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(Circulation. 1998;98:1993-1999.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Associations Between Lipoproteins and the Progression of Coronary and Vein-Graft Atherosclerosis in a Controlled Trial With Gemfibrozil in Men With Low Baseline Levels of HDL Cholesterol

Mikko Syvänne, MD; Markku S. Nieminen, MD; M. Heikki Frick, MD; Heikki Kauma, MD; Silja Majahalme, MD; Vesa Virtanen, MD; Y. Antero Kesäniemi, MD; Amos Pasternack, MD; Christian Ehnholm, MD; Marja-Riitta Taskinen, MD; ; for the Lopid Coronary Angiography Trial (LOCAT) Study Group¹

From the Department of Medicine, Helsinki University Central Hospital (M.S., M.S.N., M.H.F., M-R.T.); the Department of Medicine and Biocenter Oulu, Oulu University Hospital and University of Oulu (H.K., Y.A.K.); the Department of Medicine, Tampere University Hospital (S.M., V.V., A.P.); and the Department of Biochemistry, National Public Health Institute, Helsinki (C.E.), Finland.

Background—Lipid-lowering secondary-prevention trials of coronary artery disease (CAD) have implicated triglyceride-rich lipoproteins as the main determinants of angiographic progression after elevated LDL cholesterol levels have been lowered with therapy. The present study focuses on the lipoprotein determinants of angiographic CAD progression in men with low HDL cholesterol concentration as their main baseline lipid abnormality who underwent 32 months of randomized therapy with gemfibrozil or placebo.

Methods and Results—Men who had undergone coronary bypass surgery (n=372) completed a randomized, placebo-controlled study with gemfibrozil 1200 mg/d. They were selected primarily for HDL cholesterol levels that corresponded to the lowest third for middle-aged men. Average baseline lipid and lipoprotein levels were serum triglyceride, 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 predicted global angiographic progression, taking into account changes in native segments and in bypass grafts. HDL₃ but not HDL₂ cholesterol concentration was associated with protection against progression, especially focal disease in native coronary lesions. VLDL was the lipoprotein most predictive of new lesions in vein grafts; IDL was also significantly related.

Conclusions—This study expands the previous evidence of the triglyceride-rich lipoproteins, especially IDL, as predictors of angiographic progression of CAD but does not negate the significance of mildly elevated LDL levels. Of the HDL subfractions, only HDL₃ was protective in this group of men selected for their low initial HDL levels.

Key Words: coronary disease • bypass • lipoproteins • angiography • trials

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