cardiovascular-agents and Kidney-Diseases

Acute heart failure (AHF) is a complex, heterogeneous, clinical syndrome with high morbidity and mortality, incurring significant health care costs. Patients transition from home to the emergency department, the hospital, and home again and require decisions surrounding diagnosis, treatment, and prognosis at each step of the way. The purpose of this review is to examine the epidemiology, etiology, and classifications of AHF and specifically focus on practical information relevant to the clinician. We examine the mechanisms of decompensation relevant to clinical presentations-including precipitating factors, neuroendocrine interactions, and inflammation-along with how consideration of these factors may help select therapies for an individual patient. The prevalence and significance of end-organ manifestations such as renal, gastrointestinal, respiratory, and neurologic manifestations are discussed. We also highlight how the development of renal dysfunction relates to the choice of a variety of diuretics that may be useful in specific circumstances and review guideline-directed medical therapy. We discuss the practical use (and pitfalls) of a variety of evidence-based clinical scoring criteria available to risk stratify patients with AHF. Finally, evidence-based management of AHF is discussed, including both pharmacologic and nonpharmacologic therapies, including the lack of evidence for using old and new vasodilators and the recent evidence regarding initiation of newer therapies in hospital. Overall, we suggest that clinicians consider implementing the newer data in AHF and subject existing practice patterns and treatments to the same rigour as new therapies.

Topics: Acute Disease; Algorithms; Cardiac Rehabilitation; Cardiovascular Agents; Cognitive Dysfunction; Diagnostic Techniques, Cardiovascular; Diuretics; Evidence-Based Medicine; Gastrointestinal Diseases; Heart Failure; Humans; Inflammation; Kidney Diseases; Noninvasive Ventilation; Renin-Angiotensin System; Severity of Illness Index; Sleep Apnea Syndromes; Sympathetic Nervous System

Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKβ, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Cardiovascular Agents; Diosmin; Humans; Hypoglycemic Agents; Kidney Diseases; Liver Diseases; Neuroprotective Agents; Retinal Diseases

The kidney and cardiovascular system are closely related to each other during the modulation of the cardiovascular homeostasis. However, the search for new alternatives for the treatment and diagnosis of cardiovascular diseases does not take into account this relationship, so their evaluation results and the advantages offered by their global and integrative analysis are wasted. For example, a variety of receptors that are overexpressed in both pathologies is large enough to allow expansion in the search for new molecular targets and ligands. Nanotechnology offers pharmacological targeting strategies to kidney, heart, and blood vessels for overcoming one of the essential restrictions of traditional cardiovascular therapies the ones related to their unspecific pharmacodynamics distribution in these critical organs.. Drug or contrast agent nano-targeting for treatment or diagnosis of atherosclerosis, thrombosis, renal cancer or fibrosis, glomerulonephritis, among other renal, cardiac and blood vessels pathologies would allow an increase in their efficacy and a reduction of their side effects. Such effects are possible because, through pharmacological targeting, the drug is mainly found at the desired site. Review Purpose: In this mini-review, active, passive, and physical targeting strategies of several nanocarriers that have been assessed and proposed for the treatment and diagnosis of different cardiovascular diseases, are being addressed.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Drug Delivery Systems; Early Diagnosis; Gene Expression Regulation; Gene Regulatory Networks; Humans; Kidney Diseases; Ligands; Nanoparticles; Renal Agents

Heart failure has reached epidemic proportions given the ageing of populations and is associated with high mortality and re-hospitalization rates. This article reviews and summarizes recent advances in the diagnosis, assessment and treatment of the patients with heart failure. Data are discussed based also on the most recent guidelines indications. Open issues and unmet needs are highlighted.

Topics: Cardiovascular Agents; Heart Failure; Hemodynamics; Humans; Kidney Diseases; Practice Guidelines as Topic; Stroke Volume

Glucosamine and its acetylated derivative, N-acetyl glucosamine, are naturally occurring amino sugars found in human body. They are important components of glycoproteins, proteoglycans and glycosaminoglycans. Scientific studies have supported that glucosamine has the beneficial pharmacological effects to relieve osteoarthritis symptoms. Glucosamine can also be as a promising candidate for the prevention and/or treatment of some other diseases due to its anti-oxidant and anti-inflammatory activities. Most of its function is exerted by modulation of inflammatory responses especially through Nuclear Factor-κB (NF-κB) that can control inflammatory cytokine production and cell survival. In this review, we present a concise update on additional new therapeutic applications of glucosamine including treatment of cardiovascular disease, neurological deficits, skin disorders, cancer and the molecular mechanistic rationale for these uses. This article will also examine safety profile and adverse effects of glucosamine in human.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Cardiovascular Agents; Central Nervous System Agents; Glucosamine; Humans; Kidney Diseases; Skin Aging

Angiotensin II (Ang II) is well-considered to be the principal effector of the renin-angiotensin system (RAS), which binds with strong affinity to the angiotensin II type 1 (AT1R) and type 2 (AT2R) receptor subtype. However, activation of both receptors is likely to stimulate different signalling mechanisms/pathways and produce distinct biological responses. The haemodynamic and non-haemodynamic effects of Ang II, including its ability to regulate blood pressure, maintain water-electrolyte balance and promote vasoconstriction and cellular growth are well-documented to be mediated primarily by the AT1R. However, its biological and functional effects mediated through the AT2R subtype are still poorly understood. Recent studies have emphasized that activation of the AT2R regulates tissue and organ development and provides in certain context a potential counter-regulatory mechanism against AT1R-mediated actions. Thus, this review will focus on providing insights into the biological role of the AT2R, in particular its actions within the renal and cardiovascular system.

Topics: Angiotensin II; Animals; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Humans; Kidney; Kidney Diseases; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Signal Transduction

Renal dysfunction is a frequent finding in patients with acute heart failure (AHF) and an important prognostic factor for adverse outcomes. Worsening of renal function occurs in 30-50% of patients hospitalised for AHF, and is associated with increased mortality, prolonged hospital stay and increased risk of readmission. Likely mechanisms involved in the decrease in renal function include impaired haemodynamics and activation of neurohormonal factors, such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine-vasopressin system. Additionally, many drugs currently used to treat AHF have a detrimental effect on renal function. Therefore, pharmacotherapy for AHF should carefully take into account any potential complications related to renal function. Serelaxin, currently in clinical development for the treatment of AHF is a recombinant form of human relaxin-2, identical in structure to the naturally occurring human relaxin-2 peptide hormone that mediates cardiac and renal adaptations during pregnancy. Data from both pre-clinical and clinical studies indicate a potentially beneficial effect of serelaxin on kidney function. In this review, we discuss the mechanisms and impact of impairment of renal function in AHF, and the potential benefits of new therapies, such as serelaxin, in this context.

Topics: Acute Disease; Animals; Cardio-Renal Syndrome; Cardiovascular Agents; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Humans; Kidney; Kidney Diseases; Recombinant Proteins; Relaxin; Treatment Outcome

Due to the high prevalence of cardiovascular diseases and the corresponding prescription of cardiac drugs, side effects and interactions may occur in a substantial number of patients. They can be explained by either pharmacokinetic or pharmaco-dynamic drug interactions which may be desired, but may also be life-threatening. Despite the fact that the novel oral anticoagulants are well tolerated, several factors restricting the use of these drugs, such as renal failure, have to be considered. The use of antihypertensive drugs may be limited by concomitant use of drugs that either induce of inhibit enzymatic metabolism, respectively inhibit renal drug, electrolyte, and/or water excretion. In this respect, the interaction between beta-blockers, ACE inhibitors, angiotensin receptor blockers and thiazide diuretics with non-steroidal antiinflammatory drugs is especially important. Muscle disorders are frequent side effects in patients undergoing statin therapy and affect up to 5% of patients. They may manifest as mild myalgia, but also as life-threatening rhabdomyolysis.

Topics: Cardiovascular Agents; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Germany; Hemorrhage; Humans; Kidney Diseases; Muscular Diseases

Genetic manipulation of the kallikrein-kinin system (KKS) in mice, with either gain or loss of function, and study of human genetic variability in KKS components which has been well documented at the phenotypic and genomic level, have allowed recognizing the physiological role of KKS in health and in disease. This role has been especially documented in the cardiovascular system and the kidney. Kinins are produced at slow rate in most organs in resting condition and/or inactivated quickly. Yet the KKS is involved in arterial function and in renal tubular function. In several pathological situations, kinin production increases, kinin receptor synthesis is upregulated, and kinins play an important role, whether beneficial or detrimental, in disease outcome. In the setting of ischemic, diabetic or hemodynamic aggression, kinin release by tissue kallikrein protects against organ damage, through B2 and/or B1 bradykinin receptor activation, depending on organ and disease. This has been well documented for the ischemic or diabetic heart, kidney and skeletal muscle, where KKS activity reduces oxidative stress, limits necrosis or fibrosis and promotes angiogenesis. On the other hand, in some pathological situations where plasma prekallikrein is inappropriately activated, excess kinin release in local or systemic circulation is detrimental, through oedema or hypotension. Putative therapeutic application of these clinical and experimental findings through current pharmacological development is discussed in the chapter.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Genetic Predisposition to Disease; Genetic Variation; Humans; Kallikreins; Kidney Diseases; Kinins; Phenotype; Renal Agents; Signal Transduction

Topics: Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Clinical Protocols; Comorbidity; Comparative Effectiveness Research; Dialysis; Disease Management; Female; Heart Failure; Humans; Inactivation, Metabolic; Kidney Diseases; Male; Patient Selection; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Treatment Outcome

There is increasing evidence that endothelin receptor blockade and, in particular, ET(A) receptor blockade not only confers protection against proteinuric renal disease in diabetes but also confers vasculoprotection.. Recent clinical trials using ET(A) receptor blockade in treating proteinuria and chronic kidney disease as well as atherosclerosis show great promise; however, adverse effects are still problematic.. Endothelin receptor blockade is associated with a significant attenuation of proteinuria and these effects are mediated in part via inhibition of inflammatory and oxidative stress related pathways as well profibrotic pathways. The addition of ET(A) receptor blockade to currently established therapies such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may result in additional or synergistic renoprotection and vasculoprotection in hypertension and, in particular, in the context of diabetes.

Topics: Animals; Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Diabetic Nephropathies; Endothelin Receptor Antagonists; Endothelins; Humans; Hypertension; Kidney; Kidney Diseases; Proteinuria; Receptors, Endothelin; Signal Transduction

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH.

Topics: Anemia; Cardiovascular Agents; Cardiovascular System; Chronic Disease; Early Diagnosis; Early Medical Intervention; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Kidney Diseases; Kidney Function Tests; Metabolism; Risk Factors; Severity of Illness Index; Vascular Resistance; Water-Electrolyte Imbalance

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

Older US adults bear a substantial burden of chronic disease and take an average of five prescription and non-prescription medications per day. Recent data suggest that over 20% of older adults have chronic kidney disease (CKD) as defined by an impaired glomerular filtration rate. These individuals often have multiple comorbidities, including diabetes, hypertension, and cardiovascular disease. Although patients with CKD may receive substantial benefits from prescribed medications, they are also at high risk for adverse drug events and polypharmacy. In this review, we outline the risks and benefits of medication use in the CKD population as a specific case within geriatric pharmacoepidemiology as a framework.

Topics: Aged; Aged, 80 and over; Aging; Analgesics; Antihypertensive Agents; Cardiovascular Agents; Chronic Disease; Drug Utilization; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Kidney Diseases; Prescription Drugs; Psychotropic Drugs; Risk Factors; United States

Aldosterone is an adrenal hormone that regulates sodium, fluid, and potassium balance. Jerome Conn first described the syndrome of autonomous and excessive aldosterone secretion or "primary aldosteronism." Contrary to the historical belief, recent studies indicate that primary aldosteronism is a common cause of hypertension with a prevalence of 5-10% among general hypertensive patients. Various animal models have demonstrated that aldosterone in association with a high salt diet results in target-organ inflammation and fibrosis. Similarly, cross-sectional and observational human studies have demonstrated the association of aldosterone with development and severity of hypertension, congestive heart failure, coronary artery disease, chronic kidney disease, and metabolic syndrome. Several interventional studies have also demonstrated the beneficial effects of mineralocorticoid receptor antagonists in these disease processes, particularly hypertension, heart failure, and post myocardial infarction, further supporting the role of aldosterone in their pathogenesis. We review the role of aldosterone in these various cardiovascular disease processes along with potential mechanisms and treatment.

