LOW-DENSITY-LIPOPROTEIN PARTICLE-SIZE AND CORONARY-ARTERY DISEASE

Decreased plasma low density lipoprotein (LDL) particle size has been associated with premature coronary artery disease (CAD). We examined LDL particle size by 2-16% gradient gel electrophoresis in 275 men with CAD (> 75% cross-sectional-area stenosis) and 822 controls. Seven major LDL size bands (with LDL-1 [d = 1.025-1.033 g/ml] being the largest and LDL-7 [d = 1.050-1.063 g/ml, the smallest]) were identified. Because most subjects had two or more adjacent LDL bands, an LDL score was calculated for each subject, with the relative area in each band taken into consideration. Four major LDL particle size groups were classified in the present studies: large LDL, intermediate LDL, small LDL, and very small LDL. The use of beta-blockers was significantly associated with smaller LDL particles. After adjusting for use of this medication, small LDL particles were still more prevalent in CAD patients (39%) compared with controls (27%). The prevalence of large LDL particles was lower in CAD patients (3%) than in controls (24%). Intermediate LDL particles were the most prevalent in both groups, 49% in CAD patients and 46% in controls. The difference in LDL particle size between CAD patients and controls was not independent but was highly associated (p < 0.0001) with elevated triglyceride levels and decreased high density lipoprotein (HDL) cholesterol levels. Significantly higher LDL cholesterol levels were found in subjects with intermediate and small LDL particles than in those with large or very small LDL particles. In addition, CAD patients with intermediate or small LDL particles had significantly (p < 0.01) lower HDL cholesterol and apolipoprotein A-I levels and higher LDL cholesterol levels than did controls in the same group. Smoking, hypertension, diabetes, and HDL and LDL cholesterol levels were strong discriminators between CAD patients and controls, while triglycerides and LDL particle size did not add significant information to the model. These data indicate that small LDL particle size is not an independent discriminator for CAD after conventional risk factors and lipoprotein parameters such as LDL and HDL cholesterol have been taken into account.