Usefulness of B-type Natriuretic Peptides to Predict Cardiovascular Events in Women (from the Women's Health Study)

Natriuretic peptides are positively associated with incident cardiovascular disease (CVD), but data in women, particularly with regard to improvements in risk prediction, are sparse. We measured the N-terminal prohormone form of B-type natriuretic peptide (NT-proBNP) in 480 cases of incident CVD (myocardial infarction, stroke, and cardiovascular death) and a reference subcohort of 564 women from the Women's Health Study who were followed for a median of 12.0 (interquartile range 7.6 to 13.4) years. Median (interquartile range) NT-proBNP concentrations were greater in women who developed CVD (81 ng/l [50 to 147]) than those who did not (64 ng/l [38 to 117]; p <0.0001). For women in the highest compared to the lowest quartile, NT-proBNP was 65% greater after adjusting for established cardiovascular risk factors and kidney function (adjusted hazard ratio [aHR] 1.65, 95% confidence interval [CI] 1.03 to 2.64, p trend = 0.03). When analyzed as a continuous variable, the aHR per 1 − SD difference in Ln(NT-proBNP) was 1.22 (1.03 to 1.44; p = 0.02). The per 1 − SD change in Ln(NT-proBNP) appeared stronger for cardiovascular death (aHR 1.43, 95% CI 1.05 to 1.94, p = 0.02) and stroke (aHR 1.24, 95% CI 1.03 to 1.50, p = 0.03) than myocardial infarction (aHR 1.09, 95% CI 0.87 to 1.37, p = 0.44). When added to traditional risk co-variables, NT-proBNP did not significantly improve the C-statistic (0.751 to 0.757; p = 0.09) or net reclassification into <5%, 5 to <7.5%, and ≥7.5% 10-year CVD risk categories (0.014; p = 0.18). In conclusion, in this prospective study of initially healthy women, NT-proBNP concentrations showed statistically significant association with incident CVD that was independent of traditional cardiovascular risk factors but did not substantially improve measures of CVD risk prediction.