Topics: Adrenalectomy; Aldosterone; Animals; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Heart Failure; Humans; Hyperaldosteronism; Hypertension; Kidney Diseases; Metabolic Syndrome; Mineralocorticoid Receptor Antagonists; Treatment Outcome

Chronic kidney disease is common in patients with chronic heart failure and has important clinical implications. The coexistence of these two syndromes is associated with a higher risk of adverse outcome and increases the difficulties of heart failure treatment because of the complex interplay between renal dysfunction and pharmacologic therapy. The underrepresentation of patients with chronic kidney disease in most heart failure trials contributes to the suboptimal treatment of this high-risk population in clinical practice. In the present review, we briefly examine the pathophysiologic mechanisms connecting chronic kidney disease and chronic heart failure and discuss the therapeutic approach to patients affected by both conditions.

Topics: Cardiovascular Agents; Chronic Disease; Heart Diseases; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Treatment Outcome

Impaired renal function is a risk factor for cardiovascular disease and an adverse prognostic factor in patients with established cardiovascular disease. In addition, with current widespread use of invasive procedures in the treatment of acute myocardial infarction, contrast-induced nephropathy is a growing problem in this patient population. In acute myocardial infarction, impaired renal function may result from underlying kidney disease, acute renal failure, and the effect of drugs and contrast agents used during diagnostic procedures or treatment. These various causes may coexist, resulting in significantly worse outcomes. Prompt recognition of the degree of renal function impairment and institution of appropriate preventive and therapeutic measures are among major goals of in-hospital management of these patients. A commonly used method to evaluate renal function is the determination of glomerular filtration rate. Appropriate nephroprotective treatment should be used in patients at risk of contrast-induced nephropathy. The most commonly used methods include the use of iso-osmotic contrast agents and appropriate hydration in the periprocedural period. Studies are currently under way to evaluate nephroprotective properties of other drugs such as N-acetylcysteine, sodium chloride and sodium bicarbonate solutions, mannitol, and statins. Results of some studies suggest that these measures may effectively reduce the number of renal function deterioration events in patients with acute myocardial infarction. Regardless of the cause, impaired renal function in acute myocardial infarction is a significant adverse prognostic factor. Thus, despite some inconsistent views regarding the optimal management strategy, intensive diagnostic, preventive, and therapeutic measures are clearly necessary in patients with acute myocardial infarction and impaired renal function.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chronic Disease; Contrast Media; Disease Progression; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Myocardial Infarction; Practice Guidelines as Topic; Renal Insufficiency; Risk Assessment; Risk Factors; Severity of Illness Index; Terminology as Topic; Treatment Outcome

This review focuses on events subsequent to planning a pregnancy and addresses three components of concern for women with systemic lupus erythematosus: maternal, placental, and fetal. Flare rates are generally low for patients who are clinically stable at conception. For patients who have never had renal disease, there is no frm evidence that they will develop active renal disease simply due to being pregnant. For patients who begin pregnancy with an abnormal creatinine (> 2 mg/dl is ill advised), risks include hypertension, preeclampsia, high rate of fetal loss, and possible further deterioration of renal function. Discontinuation of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and mycophenalate is mandatory. Elevated levels of sVEGF-1 may be a harbinger of preeclampsia. For patients with anti-phospholipid antibodies detected in the frst trimester of pregnancy, the lupus anticoagulant per se may be the strongest predictor of pregnancy complications. For women with anti-SSA/Ro antibodies the risk of having a child with congenital heart block is 2% which rises to a recurrence rate of 18%. Information on current approaches to prevention and treatment of heart complications of neonatal lupus is provided.

Topics: Antibodies, Antinuclear; Cardiovascular Agents; Female; Fetus; Health Status Indicators; Heart Defects, Congenital; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk Assessment; Risk Factors; Severity of Illness Index; Steroids

Systemic sclerosis (SSc) is a complex and heterogeneous chronic illness characterized by substantial patient to patient variability in clinical manifestations, internal organ involvement, and outcome. Genetic factors contribute to disease susceptibility, but environmental influences also play a significant role. The pathogenesis of SSc encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations and morbidity and must be addressed in the treatment plan. Although vascular interventions appear to reduce the frequency and severity of complications, such as scleroderma renal crisis and pulmonary hypertension, current therapies generally target the immune component of SSc in a non-selective fashion and have largely failed as diseases-modifying interventions. Newer insights into the mechanisms underlying autoimmunity, vascular injury and destruction, and particularly tissue fibrosis provide novel potential targets for therapy. Transforming growth factor-ss is a ubiquitous cytokine that appears to contribute to fibroblast activation, collagen overproduction, and pathological tissue fibrosis. Neutralizing antibodies and small molecules that block TGF-beta activation or function are effective in shutting down TGF-beta signaling and selectively inhibit the progression of fibrosis and may be entering clinical trials for the treatment of SSc.

Topics: Blood Vessels; Cardiovascular Agents; Fibrosis; Genetic Predisposition to Disease; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Inflammation; Kidney Diseases; Lung Diseases, Interstitial; Raynaud Disease; Scleroderma, Systemic; Skin; Transforming Growth Factor beta; Treatment Outcome

Acute kidney injury (AKI) after cardiac surgery is associated with significant morbidity and mortality. Despite the proliferation of predictive clinical scoring models of renal risk after cardiac surgery, limitations in preventing AKI through the use of pharmacological agents remain. Here we review the evolution of predictive models of renal risk after cardiac surgery, and highlight the important gains made in preventing its occurrence.. Simple risk indices predicting AKI after cardiac surgery have been developed and can now be readily applied clinically. However, studies focusing on preventing AKI after surgery have yet to demonstrate any consistent renoprotective effect.. Clinical scoring systems predicting AKI risk after cardiac surgery are available and should be employed in the preoperative assessment. Elucidation of beneficial preventive strategies of AKI after cardiac surgery requires ongoing research.

Topics: Acute Disease; Anti-Inflammatory Agents; Cardiac Surgical Procedures; Cardiovascular Agents; Humans; Kidney Diseases; Natriuretic Agents; Predictive Value of Tests; Renal Circulation; Risk Assessment; Risk Factors

Topics: Adult; Anemia; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Hematinics; Humans; Kidney Diseases; Middle Aged; Practice Guidelines as Topic; Renal Dialysis; Risk Factors

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.

Topics: Animals; Anti-Asthmatic Agents; Antineoplastic Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Bone Density Conservation Agents; Cardiovascular Agents; Cerebrovascular Disorders; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Organ Transplantation; Osteoporosis; Sepsis

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

Failure of the cardiovascular system is the main reason for mortality in industrialized countries, and is a major cause of chronic morbidity. As most of the numerous ways in which it can fail will manifest in the second half of life and are exacerbated by old age, this situation is not likely to change in the near future unless fundamentally new ways of treating or preventing hypertension, atherosclerosis, myocardial infarction, chronic heart failure and cardiac arrhythmia are found. This prospect keeps the pharmaceutical industry on a constant, intense search for new therapeutic targets, new drugs, and new ways to identify such targets and drugs, as well as monitoring patient responses to drugs. This summary highlights the most interesting developments seen in cardiovascular and renal patents (other than those claiming formulations or combinations of known drugs) published during the first half of 2006.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cell- and Tissue-Based Therapy; Disease Models, Animal; Drug Delivery Systems; Drug Design; Genetic Therapy; Humans; Kidney Diseases; Renal Agents; RNA, Small Interfering

Topics: Analgesia; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Colic; Humans; Hyperthermia, Induced; Kidney Diseases; Muscarinic Antagonists; Ureteral Calculi

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

The association between chronic kidney disease and cardiovascular death is accounted for, in part, by higher rates of serious arrhythmias. Research shows an independent relationship between worsened renal function and atrial fibrillation, heart block, ventricular tachycardia, ventricular fibrillation, and asystole. These higher rates also associate with underlying structural heart disease including left ventricular hypertrophy, cardiac fibrosis, valvular disease, and left ventricular systolic and diastolic dysfunction. In addition, chronic intermittent ischemia is implicated in the arrhythmias observed during hemodialysis. The superimposed conditions of acidosis and fluxes in both potassium and magnesium also contribute to higher rates of arrhythmias. Baseline estimated glomerular filtration rate is linked to worsened outcomes and increased defibrillation thresholds in patients receiving implantable cardioverter defibrillators. Preventive strategies include meticulous management of electrolytes, baseline treatment for cardiovascular disease, and when indicated, implantable cardioverter defibrillators. Future research into the mechanisms and prevention of sudden cardiac death in patients with chronic kidney disease is warranted.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Heart Function Tests; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Kidney Function Tests; Outcome Assessment, Health Care; Risk Factors

Topics: Aged; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Diabetic Nephropathies; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Heart Failure; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Proteinuria; Rats; Renin-Angiotensin System; Ventricular Dysfunction, Left

Topics: Alcohol Drinking; Antihypertensive Agents; Cardiovascular Agents; Comorbidity; Diabetes Mellitus; Diet, Reducing; Diet, Sodium-Restricted; Heart Failure; Humans; Hypertension; Kidney Diseases; Life Style; Motor Activity; Myocardial Ischemia; Obesity; Practice Guidelines as Topic; Weight Loss

Advanced heart failure, defined as persistence of limiting symptoms despite therapy with agents of proven efficacy, accounts for the majority of morbidity and mortality in heart failure.. To review current medical therapy for advanced heart failure.. We searched MEDLINE for all articles containing the term advanced heart failure that were published between 1980 and 2001; EMBASE was searched from 1987-1999, Best Evidence from 1991-1998, and Evidence-Based Medicine from 1995-1999. The Cochrane Library also was searched for critical reviews and meta-analyses of congestive heart failure.. Randomized controlled trials of therapy for 150 patients or more were included if advanced heart failure was represented. Other common clinical situations were addressed from smaller trials as available, trials of milder heart failure, consensus guidelines, and both published and personal clinical experience.. Data quality was determined by publication in peer-reviewed literature or inclusion in professional society guidelines.. A primary focus for care of advanced heart failure is ongoing identification and treatment of the elevated filling pressures that cause disabling symptoms. While angiotensin-converting enzyme inhibitors and beta-adrenergic agents can slow disease progression and prolong survival, titration and tolerability often present challenges. Most patients are not eligible for surgical intervention but do benefit from a medical regimen tailored to individual clinical and hemodynamic profiles and from heart failure management programs that reduce rehospitalization. Survival ranges from 80% at 2 years for patients rendered free of congestion to less than 50% at 6 months for patients with refractory symptoms, in whom end-of-life options may include hospice care and inactivation of implantable defibrillators.. Current management of advanced heart failure is based more on consensus than on randomized trials. Systematic investigation should address not only new therapies but also strategies for selecting and optimizing therapies already available.

