natriuretic-peptide--brain and Albuminuria

Cardiovascular disease is an important complication for patients with chronic kidney disease (CKD), warranting accurate risk prediction, but clinical guidelines are inconsistent regarding whether or how to use information on measures of CKD for predicting risk. Recent large meta-analyses have shown that key CKD measures (estimated glomerular filtration rate and albuminuria) improve cardiovascular risk prediction beyond traditional risk factors, especially when albuminuria is added to prediction models. In addition, several recent studies have shown that the use of filtration markers other than serum creatinine, cystatin C, and β

Topics: Albuminuria; beta 2-Microglobulin; Calcium; Cardiovascular Diseases; Coronary Vessels; Creatinine; Cystatin C; Glomerular Filtration Rate; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Assessment; Troponin

Hypertension is an established risk factor of cardiovascular morbidity and mortality. Although antihypertensive treatment reduces the risk of cardiovascular disease, it is impossible to identify all hypertensive subjects among the general population and to manage them in medical facilities considering the huge number of people with hypertension. Furthermore, more than half of cardiovascular events occur in individuals with mild hypertension or in those with a lower blood pressure. In this context, primary prevention of hypertension is an important public health problem. We investigated predictive values of several possible risk factors of hypertension in a general normotensive population. Normotensive subjects who visited our hospital for a physical checkup were enrolled and followed up for 4-5 years, with the endpoint being the development of hypertension. Each factor of metabolic syndrome was closely associated with the future onset of hypertension in subjects without hypertension, and the risk of hypertension markedly increased with overlapping metabolic disorders in individuals. Similarly, serum uric acid, the glomerular filtration rate, urinary albumin (even within the normal range), and brachial-ankle pulse wave velocity were independent risk factors of hypertension. These factors were also independent determinants of a future increase in the systolic blood pressure. An intensive targeted strategy focused on identified individuals at highest risk of developing hypertension is an attractive approach for the primary prevention of hypertension. [Review].

Topics: Albuminuria; Ankle Brachial Index; Atherosclerosis; Biomarkers; Blood Pressure; Cardiovascular Diseases; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Natriuretic Peptide, Brain; Predictive Value of Tests; Primary Prevention; Pulse Wave Analysis; Risk; Risk Factors; Uric Acid

Cardiovascular disease is a significant cause of morbidity and mortality, making cardiovascular prevention an important public health goal. The use of cardiac biomarkers represents a potential, noninvasive method to identify asymptomatic individuals who are most likely to develop cardiovascular disease. Several known biomarkers predict cardiovascular risk above and beyond conventional risk factors. Nonetheless, available evidence suggests that current biomarkers do not have sufficient sensitivity or specificity to justify widespread use for cardiovascular risk prediction. New developments in molecular biology and genetics may allow the identification of additional biomarkers, likely acting via different pathways, to achieve this goal.

Topics: Albuminuria; Animals; Area Under Curve; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Inflammation; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors

Hypertension involves the entire cardiovascular system, and hypertensive vascular disease may promote and exacerbate cardiac and renal dysfunction. We discuss the coexistence of cardiorenal disease as a manifestation of vascular involvement in hypertension, and the relationship of biomarkers of renal vascular involvement in hypertension with cardiovascular endpoints.. Markers of renal dysfunction, especially microalbuminuria, have been considered recently as potent predictors of cardiovascular morbidity and mortality in all explored populations, including hypertensive individuals. Microalbuminuria, per se, is related to vascular injury and to the increased glomerular permeability of albumin as a direct manifestation of renal vascular involvement in hypertension, a systemic vascular disease. Left ventricular hypertrophy in hypertension develops even before proteinuria or impairment of renal function. Factors including anemia, inflammation and hyperuricemia are either induced or exacerbated by renal vascular disease, and each of these may exert additional influence in determining the increased incidence of cardiovascular events with progressive renal dysfunction.. The development and progression of vascular disease is the primary determinant in the progressive cardiac and renal dysfunction observed in hypertension and, therefore, is the underlying mechanism of the overall clinical manifestations of cardiorenal disease. Commonly used biomarkers of renal and vascular function are important tools for determination of the progression and, hence, management of hypertensive disease and its complications.

Topics: Albuminuria; Biomarkers; C-Reactive Protein; Disease Progression; Erythropoietin; Glomerular Filtration Rate; Humans; Hypertension; Hyperuricemia; Natriuretic Peptide, Brain; Renal Insufficiency; Uric Acid

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

Topics: Acute Disease; Adult; Age Distribution; Aged; Albuminuria; Anemia; Calcium Metabolism Disorders; Comorbidity; Coronary Disease; Diabetes Complications; Female; Humans; Hyperhomocysteinemia; Hyperlipidemias; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Phosphorus Metabolism Disorders; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Sex Distribution; Urotensins

Monitoring of 24-hour ambulatory blood pressure(ABPM), measurements of circulating vasoactive substances and microalbuminuria, and assessment of gene polymorphisms as genetic markers are introduced to detect and evaluate hypertension. Classifications of ABPM based on impact on risks of cardiovascular diseases have been currently available. Plasma level of brain natriuretic peptide(BNP), a cardiac hormone, increases markedly in congestive heart failure, in proportion to its severity, and is evaluated as a potential index of severity of heart failure. In addition, serum level of hepatocyte growth factor(HGF), a member of endothelium specific growth factors, in hypertension might be useful for evaluating the presence of complications and degree of endothelial dysfunction. In diabetes mellitus, onset of microalbuminuria appeared as an important sign of early nephropathy. There is growing evidence that microalbuminuria is an independent predictor of atherosclerosis and premature death in the general population. Current studies have shown that gene polymorphisms including components of the renin-angiotensin-aldosterone system may be possible genetic markers for hypertension and its associated cardiovascular diseases. Our data suggest positive linkages between hypertension and 4 gene polymorphisms including angiotensinogen Met235Thr, angiotensin converting enzyme I/D, aldosterone synthase CYP11B2 T-344C, and endothelial nitric oxide synthase Glu298Asp in the Aomori population.

Topics: Albuminuria; Biomarkers; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Hepatocyte Growth Factor; Humans; Hypertension; Natriuretic Peptide, Brain; Polymorphism, Genetic; Renin-Angiotensin System; Risk Factors; Severity of Illness Index

Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.. We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed.. A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m. Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).

Topics: Aged; Albuminuria; Blood Pressure; Chlorthalidone; Creatinine; Diuretics; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Severity of Illness Index; Sodium Chloride Symporter Inhibitors

The aim of the study was to examine the relationship between the brain natriuretic peptide (BNP) level and prognosis of diabetic nephropathy. The subjects were 100 Japanese outpatients with type 2 diabetes mellitus with microalbuminuria. Associations between metabolic parameters at baseline, including BNP, and prognosis of diabetic nephropathy (progression of diabetic nephropathy, cardiovascular events, and death) were examined for 7 years. In Cox proportional hazard analysis, HbA1c, albumin-creatinine ratio (ACR) and BNP were identified as significant factors for progression of diabetic nephropathy (p=0.033, p=0.037, and p=0.044, respectively), BNP was identified as significant factor for cardiovascular events (p=0.046), and estimated glomerular filtration rate (eGFR) and BNP were identified as significant factors for death (p=0.046 and p=0.048, respectively). In Kaplan-Meier analysis, risks of progression of diabetic nephropathy, cardiovascular events, and death were significantly different between patients with a low and a high BNP level (p=0.046, p=0.002, and p=0.025, respectively). ROC curve analysis gave cutoff values for BNP of 14.9 pg/ml for progression of diabetic nephropathy, 16.3 pg/ml for cardiovascular events, and 17.6 pg/ml for death (p=0.047, p=0.035, p=0.018, respectively). In conclusion, the BNP level is associated with prognosis in diabetic nephropathy.

Topics: Aged; Albuminuria; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Survival Rate

A trial of telmisartan prevention of cardiovascular disease (ATTEMPT-CVD) was performed to compare the effects of angiotensin II receptor blocker (ARB) therapy and those of non-ARB standard therapy on biomarker level changes and the incidence of cardiovascular events in hypertensive patients.. In this multicenter, open-label, randomized, parallel-group, comparative study, the effects of ARB therapy and those of non-ARB standard therapy on urinary albumin creatinine ratio (UACR) and plasma brain natriuretic peptide (BNP) level changes were investigated for three years from the start of antihypertensive treatment as the primary endpoints. The incidences of cardiovascular composite events were compared between the two groups, and the relationship between the incidence of the events and biomarker changes were investigated as secondary endpoints. The study started with 615 patients in the ARB group and 613 patients in the non-ARB group. The ARB group had a significant effect on UACR and plasma BNP level changes compared with the non-ARB group. Fewer cardiovascular events occurred in the ARB group, but the difference was not statistically significant. UACR and plasma BNP levels at baseline were associated with cardiovascular events.. This study provided the first evidence that ARB treatment caused a smaller increase in plasma BNP and a greater decrease in UACR than non-ARB treatment, independently of blood pressure control, and gives a novel insight into the significance of BNP and UACR as predictors of cardiovascular and renal risk on antihypertensive treatment.

Topics: Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Benzoates; Biomarkers; Blood Pressure; Cardiovascular Diseases; Creatinine; Female; Humans; Hypertension; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; Telmisartan; Time Factors; Treatment Outcome

To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy.. In a double-blind, randomized placebo-controlled, crossover trial, 48 participants on stable renin angiotensin aldosterone system blockade and diuretics were assigned, in random order, to 12 weeks of paricalcitol and 12 weeks of placebo therapy, separated by a 4-week washout period. Primary and secondary endpoints were changes in plasma N-terminal probrain natriuretic peptide and urinary albumin excretion rate obtained before and after each intervention. Glomerular filtration rates were estimated and measured ((51) Cr-EDTA plasma clearance glomerular filtration rate) after each intervention.. The mean (sd) age of the participants was 57 (9) years, the baseline geometric mean (95% CI) urinary albumin excretion rate was 148 (85-259) mg/24 h, the mean (sd) HbA1c was 70 (9) mmol/mol [8.6 (3)%], the mean (sd) estimated glomerular filtration rate was 47 (15) ml/min/1.73 m(2) and the mean (sd) 24-h blood pressure was 135 (17)/74 (10) mmHg. Compared with placebo therapy, vitamin D analogue therapy had no significant effect on plasma N-terminal probrain natriuretic peptide concentration (P = 0.6), urinary albumin excretion rate was reduced by 18% (P = 0.03 for comparison), estimated glomerular filtration rate was reduced by 5 ml/min/1.73 m(2) (P < 0.001) and measured glomerular filtration rate was reduced by 1.5 ml/min/1.73 m(2) (P = 0.2).. Paricalcitol therapy did not affect plasma N-terminal probrain natriuretic peptide concentration in people with Type 1 diabetes and diabetic nephropathy; however, the urinary albumin excretion rate was significantly lowered.

Topics: Adult; Aged; Albuminuria; Biomarkers; Cardiovascular Diseases; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Double-Blind Method; Ergocalciferols; Female; Glomerular Filtration Rate; Glycopeptides; Humans; Incidence; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Vitamin D

Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs.. A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention.. Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases in Hb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb.. In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention.

Topics: Aged; Albuminuria; Atrasentan; Body Fluids; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Endothelin Receptor Antagonists; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pyrrolidines; Weight Gain

Scarce data are available on the effect of the traditional Mediterranean diet (TMD) on heart failure biomarkers. We assessed the effect of TMD on biomarkers related to heart failure in a high cardiovascular disease risk population.. A total of 930 subjects at high cardiovascular risk (420 men and 510 women) were recruited in the framework of a multicentre, randomized, controlled, parallel-group clinical trial directed at testing the efficacy of the TMD on the primary prevention of cardiovascular disease (The PREDIMED Study). Participants were assigned to a low-fat diet (control, n = 310) or one of two TMDs [TMD + virgin olive oil (VOO) or TMD + nuts]. Depending on group assignment, participants received free provision of extra-virgin olive oil, mixed nuts, or small non-food gifts. After 1 year of intervention, both TMDs decreased plasma N-terminal pro-brain natriuretic peptide, with changes reaching significance vs. control group (P < 0.05). Oxidized low-density lipoprotein decreased in both TMD groups (P < 0.05), the decrease in TMD + VOO group reaching significance vs. changes in control group (P = 0.003). Changes in lipoprotein(a) after TMD + VOO were less than those in the control group (P = 0.046) in which an increase (P = 0.035) was observed. No changes were observed in urinary albumin or albumin/creatinine ratio.. Individuals at high risk of cardiovascular disease (CVD) who improved their diet toward a TMD pattern reduced their N-terminal pro-brain natriuretic peptide compared with those assigned to a low-fat diet. The same was found for in vivo oxidized low-density lipoprotein and lipoprotein(a) plasma concentrations after the TMD + VOO diet. From our results TMD could be a useful tool to mitigate against risk factors for heart failure. From our results TMD could modify markers of heart failure towards a more protective mode.

Topics: Aged; Albuminuria; Biomarkers; Diet, Fat-Restricted; Diet, Mediterranean; Female; Heart Failure; Humans; Lipoproteins, LDL; Male; Middle Aged; Natriuretic Peptide, Brain; Nuts; Olive Oil; Peptide Fragments; Plant Oils; Primary Prevention; Spain; Treatment Outcome

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD).. This randomized, controlled, phase II trial consisted of two parts. In part A, the safety and tolerability of oral BAY 94-8862 [2.5, 5, or 10 mg once daily (q.d.)] was assessed in 65 patients with HFrEF and mild CKD. In part B, BAY 94-8862 (2.5, 5, or 10 mg q.d., or 5 mg twice daily) was compared with placebo and open-label spironolactone (25 or 50 mg/day) in 392 patients with HFrEF and moderate CKD. BAY 94-8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone (0.04-0.30 and 0.45 mmol/L, respectively, P < 0.0001-0.0107) and lower incidences of hyperkalaemia (5.3 and 12.7%, respectively, P = 0.048) and WRF. BAY 94-8862 decreased the levels of B-type natriuretic peptide (BNP), amino-terminal proBNP, and albuminuria at least as much as spironolactone. Adverse events related to BAY 94-8862 were infrequent and mostly mild.. In patients with HFrEF and moderate CKD, BAY 94-8862 5-10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress, but it was associated with lower incidences of hyperkalaemia and WRF.

