Abstract MP36: APOL1 and Risk of Incident Stroke in African Americans: The Atherosclerosis Risk in Communities Study
Background: African Americans (AAs) have an increased stroke burden when compared to European Americans (EAs) even after accounting for age, sex, and socioeconomic status. Genetic factors may contribute to this disparity. Common variants (rs73885319 & rs60910145 [G1 allele] & rs71785313 [G2 allele]) in the APOL1 gene are associated with end stage renal disease (ESRD) and account for a substantial proportion of the disparity in ESRD risk between AAs and EAs. Given the strong association between ESRD and stroke, we sought to evaluate whether the APOL1 risk variants are also associated with overall stroke risk and stroke sub-types among AAs in the Atherosclerosis Risk in Communities (ARIC) study.
Methods: The study sample included 2785 AAs free of stroke at ARIC visit 1 (1987-89) and followed for stroke events through 2009. Incident strokes were identified from hospitalization surveillance and annual phone follow-up and included ischemic, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) events. Cox proportional hazards models were used to estimate the hazard ratio (HR) of overall, ischemic, & hemorrhagic (ICH, excluding SAH) stroke comparing those with 2 to those with 0 or 1 APOL1 risk allele (recessive genetic model) with adjustment for baseline age, sex, study center, and further for hypertension medication use, systolic blood pressure, diabetes, chronic kidney disease (CKD, estimated glomerular filtration rate<60mL/min/1.73m2) and % European ancestry. We selected the recessive model a priori based on prior work of APOL1 and ESRD; the codominant model suggested that those with 1 risk allele were not significantly different from those with 0 risk alleles.
Results: Overall, 12.5% (349 of 2785) of ARIC AAs carried 2 APOL1 risk alleles (5.96% G1/G1, 4.78% G1/G2, and 1.80% G2/G2). Incident stroke events occurred in 287 participants (10.3%, 252 ischemic, 30 hemorrhagic) over 20 years median follow-up. Individuals with 2 risk alleles were not at higher risk for all stroke (HR 1.09, 95% confidence interval [CI] 0.77-1.54) or ischemic stroke (HR 0.91, 95% CI 0.62-1.35) compared to those with 0 or 1 risk allele. However, AAs with 2 risk alleles were significantly more likely to develop hemorrhagic stroke (HR 2.61, 95%CI 1.16-5.87) than those with 1 or 0 risk allele, even after adjusting for cardiovascular risk factors, % European ancestry, and CKD (HR 2.71, 95%CI 1.19-6.18, p=0.03).
Conclusions: In a large community-based sample of AAs, persons with 2 APOL1 G1/G2 risk alleles were more than twice as likely to develop hemorrhagic, but not ischemic, stroke than those with either 0 or 1 risk allele. This association was independent of baseline CKD and other major cardiovascular risk factors. The association between the APOL1 risk alleles and both kidney disease and hemorrhagic stroke suggest that the mechanisms underlying APOL1 related disease may involve systemic vascular changes.
- © 2013 by American Heart Association, Inc.