APOL1 Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis

Area of Science:

• Genetics and Cardiovascular Health
• Nephrology and Public Health

Background:

• Two coding variants in the apolipoprotein L1 (APOL1) gene are strongly associated with kidney disease in Black populations.
• Kidney disease increases cardiovascular disease (CVD) risk, but the independent effect of APOL1 variants on CVD risk remains unclear due to inconsistent previous findings.

Purpose of the Study:

• To investigate the association of APOL1 kidney-risk variants with cardiovascular disease events and mortality.
• To determine if APOL1 variants have an independent effect on CVD risk, separate from kidney function measures.

Main Methods:

• A two-stage individual participant data meta-analysis was conducted.
• Included 21,305 Black individuals from eight large cohorts, assessing adjudicated cardiovascular disease events and death.
• Follow-up averaged 8.9 years, with fully-adjusted analyses considering various health factors.

Main Results:

• No association was found between two APOL1 kidney-risk variants and incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke, heart failure) or death.
• Hazard ratio for incident CVD was 1.11 (95% CI, 0.96 to 1.28) for individuals with two risk variants compared to those with zero or one.
• Associations remained non-significant across individual CVD outcomes and were not influenced by kidney function, age, diabetes, or BMI.

Conclusions:

• APOL1 kidney-risk variants are not associated with incident cardiovascular disease or death when considered independently of kidney measures.
• This large-scale meta-analysis provides robust evidence against a direct, independent role of APOL1 variants in cardiovascular risk.