natriuretic-peptide--brain and Diabetic-Angiopathies

Cardiovascular disease (CVD) risk assessment has changed substantially in recent years. While older guidelines considered diabetes a coronary disease risk equivalent, more recent guidelines recommend risk stratification on the basis of global risk scoring to target intensity of therapy. While patients with diabetes as a whole are at greater risk for CVD events, these patients may also benefit from risk stratification based on circulating biomarkers like high-sensitivity C-reactive protein, high-sensitivity cardiac troponin T, and N-terminal pro-B-type natriuretic peptide, as well as newer imaging modalities (coronary artery calcium, carotid intima-media thickness, and myocardial perfusion imaging). The addition of these CVD risk assessment modalities could play an important role for deciding how aggressive a physician should be with pharmacological therapy. Here, we discuss many of the current recommendations of CVD risk assessment in patients with diabetes including newer modalities for CVD risk assessment.

Topics: Biomarkers; C-Reactive Protein; Calcium; Cardiovascular Diseases; Carotid Intima-Media Thickness; Coronary Vessels; Diabetic Angiopathies; Echocardiography; Humans; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Troponin T

Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet; Drug Therapy, Combination; Dyslipidemias; Endothelium, Vascular; Glomerular Filtration Rate; Health Behavior; Humans; Hypertension; Insulin Resistance; Kidney; Life Style; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Risk Factors; Smoking; Smoking Cessation; Survival Analysis; Treatment Outcome; Vitamins

Topics: Albuminuria; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Heart Diseases; Humans; Natriuretic Peptide, Brain

Cardiovascular disease is the leading cause of morbidity and mortality in diabetic subjects. Diabetes, independently of the mechanism, is associated with an increased risk of left ventricular hypertrophy, left ventricular dysfunction and coronary artery disease. B-type natriuretic peptide (BNP) is a cardiac neurohormone predominantly released from the cardiac ventricles in response to left ventricular volume expansion and pressure overload. Numerous studies have shown that BNP levels are elevated in asymptomatic or symptomatic left ventricular dysfunction, hypertrophy and coronary artery disease. BNP testing plays an important role in the screening and diagnosis of left ventricular dysfunction by improving the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a 'rule out' test targeted to patients at high risk for left-ventricular dysfunction, such as those with diabetes. Studies are needed to establish if this promising biological tool, in the next future, would assist the management of diabetic patients.

Topics: Biomarkers; Blood Pressure; Diabetic Angiopathies; Diastole; Heart Ventricles; Humans; Natriuretic Peptide, Brain; Systole; Ventricular Dysfunction, Left

Topics: Biomarkers; Diabetes Mellitus; Diabetic Angiopathies; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins

Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM.. We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-Utw. After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-Utw. Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683.

Topics: Adult; Biomarkers; Biomechanical Phenomena; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Female; Glucagon-Like Peptide-1 Receptor; Greece; Humans; Hypoglycemic Agents; Incretins; Liraglutide; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Time Factors; Treatment Outcome; Vascular Stiffness; Ventricular Function, Left

Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones.. We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography.. There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol.. Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol.

Topics: Aged; Aldosterone; Angiotensin II; Blood Glucose; Blood Pressure; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Endothelium, Vascular; Female; Fibroblast Growth Factors; Glycated Hemoglobin; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain

Despite widespread testing, the utility of aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) for diagnosis or risk assessment in patients with diabetes mellitus (DM) in the emergency department (ED) remains unclear. NT-pro-BNP was measured in subjects with dyspnea in the ED. A final diagnosis of acute heart failure (HF) was determined by blinded study physicians using all available hospital records. Vital status was assessed at 1 year; independent predictors of death were identified using Cox analysis. Of 599 subjects, 157 (26.2%) had DM, which was an independent predictor of a final diagnosis of acute HF. In patients diagnosed with acute HF, median concentrations of NT-pro-BNP were similar in patients with and without DM (4,784 vs 3,382 pg/ml, respectively, p = 0.93). In dyspneic subjects without acute HF, median concentrations of NT-pro-BNP were significantly higher in patients with DM (242 vs 115 pg/ml, p = 0.01), but this difference was no longer significant after adjusting for relevant covariates. The area under the curve for NT-pro-BNP to diagnose acute HF in subjects with DM was 0.94 (p <0.001). Using age-adjusted cutpoints, NT-pro-BNP was 92% sensitive and 90% specific for the diagnosis of HF in diabetic subjects. In diabetic patients, a NT-pro-BNP level > or =986 pg/ml was independently associated with an increased risk of death at 1 year (hazard ratio 3.42, 95% confidence interval 1.09 to 10.7, p <0.001). In conclusion, NT-pro-BNP testing offers valuable diagnostic and prognostic information in the evaluation of dyspneic patients with DM in the ED, using identical cutpoints as the population as whole.

Topics: Aged; Area Under Curve; Diabetic Angiopathies; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; ROC Curve; Sensitivity and Specificity

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Hand Strength; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; Survival Analysis

To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers.. We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics.. Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [β-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%).. These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.

Topics: Aged; Alanine Transaminase; Aspartate Aminotransferases; beta 2-Microglobulin; Biomarkers; C-Reactive Protein; Cohort Studies; Coronary Disease; Creatinine; Cystatin C; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Female; Fructosamine; gamma-Glutamyltransferase; Glomerular Filtration Rate; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Self Report; Serum Albumin; Stroke; Troponin T

We evaluated the ability of 23 novel biomarkers representing several pathophysiological pathways to improve the prediction of cardiovascular event (CVE) risk in patients with type 2 diabetes mellitus beyond traditional risk factors.. We used data from 1002 patients with type 2 diabetes mellitus from the Second Manifestations of ARTertial disease (SMART) study and 288 patients from the European Prospective Investigation into Cancer and Nutrition-NL (EPIC-NL). The associations of 23 biomarkers (adiponectin, C-reactive protein, epidermal-type fatty acid binding protein, heart-type fatty acid binding protein, basic fibroblast growth factor, soluble FMS-like tyrosine kinase-1, soluble intercellular adhesion molecule-1 and -3, matrix metalloproteinase [MMP]-1, MMP-3, MMP-9, N-terminal prohormone of B-type natriuretic peptide, osteopontin, osteonectin, osteocalcin, placental growth factor, serum amyloid A, E-selectin, P-selectin, tissue inhibitor of MMP-1, thrombomodulin, soluble vascular cell adhesion molecule-1, and vascular endothelial growth factor) with CVE risk were evaluated by using Cox proportional hazards analysis adjusting for traditional risk factors. The incremental predictive performance was assessed with use of the c-statistic and net reclassification index (NRI; continuous and based on 10-year risk strata 0-10%, 10-20%, 20-30%, >30%). A multimarker model was constructed comprising those biomarkers that improved predictive performance in both cohorts. N-terminal prohormone of B-type natriuretic peptide, osteopontin, and MMP-3 were the only biomarkers significantly associated with an increased risk of CVE and improved predictive performance in both cohorts. In SMART, the combination of these biomarkers increased the c-statistic with 0.03 (95% CI 0.01-0.05), and the continuous NRI was 0.37 (95% CI 0.21-0.52). In EPIC-NL, the multimarker model increased the c-statistic with 0.03 (95% CI 0.00-0.03), and the continuous NRI was 0.44 (95% CI 0.23-0.66). Based on risk strata, the NRI was 0.12 (95% CI 0.03-0.21) in SMART and 0.07 (95% CI -0.04-0.17) in EPIC-NL.. Of the 23 evaluated biomarkers from different pathophysiological pathways, N-terminal prohormone of B-type natriuretic peptide, osteopontin, MMP-3, and their combination improved CVE risk prediction in 2 separate cohorts of patients with type 2 diabetes mellitus beyond traditional risk factors. However, the number of patients reclassified to a different risk stratum was limited.

Topics: Adult; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Matrix Metalloproteinase 3; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Osteopontin; Peptide Fragments; Prospective Studies; Risk Assessment

Cardiac allograft vasculopathy (CAV) still remains to be one of the most important limiting factors for heart transplant recipients' long-term survival. The aim of our study was to identify the perioperative risk factors impacting the occurrence of CAV during the long-term follow-up.. We retrospectively analysed the data from 198 consecutive adult patients, who underwent heart transplantation between 2007 and 2012, in whom at least one routine coronarography (CAG) was performed. CAV onset was defined as any lesion seen at least at one routine CAG.. The average follow-up was 63.6 ± 14.7 months. The frequency of CAV in the analysed population was 36 (18.1%). Multivariate stepwise logistic regression analysis confirmed that NT-proBNP plasma concentration directly before heart transplant [logNT-proBNP OR = 16.455 (4.587-31.036), P < .0001], fibrinogen plasma concentration a month after heart transplant [OR = 1.022 (1.009-1.035), P < .001] and occurrence of diabetes [OR = 12.355 (1.417-35.750), P < .001], were independent predictors of CAV. Area under the ROC curves (AUC) indicated a well discriminatory power of plasma fibrinogen [AUC 0.9278, P < .001] and plasma NTproBNP concentration [AUC 0.9514, P < .001] in CAV prediction. The optimal cut-off value of fibrinogen was 509 mg/dL, and of NT-proBNP was 10080 pg/mL.. Our data show that NT-proBNP and fibrinogen plasma concentrations as well as occurence of diabetes, both preexisting and new onset after heart transplant can be used to identify patients at risk of developing CAV.