Topics: Administration, Oral; Aged; Albuminuria; Aldosterone; Blood Pressure; Cardio-Renal Syndrome; Creatinine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Male; Mineralocorticoid Receptor Antagonists; Naphthyridines; Natriuretic Peptide, Brain; Peptide Fragments; Potassium

Aim of this study was to compare the antiproteinuric effect of imidapril (I) and ramipril (R) in diabetic hypertensive patients with microalbuminuria.. One hundred and seventy-six patients were randomised to I 10 - 20 mg once daily (od) (n = 88) or R 5 - 10 mg od (n = 88) for 24 weeks. Clinic, ambulatory, central blood pressure (BP), urinary albumin excretion (UAE), plasma Angiotensin II (Ang II), bradykinin and brain natriuretic peptide (BNP) were assessed at baseline and after 6, 12 and 24 weeks.. Both I and R produced a similar decrease in clinic, ambulatory and central BP (p < 0.001 vs baseline). Both treatments significantly reduced UAE throughout the study, but the decrease in UAE associated with I was more pronounced, being evident at week 6 (p = 0.05) and maximal at week 24 end-point (-42 vs -29%, p < 0.01). BNP and Ang II levels were similarly reduced by I and R, while bradykinin increased more with R (+132 vs +86%, p < 0.05).. These findings showed that in diabetic hypertensive patients with microalbuminuria, despite equivalent BP-lowering effect, I produced a greater antiproteinuric effect than R, which might be due to different intrinsic molecular properties of the two drugs.

Topics: Adult; Aged; Albumins; Albuminuria; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Bradykinin; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Imidazolidines; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ramipril; Treatment Outcome

Renin-angiotensin-aldosterone system (RAAS) blockade may reduce levels of biomarkers of chronic low-grade inflammation and endothelial dysfunction. We investigated the effect of spironolactone added to standard RAAS blockade on these biomarkers in an analysis of four original studies.. The studies were double-blind, randomised, placebo-controlled studies in 46 type 1 and 23 type 2 diabetic patients with micro- or macroalbuminuria treated with angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin receptor blocker (ARB), and randomised to additional treatment with spironolactone 25 mg and placebo daily for 60 days.. Changes in inflammatory (hsCRP, s-ICAM, TNFα, IL-6, IL-8, Serum amyloid A, IL1β), endothelial dysfunction (sE-selectin, s-ICAM1, s-VCAM1, VWF, p-selectin, s-thrombomodulin) and NT-proBNP after each treatment period.. During spironolactone treatment, u-albumin excretion rate was reduced from 605 (411-890) to 433 (295-636) mg/24 h, as previously reported. Markers of inflammation and endothelial dysfunction did not change; only changes in NT-proBNP (reduced by 14%, p=0.05) and serum amyloid A (reduced by 62%, p=0.10) were borderline significant.. Our results indicate that the renoprotective effect of spironolactone when added to RAAS blockade is not mediated through anti-inflammatory pathways since markers of inflammation and endothelial dysfunction are not affected during treatment.

Topics: Albuminuria; Biomarkers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Endothelium; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Spironolactone

Topics: Adrenergic alpha-1 Receptor Antagonists; Albuminuria; Doxazosin; Humans; Hypertension; Natriuretic Peptide, Brain; Prospective Studies

This study was conducted to determine the effects of a tablet combining losartan/hydrochlorothiazide (L/HCTZ) in comparison with losartan alone in Japanese diabetic patients with hypertension. Thirty consecutive Japanese diabetic patients with hypertension were randomly assigned to group A, receiving losartan alone for the first 3 months, then L/HCTZ for the next 3 months, or group B, receiving L/HCTZ for the first 3 months, then losartan alone for the next 3 months. Clinical and biological parameters were obtained before, and 3 and 6 months after the start of this study. The decreases in systolic and diastolic blood pressure (BP) during treatment with L/HCTZ were significantly greater than in treatment with losartan alone. Both treatments significantly and similarly decreased urinary albumin excretion, the cardio-ankle vascular index (CAVI) and augmentation index (AI). There was no significant difference in metabolic change during both the mono- and combination pharmacotherapies. The tablet combining L/HCTZ significantly reduced systolic and diastolic BP compared with the losartan monotherapy, and offered benefits similar to losartan monotherapy for albuminuria, arterial stiffness assessed by the CAVI and AI, and metabolic effects. Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic patients with hypertension.

Topics: Adult; Albuminuria; Aldosterone; Antihypertensive Agents; Asian People; Blood Pressure; Cross-Over Studies; Diabetes Complications; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Renin; Tablets; Treatment Outcome

Strong adherence to antihypertensive therapy has been shown to reduce the frequency of cardiovascular events by strictly controlling blood pressure. Although calcium channel blockers (CCBs) are among the most popular antihypertensive drugs in Japan, few trials have been conducted using high CCB doses in Japanese patients. In this study, we administered amlodipine 5 mg or 10 mg to patients with hypertension in order to compare the efficacy and tolerability of low and high doses, and measured two surrogate markers of hypertensive target organ damage, i.e., brain natriuretic peptide (BNP) as a risk marker of cardiac overload and microalbuminuria as a measure of renal damage. Seventy-two patients were randomly assigned to either amlodipine 5 mg (n = 35) or 10 mg (n = 37) dose groups. The latter group achieved greater reductions in clinic as well as both morning and evening home BP levels without an increase in pulse rate (the differences between the two groups in clinic/morning/evening systolic BP were 4.7/4.7/5.4 mmHg, and for diastolic BP they were 4.2/3.6/3.8 mmHg). Reductions in BNP and urinary albumin/creatinine ratio (UAR) levels were significantly correlated with the reductions in systolic BP levels (BNP, clinic/morning BP: r = 0.256, p = 0.030/r = 0.330, p = 0.005; UAR, clinic BP: r = 0.316, p = 0.007). In conclusion, the higher dose (10 mg) of amlodipine induced greater reductions in all BP levels than did the lower dose, without increasing the pulse rate. These additional reductions were significantly correlated with reductions in hypertensive cardiac overload, as evaluated by BNP levels, and a reduction in renal damage, as evaluated by microalbuminuria levels. Moreover, a reduction in the microalbuminuria may have occurred concomitant with a reduction in clinic systolic BP level.

Topics: Albuminuria; Amlodipine; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Calcium Channel Blockers; Dose-Response Relationship, Drug; Heart Rate; Humans; Hypertension; Japan; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Orthostatic blood pressure (BP) dysregulation is a risk factor for both falls and cardiovascular events. Self-measured BP, carried out at home, is both highly reproducible and useful for evaluating antihypertensive treatment. However, there have been a few reports on the clinical implications of orthostatic BP changes in home BP monitoring (HBPM). In the baseline examination for the Japan Morning Surge-1 Study, a multicenter randomized control trial, we evaluated 605 hypertensive outpatients who had a morning systolic BP above 135 mmHg. The plasma brain natriuretic peptide (BNP) level and urinary albumin excretion were measured. When the patients were divided into 10 groups, according to orthostatic BP change evaluated by HBPM, after adjusting for age, gender, body mass index and sitting home BP level, those in the top decile (n=60, orthostatic BP increase>7.8 mmHg) had a higher urinary albumin/creatinine ratio (UAR) than the lowest decile group (geometric mean [SEM range]: 209.1 [134.7-318.7] vs. 34.1 [20.1-56.2] mg/g creatinine [Cr], p=0.003) and the pooled second to ninth decile groups (n=485, 209.1 [134.7-318.7] vs. 39.7 [33.2-47.3] mg/g Cr, p<0.02). Additionally, patients in the top decile had a higher BNP level than the second to ninth decile groups (75.7 [55.0-103.1] vs. 23.6 [20.8-26.6] pg/mL, p=0.003). Evaluation of orthostatic hypertension at home might be a high-risk factor for cardiovascular events in hypertensive subjects with increased levels of BNP and a higher UAR, independent of the home sitting BP level.

Topics: Aged; Aged, 80 and over; Aging; Albuminuria; Antihypertensive Agents; Autonomic Nervous System Diseases; Blood Pressure Monitoring, Ambulatory; Creatinine; Doxazosin; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Posture; Risk Factors

Atrial natriuretic peptide (ANP) increases urinary albumin excretion in Type 1 diabetes mellitus (DM). Brain natriuretic peptide (BNP) is structurally and functionally related to ANP, but its effect on urine albumin excretion rate (UAER) is unknown.. To compare the albuminuric effects of intravenous infusion of ANP and BNP, and to assess the effect of both peptides on tubular protein excretion.. Eight subjects with Type 1 DM were randomised to a three leg, double blind, and placebo controlled study. On each study day, subjects were euglycaemic clamped and subsequently water loaded (20 mL/kg orally, plus urine losses) to steady state diuresis. When in steady state, creatinine clearance was estimated in three separate 1 hour periods. At the end of the first period, a 1 hour intravenous infusion of either placebo, ANP 0.025 microg/kg/min, or BNP 0.025 microg/kg/min was administered. There followed a 1 hour recovery period. Urine was collected at 15 min intervals for estimation of urine albumin (ACR) and alpha1 microglobulin creatinine ratio (MCR). Results were analysed by anova.. Creatinine clearance was similar on the three study days, and was unaltered by any infusion. ACR was unaltered by placebo (1.3 +/- 0.5-1.2 +/- 0.4 mg/mmol, mean +/- SD, p = 0.81), but increased compared to placebo with infusion of both ANP (1.2 +/- 0.4-9.8 +/- 8.4 mg/mmol, P = 0.0004), and BNP (1.1 +/- 0.4-13.4 +/- 8.6 mg/mmol, P = 0.0001). The MCR was unaltered by placebo infusion (P = 0.89), but increased compared with placebo after infusion of ANP (5.4 +/- 0.9-12.3 +/- 4.2 mg/mmol, P < 0.0001), and BNP (5.4 +/- 0.8-12.1 +/- 2.5 mg/mmol, P < 0.0001).. Intravenous infusion of BNP and ANP both increase the urine excretion of albumin and the tubular protein alpha1 microglobulin, independent of creatinine clearance.

Topics: Adult; Albuminuria; Alpha-Globulins; Atrial Natriuretic Factor; Creatinine; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Natriuretic Peptide, Brain; Placebos

Albuminuria is common in patients with heart failure and associated with worse outcomes. The underlying pathophysiological mechanism of albuminuria in heart failure is still incompletely understood. The association of clinical characteristics and biomarker profile with albuminuria in patients with heart failure with both reduced and preserved ejection fractions were evaluated.. Two thousand three hundred and fifteen patients included in the index cohort of BIOSTAT-CHF were evaluated and findings were validated in the independent BIOSTAT-CHF validation cohort (1431 patients). Micro-albuminuria and macro-albuminuria were defined as urinary albumincreatinine ratio (UACR) 30 mg/gCr and 300 mg/gCr in spot urines, respectively. The prevalence of micro- and macro-albuminuria was 35.4 and 10.0, respectively. Patients with albuminuria had more severe heart failure, as indicated by inclusion during admission, higher New York Heart Association functional class, more clinical signs and symptoms of congestion, and higher concentrations of biomarkers related to congestion, such as biologically active adrenomedullin, cancer antigen 125, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (all P 0.001). The presence of albuminuria was associated with increased risk of mortality and heart failure (re)hospitalization in both cohorts. The strongest independent association with log UACR was found for log NT-proBNP (standardized regression coefficient 0.438, 95 confidence interval 0.350.53, P 0.001). Hierarchical clustering analysis demonstrated that UACR clusters with markers of congestion and less with indices of renal function. The validation cohort yielded similar findings.. In patients with new-onset or worsening heart failure, albuminuria is consistently associated with clinical, echocardiographic, and circulating biomarkers of congestion.

Topics: Albuminuria; Biomarkers; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume

Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality.. Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death.. During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models.. The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Topics: Albuminuria; Biomarkers; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic

Diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high-sensitivity troponin I (hs-TnI), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers.. In all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT-proBNP/hs-TnI in 933 patients. The end point was a composite of CV events.. The median follow-up was 4.7 years (interquartile range: 4.0-5.3), and 174 patients experienced a CV disease event. All considered markers, except hs-TnI, were significantly (P < .001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70-3.39]), albuminuria 2.01 (1.47-2.76), abnormal ECG (2.27 [1.66-3.08]), high NT-proBNP (>150 pg/mL) 3.05 (2.11-4.40), and hs-TnI 1.12 (0.79-1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT-proBNP >150 pg/mL remained significantly associated with the end point (2.07 [1.28-3.34], P < .001). Measured by C-statistics, model performance was highest with log. This study identified NT-proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.. 背景: 超声心动图、蛋白尿、心电图(ECG)、高敏肌钙蛋白I(hs-TnI)和N末端前激素脑钠素(NT-proBNP)等诊断试验被认为能够预测2型糖尿病心血管(CV)的危险因素。我们研究了这些风险标记物的单独和联合预测效果。 方法: 在这项前瞻性队列研究中, 从专科诊所共招募1030名2型糖尿病患者。886例窦性心律且图像质量良好的患者进行了超声心动图的全面评估。对998例患者进行心电图检查。1009例患者检测蛋白尿, 933例患者检测NT-proBNP/hs-TnI。终点是CV事件的组合。 结果: 中位随访时间为4.7年(四分位数范围:4.0-5.3), 174名患者经历了心血管疾病事件。除hs-TnI外, 所有考虑的标志物:超声心动图异常(危险比2.40[1.70-3.39])、蛋白尿2.01(1.47-2.76)、心电图异常(2.27[1.66-3.08])、高NT-proBNP(>150pg/mL)3.05(2.11-4.40)和hs-TnI 1.12(0.79-1.59) 均与预后显著相关(P<0.001)。在调整了临床变量后, 所有这些变量仍然与终点显著相关。然而, 在变量间调整后, 只有NT-proBNP>150pg/mL与终点显著相关(2.07[1.28-3.34], P<0.001)。通过C-统计量测量, log

Topics: Aged; Albuminuria; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Risk Factors; Ultrasonography; Urinalysis

Although seasonal variation of home blood pressure (BP) has been reported to be higher in winter, seasonal difference in home BP (HBP) and its association with target organ damage (TOD) remains unclear.. This is a cross-sectional study using the dataset from the Japan Morning Surge-Home Blood Pressure (J-HOP) study to assess seasonal differences in HBP, prevalence of masked hypertension, and association of HBP with TOD. The J-HOP study is a nationwide, multicenter prospective study whose participants with cardiovascular risks underwent morning and evening HBP measurements for a 14-day period in 71 institutions throughout Japan. Urine albumin-creatinine ratio (UACR) and serum-B-type natriuretic peptide (BNP) were obtained at enrollment.. Among 4,267 participants (mean age, 64.9 ± 10.9 years; 46.9% male; 91.4% hypertensives), 1,060, 979, 1,224, and 1,004 participants were enrolled in spring, summer, autumn, and winter, respectively. Morning and evening home systolic/diastolic BP levels, and prevalence of masked hypertension (office BP <140/90 mm Hg and HBP ≥135/85 mm Hg) were significantly lower in summer than other seasons after adjustment for covariates. When we assessed the interaction between BP parameters and each season for an association with TOD, we found the association between morning home diastolic BP and each of UACR and BNP was stronger in winter than other seasons (both P for interaction <0.05).. In this study, we revealed that the prevalence of masked hypertension was higher in other seasons than in summer and found a notable association between morning home diastolic BP and TOD in winter.

