Infarction; Obesity; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Sulfonylurea Compounds; Treatment Outcome

Topics: Animals; Cardiovascular Agents; Diabetes Mellitus, Type 2; Glycosylation; Hemodynamics; Humans; Hypoglycemic Agents; Metformin; Neovascularization, Pathologic; Neovascularization, Physiologic; Oxidation-Reduction

Diabetes mellitus is a risk factor for coronarosclerosis and for high mortality after myocardial infarction (MI). The causes of this high mortality are: more extensive and premature coronarosclerosis, more frequent left ventricular dysfunction, worse glycemic control with increased myocardial oxygen consumption, sulfanylurea drugs before and during MI. The results of a multicenter study (DIGAMI) and other studies suggest that a better control of diabetes using intravenous infusion of insulin and glucose, followed by long-term (3 months) intensive insulin therapy subcutaneously, improves long-term prognosis after MI. The relative reduction of mortality at the end of follow-up (3.4 years) is 28%. Thrombolysis reduces mainly mortality in hospital,s period and does not provoke retinal haemorrhages. Aspirin lowers the relative risk of mortality to 0.72. The beta-blockers are less used in diabetic patients because they probably alter diabetic control, lipid profile and "mask" the hypoglycemic symptoms, but the results of the beta-blocker's effect concerning reduction of mortality are convincing. ACE inhibitors and statins also reduce mortality in diabetics with MI, via beneficial influence of endothelial dysfunction. The ATMA study registers reduction of rhythmogenic mortality by 29% with amiodarone in high risk of arrhythmia after MI. The invasive methods of treatment in diabetes are accompanied by higher risk of reobstruction. The attempt to reduce this tendency is realizable with intracoronary stents, glycoprotein IIb/IIIa inhibitors and aggressive early treatment of all other risk factors.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Myocardial Infarction; Risk Factors

Topics: Anticholesteremic Agents; Arteriosclerosis; Cardiovascular Agents; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Treatment Outcome

DPP4 (dipeptidyl peptidase-4) inhibitors comprise a class of oral diabetes medication that have the potential for off-target cardiovascular effects. We previously showed that DPP4 inhibition attenuates the hypotensive effect of acute ACE (angiotensin-converting enzyme) inhibition and increases norepinephrine. Here, we investigated the effects of DPP4 during sustained ACE inhibition compared with during therapy with an ARB (angiotensin receptor blocker) or calcium channel blocker (neutral comparator) in a randomized, double-blinded crossover study.. We enrolled 106 adults with type 2 diabetes and hypertension and 100 received intervention. Subjects were randomized to one of 3 blood pressure arms: ramipril, valsartan, or amlodipine for a total of 15 weeks and received 3 one-week crossover therapies in random order: placebo + placebo, sitagliptin + placebo, and sitagliptin + aprepitant separated by 4-week washout.. We found that DPP4 inhibition increased norepinephrine during ramipril but did not increase blood pressure. Aprepitant, a NK1 (substance P) receptor blocker, lowered standing heart rate during renin-angiotensin-aldosterone system blockade with ramipril or valsartan.. Increased catecholamines during concurrent ACE and DPP4 inhibition may contribute to cardiovascular complications in patients predisposed to heart failure.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Aprepitant; Blood Pressure; Cardiovascular Agents; Catecholamines; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Humans; Norepinephrine; Ramipril; Renin-Angiotensin System; Sitagliptin Phosphate; Valsartan

Dapagliflozin was shown to reduce the cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes. However, data are limited on the relationship of the effect and safety with the concurrent use of CV medications in patients with type 2 diabetes.. To assess whether the cardiorenal efficacy and safety of dapagliflozin were consistent with and without background use of CV medications commonly used for heart failure (HF) and kidney disease in patients with type 2 diabetes.. This study is a prespecified secondary analysis of DECLARE-TIMI 58, which was a randomized trial of dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and either atherosclerotic disease or multiple risk factors for CV disease. Patients were stratified by baseline use of the following CV medications: angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARBs), β-blockers, diuretics, and mineralocorticoid receptor antagonists (MRAs). The study was conducted from May 2013 to September 2018, and data were evaluated for this analysis from February 2021 to May 2022.. Dapagliflozin or placebo.. The outcomes of interest were the composite of CV death or hospitalization for HF (HHF), HHF alone, and a kidney-specific composite outcome (persistent ≥40% decrease in estimated glomerular filtration rate [eGFR], end-stage kidney disease, or kidney-related death).. Among 17 160 patients, 13 950 (81%) used ACEI/ARBs, 9030 (53%) used β-blockers, 6205 (36%) used diuretics, and 762 (4%) used MRAs at baseline. Changes in blood pressure and eGFR at 48 months with dapagliflozin compared with placebo did not differ regardless of concurrent therapy (placebo-corrected change, -1.6 mm Hg [95% CI, -4.2 to 1.0] to -2.6 mm Hg [95% CI, -3.3 to -2.9]; P > .05 for each interaction). Dapagliflozin consistently reduced the risk of CV death/HHF, HHF alone, and the kidney-specific composite outcome regardless of background use of selected medications (hazard ratio [HR] range: HR, 0.50; 95% CI, 0.39-0.63; to HR, 0.82; 95% CI, 0.72-0.95; P > .05 for each interaction). In patients receiving ACEI/ARBs + β-blockers + diuretics (n = 4243), dapagliflozin reduced the risk of CV death/HHF and of the kidney-specific outcome by 24% (HR, 0.76; 95% CI, 0.62-0.93) and 38% (HR, 0.62; 95% CI, 0.44-0.87), respectively. There were no significant treatment interactions with the concomitant CV medications for adverse events of volume depletion, acute kidney injury, or hyperkalemia (range: HR, 0.12; 95% CI, 0.02-0.99; to HR, 1.04; 95% CI, 0.83-1.32; P > .05 for each interaction).. Dapagliflozin consistently reduced the risk of CV and kidney outcomes irrespective of background use of various CV medications without any treatment interaction for key safety events. These data show the clinical benefit and safety of dapagliflozin in a broad range of patients with type 2 diabetes regardless of background therapy.. ClinicalTrials.gov Identifier: NCT01730534.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzhydryl Compounds; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diuretics; Glucosides; Heart Failure; Humans

Patients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known.. The phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied.. Patients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38-0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27-0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53-0.98], P = 0.04).. Apabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Patient Admission; Patient Readmission; Quinazolinones; Time Factors; Treatment Outcome

EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials.. EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists.. When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Biomarkers; Cardiovascular Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.. In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.. Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.. Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).

Topics: Aged; Benzhydryl Compounds; Cardiovascular Agents; Cardiovascular Diseases; Combined Modality Therapy; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left

The aim of this study was to examine the relationship of albuminuria to cardiovascular disease outcomes in diabetic patients undergoing treatment for stable coronary artery disease.. We analyzed data from 2176 participants of the Bypass Angioplasty Revascularization Investigation in type-2 diabetes (BARI-2D) trial, a randomized clinical trial comparing Percutaneous coronary intervention/Coronary artery bypass grafting (PCI/CABG) to medical therapy for people with diabetes. The population was stratified by baseline spot urine albumin-creatinine ratio (uACR) into normal (uACR <10 mg/g), mildly (uACR ≥10 mg/g < 30 mg/g), moderately (uACR ≥30 mg/g < 300 mg/g) and severely increased (uACR ≥300 mg/g) groups, and outcomes compared between groups. Death, myocardial infarction (MI) and/or stroke were experienced by 489 patients at a mean follow-up of 4.3 ± 1.5 years. Compared with normal uACR, mildly increased uACR was associated with a 1.4 times (P = 0.042) increase in all-cause mortality. Additionally, nonwhites with type-II diabetes and stable coronary artery disease who had mildly increased albuminuria had a Hazard ratio (HR) of 3.3 times (P = 0.028) for cardiovascular death, 3.1 times for (P = 0.002) all-cause mortality, and two times for (P = 0.015) MI during follow-up.. Mildly increased albuminuria is a significant predictor of all-cause mortality in those with type-II diabetes mellitus and stable coronary artery disease, as well as for cardiovascular events those who are nonwhites.

Topics: Aged; Albuminuria; Brazil; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Europe; Female; Humans; Male; Middle Aged; Myocardial Infarction; North America; Percutaneous Coronary Intervention; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome

In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown.. In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality.. Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45-0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76-1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66-1.17]) and those without HF (HR, 0.88 [95% CI, 0.74-1.03]). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43-0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62-0.92]), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34-0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89-1.31]; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40-0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86-1.10]; P for interaction=0.016).. In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.

Topics: Aged; Benzhydryl Compounds; Cardiovascular Agents; Cause of Death; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Heart Failure; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

The importance of glycosylated hemoglobin A1c (A1c) control as part of comprehensive risk factor management in patients with stable ischemic heart disease (SIHD) and diabetes mellitus (DM) is controversial.. The purpose of this study was to determine whether a greater number of controlled risk factors at 1 year, including A1c, affects survival in patients with DM and SIHD.. Of 690 patients with DM followed in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 592 (86%) had complete ascertainment of 7 pre-specified risk factors at baseline and after 1 year: systolic blood pressure, low-density lipoprotein cholesterol, nonsmoking, physical activity, diet adherence, body mass index, and A1c. The primary outcome measure was mortality beyond 1 year after randomization.. During a mean follow-up of 7.0 ± 4.2 years beyond 1 year after randomization, 186 subjects died (31.4% overall, 4.5%/year). The greater the number of risk factors controlled at 1 year, the higher the probability of survival (unadjusted log rank p = 0.002). Compared with 0 to 1 controlled risk factors, attaining 3 to 7 goals predicted progressively lower mortality (hazard ratio for control of 6 or 7 risk factors was 0.13; 95% confidence interval: 0.05 to 0.40). Importantly, only 10.3% of subjects achieved control of 6 or 7 risk factors. In multivariate analysis, the strongest predictors of improved survival were no smoking, regular physical activity, dietary adherence, and A1c <7%.. In this high-risk subset of SIHD patients with DM, the number of controlled risk factors, particularly lifestyle behaviors and A1c, were associated with improved survival. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).

Topics: Aged; Cardiovascular Agents; Cause of Death; Comorbidity; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Life Style; Male; Middle Aged; Myocardial Ischemia; Prognosis; Proportional Hazards Models; Risk Assessment; Survival Analysis

The development of microvascular complications in diabetes is a complex process in which endothelial dysfunction is important. Emerging evidence suggests that arginase is a key mediator of endothelial dysfunction in type 2 diabetes mellitus by reciprocally regulating nitric oxide bioavailability. The aim of this prospective intervention study was to test the hypothesis that arginase activity is increased and that arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction.. Microvascular endothelium-dependent and -independent dilatation was determined in patients with type 2 diabetes (n = 12) and healthy age-matched control subjects (n = 12) with laser Doppler flowmetry during iontophoretic application of acetylcholine and sodium nitroprusside, respectively, before and after administration of the arginase inhibitor N. Arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction. Arginase inhibition may represent a novel therapeutic strategy to improve microvascular endothelial function in patients with type 2 diabetes.

Topics: Acetylcholine; Aged; Arginase; Arginine; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Laser-Doppler Flowmetry; Male; Microvessels; Middle Aged; Nitroprusside; Ornithine; Peripheral Vascular Diseases; Severity of Illness Index; Vascular Resistance; Vasodilation; Vasodilator Agents

Different classes of glucose-lowering medications have been associated with varying risks of myocardial infarction and cardiovascular death, but their effect on angina is unknown. Therefore, we sought to determine the association of different glucose-lowering medication classes with angina frequency and nitroglycerin (NTG) use.. We performed a secondary, observational analysis of the TERISA multinational trial, which evaluated the antianginal effect of ranolazine versus placebo in patients with type 2 diabetes mellitus, documented coronary disease, and a 3-month history of stable angina. Patients recorded angina and NTG use in a daily dairy for 3 weeks prior to randomization, to establish their baseline angina burden for the trial. We then examined the association of different glucose-lowering medication classes with baseline angina and NTG use using multivariable linear regression.. Among 952 patients enrolled, 494 were taking metformin, 504 taking a sulfonylurea, 186 taking insulin, 29 taking DPP-4 inhibitors, 22 taking other glucose-lowering medications, and 68 were diet-controlled only. After adjustment for demographic and clinical factors, patients taking versus not taking sulfonylureas had 1.02 more episodes of angina and used 0.93 more doses of NTG per week (P = .002 and .011, respectively). The weekly angina burden or NTG use was not different for those taking versus not taking metformin (P > .7 for both). Patients taking versus not taking insulin had 0.83 more episodes of angina and used 1.40 more NTG doses per week, increases evident only in those taking insulin without concomitant metformin (Pinteraction < .05 for both).. Different classes of glucose-lowering medications were associated with varying angina burden in patients with type 2 diabetes mellitus and stable coronary disease. Patients taking sulfonylureas or insulin had more angina and used more NTG, while metformin was not associated with angina burden. Given the increasing prevalence of glucose abnormalities in patients with coronary disease, a better understanding of the relationship between glucose-lowering medications and angina is needed.

Topics: Aged; Angina, Stable; Blood Glucose; Cardiovascular Agents; Chronic Disease; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Ranolazine; Retrospective Studies

Ranolazine and metformin may be frequently co-administered in subjects with chronic angina and co-morbid type 2 diabetes mellitus (T2DM). The potential for a drug-drug interaction was explored in two phase 1 clinical studies in subjects with T2DM to evaluate the pharmacokinetics and safety of metformin 1000 mg BID when administered with ranolazine 1000 mg BID (Study 1, N = 28) or ranolazine 500 mg BID (Study 2, N = 25) as compared to metformin alone. Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively. Co-administration of ranolazine and metformin was well tolerated in these T2DM subjects, with no serious adverse events or drug-related adverse events leading to discontinuation. The most common adverse events were nausea, diarrhea, and dizziness. These findings are consistent with a dose-related interaction between ranolazine and metformin, and suggest that a dose adjustment of metformin may not be required with ranolazine 500 mg BID; whereas, the metformin dose should not exceed 1700 mg of total daily dose when using ranolazine 1000 mg BID.

Topics: Adult; Aged; Angina Pectoris; Animals; Area Under Curve; Cardiovascular Agents; CHO Cells; Chronic Disease; Comorbidity; Cricetulus; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Interactions; Female; Humans; Hypoglycemic Agents; Male; Metabolic Clearance Rate; Metformin; Middle Aged; Organic Cation Transporter 2; Polypharmacy; Ranolazine; United States

In this prospective study, we examined the effect of atorvastatin treatment on baroreflex sensitivity (BRS) in subjects with type 2 diabetes. A total of 79 patients with type 2 diabetes with dyslipidaemia were recruited. A total of 46 subjects were enrolled to atorvastatin 10 mg daily and low-fat diet and 33 patients to low-fat diet only. BRS was assessed non-invasively using the sequence method at baseline, 3, 6 and 12 months. Treatment with atorvastatin increased BRS after 12 months (from 6.46 ± 2.79 ms/mmHg to 8.05 ± 4.28 ms/mmHg, p = 0.03), while no effect was seen with low-fat diet. Further sub-analysis according to obesity status showed that BRS increased significantly only in the non-obese group (p = 0.036). A low dose of atorvastatin increased BRS in non-obese subjects with type 2 diabetes and dyslipidaemia after 1-year treatment. This finding emphasizes the beneficial effect of atorvastatin on cardiovascular system, beyond the lipid-lowering effects.

Topics: Aged; Atorvastatin; Baroreflex; Body Mass Index; Cardiovascular Agents; Cardiovascular Diseases; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Diet, Fat-Restricted; Dyslipidemias; Female; Greece; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myalgia; Obesity; Patient Dropouts; Prospective Studies; Pyrroles; Risk Factors

Patients with rapid progression of carotid intima media thickness (CIMT) were shown to have a higher future risk for cardiovascular events.The aim of this study was to investigate the impact of multiple risk factor intervention on CIMT progression and to establish whether new cardiovascular surrogate measurements would allow prediction of CIMT changes.. In this prospective, open, 2-years study, we included 97 patients with type 2 diabetes and at least two insufficiently treated cardiovascular risk factors, i.e. HbA1c > 7.5% (58 mmol/mol); LDL-cholesterol >3.1 mmol/l or blood pressure >140/90 mmHg. Treatment was intensified according to current guidelines over 3 months with the aim to maintain intensification over 2 years.The primary outcome was the change in CIMT after 2 years. We also assessed markers of mechanical and biochemical endothelial function and endothelial progenitor cells before and after 3 months of treatment intensification. For testing differences between before and after multifactorial treatment measurements we used either the paired student's t-test or the Wilcoxon signed-rank test, depending on the distribution of the data. Additional, explorative statistical data analysis was done on CIMT progression building a linear multivariate regression model.. Blood glucose, lipids and blood pressure significantly improved during the first 3 months of intensified treatment, which was sustained over the 2-year study duration. Mean CIMT significantly decreased from baseline to 2 year (0.883 ± 0.120 mm vs. 0.860 ± 0.130 mm; p = 0.021). None of the investigated surrogate measures, however, was able to predict changes in IMT early after treatment intensification.. Intensification of risk factor intervention in type 2 diabetes results in CIMT regression over a period of 2 years. None of the biomarkers used including endothelial function parameters or endothelial progenitor cells turned out to be useful to predict CIMT changes.. Clinical Trial Registration - Unique identifier: NCT00660790.

Topics: Aged; Cardiovascular Agents; Carotid Artery Diseases; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Disease Progression; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Prospective Studies; Risk Factors

This study evaluated differences in outcome among women and men enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial.. Women and men with coronary artery disease have different clinical presentations and outcomes that might be due to differences in management.. We compared baseline variables, study interventions, and outcomes between women and men enrolled in the BARI 2D trial and randomized to aggressive medical therapy alone or aggressive medical therapy with prompt revascularization.. At enrollment, women were more likely than men to have angina (67% vs. 58%, p < 0.01) despite less disease on angiography (Myocardial Jeopardy Index 41 ± 24 vs. 46 ± 24, p < 0.01; number of significant lesions 2.3 ± 1.7 vs. 2.8 ± 1.8, p < 0.01). Over 5 years, no sex differences were observed in BARI 2D study outcomes after adjustment for difference in baseline variables (death/myocardial infarction/cerebrovascular accident: hazard ratio: 1.11, 99% confidence interval [CI]: 0.85 to 1.44). However, women reported more angina than men (adjusted odds ratio: 1.51, 99% CI: 1.21 to 1.89, p < 0.0001) and had lower scores for the Duke Activity Status Index (adjusted beta coefficient: -1.58, 99% CI: -2.84 to -0.32, p < 0.01).. There were no sex differences in death, myocardial infarction, or cerebrovascular accident among patients enrolled in the BARI 2D trial. However, compared with men, women had more symptoms and less anatomic disease at baseline, with persistence of higher angina rates and lower DASI scores after 5 years of medical therapy with or without prompt revascularization. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Diet; Diuretics; Exercise; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Prevalence; Quality of Life; Risk Reduction Behavior; Severity of Illness Index; Sex Distribution; Sex Factors; Smoking Cessation; Social Support; Treatment Outcome

This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD).. Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing.. We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment.. The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up.. A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cholesterol, LDL; Comorbidity; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus, Type 2; Effect Modifier, Epidemiologic; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Monitoring, Physiologic; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Risk Factors; Risk Reduction Behavior; Secondary Prevention; Smoking Cessation

The DIABETES (DIABETes and sirolimus-Eluting Stent) trial is a prospective, multicentre, randomised, controlled trial aimed at demonstrating the efficacy of sirolimus-eluting stent (SES) as compared to bare metal stent (BMS) implantation in diabetic patients. The aim of the present analysis was to assess the five-year clinical follow-up of the patients included in this trial.. One hundred and sixty patients (222 lesions) were included: 80 patients were randomised to SES and 80 patients to BMS. Patients were eligible for the study if they were identified as non-insulin-dependent diabetics (NIDDM) or insulin-dependent diabetics (IDDM), with significant native coronary stenoses in ≥1 vessel. There was a sub-randomisation according to diabetes status. Clinical follow-up was extended up to five years. Five-year clinical follow-up was obtained in 96.2%. Overall, MACE at five years was significantly lower in the SES group as compared with the BMS arm, mainly due to a significant reduction in TLR. There were no significant differences in cardiac death or myocardial infarction (MI). This was also observed in both prespecified subgroups IDDM and NIDDM. In the SES group, the incidence density of definite/probable stent thrombosis was 0.53 per 100 person-years, whereas in the BMS group it was 0.8 per 100 person-years. Independent predictors of MACE were: SES implantation (p<0.001), multivessel stent implantation (p=0.04), and creatinine levels (p=0.001).. Five-year follow-up of the DIABETES trial suggests the effect of SES in reducing TLR is similar in both IDDM and NIDDM. No major safety concerns in terms of ST, MI or mortality were observed.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Stenosis; Coronary Thrombosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Spain; Stents; Time Factors; Treatment Outcome

Impaired cerebral vasoreactivity to endothelium-dependent stimuli were described in type 2 diabetes mellitus (T2DM), but the mechanisms underlying that impairment are still unclear. The aim of this study was to investigate the role of cyclooxygenases' metabolites in response to acute hypercapnic stimulus in cerebral vessels, in patients with T2DM.. Vascular responses in the breath-holding test (BHT) were assessed in the absence/presence of a non-selective, reversible-inhibitor of cyclooxygenases, indomethacin (INDO), by functional transcranial Doppler sonography of the middle cerebral artery (N of patients=50; 33 men and 17 women). The functional hemodynamic parameter mean flow velocity (MFV) was assessed at rest, before and 90min after 100mg of INDO, and during the BHT. Breath holding index (BHI) [(MFV at the end of BHT minus MFV at rest)/MFV at rest)×100/s of breath-holding] was calculated after BHT performed before and 90min after INDO.. MFV at rest significantly decreased after INDO administration compared with a control condition before INDO (at rest before INDO from 49.36±15.09 to 36.72±8.45 after INDO, p<0.001) However, overall cerebral vessel vasoreactivity to hypercapnia, evaluated with BHI, was significantly improved after INDO administration compared with the BHI before INDO administration (from 0.68±0.4 to 1.27±0.42, p<0.001).. The improvement in cerebral vasoreactivity in response to BHT after INDO administration suggests that the production of a vasoconstrictor metabolite of cyclooxygenase in diabetic patients was reduced by indomethacin consumption.