Topics: Allografts; Diabetic Angiopathies; Female; Follow-Up Studies; Graft Rejection; Heart Diseases; Heart Transplantation; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Risk Factors; Time Factors; Transplantation, Homologous; Treatment Outcome

Diabetes mellitus (DM) is associated with impaired prognosis in patients with heart failure (HF), but pathogenic mechanisms are unclear. In the failing heart, elevated β-adrenergic receptor (β-AR) activation by catecholamines causes G-protein-coupled receptor kinase-2 (GRK2) upregulation which is responsible for β-AR signalling dysfunction. Importantly, GRK2 expression, measured in peripheral lymphocytes of HF patients, correlates with levels of this kinase in the failing myocardium reflecting the loss of hemodynamic function. Moreover, HF-related GRK2 protein overexpression promotes insulin resistance by interfering with insulin signalling. The aim of this study was to assess lymphocyte GRK2 protein levels in HF patients with and without DM.. Patients with a diagnosis of HF were enrolled in the study. All subjects underwent a complete clinical examination (including NYHA functional class assessment and echocardiography) and blood draw for serum N-terminal pro-brain natriuretic peptide (NT-proBNP), lymphocyte GRK2 and plasma norepinephrine (NE) levels. Demographic data including age, sex, medications, cardiovascular risk factors and presence of comorbidities were also collected.. Two hundred and sixty-eight patients with HF (left ventricular ejection fraction [LVEF] 30.6 ± 7.6%) with and without DM were enrolled. No differences between the two groups were found in terms of demography, HF aetiology, LVEF, NYHA class, NE and NT-proBNP. GRK2 was significantly higher in patients with DM compared to non-DM. At multivariate linear regression analysis, LVEF, NE, NT-proBNP and diabetes came out to be independent predictors of GRK2 levels in the overall study population.. In HF patients, DM is associated with significantly more elevated lymphocyte GRK2 protein levels, likely reflecting more compromised cardiac β-AR signalling/function, despite similar hemodynamic status and neuro-hormonal activation compared to patients without DM. These findings contribute to explain the negative prognostic impact of DM in patients with HF.

Topics: Aged; Diabetic Angiopathies; Female; G-Protein-Coupled Receptor Kinase 2; Heart Failure; Humans; Lymphocytes; Male; Natriuretic Peptide, Brain; Peptide Fragments

Blood flow in lower extremity arteries is frequently impaired in diabetic patients even though they have a normal ankle-brachial index (ABI 1.0-1.4). Risk factors contributing to this lower extremity arterial disease have not been fully elucidated. We enrolled 52 type 2 diabetic patients with normal ABI and 30 age-matched nondiabetic subjects consecutively admitted to our hospital. Plasma B-type natriuretic peptide (BNP) concentrations were measured. Distensibility in ascending thoracic and abdominal aortas as well as total flow volume and resistive index at popliteal artery were evaluated by gated magnetic resonance imaging. An automatic device was used to measure ABI and brachial-ankle pulse-wave velocity (baPWV). Diabetic patients showed lower distensibility in ascending thoracic aorta (p<0.001) and total flow volume (p<0.001) and higher baPWV (p<0.001) and resistive index (p=0.005) and similar BNP and distensibility in abdominal aorta compared to nondiabetic subjects. Simple linear regression analyses revealed that distensibility in ascending thoracic (p=0.019) and abdominal (p=0.030) aortas positively as well as baPWV (p=0.020), resistive index (p<0.001) and BNP (p<0.001) negatively correlated with total flow volume. Stepwise multiple regression analysis demonstrated that increased BNP and resistive index were independent risk factors for total flow volume in diabetic patients (r(2)=0.639, p<0.001). These results indicate that increased plasma BNP levels and peripheral vascular resistance, but not decreased aortic distensibility, associate with impaired blood flow in lower extremity arteries in diabetic patients.

Topics: Aged; Ankle Brachial Index; Aorta; Aortography; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Elasticity; Female; Humans; Japan; Magnetic Resonance Angiography; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Popliteal Artery; Pulse Wave Analysis; Regional Blood Flow; Risk Factors; Up-Regulation; Vascular Resistance

OBJECTIVE Current methods of risk stratification in patients with type 2 diabetes are suboptimal. The current study assesses the ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) to improve the prediction of cardiovascular events and death in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A nested case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTS Seven hundred nine (18%) patients experienced a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and 706 (18%) died during a median of 5 years of follow-up. In Cox regression models, adjusting for all established risk predictors, the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per 1 SD increase (95% CI 1.72, 2.20) and the hazard ratio for hs-cTnT was 1.50 per 1 SD increase (95% CI 1.36, 1.65). The hazard ratios for death were 1.97 (95% CI 1.73, 2.24) and 1.52 (95% CI 1.37, 1.67), respectively. The addition of either marker improved 5-year risk classification for cardiovascular events (net reclassification index in continuous model, 39% for NT-proBNP and 46% for hs-cTnT). Likewise, both markers greatly improved the accuracy with which the 5-year risk of death was predicted. The combination of both markers provided optimal risk discrimination. CONCLUSIONS NT-proBNP and hs-cTnT appear to greatly improve the accuracy with which the risk of cardiovascular events or death can be estimated in patients with type 2 diabetes.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Risk Assessment; Troponin T

We assessed the prognostic implications of low triiodothyronine (T3) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in critically ill patients with acute heart failure. We acquired data for 144 critical care patients with acute decompensated heart failure, of which 106 were included in this study. Plasma thyroid hormones and NT-proBNP levels were determined within 48 hours of admission. We assessed these measures for predicting all-cause and cardiac mortalities. At a mean follow-up period of 25 ± 31 months, the all-cause mortality rate was 51% (54 of 106) and the cardiac mortality rate was 70% (38 of 54). A multivariate Cox regression model showed that log-transformed NT-proBNP levels (log NT-proBNP; hazard ratio [HR] 2.90, 95% confidence interval [CI] 1.38 to 6.08, p = 0.005) and T3 levels (HR 0.98, 95% CI 0.96 to 0.99, p = 0.008) were associated with all-cause mortality, and log NT-proBNP (HR 3.70, 95% CI 1.28 to 10.71, p = 0.02) and T3 (HR 0.98, 95% CI 0.96 to 0.99, p = 0.01) were associated with cardiac mortality. Based on cut-off values for NT-proBNP (10,685 pg/ml) and T3 (52.3 ng/dl), Kaplan-Meier analyses provided significant prognostic information with the highest risk for all-cause mortality in the low T3 (≤52.3 ng/dl)/high NT-proBNP (>10,685 pg/ml) group (HR 8.54, 95% CI 4.19 to 17.40, p <0.0001). In conclusion, T3 levels appear to be independent predictors for both all-cause and cardiac mortalities among critical ill patients with heart failure, and high NT-proBNP and low T3 levels predict a worse long-term outcome.

