title: Altered composition of triglyceride-rich lipoproteins and coronary artery disease in a large case-control study.
abstract: BACKGROUND
  Traditional beta-quantification of plasma lipoproteins by ultracentrifugation separates triglyceride-rich lipoproteins (TGRL) from higher density lipoproteins. The cholesterol in the TGRL fraction is referred to as measured very low-density lipoprotein cholesterol (VLDL-C) recognizing that other TGRL may be present. The measured VLDL-C to total plasma triglyceride (VLDL-C/TG) has long been considered an index of average TGRL composition with abnormally high VLDL-C/TG ratios (>or=0.30 with TG>150mg/dL) indicative of atherogenic remnant accumulation (type III hyperlipidemia). However, virtually no reports are available which examine potential associations between CAD and VLDL-C/TG at the lower end of the spectrum.
  
  
  RESULTS
  We performed ultracentrifugation in 1170 cases with premature-onset, familial CAD and 1759 population-based controls and examined the VLDL-C/TG ratio as an index of TGRL composition. As expected, we found very high CAD risk associated with severe type III hyperlipidemia (OR 10.5, p=0.02). Unexpectedly, however, we found a robust, graded, and independent association between CAD risk and lower than average VLDL-C/TG ratios (p<0.0001 as ordered categories or as a continuous variable). Among those in the lowest VLDL-C/TG category (a ratio <0.12), CAD risk was clearly increased (OR 4.5, 95% CI 2.9-6.9) and remained significantly elevated in various subgroups including those with triglycerides below 200mg/dl, in males and females separately, as well as among those with no traditional CAD risk factors (OR 5.8, 95% CI 1.5-22). Significant compositional differences by case status were confirmed in a subset whose samples were re-spun with measurement of lipids and apolipoprotein B (apo B) in each subfraction.
  
  
  CONCLUSIONS
  We found a strong, graded, independent, and robust association between CAD and lower VLDL-C/TG ratios. We consider this a novel, hypothesis-generating observation which will hopefully generate additional future studies to provide confirmation and further insight into potential mechanisms.
authors.affiliation: Cardiovascular Genetics Research, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT 84108, USA. paul.hopkins@utah.ed
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: M Nazeem
authors.initials: MN
authors.lastname: Nanjee
authors.forename: Lily L
authors.initials: LL
authors.lastname: Wu
authors.forename: Michael G
authors.initials: MG
authors.lastname: McGinty
authors.forename: Eliot A
authors.initials: EA
authors.lastname: Brinton
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000150:complications / Q000235:genetics; D008074:Lipoproteins / Q000097:blood*; D053419:Lipoproteins, IDL / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D014461:Ultracentrifugation
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D014280:Triglycerides