Background Coronary risk factors related to the insulin resistance syndrome tend to cluster in the same individual. Our previous studies have shown that the dyslipidemia characteristic of this syndrome—low HDL cholesterol and high triglyceride (TG) levels—responds well to treatment with gemfibrozil. Most factors related to insulin-resistance syndrome decrease fibrinolytic capacity, whereas a recent study showed that gemfibrozil improves it and thus may attenuate thrombotic events. To discover whether subjects with clustering of factors related to this resistance might in particular benefit from gemfibrozil, we reanalyzed the Helsinki Heart Study data.

Methods and Results We used Cox regression models to explore the effects of gemfibrozil among overweight subjects with additional coronary risk factors in this hypercholesterolemic male population of 2046 subjects randomized to gemfibrozil and 2035 to placebo. The effect of gemfibrozil was largely confined to overweight subjects: among those with body mass index (BMI) >26 kg/m², the net difference in cardiac end points between gemfibrozil and placebo groups was 21 (25 of 1119 versus 46 of 1081), and in those with BMI ≤26 kg/m², it was 7 (31 of 927 versus 38 of 954). The risk reduction with gemfibrozil was 78% (P=.002) among those with BMI >26 kg/m² and dyslipidemia (TG ≥2.3 mmol/L and HDL cholesterol <1.08 mmol/L). Among those with BMI >26 kg/m² and three or four of the following factors present—smoking, sedentary lifestyle, blood pressure ≥140/90 mm Hg, or blood glucose >4.4 mmol/L—the risk reduction was 68% (P=.03).

Conclusions Gemfibrozil reduced the coronary risk mainly in overweight subjects with additional risk factors known to contribute to the insulin-resistance syndrome or predispose to it.