Topics: Aged; Albuminuria; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Cross-Sectional Studies; Female; Humans; Japan; Male; Masked Hypertension; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Prospective Studies; Seasons

Background The incidence and clinical manifestations of cardiovascular disease (CVD) differ between blacks and whites. Biomarkers that reflect important pathophysiological pathways may provide a window to allow deeper understanding of racial differences in CVD. Methods and Results The study included 2635 white and black participants from the Dallas Heart Study who were free from existing CVD. Cross-sectional associations between race and 32 biomarkers were evaluated using multivariable linear regression adjusting for age, traditional CVD risk factors, imaging measures of body composition, renal function, insulin resistance, left ventricular mass, and socioeconomic factors. In fully adjusted models, black women had higher lipoprotein(a), leptin, d-dimer, osteoprotegerin, antinuclear antibody, homoarginine, suppression of tumorigenicity-2, and urinary microalbumin, and lower adiponectin, soluble receptor for advanced glycation end products and N-terminal pro-B-type natriuretic peptide versus white women. Black men had higher lipoprotein(a), leptin, d-dimer, high-sensitivity C-reactive protein, antinuclear antibody, symmetrical dimethylarginine, homoarginine, high-sensitivity cardiac troponin T, suppression of tumorigenicity-2, and lower adiponectin, soluble receptor for advanced glycation end products, and N-terminal pro-B-type natriuretic peptide versus white men. Adjustment for biomarkers that were associated with higher CVD risk, and that differed between blacks and whites, attenuated the risk for CVD events in black women (unadjusted hazard ratio 2.05, 95% CI 1.32, 3.17 and adjusted hazard ratio 1.15, 95% CI 0.69, 1.92) and black men (unadjusted hazard ratio 2.39, 95% CI 1.64, 3.46, and adjusted hazard ratio 1.21, 95% CI 0.76, 1.95). Conclusions Significant racial differences were seen in biomarkers reflecting lipids, adipokines, and biomarkers of endothelial function, inflammation, myocyte injury, and neurohormonal stress, which may contribute to racial differences in the development and complications of CVD.

Topics: Adiponectin; Adult; Albuminuria; Antibodies, Antinuclear; Arginine; Biomarkers; Black or African American; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Homoarginine; Humans; Interleukin-1 Receptor-Like 1 Protein; Leptin; Linear Models; Lipoprotein(a); Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Proportional Hazards Models; Receptor for Advanced Glycation End Products; Troponin T; White People

The ability of cardiovascular biomarkers to predict the incidence of stroke subtypes remains ill-defined in the general population.Methods and Results:The blood levels of B-type natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) and urinary albumin corrected by urinary creatinine (UACR) were determined in a general population (n=13,575). The ability to predict the incidence of ischemic stroke subtypes (lacunar, atherothrombotic, cardioembolic) for each biomarker was assessed based on the area under the receiver-operating characteristic curve (AUC-ROC) and using Cox proportional hazard modeling. The predictive abilities of UACR and hs-CRP for any subtype of ischemic event were found to be suboptimal. However, the ability of BNP to predict the incidence of cardioembolic stroke was excellent (AUC-ROC=0.81). When BNP was added to established stroke risk factors, the ability to predict cardioembolic stroke in terms of the AUC-ROC significantly improved (4-year follow-up, P=0.018; 8-year follow-up, P=0.009). Furthermore, when BNP was added to the JPHC score, the ability to predict cardioembolic stroke was significantly improved (net reclassification improvement=0.968, P<0.0001: integrated discrimination improvement=0.039, P<0.05).. In the general population, plasma BNP was an excellent biomarker for predicting the incidence of cardioembolic stroke when used alone or in combination with established stroke risk factors.

Topics: Aged; Albumins; Albuminuria; Area Under Curve; Biomarkers; C-Reactive Protein; Embolism; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; ROC Curve; Stroke

Analyzing the relationships between biomarkers representing distinct pathophysiologic pathways and microalbuminuria (MA) can strengthen the identifying ability for renal damage and illuminate previously unrecognized pathways for the pathogenesis of renal damage. The current analysis was to clarify the associations between biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), homocysteine and uric acid (UA), and MA in Chinese middle-aged and elderly from communities.. All 839 residents had complete set of these biomarkers and full assessment of MA.. Prevalence of participants with MA was 13.5% (113 participants). Levels of age, systolic blood pressure (SBP), fasting blood glucose (FBG), homocysteine and NT-proBNP and proportion of cigarette smoking in participants with MA significantly exceeded those in participants without MA (p < 0.05 for all). In single-marker and multi-marker models of linear and logistic regression analyses, homocysteine and NT-proBNP levels (p < 0.05 for all) rather than hsCRP and UA levels (p > 0.05 for all) were statistically significant in relation to MA. Additionally, no matter which biomarker was directed at, levels of age, SBP and FBG and proportion of cigarette smoking had significant associations with MA. Homocysteine and NT-proBNP levels (p < 0.05 for all) rather than hsCRP and UA levels (p > 0.05 for all) had significant abilities to identify MA.. Both single-marker and multi-marker analyses confirmed that homocysteine and NT-proBNP were associated with MA in Chinese middle-aged and elderly from communities after adjustment for multiple confounders.

Topics: Aged; Aged, 80 and over; Albuminuria; Biomarkers; C-Reactive Protein; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Homocysteine; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Smoking; Uric Acid

Cardiorenal syndrome (CRS) is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. CRS remains a major global health problem. Qiliqiangxin (QLQX) is a traditional Chinese herbs medication, which can improve cardiac function, urine volume, and subjective symptoms in patients with chronic heart failure. In the present study, we aim to investigate the role of QLQX in the treatment of CRS type I and the possible mechanism through establishment of a rat model of myocardial infarction. Rats in CRS-Q group were orally treated with QLQX daily for 2 weeks or 4 weeks, while in sham group and CRS-C group were treated with saline at the same time. Enzyme-linked immunosorbent assay (ELISA) analysis showed that QLQX significantly reduced the levels of angiotensin II (AngII), brain natriuretic peptides (BNP), creatinine (CRE), cystatin C (CysC), tumor necrosis factor (TNF)-α, interleukin (IL)-6, microalbuminuria (MAU), and neutrophil gelatinase-associated lipocalin (NGAL) in plasma induced by myocardial infarction. Western blot analysis showed that QLQX significantly reduced the expressions of AngII, non-phagocytic cell oxidase (NOX)2, and B-cell lymphoma (Bcl)2 associated X protein (Bax), and increased the expressions of Bcl2 and Angiotensin II Type 1 receptor (ATR) in the kidney as compared with the CRS-C group. Fluorescence microscopy showed that the content of reactive oxygen species (ROS) was significantly reduced in the kidney as compared with the CRS-C group. We also examined the apoptosis level in kidney by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, and the result showed that QLQX significantly reduced the apoptosis level in kidney induced by myocardial infarction. Taken together, we suggest that QLQX may be a potentially effective drug for the treatment of CRS by regulating inflammatory/oxidative stress signaling.

Topics: Albuminuria; Angiotensin II; Animals; Anti-Inflammatory Agents; Antioxidants; Cardio-Renal Syndrome; Creatinine; Cystatin C; Drugs, Chinese Herbal; Interleukin-6; Kidney; Male; Myocardial Infarction; NADPH Oxidase 2; Natriuretic Peptide, Brain; Oxidative Stress; Phytotherapy; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Signal Transduction; Tumor Necrosis Factor-alpha

Cardio-ankle vascular index (CAVI) was supposed to be an independent predictor for vascular-related events. Biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin(microalbumin) (UAE) have involved the pathophysiological development of arteriosclerosis. The present study was to investigate relationship between CAVI and biomarkers in vascular-related diseases.. A total of 656 subjects (M/F 272/384) from department of Vascular Medicine were enrolled into our study. They were divided into four groups according to the numbers of suffered diseases, healthy group (group 0: subjects without diseases of hypertension, diabetes mellitus (DM), coronary heart disease (CHD); n = 186), group 1 (with one of diseases of hypertension, CHD, DM; n = 237), group 2 (with two of diseases of hypertension, CHD, DM; n = 174), and group 3 (with all diseases of hypertension, CHD, DM; n = 59). CAVI was measured by VS-1000 apparatus.. CAVI was increasing with increasing numbers of suffered vascular-related diseases. Similar results were found in the parameters of biomarkers such as Hcy, log NT-ProBNP, and log UAE. There were positive correlation between log NT-proBNP, Hcy, log UAE, and CAVI in the entire study group and nonhealthy group. Positive correlation between log UAE and CAVI were found in the entire study group after adjusting for age, body mass index (BMI), blood pressure, uric acid, and lipids. Multivariate analysis showed that log UAE was an independent associating factor of CAVI in all subjects.. CAVI was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between arterial stiffness and biomarkers such as NT-proBNP, Hcy, and UAE.

Topics: Aged; Albuminuria; Biomarkers; Blood Pressure; Coronary Disease; Diabetes Mellitus; Female; Homocysteine; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Vascular Stiffness

Prehypertension is a risk factor for the development of hypertension and other cardiovascular diseases. The objective of this study was to evaluate for the evidence of subclinical target organ damage in two groups of subjects without hypertension.. This was a prospective cross-sectional study. Subjects seeking care for various clinical conditions in the hospital were invited for the survey. The subjects' were divided in to two groups according to their blood pressure: prehypertension (systolic blood pressure 120 to 139 mm Hg or diastolic blood pressure, 80 to 89 mm Hg) and normotension (systolic blood pressure, <120 mm Hg and diastolic blood pressure, <80 mm Hg). Urine albumin excretion and other biochemical analyses were performed using standard methods.. We recruited a total of 3300 subjects, the prehypertension group included 1100 individuals and the normotension group was composed of 2200 persons. The prevalence of microalbuminuria in subjects in the prehypertension group was 6.8% and in those who are the in the optimal BP group was 3.6% (P<0.001). Subjects in the prehypertension group had a mean B-type natriuretic peptide (BNP) level of 98 (72) pg/mL compared with 43.6 (20) pg/mL found among subjects in the normotension group (<0.001). In the logistic regression model, tobacco smoking aOR 2.7 (95% CI.; 1.7-5.8), higher uric acid level aOR 2.2 (1.7-3.2), microalbuminuria 7.6 (4.9-14.7) and a higher BNP level aOR 2.5 (1.8-7.6) were significantly associated with the occurrence of prehypertension.. Microalbuminuria, BNP level and hyperuricemia were significantly associated with prehypertension.

Topics: Albuminuria; Blood Pressure; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prehypertension; Prevalence; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; Uric Acid

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort.. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF.. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF.. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

Topics: Adult; Age Factors; Albuminuria; Aminopeptidases; Antihypertensive Agents; Atrial Fibrillation; Atrial Natriuretic Factor; Blood Glucose; Body Mass Index; C-Reactive Protein; Cohort Studies; Creatinine; Cystatin C; Female; Genetic Predisposition to Disease; Glomerular Filtration Rate; Heart Rate; Homeobox Protein PITX2; Homeodomain Proteins; Humans; Hypertension; Hypolipidemic Agents; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Phosphotransferases (Phosphate Group Acceptor); Polymorphism, Single Nucleotide; Risk Factors; Sex Factors; Small-Conductance Calcium-Activated Potassium Channels; Transcription Factors

Emerging acute kidney injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), have a high potential for predicting worsening renal function. Acute exacerbation of renal dysfunction has a great impact on the outcomes of cardiovascular patients in critical conditions. This study aimed to evaluate whether plasma NGAL can predict the mortality and major adverse cardiovascular events (MACEs) after discharge from the cardiac care unit (CCU).. Patients who were admitted to the CCU of the Tokyo University Hospital were prospectively enrolled (101 patients). Blood and urinary markers, including the blood NGAL, brain natriuretic peptide, creatinine, cystatin C, urinary albumin, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein, were measured at CCU discharge. The primary outcome was MACEs until at least 6 months after CCU discharge.. Thirty-five patients experienced MACEs (35%). Multivariate logistic analysis revealed that the plasma NGAL, length of CCU stay, and existence of diabetes and heart failure were independent predicting factors for MACEs. Patients with the highest NGAL at discharge (>75th percentile) showed a significantly higher risk of MACEs than those with the lowest NGAL (<25th percentile) (log-rank test; hazard ratio, 5.15; 95% confidence interval 1.84-18.20; p<0.01).. Plasma NGAL at CCU discharge is a significant prognostic indicator of outcomes at 6 months in critically ill cardiac patients treated in a CCU.

Topics: Acetylglucosaminidase; Acute Kidney Injury; Acute-Phase Proteins; Aged; Aged, 80 and over; Albuminuria; Biomarkers; Cardiovascular Diseases; Coronary Care Units; Creatinine; Cystatin C; Fatty Acid-Binding Proteins; Female; Heart Failure; Humans; Length of Stay; Lipocalin-2; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Prognosis; Proportional Hazards Models; Prospective Studies; Proto-Oncogene Proteins; Tokyo

Galectin 3 (Gal-3) reflects cardiac fibrosis in heart failure HF, but has also been associated to renal fibrosis and impaired renal function. Previous research has suggested that Gal-3 could be a cardio-renal biomarker, but it has never been tested simultaneous in a single study whether Gal-3 reflects echocardiographic measures, neurohumoral activity and renal function. The aim of this study was to evaluate the relationship between plasma concentrations of Gal-3 and neurohumoral activity, myocardial and renal function in patients with HF, including advanced echocardiographic measures and 24-h urinary albumin excretion (albuminuria).. We prospectively enrolled 132 patients with reduced left ventricular ejection fraction (LVEF) referred to an outpatient HF clinic. The patients had a median age of 70 years (interquartile rage: 64-75), 26.5 % were female, median LVEF was 33 % (27-39 %) and 30 % were in NYHA class III-IV.. Patients with plasma concentrations of Gal-3 above the median had significantly lower estimated glomerular filtration rate (eGFR) and this association remained significant in multivariate regression analysis (β: -0.010; 95 % CI -0.012--0.008; P < 0.001), adjusted for age, gender, medical treatment. Plasma concentrations of Gal-3 were not associated with albuminuria (Beta: 0.008; 95 % CI:-0.028-0.045; P = 0.652). There were no association between plasma concentrations of Gal-3 and myocardial function or structure estimated by LVEF, LVmassIndex, LVIDd, E/é or LV global longitudinal strain (P > 0.05 for all). In multivariate analyses plasma concentrations of Gal-3 were significantly associated with the cardiac biomarkers: NT-proBNP (β: 0.047; 95 % CI: 0.008-0.086; P = 0.020), proANP (β: 0.137; 95 % CI: 0.067-0.207; P < 0.001), chromogranin A (β: 0.123; 95 % CI: 0.052-0.194; P < 0.001) and Copeptin (β: 0.080; 95 % CI: 0.000-0.160; P = 0.049). Multivariate analysis was adjusted for eGFR, age, gender and medical treatment.. Increased plasma concentrations of Gal-3 are associated with reduced eGFR and increased plasma concentrations of NT-proBNP, proANP, chromogranin A and Copeptin, but not with echocardiographic parameters reflecting myocardial function. These results suggest that Gal-3 reflects both increased neurohumoral activity and reduced eGFR, but not myocardial function in patients with systolic HF.

