APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension)

Teresa K Chen; Lawrence J Appel; Morgan E Grams; Adrienne Tin; Michael J Choi; Michael S Lipkowitz; Cheryl A Winkler; Michelle M Estrella

doi:10.1161/ATVBAHA.117.309384

APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension)

Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):1765-1769. doi: 10.1161/ATVBAHA.117.309384. Epub 2017 Jun 1.

Authors

Teresa K Chen¹, Lawrence J Appel², Morgan E Grams², Adrienne Tin², Michael J Choi², Michael S Lipkowitz², Cheryl A Winkler², Michelle M Estrella²

Affiliations

¹ From the Divisions of Nephrology (T.K.C., M.E.G., M.J.C.) and General Internal Medicine (L.J.A.), Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (L.J.A., M.E.G., A.T.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (A.T.); Division of Nephrology and Hypertension, Department of Medicine, Georgetown University School of Medicine, Washington, DC (M.S.L.); Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health and Leidos Biomedical, Frederick National Laboratory, MD (C.A.W.); and Kidney Health Research Collaborative, Department of Medicine, San Francisco VA Medical Center and University of California (M.M.E.). tchen39@jhmi.edu.
² From the Divisions of Nephrology (T.K.C., M.E.G., M.J.C.) and General Internal Medicine (L.J.A.), Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (L.J.A., M.E.G., A.T.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (A.T.); Division of Nephrology and Hypertension, Department of Medicine, Georgetown University School of Medicine, Washington, DC (M.S.L.); Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health and Leidos Biomedical, Frederick National Laboratory, MD (C.A.W.); and Kidney Health Research Collaborative, Department of Medicine, San Francisco VA Medical Center and University of California (M.M.E.).

Abstract

Objective: Among African Americans, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease.

Approach and results: In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with APOL1 genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m²) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between APOL1 genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, APOL1 high-risk variants were associated with increased cardiovascular mortality.

Conclusions: Among African Americans with hypertension-attributed chronic kidney disease, APOL1 risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.

Keywords: cardiovascular disease; coronary artery disease; heart failure; hypertension; myocardial infarction.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Apolipoprotein L1
Apolipoproteins / genetics*
Black or African American / genetics*
Chi-Square Distribution
Disease Progression
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation*
Heart Failure / ethnology
Heart Failure / genetics*
Heart Failure / mortality
Heart Failure / therapy
Hospitalization
Humans
Hypertension / ethnology
Hypertension / genetics*
Hypertension / mortality
Incidence
Kaplan-Meier Estimate
Lipoproteins, HDL / genetics*
Male
Middle Aged
Myocardial Infarction / ethnology
Myocardial Infarction / genetics*
Myocardial Infarction / mortality
Myocardial Infarction / therapy
Myocardial Revascularization
Phenotype
Prognosis
Proportional Hazards Models
Renal Insufficiency, Chronic / ethnology
Renal Insufficiency, Chronic / genetics*
Renal Insufficiency, Chronic / mortality
Risk Assessment
Risk Factors
Stroke / ethnology
Stroke / genetics*
Stroke / mortality
Stroke / therapy
Time Factors
United States / epidemiology

Substances

APOL1 protein, human
Apolipoprotein L1
Apolipoproteins
Lipoproteins, HDL

Abstract

Publication types

MeSH terms

Substances

Grants and funding