PREDOMINANCE OF LARGE LDL AND REDUCED HDL(2) CHOLESTEROL IN NORMOLIPIDEMIC MEN WITH CORONARY-ARTERY DISEASE

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,eel 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.