Topics: Cardiovascular Agents; Disease Management; Heart Failure; Hemodynamics; Humans; Kidney Diseases; Prognosis; Quality of Life

Recent clinical trials have demonstrated beyond doubt that statins are effective in the prevention of acute coronary events. Critical analysis of these studies suggests that the benefits of statin therapy cannot be fully explained on the basis of reductions in plasma cholesterol levels. Accumulating knowledge of the actions of these drugs shows that they may prevent several processes that eventually lead to plaque rupture and the development of occlusive thrombosis, the basis of acute coronary events. Hence, statins may correct endothelial dysfunction (thus protecting against ischaemic injury), stabilise existing plaques and modify the coagulation pathway, thereby reducing the likelihood of a sudden vascular event. At a cellular level, these drugs inhibit the synthesis not just of cholesterol, but of other compounds important in cell proliferation. Antiproliferative effects have been demonstrated in vitro and may broaden the applications of statins to the treatment of noncardiovascular diseases. Finally, preliminary clinical studies indicate that as a result of immunosuppressive actions, statins may reduce the incidence of rejection following organ transplantation.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Enzyme Inhibitors; Graft Occlusion, Vascular; Humans; Hypolipidemic Agents; Immunosuppressive Agents; Kidney Diseases; Naphthalenes; Pravastatin

There is a fascinating and exceedingly important area of medicine that most of us have not been exposed to at any level of our medical training. This relatively new area is termed chronobiology; that is, how time-related events shape our daily biologic responses and apply to any aspect of medicine with regard to altering pathophysiology and treatment response. For example, normally occurring circadian (daily cycles, approximately 24 hours) events, such as nadirs in epinephrine and cortisol levels that occur in the body around 10 PM to 4 AM and elevated histamine and other mediator levels that occur between midnight and 4 AM, play a major role in the worsening of asthma during the night. In fact, this nocturnal exacerbation occurs in the majority of asthmatic patients. Because all biologic functions, including those of cells, organs, and the entire body, have circadian, ultradian (less than 22 hours), or infradian (greater than 26 hours) rhythms, understanding the pathophysiology and treatment of disease needs to be viewed with these changes in mind. Biologic rhythms are ingrained, and although they can be changed over time by changing the wake-sleep cycle, these alterations occur over days. However, sleep itself can adversely affect the pathophysiology of disease. The non-light/dark influence of biologic rhythms was first described in 1729 by the French astronomer Jean-Jacques de Mairan. Previously, it was presumed that the small red flowers of the plant Kalanchoe bloss feldiuna opened in the day because of the sunlight and closed at night because of the darkness. When de Mairan placed the plant in total darkness, the opening and closing of the flowers still occurred on its intrinsic circadian basis. It is intriguing to think about how the time of day governs the pathophysiology of disease. On awakening in the morning, heart rate and blood pressure briskly increase, as do platelet aggregability and other clotting factors. This can be linked to the acrophase (peak event) of heart attacks. During the afternoon we hit our best mental and physical performance, which explains why most of us state that "I am not a morning person." Even the tolerance for alcohol varies over the 24-hour cycle, with best tolerance around 5 pm (i.e. "Doctor, I only have a couple of highballs before dinner"). Thus, all biologic functions, from those of the cell, the tissue, the organs, and the entire body, run on a cycle of altering activity and function.(ABSTRACT TRUNCATED AT 400 W

Topics: Arthritis; Autonomic Nervous System Diseases; Cardiovascular Agents; Cardiovascular Diseases; Chronobiology Phenomena; Circadian Rhythm; Endocrine System Diseases; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Hypersensitivity; Kidney Diseases; Male; Nervous System Diseases; Neuromuscular Diseases; Phototherapy; Respiratory Physiological Phenomena; Respiratory Tract Diseases; Sleep; Sleep Apnea Syndromes

Diuretics are the mainstay of drug therapy in the treatment of many cardiovascular disorders. However, perusal of knowledge of their haemodynamic activities in heart failure and hypertension reveals major gaps. In left ventricular failure complicating acute myocardial infarction, intravenous frusemide reduces the elevated left heart filling pressure with little change in systemic blood pressure, heart rate or cardiac output, and restores the ability of the left heart to handle an acute increase in filling volume. But there is little knowledge of the haemodynamic effects of other intravenous diuretics, oral diuretics or diuretics other than those acting on the loop of Henle in this emergency clinical situation. Even less information is available on the haemodynamic effects of diuretics in patients in chronic heart failure. In patients with valvular heart disease, parenteral mercury and oral thiazides reduce right heart and pulmonary vascular pressures with variable (dose-dependent?) changes in cardiac output. Information on the effect of loop diuretics, the comparative effects of intravenous versus oral routes of administration and dose-response correlations are all lacking. In hypertension, the dose-blood pressure lowering response relationship of orally administered diuretics is relatively flat. The majority of information relates to oral thiazides; there is little reliable information on the anti-hypertensive efficacy of the loop diuretics. The acute and chronic effects of the majority of commonly used diuretics on cardiac and peripheral vascular functions is unexplained. More is known of their potentially adverse metabolic effects than of their possible circulatory benefits in hypertensive patients. Many unwanted side-effects of these drugs have been described; their potential importance is related directly to the disease state and doses in which they are used. In acute heart failure, their potential danger is probably minimal. In the treatment of chronic heart failure their most sinister potential is in the excessive secretion of potassium and magnesium. In hypertensive patients their long-term administration in high-doses may lead to undesirable metabolic effects that tend to offset their blood pressure lowering activity. Despite their drawbacks, diuretics continue to provide the natural first-line treatment of choice of these common cardiovascular syndromes. But more information on their mechanisms of vascular activities and the differences in non-d

Topics: Angina Pectoris; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Diuretics; Drug Interactions; Heart Failure; Humans; Hypertension; Kidney Diseases; Socioeconomic Factors

Topics: Animals; Anti-Bacterial Agents; Cardiovascular Agents; Dogs; Drug Interactions; Enzyme Induction; Humans; Intestinal Absorption; Kidney; Kidney Diseases; Kinetics; Liver; Liver Diseases; Mitochondria, Liver; Monoamine Oxidase Inhibitors; Protein Binding; Psychotropic Drugs

We studied the relationship between heart rate and renal function and the effects of heart rate reduction with ivabradine in heart failure patients with and without renal dysfunction.. From the 6505 patients who were randomized in SHIFT, baseline creatinine and at least one follow-up measurement were available in 6160 patients. Median follow-up was 22.9 months. Worsening renal function (WRF) was defined as a creatinine increase of ≥0.3 mg/dL and ≥25% from the baseline value. WRF developed in 1029 (17%) patients and was directly related to baseline heart rate, with an incremental risk of 5% for every 5 b.p.m. heart rate increment (P=0.003). WRF was associated with an increased risk of the primary composite endpoint of hospitalization for worsening heart failure or cardiovascular death [hazard ratio (HR) 1.38, P<0.001] and of all-cause mortality (HR 1.42, P<0.001). Ivabradine use was associated with a reduction of the primary composite endpoint in patients both with (HR 0.82, P=0.023) and without renal dysfunction (HR 0.81, P<0.001) at baseline (P for interaction=0.89), and tolerability of ivabradine was comparable in the two groups. No differences were found in changes in renal function over time between ivabradine- and placebo-treated patients.. In chronic stable systolic heart failure patients, heart rate is directly and independently associated with the risk of WRF, but reduction in heart rate by ivabradine had a neutral effect on renal function during 2 years of follow-up. The beneficial cardiovascular effects and safety of ivabradine were similar in patients with and without renal dysfunction.

Topics: Adult; Aged; Benzazepines; Cardiovascular Agents; Creatinine; Cyclic Nucleotide-Gated Cation Channels; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Heart Rate; Humans; Ivabradine; Kidney; Kidney Diseases; Male; Middle Aged

A nonrandomized controlled study was conducted to evaluate the effect of lipo-prostaglandin E1 (lipo-PGE1) on cystatin C (CysC), β2-microglobulin (B2MG), and estimated glomerular filtration rate (eGFR) in patients with decompensated heart failure (DHF) and renal dysfunction. A total of 286 enrolled patients with DHF and renal dysfunction were nonrandomly assigned a 7-day standard treatment without (n = 146) or with (n = 140) lipo-PGE1 intervention. According to the baseline eGFR, patients were further classified into mild, moderate, and severe renal dysfunction subgroups. By the end of study period, there was no evidence of an immense improvement in B2MG, CysC, and eGFR in response to standard treatment (all P > 0.05). On the contrary, a noticeable decrease of B2MG and CysC was observed in patients receiving lipo-PGE1 intervention, as well as an increase in eGFR (all P < 0.05). Moreover, lipo-PGE1 intervention led to greater changes in renal function variables from baseline than with standard management (all P < 0.05). Most important, the favorable renal protective effects of lipo-PGE1 were maintained in three subgroups. Lipo-PGE1 intervention brought a substantial renoprotective benefit to hospitalized DHF patients as compared with standard therapy, suggesting it might offer a promising therapeutic option for the management of renal dysfunction associated with DHF.

Topics: Aged; Aged, 80 and over; Alprostadil; beta 2-Microglobulin; Biomarkers; Cardiovascular Agents; China; Cystatin C; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Kidney; Kidney Diseases; Male; Time Factors; Treatment Outcome

Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet.. STS was given intravenously to 10 hemodialysis patients on- and off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method.. In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 ± 1.82 versus 7.1 ± 2.7 μmol/L. Renal clearance was high in volunteers (1.86 ± 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 ± 0.32 ml/min per kg) than in anuric patients (2.04 ± 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 ± 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%).. Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS.

Topics: Administration, Oral; Adult; Aged; Biological Availability; Biotransformation; Cardiovascular Agents; Chi-Square Distribution; Chromatography, High Pressure Liquid; Female; Glomerular Filtration Rate; Humans; Injections, Intravenous; Kidney; Kidney Diseases; Male; Middle Aged; Models, Biological; Renal Dialysis; Switzerland; Thiosulfates

It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD.. A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m(2) identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked.. The average decline in eGFR over 20 months was -1.9 ml/min per 1.73 m(2). eGFR declined by ≥4 ml/min per 1.73 m(2) within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year.. Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.

Topics: Aged; Biomarkers; Canada; Cardiovascular Agents; Cardiovascular Diseases; Chi-Square Distribution; Chronic Disease; Creatinine; Disease Progression; Female; General Practice; Glomerular Filtration Rate; Hematinics; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Kidney; Kidney Diseases; Linear Models; Male; Middle Aged; Nurse Clinicians; Patient Care Team; Pilot Projects; Platelet Aggregation Inhibitors; Preventive Health Services; Risk Assessment; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Smoking Cessation; Time Factors; Treatment Outcome; Up-Regulation

Potential cost and effectiveness of a nephrologist/nurse-based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease.. Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist-supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs.. Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR.. The nephrologist/nurse-based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.

