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LCAT, HDL cholesterol and ischemic cardiovascular disease: a Mendelian randomization study of HDL cholesterol in 54,500 individuals.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2012 Feb; Vol. 97 (2), pp. E248-56. Date of Electronic Publication: 2011 Nov 16. - Publication Year :
- 2012
-
Abstract
- Background: Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.<br />Methods: We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants in the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals. One variant, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.<br />Results: Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies combined was 0.49 (0.11-2.16), whereas the hazard ratio for MI for a 50% reduction in plasma HDL cholesterol in the CCHS was 2.11 (1.70-2.62) (P(comparison) = 0.03).<br />Conclusion: Low plasma HDL cholesterol levels robustly associated with increased risk of MI but genetically decreased HDL cholesterol did not. This may suggest that low HDL cholesterol levels per se do not cause MI.
- Subjects :
- Adult
Aged
Aged, 80 and over
Cardiovascular Diseases blood
Cardiovascular Diseases epidemiology
Cardiovascular Diseases genetics
Cholesterol, HDL analysis
Cholesterol, HDL genetics
Cohort Studies
Cross-Sectional Studies
Denmark
Female
Humans
Male
Middle Aged
Myocardial Ischemia epidemiology
Phosphatidylcholine-Sterol O-Acyltransferase physiology
Polymorphism, Single Nucleotide physiology
Registries
Young Adult
Cholesterol, HDL blood
Mendelian Randomization Analysis
Myocardial Ischemia blood
Myocardial Ischemia genetics
Phosphatidylcholine-Sterol O-Acyltransferase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 97
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22090275
- Full Text :
- https://doi.org/10.1210/jc.2011-1846