Potential role for plasma placental growth factor in predicting coronary heart disease risk in women.

OBJECTIVE The purpose of this study was to examine placental growth factor's (PlGF) predictive value in relation to coronary heart disease (CHD) risk in healthy women. METHODS AND RESULTS Among 32 826 women from the Nurses' Health Study who provided blood samples at baseline, 453 CHD events were documented during 14 years of follow-up. Controls were matched to cases (2:1) for age, smoking, fasting status, and date of blood sampling. PlGF was inversely correlated with HDL-cholesterol (HDL-C), and positively correlated with several coronary risk factors. In multivariate models, women in the highest versus lowest quintile of PlGF had a greater risk of CHD (RR: 1.58; 95% CI: 1.03 to 2.41). Additional adjustment for many coronary risk factors did not substantively alter this relationship, but HDL-C attenuated the association (RR: 1.25; 95% CI: 0.81 to 1.94). In exploratory time to event analysis, higher PlGF levels, measured >10 years before CHD event, but not <10 years preclinical event, were associated with increased risk of CHD, even after adjustment for comorbid conditions and HDL-C levels (RR: 2.79; 95% CI: 1.19 to 6.56). CONCLUSIONS Elevated prediagnostic PlGF levels were modestly associated with subsequent risk of CHD events and results were attenuated after controlling for HDL-C. PlGF may be most strongly associated with long-term prediction of CHD, consistent with a potential role in early plaque formation and growth.