ASSOCIATIONS BETWEEN LIPOPROTEINS AND THE PROGRESSION OF CORONARY ANDVEIN-GRAFT ATHEROSCLEROSIS IN A CONTROLLED TRIAL WITH GEMFIBROZIL IN MEN WITH LOW BASE-LINE LEVELS OF HDL CHOLESTEROL

Background-Lipid-lowering secondary-prevention trials of coronary arte ry disease (CAD) have implicated triglyceride-rich lipoproteins as the main determinants of angiographic progression after elevated LDL chol esterol levels have been lowered with therapy. The present study focus es on the lipoprotein determinants of angiographic CAD progression in men with low HDL cholesterol concentration as their main baseline lipi d abnormality who underwent 32 months of randomized therapy with gemfi brozil or placebo. Methods and Results-Men who had undergone coronary bypass surgery (n=372) completed a randomized, placebo-controlled stud y with gemfibrozil 1200 mg/d. They were selected primarily for HDL cho lesterol levels that corresponded to the lowest third for middle-aged men. Average baseline lipid and lipoprotein levels were serum triglyce ride, 1.60; serum cholesterol, 5.17; ultracentrifugally separated LDL cholesterol, 3.43; HDL2 cholesterol, 0.41; and HDL3 cholesterol, 0.61 mmol/L. In the gemfibrozil group, these levels were reduced on average by 40%, 9%, and 6% or increased by 5% and 9%, respectively. On-trial IDL and LDL triglyceride and cholesterol levels significantly predicte d global angiographic progression, taking into account changes in nati ve segments and in bypass grafts. HDL3 but not HDL2 cholesterol concen tration was associated with protection against progression, especially focal disease in native coronary lesions. VLDL was the lipoprotein mo st predictive of new lesions in vein grafts; IDL was also significantl y related. Conclusions-This study expands the previous evidence of the triglyceride-rich lipoproteins, especially IDL, as predictors of angi ographic progression of CAD but does not negate the significance of mi ldly elevated LDL levels. Of the HDL subfractions, only HDL3 was prote ctive in this group of men selected for their low initial HDL levels.