Topics: Aged; Albuminuria; Atrial Natriuretic Factor; Biomarkers; Blood Proteins; Chi-Square Distribution; Chromogranin A; Echocardiography, Doppler, Pulsed; Female; Galectin 3; Galectins; Glomerular Filtration Rate; Glycopeptides; Heart Failure; Humans; Kidney; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Factors; Stroke Volume; Up-Regulation; Ventricular Function, Left

Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort.. 8127 participants from the ARIC study (4th visit, 1996-1998) were stratified as having minimal, mild, or substantial atherosclerosis by cIMT. Levels of C-reactive protein, lipoprotein-associated phospholipase A2, cardiac troponin T, N-terminal pro-brain natriuretic peptide, lipoprotein(a), cystatin C, and urine albumin to creatinine ratio were measured in each participant. Hazard ratios were used to determine the relationship between the biomarkers and incident CHD, stroke, and CVD in each category of atherosclerosis.. While each of the biomarkers was significantly associated with risk of events overall, we found no significant differences noted in the strength of association of biomarkers with CHD, stroke, and CVD when analyzed by degree of atherosclerosis.. These findings suggest that the level of atherosclerosis does not significantly influence the association between biomarkers and CVD.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Albuminuria; Atherosclerosis; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cohort Studies; Cystatin C; Female; Humans; Incidence; Lipoprotein(a); Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Primary Prevention; Prospective Studies; Smoking; Troponin T; United States

Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p < 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m2. We divided patients into four subgroups (group 1, L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

Topics: Aged; Albuminuria; Arrhythmias, Cardiac; Biomarkers; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Electrocardiography; Fatty Acid-Binding Proteins; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors; Troponin T

CHD patients, especially those with associated hypoxaemia, usually have some level of renal function impairment, even though they are relatively young. The aim of the study was to evaluate those clinical and analytical factors that may contribute to microalbuminuria and determine the association of 24-hour proteinuria with thrombotic events and mortality.. A total of 251 CHD patients were studied and demographic characteristics, blood test, and 24-hour urinalysis were analysed.. Of the patients, 221 were non-hypoxaemic, and 30 were hypoxaemic (oxygen saturation of 84.3±5.9%). Of the non-hypoxaemic patients, 30 (13.6%), and of the hypoxaemic patients 9 (30%), showed proteinuria (>0.15 g/24 hours) (p=0.028). Hypoxaemic CHD patients also showed higher haematocrit (%) (50.7 (34.6; 72.1) versus 42.8 (34.6; 48.9), p<0.001), serum creatinine (mg/dl) (1.07±0.2 versus 0.96±1.9, p=0.004), microalbuminuria (mg/dl/24 hours) (1.2 (0.0; 261.5) versus 0.5 (0.0; 4.37), p<0.001), proteinuria (gr/24 hours) (1.0 (0.4; 3.1) versus 0.08 (0.04; 0.52), p=0.043), and N-terminal pro-B-type natriuretic peptide (pg/ml) (417.8 (35.7; 8534.0) versus 44.9 (0.0; 670.5), p<0.001) concentrations than non-hypoxaemic CHD patients. During a median follow-up of 26.0 (16.9; 57.7) months, five patients died - one patient had 24-hour proteinuria and four patients did not (p=0.581) - and three patients had some type of thrombosis - two patients had 24-hour proteinuria and one patient did not (p=0.014). Kaplan-Meier survival analysis showed no significant difference between CHD patients with and without 24-hour proteinuria (p=0.631).. CHD patients with proteinuria have significantly more thrombosis and more hypoxaemia than those patients without proteinuria.

Topics: Adolescent; Adult; Albuminuria; Creatinine; Female; Heart Defects, Congenital; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Outcome Assessment; Peptide Fragments; Proteinuria; Renal Insufficiency; Thrombosis; Young Adult

The aim of the study was to examine the relationship between the brain natriuretic peptide (BNP) level and progression or remission of diabetic nephropathy with microalbuminuria for 3 years. The subjects were 100 Japanese type 2 diabetes mellitus outpatients with microalbuminuria. Associations between metabolic parameters at baseline [HbA1c, systolic blood pressure (SBP), urine albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and BNP] and the progression or remission of diabetic nephropathy were examined for 3 years. A total of 83 patients were examined at the end of the 3-year period, including 17 with remission to normoalbuminuria, 47 with continuing microalbuminuria, and 19 with progression to macroalbuminuria. HbA1c, ACR, and BNP differed significantly among the 3 groups (p=0.024, p<0.001, p=0.002, respectively). Among baseline factors, HbA1c and BNP were significant predictors of the percentage increase in ACR for 3 years in multiple linear regression analysis (β=0.259, p=0.02; β=0.299, p=0.007, respectively). In multivariate logistic regression analysis, HbA1c and ACR were independently associated with progression of diabetic nephropathy (p=0.008, p=0.023, respectively), and ACR and BNP were independently associated with remission of diabetic nephropathy (p=0.029, p=0.012, respectively). ROC curve analysis gave a cutoff value for BNP of 14.9 pg/ml for prediction of remission of diabetic nephropathy (p=0.016). The BNP level has a relationship with diabetic nephropathy and a low BNP level predicts remission of diabetic nephropathy. Therefore, monitoring of BNP can play an important role in management of diabetic nephropathy.

Topics: Aged; Albuminuria; Asian People; Diabetic Nephropathies; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Remission Induction

In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline.. Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP > 45.2 ng/L and/or CAC ≥ 400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median).. High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31).. In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk.

Topics: Aged; Albuminuria; Asymptomatic Diseases; Biomarkers; Cardiovascular Diseases; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multidetector Computed Tomography; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Vascular Calcification

Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD.. We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort.. Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD.

Topics: Aged; Aged, 80 and over; Albuminuria; Biomarkers; Comorbidity; Coronary Disease; Creatinine; Decision Support Techniques; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Reproducibility of Results; Risk Assessment; Risk Factors; Smoking; Stroke; Time Factors; Troponin T; United States

Kidney function and cardiovascular disease are closely connected and albuminuria is a proven marker of cardiovascular risk. The present study investigated the prevalence and characteristics of albuminuria in patients with hypertension. Outpatients with essential hypertension under medical treatment were enrolled in this study (n = 350, 70.0 ± 11.4 years old). Urine samples were collected for the measurement of albumin concentration, which are expressed as the ratio of urine albumin to creatinine concentration (mg/g Cr). Cross-sectional analyses were also performed of the relationships between urinary albumin and other variables. Urinary albumin was detected in 88.3% of patients, while only 35.4% showed abnormal albuminuria (≥30 mg/g Cr). The presence of abnormal albuminuria was independently correlated with systolic blood pressure, B-type natriuretic peptide, and C-reactive protein by multivariate analysis (P < 0.05). Furthermore, multivariate regression analysis identified systolic blood pressure, serum creatinine, B-type natriuretic peptide, and C-reactive protein as the only factors showing independent correlation with urinary albumin (P < 0.05). Thus, approximately 35% of hypertensive patients had abnormal albuminuria. Urinary albumin was closely associated with blood pressure, C-reactive protein, and B-type natriuretic peptide, indicating that the severity of albuminuria parallels that of systemic inflammation, cardiac load, and blood pressure.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Albuminuria; Biomarkers; Blood Pressure; C-Reactive Protein; Creatinine; Cross-Sectional Studies; Female; Humans; Hypertension; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors; Young Adult

Several guidelines recommend that home blood pressure (HBP) be measured both in the morning and in the evening. However, there have been fewer reports about the clinical significance of morning HBP than about the clinical significance of evening HBP.. Our study included 4,310 patients recruited for the Japan Morning Surge Home Blood Pressure Study who had one or more cardiovascular risk factors. We measured morning and evening HBP, urinary albumin-creatinine ratio (UACR), left ventricular mass index (LVMI), brachial-ankle pulse wave velocity (baPWV), maximum carotid intima media thickness (IMT), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (Hs-cTnT).. The correlation coefficients for the associations between morning systolic BP (SBP) and log-transformed baPWV, NT-proBNP, or Hs-cTnT were significantly greater than the corresponding relationships for evening SBP (all P < 0.01). The goodness-of-fit of the associations between morning home SBP and UACR (P < 0.05) or baPWV (P < 0.01) was improved by adding evening home SBP to the SBP measurement. In contrast, the goodness-of-fit values of the associations between evening SBP and UACR (P < 0.001), LVMI (P < 0.05), baPWV (P < 0.001), NT-proBNP (P < 0.001), and Hs-cTnT (P < 0.001) were improved by adding morning home SBP to the SBP measurement.. Morning BP and evening BP provide equally useful information for subclinical target organ damage, yet multivariate modeling highlighted the stand-alone predictive ability of morning BP.

Topics: Aged; Albuminuria; Ankle Brachial Index; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Carotid Intima-Media Thickness; Circadian Rhythm; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

A pathological connection between the heart and kidney is well recognized as a cardiorenal syndrome, but the underlying mechanism remains undetermined. We hypothesized that this connection is attributable to central haemodynamic alterations.. In 386 patients with hypertension, the radial, carotid and femoral pressure waveforms were recorded with applanation tonometry to estimate the aortic pressure and pulse wave velocity (PWV). The plasma B-type natriuretic peptide (BNP) concentration and urinary albumin/creatinine ratio (UACR), cardiac and renal damage biomarkers, respectively, were also measured for each patient.. The BNP was correlated positively with UACR, aortic pulse pressure and PWV, but inversely with the estimated glomerular filtration rate (eGFR, P < 0.001). The aortic pulse pressure tended to more closely correlate with BNP than the brachial pulse pressure. The presence of (micro)albuminuria (UACR ≥30 mg/g) was associated with BNP elevation (≥50 pg/ml) independently of age, BMI, mean arterial pressure, eGFR and β-blocker treatment (odds ratio: 2.41; P = 0.04). However, further adjustment for the aortic pulse pressure or PWV rendered this albuminuria-BNP relationship insignificant (P = 0.25) and, instead, the aortic pulse pressure emerged as the strongest determinant of BNP elevation (odds ratio: 1.51 per 10mmHg; P = 0.001). Differently from albuminuria, lower eGFR was consistently related to higher plasma BNP, even after controlling for the aortic pressure and PWV.. Concomitant plasma BNP elevation with (micro)albuminuria can be explained by increases in aortic pulse pressure and PWV. This finding suggests that the altered central haemodynamics causes simultaneous damage/dysfunction in the heart and kidney, which could then contribute to cardiorenal syndrome in hypertension.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Aorta; Blood Pressure; Cardio-Renal Syndrome; Creatinine; Glomerular Filtration Rate; Humans; Hypertension; Middle Aged; Natriuretic Peptide, Brain

Topics: Albuminuria; Aorta; Blood Pressure; Cardio-Renal Syndrome; Humans; Hypertension; Natriuretic Peptide, Brain

Patients may develop kidney failure because of the contrast agent given during coronary angiography. Renal dysfunction and heart failure were previously shown to be associated with the development of contrast nephropathy. In our study, we aimed to investigate whether there is a relationship between subclinical renal (indicated by microalbuminuria) and/or cardiac (indicated by the height of the BNP) dysfunction between the development of contrast-induced nephropathy on patients undergoing angiography due to acute coronary syndrome.. This is an observational prospective cohort study. A total of 170 patients hospitalized with a diagnosis of acute coronary syndrome in the coronary care unit were included in this study. Blood samples were collected from 145 patients without microalbuminuria and 25 patients with microalbuminuria to determine their BNP levels before coronary angiography. The patients' urea and creatinine levels were examined before and 72 h after coronary angiography. Statistical analysis was performed using Kolmogorov-Smirnov test, Mann-Whitney U test, independent samples t-test and the chi-square test.. The study subjects included 82 females and 88 males (average age, 64.4±14.5 years). The BNP levels and height distribution of the 145 patients without microalbuminuria were compared between those with and without contrast agent-induced nephropathy, but no significant difference was found (205.6±280.6, 198.0±310.0, p=0.817). Similarly, no relationship between the microalbumin level and contrast agent-induced nephropathy was found in 25 patients.. A relationship between BNP, microalbuminuria, and contrast agent-induced nephropathy was not found in patients hospitalized in a coronary care unit with a diagnosis of acute coronary syndrome who were scheduled for coronary angiography. Additional multicenter studies with larger patient groups should be conducted to obtain more data.

Topics: Acute Coronary Syndrome; Albuminuria; Cohort Studies; Contrast Media; Coronary Angiography; Female; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

Urine albumin excretion is an important predictor of adverse cardiovascular events in various populations. Its correlation in patients with acute heart failure has not been described.. This prospective, observational study included 115 patients presenting with acute heart failure. The urine albumin/creatinine ratio (UACR) was measured from spot urine samples collected on days 1 and 7 of hospitalization. Median UACR decreased from 83 to 22 mg/gCr on days 1 and 7, respectively (P<0.0001). The proportion of patients with normoalbuminuria (UACR <30 mg/gCr) increased from 31% on day 1 to 60% on day 7, whereas the proportion with microalbuminuria (UACR between 30 and 299 mg/gCr) and macroalbuminuria (UACR ≥300 mg/gCr) decreased, respectively, from 42% and 27% on day 1 to 30% and 10% on day 7 (P<0.0001). These changes in UACR were correlated with changes in serum bilirubin and N-terminal pro b-type natriuretic peptide concentrations (correlation coefficients 1.087 and 0.384, respectively; 95% confidence interval, 0.394-1.781 and 0.087-0.680, respectively; and P=0.003 and 0.013, respectively), although they were not correlated with change in estimated glomerular filtration rate.. In this sample of patients presenting with acute heart failure, urine albumin excretion was often increased at admission to the hospital and decreased significantly within 7 days of treatment. The decrease was correlated with serum N-terminal pro b-type natriuretic peptide and bilirubin concentrations, although neither with baseline nor with changes in indices of renal function.