Topics: Aged; Aged, 80 and over; Comorbidity; Coronary Artery Disease; Critical Illness; Diabetic Angiopathies; Euthyroid Sick Syndromes; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Regression Analysis; ROC Curve; Survivors; Triiodothyronine

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Circulating levels of N-terminal fragment of probrain natriuretic peptide (NT-proBNP) are established as a risk factor for cardiovascular disease and mortality in patients with diabetes, as well as in the general population. We sought to examine the possibility of NT-proBNP as a biomarker of microvascular complications in patients with type 2 diabetes.. In total, 277 outpatients with type 2 diabetes were consecutively enrolled as a hospital cohort. Two hundred and seventeen of these patients (132 males; mean age, 63.4 years) were designated as cases with any of the diabetic complications (retinopathy, neuropathy, nephropathy, ischemic heart disease, strokes, peripheral artery disease), and 60 (42 males; mean age, 54.1 years) were set as controls without clinical evidence of diabetic complications. Diabetic complications were evaluated by medical record and routine laboratory examinations. NT-proBNP was measured and investigated with regard to the associations with diabetic complications.. Mean NT-proBNP levels were significantly higher in patients with any of the diabetic complications (59 versus 33 pg/mL; P<0.0001). In logistic regression analysis, NT-proBNP levels >79 pg/mL, which was the highest tertile, were independently associated with a 5.04 fold increased risk of all complications (P<0.0051) compared to the lowest tertile (NT-proBNP levels <31 pg/mL). Odd ratios of cardiovascular disease and nephropathy, neuropathy, and retinopathy were 9.33, 6.23, 6.6 and 13.78 respectively, in patients with NT-proBNP values in the highest tertile (>79 pg/mL), independently of age, sex, duration of diabetes or other risk factors, such as body mass index or hemoglobin A1c. In addition, NT-proBNP levels were associated with surrogate markers of atherosclerosis, such as brachial-ankle pulse wave velocity (r=0.449, P<0.0001) and left ventricular hypertrophy (r=0.212, P<0.001).. In this hospital-based cohort of type 2 diabetes, the NT-proBNP levels were associated with systemic atherosclerosis and comorbid diabetic microvascular as well as macrovascular complications. It is useful to stratify high-risk diabetic patients by measuring NT-proBNP and to start comprehensive care for preventing the progression of diabetic complications. It is necessary to elucidate the underlying mechanism for the progression of diabetic complications represented by an elevation of NT-proBNP and to demonstrate the ability of NT-proBNP as a predictive global biomarker for diabetic complications in Japanese type 2 diabetic patients.

Topics: Aged; Asian People; Atherosclerosis; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Progression; Female; Humans; Japan; Logistic Models; Male; Microcirculation; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Up-Regulation

Many risk factors are known to predict ischaemic events and mortality in the elderly people, but their ranking of importance remains uncertain. This study was designed to identify and compare the main predictors of total mortality (TM), cardiovascular mortality (CVM) and non-cardiovascular mortality (NCVM) in older adults.. Nine hundred and seventy-nine community resident adults aged ≥ 65 years, free of previous heart failure and cardiovascular events, participated in the study. The univariate and multivariate (Cox regression) relationships of baseline cardiovascular risk factors, treatments and laboratory data with TM, CVM and NCVM were assessed after a median follow up of 6.7 years.. Overall, there were 104 deaths (30 because of CVM and 74 to NCVM). In multivariate analysis, the following factors remained independently associated with mortality: NT pro-B-type natriuretic peptide (NT-proBNP) upper quintile (≥ 237 pg/ml for men, ≥ 280 pg/ml for women): hazard ratio (HR) vs. the rest of the population (95% confidence interval) 2.34 (1.52-3.60), p < 0.001 for TM; HR 5.41 (2.32-12.65), p < 0.001 for CVM; systolic blood pressure lower quintile (≤ 130 mmHg): HR 3.06 (1.80-5.21), p < 0.001 for NCVM; diabetes: HR 2.46 (1.29-4.72), p = 0.007 for NCVM; erythrocyte sedimentation rate (ESR) upper decile (≥ 41 mm/h): HR 2.33 (1.16-4.69), p = 0.02 for NCVM; platelet count lower quintile (≤ 177 × 10(9) /l): HR 2.09 (1.20-3.64), p = 0.009 for NCVM; ever-smoker status: HR 2.08 (1.23-3.52), p = 0.007 for NCVM.. In elderly community dwellers, NT-proBNP was the strongest predictor of TM and CVM, while especially low systolic blood pressure, together with diabetes, ESR, reduced platelet count and ever-smoker status, were the main predictors of NCVM.

Topics: Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cardiovascular Diseases; Diabetic Angiopathies; Female; Humans; Hypotension; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Smoking; Systole; Waist Circumference

N-terminal pro-brain natriuretic peptide (NT-proBNP), which is a useful biomarker of chronic heart failure, has been shown to be a strong predictor of cardiovascular mortality. The aim of this study was to evaluate the relationships between NT-proBNP and markers of subclinical atherosclerosis in patients with type 2 diabetes. Relationships of NT-proBNP to pulse wave velocity (PWV) or ankle-brachial index (ABI) as well as to various parameters, including body mass index, blood pressure, serum lipid concentration, serum uric acid concentration, and glycemic control (hemoglobin A1c), age, hemoglobin, serum creatinine concentration, severity of diabetic nephropathy or retinopathy, current treatment of diabetes, cardiothoracic ratio on chest radiograph, presence of left ventricular hypertrophy and/or ST-T changes evaluated by electrocardiograph, smoking status and presence of cardiovascular disease were investigated in 323 consecutive patients with type 2 diabetes. Log (NT-proBNP) correlated positively with PWV (r = 0.283, p < 0.0001) and correlated negatively with ABI (r = -0.144, p = 0.0094). Multiple regression analysis demonstrated that age (β = 0.200, p = 0.0033), systolic blood pressure (β = 0.246, p < 0.0001), total cholesterol (β = -0.135, p = 0.0326), uric acid (β = 0.133, p = 0.0462), creatinine (β = -0.184, p = 0.0122), smoking status (β = -0.129, p = 0.0499) and log (NT-proBNP) (β = 0.177, p = 0.0149) were independently correlated with PWV and that systolic blood pressure (β = -0.145, p = 0.0310), log triglyceride (β = -0.151, p = 0.0397) and log (NT-proBNP) (β = -0.207, p = 0.0094) were independently correlated with ABI. In conclusion, NT-proBNP could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.

Topics: Aged; Ankle Brachial Index; Asymptomatic Diseases; Atherosclerosis; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Hemodynamics; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Pulse Wave Analysis

Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes.. In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded.. The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 μmol/l (range 101.1-743.5 μmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model.. Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes.

Topics: Albuminuria; Atherosclerosis; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency; Risk Factors; Uric Acid

The aim of this study was to assess the prevalence of (unknown) heart failure and left ventricular dysfunction in older patients with type 2 diabetes.. In total, 605 patients aged 60 years or over with type 2 diabetes in the south west of the Netherlands participated in this cross-sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed diagnosis of heart failure. Between February 2009 and March 2010, the patients without known heart failure underwent a standardised diagnostic work-up, including medical history, physical examination, ECG and echocardiography. An expert panel used the criteria of the European Society of Cardiology to diagnose heart failure.. Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%, 31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI 3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%) with preserved ejection fraction. The prevalence of heart failure increased steeply with age. Heart failure with preserved ejection fraction was more common in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95% CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction.. This is the first epidemiological study that provides exact prevalence estimates of (previously unknown) heart failure and left ventricular dysfunction in a representative sample of patients with type 2 diabetes. Previously unknown heart failure and left ventricular dysfunction are highly prevalent. Physicians should pay special attention to 'unmasking' these patients.

Topics: Aged; Aged, 80 and over; Blood Glucose; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Echocardiography; Female; Glycated Hemoglobin; Heart Failure; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prevalence; Stroke Volume; Ventricular Dysfunction, Left

Diabetes mellitus (DM) is a strong risk factor for cardiovascular (CV) disease. Plasma B-type natriuretic peptide (BNP) levels are elevated in various types of cardiac diseases. Increased plasma BNP levels have been reported to be associated with CV risk in apparently healthy individuals. However, no studies have yet examined the specific value of plasma BNP for predicting CV incidence in unselected DM subjects in a community-based population.In a community-based DM cohort (n = 1,059, mean = 66 years), baseline BNP levels were determined, and CV events were followed and captured prospectively. The cohort was divided by plasma BNP quintiles. The Cox proportional hazard model was used to determine the relative hazard ratios (HR) among the quintiles. In addition, the effects of adding the plasma BNP or urine albumin-to-creatinine ratio (UACR) to an established CV risk scoring model was examined by calculating the area under the receiver operating characteristic (ROC) curve (AUC).During the 5.7 year follow-up period, CV events were identified in 65 of the DM cohort. There was a significant association between plasma BNP levels and CV event rate (P < 0.001). HR was significantly increased in the highest quintile compared to the lowest (HR = 4.38; 95%CI 1.69 -11.84). The AUC generated from ROC analysis of the Framingham risk score for predicting general CV events was improved by adding BNP testing (from 0.66 to 0.74; P = 0.05), but not by adding UACR (from 0.66 to 0.67; P = 0.49).In a community sample of people with DM, plasma BNP levels above the 80 percentile are directly associated with CV risk, and measurement of plasma BNP alone or in conjunction with an established CV risk score is of value in predicting CV events in these subjects.

