NT-proBNP and All-Cause and Cardiovascular Mortality in US Adults: A Prospective Cohort Study

BACKGROUND: NT-proBNP (N-terminal pro-B-type natriuretic peptide) is strongly associated with mortality in patients with heart failure. Prior studies, primarily in middle-aged and older populations, have suggested that NT-proBNP has prognostic value in ambulatory adults. METHODS AND RESULTS: We conducted a prospective cohort analysis of adults, aged ≥20 years, in the nationally representative 1999 to 2004 National Health and Nutrition Examination Survey, to characterize the association of NT-proBNP with mortality in the general US adult population overall and by age, race and ethnicity, and body mass index. We used Cox regression to characterize associations of NT-proBNP with all-cause and cardiovascular disease (CVD) mortality through 2019, adjusting for demographics and cardiovascular risk factors. We included 10 645 individuals (mean age, 45.7 years; 50.8% women; 72.8% White adults; 8.5% with a self-reported history of CVD). There were 3155 deaths (1009 CVD-related) over a median 17.3 years of follow-up. Among individuals without prior CVD, elevated NT-proBNP (≥75th percentile [81.5 pg/mL] versus <25th percentile [20.5 pg/mL]) was associated with a significantly higher risk of all-cause (hazard ratio [HR], 1.67 [95% CI, 1.39– 2.00]) and CVD mortality (HR, 2.87 [95% CI, 1.61– 5.11]). Associations of NT-proBNP with all-cause and CVD mortality were generally similar across subgroups defined by age, sex, race and ethnicity, or body mass index (all P interaction >0.05). CONCLUSIONS: In a representative sample of the US adult population, NT-proBNP was an important independent risk factor for all-cause and CVD mortality. NT-proBNP may be useful for monitoring risk in the general adult population.