APOL1 renal-risk variants do not associate with incident cardiovascular disease or mortality in the Systolic Blood Pressure Intervention Trial

Kidney Int Rep. 2017 Jul;2(4):713-720. doi: 10.1016/j.ekir.2017.03.008. Epub 2017 Mar 31.


Introduction: Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, 2,568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including non-fatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, non-fatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality.

Methods: Cox proportional hazards regression models were employed adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg versus <140 mm Hg).

Results: Fourteen percent of participants had two APOL1 RRVs; these individuals also had lower baseline estimated GFR and higher levels of albuminuria and BMI. After a median follow-up of 39 months, no significant association was observed between APOL1 RRVs and the primary composite CVD outcome, any of its components, or all-cause mortality (recessive or additive genetic models). APOL1 demonstrated a trend toward association with sustained 30% reduction in estimated GFR to <60 ml/min/1.73m2 in those with normal kidney function at baseline (hazard ratio [95% CI] 1.64 [0.85-2.93]; p=0.114, recessive model).

Conclusion: APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, non-diabetic African American participants in SPRINT.

Keywords: APOL1; African Americans; SPRINT; albuminuria; cardiovascular disease; chronic kidney disease.