Topics: Adolescent; Adult; Aged; Brain; Cardiovascular Agents; Cerebrovascular Circulation; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Hemodynamics; Humans; Hypercapnia; Indomethacin; Male; Middle Aged; Middle Cerebral Artery; Prognosis; Prospective Studies; Ultrasonography, Doppler, Transcranial; Young Adult

Development of a cardiomyopathy in diabetes mellitus is independent of traditional risk factors, with no clinical trials targeting specific therapeutic interventions. Myocardial fibrosis is one of the key mechanisms and aldosterone is a key mediator of myocardial fibrosis. We propose that aldosterone antagonism will improve cardiac function. We aim to evaluate the efficacy of selective aldosterone receptor antagonism with eplerenone added to optimal medical treatment in improving cardiac structure and function in diabetic cardiomyopathy. We will randomize 130 patients with type 2 diabetes mellitus, stable metabolic control and impaired left ventricular (LV) systolic or diastolic function, to either eplerenone (target dose 50mg) or matching placebo, in addition to optimal medical therapy for 12 months. The primary endpoints are changes in LV systolic and diastolic function, measured by echocardiographic 2-dimensional speckle tracking strain and strain rate and tissue Doppler imaging. The secondary endpoints include changes in echocardiographic markers and plasma biomarkers of collagen turnover; left atrial dimensions and function, incidence of atrial fibrillation and changes in exercise capacity and dyspnea score. The present study will assess whether specific aldosterone antagonism with eplerenone in addition to standard therapy will prevent progression or reverse cardiac dysfunction in diabetic cardiomyopathy using sensitive, robust and quantifiable echocardiographic measures that allow early detection of change. The study may offer a new direction in the management of this condition.. ACTRN12610001063000.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Clinical Protocols; Collagen; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diastole; Double-Blind Method; Drug Therapy, Combination; Echocardiography, Doppler; Eplerenone; Fibrosis; Humans; Mineralocorticoid Receptor Antagonists; Myocardium; New South Wales; Prospective Studies; Recovery of Function; Research Design; Spironolactone; Systole; Time Factors; Treatment Outcome; Ventricular Function, Left

There are few data that demonstrate a significant effect of aspirin therapy for diabetic patients. To clarify the effect of the primary prevention of aspirin therapy in diabetic patients, the relationship between blood pressure (BP) and the incidence of atherosclerotic events was investigated in participants in the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial.. We divided the JPAD participants according to their systolic (SBP) and diastolic (DBP) BPs at enrollment (SBP ≥140 mmHg and/or DBP ≥90 mmHg: unattained group, SBP <140 mmHg and DBP <90 mmHg: attained group). The incidence of the primary atherosclerotic events, especially cerebrovascular events, was higher in the unattained group than in the attained group. The incidence of cerebrovascular events was higher in the unattained group than in the attained group in patients without aspirin therapy; however, the incidence of cerebrovascular events in the unattained group was as low as the incidence in the attained group in patients undergoing aspirin therapy. Cox proportional hazards analysis revealed that BP level was an independent predictor for cerebrovascular events in diabetic patients.. Aspirin therapy may reduce cerebrovascular events in diabetic patients with higher BP. Aspirin therapy could be an additional strategy as primary prevention for diabetic patients with higher BP.

Topics: Aged; Aspirin; Blood Pressure; Cardiovascular Agents; Cerebrovascular Disorders; Chi-Square Distribution; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypertension; Incidence; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Primary Prevention; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Treatment Outcome

The gap between the level of care recommended by evidence-based clinical practice guidelines and the actual care delivered to patients in practice has been well established. The Canadian Diabetes Association (CDA) created an implementation strategy to improve the implementation of its 2008 guidelines. This study will evaluate the impact of the strategy to improve cardiovascular disease (CVD) screening, prevention and treatment for people with diabetes.. A pragmatic cluster-randomized trial will be conducted to evaluate the CDA's CVD Toolkit. All family physicians in Ontario, Canada were randomly allocated to receive the Toolkit, which includes several printed educational materials targeting CVD screening, prevention and treatment, either in spring 2009 (intervention arm) or in spring 2010 (control arm). Randomization occurred at the level of the practice. Forty family physicians from each arm will be recruited to participate, and the medical records for 20 of their diabetic patients at high risk for CVD will be retrospectively reviewed. Outcome measures will be assessed for each patient between July 2009 and March 2010. The primary outcome will be that the patient is receiving a statin. Secondary outcomes will include 1) the receipt of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, 2) various intermediate measures (A1c, blood pressure, LDL-cholesterol, total-/HDL-cholesterol ratio, body mass index and waist circumference), and 3) clinical inertia (the failure to change therapy in response to an abnormal A1c, blood pressure or cholesterol reading). The analysis will be carried out using multilevel hierarchical logistic regression models to account for the clustered nature of the data. The group assignment will be a physician-level variable. In addition, a process evaluation study with six focus groups of family physicians will assess the acceptability of the CDA's Toolkit and will explore factors contributing to any change or lack of change in behaviour, from the perspectives of family physicians.. Printed educational materials for physicians have been shown to exert small-to-moderate changes in patient care. The CDA's CVD Toolkit is an example of a practice guideline implementation strategy that can be disseminated to a wide audience relatively inexpensively, and so demonstrating its effectiveness at improving diabetes care could have important consequences for guideline developers, policy makers and clinicians.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Attitude of Health Personnel; Cardiovascular Agents; Cardiovascular Diseases; Cluster Analysis; Decision Support Techniques; Diabetes Mellitus, Type 2; Family Practice; Guideline Adherence; Health Knowledge, Attitudes, Practice; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Logistic Models; Mass Screening; Ontario; Pamphlets; Practice Guidelines as Topic; Predictive Value of Tests; Research Design; Treatment Outcome

To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation.. Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action.. Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Biomarkers; Blood Glucose; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Chemokine CCL2; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug-Eluting Stents; Female; Glycated Hemoglobin; Humans; Hyperplasia; Hypoglycemic Agents; Inflammation Mediators; Insulin; Interleukin-6; Killer Cells, Natural; Lipids; Male; Middle Aged; Myocytes, Smooth Muscle; Pioglitazone; Prospective Studies; Prosthesis Design; Receptors, CCR2; Republic of Korea; Single-Blind Method; Sirolimus; Thiazolidinediones; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Diminished levels of L-arginine and endothelial nitric oxide synthase (eNOS) uncoupling through deficiency of tetrahydrobiopterin (BH(4)) may contribute to endothelial dysfunction. We investigated the effect of L-arginine and BH(4) administration on ischemia-reperfusion (I/R)-induced endothelial dysfunction in patients with type 2 diabetes and coronary artery disease (CAD). Forearm blood flow was measured by venous occlusion plethysmography in 12 patients with type 2 diabetes or impaired glucose tolerance and CAD. Forearm ischemia was induced for 20 min, followed by 60 min of reperfusion. The patients received a 15 min intra-brachial infusion of L-arginine (20 mg/min) and BH(4) (500 microg/min) or 0.9% saline starting at 15 min of ischemia on two separate study occasions. Compared with pre-ischemia the endothelium-dependent vasodilatation (EDV) induced by acetylcholine was significantly reduced at 15 and 30 min of reperfusion when saline was infused (P<0.001), but not following L-arginine and BH(4) infusion. EDV was also significantly less reduced at 15 and 30 min of reperfusion following L-arginine and BH(4) infusion, compared to saline infusion (P<0.02). Endothelium-independent vasodilatation (EIDV) induced by nitroprusside was unaffected by I/R. Venous total biopterin levels in the infused arm increased from 37+/-7 at baseline to 6644+/-1240 nmol/l during infusion of L-arginine and BH(4) (P<0.0001), whereas there was no difference in biopterin levels during saline infusion. In conclusion L-arginine and BH(4) supplementation reduces I/R-induced endothelial dysfunction, a finding which may represent a novel treatment strategy to limit I/R injury in patients with type 2 diabetes and CAD.

Topics: Aged; Arginine; Biopterins; Blood Flow Velocity; Cardiovascular Agents; Coronary Artery Disease; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endothelium, Vascular; Female; Forearm; Humans; Infusions, Intra-Arterial; Male; Regional Blood Flow; Reperfusion Injury; Treatment Outcome; Vasodilation; Vasodilator Agents

People with non-diabetic hyperglycaemia might be at risk of lacking adequate control for cardiovascular risk factors. Our aim was to determine the extent of health care utilization and provision in primary care and to evaluate the risk of cardiovascular disease in persons with an elevated risk score in a stepwise diabetes screening programme.. A total of 56,978 non-diabetic patients, aged 50-70 years, from 79 practices in the Netherlands were invited to participate in a screening programme starting with a questionnaire. Those with an elevated score, underwent further glucose testing. Screened participants with type 2 diabetes (n = 64), impaired glucose tolerance (IGT) (n = 62), impaired fasting glucose (IFG) (n = 86), and normal glucose tolerance (NGT) (n = 142) were compared after three years regarding use of medication, care provider encounters and occurrence of CVD.. In all glucose regulation categories cardiovascular medication was prescribed more frequently during follow-up with the strongest increase in diabetic patients. Number of practice visits was higher in diabetic patients compared to those in the other categories. Glucose, lipids, and blood pressure were measured most frequently in diabetic patients. Numbers of cardiovascular events in participants with NGT, IFG, IGT and diabetes were 16.7, 32.6, 17.3 and 15.7 per 1,000 person-years (non significant), respectively.. After three years of follow-up, screened non-diabetic participants with an elevated risk score had cardiovascular event rates comparable with diabetic patients. Screened non-diabetic persons are at risk of lacking optimal control for cardiovascular risk factors while screen-detected diabetic patients were controlled adequately.

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Drug Utilization; Female; Follow-Up Studies; Humans; Hyperglycemia; Hypolipidemic Agents; Incidence; Male; Mass Screening; Middle Aged; Netherlands; Practice Patterns, Physicians'; Risk Assessment; Treatment Outcome

To clarify mildronate effects on oxidant stress and tissue oxygen in combined treatment of peripheral (sensomotor) neuropathy in patients with type 2 diabetes mellitus (DM).. An open randomized trial investigated 70 matched patients with type 2 DM and sensomotor neuropathy. They were randomized into two groups. The study group received basic anti-diabetic treatment, alpha-lipoic acid and mildronate for 3 months. Patients of the control group received the same treatment but mildronate.. Mildronate administration improved clinical condition of the study group patients vs controls by neuropathy and symptoms count scales, electrophysiological properties of the nerve fibers, optimization of oxygen tissue balance, reduced production of lipid peroxidation products and activated enzymes of antioxidant defense.. It is recommended to add 1 g/day mildronate to standard schemes of treatment for diabetes and sensomotor neuropathy.

Topics: Aged; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Fasting; Female; Humans; Male; Methylhydrazines; Middle Aged; Oxidative Stress

The effectiveness of propionyl-L-carnitine (PLC) monotherapy regimen alone or in association with pulsed muscular compression was compared to the physical therapy by itself against obliterant arteriopathy Leriche Fontaine stage II. PLC is involved in cellular metabolism and is transformed into two active substances, free L-carnitine and propionyl-coenzyme A in the mitochondria, which take part in fatty acid transfer and in the citric acid cycle, respectively.. Forty-two patients with arterial disease were selected (22 males and 20 females; mean age: 62+/-8 years; 21 type 2 diabetic [DB] and 21 non-DB [NDB]). At enrollment all patients completed a symptoms questionnaire enabling both clinical and social evaluation of the impact of the arteriopathy on the quality of life. Then, patients had: routine blood samples, echo duplex scan; evaluation of the ankle/arm (Winsor) index; impedance plethysmography (Rheoscreen) to measure the crest time (CT), index of the pathological changes due to the sclerosis on the vascular wall, and measurement of walking distance by means of treadmill test. Patients were randomized in three groups, each of them composed by 14 patients (7 DB and 7 NDB): the first group was submitted to infusional PLC therapy at a dosage of 4 fl (total: 1,200 mg PLC) in 250 cc of physiological solution for 5 days a week for 4 weeks; the second group was treated with PLC in association with pulsed muscular compression therapy by Vascupump (5 sessions a week for 4 weeks); the third group was submitted only to Vascupump.. The efficacy of both PLC and Vascupump in the treatment of the peripheral vasculopathies was confirmed. From a subjective point of view, patients referred benefits both in clinical terms, i.e. increased walking distance (average increaseaegroup I: DB 102%, NDB 118%; group II: DB 94%, NDB 193%; group III: DB 33%, NDB 67%) and of decreased intensity of the calf pain from the quality of life questionnaire (21.5 to 10.7). The instrumental parameters showed a trend towards normality, i.e decrease in CT and an increase of the Winsor index, indicators of increased peripheral blood circulation.. Combined pharmaco- and physical therapy was most efficient treatment regime and best results were seen in NDB compared to the DB patients.

Topics: Aged; Arterial Occlusive Diseases; Cardiovascular Agents; Carnitine; Combined Modality Therapy; Diabetes Mellitus, Type 2; Female; Humans; Infusions, Intravenous; Intermittent Claudication; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Quality of Life; Recovery of Function; Severity of Illness Index; Time Factors; Treatment Outcome; Walking

Diabetes is an important risk factor for stroke. We conducted analyses in patients who had entered the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) with a history of stroke or without stroke.. The prospective, double-blind PROactive (mean duration, 34.5 months) randomized 5238 patients with type 2 diabetes and a history of macrovascular disease to pioglitazone (titrated to 45 mg) or placebo, in addition to current diabetes and cardiovascular medications. Cardiovascular end-point events were independently adjudicated. This analysis evaluated the risk of stroke and other cardiovascular outcomes in patients with (n=984) and without (n=4254) prior stroke.. In patients with previous stroke (n=486 in the pioglitazone group and n=498 in the placebo group), there was a trend of benefit with pioglitazone for the primary end point of all-cause death, nonfatal myocardial infarction, acute coronary syndrome, and cardiac intervention (including coronary artery bypass graft or percutaneous coronary intervention), stroke, major leg amputation, or bypass surgery or leg revascularization (hazard ratio[HR]=0.78, event rate=20.2% pioglitazone vs 25.3% placebo; 95% CI=0.60-1.02; P=0.0670) and for the main secondary end point of all-cause death, nonfatal myocardial infarction, or nonfatal stroke (HR=0.78, event rate=15.6% pioglitazone vs 19.7% placebo; 95% CI=0.58-1.06; P=0.1095). Pioglitazone reduced fatal or nonfatal stroke (HR=0.53, event rate=5.6% pioglitazone vs 10.2% placebo; 95% CI=0.34-0.85; P=0.0085) and cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR=0.72, event rate=13.0% pioglitazone vs 17.7% placebo; 95% CI=0.52-1.00; P=0.0467). Higher event rates were observed in patients with prior stroke compared with those without prior stroke. In patients without prior stroke, no treatment effect was observed for a first stroke.. In a subgroup analysis from PROactive, pioglitazone reduced the risk of recurrent stroke significantly in high-risk patients with type 2 diabetes.

Topics: Adult; Aged; Cardiovascular Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pioglitazone; Prospective Studies; Stroke; Thiazolidinediones; Vascular Diseases

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Interactions; Enalapril; Female; Humans; Male; Middle Aged; Proteinuria

The aim of this open randomized study was to compare the clinical efficacy of mildronate in complex therapy of chronic heart failure (CHF) and basic therapy in patients with CHF and type 2 diabetes mellitus (DM2) during the postinfarction period. The subjects were 60 II to III NYHA CHF patients aged 43 to 70 yo also suffering from DM2; the patients were observed during the early postinfarction period (weeks 3 to 4 from the onset of myocardial infarction). The patients were randomized into two groups: the 30 patients of the main group received basic therapy plus mildronate in a dose of 1 g a day, while the 30 patients of the control group received basic therapy only. The observation lasted 16 weeks. The following parameters were measured dynamically: NYHA functional class (FC), 6-min walking test results, left ventricular ejection fraction (LVEF), LV isovolumic relaxation time, microalbuminuria, glomerular filtration speed (GFS), functional renal reserve (FRR), carbohydrate and lipid exchange, cardiac rhythm variability parameters, and the quality of life. The use of mildronate in addition to basic therapy was associated with a more evident decrease in CHF FC, (by 19% vs. 14%), increase in 6-min walking test distance (25.5% vs. 18%), as well as a tendency to normalization of diastolic heart function and an increase in LVEF (by 12% vs. 7%). By comparison with basic therapy, the patients in the mildronate group displayed a statistically significant improvement in renal functioning: GFS increased by 20% vs. 2% (p < 0.05), the proportion of patients with an exhausted FRR decreased (p < 0.05), the average level of MAU decreased significantly (24% vs. 9%, p < 0.05). In the main group, a significant decrease in blood triglyceride level (by 33%, p < 0.05) and total cholesterol level (by 28%, p < 0.1) was noted. A hypoglycemizing ability of mildronate was noted. The use of mildronate in the basic therapy favors the normalization of vegetative homeostasis and improves the quality of life.

Topics: Cardiovascular Agents; Chronic Disease; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Methylhydrazines; Middle Aged; Myocardial Infarction; Prospective Studies

Thiazolidinediones have been shown to have an antiproliferative vascular effect in experimental models. We sought to study the effect of rosiglitazone on in-stent restenosis in patients with established type 2 diabetes.. Patients with treated type 2 diabetes (mean duration 5.5 +/- 7.5 years) referred for coronary stenting were randomized in a double-blind fashion to receive oral rosiglitazone or placebo for 6 months. Quantitative coronary angiography and intravascular ultrasound data were obtained at baseline and follow-up. Plasma plasminogen activator inhibitor-1 levels were prospectively measured.. Sixteen patients were enrolled. There were no significant differences in follow-up in-stent luminal diameter stenosis measured by quantitative coronary angiography or in-stent luminal area stenosis and neointimal volume index obtained by intravascular ultrasound, nor were there any differences in plasma plasminogen activator inhibitor-1 levels after long-term use despite improvement in diabetes control and insulin sensitivity.. Rosiglitazone, given at the time of stent implantation in treated diabetics, did not reduce in-stent restenosis in this small series. The vascular biological effects of this agent await further clarification in humans and evaluation in larger clinical trials.

Topics: Administration, Oral; Adult; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Rosiglitazone; Stents; Thiazolidinediones

There are no prospective trial data on long-term outcomes in 80-year-old patients with chronic angina with regard to antiischemic therapy.. To assess long-term survival and quality of life (QoL) in patients from the Trial of Invasive versus Medical Therapy in the Elderly (TIME), all 276 1-year survivors (of a total 301 patients) were contacted after a median of 3.1 years (range, 1.1 to 5.9 years). At baseline, patients were 80+/-4 years old, 42% were women, and they were designated as being in angina class 3.2+/-0.7, despite their taking 2.5+/-0.7 antiischemic drugs. Patients were randomized to an invasive (n=153) or an optimized medical (n=148) strategy. Survival of invasive-strategy versus medical-strategy patients was 91.5% versus 95.9% after 6 months, 89.5% versus 93.9% after 1 year, and 70.6% versus 73.0% after 4.1 years (P=NS). Mortality was independently increased in patients >or=80 years of age, with prior heart failure, ejection fraction or=2 comorbidities, and without revascularization within the first year. Revascularization within the first year improved survival in invasive-strategy (P=0.07) and medical-strategy (P<0.001) patients. The early benefit of both treatments in angina relief and QoL was maintained long term, but freedom from major events remained higher in invasive-strategy versus medical-strategy patients (39% versus 20%, P<0.0001).. Long-term survival was similar for patients assigned to invasive and medical treatment. The benefits of both treatments in angina relief and improvement in QoL were maintained, but nonfatal events occurred more frequently in patients assigned to medical treatment. Irrespective of whether patients were catheterized initially or only after drug therapy failure, their survival rates were better if they were revascularized within the first year.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Hospitalization; Humans; Life Tables; Male; Myocardial Revascularization; Prognosis; Proportional Hazards Models; Prospective Studies; Quality of Life; Recurrence; Survival Analysis; Switzerland; Time Factors; Treatment Outcome

We aimed to assess the validity of an announced telephone pill count in people with type 2 diabetes or cardiovascular disease by comparing this method to a home-visit pill count. We also assessed whether a second telephone pill count improved accuracy. People aged ≥35 years using oral type 2 diabetes or cardiovascular disease medication were included. Thirty-four participants completed a telephone pill count followed by a home-visit pill count, and a subsample of this population (n = 11) completed a second telephone pill count. Scatterplots were used for a visual representation of the number of pills counted with both methods, intraclass correlation coefficients for agreement, and Bland-Altman plots for absolute differences and outliers. A total of 203 pill counts were conducted. The study population consisted of 53% men, with a mean age of 69.6 (±9.2) years and an average of 6.1 (±2.8) medication prescriptions per participant. Scatterplots showed that pills counted with both methods were mostly scattered around the y = x equation. Agreement between the first telephone pill count and home-visit pill count was high, with intraclass correlation coefficients of 0.96 (medication count level) and 0.98 (individual level). No learning effects were observed in the subsample (n = 11), the intraclass correlation coefficient for the first telephone pill count was 0.88 versus 0.89 for the second telephone pill count. Bland-Altman plots indicated high agreement between the two methods. An announced telephone pill count is considered a valid alternative for a home-visit pill count in people with type 2 diabetes or cardiovascular disease. A single pill count appears sufficient.

