Abstract: SA-PO624

APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults

Session Information

Category: Genetic Diseases of the Kidney

  • 803 Genetic Epidemiology and Other Genetic Studies of Common Kidney Diseases

Authors

  • Gutierrez, Orlando M., UAB School of Medicine , Birmingham, Alabama, United States
  • Sale, Michele, University of Virginia, Charlottesville, Virginia, United States
  • Nelson, George W., SAIC-Frederick/FNLCR, Frederick, Maryland, United States
  • Safford, Monika M., Weill Cornell Medicine, New York, New York, United States
  • Hacinth, Hyacinth I, Aflac Cancer and Blood Disorder Center, of Children?s Healthcare of Atlanta, Atlanta, Georgia, United States
  • Judd, Suzanne E., UAB, Birmingham, Alabama, United States
  • Kopp, Jeffrey B., NIDDK, NIH, Bethesda, Maryland, United States
  • Winkler, Cheryl Ann, NCI, NIH, Frederick National Laboratory, Frederick, Maryland, United States
  • Irvin, Marguerite, UAB, Birmingham, Alabama, United States
  • Chaudhary, Ninad S., University of Alabama at Birmingham, Birimingham, Alabama, United States
  • Cushman, Mary, University of Vermont, Colchester, Vermont, United States
  • Zakai, Neil A., University of Vermont, Colchester, Vermont, United States
  • Limou, Sophie, NIH, Leidos Biomedical Research Inc, Nantes, France
  • Pamir, Nathalie, Oregon Health and Science University, Portland, Oregon, United States
  • Reiner, Alex, University of Washington, Seattle, Washington, United States
  • Naik, Rakhi, Johns Hopkins, Baltimore, Maryland, United States
Background

APOL1 nephropathy risk variants are strongly associated with chronic kidney disease progression in Black adults, but associations with incident cardiovascular disease (CVD) are uncertain.

Methods

We examined associations of APOL1 risk variants with incident coronary heart disease (CHD,n=323), stroke (n=331), and a combined CVD end point (n=500) in 10,605 Black participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Main analyses compared those with APOL1 high-risk nephropathy genotypes (2 risk variants) to APOL1 low-risk genotypes (0/1 risk variant) in Cox models adjusted for CVD risk factors and ancestry principle components.

Results

APOL1 high-risk participants were younger and more likely to have albuminuria than APOL1 low-risk participants. The risk of incident stroke, CHD or the composite CVD endpoint did not significantly differ by APOL1 genotype in multivariable models. However, the association of APOL1 genotype with the composite CVD outcome differed by diabetes status (P<0.01). In those without diabetes, high-risk genotypes were associated with higher risk of incident composite CVD than low-risk genotypes in fully adjusted models [table]. This association appeared to be driven by incident stroke risk. In contrast, the APOL1 high-risk genotype was associated with a trend towards lower risk of CVD in diabetics.

Conclusion

APOL1 high-risk genotypes are associated with higher incidence of CVD events in individuals without diabetes, whereas the association appeared to be opposite among individuals with diabetes.

Hazard ratio (95% confidence interval) of incident CVD in APOL1 high- vs. low-risk genotypes
 N events/N at riskModel
No diabetes  
Stroke197/66212.32(1.33,4.07)
Coronary heart disease174/61731.31(0.81,2.10)
Composite Events297/57551.67(1.12,2.47)
Diabetes  
Stroke131/26600.55(0.22,1.37)
Coronary Heart Disease148/23290.53(0.24,1.14)
Composite Events200/20720.52(0.26,1.03)

Model adjusted for age, sex, smoking, medications, and principal components ancestry

Funding

  • NIDDK Support