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Original Investigation
August 2018

Association of APOL1 With Heart Failure With Preserved Ejection Fraction in Postmenopausal African American Women

Author Affiliations
  • 1Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina, Chapel Hill
  • 2Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
  • 3MedStar Heart and Vascular Institute, Washington, DC
  • 4Cardiology Division, George Washington University School of Medicine and Health Sciences, Washington, DC
  • 5Department of Statistics and Operations Research, University of North Carolina, Chapel Hill
  • 6University of Washington School of Public Health, Seattle
  • 7Division of Nephrology, Harvard Medical School, Boston, Massachusetts
  • 8Department of Epidemiology, University of Iowa College of Public Health, Iowa City
  • 9Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, National Cancer Institute Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland
JAMA Cardiol. 2018;3(8):712-720. doi:10.1001/jamacardio.2018.1827
Key Points

Question  Are APOL1 risk genotypes associated with cardiovascular disease and stroke in postmenopausal African American women?

Findings  In this study of 11 137 participants in the Women’s Health Initiative, high-risk APOL1 genotypes were not associated with coronary heart disease, stroke, and all-cause and cardiovascular mortality. However, high-risk APOL1 genotypes were associated with hospitalized heart failure with preserved ejection fraction, but associations were partly accounted for by baseline kidney function.

Meaning  This study does not support a relationship among high-risk APOL1 genotypes and cardiovascular disease in postmenopausal women, except for heart failure with preserved ejection fraction, mechanisms of which might include chronic kidney disease.

Abstract

Importance  APOL1 genotypes are associated with kidney diseases in African American individuals and may influence cardiovascular disease and mortality risk, but findings have been inconsistent.

Objective  To discern whether high-risk APOL1 genotypes are associated with cardiovascular disease and stroke in postmenopausal African American women, who are at high risk for these outcomes.

Design, Setting, and Participants  The Women's Health Initiative is a prospective cohort that enrolled 161 838 postmenopausal women into clinical trials and an observational study between 1993 and 1998. This study includes 11 137 African American women participants who had a clinical event from enrollment to June 2014. Data analyses were completed from January 2017 to August 2017.

Exposures  The variants of APOL1 were genotyped or imputed from whole-exome sequencing.

Main Outcomes and Measures  Incident coronary heart disease, stroke and heart failure subtypes, and overall and cause-specific mortality were adjudicated from hospital records and death certificates. Estimated incidence rates were determined for each outcome and hazard ratios (HR) and 95% CIs for the associations of APOL1 groups with outcomes.

Results  The mean (SD) age of participants was 61.7 (7.1) years. Carriers of high-risk APOL1 variants (n = 1370; 12.3%) had higher prevalence of hypertension, use of cholesterol-lowering medications, and reduced estimated glomerular filtration rate (eGFR). After a mean (SD) of 11.0 (3.6) years, carriers of high-risk APOL1 variants had a higher incidence rate of hospitalized heart failure with preserved ejection fraction (HFpEF) than low-risk carriers did but showed no differences for other outcomes. In adjusted models, there was a significant 58% increased hazard of hospitalized HFpEF (HR, 1.58 [95% CI, 1.03-2.41]) among carriers of high-risk APOL1 variants compared with carriers of low-risk APOL1 variants. The association with HFpEF was attenuated (HR = 1.50 [95% CI, 0.98-2.30]) and no longer significant when adjusting for baseline eGFR.

Conclusions and Relevance  Status as a carrier of a high-risk APOL1 genotype was associated with HFpEF hospitalization among postmenopausal women, which is partly accounted for by baseline kidney function. These findings do not support an association of high-risk APOL1 genotypes with coronary heart disease, stroke, or mortality in postmenopausal African American women.

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