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; HIV Infections; Humans; Male; Medication Adherence; Telephone

It has been argued that persons with severe mental illness (SMI) receive poorer treatment for somatic comorbidities. This study assesses the treatment rates of glucose-lowering and cardiovascular medications among persons with incident type 2 diabetes (T2D) and SMI compared to persons with T2D without SMI. We identified persons ≥30 years old with incident diabetes (HbA1c ≥ 48 mmol/mol and/or glucose ≥ 11.0 mmol/L) from 2001 through 2015 in the Copenhagen Primary Care Laboratory (CopLab) Database. The SMI group included persons with psychotic, affective, or personality disorders within five years preceding the T2D diagnosis. Using a Poisson regression model, we calculated the adjusted rate ratios (aRR) for the redemption of various glucose-lowering and cardiovascular medications up to ten years after T2D diagnosis. We identified 1,316 persons with T2D and SMI and 41,538 persons with T2D but no SMI. Despite similar glycemic control at diagnosis, persons with SMI redeemed a glucose-lowering medication more often than persons without SMI in the period 0.5-2 years after the T2D diagnosis; for example, the aRR was 1.05 (95% CI 1.00-1.11) in the period 1.5-2 years after the T2D diagnosis. This difference was mainly driven by metformin. In contrast, persons with SMI were less often treated with cardiovascular medications during the first 3 years after T2D diagnosis, e.g., in the period 1.5-2 years after T2D diagnosis, the aRR was 0.96 (95% CI 0.92-0.99). For people with SMI in addition to T2D, metformin is more likely to be used in the initial years after T2D diagnosis, while our results suggest potential room for improvement regarding the use of cardiovascular medications.

Topics: Adult; Cardiovascular Agents; Cohort Studies; Diabetes Mellitus, Type 2; Glucose; Humans; Mental Disorders; Metformin; Registries

Topics: Adipokines; Atherosclerosis; Cardiovascular Agents; Carotid Intima-Media Thickness; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Nicotinamide Phosphoribosyltransferase; Plaque, Atherosclerotic; Resistin; Risk Factors

Topics: Benzhydryl Compounds; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors

Although it is known that patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of coronary artery disease (CAD), the actual coronary artery burden of atherosclerotic disease in patients with and without T2DM in a real-world setting and its possible modification by preventative therapies has not been extensively documented.. Merged coronary angiography and hospital discharge data between 2013 and 2019 were obtained for analysis and a random sub-sample of patient charts were reviewed for medication use. Propensity scores were estimated using logistic regression models and used to match patients, looking at the effect of severity of CAD over time in years in an ordinal logistic regression model. A separate propensity score was estimated and used to inverse probability weight the ordinal logistic regression looking at the effect of medication use on CAD severity in patients with and without T2DM.. From 3,016 patients in the coronary angiography database, 1421 with T2DM and 1421 without T2DM were matched on propensity score. T2DM patients had more extensive CAD in 2018 compared to 2013 ((adjusted odds ratio) adjOR: 2.06 95% C.I. 1.38, 2.07), but this risk appeared to be attenuated in 2019. In contrast, there was no effect of time on CAD burden in patients without diabetes. In the sub-sample of 760 patients who underwent a chart review of their medication use, there were 367 (48%) with T2DM. For patients with T2DM 69.8% reported taking statins, 64.0% RAS inhibitors and 64.0% anti-platelet drugs. This was significantly higher than patients without diabetes of whom 46.6% reported taking statins, 49.0% RAS inhibitors and 49.9% anti-platelet drugs. As in the full matched sample, patients with diabetes had more extensive CAD (adjOR: 1.32 95% CI: 1.01, 1.74). However, after adjustment for the use of RAS inhibitors, statins and anticoagulants there was no difference in extent of CAD between patients with and without diabetes (adjOR: 1.14 95% CI: 0.85, 1.53).. Although patients with diabetes have a greater extent of CAD in comparison to those without T2DM, preventative medication use decreases this CAD burden significantly.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Databases, Factual; Diabetes Mellitus, Type 2; Drug Utilization; Female; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Male; Middle Aged; Patient Discharge; Platelet Aggregation Inhibitors; Preventive Health Services; Prognosis; Propensity Score; Risk Assessment; Time Factors; Victoria

Diabetes is a serious global health concern which severely affected public health as well as socio-economic growth worldwide. Scutellarin (SCU), a bioactive flavonoid, is known for its efficacious action against a range of ailments including cardiovascular problems. The present study was conducted to find out possible protective effect and its associated mechanisms of SCU on experimental type 2 diabetes-induced cardiac injury.. Type 2 diabetes was induced by treating animals with high fat diet for 4 weeks and a single intraperitoneal dose (35 mg/kg body weight) of streptozotocin and diabetic animals received SCU (10 or 20 mg/kg/day) for 6 weeks.. Scutellarin attenuated type 2 diabetes-induced hyperglycemia, bodyweight loss, hyperlipidaemia, cardiac functional damage with histopathological alterations and fibrosis. Scutellarin treatment to type 2 diabetic mice ameliorated oxidative stress, inflammatory status and apoptosis in heart. Furthermore, the underlying mechanisms for such mitigation of oxidative stress, inflammation and apoptosis in heart involved modulation of Nrf2/Keap1 pathway, TLR4/MyD88/NF-κB mediated inflammatory pathway and intrinsic (mitochondrial) apoptosis pathway, respectively.. The current findings suggest that SCU is effective in protecting type 2 diabetes-induced cardiac injury by attenuating oxidative stress and inflammatory responses and apoptosis, and it is also worth considering the efficacious potential of SCU to treat diabetic cardiomyopathy patients.

Topics: Animals; Apigenin; Apoptosis; Biomarkers; Blood Glucose; Body Weight; Cardiovascular Agents; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Dose-Response Relationship, Drug; Gene Expression Regulation; Glucuronates; Heart Diseases; Inflammation; Lipids; Male; Mice; Oxidative Stress; RNA, Messenger

It is unclear whether demographic characteristics and baseline use of hypoglycemic and cardiovascular drugs significantly affect the efficacy of sodium-glucose transporter 2 (SGLT2) inhibitors on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM).. Randomized trials assessing the efficacy of SGLT2 inhibitors on cardiorenal outcomes in adult patients with T2DM were included in analysis. Three endpoints of interest were major adverse cardiovascular events (MACE), hospitalization for heart failure or cardiovascular death (HHF or CV death), and kidney composite outcome (KCO). We performed random-effects meta-analysis using the aggregate data of hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were done according to 17 factors of interest, including 7 factors related to demographic characteristics and 10 related to baseline use of antihyperglycemic and cardiovascular drugs such as renin-angiotensin system (RAS) inhibitor. We conducted meta-regression analyses to calculate P values for subgroup differences.. Seven trials were included in this meta-analysis. Compared with placebo, SGLT2 inhibitors significantly lowered the risk of MACE (HR 0.90, 95% CI 0.84-0.97) regardless of demographic characteristics and baseline use of insulin, statin or ezetimibe, RAS inhibitor, beta-blocker, and diuretic (Psubgroup from 0.088-0.981); that of HHF or CV death (HR 0.78, 95% CI 0.71-0.85) regardless of demographic characteristics and baseline use of 10 antihyperglycemic and cardiovascular drugs (Psubgroup from 0.147-0.999); and that of KCO (HR 0.63, 95% CI 0.57-0.69) regardless of demographic characteristics and baseline use of statin or ezetimibe, RAS inhibitor, and diuretic (Psubgroup from 0.073-0.918).. The cardiorenal benefits of SGLT2 inhibitors were consistent in a broad population of T2DM patients. The findings of this meta-analysis suggest that SGLT2 inhibitors should be recommended in T2DM patients for the prevention of cardiorenal events, regardless of various demographic characteristics and baseline use of various hypoglycemic and cardiovascular drugs.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diuretics; Ezetimibe; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Meta-Analysis as Topic; Socioeconomic Factors; Sodium-Glucose Transporter 2 Inhibitors; Systematic Reviews as Topic

Background Evidence-based therapies are generally underused for cardiovascular risk reduction; however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Methods and Results Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence-based therapies on, or covering, the index date ±30 days: high-intensity statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence-based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the sample, 24.7% were using a high-intensity statin, 53.1% were using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence-based therapies, and 37.4% were on none of them. Over a 12-month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence-based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients. Conclusions Alarming gaps exist in the contemporary use of evidence-based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.

Topics: Cardiovascular Agents; Comorbidity; Coronary Artery Disease; Diabetes Mellitus, Type 2; Drug Utilization Review; Female; Health Services Misuse; Health Services Needs and Demand; Humans; Hypoglycemic Agents; Male; Middle Aged; Professional Practice Gaps; Referral and Consultation; United States

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were first developed as glucose-lowering therapies for the treatment of diabetes. However, these drugs have now been recognised to prevent worsening heart-failure events, improve health-related quality of life, and reduce mortality in people with heart failure with reduced ejection fraction (HFrEF), including those both with and without diabetes. Despite robust clinical trial data demonstrating favourable outcomes with SGLT2 inhibitors for patients with HFrEF, there is a lack of familiarity with the HF indication for these drugs, which have been the remit of diabetologists to date. In this article we use consensus expert opinion alongside the available evidence and label indication to provide support for the healthcare community treating people with HF regarding positioning of SGLT2 inhibitors within the treatment pathway. By highlighting appropriate prescribing and practical considerations, we hope to encourage greater, and safe, use of SGLT2 inhibitors in this population.

Topics: Cardiovascular Agents; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Heart Failure; Humans; Multicenter Studies as Topic; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Topics: Acute Coronary Syndrome; Adult; Cardiac Catheterization; Cardiovascular Agents; Cardiovascular Diseases; Combined Modality Therapy; Coronavirus Infections; COVID-19; Diabetes Mellitus, Type 2; Diagnosis, Differential; Extracorporeal Membrane Oxygenation; Female; Heart Failure; Heart Transplantation; Humans; Hyperlipidemias; Hypertension; Hypertrophy, Left Ventricular; Immunosuppressive Agents; Intra-Aortic Balloon Pumping; Kidney Transplantation; Male; Middle Aged; Pandemics; Pericarditis; Pneumonia, Viral; Postoperative Complications; Respiration, Artificial; Respiratory Distress Syndrome; Shock, Cardiogenic

In this study, we compared the outcomes of medical therapy (MT) with successful percutaneous coronary intervention (PCI) in chronic total occlusions (CTO) patients with and without type 2 diabetes mellitus.. A total of 2015 patients with CTOs were stratified. Diabetic patients (n = 755, 37.5%) and non-diabetic patients (n = 1260, 62.5%) were subjected to medical therapy or successful CTO-PCI. We performed a propensity score matching (PSM) to balance the baseline characteristics. A comparison of the major adverse cardiac events (MACE) was done to evaluate long-term outcomes.. The median follow-up duration was 2.6 years. Through multivariate analysis, the incidence of MACE was significantly higher among diabetic patients compared to the non-diabetic patients (adjusted hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.09-1.61, p = 0.005). Among the diabetic group, the rate of MACE (adjusted HR 0.61, 95% CI 0.42-0.87, p = 0.006) was significantly lower in the successful CTO-PCI group than in the MT group. Besides, in the non-diabetic group, the prevalence of MACE (adjusted HR 0.85, 95% CI 0.64-1.15, p = 0.294) and cardiac death (adjusted HR 0.94, 95% CI 0.51-1.70, p = 0.825) were comparable between the two groups. Similar results as with the early detection were obtained in propensity-matched diabetic and non-diabetic patients. Notably, there was a significant interaction between diabetic or non-diabetic with the therapeutic strategy on MACE (p for interaction = 0.036).. For treatment of CTO, successful CTO-PCI highly reduces the risk of MACE in diabetic patients when compared with medical therapy. However, this does not apply to non-diabetic patients.

Topics: Aged; Cardiovascular Agents; China; Chronic Disease; Coronary Occlusion; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prevalence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes. Diabetic macroangiopathies, particularly cardiovascular (CV) diseases, seem closely related to diabetes microvascular complications. Aspirin represents the most prescribed compound in CV prevention. Aspirin impact on DR is still object of debate. As it is already recommended among diabetics at high CV risk, aim of this study was to assess a potential relationship between DR and aspirin therapy, in a type 2 diabetes cohort of patients screened through telemedicine.. NO Blind is a cross-sectional, multicenter, observational study, which involved nine Italian outpatient clinics. Primary endpoint was the assessment of the relationship between aspirin treatment and DR. 2068 patients were enrolled in the study, subsequently split in two subpopulations according to either the presence or absence of DR. Overall, 995 subjects were under aspirin therapy. After adjusting for most common potential confounders, age and gender, aspirin reveals significantly associated with DR (OR: 1.72, 95%CI: 1.58-2.89, p = 0.002) and proliferative DR (PDR) (OR: 1.89, 95%CI: 1.24-2.84, p = 0.003). Association comes lost further adjusting for MACEs (OR: 1.28, 95%CI: 0.85-1.42, p = 0.157) (Model 4) and eGFR (OR: 0.93; 95%CI: 0.71-1.22; p = 0.591) (Model 5).. In this multicenter cross-sectional study including a large sample of outpatients with T2DM, we showed that aspirin was not associated with DR after adjustment for several cardio-metabolic confounders. However, as partially confirmed by our findings, and related to the well-known pro-hemorrhagic effect of aspirin, its use should be individually tailored, even by telemedicine tools.

Topics: Aged; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Italy; Male; Middle Aged; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

This study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of coronavirus disease 2019 (COVID-19) in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zhejiang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zhejiang, China, we tested the role of usage of cardiovascular, antidiabetic, and other medications on risk and severity of COVID-19. Analyses were adjusted for age, sex, and body mass index and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk (odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.2-2.3) of manifesting symptoms of COVID-19, whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR = 0.22, 95% CI 0.15-0.30 and OR = 0.30, 95% CI 0.19-0.58, respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR = 6.02, 95% CI 2.3-15.5) and insulin (OR = 2.71, 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR = 0.11, 95% CI 0.1-0.3) among with patients with COVID-19. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity.

Topics: Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Agents; Case-Control Studies; Comorbidity; COVID-19; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypertension; Hypoglycemic Agents; Insulin; Middle Aged; Risk Factors; SARS-CoV-2; Severity of Illness Index

Topics: Cardiovascular Agents; Cardiovascular System; Diabetes Mellitus, Type 2; Humans

Topics: Cardiologists; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Utilization; Female; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Male; Middle Aged; Practice Patterns, Physicians'; United States; United States Food and Drug Administration

With recent changes in the United Kingdom's clinical practice for diabetes mellitus care, contemporary estimates of sex disparities in cardiovascular risk and risk factor management are needed.. In this retrospective cohort study, using the Clinical Practice Research Datalink linked to hospital and death records for people in England, we identified 79 985 patients with incident type 2 diabetes mellitus (T2DM) between 2006 to 2013 matched to 386 547 patients without diabetes mellitus. Sex-stratified Cox models were used to assess cardiovascular risk.. Compared with women without T2DM, women with T2DM had a higher cardiovascular event risk (adjusted hazard ratio, 1.20 [95% confidence interval, 1.12-1.28]) with similar corresponding data in men (hazard ratio, 1.12 [1.06-1.19]), leading to a nonsignificant higher relative risk in women (risk ratio, 1.07 [0.98-1.17]). However, some important sex differences in the management of risk factors were observed. Compared with men with T2DM, women with T2DM were more likely to be obese, hypertensive, and have hypercholesterolemia, but were less likely to be prescribed lipid-lowering medication and angiotensin-converting enzyme inhibitors, especially if they had cardiovascular disease.. Compared with men developing T2DM, women with T2DM do not have a significantly higher relative increase in cardiovascular risk, but ongoing sex disparities in prescribing should prompt heightened efforts to improve the standard and equity of diabetes mellitus care in women and men.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; England; Female; Health Status Disparities; Healthcare Disparities; Humans; Hypercholesterolemia; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; Obesity; Primary Health Care; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors

Topics: Acute Coronary Syndrome; Acute Kidney Injury; Cardiovascular Agents; Clinical Trials as Topic; Contrast Media; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Liraglutide; Male; Practice Guidelines as Topic; Practice Patterns, Physicians'; Risk Reduction Behavior; Treatment Outcome

Topics: Anti-Inflammatory Agents; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Repositioning; Humans; Hypoglycemic Agents; Inflammation Mediators; Metformin; Randomized Controlled Trials as Topic; Signal Transduction

Eicosapentaenoic acid (EPA) is thought to have many beneficial effects, such as anti-atherosclerogenic and anti-inflammatory properties. However, few studies have reported its effects of endothelial dysfunction in diabetes and its direct effects on the aorta. Here, we investigated the effects of EPA treatment on impaired endothelium-dependent relaxation of the aorta in KKAy mice, a model of type 2 diabetes.. Male KKAy mice were fed a high-fat (HF) diet for 8 weeks to induce diabetes, after which they were divided into two groups. One group was fed a HF diet, and the other group was fed a HF diet containing EPA ethyl ester (EPA-E, 10 mg/day) for 4 weeks. Then, the vascular reactivities of prepared aortic rings were measured in an organ bath to determine if EPA-E administration changed vascular function in these diabetic mice. In addition, we examined effect of EPA-E and its metabolites to vascular action using aorta separated from C57BL/6 J mice.. Although EPA-E administration did not change the plasma glucose and insulin levels in diabetic mice, total cholesterol levels were significantly decreased. The aorta extracted from EPA-E untreated diabetic mice showed impaired endothelium-dependent relaxation in response to acetylcholine (ACh). However, EPA-E administration improved the relaxation response to ACh to the control levels observed in non-diabetic C57BL/6 J mice. On the other hand, endothelium-independent relaxation in response to sodium nitroprusside did not significantly differ among these three groups. The enhanced contractile response by phenylephrine in diabetic mice was not altered by the administration of EPA-E. In addition, the direct administration of EPA-E metabolites such as EPA, docosahexaenoic acid, and docosapentaenoic acid led to vasodilation in the aortic rings of C57BL/6 J mice.. These results showed that chronic EPA-E administration prevented the development of endothelial dysfunction in KKAy mice, partly via the direct action of EPA-E metabolites on the aorta.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Blood Glucose; Cardiovascular Agents; Cholesterol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Eicosapentaenoic Acid; Endothelium, Vascular; Insulin; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle Contraction; Nitroprusside; Phenylephrine; Tissue Culture Techniques; Vasodilation

The impact of treatment strategies on outcomes in patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) according to presenting angina has not been rigorously assessed.. We performed a patient-level pooled-analysis (n = 5027) of patients with stable CAD and T2DM randomized to optimal medical therapy [OMT], percutaneous coronary intervention [PCI] + OMT, or coronary artery bypass grafting [CABG] + OMT. Endpoints were death/myocardial infarction (MI)/stroke, post-randomization revascularization (both over 5 years), and angina control at 1 year.. Increasing severity of baseline angina was associated with higher rates of death/MI/stroke (p = 0.009) and increased need for post-randomization revascularization (p = 0.001); after multivariable adjustment, only association with post-randomization revascularization remained significant. Baseline angina severity did not influence the superiority of CABG + OMT to reduce the rate of death/MI/stroke and post-randomization revascularization compared to other strategies. CABG + OMT was superior for angina control at 1 year compared to both PCI + OMT and OMT alone but only in patients with ≥ Class II severity at baseline. Comparisons between PCI + OMT and OMT were neutral except that PCI + OMT was superior to OMT for reducing the rate of post-randomization revascularization irrespective of presenting angina severity.. Presenting angina severity did not influence the superiority of CABG + OMT with respect to 5-year rates of death/MI/stroke and need for post-randomization revascularization. Presenting angina severity minimally influenced relative benefits for angina control at 1 year.

Topics: Aged; Angina Pectoris; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Retreatment; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome

Previously, we had shown that a vasopeptidase inhibitor drug containing ACE and neprilysin inhibitors was an effective treatment for diabetic vascular and neural complications. However, side effects prevented further development. This led to the development of sacubitril/valsartan, a drug containing angiotensin II receptor blocker and neprilysin inhibitor that we hypothesized would be an effective treatment for diabetic peripheral neuropathy. Using early and late intervention protocols (4 and 12 weeks posthyperglycemia, respectively), type 2 diabetic rats were treated with valsartan or sacubitril/valsartan for 12 weeks followed by an extensive evaluation of vascular and neural end points. The results demonstrated efficacy of sacubitril/valsartan in improving vascular and neural function was superior to valsartan alone. In the early intervention protocol, sacubitril/valsartan treatment was found to slow progression of these deficits and, with late intervention treatment, was found to stimulate restoration of vascular reactivity, motor and sensory nerve conduction velocities, and sensitivity/regeneration of sensory nerves of the skin and cornea in a rat model of type 2 diabetes. These preclinical studies suggest that sacubitril/valsartan may be an effective treatment for diabetic peripheral neuropathy, but additional studies will be needed to investigate these effects further.