Topics: Acute Disease; Aged; Aged, 80 and over; Albuminuria; Bilirubin; Biomarkers; Cardio-Renal Syndrome; Comorbidity; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Humans; Japan; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Prospective Studies; Time Factors

Cardiovascular events are the most relevant events in patients with diabetes mellitus. We aimed to compare the predictive values of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the state-of-the-art marker, albuminuria, for cardiac events in diabetic patients.. In this prospective observational study we recruited 1071 patients with diabetes mellitus. NT-proBNP and albuminuria ⊟ defined as a urinary albumin/creatinine ratio >30 mg/g were measured at baseline. Patients were followed during a mean observation period of 33.1 months. A total of 103 patients reached the defined endpoint (unplanned hospitalization due to a cardiac event or death).. The mean duration of diabetes was 15 ± 12 years and the mean HbA(1c) was 7.5 ± 3.1%. At baseline, 23.7% of the patients presented with albuminuria and 36.6% had plasma NT-proBNP values >125 pg/ml. Multiple Cox regression analysis including age, gender, duration of diabetes HbA(1c), albuminuria, and lnNT-proBNP revealed that lnNT-proBNP (hazard ratio 2.314; 95% CI 1.914-2.798, p < 0.001) was a better predictor than albuminuria (HR 1.544; 95% CI 1.007-2.368, p = 0.047) or age (HR 1.030; 95% CI 1.008-1.053, p = 0.007). Calculating different Cox-models with (A) albuminuria, (B) NT-proBNP, or (C) both in the model revealed that the C-index was best if NT-proBNP was entered in the model (C-index for A 0.735, for B 0.809, and for C 0.786). Kaplan-Meier analysis demonstrated that albuminuria does not add substantial information if NT-proBNP is entered into the model.. NT-proBNP was superior to albuminuria for predicting cardiac events.

Topics: Albuminuria; Austria; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors

Kidney donors are a chronic kidney disease (CKD) cohort virtually guaranteed to have a low risk of CKD progression, as they are screened for CKD risk factors beforehand. However, there has been no evidence of cardiovascular disease (CVD), which is an outcome of CKD, for these donors. In this study, the conditions of CKD in kidney donors were investigated and the risk of CVD was estimated using nephrectomy patients, who are thought to have a crude risk of CKD progression, as a model. In 86 kidney donors, estimated glomerular filtration rates (eGFR) were measured, and they were classified according to the CKD stage. Plasma brain natriuretic peptide (BNP) concentrations and urinary albumin (mg/g Cre) levels were also measured as markers for cardiovascular evaluation. A total of 200 nephrectomy patients were similarly classified according to the CKD stage. A multivariate regression analysis was carried out to evaluate the risk factors of CVD. Among the kidney donors, 4.9% were CKD stage 1, 24.6% stage 2 and 70.5% stage 3. Among the nephrectomy patients, 20.5% were CKD stage 2, 66.6% stage 3, 9.5% stage 4 and 3.4% stage 5. Plasma BNP concentrations of the donors were significantly higher compared to those of healthy volunteers (24.5±24.9 vs. 8.6±7.6 pg/ml, p<0.0001). In addition, approximately 16% of the donors had microalbuminuria and 4% had overt proteinuria. The prevalence of new-onset CVD was 2.3% for the donors and 10% for the nephrectomy patients (p=0.0281). By logistic regression analysis of the nephrectomy patients, proteinuria, age and hypertension were significantly independent risk factors for new-onset CVD. Our findings suggest that the risks of CVD may be increased in kidney donors. In our analysis of new-onset CVD in nephrectomy patients, proteinuria, age and hypertension were significantly related factors. This suggests that in the follow-up of kidney donors, those who present these conditions from before or during follow-up should be carefully monitored.

Topics: Adult; Age Factors; Albuminuria; Cardiovascular Diseases; Chronic Disease; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Diseases; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nephrectomy; Odds Ratio; Prevalence; Proteinuria; Risk Factors; Serum Albumin; Tissue Donors

Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients.. We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross-sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p-25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS ≥400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry.. The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS ≥400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS ≥400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047).. In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD.

Topics: Adult; Aged; Albuminuria; Calcifediol; Calcinosis; Coronary Artery Disease; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Vitamin D Deficiency

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

Our aim was to assess whether home blood pressure (HBP) and ambulatory BP monitoring measurement (ABPM), in addition to office BP (OBP) predict changes of cardiovascular biomarkers during antihypertensive treatment.. Two hundred and fifty-two hypertensive patients (mean age, 68 years; men: 41%) underwent measurements of OBP, HBP, ABPM, and cardiovascular biomarkers (urinary albumin excretion (UAE) and brain natriuretic peptide (BNP)) before and after 6 months of treatment with candesartan (± thiazide-diuretics).. During the intervention, the OBP, HBP, daytime and night-time BP, and UAE levels were all significantly reduced (all P < 0.01). BNP was reduced only in the patients using diuretics (P = 0.003). For predicting the treatment-induced change in UAE, each of home systolic BP (SBP) and night-time SBP changes, but not daytime SBP change, had independent and significant value beyond OBP measurement (both P < 0.05). In contrast, for predicting the treatment-induced change in BNP, night-time SBP changes, but not home or daytime SBP changes, had significant value beyond OBP measurement (both P < 0.05). Patients who achieved a reduction in all three SBP parameters (office, home, and night-time SBP; n = 122) showed a more significant reduction of UAE compared with those who did not (-52.6 vs. -32.5%; P = 0.001), and patients who achieved a reduction in both office and night-time SBP (n = 134) showed a more significant reductions of BNP than those who did not (-12.9 vs. +12.8%; P < 0.05).. HBP and ABPM measurements, particularly night-time SBP values provide additional information for predicting treatment-induced changes of cardiovascular biomarkers when used in conjunction with office SBP measurement during antihypertensive treatment.

Topics: Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic

Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients with microalbuminuria receiving intensive multifactorial treatment.. Echocardiography including tissue Doppler imaging and P-NT-proBNP measurements were performed in 200 patients without prior CAD. Patients with P-NT-proBNP > 45.2 ng/L and/or coronary calcium score ≥ 400 were stratified as high risk patients for CAD(n = 133) and examined for significant CAD by myocardial perfusion imaging and/or CT-angiography and/or coronary angiography.. LV mass index was 41.2 ± 10.9 g/m2.7 and 48 (24%) patients had LV hypertrophy. LA and RA dilatation were found in 54(27%) and 45(23%) patients, respectively, and LV diastolic dysfunction was found in 109(55%) patients. Patients with increased P-NT-proBNP levels did not have more major echocardiographic abnormalities. In 70(53%) of 133 high risk patients significant CAD was demonstrated and patients with LV hypertrophy had increased risk of significant CAD(adjusted odd ratio[CI] was 4.53[1.14-18.06]).. Among asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment, P-NT-proBNP levels is not associated with echocardiographic abnormalities. LV diastolic dysfunction was frequently observed, whereas LV hypertrophy was less frequent but associated with significant CAD.

Topics: Aged; Albuminuria; Asymptomatic Diseases; Biomarkers; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Denmark; Diabetes Complications; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Female; Heart Atria; Humans; Hypertrophy, Left Ventricular; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Ventricular Dysfunction, Left

HIV-infected patients present accelerated cardiovascular disease (CVD) and CVD is among the most important causes of mortality in this population. We aimed to identify biomarkers and clinical factors associated with subclinical atherosclerosis in HIV-infected patients.. Carotid intima-media thickness (cIMT) and cardiovascular biomarkers were measured in 235 HIV-infected patients. Individuals with a cIMT ≥ 75th percentile or plaque were classified as having subclinical atherosclerosis and compared with patients without subclinical atherosclerosis.. Age was 46 (11) years old. Mean cIMT was 0.58 (0.13)mm. Sixty-five (27.8%) patients had subclinical atherosclerosis. These subjects had more frequently lipodystrophy (OR:2.7; CI95%:1.4-4.9), immunosuppression (OR:2.5; CI95%:1.1-5.8), longer time to HIV diagnosis (≥ p50 [10 years], OR:1.4; CI95%:1.1-2.9), longer exposure to nucleoside analogues (≥ p50 [132 months], OR:3.2; CI95%:1.7-6) and to protease inhibitors (≥ p50 [24 months], OR:2.2; CI95%:1.1-3.6). They also showed higher levels of several biomarkers such as NT-proBNP (≥ p75 [72.6 pg/ml], OR:2.0; CI95%:1-4.1) and albumin/creatinine urine ratio (≥ p50 [5mg/g], OR:3.8; CI95%:1.3-11). After the multivariate analysis, subclinical atherosclerosis was associated with age (OR:6.6; CI95%:2.2-19.5; P=.001), a longer time to HIV diagnosis (OR:3.1; CI95%:1.0-11.0; P=.044) and immunosuppression (OR:2.8; CI95%:1-8.3; P=.048).. Among HIV-infected patients, time to HIV diagnosis and immunosuppression were independently associated with subclinical atherosclerosis. Patients with subclinical atherosclerosis showed increased levels of vascular damage biomarkers, especially albumin/creatinine urine ratio and NT-proBNP.

Topics: Adult; Age Factors; Aged; Albuminuria; Asymptomatic Diseases; Atherosclerosis; Biomarkers; Blood Glucose; Carotid Intima-Media Thickness; Creatinine; Cross-Sectional Studies; Female; HIV Infections; HIV-1; Humans; Immunosuppression Therapy; Lipids; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Time Factors

To assess the impact of microalbuminuria on the development of acute kidney injury and to investigate its prognostic role at long term follow-up in 526 consecutive patients with ST elevation myocardial infarction without previously known diabetes.. Microalbuminuria was measured using immunonephelemetry in the urine collected in the night.. Patients with microalbuminuria were older (p = 0.013). They showed higher values of peak glycemia (p = 0.017), peak Tn I (p < 0.001), NT-pro BNP (p = 0.020), ESR (p = 0.003), CRP (p = 0.020), and leukocyte count (p < 0.001). Lower eGFR was observed in patients with microalbuminuria both on admission and during ICCU stay (p = 0.048 and p = 0.003, respectively). A positive correlation was observed between CRP and microalbuminuria (Spearman's rho 0.114, p = 0.024). The composite end point was observed in 73 patients (18 patients died and 59 patients developed acute kidney injury). At multivariable regression analysis, microalbuminuria was an independent predictor of acute kidney injury. At follow-up [42.6 (25th-75th percentile, 17.5-56.8) months], Kaplan-Meier curve analysis showed that patients with microalbuminuria had a lower survival rate in respect to patients without microalbuminuria. Cox regression analysis documented that microalbuminuria was an independent predictor of long term mortality (HR: 1.089; 97% CI 1.036-1.145; p < 0.001).. In a large series of STEMI patients without previously known diabetes submitted to PCI, microalbuminuria, as a marker of endothelial permeability following higher systemic inflammatory activation and larger infarct lesions, is an independent predictor for the development acute kidney injury. Furthermore, microalbuminuria identifies a subset of patients at higher risk for long term mortality.

Topics: Acute Kidney Injury; Aged; Albuminuria; Biomarkers; Blood Glucose; Blood Sedimentation; C-Reactive Protein; Chi-Square Distribution; Female; Glomerular Filtration Rate; Humans; Italy; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Troponin I

It has been suggested that troponins and natriuretic peptides can be falsely elevated in subjects with impaired kidney function because of decreased renal clearance. The value of these biomarkers in subjects with impaired kidney function has therefore been debated. We tested in a population-based cohort study, first, whether high-sensitive troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels are cross-sectionally associated with the estimated glomerular filtration rate (eGFR) and albuminuria, and secondly, whether these markers are associated with cardiovascular outcome, independent of eGFR, albuminuria and conventional cardiovascular risk factors.. We included 8121 subjects from the PREVEND study with both values of hsTnT and NT-pro-BNP available. High-sensitive troponin T >0.01 µg/L and NT-pro-BNP >125 ng/L were defined as elevated. We first performed linear regression analyses with hsTnT and NT-pro-BNP as dependent variables. Next, we performed Cox-regression analyses, studying the associations of hsTnT and NT-pro-BNP with incident cardiovascular events. Of our cohort, 6.7% had an elevated hsTnT and 12.2% an elevated NT-pro-BNP. Also, the estimated glomerular filtration rate, albuminuria, and ECG-assessed ischaemia and left ventricular hypertrophy were all significantly associated with hsTnT and NT-pro-BNP in the linear regression analyses. Both hsTnT and NT-pro-BNP appeared associated with cardiovascular events, and these associations remained significant after adjustment for eGFR, albuminuria, age, gender and conventional cardiovascular risk factors (P= 0.03 and P< 0.001, respectively). Only a few subjects with markedly reduced renal function were included. The results presented are therefore mainly valid for a population with mildly impaired renal function.. These data indicate that a finding of an increased hsTnT or NT-pro-BNP in subjects with chronic kidney disease stages 1/3 should be taken seriously as a prognostic marker for a worse cardiovascular outcome and not be discarded as merely a reflection of decreased renal clearance.

Topics: Adult; Aged; Albuminuria; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Troponin T

Recently, the role of aldosterone in metabolic syndrome (MS) has aroused interest and several reports have suggested that aldosterone blockade could be beneficial in reducing blood pressure (BP).. To examine the add-on effects of eplerenone (EP) on BP in patients with MS, 54 hypertensive patients with MS and 44 without MS were recruited. Systolic and diastolic BPs in mmHg before the initiation of EP was 144/84 ± 13/12 (MS group) and 147/85 ± 12/14 (non-MS group). Before the start of EP, all patients in both groups were treated with at least one antihypertensive drug. BPs were checked on every visit (at least every 2 months) and serum chemistries were measured every 4 months. The levels of microalbuminuria and aminoterminal pro-brain natriuretic peptide (NT pro-BNP) were determined before the start of and at the end of the study. Patients were followed for 1 year. If adverse effects were reported by patients or found in laboratory studies, EP was withdrawn.. One month after the start of EP, BPs were decreased to 140/80 ± 12/12 mmHg (MS group) versus 142/82 ± 11/12 mmHg (non-MS group) and there was no difference between the two groups. Towards the end of the study, BPs of both groups gradually decreased. At the end of the study, BPs of both groups were 129/76 ± 15/13 mmHg (MS group) versus 133/78 ± 13/11 mmHg (non-MS group). There was a significant difference in reduction of systolic BP between the two groups (p < 0.05). Add-on EP significantly decreased the levels of urinary excretion of albumin in MS patients but not in non-MS patients (p < 0.05). There was a significant correlation between reduction of systolic BP and NT pro-BNP but not microalbuminuria in the MS group (p < 0.05). There were no serious adverse effects in both groups.. EP may have some beneficial effects in lowering BP in patients with reduction of microalbuminuria.

