B-Type Natriuretic Peptides Improve Cardiovascular Disease Risk Prediction in a Cohort of Women

Study Questions:

Does N-terminal pro–B-type natriuretic peptide (NT-proBNP) add prognostic value when predicting incident cardiovascular disease (CVD) risk among women?


Data from the Women’s Health Initiative (WHI) Observational Study were used for the present analysis. The WHI Observational Study includes a multiethnic cohort of 93,676 postmenopausal women, ages 50-79 years at recruitment, who were enrolled between 1994 and 1998, at 40 sites across the United States. The racial/ethnic composition of the cohort is representative of US women in the included age groups. Of the 93,676 women in the WHI Observational Study, 71,872 had no prior history of myocardial infarction (MI), stroke, peripheral artery disease, venous thromboembolism, or cancer. Of those, 60,890 had baseline blood samples available for analysis. A total of 1,821 incident cases of CVD (746 myocardial infarctions, 754 ischemic strokes, 160 hemorrhagic strokes, and 161 other CV deaths) were identified and compared with a randomly selected reference cohort of 1,992 women without CVD at baseline.


Women who experienced a CVD event during follow-up had higher body mass index, systolic blood pressure, and high-sensitivity C-reactive protein, and lower high-density lipoprotein cholesterol and were more likely to be current smokers, use loop diuretics, and have diabetes, a history of angina, or family history of premature MI. NT-proBNP levels were significantly higher among women who developed incident CVD. Median (interquartile range) levels of NT-proBNP were higher at study entry among incident cases (120.3 [68.1-219.5]) than among controls (100.4 [59.7-172.6]; p < 0.0001). Women in the highest quartile of NT-proBNP (≥140.8 ng/L) were at 53% increased risk of CVD versus those in the lowest quartile after adjusting for traditional risk factors (1.53 [1.21-1.94]; p-trend: < 0.0001). Similar associations were observed after adjustment for Reynolds Risk Score (RRS) covariables (1.53 [1.20-1.95] p-trend < 0.0001); the association remained in separate analyses of CV death (2.66 [1.48-4.81]; p-trend < 0.0001), MI (1.39 [1.02-1.88] p-trend = 0.008), and stroke (1.60 [1.22-2.11), p-trend < 0.0001). When added to traditional risk covariables, NT-proBNP improved the c-statistic (0.765-0.774; p = 0.0003), categorical net reclassification (0.08; p < 0.0001), and integrated discrimination (0.0105; p < 0.0001). Similar results were observed when NT-proBNP was added to the RRS.


The investigators concluded that in this multiethnic cohort of women, NT-proBNP modestly improved measures of CVD risk prediction.


These data suggest that NT-proBNP may be useful in prediction tools for women; however, further study to demonstrate the reproducibility in other large cohorts, in addition to the cost-effectiveness of such measurements, is warranted.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and Venothromboembolism, Lipid Metabolism, Nonstatins

Keywords: Myocardial Infarction, Stroke, Neoplasms, Follow-Up Studies, Women's Health, Venous Thromboembolism, Peripheral Arterial Disease, Risk Factors, Blood Pressure, Sodium Potassium Chloride Symporter Inhibitors, Angina Pectoris, Cholesterol, C-Reactive Protein, Body Mass Index, Peptide Fragments, Diabetes Mellitus, Natriuretic Peptide, Brain

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