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

TY - JOUR

T1 - Effect of APOE ε Genotype on Lipoprotein(a) and the Associated Risk of Myocardial Infarction and Aortic Valve Stenosis

AU - Kritharides, Leonard

AU - Nordestgaard, Børge G

AU - Tybjærg-Hansen, Anne

AU - Kamstrup, Pia R

AU - Afzal, Shoaib

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Context: APOE «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 «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 «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 «33, age- and sex-adjusted lipoprotein(a) concentrations were lower by 15% in «23, by 24% in «24, and by 36% in «22; adjusted for plasma apolipoprotein E, corresponding values were 22%, 28%, and 62%. These reductions were independent of LPA genotypes. Compared with «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 «2 noncarriers with lipoprotein(a) #50 mg/dL, 1.68 (1.21 to 2.32) for «2 carriers with lipoprotein(a) .50 mg/dL, and 1.92 (1.59 to 2.32) for «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 «2/3/4 genotype had minimal influence on these risk estimates. Conclusions: APOE «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.

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

KW - Adult

KW - Age Factors

KW - Aged

KW - Aortic Valve Stenosis

KW - Apolipoproteins E

KW - Biomarkers

KW - Denmark

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Incidence

KW - Lipoprotein(a)

KW - Male

KW - Middle Aged

KW - Myocardial Infarction

KW - Prognosis

KW - Proportional Hazards Models

KW - Registries

KW - Regression Analysis

KW - Retrospective Studies

KW - Risk Assessment

KW - Sex Factors

KW - Survival Rate

KW - Comparative Study

KW - Journal Article

U2 - 10.1210/jc.2017-01049

DO - 10.1210/jc.2017-01049

M3 - Journal article

C2 - 28651346

SN - 0021-972X

VL - 102

SP - 3390

EP - 3399

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 9

ER -