Topics: Aged; Biomarkers; Canada; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Cost Savings; Cost-Benefit Analysis; Creatinine; Disease Progression; Drug Costs; Female; General Practice; Glomerular Filtration Rate; Health Care Costs; Hematinics; Hospital Costs; Hospitalization; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Kidney; Kidney Diseases; Length of Stay; Male; Middle Aged; Models, Economic; Nurse Clinicians; Patient Care Team; Platelet Aggregation Inhibitors; Preventive Health Services; Prospective Studies; Quality-Adjusted Life Years; Risk Assessment; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Smoking Cessation; Time Factors; Treatment Outcome; Up-Regulation

This study was designed to investigate the effect of low-dose nesiritide on renal function and major cardiac events in patients with acute decompensated heart failure following acute myocardial infarction. Sixty patients were randomized into nesiritide (loading dose 0.5 microg/kg, maintenance dose 0.0075 microg/kg/min) and nitroprusside groups. Compared with the nitroprusside group, the nesiritide group had a greater heart rate reduction (P < 0.05), higher 24 h urine volume (P < 0.001), and more significant alleviation in dyspnea (P < 0.001). The prevalence of hypotension in the nesiritide group was lower than in the nitroprusside group (7.4% vs 28.5%, P < 0.05). The nesiritide group had a greater reduction in serum noradrenaline, angiotensin II, aldosterone, endothelin, and N-terminal prohormone brain natriuretic peptide (all P < 0.01). The mean serum creatinine in the nesiritide group was reduced (109.4 +/- 26.6 vs 102.8 +/- 21.6 micromol/l, P < 0.01), whereas it remained unchanged in the nitroprusside group (106.8 +/- 20 vs 106.0 +/- 19.2 micromol/l, P > 0.05). The rehospitalization or mortality rate was similar between the two groups 3 months after the therapy (P > 0.05). We conclude that low-dose nesiritide is more effective in suppressing the activation of the sympathetic and renin-angiotensin systems. It also improves the clinical symptoms and enhances renal function, but its effect on hospital readmission or mortality rate needs further investigation.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; Creatinine; Female; Heart Failure; Hemodynamics; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nitroprusside; Patient Readmission; Peptide Fragments; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Blocking the tubuloglomerular feedback mechanism with adenosine A1 receptor antagonists seems to improve diuresis and sodium excretion without compromising the glomerular filtration rate in patients with heart failure. However, the direct cardiac effects of this compound class have not been investigated to date.. In total, 111 patients (109 men and 2 women) received a 1-hour infusion of 5, 10, and 15 mg SLV320, an adenosine A1 receptor antagonist, placebo, or 40 mg furosemide. Mean age was 57.9 years, mean ejection fraction was 28.1%, 82 patients were of New York Heart Association class II, and 29 patients were of New York Heart Association class III. Hemodynamic parameters (heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, systemic vascular resistance, right atrial pressure, and cardiac output) were determined. Kidney function was assessed by cystatin C measurements and by analysis of urine output and urine electrolytes. In addition, pharmacokinetics of SLV320 and ex vivo inhibition of adenosine A1 receptor activity were performed. SLV320 was well tolerated, and no serious adverse events were observed. Heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, right atrial pressure, and cardiac output were not altered by any dose of SLV320. Pulmonary capillary wedge pressure was significantly (P=0.04) decreased by furosemide (-6.2+/-5.9 mm Hg). Systemic vascular resistance was significantly (P=0.04) increased in the furosemide group (+166.70+/-261.87 dynes . s(-1) . cm(-5)), whereas all SLV320 groups showed no significant alterations of systemic vascular resistance. Changes from baseline cystatin C plasma concentrations decreased after 10 mg SLV320 (-0.093+/-0.137 mg/L, P=0.046), whereas furosemide resulted in a significant (P=0.03) increase of cystatin C (+0.052+/-0.065 mg/L) versus baseline. All values represent mean changes+/-SD from baseline at 3 hours postdosing: SLV320 (10 and 15 mg) increased significantly sodium excretion and diuresis compared with placebo during the 0- to 6-hour collection period postdosing.. SLV320 infusion shows no immediate effects on cardiac hemodynamics. SLV320 might improve glomerular filtration rate while simultaneously promoting natriuresis and diuresis. Clinical Trial Registration- clinicaltrials.gov Indentifier: NCT00160134.

Topics: Adenosine A1 Receptor Antagonists; Cardiovascular Agents; Cyclohexanes; Diuresis; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Europe; Female; Furosemide; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Heterocyclic Compounds, 2-Ring; Humans; Infusions, Intravenous; Kidney; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Myocardium; Natriuresis; Receptor, Adenosine A1; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Ranolazine is a novel compound under development as an antianginal agent. The multiple-dose pharmacokinetics of extended-release ranolazine and 3 major metabolites was investigated in healthy subjects (N = 8) and subjects with mild to severe renal impairment (N = 21). The ranolazine AUC(0-12) (area under the concentration-time curve between 0 and 12 hours after dosing) geometric mean ratio versus healthy subjects at steady state was 1.72 (90% confidence interval [CI], 1.07-2.76) in subjects with mild impairment, 1.80 (90% CI, 1.13-2.89) in those with moderate impairment, and 1.97 (90% CI, 1.23-3.16) in those with severe renal impairment. Creatinine clearance was negatively correlated with AUC(0-12) and the maximum observed concentration for ranolazine and the O-dearylated metabolite (P < .05 for all variables), as well as the N-dealkylated metabolite (P < .001), but not for the O-demethylated metabolite. Less than 7% of the administered dose was excreted unchanged in all groups, indicating that factors other than reduced glomerular filtration rate contributed to the increase in ranolazine concentrations in renal impairment. No serious adverse events were observed in the study.

Topics: Acetanilides; Adolescent; Adult; Aged; Cardiovascular Agents; Cohort Studies; Dealkylation; Delayed-Action Preparations; Electrocardiography; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney Diseases; Male; Middle Aged; Piperazines; Ranolazine

There are conflicting reports on the effects of diltiazem treatment on renal function in surgical patients. We sought to determine whether diltiazem treatment alters renal function in patients undergoing major thoracic surgery.. In a prospective study, 330 patients scheduled for elective thoracic surgery received either IV diltiazem (n = 167) or placebo (n = 163) immediately after the operation and orally thereafter for 14 days in an effort to prevent postoperative atrial arrhythmias. Serum creatinine and BUN levels were compared before and during the first postoperative week.. Patients treated with diltiazem were similar to control subjects in terms of age (mean +/-SD, 66 +/- 10 years vs 67 +/- 10 years, respectively), baseline serum creatinine or BUN levels, prevalence of comorbid conditions, and surgical characteristics. During the first 5 postoperative days, the two groups did not differ in terms of serum creatinine or BUN levels. The incidence of renal failure was 0.6% in the diltiazem group and 1.2% in the placebo group (difference was not significant). There was no difference in the length of hospitalization or mortality rate.. In patients without renal disease who are undergoing elective thoracic surgery, prophylactic diltiazem treatment did not alter postoperative renal function.

Topics: Aged; Cardiovascular Agents; Diltiazem; Female; Humans; Kidney Diseases; Male; Pneumonectomy; Postoperative Complications; Prospective Studies

Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), β-blockers (BB) and mineralocorticoid receptor antagonist (MRA) are known as guideline-directed medical therapy to improve prognosis. However, low blood pressure (BP) and renal dysfunction are often challenges prevent clinical implementation, so we investigated the association of different combinations of GDMT treatments with all-cause mortality in HFrEF population with low BP and renal dysfunction.. Among the study patients, 485 (33.1%), 672 (45.9%), 109 (7.4%) and 198 (13.5%) patients were in group 1-4. Patients in group 1 were younger, had highest hemoglobin, and most with EF < 30%. During a median of 1.33 years follow-up, 937 (64%) patients died. After adjustment for age, gender, LVEF, eGFR, hemoglobin when compared with the group 1, the hazard ratio for all-cause mortality in group 2 was 1.04 (0.89-1.21) (p = 0.62), group 3 1.40 (1.09-1.79) (p = 0.009), and group 4 1.71 (1.39-2.09) (p < 0.001).. In real-world HFrEF patients with low BP and renal dysfunction, full medication of guideline-directed medical therapy is associated with improved survival. The benefit was larger close to the index date and decreased with follow-up time.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiovascular Agents; Female; Glomerular Filtration Rate; Guideline Adherence; Heart Failure; Humans; Kidney Diseases; Male; Mineralocorticoid Receptor Antagonists; Registries; Retrospective Studies; Survival Rate; Sweden; Treatment Outcome

Although bioresorbable polymer sirolimus-eluting Ultimaster stents (BP-SESs) are likely useful for percutaneous coronary interventions (PCIs), the clinical data from real-world cases are insufficient. Furthermore, the predictors of adverse clinical outcomes after BP-SES implantation have not been fully investigated.. This study evaluated the 1-year clinical outcomes after BP-SES implantation in real-world PCI cases and identified the predictors of adverse outcomes.. In this single-center, all-comers study, we consecutively implanted BP-SESs in all patients who required coronary stents between October 2015 and August 2016. We conducted a clinical follow-up assessment of these patients.. The sample comprised 1,727 patients; 67% were men, the mean age was 72 years, and 37% had diabetes. Of the 2,085 lesions detected, 88% were type B2/C lesions, 4% were chronic total occlusions (CTOs), and 23% were bifurcations. The cumulative incidences of target lesion revascularization (TLR) and target lesion failure (TLF) at 1-year were 2.4% and 5.2%, respectively. A multivariate analysis revealed that hemodialysis (HD) (hazard ratio [HR] 8.40) and CTO (HR 4.21) were independent predictors of TLR. Stent sizes ≤2.5 mm were not associated with either TLR or TLF.. The current study indicates that patients on HD and those with CTO were more likely to experience adverse clinical outcomes after BP-SES implantation. In contrast, small vessel diameter was not significantly related to adverse outcomes. The 1-year clinical outcomes after BP-SES implantation were found to be favorable among all-comer PCI cases, including patients receiving HD and those with in-stent restenosis.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Coronary Artery Disease; Coronary Occlusion; Drug-Eluting Stents; Female; Humans; Japan; Kidney Diseases; Male; Middle Aged; Percutaneous Coronary Intervention; Prosthesis Design; Renal Dialysis; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Neurological complications including seizures have been reported with ranolazine. We sought to quantify the risk of seizure-related hospitalizations or emergency department events following ranolazine exposure in the Sentinel System (2006-2015).. Eligibility criteria were new use of ranolazine after 183 days washout period and absence of seizure diagnoses, anti-epileptic drugs, or seizure-related disorders during the baseline period.. Among 52,155 ranolazine users, we identified 28 seizures in the 1-32 days after new ranolazine dispensing: 12 occurring in days 1-10 (high-risk window), 11 in days 11-20 (moderate-risk window) and 5 in the control window (days 21-32). Assuming an equal likelihood of seizure events across the 32-day observation window, we estimate an attributable risk of 0.9 excess cases per 10,000 exposed users. Using a self-controlled risk interval design with exact logistic regression, seizures were elevated in the high-risk window (relative risk [RR] 2.88 (95% confidence interval [CI] 1.01-8.33) compared with the control window. No significant increased risk was observed in the moderate window. Half of the seizure cases had a diagnosis of renal disease, although seizure risk was not significant (RR 3.20 [CI 0.82-14.01]). A majority of patients in both risk windows were 75 years or older.. Our study suggests risk among younger ranolazine patients is rare. Given the imprecision of the risk estimates, we interpret the elevated seizure risk following ranolazine exposure with caution. Further analysis in a larger elderly population is warranted.

Topics: Aged; Anticonvulsants; Cardiovascular Agents; Cohort Studies; Humans; Kidney Diseases; Logistic Models; Ranolazine; Risk Assessment; Seizures; United States; United States Food and Drug Administration

Ginkgo biloba leaves extract has been widely used worldwide to protect against oxidative stress-induced cell damage and improves blood circulation.. The potential protective role of the standardized leaf extract of Ginkgo biloba (EGb761) on hypertension-induced renal injury was investigated in rats. Hypertension was induced in rats by L-NAME.. Repeated treatment with EGb761 produced progressive reductions in the systolic, diastolic and mean arterial blood pressure. Also, EGb761 increased the progressive reductions in blood pressure induced by losartan. Hypertension-induced marked elevation of renal malondialdehyde (MDA) and nitrite levels and reduction of reduced glutathione (GSH) level were inhibited by EGb761. In addition, hypertension-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)) levels in renal tissues were inhibited by EGb761. Also, treatment with EGb761 inhibited hypertension-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1B in the kidney tissues. EGb761 enhanced losartan effects on renal tissues oxidative stress, nitrite, and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1B. effects.. These results indicate that EGb761 has the ability to protect against hypertension-induced renal injury.

