학술논문

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi-Ethnic Study of Atherosclerosis).
Document Type
article
Source
Journal of the American Heart Association. 6(12)
Subject
Humans
Cardiovascular Diseases
DNA
Incidence
Prevalence
Risk Factors
Cross-Sectional Studies
DNA Mutational Analysis
Genotype
Mutation
Missense
Aged
Aged
80 and over
Middle Aged
Ethnic Groups
Female
Male
Atherosclerosis
Apolipoprotein L1
APOL1
Multi‐Ethnic Study of Atherosclerosis
cardiovascular disease
coronary artery calcium
heart failure
APOL1
Multi-Ethnic Study of Atherosclerosis
Prevention
Clinical Research
Genetics
Heart Disease
Heart Disease - Coronary Heart Disease
Aging
Kidney Disease
Cardiovascular
4.1 Discovery and preclinical testing of markers and technologies
Cardiorespiratory Medicine and Haematology
Language
Abstract
BACKGROUND:APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self-identified black participants of MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS:Cross-sectional associations of APOL1 genotypes (high-risk=2 alleles; low-risk=0 or 1 allele) with coronary artery calcification, carotid-intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62 years, 55% women, mean cystatin C-based estimated glomerular filtration rate 89 mL/min per 1.73 m2, 12% with albuminuria), 12% had the high-risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid-intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high-risk group was 82% more likely to develop incident heart failure compared with the low-risk group (95% confidence interval, 1.01-3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00-3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03-3.35) slightly attenuated this association. The APOL1 high-risk genotypes were not significantly associated with other clinical CVD outcomes. CONCLUSIONS:Among blacks without baseline CVD, the APOL1 high-risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD.