Role of small dense low-density lipoprotein in coronary artery disease patients with normal plasma cholesterol levels

OBJECTIVES: The relationship between plasma low-density lipoprotein (LDL) cholesterol and the risk of coronary artery disease (CAD) is known, but the other characteristics of LDL, particularly particle size and density, are unclear. The relationship between small dense LDL phenotype and non-diabetic, normocholesterolemic CAD was investigated in 70 patients with angiographically documented CAD, and 38 age-matched control subjects. METHODS: Peak LDL particle diameter was determined by using 2-16% polyacrylamide gradient gel electrophoresis. Small dense LDL phenotype was defined as particle diameter equal to or less than 255 A. RESULTS: LDL particle diameters in patients with CAD were significantly smaller than those in controls (252.4 +/- 6.9 vs 259.3 +/- 8.8 A, mean +/- SD, p < 0.0001). Prevalence of small dense LDL was markedly higher in patients with CAD (72%) than in subjects without CAD (24%). CAD patients had significantly lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels (39.3 +/- 8.8 vs 49.8 +/- 12.0, 108.1 +/- 20.6 vs 122.9 +/- 20.1 mg/dl), and higher lipoprotein (a) and apolipoprotein B levels (28.8 +/- 30.4 vs 16.8 +/- 18.8, 96.5 +/- 21.8 vs 80.2 +/- 14.9 mg/dl) than non-CAD subjects, whereas total cholesterol, LDL-cholesterol, triglyceride, remnant-like particle cholesterol and insulin levels were not increased in CAD patients compared with non-CAD subjects. Stepwise regression analysis revealed that LDL particle size was the most powerful independent determinant of CAD (F value = 20.04, p < 0.0001). Logistic regression analysis revealed that small dense LDL phenotype relative risk (RR) of 7.0, 95% confidence interval (95% CI) 2.4-20.1], low HDL-cholesterol (RR of 5.6, 95% CI 2.1-15.2), and increased apolipoprotein B (RR of 5.8, 95% CI 1.8-18.5) were independently associated with incidence of CAD. CONCLUSIONS: High prevalence of small dense LDL is a leading cause of CAD with even normal cholesterol levels.