Increased circulating amino-terminal pro–B-type natriuretic (NT-proBNP) levels are a marker of cardiac dysfunction but also associate with coronary heart disease and stroke.

We aimed to investigate whether increased circulating NT-proBNP levels have additive prognostic value for first cardiovascular and cerebrovascular events beyond classic risk factors.

In a community-based cohort of 5063 participants free of cardiovascular disease, aged 55 years, circulating NT-proBNP levels and cardiovascular risk factors were measured.

Participants were followed for the occurrence of first major fatal or nonfatal cardiovascular event. A total of 420 participants developed a first cardiovascular event (108 fatal).

After adjustment for classic risk factors, the hazard ratio for cardiovascular events was 2.32 (95% CI: 1.55 to 2.70) in men and 3.08 (95% CI: 1.91 to 3.74) in women for participants with NT-proBNP in the upper compared with the lowest tertile.

Corresponding hazard ratios for coronary heart disease, heart failure, and ischemic stroke were 2.01 (95% CI: 1.14 to 2.59), 2.90 (95% CI: 1.33 to 4.34), and 2.06 (95% CI: 0.91 to 3.18) for men and 2.95 (95% CI: 1.30 to 4.55), 5.93 (95% CI: 2.04 to 11.2), and 2.07 (95% CI: 1.00 to 2.97) for women.

Incorporation of NT-proBNP in the classic risk model significantly improved the C-statistic both in men and women and resulted in a net reclassification improvement of 9.2% (95% CI: 3.5% to 14.9%; P=0.001) in men and 13.3% (95% CI: 5.9% to 20.8%; P<0.001) in women.

We conclude that, in an asymptomatic older population, NT-proBNP improves risk prediction not only of heart failure but also of cardiovascular disease in general beyond classic risk factors, resulting in a substantial reclassification of participants to a lower or higher risk category.

Key Words: NT-proBNP • cardiovascular disease • C statistic • reclassification • population science

Hypertension. 2010;55:785

Joost H.W. Rutten; Francesco U.S. Mattace-Raso; Ewout W. Steyerberg; Jan Lindemans; Albert Hofman; Renske G. Wieberdink; Monique M.B. Breteler; Jacqueline C.M. Witteman; Anton H. van den Meiracker

From the Department of Internal Medicine (J.H.W.R., A.H.v.d.M.), Section of Pharmacology, Vascular and Metabolic Diseases; Departments of Epidemiology (F.U.S.M.-R., A.H., R.G.W., M.M.B.B., J.C.M.W.) and Internal Medicine (F.U.S.M.-R.), Section of Geriatric Medicine; and Departments of Public Health (E.W.S.) and Clinical Chemistry (J.L.), Erasmus Medical Center, Rotterdam, The Netherlands.

Correspondence to Anton H. van den Meiracker, Division of Pharmacology, Vascular and Metabolic Diseases, Department of Internal Medicine, Room D432, Erasmus Medical Center, ‘s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail a.vandenmeiracker@erasmusmc.nl