Topics: Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet, High-Fat; Disease Progression; Drug Combinations; Male; Neprilysin; Neural Conduction; Neuroprotective Agents; Protease Inhibitors; Rats, Sprague-Dawley; Tetrazoles; Valsartan; Vascular Resistance

Recent clinical trials of new glucose-lowering treatments have drawn attention to the importance of hospitalization for heart failure as a complication of diabetes mellitus. However, the epidemiology is not well described, particularly for type 1 diabetes mellitus. We examined the incidence and case-fatality of heart failure hospitalizations in the entire population aged ≥30 years resident in Scotland during 2004 to 2013.. Date and type of diabetes mellitus diagnosis were linked to heart failure hospitalizations and deaths using the national Scottish registers. Incidence rates and case-fatality were estimated in regression models (quasi-Poisson and logistic regression respectively). All estimates are adjusted for age, sex, socioeconomic status, and calendar-year.. Over the 10-year period of the study, among 3.25 million people there were 91, 429, 22 959, and 1313 incident heart failure events among those without diabetes mellitus, with type 2, and type 1 diabetes mellitus, respectively. The crude incidence rates of heart failure hospitalization were therefore 2.4, 12.4, and 5.6 per 1000 person-years for these 3 groups. Heart failure hospitalization incidence was higher in people with diabetes mellitus, regardless of type, than in people without. Relative differences were smallest for older men, in whom the difference was nonetheless large (men aged 80, rate ratio 1.78; 95% CI, 1.45-2.19). Rates declined similarly, by 0.2% per calendar-year, in people with type 2 diabetes mellitus and without diabetes mellitus. Rates fell faster, however, in those with type 1 diabetes mellitus (2.2% per calendar-year, rate ratio for type 1/calendar-year interaction 0.978; 95% CI, 0.959-0.998). Thirty-day case-fatality was similar among people with type 2 diabetes mellitus and without diabetes mellitus, but was higher in type 1 diabetes mellitus for men (odds ratio, 0.96; 95% CI, 0.95-0.96) and women (odds ratio, 0.98; 95% CI, 0.97-0.98). Case-fatality declined over time for all groups (3.3% per calendar-year, odds ratio per calendar-year 0.967; 95% CI, 0.961-0.973).. Despite falling incidence, particularly in type 1 diabetes mellitus, heart failure remains ≈2-fold higher than in people without diabetes mellitus, with higher case-fatality in those with type 1 diabetes mellitus. These findings support the view that heart failure is an under-recognized and important complication in diabetes mellitus, particularly for type 1 disease.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Heart Failure; Hospitalization; Humans; Incidence; Logistic Models; Male; Middle Aged; Odds Ratio; Risk Factors; Survival Analysis; Young Adult

Type 2 diabetes (T2D) is associated with a high burden of angina. Ranolazine has been shown to reduce angina frequency versus placebo in patients with T2D and stable angina. We sought to estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) versus SoC alone in patients with T2D and stable, but symptomatic coronary disease despite treatment with 1-2 antianginals.. A Markov model was developed and evaluated using cohort simulation. The model utilized a US societal perspective, 1-month cycle length and 1-year time horizon and was developed to estimate the cost-effectiveness of ranolazine versus SoC. Patients entered the model in 1 of 4 angina frequency health states based on baseline Seattle Angina Questionnaire Angina Frequency scores (100 = no; 61-99 = monthly; 31-60 = weekly; 0-30 = daily) and could transition between health states (first cycle only) or to death (any cycle) based on probabilities derived from the Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina trial.. Our model estimated patients treated with ranolazine lived a mean of 0.728 quality adjusted life years (QALYs) at a cost of $16,654. Those not receiving ranolazine lived a mean of 0.702 QALYs and incurred costs of $15,476. The incremental cost-effectiveness ratio for the addition of ranolazine to SoC was $45,308/QALY. Short Form-36 data suggest improvements in patients' bodily pain drove the gain in QALYs associated with ranolazine (2.73 versus 3.96, p = 0.01).. Our model suggests the addition of ranolazine to SoC is likely cost-effective from a US societal perspective for the treatment of patients with T2D and stable, symptomatic coronary disease despite treatment with 1-2 antianginals.

Topics: Angina, Stable; Cardiovascular Agents; Cohort Studies; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Humans; Male; Markov Chains; Prospective Studies; Quality of Life; Ranolazine

Atherosclerosis-predominant vasculopathy is a common complication of diabetes with high morbidity and high mortality, which is ruining the patient's daily life. As is known to all, traditional Chinese medicine (TCM) SHENQI compound and western medicine rosiglitazone play an important role in the treatment of diabetes. In particular, SHENQI compound has a significant inhibitory effect on vascular lesions. Here, to explore and compare the therapeutic mechanism of SHENQI compound and rosiglitazone on diabetic vasculopathy, we first built 7 groups of mouse models. The behavioral, physiological and pathological morphological characteristics of these mice showed that SHENQI compound has a more comprehensive curative effect than rosiglitazone and has a stronger inhibitory effect on vascular lesions. While rosiglitazone has a more effective but no significant effect on hypoglycemic. Further, based on the gene expression of mice in each group, we performed differential expression analysis. The functional enrichment analysis of these differentially expressed genes (DEGs) revealed the potential pathogenesis and treatment mechanisms of diabetic angiopathy. In addition, we found that SHENQI compound mainly exerts comprehensive effects by regulating MCM8, IRF7, CDK7, NEDD4L by pivot regulator analysis, while rosiglitazone can rapidly lower blood glucose levels by targeting PSMD3, UBA52. Except that, we also identified some pivot TFs and ncRNAs for these potential disease-causing DEG modules, which may the mediators bridging drugs and modules. Finally, similar to pivot regulator analysis, we also identified the regulation of some drugs (e.g. bumetanide, disopyramide and glyburide etc.) which have been shown to have a certain effect on diabetes or diabetic angiopathy, proofing the scientific and objectivity of this study. Overall, this study not only provides an in-depth comparison of the efficacy of SHENQI compound and rosiglitazone in the treatment of diabetic vasculopathy, but also provides clinicians and drug designers with valuable theoretical guidance.

Topics: Animals; Aorta, Abdominal; Cardiovascular Agents; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Models, Animal; Drugs, Chinese Herbal; Gene Expression; Humans; Hypoglycemic Agents; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Phytotherapy; Rosiglitazone; Signal Transduction

to assess efficacy and endotheliotropic properties of short-term addition of meldonium to basic therapy of patients with chronic ischemic heart failure and type 2 diabetes.. The study demonstrated the ability of meldonium to significantly improve endothelial function and the state of microcirculatory vascular bed, as well as to influence beneficially heart rate variability.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Diabetes Mellitus, Type 2; Female; Heart Failure; Heart Rate; Humans; Male; Methylhydrazines; Middle Aged; Myocardial Ischemia

The prevalence of type 2 diabetes in young adults is increasing, yet little is known about medication use in this population. This study aimed to describe hypoglycaemic and cardiovascular treatment patterns in young adults newly treated with oral hypoglycaemic agents.. A retrospective cohort study from 2008-2011 was conducted using the Irish national pharmacy claims database. Subjects aged 15-39 years were analysed for use of hypoglycaemic therapy, subsequent regimen changes, and any co-prescription of cardiovascular agents 1 year after treatment initiation. Cox-proportional-hazards regression and logistic regression were used to examine factors associated with non-persistence to initial hypoglycaemic therapy (in males only), insulin use as a regimen change, and use of cardiovascular agents. Hazard ratios (HR), odds ratios (OR), and 95 % confidence intervals (CI) are presented.. There were 5284 individuals initiated on hypoglycaemic agents. Most were initiated on metformin (88 %); 13 % of subjects received a hypoglycaemic agent regimen change, with insulin being used in 26 % of these cases. A total of 38 % of males were non-persistent with their initial hypoglycaemic agent, with males aged 15-29 years and those on sulphonylureas significantly more likely to be non-persistent with therapy. Over 40 % of subjects were initiated on cardiovascular agents. Females were less likely to receive cardiovascular agents [OR 0.50 (95 % CI 0.42-0.83)].. Treatment patterns were found to be associated with high levels of non-persistence, substantial use of insulin, and a low use of cardiovascular agents. This may pose problems for the management of the long-term complications associated with type 2 diabetes.

Topics: Adolescent; Adult; Cardiovascular Agents; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Logistic Models; Male; Metformin; Odds Ratio; Primary Health Care; Proportional Hazards Models; Retrospective Studies; Sulfonylurea Compounds; Young Adult

To assess changes in medication use after a diagnosis of dementia in individuals with type 2 diabetes mellitus.. Difference-in-differences analysis of changes in the number of dispensed chronic medications between individuals with and without newly diagnosed dementia.. Integrated healthcare delivery system, Kaiser Permanente Northern California.. Individuals aged 50 and older without prevalent dementia with type 2 diabetes mellitus enrolled in a baseline survey. During 5 years of follow-up, 193 individuals with a new diagnosis of dementia were identified, and risk-set sampling was used to randomly select five reference subjects per case matched on 5-year age categories and sex (965 matched participants), resulting in an analytical sample of 1,158.. The exposure was new diagnosis of dementia. The primary outcome was change in number of current chronic medications (total, cardiovascular (blood pressure and lipid control), diabetes mellitus) at three times: 1 year before index date (preindex date), date of diagnosis of dementia or matched reference date (index date), and up to 1 year after index date or end of follow-up if censored before 1 year (postindex date).. After adjustment, the number of chronic medications and the subset of cardiovascular medications declined after a dementia diagnosis in the overall cohort and in age-, sex-, and time-matched reference individuals, but the decline was significantly greater in the group with dementia (0.71 medications fewer than the reference group, P = .02). The number of diabetes mellitus medications declined in both groups, but the declines were not statistically different (0.18 medications fewer than the reference group, P = .008).. Use of cardiometabolic medications fell after a diagnosis of dementia, as recommended in national guidelines.

Topics: Aged; Aged, 80 and over; California; Cardiovascular Agents; Cohort Studies; Dementia; Diabetes Mellitus, Type 2; Drug Utilization; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Polypharmacy

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Minority Groups; Minority Health; Risk Factors; Selection Bias

To evaluate primary care drug utilisation during the last year of life, focusing on antidiabetic and cardiovascular drugs, in patients of advanced age with diabetes.. Population-based cohort study.. Primary care database in the UK.. Patients with type 2 diabetes who died at over 80 years of age between 2011 and 13.. Main outcome measures included proportions of patients prescribed different classes of drugs, comparing the first (Q1) and the fourth quarters (Q4) of the last year of life.. The study included 5,324 patients, with the median age 86 years and 50% female. Three-fourths of the patients received five or more drugs, and the total number of drugs prescribed was almost stable at 6.2 ± 3.1 (mean ± SD) during the last year of life. Substantial proportions of patients were treated with antidiabetic drugs (78%), antihypertensive drugs (76%), statins (62%) and low-dose aspirin (46%) in Q1. Prescribing of these drugs slightly decreased by 3–8% in Q4. There were increases in prescribing of anti-infectives (35% in Q1 to 50% in Q4), drugs for nervous system (63% to 73%), drugs for respiratory system (24% to 33%) and systemic hormonal drugs (22% to 27%).. Patients of advanced age with type 2 diabetes were often treated with antidiabetic and cardiovascular drugs even when approaching death. More research is needed to generate evidence to guide optimal drug utilisation for older people with a limited life expectancy.

Topics: Age Factors; Aged, 80 and over; Aging; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Databases, Factual; Diabetes Mellitus, Type 2; Drug Prescriptions; Drug Utilization Review; Female; Humans; Hypoglycemic Agents; Male; Polypharmacy; Practice Patterns, Physicians'; Primary Health Care; Terminal Care; Time Factors; United Kingdom

Approximately 24-40% of patients with type 2 diabetes mellitus (T2DM) develop kidney damage. Our objective was to evaluate the long-term evolution of renal function using isotopic determination of GFR and urinary albumin excretion (UAE) in patients with T2DM undergoing intensive treatment for renal and cardiovascular risk factors.. This was a single-center, prospective study of 201 patients with T2DM and UAE who initiated intensive treatment. They were followed for 17.2±6.5 years. Patients were divided into three groups, according to renal function: 167(85.6%) had stable renal function, 16(8.2%) had creatinine levels that doubled and 12(6.2%) began renal replacement therapy (RRT). We performed periodic isotopic determinations of GFR using (125)I-iothalamate.. There were significant differences between the three groups with respect to age, duration of T2DM at baseline, years of follow-up in the study and systolic blood pressure, serum creatinine, isotopic GFR, and UAE at baseline. Renal function evolution slopes were -1.55mL/min/1.73m(2)/year in patients with stable creatinine, -2.49mL/min/1.73m(2)/year in those with doubled creatinine, and -8.16mL/min/1.73m(2)/year in those requiring RRT. We also found that differences in renal events were determined by delayed initiation of intensive treatment.. Patients with glomerular hyperfiltration who were undergoing treatment with renin angiotensin aldosterone system blockers exhibited a better evolution in renal function, possibly because these patients initiated intensive treatment earlier. Although diabetic nephropathy is associated with classic risk factors, early initiation of intensive treatment should be a priority in order to prevent worsening renal function.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dyslipidemias; Early Medical Intervention; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Iodine Radioisotopes; Iothalamic Acid; Mineralocorticoid Receptor Antagonists; Prospective Studies; Renal Replacement Therapy; Renin-Angiotensin System; Treatment Outcome

Adaptation of drug dosage to kidney function is a common problem in general practice. The aim was to describe adaptation of cardiovascular drugs and metformin according to renal function and its association with mortality with regard to metformin in a cohort of elderly patients. This was an ancillary study to the S.AGES cohort made up of patients over 65 years of age managed by their general practitioner under real-life conditions and followed up prospectively for 3 years. The medications studied were digoxin, spironolactone and metformin. Adaptation of their daily dose according to renal function (eGFR according to CKD/EPI) was compared to that recommended in the summaries of product characteristics (SPCs) or international scientific societies (ISS). A total of 900 patients were included, including 588 on metformin. At baseline, dose adjustment according to renal function was 100% and 87.6% (95% CI: 82.6-92.6) for patients on digoxin and spironolactone respectively. For metformin, only 71.3% (95% CI: 67.6-74.9) or 78.1% (95% CI: 74.7-81.4) of patients had their dosage adapted at inclusion according to their renal function depending on whether the SPCs or ISS recommendations were considered. During the 3-year follow-up period, 42/588 patients died (none from lactic acidosis). At inclusion, a metformin dosage not adapted for renal function according to ISS was not associated with an increase in all-cause mortality (OR 1.7; 95% CI 0.6-5.0, p = 0.32). In conclusion, approximately one-quarter of elderly patients treated with metformin do not have their dosage adapted for renal function according to ISS although there is no increase in mortality after follow-up for 3 years.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Agents; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; France; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Kidney; Male; Metformin; Prospective Studies; Risk Factors

To describe the drug utilisation patterns of aspirin, antihypertensives, vasodilators, and statins in a cohort of newly treated type 2 diabetes subjects previously unexposed to CVD agents.. A population-based retrospective cohort study was conducted using a national pharmacy claims database of newly treated type 2 diabetes subjects aged 40 years or older. Data on the use of aspirin, antihypertensives, vasodilators, and statins 1 year after antidiabetic agent initiation were analysed. Poisson regression with a robust error variance was used to estimate adjusted relative risk (RRadj) and 95% CIs between socio-demographic and treatment factors on CVD agent use.. Over a 2-year period (2008-2009), 6093 subjects were identified. One year after antidiabetic agent initiation, 82% of the study population received at least one CVD agent, with 54% receiving aspirin, 64% receiving antihypertensives, 6% vasodilators, and 62% receiving statins. Subjects aged 40-49 years were significantly less likely than those aged 60-69 years to receive CVD agents (RRadj 0.83, 95% CI 0.80-0.87). Over 40% of subjects received antihypertensives without aspirin and statins, while 30% of subjects on statins did not receive aspirin.. Substantial CVD agent utilisation was noted 1 year after antidiabetic agent initiation. Being aged younger than 60-69 years was associated with decreased utilisation of CVD agents.

Topics: Administrative Claims, Healthcare; Adult; Age Factors; Aged; Aged, 80 and over; Antihypertensive Agents; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Utilization Review; Female; General Practice; Guideline Adherence; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Ireland; Male; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vasodilator Agents

To measure the costs associated with the use of antidiabetic agents, monitoring materials and cardiovascular disease (CVD) agents in the management of newly treated type 2 diabetes, and to investigate the factors associated with these costs.. A population-based retrospective cohort study was conducted using the Irish national pharmacy claims database. Newly treated patients were identified for 2012 and followed for one year post treatment initiation. Factors associated with costs were assessed using a generalised linear model with gamma family and log-link function. Cost ratios (CR) and 95% CIs were used to determine the contributors of prescription costs. Adjusted odd ratios (OR) and 95% CIs were used to investigate factors associated with high frequency self-monitoring of blood glucose (SMBG).. Mean prescription costs for the 12,941 subjects was €871, while total costs were €11 million. CVD agents accounted for 58% of total costs; 22% of costs were for SMBG; antidiabetic agents accounted for 17% of costs. SMBG resulted in costs that were 80% higher than those without, CR 1.80 (95% CI 1.76-1.84). No significant differences were observed between initiation on metformin or sulphonylureas and high frequency SMBG (OR 1.01 95% CI 0.97-1.04 vs reference). Initiation on newer antidiabetic agents was a significant positive predictors of prescription costs (CR 2.36 95% CI 2.21-2.51 vs metformin).. Type of initial antidiabetic agent, and SMBG were significant predictors of prescription costs. SMBG represent a major proportion of total costs; however, its use in combination with antidiabetic agents that do not cause hypoglycaemia is questionable.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose Self-Monitoring; Cardiovascular Agents; Diabetes Mellitus, Type 2; Disease Management; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Odds Ratio; Retrospective Studies; Sulfonylurea Compounds

Preclinical and clinical studies have demonstrated that berberine (BBR) improves diabetic complications and reduces mortality of patients with congestive heart failure. The therapeutic effects of BBR have been reported to be mediated by its regulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). We previously reported that BBR protects against ischemia-reperfusion injury via regulating AMPK activity in both ischemic and nonischemic areas of the rat heart. Since diabetic hearts are more sensitive to ischemia-reperfusion injury, we examined whether BBR treatment exhibited cardioprotective effects in the diabetic heart. Type 2 diabetic rats were pretreated plus or minus BBR for 7 days and subjected to 30-minute ischemia followed by 120-minute reperfusion. Pretreatment of type 2 diabetic rats with BBR reduced ischemia-reperfusion injury infarct size and attenuated arrhythmia compared to untreated diabetic controls. Subsequent to ischemia-reperfusion, serum triglyceride, total cholesterol, and malondialdehyde levels were reduced by pretreatment of type 2 diabetic rats with BBR compared to untreated diabetic controls. In contrast, serum glucose and superoxide dismutase levels were unaltered. The mechanism for the BBR-mediated cardioprotective effect was examined. Pretreatment with BBR did not alter AMPK activity in ischemic areas at risk but increased AMPK activity in nonischemic areas compared to untreated diabetic controls. The increased AMPK activity in nonischemic areas was due an elevated ratio of AMP to adenosine triphosphate (ATP) and adenosine diphosphate to ATP. In addition, pretreatment with BBR increased protein kinase B (AKT) phosphorylation and reduced glycogen synthase kinase 3β (GSK3β) activity in nonischemic areas compared to untreated diabetic controls. These findings indicate that BBR protects the diabetic heart from ischemia-reperfusion injury. In addition, BBR may mediate this cardioprotective effect through AMPK activation, AKT phosphorylation, and GSK3β inhibition in the nonischemic areas of the diabetic heart.

Topics: AMP-Activated Protein Kinases; Animals; Arrhythmias, Cardiac; Berberine; Biomarkers; Blood Glucose; Cardiovascular Agents; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Energy Metabolism; Enzyme Activation; Glycogen Synthase Kinase 3 beta; Lipids; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Wistar; Signal Transduction

Bariatric surgery can facilitate weight loss and improvement in medical comorbidities. It has a profound impact on nutrition, and patients need access to follow-up and aftercare. NICE CG189 Obesity emphasized the importance of a minimum of 2 years follow-up in the bariatric surgical service and recommended that following discharge from the surgical service, there should be annual monitoring as part of a shared care model of chronic disease management. NHS England Obesity Clinical Reference Group commissioned a multi-professional subgroup, which included patient representatives, to develop bariatric surgery follow-up guidelines. Terms of reference and scope were agreed upon. The group members took responsibility for different sections of the guidelines depending on their areas of expertise and experience. The quality of the evidence was rated and strength graded. Four different shared care models were proposed, taking into account the variation in access to bariatric surgical services and specialist teams across the country. The common features include annual review, ability for a GP to refer back to specialist centre, submission of follow-up data to the national data base to NBSR. Clinical commissioning groups need to ensure that a shared care model is implemented as patient safety and long-term follow-up are important.

