Multimarker prediction of coronary heart disease risk: the Women's Health Initiative

Objectives: The aim of this study was to investigate whether multiple biomarkers contribute to improved coronary heart disease (CHD) risk prediction in post-menopausal women compared with assessment using traditional risk factors (TRFs) only.

Background: The utility of newer biomarkers remains uncertain when added to predictive models using only TRFs for CHD risk assessment.

Methods: The Women's Health Initiative Hormone Trials enrolled 27,347 post-menopausal women ages 50 to 79 years. Associations of TRFs and 18 biomarkers were assessed in a nested case-control study including 321 patients with CHD and 743 controls. Four prediction equations for 5-year CHD risk were compared: 2 Framingham risk score covariate models; a TRF model including statin treatment, hormone treatment, and cardiovascular disease history as well as the Framingham risk score covariates; and an additional biomarker model that additionally included the 5 significantly associated markers of the 18 tested (interleukin-6, d-dimer, coagulation factor VIII, von Willebrand factor, and homocysteine).

Results: The TRF model showed an improved C-statistic (0.729 vs. 0.699, p = 0.001) and net reclassification improvement (6.42%) compared with the Framingham risk score model. The additional biomarker model showed additional improvement in the C-statistic (0.751 vs. 0.729, p = 0.001) and net reclassification improvement (6.45%) compared with the TRF model. Predicted CHD risks on a continuous scale showed high agreement between the TRF and additional biomarker models (Spearman's coefficient = 0.918). Among the 18 biomarkers measured, C-reactive protein level did not significantly improve CHD prediction either alone or in combination with other biomarkers.

Conclusions: Moderate improvement in CHD risk prediction was found when an 18-biomarker panel was added to predictive models using TRFs in post-menopausal women.