APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults.
BACKGROUND
APOL1 renal risk variants are strongly associated with chronic kidney disease in Black adults, but reported associations with cardiovascular disease (CVD) have been conflicting.


METHODS
We examined associations of APOL1 with incident coronary heart disease (n=323), ischemic stroke (n=331), and the composite CVD outcome (n=500) in 10 605 Black participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Primary analyses compared individuals with APOL1 high-risk genotypes to APOL1 low-risk genotypes in Cox proportional hazards models adjusted for CVD risk factors and African ancestry.


RESULTS
APOL1 high-risk participants were younger and more likely to have albuminuria at baseline than APOL1 low-risk participants. The risk of incident stroke, coronary heart disease, or composite CVD end point did not significantly differ by APOL1 genotype status in multivariable models. The association of APOL1 genotype with incident composite CVD differed by diabetes mellitus status (Pinteraction=0.004). In those without diabetes mellitus, APOL1 high-risk genotypes associated with greater risk of incident composite CVD (hazard ratio, 1.67; 95% confidence interval, 1.12-2.47) compared with those with APOL1 low-risk genotypes in multivariable adjusted models. This latter association was driven by ischemic strokes (hazard ratio, 2.32; 95% confidence interval, 1.33-4.07), in particular, those related to small vessel disease (hazard ratio, 5.10; 95% confidence interval, 1.55-16.56). There was no statistically significant association of APOL1 genotypes with incident CVD in subjects with diabetes mellitus. The APOL1 high-risk genotype was associated with higher stroke risk in individuals without but not those with chronic kidney disease in fully adjusted models.


CONCLUSIONS
APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus.
['Gutiérrez|Orlando M|OM|', 'Irvin|Marguerite R|MR|', 'Chaudhary|Ninad S|NS|', 'Cushman|Mary|M|', 'Zakai|Neil A|NA|', 'David|Victor A|VA|', 'Limou|Sophie|S|', 'Pamir|Nathalie|N|', 'Reiner|Alex P|AP|', 'Naik|Rakhi P|RP|', 'Sale|Michele M|MM|', 'Safford|Monika M|MM|', 'Hyacinth|Hyacinth I|HI|', 'Judd|Suzanne E|SE|', 'Kopp|Jeffrey B|JB|', 'Winkler|Cheryl A|CA|']
D000328:Adult D001741:African Americans D000075944:Apolipoprotein L1 D002318:Cardiovascular Diseases D005260:Female D005838:Genotype D006801:Humans D015994:Incidence D008297:Male D008875:Middle Aged D009154:Mutation D051436:Renal Insufficiency, Chronic D012307:Risk Factors D014481:United States D044465:Whites
cardiovascular diseases stroke cardiac catheterization genetics myocardial infarction