Topics: Aftercare; Bariatric Surgery; Bone Density; Cardiovascular Agents; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Male; Mental Health; Obesity, Morbid; Practice Guidelines as Topic; Pregnancy; Vitamin D

The aim of this pilot study was to evaluate if ranolazine (R) could improve insulin resistance (IR) in obese/overweight non-diabetic patients with coronary heart disease (CHD).. The study enrolled 40 patients with already diagnosed CHD, previous revascularization, residual ischemia at ergometric test and IR. Mean age was 62.4±9years, M/F=31/9. Patients were randomly assigned to one of the two following groups: group 1 (20 patients) started R at dose of 500mg/bid; group 2 (20 patients) increased the dose of beta/blockers or calcium-channel blockers without introducing R. IR was defined as having HOMA-IR>2.5. At baseline and after 12weeks, all subjects performed an ergometric test and 12h fasting blood sample collection for determining glucose and insulin levels.. At 12weeks follow-up visit HOMA-IR significantly decreased in group 1 (from 3.1±1.7 to 2.3±0.9; p=0.02) while it remained unchanged in group 2 (from 3.0±1.4 to 2.8±1.2; p=0.14) (between groups p=0.009). At 12weeks follow-up visit patients of both groups obtained a significant increase of ischemic threshold at ergometric test, compared to baseline, (group 1 from 308.4±45s to 423.9±57s, p=0.0004); (group 1 from 315.7±63s to 441.2±51s, p=0.0001); without between groups difference (p=0.25).. Our data suggest that starting R, instead of increasing the dose of beta-blockers/calcium-channel blockers, could be a preferable choice in obese/overweight CHD subjects with residual ischemia after revascularization.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Disease; Diabetes Mellitus, Type 2; Exercise Test; Female; Follow-Up Studies; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Pilot Projects; Ranolazine

The objective of this study was to use instrumental variable (IV) analyses to evaluate the clinical effectiveness of percutaneous stent revascularization versus bypass surgery in the treatment of peripheral artery disease (PAD) among type 2 diabetic patients. Type 2 diabetic patients who received peripheral artery bypass surgery (n = 5,652) or stent revascularization (n = 659) for lower extremity arterial stenosis between 2000 and 2007 were identified from the Taiwan National Health Insurance claims database. Patients were followed from the date of index hospitalization for 2 years for lower-extremity amputation, revascularization, and hospitalization for medical treatment. Analysis using treatment year, patients' monthly income level, and regional difference as IVs were conducted to reduce unobserved treatment selection bias. The crude analysis showed a statistically significant risk reduction in favor of stent placement in lower extremity amputation and in the composite endpoint of amputation, revascularization, or hospitalization for medical treatment. However, peripheral artery stent revascularization and bypass surgery had similar risk of lower limb amputation and composite endpoints in the analyses using calendar year or patients' monthly income level as IVs. These two treatment modalities had similar risk of lower limb amputation among DM patients with PAD.

Topics: Age Distribution; Aged; Amputation, Surgical; Cardiovascular Agents; Comorbidity; Databases, Factual; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Endovascular Procedures; Female; Graft Occlusion, Vascular; Hospitalization; Humans; Hypoglycemic Agents; Leg; Limb Salvage; Lung Diseases; Male; Middle Aged; Minimally Invasive Surgical Procedures; Peripheral Arterial Disease; Risk Reduction Behavior; Stents; Taiwan; Treatment Outcome; Vascular Grafting

Meta-analysis has been used extensively for evaluation of efficacy and safety of medical interventions. Its advantages and utilities are well known. However, recent studies have raised questions about the accuracy of the commonly used moment-based meta-analytic methods in general and for rare binary outcomes in particular. The issue is further complicated for studies with heterogeneous effect sizes. Likelihood-based mixed-effects modeling provides an alternative to moment-based methods such as inverse-variance weighted fixed- and random-effects estimators. In this article, we compare and contrast different mixed-effect modeling strategies in the context of meta-analysis. Their performance in estimation and testing of overall effect and heterogeneity are evaluated when combining results from studies with a binary outcome. Models that allow heterogeneity in both baseline rate and treatment effect across studies have low type I and type II error rates, and their estimates are the least biased among the models considered.

Topics: Biomedical Research; Cardiovascular Agents; Chi-Square Distribution; Computer Simulation; Coronary Disease; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Likelihood Functions; Logistic Models; Meta-Analysis as Topic; Numerical Analysis, Computer-Assisted; Odds Ratio; Percutaneous Coronary Intervention; Pregnancy; Research Design; Risk Assessment; Risk Factors; Treatment Outcome

Although many elderly individuals suffer from type 2 diabetes, the effectiveness of cardioprotective drugs in primary prevention of cardiovascular events in clinical practice in this population has rarely been evaluated. We aimed to assess the effectiveness of, (i) angiotensin converting enzyme inhibitors or angiotensin receptor blockers, (ii) statins, (iii) antiplatelet drugs and (iv) the combination of these three drugs, in the prevention of myocardial infarction (MI) and stroke in elderly individuals with type 2 diabetes.. Using Quebec administrative databases, we conducted nested case-control analyses among a cohort of 17,384 individuals without a history of cardiovascular disease. Individuals were aged ≥ 66 years, newly treated with oral antidiabetes drugs and had not used any of the three above classes of cardioprotective drugs in the year before cohort entry. For each case (MI/stroke during follow-up), five controls were matched for age, year of cohort entry and sex. Use of each drug and of their combination was defined as current, past or no use. We calculated adjusted odds ratios (AOR) of MI/stroke.. We observed no reduction in the MI/stroke risk for users of ACEI/ARB nor for users of the three drugs combination. Longer exposure to statins was associated with a lower risk (AOR for every 30 days of therapy: 0.97; 95% CI: 0.96-0.99). By contrast, current use of antiplatelet drugs was associated with an increased risk of MI/stroke (1.40; 1.12-1.75).. The benefit of cardioprotective drugs in primary prevention was not clear in this cohort of elderly individuals with type 2 diabetes. A short duration of exposure to these drugs might explain the lack of benefit.

Topics: Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Incidence; Male; Primary Prevention; Prognosis; Quebec; Retrospective Studies; Risk Factors

Concern about the renal safety of commonly used cardiovascular drugs with demonstrated clinical benefit appears to be an obstacle to their use in the elderly. The objective was to describe the relationship between cardiovascular drugs and chronic kidney disease (CKD) in elderly individuals in the real-life setting. This is an ancillary study of the prospective non-interventional S.AGE (aged individuals) cohort. General physicians were free to prescribe any drug their patients needed. The participants were non-institutionalized patients aged 65 years and older treated by their primary physician for either chronic pain or atrial fibrillation or type 2 diabetes mellitus. The estimated glomerular filtration rate (eGFR) derived from the CKD-EPI formula was determined at inclusion and every year during 2 years of follow-up. This study comprised 2505 patients aged 77.8 ± 6.2 years. At inclusion, the factors associated with CKD (eGFR < 60 ml/min/1.73 m(2) ) in multivariate analysis were age, female gender, hypertension, heart failure, history of atherothrombotic disease and renin angiotensin system blockers, loop diuretics and calcium channel inhibitors. Introduction of each of these three drug classes during the follow-up period led to only a small decrease in the eGFR: -3.8 ± 12.7 (p < 0.0006), -2.2 ± 12.0 (p < 0.003) and -1.0 ± 13.4 ml/min./1.73 m(2) (NS), respectively. Only the introduction of loop diuretics was associated with CKD (OR 1.91, 95% CI: 1.25-2.90; p = 0.002). Renal safety of cardiovascular drugs in the elderly appears acceptable and should not be a barrier to their use.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Agents; Chronic Pain; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Multivariate Analysis; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Sex Factors; Sodium Potassium Chloride Symporter Inhibitors

there is a lack of evidence to inform treatment recommendations for very old people with type 2 diabetes mellitus (T2DM).. to evaluate trends in antidiabetic and cardiovascular drug utilisation for patients developing T2DM over 80 years of age.. a population-based cohort was sampled from the UK Clinical Practice Research Datalink between 1990 and 2013. Eligible patients were those with T2DM diagnosed after the age of 80 years and prescribed antidiabetic drugs.. twelve thousand eight hundred and eighty-one patients, with 61% of females, were included. From 1990 to 2013, use of sulphonylureas declined from 94 to 29%, while metformin use increased from 22 to 86%. Prescribing of antihypertensive drugs increased substantially from 46 to 77%, lipid-lowering drugs from 1 to 64%, antiplatelets from 34 to 47% and oral anticoagulants from 5 to 19%. Women were more frequently prescribed antihypertensive drugs (odds ratio 1.26, 95% confidence interval 1.17 to 1.37) but less prescribed antiplatelets (0.83, 0.78 to 0.89). Compared with those diagnosed with T2DM from 80 to 89 years (n = 11,467, 89%), patients diagnosed after the age of 90 years (n = 1,414, 11%) were less likely to be prescribed insulin (0.37, 0.24 to 0.58), metformin (0.67, 0.60 to 0.75), antihypertensive drugs (0.42, 0.38 to 0.48), lipid-lowering drugs (0.26, 0.23 to 0.30) and anticoagulants (0.55, 0.44 to 0.68).. there have been major increases in the intensity of pharmacological management of patients diagnosed with T2DM over 80 years of age, but the effectiveness and safety of these interventions in very old people require further evaluation.

Topics: Aged, 80 and over; Blood Glucose; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Utilization; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Population Surveillance; Retrospective Studies

We previously reported ethnic disparity in adverse outcomes among Asians with type 2 diabetes (T2DM) in Singapore. Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to study ethnic disparity in central arterial stiffness and its determinants in a multi-ethnic T2DM Asian cohort.. Arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV) and augmentation index (AI) using applanation tonometry method in Chinese (N = 1045), Malays (N = 458) and Indians (N = 468). Linear regression model was used to evaluate predictors of PWV and AI.. PWV was higher in Malays (10.1 ± 3.0 m/s) than Chinese (9.7 ± 2.8 m/s) and Indians (9.6 ± 3.1 m/s) (P = 0.018). AI was higher in Indians (28.1 ± 10.8%) than Malays (25.9 ± 10.1%) and Chinese (26.1 ± 10.7%) (P < 0.001). Malays remain associated with higher PWV (β = 0.299, P = 0.048) post-adjustment for age, gender, duration of diabetes, hemoglobin A1c, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), soluble receptor for advanced glycation end-products, urinary albumin-to-creatinine ratio, and insulin usage, which were all independent predictors of PWV. Indians remain associated with higher AI (β = 2.776, P < 0.001) post-adjustment for age, gender, BMI, SBP, DBP, and height, which were independent predictors of AI. These variables explained 27.7% and 33.4% of the variance in PWV and AI respectively.. Malays and Indians with T2DM have higher central arterial stiffness, which may explain their higher risk for adverse outcomes. Modifying traditional major vascular risk factors may partially alleviate their excess cardiovascular risk through modulating arterial stiffness.

Topics: Aged; Arteriosclerosis; Asian People; Cardiovascular Agents; China; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Susceptibility; Female; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Hypertension; Hypoglycemic Agents; India; Malaysia; Male; Middle Aged; Obesity; Pulse Wave Analysis; Risk Factors; Singapore; Vascular Stiffness

Critical limb ischemia (CLI), a frequently encountered disorder, is associated with a high rate of limb amputation and mortality. To identify patients at high risk for CLI, we developed a simple risk score for peripheral arterial occlusive disease (PAOD).In our cross-sectional study, we first evaluated 1000 consecutive PAOD patients treated at our institution from 2005 to 2007, documenting clinical symptoms, comorbidities, and concomitant medication. We calculated odds ratios (OR) in a binary logistic regression model to find possible risk factors for CLI. We then verified the score in a second step that included the 1124 PAOD patients we treated between 2007 and 2011.In the first patient group, the greatest risk factors for CLI were age ≥75 years (OR 2.0), type 2 diabetes (OR 3.1), prior myocardial infarction (OR 2.5), and therapy with low molecular weight heparins (2.8). We scored 1 point for each of those conditions. One point was given for age between 65 and 75 years (OR 1.6) as well as for therapy with cardiac glycosides (OR 1.9) or loop diuretic therapy (OR 1.5). As statin therapy was protective for CLI with an OR of 0.5, we subtracted 1 point for those patients.In the second group, we could prove that frequency of CLI was significantly higher in patients with a high CLI score. The score correlated well with inflammatory parameters (c-reactive protein and fibrinogen). We were also able to define 3 different risk groups for low (score -1 to 1), intermediate (score 2-4), and high CLI risk (score >4).We developed a simple risk stratification scheme that is based on conditions that can be easily assessed from the medical history, without any laboratory parameters. This score should help to identify PAOD patients at high risk for CLI.

Topics: Age Factors; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Extremities; Female; Humans; Hypoglycemic Agents; Ischemia; Male; Microcirculation; Middle Aged; Myocardial Infarction; Odds Ratio; Peripheral Arterial Disease; Risk Assessment; Risk Factors

Comparative studies evaluating traditional versus newer antianginal (AA) medications in chronic stable angina pectoris (CSA) on cardiovascular (CV) outcomes and utilization are limited, particularly in patients with diabetes mellitus (DM). Claims data (2008 to 2012) were analyzed using a commercial database. Patients with CSA receiving a β blocker (BB), calcium channel blocker (CCB), long-acting nitrate (LAN), or ranolazine were identified and followed for 12 months after a change in AA therapy. Patients on traditional AA medications were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional AA medication or ranolazine to identify patients whose angina was inadequately controlled with previous therapy. Four groups were identified (BB, CCB, LAN, or ranolazine users) and matched on relevant characteristics. A DM subset was identified. Logistic regression compared revascularization at 30, 60, 90, 180, and 360 days. Negative binomial regression compared all-cause, CV-, and DM-related (in the DM cohort) health care utilization. A total of 8,008 patients were identified with 2,002 patients in each matched group. Majority were men (mean age 66 years). A subset of 3,724 patients with DM (BB, n = 933; CCB, n = 940; LAN, n = 937; and ranolazine, n = 914) resulted from this cohort. Compared to ranolazine in the overall cohort, traditional AA medication exhibited greater odds for revascularization and higher rates in all-cause outpatient, emergency room visits, inpatient length of stay, and CV-related emergency room visits. In the DM cohort, ranolazine demonstrated similar benefits over traditional AA medication. In conclusion, ranolazine use in patients with inadequately controlled chronic angina is associated with less revascularization and all-cause and CV-related health care utilization compared to traditional AA medication.

Topics: Adrenergic beta-Antagonists; Aged; Angina, Stable; Calcium Channel Blockers; Cardiovascular Agents; Chronic Disease; Comparative Effectiveness Research; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Health Resources; Humans; Male; Nitroglycerin; Ranolazine; Retrospective Studies; Risk Factors; Treatment Outcome; United States; Vasodilator Agents

This study sought to compare everolimus-eluting stents (EES) versus Resolute zotarolimus-eluting stents (ZES) in terms of patient- or stent-related clinical outcomes in an "all-comer" group of patients with diabetes mellitus (DM) who underwent percutaneous coronary intervention.. DM significantly increases the risk of adverse events after percutaneous coronary intervention. The efficacy and safety of second-generation drug-eluting stents, in particular EES versus ZES, in patients with DM have not been extensively evaluated.. Patients with DM (1,855 of 5,054 patients, 36.7%) from 2 prospective registries (the EXCELLENT [Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting] registry and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]) who were treated with EES (n = 1,149) or ZES (n = 706) were compared. Stent-related outcome was target lesion failure (TLF), and patient-oriented composite events were a composite of all-cause mortality, any myocardial infarction, and any revascularization.. Despite a higher risk patient profile in the ZES group, both TLF (43 of 1,149 [3.7%] vs. 25 of 706 [3.5%], p = 0.899) and patient-oriented composite events (104 of 1,149 [9.1%] vs. 72 of 706 [10.2%], p = 0.416) were similar between the EES and ZES in patients with DM at 1 year. In those without DM, EES and ZES also showed comparable incidence of TLF (39 of 1,882 [2.1%] vs. 33 of 1,292 [2.6%], p = 0.370) and patient-oriented composite events (119 of 1,882 [6.3%] vs. 81 of 1,292 [6.3%], p = 0.951), which were all significantly lower than in the DM patients. These results were corroborated by similar findings from the propensity score-matched cohort. Upon multivariate analysis, chronic renal failure was the most powerful predictor of TLF in DM patients (hazard ratio: 4.39, 95% confidence interval: 1.91 to 10.09, p < 0.001).. After unrestricted use of second-generation drug-eluting stents in all-comers receiving percutaneous coronary intervention, both EES and ZES showed comparable clinical outcomes in the patients with DM up to 1 year of follow-up. DM compared with non-DM patients showed significantly worse patient- and stent-related outcomes. Nonetheless, overall incidences of TLF were low, even in the patients with DM, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents in this high-risk subgroup of patients.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Patient Selection; Percutaneous Coronary Intervention; Propensity Score; Proportional Hazards Models; Prosthesis Design; Registries; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Artery Disease; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Percutaneous Coronary Intervention; Sirolimus

Patient information leaflets (PILs) are the most important information source for older patients to effectively manage their drug therapy.. The objective of this study is to evaluate the appropriateness of current available PILs for use by older adults.. The content of the PILs were assessed by checking the availability of information relevant to older patients including pharmacokinetics, safety and dose instructions. The layout of the PILs was evaluated using criteria derived from the relevant regulatory guidelines on the design of PILs. The Gunning Fog Index was used to determine the readability of the PILs to older adults.. Total of 48 PILs were analysed involving 25 drug substances for the treatment of cardiovascular disease and type 2 diabetes. One out of the 48 PILs contained information on pharmacokinetic changes in older patients and only 15 % of the PILs specified the age of the older person. Thirty-one percent of the PILs provided nonspecific warnings to the older population, while only 15 % included specific side effects that could occur in the older generation. Text font sizes of the PILs were generally too small for older adults to read, with only 9 % of the PILs used type size 12 or over. The readability of 63 % of the PILs had a score above 12, which is considered difficult for older people to understand.. Currently available medication PILs are inappropriate for use by older adults to manage their medications effectively, which could adversely affect patient safety and adherence to drug therapy.

Topics: Aged; Aged, 80 and over; Aging; Cardiovascular Agents; Cardiovascular Diseases; Comprehension; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Industry; Drug Packaging; England; Humans; Hypoglycemic Agents; Medical Writing; Patient Education as Topic; Practice Guidelines as Topic; Prescription Drugs; Quality of Health Care

To assess the role of percutaneous coronary intervention (PCI) for in-hospital and one-year prognosis of ST elevation (STE) myocardial infarction (MI) patients with impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM).. This registry study included 601 STEMI patients admitted to hospital within 24 hours after STEMI onset during one year. According to medical history, dynamics of glycemia and results of oral glucose tolerance test patients were divided into 3 groups: (1) without disturbances of carbohydrate metabolism (DCM), (2) with IGT and (3) with T2DM. Primary PCI was performed in 373 (62.06%) patients while 228 (37.94%) received pharmacological treatment only. The following events were registered during one year after PCI: recurrent MI, stroke, admission for decompensated chronic heart failure (CHF), repeat emergency PCI.. Patients with IGT and DM compared with those without DCM had similarly more severe course of the index MI and worse one-year prognosis. PCI significantly improved one-year prognosis in patients with and without DCM.. Use of urgent PCI in STEMI patients with both DM and IGT is prognostically more beneficial in terms of lowering rate of adverse events during one year after MI.

Topics: Carbohydrate Metabolism; Cardiovascular Agents; Diabetes Mellitus, Type 2; Electrocardiography; Female; Follow-Up Studies; Glucose Intolerance; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Complications; Prognosis; Registries; Risk Factors; Russia; Severity of Illness Index; Treatment Outcome

Topics: Cardiovascular Agents; Contraceptive Agents; Contraindications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Pregnancy

Topics: Angioplasty, Balloon, Coronary; Cardiomyopathy, Dilated; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; False Negative Reactions; Follow-Up Studies; Humans; Hypertension; Internal Mammary-Coronary Artery Anastomosis; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Infarction; Myocardial Perfusion Imaging; Myocardial Stunning; Overweight; Reoperation; Stents; Stroke Volume

The management of coronary artery disease has made important progress. Adherence to therapeutic measures is a great challenge for improving the long-term prognosis. In this work, we evaluate factors related to therapeutic adherence in black African patients with stable coronary artery disease.. We conducted a survey over three months (February-May 2008) in three cardiology departments in Dakar. We studied the regularity of drug intake, the adherence to the dietary advices and the appointments for consultation as well as the factors related to adherence. Good adherence was defined by a compliance rate greater or equal to 80% and a compliance rate less than 40% defined poor adherence.. We included 105 patients (61 men) with a mean age of 60.67±11.29 years. Good compliance was noted in 56.2% of cases for drug treatment, 42% for dietary advices and 65% for appointments for consultation. A history of acute coronary events (P=0.04), a good knowledge of the disease (P=0.03) and a healthcare (P=0.02) were the factors related to a good adherence to drug treatment, whereas ischemic cardiomyopathy was a factor for poor adherence (P=0.002). Knowledge of coronary disease was the only factor correlated with good adherence to lifestyle (P=0.014).. Therapeutic adherence remains unsatisfactory in Black African patients with stable coronary artery disease, hence the importance of patient education to reach a good adherence for therapeutic, because better adherence improves long-term prognosis of coronary artery disease.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Black People; Cardiovascular Agents; Combined Modality Therapy; Coronary Artery Disease; Developing Countries; Diabetes Mellitus, Type 2; Exercise; Female; Humans; Hypercholesterolemia; Hypertension; Male; Medication Adherence; Middle Aged; Obesity, Abdominal; Risk Factors; Sedentary Behavior; Senegal; Smoking

Diabetic patients with coronary artery disease (CAD) demonstrate accelerated progression of coronary atherosclerosis. The impact of multiple risk factor intervention on disease progression has not been investigated.. We investigated 448 diabetic patients with angiographic CAD who underwent serial intravascular ultrasound imaging to monitor the change in atheroma burden in seven clinical trials.. Disease progression was compared in patients stratified according to whether they achieved increasing numbers of treatment goals of individual risk factors (HbA1c <7.0%, LDL cholesterol <2.5 mmol/l, triglyceride <1.7 mmol/l, systolic blood pressure <130 mmHg, high sensitivity C-reactive protein <2.0 mg/l).. A high rate of established medical therapies was used in all patients (89% statins, 94% aspirin, 76% β-blockers, 66% ACE inhibitors, 66% metformin, 62% thiazolidinediones, 17% insulin). No differences were observed with regard to percentage atheroma volume (PAV) and total atheroma volume (TAV) at baseline. On serial evaluation, slowing of progression of PAV (p = 0.01) and TAV (p < 0.001) was observed with increasing numbers of risk factors achieving treatment goals. On multivariate analysis adjusting for baseline risk factors, increasing the number of factors meeting treatment goals continued to be associated with a beneficial impact on progression of PAV (p = 0.03) and TAV (p < 0.001).. The benefit of achieving optimal control of multiple risk factors underscores the need for modification of global risk in patients with diabetes.

