This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johannsen, T. H. Articles by Nordestgaard, B. G. Search for Related Content PubMed PubMed Citation Articles by Johannsen, T. H. Articles by Nordestgaard, B. G. Related Collections Lipid Cardiovascular Endocrinology

Hepatic Lipase, Genetically Elevated High-Density Lipoprotein, and Risk of Ischemic Cardiovascular Disease

Department of Clinical Biochemistry (T.H.J., P.R.K., R.V.A., B.G.N.), Herlev Hospital, Copenhagen University Hospital, DK-2730 Herlev, Denmark; The Copenhagen City Heart Study (G.B.J., A.T.-H., B.G.N.), Bispebjerg Hospital, Copenhagen University Hospital, DK-2400 Copenhagen, Denmark; Department of Vascular Surgery (H.S.), and Department of Clinical Biochemistry (A.T.-H.), Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; and Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Børge G. Nordestgaard, M.D., D.M.Sc., Professor, Chief Physician, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. E-mail: brno{at}heh.regionh.dk.

Context: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease).

Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and –480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD.

Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete.

Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in –480c>t heterozygotes, and by 0.13 mmol/liter in –480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84–0.90], 0.96 (95% CI 0.95–0.97), and 0.91 (95% CI 0.89–0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76–1.88), 1.04 (0.96–1.13), and 1.08 (0.89–1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0.

Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD.

This article has been cited by other articles:

				S. Fazio and M. F. Linton Elevated High-Density Lipoprotein (HDL) Levels due to Hepatic Lipase Mutations Do Not Reduce Cardiovascular Disease Risk: Another Strike against the HDL Dogma J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1081 - 1083. [Full Text] [PDF]