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Circulation. 2019 Jul 24. doi: 10.1161/CIRCULATIONAHA.118.036589. [Epub ahead of print]

Association of APOL1 Risk Alleles with Cardiovascular Disease in African Americans in the Million Veteran Program.

Author information

1
Boston VA Healthcare System, Boston, MA; Massachusetts General Hosp, Boston, MA and Broad Institute of MIT and Harvard, Cambridge, MA.
2
Nashville VA Medical Center, Nashville, TN; Vanderbilt University Medical Center, Nashville, TN.
3
Edith Norse Rogers Memorial VA Medical Center, Bedford, MA.
4
Edith Norse Rogers Memorial VA Medical Center, Bedford, MA; University of Massachusetts College of Nursing & Health Sciences, Boston, MA; VA Informatics and Computing Infrastructure, Salt Lake City, UT.
5
Palo Alto VA Health Care, Palo Alto, CA; Stanford University School of Medicine, Stanford, CA.
6
Boston VA Healthcare System, Boston, MA; Edith Norse Rogers Memorial VA Medical Center, Bedford, MA.
7
Corporal Michael Crescenz VA Med Cntr, Philadelphia, PA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
8
Edith Norse Rogers Memorial VA Medical Center, Bedford, MA; Boston University, Boston, MA; Nashville VA Medical Center, Nashville TN.
9
Massachusetts General Hosp, Boston, MA and Broad Institute of MIT and Harvard, Cambridge, MA.
10
Atlanta VA Medical Ctr, Atlanta, GA; Emory University, Atlanta, GA.
11
Nashville VA Medical Center, Nashville, TN.
12
VA Connecticut HealthCare System, New Haven, CA.
13
Boston VA Healthcare System, Boston, MA; Harvard Medical School, Boston, MA.
14
Massachusetts General Hosp, Boston, MA and Broad Institute of MIT and Harvard, Cambridge, MA; Harvard Medical School, Boston, MA.
15
Corporal Michael Crescenz VA Med Cntr, Philadelphia, PA.
16
Stanford University School of Medicine, Stanford, CA; Corporal Michael Crescenz VA Med Cntr, Philadelphia, PA.

Abstract

BACKGROUND:

Approximately 13% of African-American individuals carry two copies of the APOL1 risk alleles G1 or G2, which are associated with 1.5-2.5 fold increased risk of chronic kidney disease (CKD). There have been conflicting reports as to whether an association exists between APOL1 risk alleles and cardiovascular disease, independent of the effects of APOL1 on kidney disease. We sought to test the association of APOL1 G1/G2 alleles with coronary artery disease (CAD), peripheral artery disease (PAD), and stroke among African American individuals in the Million Veteran Program (MVP).

METHODS:

We performed a time-to-event analysis of retrospective electronic health record (EHR) data using Cox proportional hazard and competing risks Fine and Gray sub-distribution hazard models. The primary exposure was APOL1 risk allele status. The primary outcome was incident CAD amongst individuals without CKD during the 12.5 year follow up period. Separately we analyzed the cross-sectional association of APOL1 risk allele status with lipid traits and 115 cardiovascular diseases using phenome-wide association.

RESULTS:

Among 30,903 African American MVP participants, 3,941 (13%) carried the two APOL1 risk allele high-risk genotype. Individuals with normal kidney function at baseline with two risk alleles had slightly higher risk of developing CAD compared to those with no risk alleles (Hazard Ratio (HR): 1.11, 95% Confidence Interval (CI): 1.01-1.21, p=0.039). Similarly, modest associations were identified with incident stroke (HR: 1.20, 95% CI: 1.05-1.36, p=0.007) and PAD (HR: 1.15, 95% CI:1.01-1.29, p=0.031). When modeling both cardiovascular and renal outcomes, APOL1 was strongly associated with incident renal disease, while no significant association with the cardiovascular disease endpoints could be detected. Cardiovascular phenome-wide association analyses did not identify additional significant associations with cardiovascular disease subsets.

CONCLUSIONS:

APOL1 risk variants display a modest association with cardiovascular disease and this association is likely mediated by the known APOL1 association with CKD.

KEYWORDS:

Apolipoprotein L

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