Topics: Aged; Albuminuria; Antihypertensive Agents; Blood Pressure; Eplerenone; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Spironolactone

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

Elevated plasma N-terminal (NT)-proBNP levels and coronary calcium score (CCS) not only predicts myocardial ischaemia and coronary artery stenosis but also adverse cardiovascular events and mortality in type 2 diabetic patients with an increased urinary albumin excretion rate (UAER), whereas low levels are associated with low frequency of coronary artery disease (CAD) and good prognosis. The underlying causes of poor prognosis in patients with elevated NT-proBNP are not known; thus, we investigated the role of putative asymptomatic CAD in type 2 diabetic patients with UAER >30 mg/24 h and elevated P-NT-proBNP and/or CCS.. We identified 200 type 2 diabetic patients without known CAD and with normal creatinine levels. Patients with P-NT-proBNP >45.2 ng/L (the median P-NT-proBNP value in this cohort and in accordance with our previous findings) and/or CCS ≥ 400 were stratified as high-risk patients for CAD (n = 133) and all other patients as low-risk patients (n = 67). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109) and/or computer tomography angiography (n = 20) and/or coronary angiography (CAG; n = 86).. All patients received intensive mulitifactorial intervention. In 70 of 133 (53%) high-risk patients, significant CAD was demonstrated by MPI and/or CAG, corresponding to 35% (70/200) of the total cohort. Among high-risk patients, CCS but not P-NT-proBNP was paralleled by increased prevalence of significant CAD and in the 86 patients where CAG was performed, a CCS <100 had a negative predictive value for coronary artery stenosis of 94% (P = 0.04).. Our study revealed that >50% of asymptomatic type 2 diabetic patients with UAER >30 mg/24 h had significant CAD based on risk stratification with P-NT-proBNP and CCS. This provides some explanation to the previously reported poor prognosis in these asymptomatic patients. Optimized cardio protective treatment in these patients is warranted.

Topics: Adult; Aged; Albuminuria; Algorithms; Biomarkers; C-Reactive Protein; Calcium; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Factors; Young Adult

Plasma osteoprotegerin (P-OPG) is an independent predictor of cardiovascular disease in diabetic and other populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells and increased P-OPG may reflect arterial damage. We investigated the correlation between P-OPG and coronary artery disease (CAD) in asymptomatic type 2 diabetic patients with microalbuminuria.. P-OPG was measured in 200 asymptomatic diabetic patients without known cardiac disease. Patients with P-NT-proBNP >45.2 ng/l and/or coronary calcium score (CCS) ≥400 were stratified as high risk of CAD (n = 133), and all other patients as low risk patients (n = 67). High risk patients were examined by myocardial perfusion imaging (MPI; n = 109), and/or CT-angiography (n = 20), and/or coronary angiography (CAG; n = 86). Significant CAD was defined by presence of significant myocardial perfusion defects at MPI and/or >70% coronary artery stenosis at CAG.. Significant CAD was demonstrated in 70 of the high risk patients and of these 23 patients had >70% coronary artery stenosis at CAG. Among high risk patients, increased P-OPG was an independent predictor of significant CAD (adjusted odds ratio [CI] 3.11 [1.01-19.54] and 3.03 [1.00-9.18] for second and third tertile vs.first tertile P-OPG, respectively) and remained so after adjustments for NT-proBNP and CCS. High P-OPG was also associated with presence of >70% coronary artery stenosis(adjusted odds ratio 14.20 [1.35-148.92] for third vs. first tertile P-OPG), and 91% of patients with low (first tertile) P-OPG did not have >70% coronary artery stenosis.. Elevated P-OPG is an independent predictor of the presence of CAD in asymptomatic type 2 diabetic patients with microalbuminuria.

Topics: Adult; Aged; Albuminuria; Biomarkers; Calcium; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Risk Factors

Intensive multifactorial treatment aimed at cardiovascular (CV) risk factor reduction in type 2 diabetic patients with microalbuminuria can diminish fatal and non-fatal CV. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the utility of P-NT-proBNP in screening for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment.. P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score≥400, carotid intima-media thickness (CIMT)>0.90 mm, ankle-brachial index<0.90, and/or toe-brachial index<0.64, respectively. Carotid artery compliance was also determined and the reactive hyperaemia index (RHI) measured by peripheral artery tonometry was used as a surrogate for endothelial function.P-NT-proBNP was associated with atherosclerosis in the unadjusted analysis, but not after adjustment for conventional risk factors. P-NT-proBNP was not associated with vascular dysfunction. The prevalence of atherosclerosis in the coronary, carotid and peripheral arteries was 35%, 10% and 21% of all patients, respectively. In total 49% had atherosclerosis in one territory and 15.6% and 1.0% in two and three territories. Low RHI was an independent predictor of coronary atherosclerosis (odds ratio [CI], 2.60 [1.15-5.88] and systolic blood pressure was the only independent determinant of CIMT (0.02 mm increase in CIMT per 10 mmHg increase in systolic blood pressure [p=0.003]).. Half of asymptomatic patients with type 2 diabetes mellitus and microalbuminuria had significant atherosclerosis in at least one vascular territory despite receiving intensive multifactorial treatment for CV risk reduction. Coronary atherosclerosis was most prevalent, whereas carotid disease was more rarely observed. RHI but not plasma NT-proBNP was predictive of coronary atherosclerosis.

Topics: Aged; Albuminuria; Ankle Brachial Index; Biomarkers; Carotid Arteries; Carotid Intima-Media Thickness; Comorbidity; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Hyperemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Factors

To evaluate the changes of plasma levels of N-terminal pro-brain natriuretic pepide (NT-proBNP) and microalbuminuria (MAU) in patients with heart failure and the correlation between them.. Ninety-one patients with heart failure were divided into different groups according to different stages of heart failure. Plasma levels of NT-proBNP were measured by microsome enzyme immunoassay (MEIA). Plasma levels of MAU were determined by immune scattering turbidimetry (ICTM). Simultaneously, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were measured by Doppler echocardiography for all patients. The correlation of NT-proBNP and MAU was evaluated at different stages of heart failure.. The plasma levels of NT-proBNP and MAU increased with the severity of heart failure. There was a high correlation between NT-proBNP and MAU (r = 0.885, p < 0.001).. Both NT-proBNP and MAU levels were closely associated with the severity of heart failure.

Topics: Aged; Albuminuria; Analysis of Variance; Biomarkers; Echocardiography, Doppler; Female; Heart Failure; Heart Function Tests; Humans; Immunoenzyme Techniques; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Severity of Illness Index

In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt-proBNP), related to hemodynamic cardiovascular risk factors, high sensitivity C-reactive protein (hsCRP), related to metabolic cardiovascular risk factors and urine albumin/creatinine ratio (UACR), related to hemodynamic as well as metabolic risk factors. In healthy subjects with a 10-year risk of cardiovascular death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified a larger subgroup of 16% with high cardiovascular risk in which primary prevention may be advised despite low-moderate cardiovascular risk based on HeartScore. Furthermore, combined use of high UACR or high Nt-proBNP in subjects with known cardiovascular disease or diabetes identified a large subgroup of 48% with extremely high cardiovascular risk who should be referred for specialist care to optimize treatment.

Topics: Adult; Aged; Aging; Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Diabetes Complications; Early Diagnosis; Female; Follow-Up Studies; Glycoproteins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Serum Albumin; Serum Albumin, Human; Severity of Illness Index; Sex Factors

Congestive heart failure (CHF) has been associated with elevated biomarker levels reflecting chronic low-grade inflammation. YKL-40 is a biomarker with increasing levels in patients with cardiovascular disease (CVD) of increasing severity. Furthermore, YKL-40 is associated with all-cause and cardiovascular mortality. We investigated plasma YKL-40 levels in patients with CHF and evaluated the possible predictive value with respect to overall mortality and recurrent cardiovascular outcomes.. Plasma YKL-40 was measured in 194 CHF patients and in 117 age-matched individuals without CVD.. Median YKL-40 levels were approximately 77% higher in patients with CHF (106 (IQR, 66-184) ng/ml vs. 60 (IQR, 42-97) ng/ml, p < 0.0001). We found a trend towards an association of YKL-40 levels with urinary albumin/creatinine ratio (UACR) (beta = 0.12, p = 0.08). YKL-40 levels were not predictive of overall mortality (p = 0.59), major cardiovascular events (p = 0.23) or events of incompensation (p = 0.56).. Plasma YKL-40 levels are elevated in patients with CHF but show no association with other clinical or paraclinical variables. YKL-40 levels were not predictive of overall mortality or incident cardiovascular events. Most likely, elevated YKL-40 levels in CHF patients are explained by the presence of concomitant diseases but a role of YKL-40 in low-grade inflammation is not excluded.

Topics: Adipokines; Aged; Albuminuria; Biomarkers; C-Reactive Protein; Case-Control Studies; Chitinase-3-Like Protein 1; Chronic Disease; Comorbidity; Creatinine; Denmark; E-Selectin; Female; Glycoproteins; Heart Failure; Humans; Lectins; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Up-Regulation; von Willebrand Factor

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

The objective of this study was to assess a possible link between microalbuminuria (MA), a major risk factor of the cardiorenal syndrome and the brain natriuretic peptide (BNP), a marker of cardiac hypertrophy. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (weighing 220-250 g). Rats were randomized into four groups for 8 weeks: Sham, not treated; Bos, treated with bosentan; Cap, treated with captopril; Bos/Cap, treated with both drugs. Blood pressure, plasma BNP and transforming growth factor beta1 (TGF-β1) concentrations, microalbuminuria and creatininemia as well as cardiac mass, BNP, alpha- and beta-myosin heavy chain (MHC) gene expression and kidney histology were determined. Following stenosis, Sham rats developed hypertension (p < 0.001), an increase in BNP (p < 0.05) and TGF-β1 (p < 0.005) concentrations, creatinine levels (p < 0.001), and urinary albumin (p < 0.001). Under drug treatment, decreases in blood pressure (p < 0.001), creatinine levels (p < 0.05), plasma TGF-β1 (p < 0.005) and BNP (p < 0.05) concentrations, were concomitant with the absence of MA which was significantly correlated with reductions in cardiac mass (p < 0.05) and hypertrophy markers (BNP and β-MHC gene expression) (p < 0.005) as well as in renal fibrosis. These findings suggest a potential link between microalbuminuria evolution and BNP as well as a possible effect of microalbuminuria-lowering therapy on halting the progression, or even inducing the regression of cardiac hypertrophy.

Topics: Albuminuria; Animals; Blood Pressure; Cardiomegaly; Creatinine; Hypertension; Hypertension, Renovascular; Male; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1

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

Several biological pathways are activated in ventricular remodeling and in overt heart failure (HF). There are no data, however, on the incremental utility of a parsimonious set of biomarkers (reflecting pathways implicated in HF) for predicting HF risk in the community.. We related a multibiomarker panel to the incidence of a first HF event in 2754 Framingham Heart Study participants (mean age, 58 years; 54 women) who were free of HF and underwent routine assays for 6 biomarkers (C-reactive protein, plasminogen activator inhibitor-1, homocysteine, aldosterone-to-renin ratio, B-type natriuretic peptide, and urinary albumin-to-creatinine ratio). We estimated model c statistic, calibration, and net reclassification improvement to assess the incremental predictive usefulness of biomarkers. We also related biomarkers to the incidence of nonischemic HF in participants without prevalent coronary heart disease. On follow-up (mean, 9.4 years), 95 first HF events occurred (54 in men). In multivariable-adjusted models, the biomarker panel was significantly related to HF risk (P=0.00005). On backward elimination, B-type natriuretic peptide and urinary albumin-to-creatinine ratio emerged as key biomarkers predicting HF risk; hazards ratios per 1-SD increment in log marker were 1.52 (95 confidence interval, 1.24 to 1.87) and 1.35 (95 confidence interval, 1.11 to 1.66), respectively. B-type natriuretic peptide and urinary albumin-to-creatinine ratio significantly improved the model c statistic from 0.84 (95 confidence interval, 0.80 to 0.88) in standard models to 0.86 (95 confidence interval, 0.83 to 0.90), enhanced risk reclassification (net reclassification improvement=0.13; P=0.002), and were independently associated with nonischemic HF risk.. Using a multimarker strategy, we identified B-type natriuretic peptide and urinary albumin-to-creatinine ratio as key risk factors for new-onset HF with incremental predictive utility over standard risk factors.

Topics: Aged; Albuminuria; Aldosterone; Biomarkers; C-Reactive Protein; Creatinine; Female; Follow-Up Studies; Heart Failure; Homocysteine; Humans; Male; Middle Aged; Models, Statistical; Natriuretic Peptide, Brain; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Renin; Risk Factors

To investigate the relationship between B-type natriuretic peptides (BNP) and subclinical target organ damage in essential hypertensive (EH) patients.. A total of 317 EH patients were divided into 3 groups according to BNP levels, namely normal (BNP<600 ng/L) group (n=102), moderate (600-883.5 ng/L) group (n=116), and elevated BNP (>883.5 ng/L) group (n=99). The blood pressure, left ventricular mass index (LVMI), the intima media thickness (IMT) of the common carotid artery, the plaque size in the coronary artery (CS) and microalbuminuria levels were analyzed in these patients.. The EH patients with moderate and elevated BNP showed significantly higher LVMI, IMT, CS and microalbuminuria levels than those with normal BNP level (LVMI: 102.8∓23.12 and 123.9∓26.47 vs 91.09∓18.71 g/m2; IMT: 0.95∓0.32 and 1.16∓0.37 vs 0.84∓0.28 mm; microalbuminuria: 31.36∓20.55 and 36.73∓22.07 vs 23.21∓18.68, P<0.01). After adjustment, BNP was positively correlated to LVMI, IMT, CS and microalbuminuria level (r=0.45, 0.43, 0.39 and 0.41, respectively, P<0.01). Multivariate logistic regression analysis showed that age, systolic blood pressure, BNP, FPG, and microalbuminuria, LDL-C, and BMI were all related to the occurrence of subclinical target organ damages.. BNP is positively correlated to subclinical target organs damages in EH patients.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Carotid Artery, Common; Carotid Intima-Media Thickness; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain

Traditional risk factors do not adequately identify individuals at risk for CKD. We related a multi-marker panel consisting of the following seven circulating biomarkers to the incidence of CKD and microalbuminuria (MA) in 2345 participants who attended the sixth Framingham Offspring Study examination (1995 to 1998): C-reactive protein, aldosterone, renin, B-type natriuretic peptide (BNP), plasminogen-activator inhibitor type 1, fibrinogen, and homocysteine. We defined CKD at follow-up (2005 to 2008) as estimated GFR (eGFR) <60 ml/min per 1.73 m²; we defined MA as urine albumin-to-creatinine ratio ≥25 (women) or 17 (men) mg/g on spot urine samples. We identified a parsimonious set of markers related to outcomes adjusting for standard risk factors and baseline renal function, and we assessed their incremental predictive utility. During a mean 9.5-year follow-up, 213 participants developed CKD and 186 developed MA. In multivariable logistic regression models, the multi-marker panel was associated with incident CKD (P < 0.001) and MA (P = 0.003). Serum homocysteine and aldosterone both were significantly associated with CKD incidence, and log-transformed aldosterone, BNP, and homocysteine were significantly associated with incident MA. Biomarkers improved risk prediction as measured by improvements in the c-statistics for both CKD and MA and by a 7% increase in net risk reclassification. In conclusion, circulating homocysteine, aldosterone, and BNP provide incremental information regarding risk for incident CKD and MA beyond traditional risk factors.

