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 - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 9
ER -