Topics: Aged; Albuminuria; Cardiovascular Diseases; Cohort Studies; Diabetic Angiopathies; Diabetic Nephropathies; Female; Glycated Hemoglobin; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; ROC Curve; Statistics as Topic; Stroke

: The aim of this study was to determine serum NT-proBNP and plasma Hcy levels and to explore the relationship between serum NT-proBNP and plasma Hcy levels in type 2 diabetic patients with and without asymptomatic LVDD.. : NT-proBNP and Hcy levels were measured 31 patients with type 2 diabetes mellitus. According to echocardiographic data, diabetic patients were divided into two groups: normal LV function or LV diastolic dysfunction.. : Serum NT-proBNP levels in diabetic patients with LVDD were significantly higher than in diabetic patients with normal LV function and controls. The area under the receiver-operating characteristic (ROC) curve for NT-proBNP to separate normal vs. diastolic dysfunction was 0.96 in type 2 diabetic patients. Plasma Hcy levels were significantly higher in both diabetic groups than in controls. Positive correlation was noted between NT-proBNP and Hcy levels in diabetic patients with LVDD (r=0.881, p=0.0001).. : The correlation between elevated NT-proBNP and Hcy levels in diabetic patients with LVDD suggest an association between homocysteinemia and increased NT-proBNP secretion. Our data indicate that NT-proBNP may be a simple screening tool to select diabetic patients with LVDD requiring further examination with echocardiography.

Topics: Blood Pressure; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Echocardiography; Echocardiography, Transesophageal; Female; Homocysteine; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left; Ventricular Function, Left

The aims of this study were to estimate the prevalence of left ventricular systolic (LVSD) and diastolic (LVDD) dysfunction, and to test if BNP and urinary albumin excretion rate (AER) are related to LVSD, LVD and left ventricular mass (LVM) in asymptomatic type 2 diabetes patients.. Presence of LVSD, LVDD and LVM, determined with echocardiography, was related to levels of BNP and AER in 153 consecutive asymptomatic patients with type 2 diabetes.. LVSD was present in 6.1% of patients whereas 49% (29% mild, 19% moderate and 0.7% severe) had LVDD and 9.4% had left ventricular hypertrophy. Increasing age (P < 0.0001) was the only independent variable related to mild LVDD whereas increasing BNP (P = 0.01), systolic blood pressure (P = 0.01), age (P = 0.003) and female gender (P = 0.04) were independent determinants of moderate to severe LVDD. AER (P = 0.003), age (P = 0.01) and male gender (P = 0.006) were directly and independently related to LVM.. About half of asymptomatic type 2 diabetes patients have LVDD. Of those, more than one third display moderate LVDD pattern paralleled by increases in BNP, suggesting markedly increased risk of heart failure, especially in females, whereas AER and male sex are related to LVM.

Topics: Adult; Albuminuria; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Ventricular Dysfunction, Left

To evaluate N-terminal pro brain natriuretic peptide (NT-proBNP) as a marker of long-term micro- and macrovascular complications in type 1 diabetes.. This was a cross-sectional study of 208 long-term surviving type 1 diabetic patients from a population-based cohort from Fyn County, Denmark. In a clinical examination in 2007-2008, NT-proBNP was measured and related to proliferative diabetic retinopathy (PDR), nephropathy, neuropathy and macrovascular disease.. Median age and duration of diabetes was 58.7 and 43 years, respectively. Median NT-proBNP concentration was 78 pg/ml (10th-90th percentile 25-653 pg/ml). The NT-proBNP level (89 vs. 71 pg/ml, p = 0.02) was higher in women. In univariate analyses, NT-proBNP was associated with age, duration of diabetes, diastolic blood pressure (inversely), nephropathy, neuropathy and macrovascular disease. For instance, median NT-proBNP concentrations were 70, 91 and 486 pg/ml for patients with normo-, micro- and macroalbuminuria, respectively (p < 0.01). When adjusted for age, sex, duration of diabetes, high sensitivity CRP, HbA(1c), diastolic blood pressure and smoking, higher NT-proBNP concentrations (4th vs. 1st quartile) were related to nephropathy (odds ratio [OR] 5.03; 95% confidence interval [CI] 1.77-14.25), neuropathy (OR 4.08; 95% CI 1.52-10.97) and macrovascular disease (OR 5.84; 95% CI 1.65-20.74). There was no association with PDR.. NT-proBNP has traditionally been described as a marker of heart failure and left ventricular dysfunction. In this study of long-term surviving type 1 diabetic patients, we found NT-proBNP associated with nephropathy, neuropathy and macrovascular disease. If confirmed by prospective studies, NT-proBNP might be a useful prognostic marker of diabetes-related complications.

Topics: Adult; Aged; Albuminuria; Blood Pressure; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments

In the early identification of cardiovascular risk, it is essential to establish a biological marker for cardiac complications that is comparable to albuminuria for nephropathy. We tested the hypothesis that N-terminal pro-brain natriuretic peptide (NT-proBNP) might be a marker for silent myocardial ischaemia in diabetes.. In forty consecutively recruited subjects without evident coronary artery disease, serum NT-proBNP was measured together with multi-slice computed tomography. With patients suspected of having significant coronary artery stenosis by multi-slice computed tomography, coronary angiography was performed. Silent myocardial ischaemia was defined as the presence of significant coronary artery stenosis with more than 50% luminal narrowing by angiography.. Thirteen patients (32.5%) had silent myocardial ischaemia. NT-proBNP levels were significantly higher in these patients (181.1 ± 43.8 versus 55.2 ± 9.7 pg/mL, p < 0.005) but HbA(1c), lipid profiles, and creatinine were similar in the two groups. Moreover, log NT-proBNP was identified as an independent predictor of silent myocardial ischaemia (R(2) = 0.502, p < 0.05) after adjustment for HbA(1c), creatinine, albuminuria, hypertension, hyperlipidaemia, or smoking. After stratifying patients by NT-proBNP, the upper tertile compared to the lowest tertile was significantly associated with silent myocardial ischaemia (odds ratio: 26.7, p < 0.05). Receiver operation characteristics analysis with a cut-off value of 52 pg/mL showed 92% sensitivity and 75% specificity for predicting silent myocardial ischaemia (positive predictive value 64.7%, negative predictive value 94.3%).. The outstandingly high negative predictive value of NT-proBNP enables us to focus on diabetic patients with occult coronary disease, independently of microalbuminuria.

Topics: Aged; Albuminuria; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

Multiple coronary artery occlusive disease (multiple CAOD) is the most fatal and frequently observed coronary artery disease in type 2 diabetes patients, but no simple, non-invasive screening tool is available yet. The aim of this study is to evaluate the arterial stiffness in type 2 diabetes patients using brachial-ankle pulse wave velocity (baPWV), to demonstrate the correlation between arterial stiffness and multiple CAOD, and to suggest the cutoff point of baPWV for predicting multiple CAOD in Korean type 2 diabetes patients. One hundred and eighty-one diabetes and 262 non-diabetes patients were enrolled in the study. Routine anthropometric and serologic data were collected. baPWV was measured the day before coronary angiography, and the severity of CAOD was assessed with Gensini score after angiography. baPWV and Gensini score were significantly increased in diabetes patients and Gensini score had a positive correlation with baPWV. Subjects in the highest tertile of baPWV showed odds ratio of 3.06 for multiple CAOD compared to the lowest tertile. In ROC curve, baPWV at 1635 cm/s showed 73% sensitivity and 75% specificity with AUC 0.76 in diabetes patients in detecting multiple CAOD. Therefore, baPWV may be utilized a screening tool for predicting multiple CAOD, especially in type 2 diabetes patients.

Topics: Aged; Ankle; Ankle Brachial Index; Arterial Occlusive Diseases; Blood Pressure; C-Reactive Protein; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Korea; Male; Middle Aged; Natriuretic Peptide, Brain; Pulse; Sensitivity and Specificity

Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function.. This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro-B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester.. Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05).. Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.

