NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population

Background: Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. Methods: Serum NT-ProBNP levels were measured in 5502 people aged 45–79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999–2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. Results: After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100–300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12–2.32, p = 0.012 and HR 2.96, 95% CI 1.75–5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17–2.10, p = 0.011 and HR 2.08, 95% CI 1.47–2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex. Conclusions: Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.