title: Apolipoprotein C-III as a Potential Modulator of the Association Between HDL-Cholesterol and Incident Coronary Heart Disease.
abstract: BACKGROUND
  High-density lipoproteins (HDL) are structurally and metabolically heterogeneous and subclasses with differential effects on coronary heart disease (CHD) might exist. Apolipoprotein (apo) C-III, a small proinflammatory protein that resides on the surface of lipoproteins, enhances the atherogenicity of VLDL and LDL particles, but little is known about the role apoC-III on HDL. We investigated whether the presence or absence of apoC-III differentiates HDL into subtypes with nonprotective or protective associations with risk of future CHD.
  
  
  RESULTS
  High-density lipoprotein cholesterol (HDL-C) levels were measured in plasma separated according to apoC-III (by immunoaffinity chromatography) in two prospective case-control studies nested within the Nurses' Health and the Health Professionals Follow-Up Studies. Baseline was in 1990 and 1994, and 634 incident CHD cases were documented through 10 to 14 years of follow-up. The relative risk of CHD per each standard deviation of total HDL-C was 0.78 (95% confidence intervals, 0.63-0.96). The HDL-C subtypes were differentially associated with risk of CHD, HDL-C without apoC-III inversely and HDL-C with apoC-III directly (P=0.02 for a difference between the HDL types). The relative risk per standard deviation of HDL-C without apoC-III was 0.66 (0.53 to 0.93) and 1.18 (1.03 to 1.34) for HDL-C with apoC-III. HDL-C with apoC-III comprised ∼13% of the total HDL-C. Adjustment for triglycerides and apoB attenuated the risks; however, the two HDL-C subgroups remained differentially associated with risk of CHD (P=0.05).
  
  
  CONCLUSIONS
  Separating HDL-C according to apoC-III identified two types of HDL with opposing associations with risk of CHD. The proatherogenic effects of apoC-III, as a component of VLDL and LDL, may extend to HDL. (J Am Heart Assoc. 2012;1:jah3-e000232 doi: 10.1161/JAHA.111.000232.).
authors.affiliation: Department of Nutrition, Harvard School of Public Health,  Boston, MA (M.K.J., E.B.R., J.D.F., F.M.S.).
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Furtado
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
keywords: apolipoproteins; cardiovascular disease; epidemiology; lipids