Topics: Adult; Age of Onset; Apgar Score; Birth Weight; Body Mass Index; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Fetal Blood; Fetal Macrosomia; Glycated Hemoglobin; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Parity; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Prospective Studies; Reference Values; Troponin T

To determine whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, a marker for cardiac failure and potentially for the severity of coronary artery disease (CAD), predicts silent myocardial ischaemia (SMI) and silent CAD in asymptomatic high-risk diabetic patients.. Five hundred and seventeen asymptomatic diabetic patients with > or = 1 additional cardiovascular risk factor but without heart failure were prospectively screened between 1998 and 2008 for SMI, defined as an abnormal stress myocardial scintigraphy, and subsequently for significant (> 70%) angiographic CAD. The 323 patients with interpretable echocardiography and for whom NT-proBNP was measured were included in this analysis.. SMI was found in 108 (33.4%) patients, 39 of whom had CAD. NT-proBNP was higher in the patients with CAD than in the patients without CAD [45.0 (1-3199) vs. 20.0 (1-1640) pg/ml; P < 0.0001 median (range)], even after adjustment for confounding factors: age, gender, body mass index, glycated haemoglobin (HbA(1c)), retinopathy, nephropathy, hypertension, echocardiographic parameters (P < 0.05). NT-proBNP in the third tertile (> or = 38 pg/ml) predicted CAD with a sensitivity of 59% and a specificity of 67%. In a multiple logistic regression analysis including NT-proBNP > or = 38 pg/ml, age, body mass index, gender, HbA(1c), hypertension, retinopathy, nephropathy, peripheral occlusive arterial disease, left ventricular systolic dysfunction, dilatation and hypertrophy and Type 1 transmitral flow, NT-proBNP > or = 38 pg/ml was the only significant independent predictor of silent CAD [odds ratio (OR) 3.1 (95% confidence interval 1.3-7.6), P = 0.015].. NT-proBNP measurement helps to better define asymptomatic diabetic patients with an increased likelihood for CAD, independently of cardiac function and structure.

Topics: Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography; Ventricular Dysfunction, Left

This study evaluated the predictive value of NT-proBNP for patients with diabetes mellitus and compared the prognostic aptitude of this neurohumoral marker to traditional markers of cardiovascular events.. A prospective observational study was conducted in 631 diabetic patients. The composite endpoint consisted of unplanned hospitalization for cardiovascular events or death within the observation period of 12 months. Of all variables analysed (age, gender, history of hypertension, ischaemic heart disease/any cardiac disease, smoking, duration of diabetes, body mass index, blood pressure, New York Heart Association-class, Dyspnoea score, Minnesota Living with Heart Failure Questionnaire, LDL-cholesterol, HbA(1c), creatinine, glomerular filtration rate), the logarithm of NT-proBNP gave the most potent information in a stepwise Cox regression analysis (P < 0.0001). Bootstrapping with 500 samples supports this result in 95% samples. The negative predictive value of a normal value (<125 pg/mL) of NT-proBNP for short-term cardiovascular events in diabetic patients is 98%.. We have demonstrated a strong and independent correlation between NT-proBNP and short-term prognosis of cardiovascular events for patients with diabetes mellitus. With a high negative predictive value it can identify individuals who are not at intermediate risk for cardiovascular events. NT-proBNP proved to be of higher predictive value than traditional cardiovascular markers, in this unselected cohort.

Topics: Biomarkers; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Minnesota; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Sensitivity and Specificity

We sought to study the association between brain natriuretic peptide (BNP) levels and the occurrence of ventricular arrhythmias in patients with left ventricular dysfunction (LVD) and an implantable cardioverter defibrillator (ICD).. This was a prospective study of consecutive, stable, ambulatory patients with moderate and severe ischemic LVD and an ICD. A plasma BNP level was obtained at recruitment. Patients were evaluated every 3-6 mo for a minimum of 1 y. The primary end point was the occurrence of malignant ventricular arrhythmia or sudden cardiac death (SCD).. The cohort consisted of 94 subjects (6 women) with a mean +/- standard deviation (SD) age of 69 +/- 10 y. The ICD implantation indication was primary and secondary prevention of SCD in 49% and 51% of subjects, respectively. A primary end point occurred in 27 patients (29%), and was more frequent in symptomatic heart failure patients and those implanted for secondary prevention of SCD. The median BNP level was significantly higher among patients who experienced an end point (191 pg/ml versus 142 pg/ml, p = 0.03). After controlling for New York Heart Association heart failure class and ICD implantation indication, the odds ratio (OR) for experiencing an adverse outcome among the upper BNP quartile versus all others was 3.5 (95% confidence interval [CI]: 1.2-10.2). Among patients implanted for primary prevention of SCD, none of the patients in the lower BNP quartile (BNP < 91 pg/ml) experienced an adverse outcome.. These results suggest that abnormally high BNP levels not only predict cardiac death, but also arrhythmic death in this patient population, and a low BNP level can serve to identify low risk patients. (c)

Topics: Aged; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Defibrillators, Implantable; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment

Plasma N-terminal Pro-Brain Natriuretic Peptide (Nt-proBNP) level has been shown to provide valuable prognostic information on short and long-term mortality in patients with acute Myocardial Infarction, in the general population. Increased plasma Nt-proBNP levels have been found in Type 2 diabetic patients with vascular complications or with hypertension. In a large prospective study performed in 560 patients hospitalized for acute Myocardial Infarction (RICO), we found that median Nt-proBNP levels were significantly higher in the 199 diabetic patients compared to the 361 non-diabetic patients (245 (81-77) vs. 130 (49-199) pmol/L, P<0.0001). This difference remained highly significant after adjustment for confounding factors and we have been able to show that diabetes, per se, was a strong and independent factor for increased plasma Nt-proBNP levels, in this population. In the prospective RICO survey, we have found, in multivariable analysis, that diabetes was an independent factor for in-hospital mortality (OR: 1.79 [1.45-2.20]; P=0.0064) and cardiogenic shock (OR: 1.45(1.22-1.72); P =0.0364) when the variable Nt-proBNP level was not introduced into the model, but was less significantly associated with mortality (OR: 1.73 (1.39-2.16); P=0.0107) and no longer associated with cardiogenic shock when Nt-proBNP was in the model. This data suggest that increased plasma Nt-proBNP may be one of the links between diabetes and poor short-term prognosis after Myocardial Infarction and provides highly valuable prognostic information on in-hospital outcome in diabetic patients.

Topics: Biomarkers; Blood Pressure; Creatinine; Diabetic Angiopathies; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

B-type natriuretic peptide (BNP) is a blood test which detects ventricular wall stretch and is being increasingly used in primary care on limited evidence.. To assess the practical implications and potential clinical benefit of measuring BNP to identify and guide the treatment of undiagnosed or under-treated ventricular dysfunction in at-risk patients.. Screening study with single-arm intervention.. A total of 1918 patients with diabetes mellitus or ischaemic heart disease aged > or =65 years registered with 12 general practices were invited; 76 patients with elevated BNP underwent BNP-guided treatment titration.. Eligible patients were invited to attend for a blood test at their own practice; those with a persistently elevated plasma BNP concentration (>43.3 pmol/l) after repeat measurement were offered initiation or up-titration of treatment guided by remeasurement of BNP with a target concentration of <36 pmol/l.. Seven-hundred and fifty-nine patients (40%) attended for screening; 76 (10% of 759) commenced treatment titration. Of these 76 patients, 64 (84%) were asymptomatic or had only mild breathlessness. Maximum titration effect was achieved by the second visit when 27 (36%) had achieved the BNP target concentration and the mean reduction was 10.8 pmol/l (P<0.001). The most effective therapeutic step was a switch in beta-blocker to carvedilol or bisoprolol (P<0.001).. About 10% of patients with diabetes or cardiovascular disease on GP morbidity registers have a persistently raised plasma BNP concentration. Simple adjustment of their drug treatment may reduce their BNP and associated mortality risk, but further up-titration against BNP is only possible if the within-person biological variability of measurement can be reduced.

Topics: Adrenergic beta-Antagonists; Aged; Biomarkers; Diabetic Angiopathies; Family Practice; Feasibility Studies; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Risk Factors; Ventricular Dysfunction

Several studies have reported the prognostic value of natriuretic peptides, but their predictive value in patients with diabetes mellitus is unknown. The aim of the study was to test the hypothesis that measurement of brain natriuretic peptide (BNP) levels in ambulatory patients with congestive heart failure (CHF) and diabetes can predict the occurrence of cardiovascular events at 6-month follow-up.. We enrolled 145 consecutive patient with diabetes [age 72 +/- 9 years, hypertension (21%), ischaemic heart disease (52%), atrial fibrillation (22%), preserved left ventricular function (29%)] seen in the outpatient heart failure clinic after an acute episode of cardiac failure.. The median (25th/75th interquartile range) BNP concentrations at discharge were 186 (75-348) pg/ml. At 6-month clinical follow-up 10/145 (7%) subjects had died and 31/145 (21%) had been readmitted because of cardiac decompensation. BNP values of 200 and 500 pg/ml were found to have the best compromise between sensitivity (88 and 46%, respectively) and specificity (71 and 89%, respectively) for predicting events at 6 months. Multivariate Cox regression analysis identified only two parameters as predictors of events: serum creatinine [hazard ratio (HR) = 3.3; P = 0.02], and BNP plasma level BNP cut-off values (HR = 3.8; P = 0.03 for 201-499 pg/ml and HR = 7.7; P = 0.001 for > or = 500 pg/ml).. These results suggest that BNP and serum creatinine are strong predictors of clinical events in patients with diabetes and CHF. In these patients, clinical outcome might be stratified by plasma BNP levels.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Diabetic Angiopathies; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity

