Predominance of Large LDL and Reduced HDL 2 Cholesterol in Normolipidemic Men With Coronary Artery Disease

Abstract

Abstract Previous studies have indicated that a predominance of small, dense LDL particles is associated with coronary artery disease (CAD) risk. In the present study we examined the LDL peak particle diameter (determined by lipid-stained 2% to 16% gradient gel electrophoresis) in 92 normolipidemic men with CAD (total cholesterol <200 mg/dL and triglyceride <250 mg/dL) and 92 matched healthy controls. Plasma triglyceride, LDL cholesterol, and apo B levels were similar in subjects with CAD and in control subjects, whereas subjects with CAD had decreased HDL 2 cholesterol levels (mean±SEM, 10±0.7 compared with 15±0.7 mg/dL in control subjects; P <.0002). Mean LDL particle diameter (±SEM) was increased in the subjects with CAD compared with control subjects (26.8±0.08 and 26.4±0.08 nm, respectively; P <.001). The association between large LDL size and CAD was significant ( P <.0001) after adjustments were made for age, body mass index, HDL cholesterol levels, and VLDL cholesterol levels. An LDL particle size distribution characterized by a predominance of the largest of three classes of LDL particles (>26.8 nm) was more prevalent among subjects with CAD (43%) than among control subjects (25%) ( P <.002). Among subjects with this LDL size profile, subjects with CAD had significantly higher ( P <.05) VLDL triglyceride, VLDL cholesterol, and VLDL apo B levels and significantly lower ( P <.0001) HDL 2 cholesterol levels than controls. Thus, in this normolipidemic population with CAD, a predominance of very large rather than small LDL particles was associated with increased VLDL and reduced HDL 2 cholesterol levels and with increased CAD risk, independent of other plasma lipid and lipoprotein levels.