N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Levels are Increased in Patients With Transient Ischemic Attack Accompanied by Nonfocal Symptoms.
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SUBMITTER: Plas GJ
PROVIDER: S-EPMC4845269 | biostudies-other | 2015 Dec
REPOSITORIES: biostudies-other
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Project description:BackgroundNT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).Methods and resultsGenotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation.ConclusionIn this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD.
| S-EPMC7959346 | biostudies-literature
Project description:BackgroundNT-proBNP (N-terminal pro-B-type natriuretic peptide) levels are variably elevated in heart failure with preserved ejection fraction (HFpEF), even in the presence of increased left ventricular filling pressures. NT-proBNP levels are prognostic in HFpEF and have been used as an inclusion criterion for several recent randomized clinical trials. However, the underlying biologic differences between HFpEF participants with high and low NT-proBNP levels remain to be fully understood.MethodsWe measured 4928 proteins using an aptamer-based proteomic assay (SOMAScan) in available plasma samples from 2 cohorts: (1) Participants with HFpEF enrolled in the PHFS (Penn Heart Failure Study; n=253); (2) TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) participants in the Americas (n=218). We assessed the relationship between SOMAScan-derived plasma NT-proBNP and levels of other proteins available in the SOMAScan assay version 4 using robust linear regression, with correction for multiple comparisons, followed by pathway analysis.ResultsNT-proBNP levels exhibited prominent proteome-wide associations in PHFS and TOPCAT cohorts. Proteins most strongly associated with NT-proBNP in both cohorts included SVEP1 (sushi, von Willebrand factor type-A, epidermal growth factor, and pentraxin domain containing 1; βTOPCAT=0.539; P<0.0001; βPHFS=0.516; P<0.0001) and ANGPT2 (angiopoietin 2; βTOPCAT=0.571; P<0.0001; βPHFS=0.459; P<0.0001). Canonical pathway analysis demonstrated consistent associations with multiple pathways related to fibrosis and inflammation. These included hepatic fibrosis and inhibition of matrix metalloproteases. Analyses using cut points corresponding to estimated quantitative concentrations of 360 pg/mL (and 480 pg/mL in atrial fibrillation) revealed similar proteomic associations.ConclusionsCirculating NT-proBNP levels exhibit prominent proteomic associations in HFpEF. Our findings suggest that higher NT-proBNP levels in HFpEF are a marker of fibrosis and inflammation. These findings will aid the interpretation of NT-proBNP levels in HFpEF and may guide the selection of participants in future HFpEF clinical trials.
| S-EPMC7615693 | biostudies-literature
Project description:BackgroundBrain natriuretic peptide (BNP) is released by the heart in response to ventricular and auricular wall stress. Release of BNP is traditionally considered part of the body's protective mechanism against pressure overload by inducing vasodilatation and diuresis. More recent evidence demonstrates that BNP also promotes vessel wall stress and preliminary studies suggest that chronic increased levels may increase risk of hypertension. This study aimed to evaluate the prospective association of N-terminal BNP (NT-proBNP), a cleavage product of BNP, with risk of hypertension in the Atherosclerosis Risk in Communities cohort study.MethodsWe conducted a prospective analysis of 3,798 middle-aged participants in the ARIC study without hypertension at baseline (1996-1998). Using Cox proportional hazards models, we characterized the association between NT-proBNP at baseline and newly diagnosed hypertension for a maximum of 14 years of follow-up (median = 9 years).ResultsWe observed 2,113 new hypertension cases over the follow-up period. Higher baseline NT-proBNP was independently associated with an increased risk of hypertension. Adjusted hazard ratios for incident hypertension in the highest quartile compared to the lowest quartile of NT-proBNP at baseline was 1.24 (95% CI: 1.08-1.42). Each log-unit increase in NT-proBNP was associated with an 8% increased risk of hypertension (95% CI: 1.03-1.13).ConclusionsPersons with elevated NT-proBNP, even with normal blood pressure at baseline, were at increased risk of developing hypertension. Our results suggest that elevated circulating BNP might contribute to the development of hypertension in previously normotensive individuals.
| S-EPMC4580540 | biostudies-literature
Project description:ObjectivesN-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association.MethodsBaseline data of 4598 participants aged 45-75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models.ResultsWith an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations.ConclusionsIn the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.
| S-EPMC8378685 | biostudies-literature
Project description:BackgroundCirculating N-terminal pro B-type natriuretic peptide (NT-proBNP) predicts incidence of atrial fibrillation (AF), but the association of longitudinal changes in NT-proBNP concentrations with incident AF has not been explored.MethodsWe studied 9705 individuals without prevalent AF in 1996-1998 and with available NT-proBNP measurements obtained in samples collected during two visits in 1990-1992 (visit 2) and 1996-1998 (visit 4) in the Atherosclerosis Risk in Communities (ARIC) Study. Participants were followed through the end of 2013. AF was ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox regression was used to evaluate the association of absolute change in log-transformed NT-proBNP [ln(NT-proBNP)] with incident AF. We also assessed the impact of adding ln(NT-proBNP) change as a predictor of AF by difference in the C-statistic and net reclassification improvement (NRI).ResultsOver a median follow up of 16 years, there were 1503 incident cases of AF. The means (SD) ln(NT-proBNP) at visit 2 and visit 4 were 3.83 (1.01) and 4.35 (0.94), respectively. There was a 0.52 (0.79) increase in ln(NT-proBNP) over the 6-year period. Greater increases in ln(NT-proBNP) were associated with higher risk of AF [hazard ratio, 2.82 (95% confidence interval 2.34, 3.39), comparing top to bottom quintiles, and 1.74 (1.61, 1.87) per 1-unit increase in ln(NT-proBNP)]. Adding ln(NT-proBNP) change to a model with multiple predictors including baseline NT-proBNP had relatively limited impact in the C-statistic (increase from 0.748, 95%CI 0.736-0.761, to 0.762, 95%CI 0.750, 0.774). Adding ln(NT-proBNP) change to initial predictive models resulted in a categorical NRI of 0.062 (95% CI 0.033, 0.092) and a continuous NRI of 0.092 (95%CI, 0.017, 0.182).ConclusionPositive NT-proBNP change is associated with an increased incidence rate of AF. Adding NT-proBNP change into the prediction model modestly improved incident AF prediction. Future studies should assess the value of monitoring NT-proBNP concentration among individuals at high risk of developing AF.
