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Background    APOL 1  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   APOL 1  genotypes among self‐identified black participants of MESA (Multi‐Ethnic Study of Atherosclerosis).    Methods and Results  Cross‐sectional associations of   APOL 1  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   APOL 1  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   APOL 1  genotyping (mean age 62 years, 55% women, mean cystatin C–based estimated glomerular filtration rate 89 mL/min per 1.73 m 2 , 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   APOL 1  genotypes. The   APOL 1  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   APOL 1  high‐risk genotypes were not significantly associated with other clinical  CVD  outcomes.    Conclusions  Among blacks without baseline  CVD , the   APOL 1  high‐risk variants may be associated with increased risk for incident heart failure but not subclinical  CVD  or incident clinical atherosclerotic  CVD .

Association Between APOL 1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)