title: A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men.
abstract: BACKGROUND
  The current interpretation of the increased risk of ischemic heart disease (IHD) associated with reduced low density lipoprotein (LDL) particle size is based entirely on data derived from relatively small case-control studies, with a lack of evidence from large, prospective, population-based cohort data.
  
  
  OBJECTIVE
  To investigate the association between LDL particle size and incident IHD on the basis of data from the entire population-based, prospective cohort of men from the Quebec Cardiovascular Study.
  
  
  METHODS
  Analyses were conducted in a cohort of 2057 men who were all initially free of IHD, and who were followed up over a five-year period, during which 108 first IHD events (myocardial infarction, angina or coronary death) were recorded. LDL particle size was measured by nondenaturing 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 A 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 A. Multivariate and subgroup analyses indicated that small, dense LDL particles predicted the rate of IHD independent of LDL cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, apolipoprotein B and the total cholesterol to HDL cholesterol ratio. Finally, the magnitude of the increase in IHD risk attributed to lipid risk factors was modulated to a significant extent by variations in LDL particle size.
  
  
  CONCLUSIONS
  The present study provides the first large scale, population-based, 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 predict IHD risk accurately over traditional lipid variables.
authors.affiliation: Department of Food Sciences and Nutrition, Laval University, Québec City, Québec, Canada. benoit.lamarche@crchul.ulaval.ca
authors.forename: B
authors.initials: B
authors.lastname: Lamarche
authors.forename: A C
authors.initials: AC
authors.lastname: St-Pierre
authors.forename: I L
authors.initials: IL
authors.lastname: Ruel
authors.forename: B
authors.initials: B
authors.lastname: Cantin
authors.forename: G R
authors.initials: GR
authors.lastname: Dagenais
authors.forename: J P
authors.initials: JP
authors.lastname: Després
mesh_terms: D017677:Age Distribution; D000368:Aged; D001054:Apolipoproteins A / Q000032:analysis; D002170:Canada / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000032:analysis; D008078:Cholesterol, LDL / Q000032:analysis*; D015331:Cohort Studies; D015897:Comorbidity; D004587:Electrophoresis, Agar Gel; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis* / Q000453:epidemiology*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000453:epidemiology*; D010316:Particle Size; D011159:Population Surveillance; D011336:Probability; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D014280:Triglycerides / Q000032:analysis
chemical_list: D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides