Effect of APOE ε Genotype on Lipoprotein(a) and the Associated Risk of Myocardial Infarction and Aortic Valve Stenosis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Context: APOEε2/3/4 genotypes affect plasma lipoprotein(a); however, the effects of APOE genotypes on the prediction of myocardial infarction and aortic valve stenosis by lipoprotein(a) are unknown.
Objective: We tested the hypothesis that APOEε2/3/4 genotype affects plasma lipoprotein(a), the contribution of plasma apoE levels to this association as well as the associated risk of myocardial infarction and aortic valve stenosis.
Design and Outcome Measures: In 46,615 individuals from the general population, we examined plasma lipoprotein(a), APOE ε2/3/4, and incidence of myocardial infarction (n = 1807) and aortic valve stenosis (n = 345) over 37 years of follow-up (range: 0.3 to 38 years).
Results: Compared with ε33, age- and sex-adjusted lipoprotein(a) concentrations were lower by 15% in ε23, by 24% in ε24, and by 36% in ε22; adjusted for plasma apolipoprotein E, corresponding values were 22%, 28%, and 62%. These reductions were independent of LPA genotypes. Compared with ε2 carriers with lipoprotein(a) ≤50 mg/dL, the hazard ratio for myocardial infarction was 1.26 (95% confidence interval: 1.06 to 1.49) for ε2 noncarriers with lipoprotein(a) ≤50 mg/dL, 1.68 (1.21 to 2.32) for ε2 carriers with lipoprotein(a) >50 mg/dL, and 1.92 (1.59 to 2.32) for ε2 noncarriers with lipoprotein(a) >50 mg/dL (interaction, P = 0.57); corresponding values for aortic valve stenosis were 1.05 (0.74 to 1.51), 1.49 (0.72 to 3.08), and 2.04 (1.46 to 2.26) (interaction, P = 0.50). Further adjustment for APOE ε2/3/4 genotype had minimal influence on these risk estimates.
Conclusions: APOE ε2 is a strong genetic determinant of low lipoprotein(a) concentrations but does not modify the causal association of lipoprotein(a) with myocardial infarction or aortic valve stenosis.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Clinical Endocrinology and Metabolism |
Vol/bind | 102 |
Udgave nummer | 9 |
Sider (fra-til) | 3390-3399 |
Antal sider | 10 |
ISSN | 0021-972X |
DOI | |
Status | Udgivet - 1 sep. 2017 |
ID: 184876195