Multimarker prediction of coronary heart disease risk: the Women's Health Initiative
Authors
Hyeon Chang Kim ; Philip Greenland ; Jacques E. Rossouw ; JoAnn E. Manson ; Barbara B. Cochrane ; Norman L. Lasser ; Marian C. Limacher ; Donald M. Lloyd-Jones ; Karen L. Margolis ; Jennifer G. Robinson
Citation
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol.55(19) : 2080-2091, 2010
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.