Smallest LDL particles are most strongly related to coronary disease progression in men.

OBJECTIVE LDLs include particle subclasses that have different mobilities on polyacrylamide gradient gels: LDL-I (27.2 to 28.5 nm), LDL-IIa (26.5 to 27.2 nm), LDL-IIb (25.6 to 26.5 nm), LDL-IIIa (24.7 to 25.6 nm), LDL-IIIb (24.2 to 24.7 nm), LDL-IVa (23.3 to 24.2 nm), and LDL-IVb (22.0 to 23.3 nm in diameter). We hypothesized that the association between smaller LDL particles and coronary artery disease (CAD) risk might involve specific LDL subclasses. METHODS AND RESULTS Average 4-year onstudy lipoprotein measurements were compared with annualized rates of stenosis change from baseline to 4 years in 117 men with CAD. The percentages of total LDL and HDL occurring within individual subclasses were measured by gradient gel electrophoresis. Annual rate of stenosis change was related concordantly to onstudy averages of total cholesterol (P=0.04), triglycerides (P=0.05), VLDL mass (P=0.03), total/HDL cholesterol ratio (P=0.04), LDL-IVb (P=0.01), and HDL(3a) (P=0.02) and inversely to HDL(2)-mass (P=0.02) and HDL(2b) (P=0.03). The average annual rate in stenosis change was 6-fold more rapid in the fourth quartile of LDL-IVb (>or=5.2%) than in the first quartile (<2.5%, P=0.03). Stepwise multiple regression analysis showed that LDL-IVb was the single best predictor of stenosis change. CONCLUSIONS LDL-IVb was the single best lipoprotein predictor of increased stenosis, an unexpected result, given that LDL-IVb represents only a minor fraction of total LDL.