| S-EPMC6214728 | biostudies-literature
Project description:BACKGROUND:Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. METHODS:A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCE-MRI and the pharmacokinetic modeling parameter Ktrans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. RESULTS:The 75th percentile adventitial (OR 1.97, 95% CI 1.18-3.29) Ktrans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. CONCLUSIONS:This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether Ktrans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events.
| S-EPMC5804829 | biostudies-literature
Project description:Cross-sectionally measured NT-proBNP (N-terminal pro-B-type natriuretic peptide) is related to incident dementia. However, data linking changes in NT-proBNP to risk of future dementia are lacking. We aimed to examine the association of change in NT-proBNP over 3.2 years with incident dementia. We included 4563 participants in MESA (Multi-Ethnic Study of Atherosclerosis) prospective cohort who were free of cardiovascular disease at enrollment, had NT-proBNP level measured at MESA exams 1 (baseline, 2000-2002) and 3 (2004-2005), and had no diagnosis of dementia before exam 3. The association of change in NT-proBNP level between MESA exams 1 through 3 and all-cause hospitalized dementia (by International Classification of Diseases, Ninth Revision, codes) after MESA exam 3 (2004-2005) through 2015 was assessed using competing-risks Cox proportional hazard regression analysis. During 45 522 person-years of follow-up, 223 dementia cases were documented. Increase in log-NT-proBNP from MESA exams 1 through 3 was positively associated with incidence of dementia (multivariable hazard ratio, 1.28 [95% CI, 1.001-1.64]; P=0.049). An increase of at least 25% in NT-proBNP level from MESA exam 1 through 3 was associated with a 55% (P=0.02) increase in the risk of dementia in multivariable analysis. Addition of temporal NT-proBNP change to a model including risk factors and baseline NT-proBNP improved the prediction of dementia (Harrell C statistic from 0.85 to 0.87, P=0.049). Increase in NT-proBNP is independently associated with future all-cause hospitalized dementia and offers a moderately better predictive performance for risk of dementia compared with risk factors and baseline NT-proBNP. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005487.
| S-EPMC7482429 | biostudies-literature
Project description:Many advances have been made in the diagnosis and management of heart failure (HF) in recent years. Cardiac biomarkers are an essential tool for clinicians: point of care B-type natriuretic peptide (BNP) and its N-terminal counterpart (NT-proBNP) levels help distinguish cardiac from non-cardiac causes of dyspnea and are also useful in the prognosis and monitoring of the efficacy of therapy. One of the major limitations of HF biomarkers is in obese patients where the relationship between BNP and NT-proBNP levels and myocardial stiffness is complex. Recent data suggest an inverse relationship between BNP and NT-proBNP levels and body mass index. Given the ever-increasing prevalence of obesity world-wide, it is important to understand the benefits and limitations of HF biomarkers in this population. This review will explore the biology, physiology, and pathophysiology of these peptides and the cardiac endocrine paradox in HF. We also examine the clinical evidence, mechanisms, and plausible biological explanations for the discord between BNP levels and HF in obese patients.
| S-EPMC4201035 | biostudies-literature
Project description:BackgroundPatients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.MethodsIn this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.ResultsBy 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).ConclusionsIn this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).
| S-EPMC4887756 | biostudies-literature
Project description:N-terminus pro-brain natriuretic peptide (NT-proBNP) has been studied and recognized as a biomarker of cardiac thrombogenicity and stroke risk. However, the association between NT-proBNP and functional outcomes following acute ischemic stroke is still debated. This study aimed to investigate whether serum NT-proBNP level is associated with functional outcomes in acute ischemic stroke individuals. This prospective cohort study included patients diagnosed with acute ischemic stroke, and serum NT-proBNP levels were measured within 72 h. At 3 months, all patients were followed up for a modified Rankin Scale (mRS), and logistic regression models were used to evaluate the association of NT-proBNP on the primary outcome, in which a score of 3-6 was classified as an unfavorable functional outcome. Sixty-seven patients were enrolled in the study, and 23 (34.3%) patients were identified with an unfavorable functional outcome. Elevated serum NT-proBNP levels (> 100 pg/mL) were observed in 57 (85.1%) patients, and the Youden index demonstrated a cutpoint estimation of poor outcomes at 476 pg/mL with 74% sensitivity and 63% specificity. Multivariate regression analysis showed an elevation of NT-proBNP above the cutpoint level was an independent predictor for unfavorable functional outcomes, odds ratio 3.77, 95% confidence interval (1.04-13.62), P = 0.04. The present study demonstrated that elevated serum NT-proBNP levels were expected among acute ischemic stroke patients and represented the risk of unfavorable functional outcomes, suggesting that NT-proBNP might be a useful biomarker for predicting prognosis after ischemic stroke.
| S-EPMC10457328 | biostudies-literature