APOL1 Renal-Risk Variants Do Not Associate With Incident Cardiovascular Disease or Mortality in the Systolic Blood Pressure Intervention Trial

Introduction: Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, a total of 2568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including nonfatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality. Methods: Cox proportional hazards regression models were used, adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg vs. <140 mm Hg). Results: Of the participants, 14% had 2 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/1.73 m(2) in those with normal kidney function at baseline (hazard ratio 1.64; 95% confidence interval = 0.85-2.93; P = 0.114, recessive model). Discussion: APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, nondiabetic African American participants in SPRINT.