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No Link Between Genetically Low HDL Cholesterol and Heart Disease Risk CHICAGO -- June 4, 2008 -- Lower levels of high-density lipoprotein (HDL) cholesterol due to a gene mutation is not associated with an increased risk of ischemic heart disease (IHD), according to a study in the June 4 issue of JAMA. Ruth Frikke-Schmidt, MD, PhD, University of Copenhagen, Denmark, and colleagues examined whether mutations in the gene ABCA1, which genetically reduce HDL cholesterol levels but do not increase plasma triglyceride levels, are associated with an increased risk of IHD. Three studies were used: the Copenhagen City Heart Study (CCHS), a 31-year general population study; the Copenhagen General Population Study (CGPS); and the Copenhagen Ischemic Heart Disease Study (CIHDS). Data in all 3 studies were collected during the period of January 1976 through July 2007. Researchers analysed data on HDL cholesterol levels and the association between IHD and HDL cholesterol and genotype. The researchers found that heterozygotes versus noncarriers for 4 ABCA1 mutations had HDL cholesterol levels of 41 mg/dL versus 58 mg/dL, corresponding to a reduction in HDL cholesterol of 17 mg/dL. A 17-mg/dL lower HDL cholesterol level in the CCHS was associated with a 70% higher risk for IHD. However, for IHD in heterozygotes versus noncarriers, the risk was 33% lower in the CCHS, 18% lower in the CGPS, and 14% lower in the CIHDS. When the studies were combined, there was no association between heterozygotes and a higher risk of IHD. "The principal finding of this study is that heterozygosity for loss-of-function mutations in ABCA1 associated with substantial, lifelong lowering of plasma levels of HDL cholesterol, but not with corresponding higher levels of plasma triglycerides or atherogenic remnant lipoproteins, did not predict an increased risk of IHD," the authors concluded. SOURCE: Journal of the American Medical Association E-mail this page to a friend or colleague! To print, use this version