Topics: Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiovascular Agents; Chi-Square Distribution; Cholesterol, LDL; Clinical Trials as Topic; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Progression; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Least-Squares Analysis; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Ultrasonography, Interventional

We estimated the prevalence of cardiovascular disease (CVD) risk and its clinical implications among 1 110 Omani patients with type 2 diabetes mellitus (DM) using 2 different CVD risk tools: the general Framingham risk profile (GFRP) and the joint World Health Organization/International Society of Hypertension (WHO/ISH) risk prediction charts. The GFRP tool identified higher proportion of patients compared with joint WHO/ISH tool at 10-year CVD risk 10% to <20% and at 20% to <30%. At CVD risk ≥30%, both assessment tools identified similar proportions of patients (22% vs 24%; P=.120). Compared with WHO/ISH charts, the GFRP identified almost double the number of men eligible for aspirin treatment at CVD risk thresholds of ≥10% (86% vs 43%). In women, the proportions were, 66% and 45%, respectively. For statins, the figures were, 60% and 37%, for men and 28% and 36%, for women. In conclusion, the GFRP overestimates the number of patients eligible for primary prevention of CVD compared with the joint WHO/ISH method.

Topics: Adult; Aged; Arabs; Cardiovascular Agents; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Drug Costs; Female; Health Status Indicators; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Oman; Practice Patterns, Physicians'; Prevalence; Risk Factors

Topics: Angiography; Anti-Inflammatory Agents; Arterial Occlusive Diseases; Cardiovascular Agents; Cryoglobulinemia; Cryoglobulins; Diabetes Mellitus, Type 2; Diagnostic Imaging; Drug Therapy, Combination; Female; Fibrinogens, Abnormal; Fingers; Humans; Hypertension; Ischemia; Ischemic Attack, Transient; Middle Aged

To describe contraception use and the prescription of drugs that are either not recommended in pregnancy or are potentially teratogenic by diabetes type in women of child-bearing age.. Retrospective, cross-sectional chart review undertaken in 22 general practices in Warwickshire, UK. Demographic, anthropometric, medical history, medication and contraception data were extracted from women aged 14 to 49 years with pre-existing diabetes. Independent sample t-test, Mann-Whitney test and χ(2) -test were used to test for univariable associations and multiple logistic regression was used to adjust for confounders.. Four hundred and seventy eligible women were identified; the majority had a diagnosis of Type 2 diabetes (67%). Thirty-six per cent and 64% of women with Type 1 and Type 2 diabetes, respectively, were prescribed drugs not recommended for use in pregnancy (P < 0.001). Less than half were using concomitant contraception (P < 0.001). No significant difference of contraception use was observed between women who were and were not taking drugs not recommended for use in pregnancy (40 vs. 41%, P = 0.4).. Use of drugs not recommended during pregnancy in women with diabetes of child-bearing age is common but is not associated with increased use of contraception. There is need to identify and overcome barriers to effective contraception use for this population group in order to facilitate optimal management of cardiovascular risk.

Topics: Adolescent; Adult; Cardiovascular Agents; Contraceptive Agents; Contraindications; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Middle Aged; Pregnancy; Prescription Drugs; Retrospective Studies; Risk Factors; Teratogens; Young Adult

There are conflicting data regarding the benefits of omega-3 (n-3) fatty acids, most recently in patients with type 2 diabetes.. Our goal was to evaluate the impact of licensed, highly purified n-3 fatty acids on all-cause mortality after myocardial infarction (MI).. This was a retrospective, matched-cohort study using data from the General Practice Research Database. Patients initiating treatment with 1 g of n-3 fatty acids in the 90 days after first MI were identified and each matched to 4 nonexposed patients. Progression to death was compared using time-dependent Cox models to account for potential differences in exposure to other cardiovascular risk-modifying treatments.. A total of 2466 eligible subjects exposed to n-3 fatty acids were matched. The majority of patients had concurrent treatment with lipid-lowering therapies, antihypertensives, and antiplatelets after first MI, with subjects exposed to n-3 fatty acids having a greater likelihood of concurrent exposure. For those initiating n-3 fatty acids within 90 days of first MI, the adjusted hazard ratio (aHR) was 0.782 (95% CI, 0.641-0.995; P = 0.0159); for those initiating treatment within 14 days, the aHR was 0.680 (95% CI, 0.481-0.961; P = 0.0288). In patients with type 2 diabetes at baseline, the aHRs were 0.714 (95% CI, 0.454-1.124) and 0.597 (95% CI, 0.295-1.211) when initiation was within 90 and 14 days, respectively. Use of n-3 fatty acids resulted in a consistent survival benefit under a range of scenarios quantitatively consistent with the overall effect.. After MI, early treatment with licensed n-3 fatty acids was associated with improvement in all-cause mortality in patients with and without type 2 diabetes, against a background of contemporary cardiovascular risk-modifying treatments.

Topics: Aged; Cardiovascular Agents; Diabetes Mellitus, Type 2; Disease Progression; Fatty Acids, Omega-6; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Primary Health Care; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United Kingdom

Diabetes mellitus has been associated with changes in the structure and function of the myocardium manifesting in the early stages of the disease as subtle systolic and diastolic dysfunction; the role of dobutamine stress echocardiography (DSE) in this setting remains unclear. We sought to evaluate the prevalence of dobutamine-induced systolic dysfunction amongst diabetic patients with normal at rest left ventricular ejection fraction and no coronary artery disease and to investigate whether an optimized therapeutic approach can reverse these abnormalities. 1,363 patients with DM referred to our echocardiography laboratory for DSE between January 2008 and June 2010 were prospectively investigated. Patients with normal left ventricular ejection fraction (LVEF) at rest and significant deterioration during peak dobutamine infusion (defined as a ≥10% decrease) in the absence of coronary artery disease or vasospasm were enrolled. They received on top of their usual treatment 5 mg perindopril and had their glycemic control intensified. At 60 days, all of them were controlled for clinical status and underwent a control DSE. 18 patients were included, there were 9 males and 9 females, mean age was 66.1 ± 10.2 years. All the patients had type II DM with a mean duration of 12.7 ± 6.6 years. They all had normal at rest echocardiographic findings with no wall motion abnormalities; mean LVEF was 62 ± 6%. At peak dobutamine, LVEF significantly deteriorated in all the patients with a mean 15 ± 5% decrease compared to baseline. After therapeutic optimization, Glycated haemoglobin improved from 8.53 ± 2.05% to 6.8 ± 0.6% (δ HbA1C = 1.73%, P = 0.001), mean LVEF at peak dobutamine infusion evolved from 47.17 ± 4.2% pre-optimization to 58 ± 4.8% at control (10.83% improvement; P < 0.001). In patients with DM and normal at rest LVEF, Dobutamine infusion during DSE can induce a significant deterioration in LVEF in the absence of coronary artery disease or vasospasm. This specific condition could be largely reversed through an optimized therapy based on a tighter metabolic control and a more stringent renin-angiotensin-aldosterone system inhibition.

Topics: Adrenergic Agonists; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Dobutamine; Echocardiography, Stress; Female; France; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Predictive Value of Tests; Prevalence; Prospective Studies; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Amides; Animals; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Fumarates; Humans; Male; Myocardial Infarction; Renin; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Aspirin; Blood Pressure; Cardiovascular Agents; Cerebrovascular Disorders; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypertension; Male; Primary Prevention

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Blood Pressure; Cardiology; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Delivery of Health Care; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diagnostic Imaging; Diet; Drug Combinations; Early Diagnosis; Electronic Health Records; Evidence-Based Medicine; Exercise; Female; General Practice; Health Promotion; Hospitalization; Humans; Hypercholesterolemia; Hypertension; Life Style; Lipids; Male; Medication Adherence; Middle Aged; Nurse's Role; Obesity; Patient Selection; Physician's Role; Primary Health Care; Prognosis; Risk Assessment; Risk Reduction Behavior; Self Care; Smoking; Smoking Cessation; Smoking Prevention; Socioeconomic Factors; Stress, Psychological

Coronary heart disease (CHD) is one of the most common long-term complications in people with type 2 diabetes. We analyzed whether or not gender differences exist in diabetes and CHD medication among people with type 2 diabetes.. The study was based on data from the baseline examination of the DIANA study, a prospective cohort study of 1,146 patients with type 2 diabetes conducted in South-West Germany. Information on diabetes and CHD medication was obtained from the physician questionnaires. Bivariate and multivariate analyses using logistic regression were employed in order to assess associations between gender and prescribed drug classes.. In total, 624 men and 522 women with type 2 diabetes with a mean age of 67.2 and 69.7 years, respectively, were included in this analysis. Compared to women, men had more angiopathic risk factors, including smoking, alcohol consumption and worse glycemic control, and had more often a diagnosed CHD. Bivariate analyses showed higher prescription of thiazolidinediones and oral combination drugs as well as of angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers and aspirin in men than in women. After full adjustment, differences between men and women remained significant only for ACE inhibitors (OR=1.44; 95%-confidence interval (CI): 1.11-1.88) and calcium channel blockers (OR=1.42, 95%-CI: 1.05-1.91).. These findings contribute to current discussions on gender differences in diabetes care. Men with diabetes are significantly more likely to receive oral combination drugs, ACE inhibitors and calcium channel blockers in the presence of coronary heart disease, respectively. Our results suggest, that diabetic men might be more thoroughly treated compared to women. Further research is needed to focus on reasons for these differences mainly in treatment of cardiovascular diseases to improve quality of care.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Prescriptions; Female; Germany; Healthcare Disparities; Humans; Hypoglycemic Agents; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Practice Patterns, Physicians'; Prevalence; Prospective Studies; Quality of Health Care; Risk Assessment; Risk Factors; Sex Factors

Aim of the study was investigation of influence of diabetes mellitus (DM) on rate of detection of multifocal atherosclerosis (MFA) in patients with ischemic heart disease (IHD) at examination before coronary artery bypass grafting (CABG). We retrospectively analyzed 2411 hospital forms of patients with IHD subjected to CABG. DM was found in 317 patients (group 1). Control group (n=350) comprised patients of comparable sex and age without DM. Clinico-anamnestic data, parameters of coronary angiography, ultrasound and angiographic study of the aorta, brachiocephalic and peripheral arterial beds were compared between these groups. Patients with diabetes compared with patients of the control group more frequently had increased thickness of intima media complex (92 and 77%, respectively; p=0.0001). Simultaneous involvement of 2 or more arterial beds were detected in 46.1% of patients with DM and in 33.1% of control patients. Involvement of only one (coronary) arterial basin was more frequent in patients without DM (p=0.0001). Multifactorial analysis showed that independent effect on detection of MFA produced intima media thickness, presence of DM and history of acute disturbance of brain circulation. Thus among patients with IHD MFA before CABG was found in 46.1% of patients with DM and 33.1% of similar sex and age patients without DM. Patients with DM require focused examination for detection of manifestations of MFA and conduct of necessary curative and preventive interventions.

Topics: Aged; Angiography; Atherosclerosis; Cardiovascular Agents; Carotid Intima-Media Thickness; Coronary Artery Bypass; Coronary Artery Disease; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Preventive Medicine; Risk Assessment; Risk Factors; Russia; Severity of Illness Index; Ultrasonography, Doppler, Color; Vascular Patency

The consideration of economic evidence in guideline development may be particularly important in health care management when different (drug) therapies show similar efficacy on clinical endpoints, such as in cardiovascular diseases. This article investigates to what extent the Dutch guideline 'cardiovascular risk management' (2006) considers cost-effectiveness and budget impact according to the most recent economic evidence.. We carried out a systematic review of economic evaluations on cholesterol-lowering drugs and antihypertensives followed by an assessment of guideline recommendations.. The guideline does not consider the most recent economic evidence but does consider cost-effectiveness based on economic evaluations performed in conjunction with clinical trials. Their conclusions are largely in agreement with the most recent economic evidence. An innovative aspect in the guideline is the application of a budget impact analysis to take accessibility and affordability constraints into account when considering cost-effectiveness.. Based on the most recent economic evidence, the guideline could be improved by more firmly formulating recommendations in favour of cost-effective drug therapies (simvastatin, pravastatin and low-dose diuretics) to stimulate compliance to the guideline in clinical practice.

Topics: Age Factors; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Utilization; Female; Guideline Adherence; Humans; Hypolipidemic Agents; Male; Middle Aged; Netherlands; Practice Guidelines as Topic; Quality-Adjusted Life Years; Risk Management; Sex Factors

Information relating the outcome of percutaneous coronary intervention to diabetes mellitus or hypertension is limited. The study objective was to describe the outcome in patients undergoing percutaneous coronary intervention in relation to diabetes and hypertension.. Data were extracted from 5 national registers: the Swedish Coronary Angiography and Angioplasty Register (all percutaneous coronary interventions), the Prescribed Drug Registry (all prescribed pharmaceuticals purchased in Swedish pharmacies), the Swedish Hospital Discharge Register (data on myocardial infarction, revascularization, stroke, and congestive heart failure from in-hospital and specialist health care), and the National Population Register and Cause of Death Register (data on death). We included all "first percutaneous coronary interventions" between January 1, 2006, and December 31, 2008 (n=44,268; followed an average of 1.9 [± 0.9] years).. Mortality was 6.4% and highest in patients with diabetes plus hypertension. Hypertension per se did not increase mortality or the risk for repeat intervention, but carried a 10% increased risk for subsequent myocardial infarction, increasing to a 4-fold increase when combined with diabetes. Stroke occurred in 2%; the importance of hypertension was evident in nondiabetic patients, but even stronger in diabetic patients. Congestive heart failure caused hospital admission in 8%, with a negative influence from hypertension with and without diabetes.. After percutaneous coronary intervention and with modern pharmacotherapy, diabetes had a negative effect on the outcome, especially when combined with hypertension. Hypertension per se was not associated with increased mortality but with an increased risk for myocardial infarction, stroke, and congestive heart failure, probably related to widespread coronary artery disease. Improved diabetes care might improve the prognosis.

Topics: Adult; Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Confounding Factors, Epidemiologic; Coronary Disease; Coronary Restenosis; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Prognosis; Registries; Retreatment; Stroke; Sweden; Treatment Outcome

Statins, a major component of the prevention of cardiovascular disease, aid progenitor cell functions in vivo and in vitro. Statins bearing a NO-releasing moiety were developed for their enhanced anti-inflammatory/anti-thrombotic properties. Here, we investigated if the NO-donating atorvastatin (NCX 547) improved the functions of circulating angiogenic cells (CACs).. Circulating angiogenic cells (CACs) were prepared from peripheral blood monocytes of healthy volunteers and type-2 diabetic patients and were cultured in low (LG) or high glucose (HG) conditions, in presence of atorvastatin or NCX 547 (both at 0.1 µM) or vehicle. Functional assays (outgrowth, proliferation, viability, senescence and apoptosis) were performed in presence of the endothelial NOS inhibitor L-NIO, the NO scavenger c-PTIO or vehicle.. Culturing in HG conditions lowered NO in CACs, inhibited outgrowth, proliferation, viability and migration, and induced cell senescence and apoptosis. NCX 547 fully restored NO levels and functions of HG-cultured CACs, while atorvastatin prevented only apoptosis in CACs. The activity of Akt, a pro-survival kinase, was increased by atorvastatin in LG-cultured but not in HG-cultured CACs, whereas NCX 547 increased Akt activity in both conditions. L-NIO partially blunted and c-PTIO prevented NCX 547-induced improvements in CAC functions. Finally, NCX 547 improved outgrowth and migration of CACs prepared from patients with type 2 diabetes.. NCX 547 was more effective than atorvastatin in preserving functions of CACs. This property adds to the spectrum of favourable actions that would make NO-releasing statins more effective agents for treating cardiovascular disease.

Topics: Aged; Anticholesteremic Agents; Apoptosis; Benzoates; Cardiovascular Agents; Cardiovascular Diseases; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellular Senescence; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazoles; Leukocytes, Mononuclear; Male; Middle Aged; Neovascularization, Physiologic; Nitrates; Nitric Oxide Donors; Nitric Oxide Synthase Type III; Ornithine; Proto-Oncogene Proteins c-akt; Pyrroles; Stem Cells

Diabetic retinopathy is a microvascular complication of diabetes mellitus whose prevalence is closely related to the presence of nephropathy and hypertension. The aim was to study clinical and pharmacological factors that are associated with an increased need for laser photocoagulation in patients with diabetic nephropathy and retinopathy.. Cross sectional study of 63 patients followed in the Diabetic Nephropathy consultation. Patients were divided into 2 groups according to whether or not previously have received photocoagulation. In each subgroup were studied demographic variables, anthropometric, laboratory, cardiovascular risk factors and treatment received by each patient for the control of hypertension, diabetes and others diseases.. We observed that the group had received photocoagulation had more years of diabetes evolution, more history of cardiovascular disease and a lower creatinine clearance. Similarly, the percentage of patients treated with carvedilol was significantly higher in the subgroup who had not received photocoagulation while the percentage of patients treated with beta-blockers was significantly higher in the subgroup that received photocoagulation; no significant differences was observed in the degree of control blood pressure.. Clinical and pharmacological factors related to the requirements of laser photocoagulation were years of diabetes evolution, history of cardiovascular disease, the stage of kidney disease and the treatment with beta-blockers.

Topics: Aged; Antihypertensive Agents; Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Female; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Laser Coagulation; Male; Middle Aged; Recurrence; Risk Factors; Smoking

Efficacy, efficiency, value, and harm constitute the terminology that is used to decide about drug licensing and reimbursement. This article discusses to what extent legal requirements dictate the way clinical trials are planned and assessed. Cardiovascular disease is the best example of indications where efficacy and safety are described with the same set of endpoints. It is explained that the assessment of clinical trials must not be restricted to the assessment of primary endpoints. Instead components of a composite endpoint, secondary endpoints, and relevant subgroups of the patient population all require careful inspection. In cases where efficacy and safety are not two sides of the same medal, assessment is either trivial, or extremely difficult, and eventually benefit and risk can be balanced only for individual cases.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Approval; Drug-Related Side Effects and Adverse Reactions; Endpoint Determination; Germany; Humans; Hypoglycemic Agents; Insurance, Pharmaceutical Services; Product Surveillance, Postmarketing; Risk Assessment; Rosiglitazone; Survival Analysis; Thiazolidinediones

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Comparative Effectiveness Research; Cross-Cultural Comparison; Diabetes Mellitus, Type 2; Effect Modifier, Epidemiologic; Europe; Female; Health Services Accessibility; Humans; Hyperlipidemias; Hypolipidemic Agents; International Cooperation; Male; Middle Aged; Monitoring, Physiologic; Myocardial Ischemia; Patient Compliance; Physical Fitness; Risk Factors; Secondary Prevention; Smoking

Metformin is an antihyperglycemic agent commonly used in diabetic patients. It is very effective and is able to reduce the plasma glucose and HbA1C. However, in some patients, specially those with comorbidities, metformin can provoke severe lactic acidosis with high morbimortality. Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures; in severe cases, procedures of extrarrenal purification like hemodialysis or continuous hemodiafiltration have been successfully used.

Topics: Acidosis, Lactic; Acute Kidney Injury; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antidepressive Agents; Cardiovascular Agents; Cardiovascular Diseases; Coma; Diabetes Mellitus, Type 2; Drug Synergism; Drug Therapy, Combination; Emergencies; Fatal Outcome; Female; Humans; Hypoglycemic Agents; Ibuprofen; Male; Metformin; Middle Aged; Nephrology; Physician's Role; Polypharmacy

To investigate time trends in vascular risk factors and medication use for patients referred to a vascular specialist with manifest vascular disease or type 2 diabetes mellitus (DM2).. Change in risk factor profile and medication use at referral over a 12-year period was evaluated and compared between patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, and DM2, who participated in the Second Manifestations of ARTerial disease study in the period of 1996-2007. A total of 4731 patients were included (mean age 59±11 years, 75% male) in the period 1996-2007. Obesity (body mass index ≥30 kg/m²) prevalence increased from 14 to 24%, and no change in smoking behavior was observed. The prevalence of hyperlipidemia (total cholesterol ≥4.5 mmol/l or low-density lipoprotein cholesterol ≥2.5 mmol/l) at referral declined from 92% in 1996-1997 to 45% in 2006-2007. The proportion of patients with blood pressure above 140/90 mmHg decreased from 66 to 51%. The use of lipid-lowering, blood pressure-lowering, and antithrombotic medication at referral increased over the observation period.. An improvement in risk factor profile was seen in patients referred with manifest vascular disease or DM2 over a 12-year period. Nevertheless, the prevalence of modifiable risk factors is still high leaving patients at elevated vascular risk.