Topics: Animals; Antihypertensive Agents; Arterial Pressure; Cardiovascular Agents; Ginkgo biloba; Glutathione; Hypertension; Hypertension, Renal; Interleukin-1beta; Interleukin-6; Kidney; Kidney Diseases; Losartan; Male; Malondialdehyde; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Plant Extracts; Rats; Tumor Necrosis Factor-alpha

AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been related to clinical outcomes of acute heart failure. However, the prognostic value of the AHEAD score in acute heart failure patients with either reduced or preserved left ventricular ejection fraction (HFrEF and HFpEF) remain to be elucidated.. The study population consisted of 2143 patients (age 77±12 years, 68% men, 38% HFrEF) hospitalized primarily for acute heart failure with a median follow-up of 23.75 months. The performance of the AHEAD score (atrial fibrillation, hemoglobin <13 mg/dL for men and 12 mg/dL for women, age >70 years, creatinine >130 μmol/L, and diabetes mellitus) was evaluated by Cox's regression analysis for predicting cardiovascular and all-cause mortality. The mean AHEAD scores were 2.7±1.2 in the total study population, 2.6±1.3 in the HFrEF group, and 2.7±1.1 in the HFpEF group. After accounting for sex, sodium, uric acid, and medications, the AHEAD score remained significantly associated with all-cause and cardiovascular mortality (hazard ratio and 95% CI: 1.49, 1.38-1.60 and 1.48, 1.33-1.64), respectively. The associations of AHEAD score with mortality remained significant in the subgroups of HFrEF (1.63, 1.47-1.82) and HFpEF (1.34, 1.22-1.48). Moreover, when we calculated a new AHEAD-U score by considering uric acid (>8.6 mg/dL) in addition to the AHEAD score, the net reclassification was improved by 19.7% and 20.1% for predicting all-cause and cardiovascular mortality, respectively.. The AHEAD score was useful in predicting long-term mortality in the Asian acute heart failure cohort with either HFrEF or HFpEF. The new AHEAD-U score may further improve risk stratification.

Topics: Acute Disease; Aged; Aged, 80 and over; Asian People; Atrial Fibrillation; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; Comorbidity; Creatinine; Decision Support Techniques; Diabetes Mellitus; Female; Heart Failure; Hemoglobins; Hospitalization; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Registries; Risk Assessment; Risk Factors; Sodium; Stroke Volume; Systole; Taiwan; Uric Acid; Ventricular Function, Left

Characteristics and prognosis of hemodialysis patients with severe aortic stenosis have not yet been well defined.. The CURRENT AS (contemporary outcomes after surgery and medical treatment in patients with severe aortic stenosis) registry, a Japanese multicenter registry, enrolled 3815 consecutive patients with severe aortic stenosis. There were 405 hemodialysis patients (initial aortic valve replacement [AVR] group: N=135 [33.3%], and conservative group: N=270) and 3410 nonhemodialysis patients (initial AVR group: N=1062 [31.1%], and conservative group: N=2348). The median follow-up duration after the index echocardiography was 1361 days, with 90% follow-up rate at 2 years. The cumulative 5-year incidence of all-cause death was significantly higher in hemodialysis patients than in nonhemodialysis patients in both the entire cohort (71% versus 40%,. Among hemodialysis patients with severe aortic stenosis, the initial AVR strategy as compared with the conservative strategy was associated with significantly lower long-term mortality risk, particularly the risk for sudden death, although the effect size for the survival benefit of the initial AVR strategy was smaller than that in the nonhemodialysis patients.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Cardiovascular Agents; Cause of Death; Female; Heart Valve Prosthesis Implantation; Humans; Japan; Kidney Diseases; Male; Protective Factors; Registries; Renal Dialysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome

Compared with medical therapy, percutaneous coronary intervention (PCI) does not reduce mortality or myocardial infarction in patients with stable angina. Therefore, PCI should be guided by refractory anginal symptoms and not just lesion characteristics.. We hypothesized that angiographic lesion characteristics and stress test results would have a greater role in the decision to proceed with PCI than would symptom severity.. We performed a retrospective cohort study of patients undergoing elective cardiac catheterization and possible PCI at an academic medical center. Anginal symptoms, optimal medical therapy, antianginal therapy, stress test results, and angiographic lesions (including American College of Cardiology/American Heart Association [ACC/AHA] lesion type) were analyzed. Logistic regression was used to determine predictors of medical management among patients not referred for coronary artery bypass surgery.. Of the 207 patients with obstructive lesions amenable to PCI, 163 underwent PCI and 44 were referred to medical therapy. In the multivariable logistic model, the following variables were associated with medical management: advancing age (odds ratio [OR] per 1 year: 0.94, 95% confidence interval [CI]: 0.91-0.98), chronic kidney disease (OR: 0.23, 95% CI: 0.06-0.95), distal location (OR: 0.21, 95% CI: 0.09-0.48), and ACC/AHA type C lesion (OR: 0.08, 95% CI: 0.03-0.22). There was no association with sex, race, symptoms, optimal medical therapy, maximal antianginal therapy, referral status, or type of interventional cardiologist (academic vs private practice).. For patients undergoing cardiac catheterization for stable angina, the decision to proceed to PCI vs medical management appears to depend largely on patient and angiographic characteristics, but not on symptoms or ischemia. Distal and high-risk lesions (ACC/AHA type C) are more often referred for medical therapy.

Topics: Academic Medical Centers; Age Factors; Aged; Aged, 80 and over; Angina, Stable; Cardiac Catheterization; Cardiovascular Agents; Coronary Angiography; Exercise Test; Female; Humans; Kidney Diseases; Logistic Models; Male; Massachusetts; Middle Aged; Multivariate Analysis; Odds Ratio; Patient Selection; Percutaneous Coronary Intervention; Predictive Value of Tests; Referral and Consultation; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Outcome

Serelaxin showed beneficial effects on clinical outcome and trajectories of renal markers in patients with acute heart failure. We aimed to study the interaction between renal function and the treatment effect of serelaxin.. In the current post hoc analysis of the RELAX-AHF trial, we included all patients with available estimated glomerular filtration rate (eGFR) at baseline (n = 1132). Renal impairment was defined as an eGFR <60 ml/min/1.73 m(2) estimated by creatinine.. 817 (72.2 %) patients had a baseline eGFR <60 ml/min/1.73 m(2). In placebo-treated patients, baseline renal impairment was related to a higher 180 day cardiovascular (HR 3.12, 95 % CI 1.33-7.30) and all-cause mortality (HR 2.81, 95 % CI 1.34-5.89). However, in serelaxin-treated patients, the risk of cardiovascular and all-cause mortality was less pronounced (HR 1.19, 95 % CI 0.54 -2.64; p for interaction = 0.106, and HR 1.15 95 % CI 0.56-2.34 respectively; p for interaction = 0.088). In patients with renal impairment, treatment with serelaxin resulted in a more pronounced all-cause mortality reduction (HR 0.53, 95 % CI 0.34-0.83), compared with patients without renal impairment (HR 1.30, 95 % CI 0.51-3.29).. Renal dysfunction was associated with higher cardiovascular and all-cause mortality in placebo-treated patients, but not in serelaxin-treated patients. The observed reduction in (cardiovascular) mortality in RELAX-AHF was more pronounced in patients with renal dysfunction. These observations need to be confirmed in the ongoing RELAX-AHF-2 trial.

Topics: Acute Disease; Aged; Aged, 80 and over; Cardiovascular Agents; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kaplan-Meier Estimate; Kidney; Kidney Diseases; Male; Middle Aged; Randomized Controlled Trials as Topic; Recombinant Proteins; Relaxin; Retrospective Studies; Time Factors; Treatment Outcome

To review the product information (PI) for various brands of the same generic drugs and investigate the extent to which information is currently available on dosing in renal impairment and the concordance between the dosing recommendations for the same generic drug.. The Monthly Index of Medical Specialities (MIMS) was examined for 28 generic drugs recommended to be used with caution in renal impairment. For each generic drug all available brands listed as having solid oral dosage form were recorded. For each identified brand, the current PI was consulted and data referring to renal impairment was collated. The dissimilarity between these PI regarding the renal dosage recommendation was determined.. There was generally a lack of detailed information in the PI on the use of drugs in patients with renal impairment. The majority of PI documents (88 of 155 PI; 57%) provided quantitative dosage recommendations, but this was often not detailed enough to help users to make an informed decision. For 37 PI documents (24%), an altered dosage regimen was proposed without a quantifiable measure of renal function reported in the dose recommendation. The renal function severity category terms used and the associated quantitative values were also not consistent. It was observed that the recommendations varied among different brands of hydromorphone, morphine, oxycodone, tramadol, metformin and topiramate.. The reporting of renal function quantification methods, and associated dosage recommendations, in PI requires standardisation to ensure optimal drug dosing. Regularly updating of PI is also necessary.

Topics: Administration, Oral; Alendronate; Cardiovascular Agents; Central Nervous System Agents; Contraindications; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Labeling; Drugs, Generic; Glomerular Filtration Rate; Gout Suppressants; Humans; Hypoglycemic Agents; Kidney; Kidney Diseases; Kidney Function Tests; Narcotics; Pharmaceutical Preparations; Psychotropic Drugs; Ranitidine; Renal Insufficiency, Chronic

Cardiovascular disease (CVD) is a major source of mortality and morbidity in dialysis patients. Population-level descriptions of CVD medication use are lacking in this population.. Retrospective cohort study.. Adult dialysis patients in the United States, alive on December 31, 2006, with Medicare Parts A and B and enrollment in Medicare Part D continuously in 2007.. CVDs and demographic characteristics.. ≥1 prescription fill during follow-up (2007).. Average out-of-pocket costs per user per month and average total drug costs per member per month were calculated.. Of 225,635 dialysis patients who met inclusion criteria during the entry period, 70% (n = 158,702) had continuous Part D coverage during follow-up. Of these, 76% received the low-income subsidy. β-Blockers were the most commonly used CVD medication (64%), followed by renin-angiotensin system inhibitors (52%), calcium channel blockers (51%), lipid-lowering agents (44%), and α-agonists (23%). Use varied by demographics, geographic region, and low-income subsidy status. For CVD medications, mean out-of-pocket costs per user per month were $3.44 and $49.59 and mean total costs per member per month were $124.02 and $110.32 for patients with and without the low-income subsidy, respectively.. Information was available for only filled prescriptions under the Part D benefit; information for clinical contraindications was lacking, information for over-the-counter medications was unavailable, and medication adherence and persistence were not examined.. Most Medicare dialysis patients in 2007 were enrolled in Part D, and most enrollees received the low-income subsidy. β-Blockers were the most used CVD medication. Total costs of CVD medications were modestly higher for low-income subsidy patients, but out-of-pocket costs were much higher for patients not receiving the subsidy. Further study is warranted to delineate sources of variation in the use and costs of CVD medications across subgroups.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Calcium Channel Blockers; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Cost of Illness; Female; Follow-Up Studies; Health Care Costs; Humans; Kidney Diseases; Male; Medicare Part D; Middle Aged; Renal Dialysis; Retrospective Studies; United States

The association between changes in systolic and diastolic blood pressure, and the use of cardioprotective drugs on survival of incident hemodialysis patients, was examined in this retrospective cohort study. Pre-hemodialysis systolic and diastolic blood pressures were averaged over the first month of hemodialysis. Slopes, reflecting temporal changes, were computed by linear regression of systolic blood pressures and Cox regression was used for survival analyses. Patients were initially stratified into four cohorts (below 120, 120 to 150, 151 to 180, and above 180 mm Hg) and further subdivided into groups with stable (no more than a 1-mm Hg change per month), increasing (over 1-mm Hg per month), and decreasing (less than 1-mm Hg per month) slopes during the first year. Analyses were repeated for patients who were treated with cardioprotective drugs for 1 month or more in the second year. In 10,245 patients (59% prescribed cardioprotective drugs), both increases and decreases in all ranges of blood pressure were associated with worse outcomes, whereas stable blood pressure had a survival advantage at all levels of systolic and diastolic pressures. Use of cardioprotective drugs attenuated changes and improved survival. Validation and sensitivity analyses confirmed the primary findings. Therefore, previous temporal trends need to be considered in patient care, and the use of cardioprotective agents is associated with enhanced survival at all blood pressure levels.

