A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men

BACKGROUND: The current interpretation of the increased risk of ischemic he art disease (IHD) associated with reduced low density lipoprotein (LDL) par ticle size is based entirely on data derived from relatively small case-con trol studies, with a lack of evidence from large, prospective, population,b ased cohort data. OBJECTIVES: To investigate the association between LDL particle size and in cident IHD on the basis of data from the entire population-based, prospecti ve cohort of men from the Quebec Cardiovascular Study. PATIENTS AND METHODS: Analyses were conducted in a cohort of 2057 men who w ere all initially free of IHD, and who were followed up over a five-year pe riod, during which 108 first IHD events (myocardial infarction, angina or c oronary death) were recorded. LDL particle size was measured by nondenaturi ng gradient gel electrophoresis. RESULTS: Cox proportional hazards analysis indicated that the relationship between LDL particle size and the risk of future IHD events was not linear. Men with an LDL particle size less than 256.0 Angstrom had a significant 2 .2-fold increase in the five-year rate of IHD (P <0.001) compared with men having an LDL particle size greater than 256.0 Angstrom. Multivariate and s ubgroup analyses indicated that small, dense LDL particles predicted the ra te of IHD independent of LDL cholesterol, triglycerides, high density lipop rotein (HDL) cholesterol, apolipoprotein B and the total cholesterol to HDL cholesterol ratio. Finally, the magnitude of the increase in IHD risk attr ibuted to lipid risk factors was modulated to a significant extent by varia tions in LDL particle size. CONCLUSIONS: The present study provides the first large scale, population-b ased, prospective evidence supporting the hypothesis that small, dense LDL particles may be associated with an increased risk of IHD. The results also suggest that information on LDL diameter may improve the ability to predic t IHD risk accurately over traditional lipid variables.