Dataset Information

Association of N-terminal pro B-type natriuretic peptide (NT-proBNP) change with the risk of atrial fibrillation in the ARIC cohort.

ABSTRACT: BACKGROUND:Circulating 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. METHODS:We 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). RESULTS:Over 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). CONCLUSION:Positive 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.

SUBMITTER: Li L

PROVIDER: S-EPMC6214728 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Association of N-terminal pro B-type natriuretic peptide (NT-proBNP) change with the risk of atrial fibrillation in the ARIC cohort.

Li Linzi L Selvin Elizabeth E Lutsey Pamela L PL Hoogeveen Ron C RC O'Neal Wesley T WT Soliman Elsayed Z EZ Chen Lin Y LY Alonso Alvaro A

American heart journal 20180810

<h4>Background</h4>Circulating 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.<h4>Methods</h4>We 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 Communitie ...[more]

PMID: 30099337

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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.

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.

Project description:Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02358-y.

Dataset Information

Association of N-terminal pro B-type natriuretic peptide (NT-proBNP) change with the risk of atrial fibrillation in the ARIC cohort.

Publications

Association of N-terminal pro B-type natriuretic peptide (NT-proBNP) change with the risk of atrial fibrillation in the ARIC cohort.

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