Topics: Aged; Blood Pressure; Cardiovascular Agents; Female; Humans; Kaplan-Meier Estimate; Kidney Diseases; Linear Models; Male; Middle Aged; Proportional Hazards Models; Renal Dialysis; Reproducibility of Results; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States

Persons with kidney disease often have cardiovascular disease, but they are less likely to use recommended medications for secondary prevention. The hypothesis was that participants with reduced estimated GFR have lower use of medications recommended for secondary prevention of cardiovascular events (antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, β-blockers, and statins) and lower medication adherence than participants with preserved estimated GFR.. In this cross-sectional analysis, we analyzed data from 6913 participants in the Reasons for Geographic and Racial Differences in Stroke study with a history of cardiovascular disease. Medication use was ascertained by an in-home pill bottle review. Medication adherence was assessed using a validated four-item scale.. Among participants with a history of cardiovascular disease, 59.8% used antiplatelet agents, 49.9% used angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, 41.6% used β-blockers, and 53.0% used statins. Compared with the referent group (estimated GFR ≥60 ml/min per 1.73 m(2)), participants with estimated GFR <45 ml/min per 1.73 m(2) were more likely to use angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (adjusted prevalence ratio=1.14, 95% confidence interval=1.06-1.23), β-blockers (adjusted prevalence ratio=1.20, 95% confidence interval=1.09-1.32), and statins (adjusted prevalence ratio=1.10, 95% confidence interval=1.01-1.19). Antiplatelet agent use did not differ by estimated GFR category; 30% of participants reported medication nonadherence across all categories of estimated GFR.. Among participants with a history of cardiovascular disease, mild to moderate reductions in estimated GFR were associated with similar and even more frequent use of medications for secondary prevention compared with participants with preserved estimated GFR. Overall medication use and adherence were suboptimal.

Topics: Aged; Aged, 80 and over; Black or African American; Cardiovascular Agents; Cardiovascular Diseases; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Regression Analysis; Secondary Prevention; Time Factors; Treatment Outcome; United States; White People

Preterm infants are delivered while glomerulogenesis is ongoing and may be exposed to insults, including medications that may affect renal development. Podocytes detected in the urine are an indicator of glomerular injury. The aims of this study were to determine whether preterm and term infants excrete podocytes in their urine and whether exposure to gentamicin and indomethacin increase podocyte excretion in their urine.. Preterm infants <33 weeks gestation had urine collected each day while receiving either gentamicin or indomethacin. Preterm and term control infants had urine collected for 3 days. The number of casts and podocytes present in the urine of infants receiving indomethacin and gentamicin were compared with preterm and term control infants.. Forty-two neonates were included in the study. Podocytes were present in small numbers (< 2) in the urine of both preterm and term control neonates. The number of podocytes in the preterm group receiving indomethacin was significantly higher than in all other groups (p=0.02) ,as was urinary albumin (p=0.02).. Increased number of podocytes in preterm neonates receiving indomethacin and higher excretion of albumin suggest glomerular injury is occurring. It is unknown whether injury to glomeruli during glomerulogenesis in preterm neonates has long-term sequelae for renal development and function into adulthood.

Topics: Anti-Bacterial Agents; Cardiovascular Agents; Drug Therapy, Combination; Ductus Arteriosus, Patent; Female; Gentamicins; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Kidney Diseases; Kidney Glomerulus; Male; Podocytes

Topics: Cardiovascular Agents; Cardiovascular Diseases; Female; Humans; Kidney Diseases; Male; Medicare Part D; Renal Dialysis

Patients with chronic kidney disease (CKD) frequently suffer from heart disease as well. The combination of the two processes can exacerbate inflammation, resulting in increases in both resistance to erythropoietin (EPO) and mortality.. The aim of this study was to determine the prevalence of heart disease in a representative group of non-dialysis patients with stage 4-5 CKD, and the influence of that entity on EPO requirements and on mortality during a period of 36 months.. 134 patients (68% on EPO at the beginning, increasing to 72.3% during follow-up) were monitored for 36 months. To evaluate the dose-response effect of EPO therapy, we used the erythropoietin resistance index (ERI) calculated as the weekly weight-adjusted dose of EPO divided by the haemoglobin level. The ERI was determined both initially and during the last six months before the end of the study.. 39 patients (29.1%) had history of heart disease; 22 (16.4%) had suffered from heart failure (HF). The ERI was higher in patients with a history of heart disease or HF and those treated with drugs acting on the renin-angiotensin system (ACE inhibitors or ARBs). Using ERI as the dependent variable in the multivariate analysis, the variables that composed the final model were ferritin, haemoglobin, glomerular filtration rate and history of HF. The 36 month mortality rate (n=39 patients) was higher in the group having ERI above the median (2.6IU/week/kg/gram of haemoglobin in 100ml) (P=.002), and in the groups with heart disease (P=.001) or HF (P=.001) according to the Kaplan-Meier survival analysis.. Patients with history of heart disease or HF have a higher ERI, and all of these characteristics are associated with lower survival. ERI can be considered a marker for risk of death in the short to-medium term.

Topics: Aged; Aged, 80 and over; Anemia; Autoimmune Diseases; Cardio-Renal Syndrome; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Resistance; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Heart Diseases; Heart Failure; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Severity of Illness Index

Chronic kidney disease (CKD) is associated with poor outcomes after acute coronary syndromes, yet selection for invasive investigation and management is low.. Patients presenting with ST segment elevation myocardial infarction (STEMI) or intermediate- to high-risk non-ST segment elevation acute coronary syndrome (NSTEACS) (n=2597) were stratified into groups based on kidney function, defined as normal (glomerular filtration rate (GFR)≥60mL/min/1.73m(2) ), moderate CKD (GFR 30-59mL/min/1.73m(2) ) and severe CKD (GFR <30mL/min/1.73m(2)). Based on these stratums of kidney function, incidence and outcome measures were obtained for: rates of angiography and revascularization; 6-month mortality; and the incidence and outcome of in-hospital acute kidney impairment (AKI).. Patients with CKD were less likely to be offered coronary angiography after STEMI/NSTEACS (P<0.001); however, after selection, revascularization rates were similar (percutaneous coronary intervention (P=0.8); surgery (P=0.4)). Six-month mortality rates increased with CKD (GFR≥60, 2.8%; GFR 30-59, 9.9%; GFR<30, 16.5%, P≤0.001), as well as the combined efficacy/safety end-point (GFR≥60, 9.4%; GFR 30-59, 20.2%; GFR<30, 27.1%, P≤0.001). Six-month mortality was lower in patients who had received prior angiography (GFR≥60, 1.5% vs 3.6%, P=0.001; GFR 30-59, 5.1% vs 12.7%, P<0.001; GFR<30, 7.3% vs 18.5%, P=0.094). Risk of AKI increased with CKD (GFR≥60, 0.7%; GFR 30-59, 3.4%; GFR<30, 6.8%, P≤0.001), and was associated with high 6-month mortality (35.6% vs 4.1%, P<0.001).. In patients with CKD after STEMI/NSTEACS, 6-month mortality and morbidity is high, selection for angiography is lower, yet angiography is associated with a reduced long-term mortality, and with comparable revascularization rates to those without CKD. In-hospital AKI is more common in CKD and predicts a high 6-month mortality.

Topics: Acute Coronary Syndrome; Acute Kidney Injury; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chronic Disease; Combined Modality Therapy; Coronary Angiography; Disease Management; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Incidence; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Myocardial Revascularization; New South Wales; Risk; Selection Bias; Treatment Outcome

Topics: Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Cost-Benefit Analysis; Creatinine; Disease Progression; General Practice; Glomerular Filtration Rate; Health Care Costs; Hematinics; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Kidney; Kidney Diseases; Nurse Clinicians; Patient Care Team; Platelet Aggregation Inhibitors; Preventive Health Services; Risk Assessment; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Smoking Cessation; Treatment Outcome; Up-Regulation

Around 16% of all patients who present with atheromatous renovascular disease (ARVD) in the United States undergo revascularization. Historically, patients with advanced chronic kidney disease (CKD) have been considered least likely to show improvement in renal functional terms, or survival. We aimed to investigate whether differences in outcomes after revascularization compared to medical management might be observed in ARVD patients if stratified by their CKD classes.. Two prospective cohorts, a UK center with a traditionally conservative approach, and a German center who undertook a proactive revascularization approach, were compared. An improvement in renal function was defined as > 20% renal improvement at one year's follow-up. To improve validity and comparability, revascularized patients in the UK center were also used within analyses,. 347 (UK conservative group), 89 (UK revascularized group), and 472 (German center) patients were included in the analysis. When subdivided by CKD stage, patient ages between the two centers were comparable. Improvements in renal function were observed in twice as many patients who underwent revascularization as compared to medical treatment, particularly in the latter CKD stages, 15.2 (German revascularization) vs. 0% in CKD 1-2, 12.2 (UK), and 32.8 (German) revascularization vs. 14.1% in CKD3, and 53.1 and 53.8 vs. 28.3 in patients with CKD 4-5. The improvements in eGFR were 10.2 (16) and 8.1 (12.5) ml/min/year in the German and UK revascularized groups, respectively, vs. -0.05 (6.8) ml/min/year in the medical cohort in CKD 4-5. Improvements in blood pressure control were noted at 1 year overall and within each CKD category. Multivariate analysis revealed that revascularization independently reduced the risk of death by 45% in all patients combined (RR 0.55, P = 0.013).. Although this study has significant methodological limitations, it does shows that percutaneous renal revascularization can improve renal function in advanced CKD (stages 4-5), and that this can provide a survival advantage in prospective analysis.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon; Atherosclerosis; Cardiovascular Agents; Chronic Disease; Databases as Topic; Female; Germany; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Logistic Models; Male; Middle Aged; Odds Ratio; Prospective Studies; Recovery of Function; Renal Artery Obstruction; Risk Assessment; Risk Factors; Severity of Illness Index; Stents; Time Factors; Treatment Outcome; United Kingdom

We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD).. We analyzed 519 patients with CKD (56+/-9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography.. In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction > or =70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft-intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48-15.10; death: hazard ratio=3.39; % confidence interval 1.41-8.45).. In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

Topics: Aged; Angioplasty, Balloon, Coronary; Brazil; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Bypass; Coronary Stenosis; Disease Progression; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Practice Guidelines as Topic; Proportional Hazards Models; Registries; Renal Dialysis; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Treatment Refusal; Waiting Lists

Topics: Angioplasty, Balloon; Atherosclerosis; Cardiovascular Agents; Chronic Disease; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Recovery of Function; Renal Artery Obstruction; Risk Assessment; Risk Factors; Severity of Illness Index; Stents; Time Factors; Treatment Outcome

Antiplatelet agents, beta-blockers, statins and ACE inhibitors have been shown to reduce mortality in patients following myocardial infarction (MI). However, it is uncertain if the combination of these agents has a similar impact on mortality following MI in patients with renal dysfunction.. We studied 5529 consecutive patients with confirmed MI between January 2000 and December 2003. Data on baseline demographics, co-morbidities and in-hospital management were collected prospectively. Glomerular filtration rate (GFR) was estimated using the 4-component Modification of Diet in Renal Disease equation. Based on discharge use of evidence-based medications, the patients were divided into those using 0, 1, 2, 3 or 4 medications. The impact of medication use on 1-year mortality was then assessed for patients with GFR > or =60 ml/min/1.73 m2 (group I) and GFR < 60 ml/min/1.73 m2 (group 2).. Mean age was 63 +/- 13 years with 71% men.The prevalence of reduced GFR was 35% and the adjusted odds ratio for I-year mortality of patients in group 2 compared to those in group I was 1.86 (95% CI 1.54-2.25, P < 0.001). Compared with patients with no medication, the adjusted odds ratio for 1-year mortality was lower in patients with 1, 2, 3 and 4 medications in both groups. There was no significant interaction between the number of medications used and GFR.. Increased use of combined evidence-based medications was independently associated with a lower 1-year post MI mortality. Such therapies offer similar survival benefit in patients with and without renal dysfunction.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Drug Therapy, Combination; Evidence-Based Medicine; Female; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Odds Ratio; Platelet Aggregation Inhibitors; Prevalence; Prospective Studies; Risk Factors; Singapore; Survival Rate; Treatment Outcome