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Utilization; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Netherlands; Practice Patterns, Physicians'; Prevalence; Prospective Studies; Risk Assessment; Risk Factors; Time Factors

This study aimed to evaluate the impact of angiographic and intravascular ultrasound (IVUS) features on clinical outcome in nondiabetic and type 2 diabetic patients after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation.. Repeat coronary angiography with IVUS imaging was performed after SES-based PCI for de-novo lesions in 128 diabetic and 327 nondiabetic patients (189 lesions and 504 lesions, respectively). The rate of major adverse cardiac events including cardiac death, non fatal myocardial infarction (MI), and target lesion revascularization during clinical follow-up was recorded.. In-stent and in-segment late loss, intimal hyperplasia volume, and percentage volumetric obstruction were similar, but stented external elastic membrane cross-sectional area and reference/stented segment ratio were lower in diabetic than in nondiabetic patients. Incomplete stent apposition (ISA) was less frequent, but occurrence of new coronary lesions was higher in diabetic than in nondiabetic patients. Despite similar target lesion revascularization, cumulative survival rates freedom from composite cardiac death and nonfatal MI or major adverse cardiac events were reduced in diabetic patients. Cox proportional hazards model identified diabetes, left ventricular ejection fraction, minimal stent CSA, maximal ISA area, atherosclerotic progression and lesion length as independent predictors of non fatal MI or mortality at follow-up.. In diabetic patients, PCI with SES implantation neutralizes the excess risk of intimal hyperplasia and decreases occurrence of ISA, but could not modify the propensity of increased adverse clinical outcomes at follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Heart Diseases; Humans; Hyperplasia; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The results of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) and Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) clinical trials raise important questions about the prevention and treatment of coronary heart disease among type 2 diabetics and nondiabetics. The BARI 2D and COURAGE trials showed that pharmacological therapy is as effective as surgery or angioplasty, because of the incidence of total mortality and cardiovascular disease events. The results are consistent with the clinical trials of lipid-lowering, antihypertensive therapy. The efficacy of lowering glycohemoglobin below 7% or benefits of specific glucose-lowering drugs is still unresolved. The BARI 2D trial focused on more advanced atherosclerotic disease. An important question is whether newly incident diabetics should be screened for subclinical atherosclerosis and treated aggressively with pharmacological therapy as in the BARI 2D trial. We are still uncertain whether raising high-density lipoprotein cholesterol will provide further benefit in reducing coronary heart disease. Better measurement of plaque morphology, determinants of hypercoagulable status, and drugs to reduce thrombosis and plaque are of high priority. Longer follow-up of the BARI 2D and COURAGE trials will provide important information about the risks of cardiovascular disease events and disability. It will be important but difficult to translate the results of the trials to community practice under the current health care system.

Topics: Angioplasty; Cardiovascular Agents; Community Medicine; Coronary Artery Bypass; Coronary Artery Disease; Delivery of Health Care; Diabetes Mellitus, Type 2; Drug Monitoring; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial established that, for patients with stable coronary artery disease (CAD), an initial management strategy of percutaneous coronary intervention plus optimal medical therapy did not reduce the long-term rates of death, myocardial infarction, or other cardiovascular events as compared with optimal medical therapy alone. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial reported that for patients with type 2 diabetes and stable CAD, a strategy of prompt coronary revascularization and intensive medical therapy did not reduce all-cause mortality or the composite of death, myocardial infarction or stroke compared with intensive medical therapy alone; however, in the group of patients appropriate for coronary artery bypass graft surgery (CABG), prompt revascularization with CABG resulted in significantly lower rates of major cardiovascular events, specifically myocardial infarction, than intensive medical therapy alone. The results from these two large multicenter clinical trials have led the medical community to re-evaluate how one should approach and treat patients with CAD and stable ischemic symptoms. In this special issue, experts from several disciplines discuss how the COURAGE and BARI 2D results have affected clinical practice and highlight the key questions that remain unanswered.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Case Management; Clinical Trials as Topic; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Critical Care; Diabetes Mellitus, Type 2; Guideline Adherence; Health Knowledge, Attitudes, Practice; Humans; Mortality; Multicenter Studies as Topic; Myocardial Infarction; Practice Guidelines as Topic; Risk Assessment; Stroke; Treatment Outcome

Topics: Atherosclerosis; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Humans; Hypoglycemic Agents; Nitric Oxide

Electrocardiographic ventricular repolarization QT parameters are independent risk factors for cardiovascular events and sudden cardiac death in diabetic patients. The aim of the study was to investigate the association of polymorphisms of the nitric oxide synthase 1 adaptor protein (NOS1AP) gene with QT interval in Chinese subjects with or without Type 2 diabetes.. Three single nucleotide polymorphisms (SNPs) (rs10494366, rs12143842 and rs12029454) were genotyped in 1240 Type 2 diabetic patients (631 men and 609 women) and 1196 normal controls (433 men and 763 women). Individuals with overt diseases other than diabetes were excluded. Heart-rate corrected QT interval (QTc) was determined by standard 12-lead ECG and Bazett formula. Sex-pooled analysis and sex-specific analysis for genotype-phenotype association were both conducted.. In the diabetic group, the rs12143842 T allele was associated with a 3.87-ms (P = 0.014, empirical P = 0.039) increase in QTc duration for each additional allele copy, while rs10494366 and rs12029454 exhibited no significant association with QTc. We found no evidence of association for the three SNPs in subjects with normal glucose regulation. No significant SNP-gender and -diabetes affection interaction was observed.. The genetic variant rs12143842 in NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes. Future studies in different populations are needed to validate this finding and to evaluate the impact of NOS1AP variants on cardiovascular events and sudden cardiac death in diabetic patients.

Topics: Adaptor Proteins, Signal Transducing; Asian People; Cardiovascular Agents; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Genetic Variation; Genotype; Humans; Long QT Syndrome; Male; Middle Aged; Myocardial Infarction; Phenotype; Polymorphism, Single Nucleotide; Risk Factors

To verify that adiponectin and tumor necrosis factor (TNF)-α reciprocally regulate their expression, thereby synergistically affecting both coronary and aortic endothelial dysfunction in type 2 diabetic mice.. We examined endothelium-dependent and endothelium-independent vasodilation/vasorelaxation of coronary arterioles and aortas in control mice, diabetic mice (Lepr(db)), and Lepr(db) treated with adiponectin or neutralizing antibody to TNF-α (anti-TNF-α). Endothelium-dependent vasodilation to acetylcholine in both coronary arterioles and aortas was blunted in Lepr(db) compared with control mice. Endothelium-independent vasodilation to sodium nitroprusside was comparable. Adiponectin and anti-TNF-α improved acetylcholine-induced vasodilation of coronary arterioles and aortas in Lepr(db) without affecting dilator response to sodium nitroprusside. Adiponectin protein expression was significantly reduced, and TNF-α protein expression was significantly greater, in coronary arterioles and aortas of Lepr(db) compared with control mice. Immunofluorescence staining results indicate that adiponectin was colocalized with endothelial cells. Anti-TNF-α treatment upregulated adiponectin protein expression in Lepr(db) coronary arterioles and aortas. Adiponectin administration reduced TNF-α protein expression in Lepr(db). Although adiponectin receptor 1 protein expression in coronary arterioles and aortas was similar between control and diabetic mice, adiponectin receptor 2 protein expression was significantly reduced in Lepr(db). Both adiponectin and anti-TNF-α inhibited IκBα phosphorylation and nuclear factor κB protein expression in Lepr(db), suggesting that adiponectin and TNF-α signaling may converge on nuclear factor κB to reciprocally regulate their expression.. A reciprocal suppression occurs between adiponectin and TNF-α that fundamentally affects the regulation of coronary and aortic endothelial function in type 2 diabetic mice.

Topics: Adiponectin; Animals; Antibodies, Monoclonal; Aorta; Arteries; Cardiovascular Agents; Coronary Vessels; Diabetes Mellitus, Type 2; Endothelium, Vascular; Feedback, Physiological; Male; Mice; Tumor Necrosis Factor-alpha; Vasodilation

Topics: Aged; Ankle Brachial Index; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Female; Humans; Male; Middle Aged; Patient Selection; Peripheral Arterial Disease; Primary Prevention; Time Factors; Treatment Outcome

Glucagon-like peptide-1 (GLP-1) is an incretin secreted in response to nutrient ingestion. Understanding the incretin effect on diabetes pathophysiology has led to development of a new class of agents termed incretin mimetics. Exenatide is the first GLP-1 agonist approved to treat type 2 diabetes mellitus (T2DM). Clinical studies have demonstrated exenatide's efficacy in improving glycemic control, often coupled with weight loss. Studies are investigating the potential cardiovascular benefits of GLP-1 agonists. Blood pressure, cholesterol levels, C-reactive protein, and insulin resistance may improve in patients treated with exenatide. The direct effect of GLP-1 on cardiac myocytes and vascular smooth muscle has been an active area of investigation. Infusions of GLP-1 in animal models and human subjects with heart failure have demonstrated significantly improved cardia parameters. In patients with T2DM, GLP-1 infusion has been shown to improve endothelial function, irrespective of changes in insulin sensitivity. These pilot studies provide a foundation for developing therapies aimed at modulating incretin physiology for the additional benefit on the cardiovascular system in patients with T2DM and heart disease.

Topics: Cardiovascular Agents; Cardiovascular System; Diabetes Mellitus, Type 2; Exenatide; Humans; Incretins; Peptides; Venoms

Cardiovascular diseases have the pole-position on the list of morbidity and mortality statistics. Despite the great advances have been made in management of cardiovascular diseases, prevalence of these disorders increases worldwide, and even younger and younger ages are threatened. This phenomenon is strongly related to obesity and type 2 diabetes pandemic, which shows an unequivocal association with expansion of modernized life-style. The pathomechanism proposed to have central role is the chronic stress induced by civilized life-conduct. The authors criticizes the everyday practice suggested for management of cardiovascular diseases, focusing on normalization of cardiovascular risk factors, instead of fighting against the primary cause ie. chronic stress. There is growing evidence, that achieving the target values defined in guide-lines will not necessarily result in improvement of patient related clinical outcomes. The statistical approach generally practiced in randomized clinical trials is primarily striving for the drug-sale, instead of discovering novel pathophysiological relations. Pharmaceutical industry having decisive role in research and patient-care is mainly interested in profit-sharing, therefore patients' interest can not be optimally realized, and costs are unnecessarily augmented. Separation of patient-, and business-oriented medical care is an ethical question of fundamental importance.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Civilization; Data Interpretation, Statistical; Delivery of Health Care; Diabetes Mellitus, Type 2; Drug Costs; Drug Industry; Evidence-Based Medicine; Global Health; Health Care Costs; Humans; Life Style; Metabolic Syndrome; Obesity; Patient Advocacy; Physician's Role; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Factors; Stress, Psychological

Mildronate [3-(2,2,2-trimethylhydrazinium) propionate] is an anti-ischaemic drug whose mechanism of action is based on its inhibition of L-carnitine biosynthesis and uptake. As L-carnitine plays a pivotal role in the balanced metabolism of fatty acids and carbohydrates, this study was carried out to investigate whether long-term mildronate treatment could influence glucose levels and prevent diabetic complications in an experimental model of type 2 diabetes in Goto-Kakizaki (GK) rats.. GK rats were treated orally with mildronate at doses of 100 and 200 mg.kg(-1) daily for 8 weeks. Plasma metabolites reflecting glucose and lipids, as well as fructosamine and beta-hydroxybutyrate, were assessed. L-carnitine concentrations were measured by ultra performance liquid chromatography with tandem mass spectrometry. An isolated rat heart ischaemia-reperfusion model was used to investigate possible cardioprotective effects. Pain sensitivity was measured with a tail-flick latency test.. Mildronate treatment significantly decreased L-carnitine concentrations in rat plasma and gradually decreased both the fed- and fasted-state blood glucose. Mildronate strongly inhibited fructosamine accumulation and loss of pain sensitivity and also ameliorated the enhanced contractile responsiveness of GK rat aortic rings to phenylephrine. In addition, in mildronate-treated hearts, the necrosis zone following coronary occlusion was significantly decreased by 30%.. These results demonstrate for the first time that in GK rats, an experimental model of type 2 diabetes, mildronate decreased L-carnitine contents and exhibited cardioprotective effects, decreased blood glucose concentrations and prevented the loss of pain sensitivity. These findings indicate that mildronate treatment could be beneficial in diabetes patients with cardiovascular problems.

Topics: 3-Hydroxybutyric Acid; Administration, Oral; Animals; Blood Glucose; Cardiovascular Agents; Carnitine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Fructosamine; Heart; Hyperalgesia; Hypoglycemic Agents; In Vitro Techniques; Lipids; Male; Methylhydrazines; Myocardial Ischemia; Pain Threshold; Rats; Rats, Wistar

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Diabetes Mellitus, Type 2; Humans; Information Dissemination; Myocardial Ischemia; Patient Selection; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Severity of Illness Index; Treatment Outcome

The literature indicates that cardiovascular drug use is higher during the years prior to diagnosis of type 2 diabetes mellitus. As there are pharmaco-epidemiological and economic consequences of enhanced medication use prior to diagnosis of diabetes, there is a need for a comparative analysis of the drug-use pattern by patients with a subsequent diagnosis of diabetes and control patients. This pilot study aimed to investigate cardiovascular drug use in patients with a subsequent diagnosis of diabetes using data extracted from 200 community pharmacies in the Belgian township of Hasselt.. Based on community pharmacy data, a retrospective case-control study compared the drug use of patients with a subsequent diagnosis of type 2 diabetes (cases) with patients without a subsequent diagnosis (controls). Cases were identified if patients started taking metformin (and possibly other drugs used in diabetes) during the 2004-2006 study period. Drug use was expressed as a binary variable, reflecting whether or not a patient took drugs belonging to a specific cardiovascular subclass.. Our dataset consisted of 158 cases with a subsequent diagnosis of type 2 diabetes and 632 control patients. Patients with a subsequent diagnosis of type 2 diabetes had a higher propensity to take cardiovascular drugs prior to diagnosis than control patients. This trend was observed across all cardiovascular drug classes, except for calcium-channel blockers, and was statistically significant for beta-blocking agents and agents acting on the renin-angiotensin system.. A positive association was observed between cardiovascular drug use and subsequent diagnosis of type 2 diabetes. This study emphasizes the potential role for community pharmacy in early identification of diabetes using more targeted screening based on cardiovascular drug use as derived from pharmacy databases.

Topics: Adrenergic beta-Antagonists; Aged; Belgium; Cardiovascular Agents; Case-Control Studies; Community Pharmacy Services; Diabetes Mellitus, Type 2; Female; Humans; Male; Mass Screening; Middle Aged; Pilot Projects; Renin-Angiotensin System; Retrospective Studies

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Inflammation; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Signal Transduction; Tumor Necrosis Factor-alpha

Topics: Administration, Oral; Blood Glucose; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Treatment Outcome

Cardiovascular diseases or risk factors (CVDR) seem to be more common in psoriasis patients than in the general population.. We assessed the relationship of psoriasis with CVDR by analysis of healthcare claims data using a cross-sectional, prevalence-based study design.. The IMS Health and MarketScan claims databases were used to identify adults with psoriasis diagnostic codes. Non-psoriasis controls were matched 3:1 based on age, gender, census region and previous medical insurance coverage. Odds ratios evaluated the relative prevalence of CVDR, and Mantel-Haenszel confidence intervals were estimated.. CVDR prevalence was generally higher in psoriasis patients than controls in both datasets. Odds ratios for atherosclerosis, congestive heart failure, type 2 diabetes, and peripheral vascular disease were >or=1.20 for psoriasis patients. Elevated disease severity was associated with a higher rate of CVDR, but varied somewhat by dataset and condition.. Elevated CVDR rates were found in psoriasis patients compared with controls. This pattern merits further examination.

Topics: Adult; Aged; Anti-Obesity Agents; Cardiovascular Agents; Cardiovascular Diseases; Cross-Sectional Studies; Databases as Topic; Dermatologic Agents; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; International Classification of Diseases; Male; Middle Aged; Phototherapy; Prevalence; Psoriasis; Risk Factors; United States

Topics: Cardiovascular Agents; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Humans; Hyperkalemia; Hypertension; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Sulfonylurea Compounds

Previous studies reveal major differences in the estimated cardiovascular risk in diabetes mellitus, including uncertainty about the risk in young patients. Therefore, large studies of well-defined populations are needed.. All residents in Denmark > or = 30 years of age were followed up for 5 years (1997 to 2002) by individual-level linkage of nationwide registers. Diabetes patients receiving glucose-lowering medications and nondiabetics with and without a prior myocardial infarction were compared. At baseline, 71 801 (2.2%) had diabetes mellitus and 79 575 (2.4%) had a prior myocardial infarction. Regardless of age, age-adjusted Cox proportional-hazard ratios for cardiovascular death were 2.42 (95% confidence interval [CI], 2.35 to 2.49) in men with diabetes mellitus without a prior myocardial infarction and 2.44 (95% CI, 2.39 to 2.49) in nondiabetic men with a prior myocardial infarction (P=0.60), with nondiabetics without a prior myocardial infarction as the reference. Results for women were 2.45 (95% CI, 2.38 to 2.51) and 2.62 (95% CI, 2.55 to 2.69) (P=0.001), respectively. For the composite of myocardial infarction, stroke, and cardiovascular death, the hazard ratios in men with diabetes only were 2.32 (95% CI, 2.27 to 2.38) and 2.48 (95% CI, 2.43 to 2.54) in those with a prior myocardial infarction only (P=0.001). Results for women were 2.48 (95% CI, 2.43 to 2.54) and 2.71 (95% CI, 2.65 to 2.78) (P=0.001), respectively. Risks were similar for both diabetes types. Analyses with adjustments for comorbidity, socioeconomic status, and prophylactic medical treatment showed similar results, and propensity score-based matched-pair analyses supported these findings.. Patients requiring glucose-lowering therapy who were > or = 30 years of age exhibited a cardiovascular risk comparable to nondiabetics with a prior myocardial infarction, regardless of sex and diabetes type. Therefore, requirement for glucose-lowering therapy should prompt intensive prophylactic treatment for cardiovascular diseases.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Denmark; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Forecasting; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Recurrence; Registries; Risk; Stroke; Survival Analysis

Vascular dysfunction, which presents either as an increased response to vasoconstrictors or an impaired relaxation to dilator agents, results in worsened cardiovascular outcomes in diabetes. We have established that the mesenteric circulation in Type 2 diabetes is hyperreactive to the potent vasoconstrictor endothelin-1 (ET-1) and displays increased nitric oxide-dependent vasodilation. The current study examined the individual and/or the relative roles of the ET receptors governing vascular function in the Goto-Kakizaki rat, a mildly hyperglycemic, normotensive, and nonobese model of Type 2 diabetes. Diabetic and control rats received an antagonist to either the ET type A (ETA; atrasentan; 5 mg x kg(-1) x day(-1)) or type B (ET(B); A-192621; 15 or 30 mg x kg(-1) x day(-1)) receptors for 4 wk. Third-order mesenteric arteries were isolated, and vascular function was assessed with a wire myograph. Maximum response to ET-1 was increased in diabetes and attenuated by ETA antagonism. ETB blockade with 15 mg/kg A-192621 augmented vasoconstriction in controls, whereas it had no further effect on ET-1 hyperreactivity in diabetes. The higher dose of A-192621 showed an ETA-like effect and decreased vasoconstriction in diabetes. Maximum relaxation to acetylcholine (ACh) was similar across groups and treatments. ETB antagonism at either dose had no effect on vasorelaxation in control rats, whereas in diabetes the dose-response curve to ACh was shifted to the right, indicating a decreased relaxation at 15 mg/kg A-192621. These results suggest that ETA receptor blockade attenuates vascular dysfunction and that ETB receptor antagonism exhibits differential effects depending on the dose of the antagonists and the disease state.

Topics: Acetylcholine; Animals; Atrasentan; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Male; Mesenteric Arteries; Microcirculation; Myography; Peptides, Cyclic; Pyrrolidines; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B; Up-Regulation; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Viper Venoms

Topics: Administration, Oral; Aged; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Male; Platelet Aggregation Inhibitors

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Hypoglycemic Agents; Nitric Oxide; Signal Transduction; Treatment Outcome

Transient reduction in coronary perfusion pressure in the isolated mouse heart increases microvascular resistance (paradoxical vasoconstriction) by an endothelium-mediated mechanism. To assess the presence and extent of paradoxical vasoconstriction in hearts from normal and diabetic rats and to determine whether increased heme oxygenase (HO)-1 expression and HO activity, using cobalt protoporphyrin (CoPP), attenuates coronary microvascular response, male Wistar rats were rendered diabetic with nicotinamide/streptozotocin for 2 wk and either CoPP or vehicle was administered by intraperitoneal injection weekly for 3 wk (0.5 mg/100 g body wt). The isolated beating nonworking heart was submitted to transient low perfusion pressure (20 mmHg), and coronary resistance (CR) was measured. During low perfusion pressure, CR increased and was associated with increased lactate release. In diabetic rats, CR was higher, HO-1 expression and endothelial nitric oxide synthase were downregulated, and inducible nitric oxide synthase and O(2)(-) were upregulated. After 3 wk of CoPP treatment, HO activity was significantly increased in the heart. Upregulation of HO-1 expression and HO activity by CoPP resulted in the abolition of paradoxical vasoconstriction and a reduction in oxidative ischemic damage. In addition, there was a marked increase in serum adiponectin. Elevated HO-1 expression was associated with increased expression of cardiac endothelial nitric oxide synthase, B-cell leukemia/lymphoma extra long, and phospho activator protein kinase levels and decreased levels of inducible nitric oxide synthase and malondialdehyde. These results suggest a critical role for HO-1 in microvascular tone control and myocardial protection during ischemia in both normal and mildly diabetic rats through the modulation of constitutive and inducible nitric oxide synthase expression and activity, and an increase in serum adiponectin.

Topics: Adiponectin; Animals; bcl-X Protein; Cardiovascular Agents; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Enzyme Induction; Heme Oxygenase (Decyclizing); Lactic Acid; Male; Malondialdehyde; Microcirculation; Myocardial Reperfusion Injury; Myocardium; Niacinamide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Phosphorylation; Proto-Oncogene Proteins c-akt; Protoporphyrins; Rats; Rats, Wistar; Severity of Illness Index; Streptozocin; Superoxides; Time Factors; Up-Regulation; Vascular Resistance; Vasoconstriction

There have been increasing evidences that atherosclerosis is not the result of diabetes mellitus, but that both type 2 diabetes mellitus and atherosclerosis may share common pathogenesis, as Stern proposed as 'common soil' hypothesis in 1995. There are several candidates for 'common soil', such as insulin resistance, vascular inflammation and endothelial dysfunction. Recently many of clinical studies have indicated that some drugs can prevent or delay the development of cardiovascular diseases (CVD). Furthermore, many studies have suggested that some classes of drugs may prevent the development of type 2 diabetes. It is to be noted that most of the drugs may have both actions, i.e., to prevent development of new diabetes and to prevent CVD. Furthermore, they are reported to inhibit inflammation or endothelial dysfunction. Taken together, it is hypothesized that the drug which may have antiatherogenetic action may also have antidiabetic action, and vice versa. This hypothesis may provide the new insights into perspectives of drug development both to prevent type 2 diabetes and to prevent CVD.

