Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide: biomarkers for mortality in a large community-based cohort free of heart failure

Abstract

Recent studies report that, in the absence of heart failure and renal failure, plasma B-type natriuretic peptide (BNP) has prognostic value for mortality. We sought to confirm and extend these previous studies to assess BNP, measured by 3 distinct assays, as a biomarker for mortality in a strategy to enhance efforts at primary prevention and to better understand the clinical phenotype of such subjects at risk. We used a community-based cohort of 2042 subjects from Olmsted County, Minn, and individuals with heart or renal failure were excluded. BNP was assessed using 3 assays including Biosite and Shionogi for mature, biologically active BNP and the Roche assay for apparently nonbiologically active amino-terminal pro-BNP (NT-proBNP). Thorough echocardiographic and clinical data were recorded for all of the participants. Median follow-up for mortality was 5.6 years. BNP by all 3 of the assays was predictive of mortality. NT-proBNP and Biosite assays remained significant even after adjustment for traditional clinical risk factors and echocardiographic abnormalities including left ventricular hypertrophy and diastolic dysfunction. Echocardiography documented widespread structural changes in those with increasing BNP levels yet below levels observed in heart failure. We report in a large, well-characterized community-based cohort, free of heart failure, the first study to compare 3 distinct BNP assays as biomarkers for mortality in the same cohort. Our findings confirm the potential use of NT-proBNP and BNP biomarkers for future events and underscore that these peptides may also serve as biomarkers for underlying cardiac remodeling secondary to diverse cardiovascular disease entities.

Figure 1

Kaplan-Meier curves for unadjusted cumulative survival in the total population according to tertiles of BNP by NT-proBNP, Biosite, and Shionogi assays. The peptide levels of tertiles 1, 2, and 3 were ≤ 36.7 pg/mL, 36.7 to 109.0 pg/mL, and > 109.0 pg/mL, respectively, for NT-proBNP (A); < 7.9 pg/mL, 7.9 to 23.0 pg/mL, and > 23.0 pg/mL, respectively, Shionogi (B); < 13.4 pg/mL, 13.4 to 39.7 pg/mL, and > 39.7 pg/mL, respectively, for Biosite (C). P for trend across the tertiles was < 0.001 for NT-proBNP, Biosite, and Shionogi assays.

Figure 2

Age- and gender-adjusted sequential modeling to determine the incremental value of each assay over the remaining 2 assays as a predictor of mortality. For a particular assay, the change in overall model fit (log likelihood statistic) relative to the addition of 1 or both of the remaining assays was calculated to determine whether there was incremental value in performing an additional assay. P values represent the statistical significance of the difference between models.

Figure 3

Percentage prevalence of clinical characteristics and echocardiographic abnormalities according to tertiles of NT-proBNP. The lowest, middle, and highest tertiles for NT-proBNP were < 36.7 pg/mL, 36.7 to 109.0 pg/mL, and > 109.0 pg/mL, respectively. The prevalence of all clinical and echocardiographic phenotypes was significantly increased (P < 0.001) across the tertiles with the exception of diabetes mellitus (P = 0.030). A Fib indicates atrial fibrillation; CAD, coronary artery disease; CM, cardiomyopathy; COPD, chronic obstructive pulmonary disease; CV drug, cardiovascular drug use; DM, diabetes mellitus; EF, ejection fraction; HTN, hypertension; LAE, left atrial enlargement; LVH, left ventricular enlargement; MI, myocardial infarction; and RWMA, regional wall motion abnormality.