natriuretic-peptide--brain and Peripheral-Vascular-Diseases

N-terminal fragment of pro B-type natriuretic peptide (NT-proBNP) has emerged as an important adjunct in the management of heart failure (HF) and other cardiovascular diseases. NT-proBNP is a 76-amino acid peptide created during cleavage of the precursor molecule, Pro B-type natriuretic peptide (ProBNP). NT-proBNP is of significant diagnostic value in patients presenting with possible HF and is an important prognostic factor in this condition and other cardiovascular diseases. Ongoing research supports the potential value of this biomarker in non-cardiovascular disease. This review will describe clinical applications of NT-proBNP in HF and a broad range of other conditions.

Topics: Biomarkers; Cardiovascular Diseases; Coronary Artery Disease; Diastole; Dyspnea; Heart Failure; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Vascular Diseases; Prognosis; Ventricular Function, Left

The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that provides additional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluate its clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men). Patients were followed for 23 months (range, 13-32 months) for cardiovascular (CV) events and/or death. Strain patients (n = 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking, and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors of Strain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI. Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in 12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that of ECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients.

Topics: Aged; Antihypertensive Agents; C-Reactive Protein; Cardiovascular Diseases; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Vascular Diseases; Prognosis; Renal Insufficiency, Chronic; Smoking; Troponin

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has emerged as predictor of mortality endpoints in cardiac disease. In contrast, the prognostic value of NT-proBNP in patients with peripheral arterial disease (PAD) is unclear. Therefore, we aimed to evaluate the capability of NT-proBNP as a marker for long-term prognosis in atherosclerotic PAD.. We obtained NT-proBNP serum concentrations in 487 consecutive patients with symptomatic PAD admitted to a tertiary-care hospital. The endpoint was defined as all-cause mortality, and the study participants were followed for 5 years.. Of the 487 patients enrolled, 114 died and 373 survived during follow-up. The median NT-proBNP concentration was higher among decedents than survivors (692 vs 143 ng/L; P < 0.001). Using the median NT-proBNP concentration of the entire cohort (213 ng/L) as threshold level, Kaplan-Meier curve analysis demonstrated that the survival probability was lower in patients with NT-proBNP above the median (log-rank test, P < 0.001). In the fully adjusted Cox proportional-hazards regression analysis, NT-proBNP >213 ng/L had a risk ratio of 2.27 (95% CI 1.27-4.03; P = 0.005) independent of age, sex, glomerular filtration rate, clinical stage of PAD, cardiovascular comorbidity, and other potential confounders. Further analyses showed that NT-proBNP added significantly to the value of established and emerging outcome predictors of PAD.. In this study, a NT-proBNP serum concentration >213 ng/L was a robust and independent predictor of 5-year all-cause mortality in patients with symptomatic PAD. Thus, NT-proBNP measurements can be considered a valuable tool for risk stratification in these patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Humans; Immunoassay; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Vascular Diseases; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Survival Analysis

To determine preoperative ventricular function in vascular amputees by measuring N-terminal pro-brain natriuretic peptide (NT-proBNP) and to analyse the relationship between NT-proBNP levels and 30-day postoperative mortality.. Prospective pilot study.. In 19 patients planned for a lower limb amputation for non-reconstructable peripheral arterial disease NT-proBNP was measured the day before amputation.. Four amputees died within 30 days after the amputation. In 17 of 19 patients NT-proBNP values were found more than 2 standard deviations above the age corrected reference value. Pre-amputation NT-proBNP levels did not differ significantly between non-survivors and survivors (P = 0.162).. Preoperative NT-proBNP levels are not significantly related to 30-day mortality after lower limb amputation procedure. Preoperative NT-proBNP levels are very high, indicating that serious ventricular dysfunction may be present in vascular amputees.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Biomarkers; Female; Humans; Leg; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Vascular Diseases; Pilot Projects; Predictive Value of Tests; Prospective Studies; Ventricular Function

The aim of the present study was to investigate the relationship of adiponectin, a novel adipocytokine, and amino terminal proBNP (NT-proBNP) in patients with peripheral arterial disease (PAD).. Serum concentrations of adiponectin and NT-proBNP were measured in 487 patients with symptomatic PAD from the Linz Peripheral Arterial Disease (LIPAD) study.. Correlation analysis revealed an association of adiponectin and NT-proBNP (r, +0.47; p<0.001). Even after adjustment for age, sex, body mass index, diabetes mellitus, smoking, arterial hypertension, estimated glomerular filtration rate (eGFR), fasting glucose, LDL-cholesterol, HDL-cholesterol, triglycerides, high-sensitivity C-reactive protein, and total homocysteine the relationship of adiponectin and NT-proBNP remained significant (r, +0.35; p<0.001). Furthermore, a subgroup analysis of patients with first manifestation of symptomatic PAD (n=287) demonstrated that disease severity (classified by Fontaine stages) was positively related to adiponectin (r, +0.13; p=0.003) and NT-proBNP (r, +0.28; p<0.001).. Adiponectin was positively associated with NT-proBNP in symptomatic atherosclerotic PAD, independent of traditional and non-traditional risk factors. Moreover, adiponectin and NT-proBNP were related to disease severity, indicating a possible role for assessment of future morbidity and mortality in patients with PAD.

