Effect of APOE &egr; Genotype on Lipoprotein(a) and the Associated Risk of Myocardial Infarction and Aortic Valve Stenosis

Context: APOE &egr;2/3/4 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 APOE&egr;2/3/4 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 &egr;2/3/4, 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 &egr;33, age‐ and sex‐adjusted lipoprotein(a) concentrations were lower by 15% in &egr;23, by 24% in &egr;24, and by 36% in &egr;22; adjusted for plasma apolipoprotein E, corresponding values were 22%, 28%, and 62%. These reductions were independent of LPA genotypes. Compared with &egr;2 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 &egr;2 noncarriers with lipoprotein(a) ≤50 mg/dL, 1.68 (1.21 to 2.32) for &egr;2 carriers with lipoprotein(a) >50 mg/dL, and 1.92 (1.59 to 2.32) for &egr;2 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 &egr;2/3/4 genotype had minimal influence on these risk estimates. Conclusions: APOE &egr;2 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.

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