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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.

Background-Several cross-sectional studies and 3 prospective, nested, case-control studies have indicated that individuals with small, dense low density lipoprotein (LDL) particles are at increased risk for ischemic heart disease (IHD). However, whether LDL particle size is an independent risk factor for future IHD events remains controversial. The objective of the present study was to further analyze the cardiovascular risk associated with various electrophoretic characteristics of LDL particles in men. Methods and Results-LDL particles were characterized by polyacrylamide gradient gel electrophoresis (PAGGE) in a cohort of 2034 men of the Quebec Cardiovascular Study. All men were initially free of IHD and were followed up for a period of 5 years, during which 108 first IHD events were recorded. Among all LDL characteristics investigated by PAGGE, including LDL peak particle size, the cholesterol concentration in LDL particles with a diameter smaller than 255 Å showed the strongest association with the risk of IHD (relative riskϭ4.6 in men in the third vs first tertile of the distribution, PϽ0.001). Multivariate logistic and survival models indicated that the relationship between LDL cholesterol levels in particles with a diameter Ͻ255 Å and IHD risk was independent of all nonlipid risk factors and of LDL cholesterol, high density lipoprotein cholesterol, triglyceride, and lipoprotein(a) levels. Conclusions-Results from this large, population-based, prospective study suggest that further characterization of LDL particles by PAGGE, in addition to the traditional lipid profile, may improve our ability to predict IHD events in men.

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