Plasma N-terminal proBNP (NT-proBNP) is released in response to pressure overload, intravascular volume expansion and myocardial ischemia from cardiac ventricles. We studied the relationship between NT-proBNP levels and left ventricular dysfunction and urinary albumin excretion in Type 2 diabetes. The study group consisted of 130 diabetic patients referred for echocardiography. They were divided into four groups according to echocardiographic finding and into three groups according to urinary albumin excretion. NT-proBNP levels were measured by electrochemiluminescence. There were significant differences in NT-proBNP levels among four groups (P=0.012), with a highly significant difference between normal and other groups with left ventricular dysfunction. NT-proBNP levels in diastolic dysfunction were significantly higher than normal group (1491.1 pg/mL versus 232.3 pg/mL, P=0.01), even though there was no difference in ejection fraction (EF) (61.2+/-7.9% versus 60+/-8.4%, P=0.773). NT-proBNP levels showed positive correlation with age (Rs=0.37, P<0.001), creatinine (Rs=0.38, P=0.001), LVIDS (Rs=0.56, P=0.001) and LVIDD (Rs=0.34, P=0.04) and negative correlation with EF (Rs=-0.66, P=0.001). NT-proBNP levels significantly differed among three groups according to urinary albumin excretion (P=0.031). These results suggest that NT-proBNP could be used to identify any impairment of left ventricular function in diabetes.

Topics: Aged; Albuminuria; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Echocardiography; Female; Humans; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

The prognostic value of NT-pro-BNP has not been thoroughly evaluated in diabetic inpatients with manifest cardiovascular disease. NT-pro-BNP was measured in 156 patients with type 2 diabetes mellitus hospitalised due to cardiovascular disease. The association of NT-pro-BNP with mortality and the combined endpoint (CE) of death, heart failure decompensation, stroke and myocardial infarction was analysed during a median follow-up time of 1183 days. Patients who died (1669 IQR 788-5640 vs. 398, IQR 158-990 pg/ml) and patients with CE (1353, IQR 730-4289 vs. 304, IQR 128-784 pg/ml, both p=0.0001) had significantly elevated NT-pro-BNP compared to patients without the corresponding endpoint. Patients with supramedian NT-pro-BNP (>518 pg/ml) had significantly worse outcome regarding mortality (HR 5.5, 95%CI 2.0-14.8) and CE (HR 5.0, 95%CI 2.2-11.2) than patients with inframedian values even after adjustment for age, NYHA class and renal function. At a cut-off of 422 pg/ml, NT-pro-BNP showed a sensitivity of 89.6% and a negative predictive value of 92.8% for detection of patients with future CE. In this sample of diabetic patients with a broad spectrum of cardiovascular disease, NT-pro-BNP was a strong predictor of long-term outcome. NT-pro-BNP measured at discharge identifies high-risk patients independently of the underlying heart disease.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Creatinine; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Inpatients; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Prognosis; Survival Analysis; Treatment Outcome

Aims The incidence of diabetic cardiomyopathy, independent of arterial hypertension (AH) and coronary heart disease (CHD), remains controversial. The present study aimed to determine the influence of type 1 diabetes mellitus (T1DM) of long duration (>10 years) on myocardial function estimated by echocardiography (ECHO) and serum level of N-terminal pro-B type natriuretic peptide (NT-proBNP) in patients without CHD and AH. We also retrospectively investigated the relationship between the structural changes in the hearts of other deceased T1DM patients, and had their myocardial function echocardiographically assessed before death. Methods and results In 185 patients (96 males) with T1DM (mean duration 22.8 years) and 105 non-diabetic control subjects (57 males), detailed ECHO parameters and NT-proBNP were assessed. No significant differences were found between the respective groups. Histological studies of 17 hearts of deceased T1DM patients were carried out and retrospectively compared with their ECHO performed before death. Histological changes were identified, although without the signs of myocardial dysfunction on ECHO prior to death. Conclusion Even the application of echocardiographic, biochemical and morphologic techniques hardly gives sufficient grounds to believe that type 1 diabetes alone may actually precipitate myocardial dysfunction, despite long-term course of the disease and typical histological changes in the myocardium.

Topics: Adult; Age Factors; Biomarkers; Cardiomyopathies; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Echocardiography; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Sex Factors; Statistics as Topic; Time Factors

Topics: Administration, Oral; Aged; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Age Factors; Animals; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Heart Failure; Humans; Male; Mice; Natriuretic Peptide, Brain; Rats; Sex Factors

To identify in a prospective observational study the cardiac structural and functional abnormalities and mortality in patients with end stage renal disease (ESRD) with a raised cardiac troponin T (cTnT) concentration.. 126 renal transplant candidates were studied over a two year period. Clinical, biochemical, echocardiographic, coronary angiographic, and dobutamine stress echocardiographic (DSE) data were examined in comparison with cTnT concentrations dichotomised at cut off concentrations of < 0.04 microg/l and < 0.10 microg/l.. Left ventricular (LV) size and filling pressure were significantly raised and LV systolic and diastolic function parameters significantly impaired in patients with raised cTnT, irrespective of the cut off concentration. The proportions of patients with diabetes and on dialysis were higher in both groups with raised cTnT. With a cut off cTnT concentration of 0.04 microg/l but not 0.10 microg/l, significantly more patients had severe coronary artery disease and a positive DSE result. The total ischaemic burden during DSE was similar in cTnT positive and negative patients, irrespective of the cut off concentration used. LV end systolic diameter index and E:Ea ratio were independent predictors of cTnT rises > or = 0.04 microg/l and > or = 0.10 microg/l, respectively. Diabetes was independently associated with cTnT at both cut off concentrations. Mortality was higher in all patients with raised cTnT.. Patients with ESRD with raised cTnT concentrations have increased mortality. Raised concentrations are strongly associated with diabetes, LV dilatation, and impaired LV systolic and diastolic function, but not with severe coronary artery disease.

Topics: Cardiomyopathy, Dilated; Diabetic Angiopathies; Echocardiography; Echocardiography, Stress; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Troponin T; Ventricular Dysfunction, Left

To find out whether B-type natriuretic peptide (BNP) detects silent myocardial ischaemia in patients with type 2 diabetes, since many of these patients have silent ischaemia leading to unexpected cardiac deaths.. Prospective cross-sectional study with consecutive recruitment of patients.. Outpatient, single centre.. 219 patients with type 2 diabetes. Patients were excluded if they had a history or evidence of cardiac failure.. BNP, echocardiography and exercise tolerance test (ETT). BNP was compared with the ETT result in all patients and specifically in those who had no apparent ischaemic heart disease (IHD).. 121 patients had no history of IHD or cardiac failure and of these patients 85 had a clearly abnormal or normal ETT result. BNP was higher in patients with an abnormal than with a normal ETT (mean 58.2 (SD 46.3) v 24.4 (SD 15.7) pg/ml, p < 0.001). In univariate analysis BNP was an independent predictor of an abnormal ETT (p < 0.001). In multivariate analysis BNP remained an independent predictor of the ETT result. BNP concentration over 20 pg/ml predicted an abnormal ETT result with a sensitivity of 87% and specificity of 37%, and BNP over 40 pg/ml had a sensitivity of 63% and a specificity of 81%.. BNP is of value in predicting silent ischaemia on exercise testing in asymptomatic patients with type 2 diabetes.

Topics: Area Under Curve; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

The present study evaluated whether biomarkers of ischemia, inflammation, myocardial damage, and dysfunction are equally useful in patients who have diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who had non-ST-elevation ACS and were included in the Fourth Global Utilization of Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and interleukin-6 were analyzed in serum samples that were obtained at a median of 9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas troponin T levels did not differ by DM status. Mortality increased with ascending quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses, factors that were predictive of 1-year mortality in patients who did not have DM were also significant for those who did. Presence of ST depression > 0.5 mm had the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to 3.0) were significant biomarker predictors. In conclusion, DM confers a high long-term mortality in non-ST-elevation ACS. Despite a larger proportion of ST depression and increased levels of NT-pro-BNP and interleukin-6 at admission, these factors provide independent prognostic information that may improve risk stratification and guidance of treatment.