Topics: Adiponectin; Aged; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Vascular Diseases

Cardiovascular disease is the leading cause of mortality and morbidity in Western countries. Despite its remarkable medical and social consequences, the prevalence of peripheral arterial disease (PAD) is often underestimated among atherosclerotic disorders. So far, little is known about the behavior of traditional and emerging markers of ischemic heart disease that should allow the reliable identification of PAD patients at increased risk of developing myocardial ischemia and heart failure or dysfunction. To investigate this topic, we measured cardiac troponin T (cTnT), ischemia-modified albumin (IMA) and NT-prohormone-brain natriuretic peptide (NT-proBNP) in 35 consecutive patients with clinically ascertained PAD (stage 2-4, according to Lériche-Fontaine) asymptomatic for chest pain and current heart failure, and 20 controls displaying moderate to high cardiovascular risk factors (hypertension, diabetes, hyperlipidemia), but with no clinical evidence of PAD. Although the concentrations of cTnT and IMA were not statistically increased in PAD patients, NT-pro-BNP values were substantially higher in PAD patients than in controls (62.6 vs. 7.4 pmol/L, p<0.0001). The percentage of subjects displaying values exceeding the specific NT-proBNP diagnostic threshold (>14.8 pmol/L) was also significantly different between PAD patients and controls (74% vs. 10%, p<0.001). After excluding PAD patients exceeding the 0.01 ng/mL cTnT cutoff value indicative of current ischemic cardiac involvement, the median concentration of NT-proBNP remained statistically increased (28.0 vs. 5.8 pmol/L, p<0.0001). Taken together, these results indicate that NT-proBNP, but not IMA, is substantially increased in PAD patients. This finding suggests that such patients, even though asymptomatic, might develop myocardial dysfunction, and thus warrant further investigation.

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Vascular Diseases; Serum Albumin

Topics: Aortic Diseases; Female; Humans; Intraoperative Complications; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peripheral Vascular Diseases; Predictive Value of Tests; Preoperative Care; Risk Assessment

Hypoxia-inducible factor-1 (HIF-1) is a primary regulator of the physiological response to hypoxia. A recombinant adenovirus expressing a constitutively active hybrid form of the HIF-1alpha subunit (Ad2/HIF-1alpha/VP16) is being evaluated as a gene therapy for the treatment of peripheral vascular disease. Ad2/HIF-1alpha/VP16 up-regulates known HIF-1-responsive genes, including those involved in angiogenesis. Expression profile analysis revealed that the brain natriuretic peptide (BNP) gene was significantly up-regulated in response to HIF-1alpha/VP16 in human fetal cardiac cells. Real-time reverse transcription-polymerase chain reaction analyses confirmed transcriptional activation of the BNP gene by HIF-1alpha/VP16 in human but not rat cardiac cells. Because hypoxia itself did not increase human BNP gene expression in these analyses, the mechanism of the HIF-1alpha/VP16 effect was determined. Analyses of promoter deletion mutants suggested that the cis-acting sequence in the human BNP promoter mediating activation by HIF-1alpha/VP16 was a putative HIF-1 responsive element (HRE) located at -466. An SV40 basal promoter-luciferase plasmid containing a minimal BNP HRE was up-regulated by HIF-1alpha/VP16, whereas a similar construct carrying a mutation within the HIF-1 binding site was not. Mutation of an E-box motif within the BNP HRE reduced HIF-1alpha/VP16-mediated transcriptional activation by 50%. Gel-shift analyses showed that both the native HIF-1alpha and HIF-1alpha/VP16 are able to bind to a probe containing the HIF-1 binding site. These experiments demonstrate the existence of a functional HRE in the BNP promoter and further define the scope and mechanism of action of Ad2/HIF-1alpha/VP16.

Topics: Base Sequence; Cells, Cultured; DNA Mutational Analysis; Electrophoretic Mobility Shift Assay; Gene Expression; Genetic Therapy; Humans; Molecular Sequence Data; Natriuretic Peptide, Brain; Peripheral Vascular Diseases; Promoter Regions, Genetic; Recombinant Fusion Proteins; Sequence Deletion; Transcriptional Activation