Metabolic syndrome: Risk factor distribution and 18-year mortality in the multiple risk factor intervention trial

OBJECTIVE - To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS - A total of 10,950 Multiple Risk Factor Intervention Trial (MRFIT) survivors were followed for mortality an additional median 18.4 years (1980-1999). Proportional hazards models examined multivariate-adjusted risks associated with Adult Treatment Panel III-defined metabolic syndrome conditions, with BMI substituted for waist circumference. RESULTS - At MRFIT annual visit 6, 4,588 (41.9%) men, mean age (±SD) 53.0 ± 5.9 years, had metabolic syndrome and 6,362 did not. Comparing men with metabolic syndrome to men without, adjusted hazard ratios (HRs) were 1.21 (95% CI 1.13-1.29), 1.49 (1.35-1.64), and 1.51 (1.34-1.70) for 18-year total, CVD, and coronary heart disease mortality, respectively. Among men with metabolic syndrome, elevated glucose (1.54 [1.34-1.78]) and low HDL cholesterol (1.45 [1.17-1.54]) were most predictive of CVD mortality, followed by elevated BMI (1.34 [1.17-1.54]), elevated blood pressure (1.25 [0.98-1.58]), and elevated triglycerides (1.06 [0.86-1.30]). In contrast, for men without metabolic syndrome, the HR for low HDL cholesterol was 1.02 (0.86-1.22). Among metabolic syndrome men with no nonfatal CVD event, smokers with elevated LDL cholesterol showed higher CVD mortality (1.79 [1.22-2.63]) compared with nonsmokers without elevated LDL cholesterol; this additional risk was even greater for metabolic syndrome men with a nonfatal CVD event (2.11 [1.32-3.38]). CONCLUSIONS - Metabolic syndrome is associated with an increased risk of mortality. Among those with metabolic syndrome, risk is further increased by having more metabolic syndrome conditions, by cigarette smoking, and by elevated LDL cholesterol. Primary prevention of each metabolic syndrome condition should be emphasized, and presence of each condition should be treated in accordance with current guidelines.