Topics: Aged; Biomarkers; C-Reactive Protein; Diabetes Mellitus; Diabetic Angiopathies; Female; Humans; Interleukin-6; Logistic Models; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Risk Assessment; Survival Analysis; Syndrome; Troponin T

Raised N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with a poor cardiac outcome in non-diabetic populations. Elevated NT-proBNP predicts excess morbidity and mortality in diabetic patients with an elevated urinary albumin excretion rate. This study investigated the prognostic value of NT-proBNP in a cohort of type 2 diabetic patients.. In a prospective observational follow-up study, 315 type 2 diabetic patients with normoalbuminuria (n=188), microalbuminuria (n=80) and macroalbuminuria (n=47) at baseline were followed for a median (range) of 15.5 (0.2-17.0) years. Plasma NT-proBNP concentrations were determined by immunoassay at baseline. Endpoints were overall and cardiovascular mortality.. Of the patients, 162 died (51%), 119 of them (74%) due to cardiovascular causes. All-cause mortality was increased in patients with NT-proBNP in the second and third tertiles (hazard ratios [95% CI] compared with the first tertile, 1.70 [1.08-2.67] and 5.19 [3.43-7.88], p<0.001). These associations persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate and conventional cardiovascular risk factors (covariate adjusted hazard ratios 1.46 [0.91-2.33] and 2.54 [1.56-4.14], p<0.001). This increased mortality was attributable to more cardiovascular deaths in the second and third NT-proBNP tertile (unadjusted hazard ratios 1.63 [0.96-2.77] and 4.88 [3.01-7.91], p<0.001; covariate adjusted 1.37 [0.79-2.37] and 2.26 [1.27-4.02], p=0.01). When patients with normo-, micro- and macroalbuminuria were analysed separately, NT-proBNP levels above the median (62 ng/l) were consistently associated with increased overall and cardiovascular mortality in all three groups (p<0.001).. In patients with type 2 diabetes, elevated circulating NT-proBNP is a strong predictor of the excess overall and cardiovascular mortality, this predictor status being independent of urinary albumin excretion rate and conventional cardiovascular risk factors.

Topics: Albuminuria; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Survival Analysis; Time Factors

We examined whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) predicts cardiovascular outcome in patients with type 2 diabetes.. A total of 160 microalbuminuric type 2 diabetic patients (mean age 55.1 years [SD 7.2], 119 men) were enrolled in the Steno-2 Study examining the effect of multifactorial treatment, and were divided into two groups according to baseline levels of plasma NT-proBNP below or above the median for the cohort, which was followed for an average of 7.8 years. Cardiovascular outcome was a composite of cardiovascular mortality, myocardial infarction, stroke, revascularisation procedures in the heart or legs, and amputations.. In the whole group, plasma NT-proBNP being above the median was associated with an increased risk of cardiovascular disease during follow-up, with an unadjusted hazard ratio of 4.4 (95% CI 2.3-8.4; p<0.0001). A decrease in plasma NT-proBNP of 10 pg/ml during the first 2 years of intervention was associated with a 1% relative reduction in the primary endpoint (p<0.001). Despite polypharmacological treatment targeting cardiovascular disease, the mean plasma NT-proBNP level increased during follow-up.. We conclude that high plasma NT-proBNP is a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.

Topics: Albuminuria; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Proportional Hazards Models; Smoking; Time Factors

To examine levels of NT-proBNP and its relation to hypertension, as well as diastolic function in normoalbuminuric patients with Type 2 diabetes.. The study comprised 60 Type 2 diabetic patients without albuminuria. Thirty patients were normotensive and 30 had hypertension. Exclusion criteria were cardiac symptoms and an ejection fraction < 55%. Thirty age- and sex-matched normal subjects served as controls. Diastolic dysfunction was assessed with echocardiography, by means of mitral inflow and colour M-Mode flow propagation recordings.. Overall NT-proBNP was significantly elevated in the Type 2 diabetes group, compared with the controls [54.5 pg/ml (5-162) vs. 32.7 pg/ml (5-74.3) P = 0.02]. NT-proBNP was significantly higher among hypertensive patients compared with both normotensive patients and controls but no difference was found between the normotensive patients and the controls [58.0 pg/ml (8.5-162), P < 0.05 vs. 50.8 pg/ml (5-131) P = 0.4]. Patients with concentric and eccentric hypertrophy had significantly higher NT-proBNP levels compared with the control group [81.0 pg/ml (5-147), P < 0.001 and 66.8 pg/ml (42-128), P < 0.001], whereas patients with left ventricular remodelling (enlarged relative wall diameter but normal left ventricular mass) were comparable with the control group [42.3 pg/ml (8.3-142) P = 0.55]. Patients with left atrial enlargement also had incremental NT-proBNP values. NT-proBNP was only moderately correlated to age (r = 0.33, P < 0.05) and left ventricular diastolic diameter (r = 0.41, P < 0.05), but unrelated to diastolic function.. NT-proBNP is significantly increased in hypertensive, normoalbuminuric patients with Type 2 diabetes. These findings were related to left ventricular hypertrophy and increased left atrial and ventricular diameters.

Topics: Albuminuria; Cardiomyopathy, Dilated; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Female; Heart Atria; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments

We recently showed that plasma concentration of N-terminal atrial natriuretic peptide (Nt-proANP) is strongly directly related to salt sensitivity. The aims of the present study were to test (i) whether plasma concentration of N-terminal brain natriuretic peptide (Nt-proBNP) is related to salt sensitivity and (ii) whether Nt-proANP, as a marker of salt sensitivity, differs between type 2 diabetes patients and nondiabetic subjects without a history of coronary heart disease.. Nt-proBNP was determined in 30 Swedish normal subjects with heredity for primary hypertension and salt sensitivity was defined as the difference between mean arterial blood pressure after 1 week on a high-salt diet (240 mmol day(-1)) and 1 week on a low-salt diet (10 mmol day(-1)). Nt-proANP was measured in 253 patients with type 2 diabetes and in 230 nondiabetic subjects aged 40-70 years, all without a history of coronary heart disease.. Amongst the 30 subjects, in whom salt sensitivity was directly measured, Nt-proBNP was not correlated with salt sensitivity (R=-0.18, P=0.35). Nt-proANP (median, interquartile range) was lower in patients with type 2 diabetes (505, 387-661 pmol L(-1)) than in nondiabetic subjects (536, 421-696 pmol L(-1)) (P=0.02). In a multiple regression analysis heart rate (P <0.00001), diastolic blood pressure (P=0.02) and diabetes status (P=0.02) were inversely related whereas age (P <0.00001), cystatin C (P=0.0006), hypertension treatment (P=0.002) and female sex (P=0.006) were directly related to ln(Nt-proANP).. In contrast to Nt-proANP, Nt-proBNP is not related to salt sensitivity. Salt sensitivity, as estimated by Nt-proANP, seems to be reduced in type 2 diabetes.

Topics: Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Sodium Chloride, Dietary

No studies have yet been conducted concerning plasma N-terminal pro-brain natriuretic peptide (Nt-pro-BNP) levels after Myocardial Infarction (MI) and their relationship with short-term outcomes in diabetic patients.. Five hundred and sixty patients hospitalized for MI from the RICO survey, including 199 diabetic and 361 non-diabetic subjects, were included in the study. Plasma Nt-pro-BNP levels were measured on admission. Median Nt-pro-BNP levels were significantly higher in diabetic patients compared with non-diabetic patients [245 (81-77) vs. 130 (49-199) pmol/L, P<0.0001]. This difference remained highly significant after adjustment for age, female gender, creatinine clearance, left ventricular ejection fraction (LVEF), plasma peak troponin, anterior wall necrosis, and hypertension. In multivariable analysis, Nt-pro-BNP levels were negatively associated with creatinine clearance (P<0.0001) and LVEF (P<0.0001) and positively associated with plasma peak troponin (P<0.0001), age (P=0.0029), diabetes (P=0.0031), and female gender (P=0.0102). Diabetic patients showed a 4.7-fold increase in hospital mortality (15.6 vs. 3.3%, P<0.0001) and a 2.2-fold increase in cardiogenic shock (17.6 vs. 7.7%, P=0.0004). In multivariable analysis, diabetes was an independent factor for mortality [OR: 1.79 (1.45-2.20); P=0.0064] and cardiogenic shock [OR: 1.45 (1.22-1.72); P=0.0364] when the variable Nt-pro-BNP level was not introduced into the model, but was less significantly associated with mortality [OR: 1.73 (1.39-2.16); P=0.0107] and no longer associated with cardiogenic shock when Nt-pro-BNP was in the model.. After MI, diabetes is independently associated with high plasma Nt-pro-BNP levels. This elevated Nt-pro-BNP is strongly associated with the increased incidence of in-hospital mortality and cardiogenic shock observed in diabetes. Our findings clearly indicate that plasma Nt-pro-BNP provides highly valuable prognostic information on in-hospital outcome after MI, in particular in diabetic patients.