Topics: Aged; Albuminuria; Aldosterone; Biomarkers; C-Reactive Protein; Causality; Cohort Studies; Comorbidity; Creatinine; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renin; Severity of Illness Index

Microalbuminuria (MAU), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) are risk markers used to predict the prognosis of hypertensive patients; however, they have not been prospectively evaluated in primary care. An investigation was conducted using i-SEARCH Plus, a registry documenting 1649 patients with hypertension who received irbesartan at office-based cardiologists over 12 months. Mean age at baseline was 61.4±11.3 years, 43.2% were women, and blood pressure was 159.8±20.1/93.4±11.9mm Hg. Median albumin/creatinine ratio (ACR) at baseline was 9.90 (interquartile range [IQR], 5.76--25.52) mg/g, hsCRP 2.46 (IQR, 1.16--5.14) mg/L, and NT-proBNP 89.28 (IQR, 38.63-203.40) pg/mL. In patients with MAU (ACR ≥20mg/g), the age-adjusted risk of a combined end point of newly diagnosed coronary artery disease (CAD), myocardial infarction, stroke/transitory ischemic attack, and death at 12-month follow-up was increased (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.49-4.76), as was the incidence of CAD (OR, 3.27; 95%CI, 1.39-7.68) and death (OR, 4.63; 95%CI, 1.44-14.94). No correlations with end points were found for hsCRP or NT-proBNP after adjusting for age and the presence of MAU. MAU is an independent predictor of cardiovascular events in hypertensive patients. These findings confirm previous reports on the prognostic value of MAU and establish its incremental value over hsCRP and NT-proBNP.

Topics: Aged; Albuminuria; Antihypertensive Agents; Biomarkers; Biphenyl Compounds; C-Reactive Protein; Cardiovascular Diseases; Coronary Artery Disease; Female; Follow-Up Studies; Humans; Hypertension; Irbesartan; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Registries; Risk Factors; Stroke; Tetrazoles

The study aim was to determine whether urine albumin/creatinine ratio (UACR), high-sensitivity C-reactive protein (hsCRP) or N-terminal pro-brain natriuretic peptide (Nt-proBNP) added to risk prediction based on HeartScore and history of diabetes or cardiovascular disease. A Danish population sample of 2460 individuals was divided in three groups: 472 subjects receiving cardiovascular medication or having history of diabetes, prior myocardial infarction or stroke, 559 high-risk subjects with a 10-year risk of cardiovascular death above 5% as estimated by HeartScore, and 1429 low-moderate risk subjects with estimated risk below 5%. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (CEP) occurred in 204 subjects. CEP was predicted in all three groups by UACR (HRs: 2.1, 2.1 and 2.3 per 10-fold increase, all P<0.001) or by hsCRP (HRs: 1.9, 1.9 and 1.7 per 10-fold increase, all P<0.05), but not by Nt-proBNP (HRs: 1.1, 2.6 and 3.7 per 10-fold increase, last two P<0.001) (P<0.05 for interaction). In the low-moderate risk group, pre-specified gender adjusted (men/women) cutoff values of UACR> or =0.73/1.06 mg mmol(-1) or hsCRP> or =6.0/7.3 mg l(-1) identified a subgroup of 16% who experienced one-third of the CEPs. In the patient group, combined absence of high UACR and high Nt-proBNP> or =110/164 pg ml(-1) (men/women) identified a subgroup of 52% who experienced only 15% of the CEPs. Additional use of UACR and hsCRP in subjects with low-moderate risk and UACR and Nt-proBNP in subjects with known diabetes of cardiovascular disease changed HeartScore risk classification significantly in 19% of the population.

Topics: Adult; Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Creatine; Female; Health Status Indicators; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Assessment

Although the metabolic syndrome (MetS) is positively associated with high-sensitivity C-reactive protein (hsCRP), negatively associated with N-terminal pro-brain natriuretic peptide (Nt-proBNP) and inconsequently related to urine albumin/creatinine ratio (UACR) they are all associated with cardiovascular events. Therefore, we wanted to determine the influence of MetS on the predictive values of UACR, hsCRP and Nt-proBNP. On the basis of the definition of MetS by the International Diabetes Federation, a Danish population sample of 1983 apparently healthy subjects was divided into three groups: 530 subjects without any elements of MetS, 1093 subjects with some elements of MetS and 360 subjects with MetS. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (composite cardiovascular end point, CEP) occurred in 204 subjects. In Cox-regression analyses adjusting for age, gender and smoking, all three cardiovascular risk markers predicted CEP independently of MetS. Despite no significant interaction with MetS, high log(hsCRP) was associated with CEP primarily in subjects without any elements of MetS (hazard ratio (HR)=4.5 (1.5-14.0), P<0.01), log(Nt-proBNP) primarily in subjects with some elements of MetS (HR=3.0 (1.6-5.6), P<0.01), and logUACR independently of elements of MetS. Pre-specified gender-adjusted (men/women) cutoff values of hsCRP > or = 6.0/7.3 mg l(-1) predicted CEP in subjects without elements of MetS with positive and predictive values of 11.5 and 98%, respectively. UACR > or = 0.73/1.06 mg mmol(-1) predicted CEP in subjects with MetS with positive and predictive values of 23.5 and 93%, respectively. In apparently healthy subjects, high hsCRP was associated with CEP primarily in subjects without MetS, high Nt-proBNP in subjects with elements of MetS and UACR independently of MetS.

Topics: Adult; Aged; Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Regression Analysis; Risk Factors

Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated the impact of age and sex on their prognostic performance in a subgroup of 1994 apparently healthy individuals without diabetes, previous stroke or myocardial infarction, who did not receive any cardiovascular, antidiabetic or lipid-lowering medication.. In 1993-1994 we recorded cardiovascular risk factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years.. In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P < 0.05) and age (P < 0.05), respectively. The effect of logUACR was not significantly modulated by age or sex. Log(hsCRP)/SD did not predict CEP in women, but did predict CEP in 41 plus 51-year-old men [hazard ratio (HR) 1.71; 95% confidence interval, 1.1-2.6; P < 0.05] and 61 plus 71-year-old men (HR 1.64; 1.3-2.2; P < 0.001). Log(Nt-proBNP)/SD predicted CEP in 61 plus 71-year-old women (HR 1.74; 1.2-2.5; P < 0.01) and in 61 plus 71-year-old men (HR 1.58; 1.3-2.0; P < 0.001).. Elevated hsCRP, reflecting early atherosclerosis, predicted CEP even in 41 plus 51-year-old men. Elevated Nt-proBNP, reflecting subclinical cardiovascular damage, predicted CEP in 61 plus 71-year-old subjects. Elevated UACR, reflecting endothelial dysfunction as well as microvascular damage, predicted events independently of age and sex, but primarily in 61 plus 71-year-old subjects.

Topics: Adult; Age Factors; Aged; Albuminuria; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Denmark; Echocardiography; Female; Follow-Up Studies; Health Surveys; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Regression Analysis; Risk Factors; Sensitivity and Specificity; Sex Factors

To measure left ventricular mass (LVM), left ventricular volumes, and left ventricular function (LVF) in a cohort of type 1 diabetic patients and to correlate measures of imaging to NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP).. In a cross-sectional study, all patients with type 1 diabetes underwent cardiovascular magnetic resonance imaging. We included 63 patients with diabetic nephropathy and 73 patients with normoalbuminuria.. All patients had normal global LVF. LVM was increased in patients with diabetic nephropathy compared with patients with persistent normoalbuminuria. Patients with nephropathy had smaller left ventricular volumes and increased levels of NT-proBNP. Linear regression analysis in patients with diabetic nephropathy showed that NT-proBNP and creatinine were associated with LVM.. Increased LVM is identified in asymptomatic type 1 diabetic patients with nephropathy compared with normoalbuminuric patients. Elevated levels of NT-proBNP were associated with increased LVM, which are both markers of increased cardiovascular risk.

Topics: Adult; Age of Onset; Albuminuria; Body Mass Index; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left

Hyperuricaemia is a constant finding in patients with heart failure (HF). Upregulated xanthine-oxidase activity seems to contribute to progression of the disease through the production of oxidative stress and the development of vascular and endothelial dysfunction. On this basis we speculated that in HF serum uric acid levels correlated with a reliable marker of endothelial dysfunction as urinary albumin excretion.. Fifty-three patients with HF underwent assessment of serum uric acid, N-terminal probrain natriuretic peptide (NT-proBNP), glomerular filtration rate (GFR), other metabolic parameters and determination of urinary albumin concentration (UAC) in a morning urine sample.. In univariate analysis there is a direct correlation between serum uric acid levels and log UAC (r = 0.43, P < 0.01); uric acid correlates also positively with log NT-proBNP (r = 0.31, P < 0.05) and negatively with log-GFR (r = -0.38, P < 0.01). In stepwise regression analysis serum uric acid emerged as the only predictor of increased UAC (standardized coefficient = 0.42, P = 0.001) independent of other clinical determinants and metabolic factors.. Serum uric acid represents the strongest predictor of elevated UAC in HF. Regression of albuminuria may be a simple target to verify the efficacy of xanthine-oxidase inhibition in these patients.

Topics: Aged; Albuminuria; Biomarkers; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Hyperuricemia; Male; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index; Uric Acid

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 authors examined the relationship of clinic and self-measured pulse pressure with target organ damage in 597 treated hypertensive patients without clinical evidence of renal dysfunction or a history of heart failure. The cross-sectional relationships of plasma brain natriuretic peptide (BNP) and urinary albumin/creatinine ratio with clinic and self-monitored pulse pressures were estimated in age tertile groups: younger than 67 years (n=193), 67 to 75 years (n=216), and older than 75 years (n=188), controlling for various confounding factors. In multivariable analyses, both clinic and self-monitored higher pulse pressures were associated with increased urinary albumin/creatinine ratio in all 3 age groups. Self-monitored higher pulse pressure, but not clinic pulse pressure, was consistently associated with increased BNP in the younger and middle-aged patients. In the very old (older than 75 years), however, there were no consistent associations between pulse pressure measures and BNP. More studies are needed in the evaluation of cardiac risk with hemodynamic measures in the very old.

Topics: Age Factors; Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Creatine; Female; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Statistics as Topic

Cardiovascular risk markers like microalbuminuria (MAU), highly sensitive C-reactive protein (hsCRP) and brain natriuretic peptide (BNP) currently gain importance to estimate risk in trials and clinical practice. Blockade of the renin-angiotensin system (RAS) has been shown to reduce some of these risk markers in clinical trials, but validation of their time course and role in clinical practice is still pending.. To fill this gap, the design of a nationwide registry study was chosen in which patients attending their cardiologist were observed for 12 months and the effect of blocking the RAS with the angiotensin II receptor blocker irbesartan was documented. Primary question: risk for mortality and the incidence of cardiovascular events in relation to baseline values of MAU, hsCRP, and BNP. Secondary questions: correlations between cardiovascular risk markers (1) amongst each other with respect to cardiovascular events, (2) with clinical findings (echocardiography, electrocardiogram), (3) with the heart rate, (4) with further metabolic parameters (blood sugar, HbA(1c), etc.), and (5) with blood pressure control.. Until April 1, 2006, 2,149 patients were recruited in 305 centers in Germany. Patients had a mean age of 61.4 (+/- 11.3) years. Waist circumference was 103.6 (+/- 13.5) cm. 95.1% of all patients had arterial hypertension at inclusion (> or = 140/90 mmHg). The mean value for albumin/creatinine was 68.9 (+/- 307.5) mg/g (n = 2,100), for hsCRP 4.6 (+/- 8.3) mg/l (n = 2,136), and for proBNP 236.5 (+/- 557.3) pg/ml (n = 2,138).. The present register will elucidate the time course and the interdependence of the cardiovascular risk markers MAU, hsCRP and proBNP as well as their prediction of cardiovascular endpoints in hypertensive individuals. In addition, the role of RAS-blocking agents will be evaluated. A valuable contribution to estimate risk and to optimize care for cardiovascular high-risk patients in clinical practice can be expected.

Topics: Adult; Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biphenyl Compounds; C-Reactive Protein; Cardiovascular Diseases; Cause of Death; Creatinine; Female; Follow-Up Studies; Germany; Humans; Hypertension; Irbesartan; Male; Middle Aged; Natriuretic Peptide, Brain; Registries; Risk Factors; Survival Rate; Tetrazoles

Pulse pressure (PP) is an independent marker of cardiovascular risk, even in treated hypertensive subjects, but is often little changed by antihypertensive treatment. We assessed the hypothesis that changes in PP during antihypertensive therapy correlate with changes in surrogate markers of target-organ damage.. We studied 540 treated hypertensive subjects whose home systolic blood pressure (SBP) was >/=135 mm Hg. They were followed for 6 months after allocation to either a control group or an added treatment group (doxazosin, 1 to 4 mg plus beta-blocker when needed). The changes in PP and various blood pressure (BP) measures, including mean BP (MP), SBP, and diastolic BP (DBP) during follow-up, were related to changes in plasma B-type natriuretic peptide (BNP) and the urine albumin-creatinine ratio (UAR).. Although self-measured MP was significantly lowered in the added treatment group, PP was not changed overall, although some patients showed a decrease, and others showed an increase. In multivariable analyses, changes in both clinic and home PP were positively associated with changes in log BNP, such that increases in clinic and home PP were paralleled by corresponding increases in BNP. However, no such corresponding relationships were observed when home PP decreased. The change in home PP, but not clinic PP, was positively and linearly associated with the change in UAR.. Changes in PP during antihypertensive treatment are important because PP may increase in some patients, in whom there are adverse changes in surrogate markers of target-organ damage. These changes of PP are best evaluated by home monitoring.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.

