Independent Metabolic Syndrome Variants Predict New-Onset Coronary Artery Disease

OBJECTIVE: Any combination of metabolic abnormalities may constitute the metabolic syndrome (MetS), conferring coronary artery disease (CAD) risk, but the independent effect of different combinations on CAD onset remains unknown. RESEARCH DESIGN AND METHODS: Healthy adult siblings (n = 987) of premature CAD (<60 years) case subjects were followed for 9.8 ± 3.8 years. Baseline MetS variables (insulin sensitivity index, waist circumference, systolic blood pressure, HDL cholesterol, and triglycerides) were recombined into five principal components (PC1–5), and risk factor–adjusted proportional hazards for CAD onset of median-dichotomized PCs were estimated. RESULTS: The significant hazard ratios were as follows: for PC1 (all abnormalities except blood pressure) 1.66 (P = 0.036), PC2 (high blood pressure levels, high HDL cholesterol) 1.71 (P = 0.016), and PC4 (low HDL cholesterol, high insulin sensitivity, low triglycerides) 2.0 (P = 0.001). Traditionally defined MetS had a hazard ratio of 1.32 (P = 0.18). CONCLUSIONS: Independent MetS variants identified by PC analysis may explain metabolic mechanisms that increase CAD risk better than the presence of traditional MetS.