Albuminuria is a marker for renal and cardiovascular (CV) risk, allowing early diagnosis of subjects with elevated renal and CV risk.. This study aimed to estimate the cost-effectiveness and budget impact of various population-based screen-and-treat scenarios for elevated albuminuria levels (ie, microalbuminuria) in the Netherlands.. A multistate transition Markov model was developed to simulate the natural course of albuminuria-based disease progression to dialysis and occurrence of CV events. Several population-based strategies directed at screening for elevated albuminuria were evaluated. These strategies depended on urinary albumin concentration (UAC), urinary albumin excretion (UAE), and age. Transition probabilities were derived from the observational community-based Prevention of Renal and Vascular End Stage Disease (PREVEND) cohort study. Health care costs (in year-2008 euros) and life-years gained were calculated over an 8-year period. In the base-case analysis, we analyzed screening for and treatment of microalbuminuria. Screening for microalbuminuria involved prescreening for UAC >or=20 mg/L, followed by a confirmation test for UAE >or=30 mg/d. Other options based on combinations of albuminuria for UAC prescreening (no prescreening, and >or=10, >or=20, >or=100, and >or=200 mg/L) and UAE confirmation test (>or=15, >or=30, and >or=300 mg/d) for treatment were investigated in scenario analyses. Furthermore, these various strategies based on UAC and UAE values were analyzed in different subgroups based on age (all ages, aged >or=50 years, and aged >or=60 years).. The PREVEND study included 8592 Dutch residents aged 28 to 75 years at the time of initial screening. Among a hypothetical cohort of 1000 subjects identified and treated in the base-case analysis, it was estimated (based on PREVEND follow-up data) that, in the screening/treatment and no-screening scenarios, 76 versus 124 CV events occurred, 16 versus 27 CV deaths, and 3 versus 5 dialysis cases, respectively. The per-person difference in net costs for screening was calculated at euro926 (euro2003 vs euro1077), and prevention of CV deaths was estimated to gain 0.0421 discounted life-year per person. Correspondingly, the cost-effectiveness was estimated at euro22,000 per life-year gained. In the base-case analysis, probabilistic sensitivity analysis indicated that the likelihood of cost-effectiveness of a screen-and-treat strategy was 54%, 90%, and 95% for a maximum acceptable cost-effectiveness threshold of euro20,000, euro50,000, and euro80,000 per life-year gained, respectively. Higher albuminuria thresholds for screening and start of treatment further improved the cost-effectiveness but reduced the overall health gains achieved. Limiting screening to those subjects aged >or=50 and >or=60 years resulted in more favorable cost-effectiveness compared with population-based screening without age restriction.. Our analyses suggest the potentially favorable cost-effectiveness of population-based screening for albuminuria in the general Dutch population. The results offer health care decision-makers new tools for considering actual implementation of such screening.

Topics: Adult; Age Factors; Aged; Albuminuria; Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Cohort Studies; Cost-Benefit Analysis; Early Diagnosis; Female; Humans; Kidney Diseases; Male; Markov Chains; Mass Screening; Middle Aged; Netherlands

Topics: Animals; Cardiomegaly; Cardiovascular Agents; Heart; Humans; Kidney; Kidney Diseases; Mice; Myocardium; Rats; Renin-Angiotensin System; rho-Associated Kinases; Ventricular Remodeling

Contemporary trends in the management and outcomes of chronic kidney disease patients who develop an acute myocardial infarction have not been adequately described, particularly from the more generalizable perspective of a population-based investigation.. The study population consisted of 6219 residents of the Worcester, Massachusetts, metropolitan area who were hospitalized with acute myocardial infarction in 6 annual periods between 1995 and 2005. Patients were categorized as having preserved kidney function (n=3154), mild to moderate chronic kidney disease (n=2313), or severe chronic kidney disease (n=752) at the time of hospital admission.. Patients with chronic kidney disease were more likely to be older, to have a greater prevalence of comorbidities, and to experience significant in-hospital complications or die during hospitalization in comparison with patients with preserved kidney function. Although patients with chronic kidney disease were less likely to receive effective cardiac medications or undergo coronary interventional procedures than patients without kidney disease, we observed a marked increase in the use of effective cardiac medications and coronary interventional procedures in patients with chronic kidney disease during the period under study. In-hospital death rates declined over time among patients with chronic kidney disease, whereas these death rates remained unchanged among persons with normal kidney function.. The results of this study in residents of a large New England metropolitan area provide insights into changing trends in the treatment and impact of chronic kidney disease in patients hospitalized with acute myocardial infarction.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Biomarkers; Blood Pressure; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Artery Bypass; Creatinine; Drug Prescriptions; Female; Glomerular Filtration Rate; Heart Rate; Humans; Kidney Diseases; Length of Stay; Male; Massachusetts; Middle Aged; Myocardial Infarction; Practice Patterns, Physicians'; Prevalence; Research Design; Retrospective Studies

In recent decades, the increased use of novel pharmacologic therapies and primary percutaneous coronary intervention has considerably improved survival in the setting of ST-segment elevation myocardial infarction. Nevertheless, optimal management and care of particular subgroups of patients such as the elderly and individuals with diabetes mellitus, renal dysfunction, or cardiogenic shock are still debated. In fact, because of their clinically relevant comorbidities, these patients are often excluded from randomized trials; thus, data are largely limited to those from retrospective cohorts or subgroup analyses of large clinical studies. These particular subgroups of patients require special management during and after prompt mechanical reperfusion because of their high risk of both thrombotic and bleeding events. Therefore, cardiologists should accurately assess the risk-benefit equation before administrating and dosing currently available antithrombotic and antiplatelets agents in these high-risk populations.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Diabetes Complications; Electrocardiography; Fibrinolytic Agents; Heart-Assist Devices; Humans; Kidney Diseases; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Assessment; Shock, Cardiogenic

Topics: Adenosine A1 Receptor Antagonists; Cardiovascular Agents; Cyclohexanes; Diuretics; Evidence-Based Medicine; Heart Failure; Hemodynamics; Heterocyclic Compounds, 2-Ring; Humans; Kidney; Kidney Diseases; Myocardium; Receptor, Adenosine A1; Treatment Outcome; Ventricular Function, Left

Topics: Albuminuria; Aortic Aneurysm, Abdominal; Biomarkers; Cardiovascular Agents; Elective Surgical Procedures; Glomerular Filtration Rate; Humans; Ischemic Preconditioning; Kidney Diseases; Lower Extremity; Minimally Invasive Surgical Procedures; Myocardial Reperfusion Injury; Reperfusion Injury; Time Factors; Tourniquets; Treatment Outcome; Vascular Surgical Procedures

Percutaneous coronary intervention (PCI) using drug-eluting stents significantly reduces the risk of restenosis in the general population. However, in patients on hemodialysis, adverse cardiac events are frequently seen even if treated with drug-eluting stents. Recent studies suggest that C-reactive protein (CRP) reflects vascular wall inflammation and can predict adverse cardiac events. We evaluated possible prognostic values of CRP on outcomes in patients on hemodialysis undergoing PCI with drug-eluting stents.. A total of 167 patients undergoing PCI with sirolimus-eluting stents for stable angina (322 lesions) were enrolled. They were divided into tertiles according to serum CRP levels. We analyzed the incidence of major adverse cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization after PCI as well as quantitative coronary angiographic data. The mean follow-up was 31 months (SD, 14). Major adverse cardiac events occurred in 11 patients (19.6%) of the lowest tertile, in 22 patients (39.3%) of the middle tertile, and in 28 patients (50.9%) of the highest tertile during follow-up period (P=0.0009). There was a progressive increase in neointimal growth after sirolimus-eluting stent implantation during follow-up because preprocedural CRP levels were higher, despite similar angiographic data just after PCI. Angiographic restenosis at 6 to 8 months after PCI was seen in 10.6% in the lowest tertile, 17.9% in the middle tertile, and 32.0% in the highest tertile (P=0.0007).. Increased preprocedural serum CRP levels would predict higher major adverse cardiac events and restenosis rates after sirolimus-eluting stents implantation in patients on hemodialysis.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Inflammation Mediators; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Protein C; Renal Dialysis; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Up-Regulation

A 69 year old man was admitted with unstable angina (Class IIB). He had a history of chronic renal impairment, diabetes mellitus, hypertension and coronary bypass surgery in 1997 (LIMA graft to the LAD anf diagonal branch, saphenous vein grafts to the RCA and first marginal branch of LCx.. Coronary angiography.. Unstable angina (Class IIB). Occlusion of the LCx and RCA. Functionally occluded LIMA on the LAD and diagonal branch. Diffuse disease of the LAD with two significant lesions at the LAD-first diagonal and mid-distal LAD.. Revascularisation.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Complications; Drug-Eluting Stents; Everolimus; Graft Occlusion, Vascular; Hemodynamics; Humans; Hypertension; Kidney Diseases; Male; Sirolimus; Treatment Outcome

It is unknown whether adherence to recommended medications after myocardial infarction (MI) differs by kidney function.. This was a retrospective cohort study of older patients who were discharged after MI in two Eastern states between 1995 and 2004. Patients were categorized as having ESRD, having chronic kidney disease (CKD), and being free from diagnosed CKD. Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), beta blockers (BB), and statins was assessed within 30 d after discharge. Good adherence was defined as proportion of days covered >80% during the first year after discharge.. Compared with patients with no CKD, patients with CKD had 22% lower adjusted use of ACEI/ARB but similar rates of BB and statin use. Patients with ESRD experienced 43% lower ACEI/ARB and 17% lower statin use. Only 64% (BB), 57% (statins), and 54% (ACEI/ARB) of patients had good 1-yr adherence. Adherence was similar between patients with CKD and with no CKD for all study drugs. Fewer patients with ESRD had good adherence to BB.. With the exception of lower ACEI/ARB use in patients with CKD, we found no differences between patients with CKD and with no CKD in their use of and adherence to these cardiovascular medications after MI. Patients with ESRD experienced lower use of ACEI/ARB and statins and lower adherence to BB regimens. Postulated differences in medication use after MI across levels of kidney function are unlikely to explain the observed differences in long-term outcomes.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Chronic Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney; Kidney Diseases; Kidney Failure, Chronic; Male; Myocardial Infarction; New Jersey; Patient Compliance; Pennsylvania; Retrospective Studies; Time Factors; Treatment Outcome

Heart failure (HF) represents a major public health issue in an aging population. Although HF is a leading cause of morbidity and mortality in developed countries, the clinical features of HF in Japan remain unclear.. This observational cohort study analyzed data from the Heart Institute of Japan--Department of Cardiology (HIJC)-HF Registry, which is based on a nationwide survey by the HIJC, Tokyo Women's Medical University and its affiliated hospitals. Of 3,578 consecutive patients (average age, 69.8 years; females 40.7%) hospitalized for HF between January 2001 and December 2002, 95.0% were followed up until the end of 2005 (median, 2.8 years). The 1- and 3-year mortality rates were 11.3% and 29.2%, respectively. Multivariate analysis revealed that advanced age (hazard ratio 1.71 [95% confidence interval 1.38-2.12]; p<0.001), symptomatic HF at hospital discharge (3.76 [2.30-6.17]; p<0.001), renal impairment (1.96 [1.50-2.57]; p=0.008), anemia (1.46 [1.18-1.80]; p=0.02) and low pulse pressure (2.88 [1.62-5.13]; p=0.0003) were significantly associated with total death.. Although the long-term mortality rate for Japanese patients with HF is lower than in other countries, several markers are modifiable. The data demonstrate that continued improvements in the treatment of Japanese patients with HF are still needed.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia; Cardiovascular Agents; Female; Health Care Surveys; Heart Failure; Humans; Hypotension; Inpatients; Japan; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The treatment of acute decompensated heart failure remains problematic and most often requires parenteral therapies. Significant concerns have been expressed regarding risks and benefits of individual therapies, especially nesiritide (NES), but few studies have compared the relative safety of varied intravenous therapies on clinical outcomes.. We compared the safety of intravenous diuretics (DIUR), inotropes (INO), and vasodilators (nitroglycerin [NTG]) on mortality rates and worsening renal function in 99,963 inpatients with acutely decompensated heart failure (ADHF). Patients with a diagnosis of ADHF within 48 hours were grouped by intended primary treatment (intravenous agents administered during the first 2 hours of intravenous therapy). Treatments studied were (a) intended monotherapy (DIUR), (b) intended combination therapy (DIUR + NES, NTG, or INO), and (c) sequential therapy (intended DIUR monotherapy followed by a second agent administered >2 hours later). Propensity-matched cohorts and instrumental analysis were used to adjust for differences among patients in treatment groups.. Intended DIUR monotherapy yielded an unadjusted inpatient mortality rate of 3.2%. After intended DIUR monotherapy, inpatient mortality was not higher for sequential use of NES than for sequential use of NTG (3.4% vs 6.2%, P = .0028). In all regimens, INOs were associated with higher inpatient mortality than were diuretics or vasodilators used alone. The rate of worsening renal function was higher with combination of diuretic-based regimens with NES (risk ratio 1.44, P < .0001) or NTG (RR 1.2, P = .012) compared with diuretics alone.. Compared with alternative intravenous regimens, administration of vasodilators, including NES, was not associated with increased inpatient mortality. A large randomized controlled clinical trial is being planned to prospectively address the question of risks and benefits of NES for ADHF.

