Low-Density Lipoprotein Subfractions and the Long-Term Risk of Ischemic Heart Disease in Men

Abstract

Objective— The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Québec Cardiovascular Study. Methods and Results— Cholesterol levels in the large and small LDL subfractions (termed LDL-C ≥260Å and LDL-C <255Å , respectively) were estimated from polyacrylamide gradient gel electrophoresis of whole plasma in the cohort of 2072 men of the population-based Québec Cardiovascular Study. All men were free of IHD at the baseline examination and followed-up for a period of 13 years, during which 262 first IHD events (coronary death, nonfatal myocardial infarction, and unstable angina pectoris) were recorded. Our study confirmed the strong and independent association between LDL-C <255Å levels as a proxy of the small dense LDL phenotype and the risk of IHD in men, particularly over the first 7 years of follow-up. However, elevated LDL-C ≥260Å levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P =0.07). Conclusions— These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles. Results from this large population-based study indicated that large LDL were not associated with an increased long-term risk of ischemic heart disease in men and that the risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.