Topics: Albuminuria; Antihypertensive Agents; Blood Pressure Determination; Circadian Rhythm; Clinical Protocols; Creatine; Doxazosin; Humans; Hypertension; Japan; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic

1. Chronic renal disease is associated with oxidative stress, reduced nitric oxide (NO) availability and soluble guanylate cyclase (sGC) dysfunction. Recently, we discovered BAY 58-2667, a compound activating heme-deficient or oxidized sGC in a NO-independent manner. 2. We assessed potential of BAY 58-2667 in preventing cardiac and renal target organ damage in rats with 5/6 nephrectomy. 3. Male Wistar rats were allocated to three groups: 5/6 nephrectomy, 5/6 nephrectomy treated with BAY 58-2667 and sham operation. Study period was 18 weeks: blood pressure and creatinine clearance were assessed repeatedly. At study end blood samples were taken and hearts and kidneys harvested for histological studies. 4. BAY 58-2667 markedly lowered blood pressure in animals with 5/6 nephrectomy (untreated versus treated animals: 189+/-14 versus 146+/-11 mmHg, P<0.001). Left ventricular weight, cardiac myocyte diameter as well as cardiac arterial wall thickness significantly decreased in comparison to untreated animals with 5/6 nephrectomy. Natriuretic peptide plasma levels were also improved by BAY 58-2667. Kidney function and morphology as assessed by creatinine clearance, glomerulosclerosis, interstitial and perivascular fibrosis of intrarenal arteries were likewise significantly improved by BAY 58-2667. 5. This is the first study showing that BAY 58-2667 effectively lowers blood pressure, reduces left ventricular hypertrophy and slows renal disease progression in rats with 5/6 nephrectomy by targeting mainly oxidized sGC. Therefore, BAY 58-2667 represents a novel pharmacological principle with potential clinical value in treatment of chronic renal disease.

Topics: Albuminuria; Animals; Benzoates; Blood Pressure; Creatinine; Disease Progression; Guanylate Cyclase; Kidney; Kidney Diseases; Male; Myocardium; Natriuretic Peptide, Brain; Nephrectomy; Nitric Oxide; Rats; Rats, Wistar

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

B-type natriuretic peptides have been shown to predict cardiovascular disease in apparently healthy individuals but their predictive ability for mortality and future cardiovascular events compared with C-reactive protein (CRP) and urinary albumin/creatinine ratio is unknown.. To assess the prognostic value of the N-amino terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) vs CRP and urinary albumin/creatinine ratio in an older adult population.. A population-based prospective study of 764 participants aged 50 to 89 years from a community in Copenhagen, Denmark, in which 658 participants provided blood and urinary samples and were examined between September 1, 1998, and January 24, 2000. Of these participants, 626 without heart or renal failure were enrolled. A subgroup of 537 had no history of cardiovascular disease at baseline. During 5 years of follow-up (to December 31, 2003), 94 participants died and 65 developed a first major cardiovascular event.. Risk of mortality and first major cardiovascular event by baseline levels of NT-proBNP, CRP, and urinary albumin/creatinine ratio levels.. After adjustment for the cardiovascular risk factors of age, sex, smoking, diabetes mellitus, hypertension or ischemic heart disease, total cholesterol, and serum creatinine, the hazard ratio (HR) of mortality for values above the 80th percentile of NT-proBNP was 1.96 (95% confidence interval [CI], 1.21-3.19); for CRP, 1.46 (95% CI, 0.89-2.24); and for urinary albumin/creatinine ratio, 1.88 (95% CI, 1.18-2.98). Additional adjustment for left ventricular systolic dysfunction did not markedly attenuate the predictive value of NT-proBNP (HR, 1.82; 95% CI, 1.11-2.98). The absolute unadjusted increase in mortality risk for participants with values above the 80th percentile vs equal to or below the 80th percentile was 24.5% for NT-proBNP, 7.8% for CRP, and 19.5% for urinary albumin/creatinine ratio. The NT-proBNP levels were associated with first major cardiovascular events (nonfatal myocardial infarction, fatal coronary heart disease, unstable angina, heart failure, stroke, and transient ischemic attack) with an adjusted HR of 3.24 (95% CI, 1.80-5.79) vs 1.02 (95% CI, 0.56-1.85) for CRP and 2.32 (95% CI, 1.33-4.05) for urinary albumin/creatinine ratio when comparing participants with values above the 80th percentile with those with values equal to or below the 80th percentile.. Measurements of NT-proBNP provide prognostic information of mortality and first major cardiovascular events beyond traditional risk factors. NT-proBNP was a stronger risk biomarker for cardiovascular disease and death than CRP was in nonhospitalized individuals aged 50 to 89 years.

Topics: Aged; Aged, 80 and over; Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Denmark; Female; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Assessment; Survival Analysis

Topics: Aged; Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Risk Assessment

This study investigates whether the plasma brain natriuretic peptide (BNP) level is increased by the clinical traits of diabetes, including its complications, and whether these levels are affected by the presence of other combined diseases such as hypertension, hyperlipidemia, and coronary heart disease (CHD) in patients with diabetes. In 223 patients with Type 2 diabetes, the mean value of plasma BNP reached 32.3+/-4.1 pg/mL. The levels significantly increased with age, hypertension, and CHD but not with the duration of diabetes, HbA1c level, or hyperlipidemia. With regard to the type of therapy, the BNP levels were significantly lower in the combinations of both sulfonylurea and metformin and sulfonylurea and pioglitazone than those in insulin alone. In addition, the BNP levels in the group with diabetic complications, including retinopathy and nephropathy, and macroalbuminuria were significantly elevated in comparison with those without these complications and macroalbuminuria. Interestingly, however, no difference was observed between these groups after removal of the values in patients with CHD. These results have clarified that the plasma BNP levels in diabetic patients could increase only by the progression of macrovascular diseases, such as CHD, but not by the current diabetic control or diabetic microvascular complications.

Topics: Age Factors; Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain

Topics: Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Female; Humans; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Risk Assessment

Microalbuminuria is associated with increased risk for cardiovascular morbidity and mortality. However, the relation between microalbuminuria and chronic heart failure has not been well described yet. In this cross-sectional study, we aim to evaluate the prevalence of microalbuminuria and the association with neurohormonal parameters in severe chronic heart failure patients.. We studied 94 stable chronic heart failure patients (New York Heart Association class III/IV) receiving therapy with angiotensin-converting enzyme (ACE) inhibitors for over three months. In all patients, renal function and neurohormonal status were evaluated and correlated with urinary albumin/creatinine ratio. The studied population consisted of 70 men and 21 women (mean age 69 +/- 12 years). Ischemia was the underlying cause of heart failure in 61 patients. Overall, 100% of the patients were treated with an ACE inhibitor, 72% with a beta-blocker, and 47% with spironolactone. In 32% (95% confidence interval 22-42) of the patients, microalbuminuria was present, which is significantly higher than in the general population. However, we found no significant association between the presence of microalbuminuria and renal function. Plasma NT-proBNP, active renin protein, angiotensin I, angiotensin II, and aldosterone did not differ significantly between groups with and without microalbuminuria.. In 32% of the patients, microalbuminuria was present. No association was found with either renal or neurohormonal parameters.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Albuminuria; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prevalence; Renin; Research Design; Spironolactone; Treatment Outcome

Plasma N-terminal pro-brain natriuretic peptide (NT proBNP) is produced and released from cardiac ventricles; it is elevated in patients with heart failure, hypertension and chronic renal failure. This study aimed to examine the plasma levels of NT proBNP and their relationship in Type 1 diabetic patients with and without diabetic nephropathy.. We developed a non-competitive immunoluminometric assay with in-house antibodies to the N- and C-terminal domains of NT proBNP. We compared NT proBNP levels between 47 normoalbuminuric patients (group 1), 12 microalbuminuric patients (group 2) and 12 patients with macroalbuminuria (group 3).. There were significant differences in 24-h systolic and diastolic blood pressure, diabetes duration, serum creatinine, LDL-cholesterol and HbA1c between the three groups; other parameters did not differ significantly. NT proBNP (median and range) levels were 5 (0.75-68), 22 (0.75-82) and 23 (0.75-374) fmol/ml for groups 1-3, respectively. Log-transformed data of NT proBNP were used to compare all three groups (P=0.016). The Pearson correlation between NT proBNP and albuminuria (R=0.27; P=0.02) was positive; HbA1c (R=0.25; P=0.03) and age (R=0.33; P=0.005) correlated significantly as well. On the basis of multiple regression analysis, the adjusted difference remained significant between the three groups.. This is the first demonstration that NT proBNP levels are significantly higher in Type 1 diabetic patients with albuminuria. This may be caused by a down-regulation of A-type guanylate cyclase-coupled natriuretic peptide receptors in renal tubules or by elevated NT proBNP levels leading to higher glomerular hydraulic pressure or higher capillary permeability and possibly increased albumin excretion. Further studies are required to investigate the potential role of NT proBNP in patients with diabetic nephropathy and such other co-morbidities as cardiovascular disease.

Topics: Adult; Albuminuria; Blood Pressure; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Down-Regulation; Female; Humans; Immunoassay; Male; Natriuretic Peptide, Brain; Regression Analysis

We investigated plasma brain natriuretic polypeptide (BNP) in Type 2 NIDDM patients with albuminuria. This study involved normal control subjects (Controls), hypertensive patients without diabetes mellitus (HT) and Type 2 NIDDM patients. Diabetic patients were divided into 4 groups by urinary albumin index (Alb-I): group I <30; group II 30-149; group III 150-300; group IV >300 mg/g creatinine. BNP levels in group III or IV were significantly higher than in Controls. The diabetic patients were re-divided into 4 groups (DM: with neither diabetic retinopathy (which was one of indicators of microangiopathy) nor hypertension, DM+HT: without diabetic retinopathy and with hypertension, DM+R: with diabetic retinopathy and without hypertension and DM+R+HT: with both diabetic retinopathy and hypertension). The Alb-I levels in DM+HT and DM+R+HT were significantly higher than the Controls, indicating the development of diabetic nephropathy in those groups. BNP levels in DM+HT, DM+R or DM+R+HT were significantly higher than in Controls. This indicates that BNP levels elevate in diabetic patients with increased albuminuria due to hypertension or microangiopathy deteriorating diabetic nephropathy. Elevated plasm BNP may play a pathophysiological role in the development of diabetic nephropathy.

Topics: Albuminuria; Atrial Natriuretic Factor; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glycated Hemoglobin; Humans; Middle Aged; Natriuretic Peptide, Brain

One of major causes of end-stage renal disease is glomerulonephritis, the treatment of which remains difficult clinically. It has already been shown that transgenic mice that overexpress brain natriuretic peptide (BNP), with a potent vasorelaxing and natriuretic property, have ameliorated glomerular injury after subtotal nephrectomy. However, the role of natriuretic peptides in immune-mediated renal injury still remains unknown. Therefore, the effects of chronic excess of BNP on anti-glomerular basement membrane nephritis induced in BNP-transgenic mice (BNP-Tg) were investigated and the mechanisms how natriuretic peptides act on mesangial cells in vitro were explored. After induction of nephritis, severe albuminuria (approximately 21-fold above baseline), tissue damage, including mesangial expansion and cell proliferation, and functional deterioration developed in nontransgenic littermates. In contrast, BNP-Tg exhibited much milder albuminuria (approximately fourfold above baseline), observed only at the initial phase, and with markedly ameliorated histologic and functional changes. Up-regulation of transforming growth factor-beta (TGF-beta) and monocyte chemoattractant protein-1 (MCP-1), as well as increased phosphorylation of extracellular signal-regulated kinase (ERK), were also significantly inhibited in the kidney of BNP-Tg. In cultured mesangial cells, natriuretic peptides counteracted the effects of angiotensin II with regard to ERK phosphorylation and fibrotic action. Because angiotensin II has been shown to play a pivotal role in the progression of nephritis through induction of TGF-beta and MCP-1 that may be ERK-dependent, the protective effects of BNP are likely to be exerted, at least partly, by antagonizing the renin-angiotensin system locally. The present study opens a possibility of a novel therapeutic potential of natriuretic peptides for treating immune-mediated renal injury.

Topics: Albuminuria; Animals; Antihypertensive Agents; Blood Pressure; Chemokine CCL2; Complement C3; Glomerular Mesangium; Hydralazine; Immunoglobulin G; Kidney; Kidney Diseases; Kidney Glomerulus; Macrophages; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Natriuretic Agents; Natriuretic Peptide, Brain; Phosphorylation; Rats; Rats, Inbred WKY; Serum Albumin; Transforming Growth Factor beta; Transforming Growth Factor beta1

Brain natriuretic peptide (BNP), a member of the natriuretic peptide family, is produced and released from cardiac ventricles. BNP regulates the body fluid volume, blood pressure, and vascular tones through the A-type guanylate cyclase-coupled receptor. The presence of renal dysfunction in patients with diabetes affects the plasma levels of atrial natriuretic peptide (ANP). In the present study, we investigated the plasma levels of BNP and ANP and their relationship in normotensive diabetic patients with normoalbuminuria and microalbuminuria. Forty-seven normotensive lean noninsulin-dependent diabetic patients (31 with normoalbuminuria, 16 with microalbuminuria), with normal cardiac function, and 30 age-matched control subjects were enrolled in this study. The plasma levels of BNP in diabetic patients with microalbuminuria were significantly higher than those in diabetic patients with normoalbuminuria (16.7+/-2.4 vs. 9.6+/-1.3 pg/mL, P<0.01) or normal subjects (16.7+/-2.4 vs. 7.0+/-0.6 pg/mL, P<0.01). There was a significant positive correlation between plasma BNP levels and urinary albumin excretion rate in all diabetic patients (r = 0.58, P<0.0001). There was also a significantly positive correlation between plasma BNP and ANP levels in diabetic patients (r = 0.62, P<0.0001). The increased plasma level of BNP in patients with microalbuminuria and its significant correlation with urinary albumin excretion rate suggest that the elevated circulating levels of BNP are caused by the presence of diabetic nephropathy. Down-regulation of A-type guanylate cyclase-coupled receptor of renal tubules may explain the increased plasma levels of both BNP and ANP in normotensive diabetic patients with microalbuminuria.

Topics: Albuminuria; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Reference Values