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Cardiovascular Agents; Databases as Topic; Diuretics; Female; Heart Failure; Hospitalization; Humans; Infusions, Intravenous; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Vasodilator Agents

Topics: Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus; Dyslipidemias; Europe; Female; Genetic Predisposition to Disease; Guideline Adherence; Health Promotion; Heart Rate; Humans; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Inflammation; Kidney Diseases; Life Style; Lipids; Male; Metabolic Syndrome; Motor Activity; Nutritional Physiological Phenomena; Obesity; Overweight; Primary Prevention; Risk Assessment; Risk Factors; Sex Factors; Smoking; Smoking Cessation; Stress, Psychological; Treatment Outcome

Topics: Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus; Dyslipidemias; Female; Genetic Predisposition to Disease; Guideline Adherence; Health Promotion; Heart Rate; Humans; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Inflammation; Kidney Diseases; Life Style; Lipids; Male; Metabolic Syndrome; Motor Activity; Nutritional Physiological Phenomena; Obesity; Overweight; Primary Prevention; Risk Assessment; Risk Factors; Sex Factors; Smoking; Smoking Cessation; Stress, Psychological; Treatment Outcome

Recent studies have emphasized the prognostic value of baseline creatinine or estimated creatinine clearance in the setting of acute coronary syndromes. However, the prevalence and prognostic significance of worsening renal function (WRF) in patients with acute ST-elevation myocardial infarction are unknown.. We studied 1038 patients presenting with acute ST-elevation infarction. WRF was defined as an increase of > or =0.5 mg/dL in creatinine level at any point during hospital stay. The relation between WRF and subsequent inhospital and 1-year mortality was analyzed by use of multivariate logistic regression and Cox proportional hazards models, respectively, controlling for covariates.. WRF occurred in 98 (9.6%) patients during hospital stay. Baseline renal dysfunction (calculated glomerular filtration rate <60 mL/min) and WRF were strong independent predictors of inhospital mortality (adjusted odds ratios 2.8, 95% CI 1.3-5.9; and 11.4, 95% CI 6.6-19.5, respectively). In a Cox multivariate analysis, both baseline renal dysfunction (adjusted hazard ratio 2.8, 95% CI 1.6-4.9) and WRF (adjusted hazard ratio 7.2, 95% CI 4.9-10.4) remained independent predictors of 1-year mortality. WRF provided incremental prognostic value toward the prediction of 1-year mortality when added to clinical risk predictors and baseline renal function. The increased mortality associated with impaired baseline renal function was largely caused by events occurring in patients with WRF.. WRF occurring during admission for ST-elevation myocardial infarction is a powerful and independent predictor of inhospital and 1-year mortality. Small elevations of serum creatinine may serve as a simple marker to identify patients at a very high risk.

Topics: Aged; Cardiovascular Agents; Comorbidity; Creatinine; Disease Progression; Disease-Free Survival; Female; Glomerular Filtration Rate; Hospital Mortality; Humans; Israel; Kidney; Kidney Diseases; Life Tables; Logistic Models; Male; Middle Aged; Mortality; Myocardial Infarction; Prognosis; Proportional Hazards Models; Risk; Stroke Volume; Survival Analysis

Patients with kidney disease and acute myocardial infarction (AMI) receive standard therapy, including thrombolytic medication, less frequently than patients with normal kidney function. Our goal is to identify potential differences in thrombolytic medication delays and thrombolytic-associated bleeding events by severity of kidney disease.. This is a retrospective cohort analysis of Cooperative Cardiovascular Project data for all Medicare patients with AMI from 4,601 hospitals. Outcome measures included time to administration of thrombolytic medication censored at 6 hours and bleeding events.. Of 109,169 patients (mean age, 77.4 years; 50.6% women), 13.9% received thrombolysis therapy. Average time to thrombolytic therapy was longer in patients with worse kidney function. Adjusted hazard ratios for minutes to thrombolytic therapy were 0.83 (95% confidence interval [CI], 0.79 to 0.87) for patients with a serum creatinine level of 1.6 to 2.0 mg/dL (141 to 177 micromol/L) and 0.58 (95% CI, 0.53 to 0.63) for patients with a creatinine level greater than 2.0 mg/dL (>177 micromol/L) or on dialysis therapy compared with those with normal kidney function. Odds ratios for bleeding events in patients administered thrombolytics versus those who were not decreased with worse kidney function: adjusted odds ratios, 2.28 (95% CI, 2.16 to 2.42) in patients with normal kidney function and 1.84 (95% CI, 1.09 to 3.10) in dialysis patients.. Patients with worse kidney function experienced treatment delays, but were not at greater risk for thrombolysis-associated excess bleeding events. Physician concerns of thrombolytic-associated bleeding may not be sufficient reason to delay the administration of thrombolytic medication.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Cohort Studies; Comorbidity; Creatinine; Databases, Factual; Diabetes Mellitus; Female; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Humans; Hypertension; Kidney Diseases; Life Tables; Male; Medicare; Myocardial Infarction; Peptic Ulcer; Proportional Hazards Models; Retrospective Studies; Sampling Studies; Thrombolytic Therapy; Time Factors; United States

We evaluated the factors related to indomethacin responsiveness of the patent ductus arteriosus (PDA) and subsequent renal and electrolyte abnormalities in a large number of low birth weight infants.. The ductus was evaluated by Doppler echocardiogram or clinical signs after the last administration of indomethacin for 2538 low birth weight infants, through the use of postmarketing surveillance data.. Multivariate logistic regression analyses demonstrated that clinical closure of PDA was significantly associated with pregnancy-induced hypertension and respiratory distress syndrome. In contrast, a 1-point increase of cardiovascular dysfunction score or a 1-day increase in postnatal age at the first indomethacin treatment decreased the responsiveness of the ductus to indomethacin. Clinical ductal reopening was significantly less likely to occur for each week of increased gestational age. Ductal reopening was more likely for each day of postnatal life at the first administration of indomethacin. Infants with preexisting renal and electrolyte abnormalities and infants whose mothers had received indomethacin tocolysis or who had chorioamnionitis were at increased risk of development of renal impairment.. Both antenatal and postnatal factors predict good or poor response to indomethacin therapy for PDA.

Topics: Cardiovascular Agents; Chorioamnionitis; Ductus Arteriosus, Patent; Echocardiography, Doppler; Female; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Male; Multivariate Analysis; Pregnancy; Pregnancy Complications; Water-Electrolyte Imbalance

The occurrence of apoptosis in heart, kidney and small intestine was investigated in spontaneously hypertensive rats (SHR) treated with doxorubicin (1 mg/kg/week for 6, 9 and 12 weeks) with and without pretreatment with the iron chelator ICRF-187 [(+)1.2-bis(3.5-dioxopiperazinyl-l-yl)propane] (25 mg/kg, i.p., given 30 min before doxorubicin). Animals receiving either ICRF-187 alone or saline were used as controls. Cells undergoing apoptosis were identified ultrastructurally and by staining using the nick-end labeling method. The results obtained by counting cells with positive nick-end labeling showed that, when given in cumulative doses of 9 and 12 (but not 6) mg/kg, doxorubicin induced significant toxicity in the heart, kidneys and intestine in association with apoptosis in epithelial cells of the intestinal mucosa and renal tubules but not in cardiac myocytes. At these doses nick end labeling in the heart was confined to occasional endothelial cells, interstitial dendritic cells and macrophages. The frequency of doxorubicin-induced apoptosis in renal and intestinal epithelial cells was decreased by pretreatment of the SHR with ICRF-187. Our data support the concept that the chronic cardiomyopathy induced by doxorubicin is not mediated by apoptosis of the cardiac myocytes.

Topics: Animals; Apoptosis; Cardiomyopathies; Cardiovascular Agents; Dose-Response Relationship, Drug; Doxorubicin; Heart; Hypertension; Immunohistochemistry; Intestines; Iron Chelating Agents; Kidney; Kidney Diseases; Male; Microscopy, Electron; Myocardium; Rats; Rats, Inbred SHR; Razoxane

The susceptibility of a tissue to the toxic and/or carcinogenic effects of chemicals is determined by a variety of factors, which include their rate of metabolic activation by the cytochrome P450-dependent monooxygenases. Individual differences in the levels of cytochrome P450 expression would be expected, and are known, to give rise to profound differences in toxicological response. Such effects are almost best exemplified by the sex differences observed in the toxic effects of a variety of nephrotoxins and carcinogens. In recent work, we have shown that in species such as the mouse and rat almost all cytochrome P450 enzymes in the kidney are sexually differentiated. This difference in cytochrome P450 regulation is mediated by testosterone and explains the large differences observed in the metabolic activation, toxicity and carcinogenicity of chloroform and possibly of other compounds such as ochratoxin A. In addition to hormonal or environmental influences on cytochrome P450 expression, genetic factors have also been shown to be important. In man, this is best exemplified by the genetic polymorphism observed in the metabolism of debrisoquine and approximately 25 other drugs. This genetic defect affects approximately 5-10% of the Caucasian population and has been associated with altered susceptibility to cancer. In this presentation, the development of a simple DNA-based assay to identify affected individuals is described. Use of this assay will allow clarification of the reported association of this genetic polymorphism to susceptibility to Balkan nephropathy and cancer.

Topics: Animals; Balkan Nephropathy; Base Sequence; Biotransformation; Carcinogens; Cardiovascular Agents; Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme System; Disease Susceptibility; DNA; DNA Mutational Analysis; Dogs; Enzyme Induction; Female; Genes; Genetic Predisposition to Disease; Humans; Inactivation, Metabolic; Incidence; Isoenzymes; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mixed Function Oxygenases; Molecular Sequence Data; Neoplasms; Phenotype; Polymorphism, Genetic; Psychotropic Drugs; Rabbits; Rats; Sex Factors

Topics: Cardiovascular Agents; Humans; Kidney; Kidney Diseases; Muscle Relaxants, Central; Zoxazolamine

Topics: Cardiovascular Agents; Kidney Diseases; Muscle Relaxants, Central; Parasympatholytics; Renal Insufficiency; Theophylline

Topics: Acute Disease; Cardiovascular Agents; Ergoloid Mesylates; Ergot Alkaloids; Kidney Diseases

Topics: Cardiovascular Agents; Eclampsia; Ergot Alkaloids; Female; Humans; Kidney Diseases; Oxytocics; Pregnancy; Pregnancy Complications; Secale