Topics: Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Hypoglycemic Agents; Inflammation; Models, Biological

The placebo-controlled Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) is the only study of secondary prevention in patients with type 2 diabetes to have shown a benefit. While treatment with pioglitazone did not significantly reduce the primary composite endpoint, it did significantly lower the incidence of many of its components, including all-cause mortality, nonfatal myocardial infarction (including silent infarctions), stroke, acute coronary syndrome and limb amputation. Pioglitazone also reduced the relative risk of the combined endpoint of death, myocardial infarction and stroke by 16% compared to placebo. In the subgroup of patients with myocardial infarction, the risk of myocardial infarction and acute coronary syndromes was reduced with the active treatment, which also substantially reduced (-47%) the risk of stroke in patients with prior stroke. Pioglitazone has furthermore demonstrated numerous antiatherogenic effects in clinical and preclinical investigations.

Topics: Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Pioglitazone; Randomized Controlled Trials as Topic; Thiazolidinediones

Most studies of cardiovascular risk factors (CVRF) conducted in our environment concentrate in a single CVRF. The PREVENCAT study was designed to estimate the control of CVRF in the population attended in primary care presenting arterial hypertension (HT), type 2 diabetes mellitus (DM2) and/or hypercholesterolemia (HC) as well as to assess the prevalence of Metabolic Syndrome in these patients.. Multicenter, cross-sectional study, in patients with HT, DM2 and/or HC, consecutively recruited by primary care physicians in Spain. The blood pressure, cholesterol, basal glycaemia, obesity, smoking and physical activity were assessed. The degree of control of these CVRF and the prevalence of MS were estimated.. 2,649 patients were recruited, aged 64 (11.3) years, with a 51.6% of women. The most frequent diagnosis was HT (78.9%), followed by HC (58.4%) and DM2 (37.4%). In the whole sample, the percentages of patients who had a control or had initially normal values of blood pressure, cholesterol and basal glycemia were 40.0% (confidence interval [CI], 95% 38.2-41.9), 42.6% (95% CI, 40.5-44.7) and 62.7% (95% CI, 60.8-64.5), respectively. 15.6% of cases (95% CI, 14.3-17.0) had body mass index < or = 25 kg/m2; 87.5% were non-current smokers (95% CI, 86.2-88.8); and 46.2% practiced regular physical activity (95% CI, 44.3-48.1). 40% of patients had < or = 2 CVRF in good control. The prevalence of metabolic syndrome was 50.6% (95% CI, 48.7-52.5).. The control of the CVRF considered in primary care attended population is insufficient. Hardly one of each 2 patients with HT, DM2 and HC is under control. The overweight and sedentarism control is still poorer.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Prevalence; Primary Health Care; Risk Factors; Spain

This article serves as an introductory overview to this supplement which covers type 2 diabetes as an atherosclerotic disease, the evidence base for treatment of the various vascular risk factors, and provides a detailed appraisal of the potential for thiazolidinediones to play a major role in overall diabetes management, not just for glycaemia, but also from the point of view of cardio vascular disease.. We are clearly entering into an extremely interesting time in the management of type 2 diabetes. The thiazolidinediones have the potential to target a fundamental defect in type 2 diabetes as well as to improve CV risk in this extremely high risk group of patients. Time will tell whether the obvious potential of these agents will result in dramatically improved clinical outcomes.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hypoglycemic Agents; Thiazolidinediones

The prevalence of type 2 diabetes mellitus is rapidly increasing. Myocardial dysfunction may be a consequence of diabetic cardiomyopathy and it contributes to the poor prognosis of diabetic patients.. This study was designed to test whether tissue Doppler imaging might be a suitable tool for early detection of myocardial dysfunction in diabetic patients.. Forty-three diabetic patients and 33 non-diabetic controls, including age-matched subgroups without evidence of coronary artery disease (n=12), were recruited if they had normal LV-function by standard 2-D echocardiography and no clinical signs of heart failure. They were investigated with tissue Doppler imaging at rest and during pharmacological stress with dipyridamole and/or dobutamine. Myocardial function was calculated as the mean value from six basal myocardial segments for peak velocity at systole (Vs), early diastole (Ve) and atrial contraction (Va).. Compared to controls, diabetic patients had compromised Ve at rest (8.5 +/- 1.7 vs. 9.6 +/- 1.9 cm/sec, p < 0.02), as did the subgroups without coronary artery disease (9.3 +/- 1.7 vs. 10.7 +/- 1.5 cm/sec, p < 0.05). Dobutamine stress resulted in lower Vs (10.7 +/- 2.7 vs. 13.6 +/- 3.4 cm/sec, p < 0.05) and Ve (10.0 +/- 2.1 vs. 13.1 +/- 3.8 cm/sec, p < 0.05) in the diabetic patients, demonstrating an impaired increase of Vs, Vd and Va (p < 0.05, p < 0.0003 and p < 0.03, respectively). An inverse correlation was observed between Ve and age in both control and diabetic individuals. Thus, abnormal values were defined in relation to age.. Diastolic and systolic myocardial dysfunction in patients with type 2 diabetes may be identified by quantitative tissue Doppler imaging before the onset of clinical signs of heart failure and before the appearance of traditional echocardiographic indices of systolic myocardial dysfunction.

Topics: Age Factors; Aged; Cardiomyopathies; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diastole; Dipyridamole; Dobutamine; Echocardiography, Doppler, Pulsed; Echocardiography, Stress; Female; Humans; Male; Middle Aged; Myocardial Contraction; Systole

To review the role of cardiovascular disease and therapy in the onset and recurrence of preretinal/vitreous haemorrhage in diabetic patients.. Retrospective case note analysis of diabetic patients with vitreous haemorrhage from the Diabetic Eye Clinic at Birmingham Heartlands Hospital.. In total, 54 patients (mean age 57.1, 37 males, 20 type I vs 34 type II diabetic patients) were included. The mean (SD) duration of diagnosed diabetes at first vitreous haemorrhage was significantly longer, 21.9 (7.6) years for type I and 14.8 (9.3) years for type II diabetic patients (P < 0.01, unpaired t-test, two-tailed).Aspirin administration was not associated with a significantly later onset of vitreous haemorrhage. Four episodes were associated with ACE-inhibitor cough. There was a trend towards HMGCoA reductase inhibitor (statin) use being associated with a delayed onset of vitreous haemorrhage: 21.4 years until vitreous haemorrhage (treatment group) vs 16.2 years (nontreatment group) (P = 0.09, two-tailed, unpaired t-test, not statistically significant). During follow-up 56 recurrences occurred, making a total of 110 episodes of vitreous haemorrhage in 79 eyes of 54 patients. The mean (range) follow-up post haemorrhage was 1067 (77-3842) days, with an average of 1.02 recurrences. Age, gender, diabetes type (I or II) or control, presence of hypertension or hypercholesterolaemia, and macrovascular complications were not associated with a significant effect on the 1-year recurrence rate. Aspirin (and other antiplatelet or anticoagulant agents) and ACE- inhibitors appeared to neither increase nor decrease the 1-year recurrence rate. However, statin use was significantly associated with a reduction in recurrence (Fisher exact P < 0.05; two-tailed) with an odds ratio (95% CI) of 0.25 (0.1-0.95).. In this retrospective analysis, the onset of preretinal/vitreous haemorrhage was not found to be accelerated by gender, hypertension, hypercholesterolaemia, evidence of macrovascular disease, or HbA1c. Neither aspirin nor ACE-inhibitor administration accelerated the onset or recurrence of first vitreous haemorrhage. Statins may have a protective role, both delaying and reducing the recurrence of haemorrhage.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Retinal Hemorrhage; Retrospective Studies; Vitreous Hemorrhage

Topics: Animals; Anti-Obesity Agents; Cardiovascular Agents; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Enzyme Inhibitors; Humans; Metabolism; Narcotic Antagonists; Receptors, Somatostatin

Atherothrombosis is a systemic disease affecting coronary, cerebral, and lower limb arteries, and requiring secondary prevention measures.. Data from three observational studies carried out in 1999-2000 (ECLAT1, APRES, PRISMA) were pooled to describe the prevalence of cardiovascular risk factors and the patterns of drug use in atherothrombotic patients.. General practitioners and cardiologists engaged in a private practice and evenly distributed in France recruited consecutive patients who had a history of at least one atherothrombotic event: myocardial infarction (MI), ischaemic stroke, and/or peripheral arterial disease (PAD).. The sample was composed of 14 544 patients (men: 75.0%, age 75 or older: 31.0%). At least one of the four major risk factors (smoking, hypertension, hypercholesterolaemia, diabetes) was present in 94.3% of the sample. Prevalence of drug use was: 78.8% (antiplatelet agents), 48.5% (statins), 36.7% (beta-blockers), and 33.4% [angiotensin-converting enzyme (ACE) inhibitors]. After adjustment for confounders, statins were taken in a significantly larger extent in patients with a history of isolated MI than in those with a previous ischaemic stroke or PAD, or in patients who suffered from both MI and ischaemic stroke. Isolated MI (as compared with ischaemic stroke and PAD) was significantly and independently associated with a higher probability to take antiplatelet agents, beta-blockers or ACE inhibitors.. At least one conventional risk factor was observed in almost all atherothrombotic patients. Use of preventive drugs was lower in patients with a history of ischaemic stroke or PAD, and should increase, accordingly to the results of recent randomized controlled trials.

Topics: Adult; Aged; Brain Ischemia; Cardiovascular Agents; Diabetes Mellitus, Type 2; Female; France; Humans; Hypercholesterolemia; Hypertension; Life Style; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Prevalence; Risk Factors; Smoking; Stroke

To determine the extent to which cardiovascular therapies are prescribed in primary care for those with diabetes, compared with those without diabetes.. Population study of patients with and without diabetes identified using a national primary care prescribing database. All patients receiving a prescription for any diabetes therapy, including insulin and oral hypoglycaemic drugs, or diagnostic test kit for glucose ( n=8523) and those receiving no such therapies ( n=145,756) during a 1-year period (September 1999-August 2000) in the Eastern Regional Health Authority of Ireland were identified. In addition, a sub-set of patients receiving a nitrate prescription, a marker for ischaemic heart disease (IHD), were also identified ( n=14,826). Odds ratios and 95% confidence intervals for prescribing of cardiovascular therapies between those with diabetes and those without, adjusted for age and gender, were calculated using logistic regression.. The proportion of those (and 95% CES) with diabetes and IHD prescribed secondary preventative therapies was 37.3% (35.0, 39.6) for statins, 55.3% (53.0, 57.6) for angiotension converting enzyme inhibitors, 34.7% (32.5, 36.9) for beta blockers, 73.3% (71.2, 75.4) for aspirin, 4.4% (3.4, 5.4) for angiotensin-II antagonists and 2.5% (1.8, 3.2) for fibrates. The adjusted odds ratios for prescribing in those with diabetes compared with those without are 1.44 (1.30, 1.61) for statins, 3.09 (2.79, 3.42) for angiotension converting enzyme inhibitors, 0.82 (0.74, 0.91) for beta blockers, 1.23 (1.09, 1.38) for aspirin, 1.47 (1.13, 1.87) for angiotensin-II receptor blockers and 4.23 (2.88, 6.14) for lipid-lowering fibrates.. The greater rate of prescribing of cardiovascular therapies in those with diabetes relative to those without is not unexpected given the higher risk of coronary heart disease in those with diabetes. However, the proportion of patients with diabetes, particularly those with established IHD, prescribed cardiovascular therapies is considerably below that recommended in local and international guidelines.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Prescriptions; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardial Ischemia; Nitrates; Pharmacoepidemiology; Primary Health Care

1. The current study examined the hypothesis that endothelial production of hydrogen peroxide (H2O2) mediates relaxations to acetylcholine (ACh) in aorta and small mesenteric arteries (SMA) from mice. 2. Relaxations to ACh (0.01-10 microM) and H2O2 (0.1-1000 microM) were produced in aorta and SMA isolated from wild-type C57BL/6 mice and type II diabetic mice (db/db). In SMA, relaxations to ACh were produced in the presence of N omega-nitro-L-arginine methyl ester (100 microM) and indomethacin (Indo, 10 microM). 3. 1-H[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one (10 microM) significantly reduced ACh-induced relaxations in SMA, abolished responses in aorta, but had no effect on relaxations induced by H2O2. Catalase (2500 U ml-1) abolished responses to H2O2, but did not alter relaxations to ACh in the SMA and only caused a small rightward shift in responses to ACh in the aorta. 4. ACh-, but not H2O2-, mediated relaxations were significantly reduced by tetraethylammonium (10 mM), the combination of apamin (1 microM) and charybdotoxin (100 nM), and 25 mm potassium chloride (KCl). Higher KCl (60 mM) abolished relaxations to both ACh and H2O2. Polyethylene glycolated superoxide dismutase (100 U ml-1), the catalase inhibitor 3-amino-1,2,4-triazole (3-AT, 50 mM) and treatment with the copper chelator diethyldithiolcarbamate (3 mM) did not affect relaxations to ACh. 5. H2O2-induced relaxations were endothelium-independent and were not affected by ethylene diamine tetraacetic acid (EDTA 0.067 mM), 4-aminopyridine (1 mM), ouabain (100 microM) and barium (30 microM), 3-AT or Indo. 6. Although the data from this study show that H2O2 dilates vessels, they do not support the notion that H2O2 mediates endothelium-dependent relaxations to ACh in either aorta or SMA from mice.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Apamin; Cardiovascular Agents; Catalase; Charybdotoxin; Diabetes Mellitus, Type 2; Endothelium, Vascular; Enzyme Inhibitors; Hydrogen Peroxide; Indomethacin; Male; Mesenteric Arteries; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Muscle Relaxation; Muscle, Smooth, Vascular; NG-Nitroarginine Methyl Ester; Potassium Channel Blockers; Potassium Chloride; Quinoxalines; Tetraethylammonium; Vasodilator Agents

Although patients with type 2 diabetes mellitus and cardiovascular disease share common risk factors, the link between these diseases remains largely unexplained. In this case-control study, the earlier use of cardiovascular drugs (before the diagnosis of diabetes) was investigated among cases with type 2 diabetes mellitus and controls without diabetes. Using the PHARMO database, we identified 4,864 patients who were prescribed oral hypoglycaemic agent (OHA) therapy between 1985-1998 in the Netherlands. For each case, two controls matched on age, sex and pharmacy were randomly selected. Controls had not received insulins or OHA therapy. There were 2,656 (55.0%) cases compared with 2,727 (28.1%) controls who used cardiovascular drugs at the start of OHA therapy. Cases had a 3.5-fold increased risk of cardiovascular drug use (OR(95% CI) = 3.5 [3.2-3.8]) compared to controls. Differences in cardiovascular drug use were noted as early as 7 years before the start of OHA therapy, distinguishing cases from controls. Our finding that patients with type 2 diabetes mellitus were more likely to receive treatment for cardiovascular disease several years before they start diabetes therapy supports the hypothesis of a common underlying mechanism of these two disorders and stresses the importance of the pre-diabetic state.

Topics: Administration, Oral; Adult; Aged; Cardiovascular Agents; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Risk Factors

To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from 1 year before until 6 years after the start of oral antidiabetic therapy.. In this cohort study, 2,584 patients with type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997. Nondiabetic subjects were 1:1-matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies.. Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23-1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33-1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects. Differences between patients with type 2 diabetes and nondiabetic subjects lessened from 1 year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks for diuretics, beta-blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were approximately 50% in the years close to the start of oral antidiabetic treatment and decreased to approximately 33% in the following years.. Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially beta-blockers, whereas cardiovascular hospitalizations first decreased and then stabilized.

Topics: Cardiovascular Agents; Databases as Topic; Diabetes Mellitus, Type 2; Drug Therapy; Female; Hospitalization; Humans; Male; Netherlands; Pharmacies; Records

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Utilization; Family Practice; Female; Guideline Adherence; Humans; Male; Middle Aged; Practice Guidelines as Topic; Risk Factors; Sweden

We examined endothelium-dependent relaxation in the aortas and renal arteries of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus, in comparison with non-diabetic Long-Evans Tokushima Otsuka rats as controls. Acetylcholine-induced relaxation in both arteries was attenuated, and the attenuation was restored to the control level by indomethacin. The relaxation was inhibited completely in the aortas, but only partially in renal arteries by N(G)-nitro-L-arginine methyl ester, and the degree of the latter inhibition was greater in OLETF rats than in the controls. The relaxation was inhibited by aminoguanidine in both arteries of OLETF rats but not in the controls. Serum NO(2) plus NO(3) levels significantly increased in OLETF rats. These results suggest that impairment of relaxation in OLETF rat arteries is due to increased release of contractile factors but not decreased release of nitric oxide.

Topics: Acetylcholine; Animals; Aorta; Biological Factors; Blood Glucose; Body Weight; Cardiovascular Agents; Charybdotoxin; Diabetes Mellitus, Type 2; Drug Interactions; Endothelium, Vascular; Enzyme Inhibitors; Guanidines; In Vitro Techniques; Indomethacin; Lipids; NG-Nitroarginine Methyl Ester; Nitrates; Nitric Oxide; Nitrites; Rats; Rats, Inbred OLETF; Renal Artery; Vasodilation

To describe and compare the distribution of prescribed drugs in diabetic patients between 1992 and 1995.. Two cross-sectional surveys of a random selection of medical records of diabetic patients, from three community health centres (CHCs) in the Stockholm metropolitan area, were carried out. The age of the subjects ranged from 20 to 84 years. The number of prescriptions of pharmaceutical preparations given to the diabetic patients was noted, as well as classification of the diabetes, the metabolic outcome, and concomitant hypertension.. Between 1992 and 1995, the use of oral antidiabetics increased significantly from 43 to 57% of the patients and the rate of treatment with diet only decreased from 30 to 20%. Combination treatment with oral drugs and insulin rose significantly from 1 to 8% of the patients. However, the greatest increase observed between 1992 and 1995 concerns cardiovascular drugs. The prescription rate of ACE inhibitors increased from 5 to 21%, of loop diuretics from 19 to 28%, of ASA from 9 to 21%, and of lipid-lowering agents from 1 to 7%. There was also a considerable variation between the three CHCs. Despite the more aggressive diabetic treatment strategies, the metabolic state was unchanged and unsatisfactory for 40-50% of the patients.. There have been major changes towards more active pharmacological treatment regarding antidiabetic, cardiovascular, and lipid-lowering agents.

Topics: Adolescent; Adult; Aged; Anticoagulants; Cardiovascular Agents; Community Health Centers; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diuretics; Drug Prescriptions; Drug Utilization; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; Pharmacoepidemiology; Sweden

Mortality follow-up for a cohort defined in 1980 with diabetes diagnosed at 30 years of age or older has been completed through 1988. History of medication use was obtained during the initial evaluation. There were 605 (44.2%) confirmed deaths; heart disease was the underlying cause in 49.9% of the deaths. Use of loop diuretics was associated with an odds ratio of death of 1.8 (95% CI = 1.4, 2.2). Although a causal relationship cannot be inferred, it is reasonable to suggest that blood chemistries be monitored regularly in persons on these drugs since electrolyte imbalance may be related to death.

Topics: Adult; Cardiovascular Agents; Cardiovascular Diseases; Cause of Death; Cohort Studies; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Proportional Hazards Models; Risk Factors

The drug therapy prescribed for 412 diabetic patients attending an outpatient clinic over a 12 week period was recorded to try and identify potential therapeutic problems. Over 90% of the patients were prescribed at least one drug (including insulin) with oral hypoglycaemic agents prescribed for 86% of non-insulin requiring diabetics. 19% of patients were prescribed more than three drugs and few patients took drug combinations. Of patients prescribed either glibenclamide or chlorpropamide, 63% were aged 65 yr or older. Despite their potential adverse clinical and biochemical effects, diuretics and beta-blockers were commonly prescribed, especially in hypertension. The prescribing of "newer" anti-hypertensive drugs, combination products in patients taking a multiple drug regimen, and the potential dangers of sulphonylureas in the elderly are three areas where alteration of prescribing habits may be of value.

Topics: Adrenergic beta-Antagonists; Cardiovascular Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diuretics; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Hypoglycemic Agents; Insulin; Medical Audit; Patient Compliance

Diabetes mellitus is a multifaceted disease which intervenes in the personal lives of those afflicted in many different ways. In this study prescription drug use among diabetics was analyzed in order to shed light on the characteristics of diabetic morbidity. Prescription drug use among diabetics and non-diabetics in a total population of 21,000 inhabitants in a defined geographic area were studied. The diabetic population was categorized according to the type of treatment received: insulin treatment, oral anti-diabetic treatment or dietary treatment or dietary treatment only. The pattern of prescription drug use differed between diabetics and non-diabetics and important differences were observed also between diabetics according to type of treatment. Drug use among those treated with insulin and those treated orally was substantially higher than among non-diabetics while the difference between diabetics on dietary regimen and non-diabetics was much smaller. All three treatment groups had considerably higher consumption of cardiovascular drugs than non-diabetics. Additional findings include more frequent antibiotic use among diabetics treated orally and on diet only than among non-diabetics. The use of these drugs was also common among insulin treated diabetics but did not differ significantly from among non-diabetics. Use of psychotropics was more common among diabetics treated with insulin and orally than among non-diabetics.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Prescriptions; Drug Utilization; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Psychotropic Drugs; Regression Analysis; Sweden