Topics: Age Factors; Aged; Biomarkers; Diabetic Angiopathies; Female; Hospital Mortality; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Recurrence; Sex Factors; Shock, Cardiogenic; Stroke Volume

The plasma levels of either brain natriuretic peptide (BNP) or the N-terminal fragment of the prohormone (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction. Patients with type 2 diabetes are at high risk of developing cardiovascular complications. This study was aimed to assess whether plasma NT-proBNP levels are at similar levels in type 2 diabetics with or without overt cardiovascular diseases.. We assayed plasma NT-proBNP in 54 type 2 diabetics, 27 of whom had no overt macro- and/or microvascular complications, while the remaining ones had either or both. The same assay was carried out in 38 healthy control subjects age and sex matched as a group with the diabetics.. Plasma NT-proBNP was higher in diabetics (median 121 pg/ml, interquartile range 50-240 pg/ml, ) than in those without complications (37 pg/ml, 21-54 pg/ml, P<0.01). Compared with the controls (55 pg/ml, 40-79 pg/ml), only diabetics with vascular complications had significantly increased plasma NT-proBNP levels (P<0.001). In the diabetics, coronary heart disease and nephropathy (defined according to urinary excretion of albumin) were each independently associated with elevated values of plasma NT-proBNP.. In type 2 diabetes mellitus, patients with macro- and/or micro-vascular complications exhibit an elevation of plasma NT-proBNP levels compared to corresponding patients with no evidence of vascular disease. The excessive secretion of this peptide is independently associated with coronary artery disease and overt nephropathy. The measurement of circulating NT-proBNP concentration may therefore be useful to screen for the presence of macro- and/or microvascular disease.

Topics: Blood Pressure; Body Mass Index; Coronary Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Reference Values

Topics: Biomarkers; Diabetic Angiopathies; Humans; Mass Screening; Natriuretic Peptide, Brain; Reproducibility of Results; Ventricular Dysfunction, Left

We hypothesized that B-type natriuretic peptide (BNP) levels can predict cardiac mortality in diabetic patients.. Detection of cardiovascular disease in diabetics can be difficult until overt events occur.. A total of 482 diabetics (majority male with type 2 diabetes) at the Veterans Affairs Medical Center San Diego were divided into two groups: 1) referred patients for echocardiogram on the basis of clinical suspicion of cardiac dysfunction (referred [R], n = 180); 2) patients randomly selected from the diabetic clinic without any suspicion of cardiac dysfunction (not referred [N-R], n = 302). We examined cardiac events and all-cause mortality in relation to initial BNP levels during the follow-up.. A total of 71 (14.7%) patients died during this period: 52 of 180 (29%) in the R group (30 of 52 [58%] cardiac, 10 of 52 [19%] non-cardiac, 2 of 52 [4%] renal, 10 of 52 [19%] unknown cause) and 19 of 302 (6%) in N-R group (6 of 19 [32%] cardiac). The median BNP level in the R and N-R groups who died of cardiac, non-cardiac, and unknown cause was 537 and 87, 80 and 53, and 343 and 38 pg/ml, respectively. The receiver-operating characteristic (ROC) values for mortality in two groups in relation to BNP revealed the area under the curve to be 0.720 and 0.691, respectively (p < 0.01 in both). Among commonly used prognostic indicators in diabetics, only the ROC for triglycerides was significant. The most accurate cut-point in both the N-R group (87%) and R group (61%) was 120 pg/ml of BNP. Cox regression analysis showed BNP to be the most significant predictor of all-cause mortality in the R group. There was a marked decrease in survival in the patient group with BNP >120 pg/ml.. B-type natriuretic peptide appears to be a reliable predictor of future cardiac and all-cause mortality in diabetic patients.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; ROC Curve; Sensitivity and Specificity; Triglycerides

To identify potentially confounding variables for the interpretation of plasma N-terminal pro brain natriuretic peptide (NT-proBNP).. Randomly selected subjects filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, ECG, echocardiography, and blood sampling.. Subjects were recruited from four Copenhagen general practices located in the same urban area and were examined in a Copenhagen University Hospital.. 382 women and 290 men in four age groups: 50-59 years (n = 174); 60-69 years (n = 204); 70-79 years (n = 174); and > 80 years (n = 120).. Associations between the plasma concentration of NT-proBNP and a range of clinical variables.. In the undivided study sample, female sex (p < 0.0001), greater age (p < 0.0001), increasing dyspnoea (p = 0.0001), diabetes mellitus (p = 0.01), valvar heart disease (p = 0.002), low heart rate (p < 0.0001), left ventricular ejection fraction < or = 45% (p < 0.0001), abnormal ECG (p < 0.0001), high log10[plasma creatinine] (p = 0.0009), low log10[plasma glycosylated haemoglobin A1c] (p = 0.0004), and high log10[urine albumin] (p < 0.0001) were independently associated with a high plasma log10[plasma NT-proBNP] by multiple linear regression analysis.. A single reference interval for the normal value of NT-proBNP is unlikely to suffice. There are several confounders for the interpretation of a given NT-proBNP concentration and at the very least adjustment should be made for the independent effects of age and sex.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Cardiac Output, Low; Diabetic Angiopathies; Female; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Sex Factors; Surveys and Questionnaires; Urban Health

Routine screening of diabetic patients with echocardiography is not feasible due to its limited availability and high cost. B-type natriuretic peptide (BNP) is secreted from the left ventricle in response to pressure overload and is elevated in both systolic and diastolic dysfunction.. BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication for echocardiography (CIE) (n = 172) and those without clinical indication for echocardiography (no-CIE) (n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP.. The 91 patients with no-CIE with echoes had similar BNP levels (83 +/- 16 pg/ml) to the 215 patients with no-CIE without echoes (63 +/- 10, P = 0.10). Patients with CIE and subsequent abnormal left ventricular function (n = 112) had a mean BNP concentration of 435 +/- 41 pg/ml, compared with those with no-CIE, but had abnormal left ventricular function on echo (n = 32) (161 +/- 40 pg/ml). Twenty-one of 32 patients with no-CIE but with abnormal left ventricular function had diastolic dysfunction (BNP 190 +/- 60 pg/ml). A receiver-operating characteristic (ROC) curve revealed that the area under the curve was 0.91 for CIE patients and 0.81 for no-CIE patients (P < 0.001). For those with no congestive heart failure (CHF) symptoms, BNP levels showed a high negative predictive value (91% for BNP values <39 pg/ml), while in those patients who had a CIE, BNP levels showed a high positive predictive value for the detection of left ventricular dysfunction (96% with BNP levels >90 pg/ml).. BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction.

Topics: Atrial Fibrillation; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Function, Left

We investigated whether plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) reflect impaired diastolic relaxation or its improvement after ACE inhibition.. 7 long-term Type 1 diabetic patients with normal systolic but impaired diastolic function and with sympathetic myocardial dysinnervation and 10 controls were included. Exercise tolerance and maximal O 2 uptake were evaluated by bicycle exercise prior to the study. ANP, BNP and norepinephrine/epinephrine (NE/E) were determined at baseline and at 80 % .VO2 max workload and after recovery, before and following 12 weeks of treatment with fosinopril (10 mg/d).. Isovolumetric relaxation time (IVRT) and A/E wave ratio were increased by 26.7 +/- 11.5 % and 54.4 +/- 26.1 % in diabetic patients as compared to controls, respectively (p < 0.02). After 12 weeks of fosinopril treatment, no differences in IVRT or A/E wave ratio were detectable between groups. ANP was enhanced in Type 1 diabetes as compared to controls (baseline: 9.2 +/- 3.0 vs. 4.5 +/- 1.1; exercise: 22.4 +/- 7.7 vs. 7.9 +/- 1.2; recovery: 20.3. +/- 4.6 vs. 9.5 +/- 2.0 fmol/ml, p < 0.02). Fosinopril treatment abolished any differences between groups. BNP plasma levels did not differ between groups and no exercise dependent changes were observed. NE- and E-increase was greater at 80 % .VO2 max work load in Type 1 diabetes than in controls (p < 0.05). Again, fosinopril abolished differences between groups.. In Type 1 diabetes, impaired diastolic function is associated with elevated ANP and catecholamine plasma levels that are normalized after ACE inhibition. Thus, ANP but not BNP appears to be a sensitive biochemical marker for early diastolic dysfunction in Type 1 diabetes.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiomyopathies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diastole; Female; Fosinopril; Glycated Hemoglobin; Heart; Hemodynamics; Humans; Male; Natriuretic Peptide, Brain