Association of Genotypes With Measures of Microvascular and Endothelial Function, and Blood Pressure in MESA.

Background high-risk genotypes are associated with increased risk for hypertension-attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by status; less is known about the variants' associations with systemic vascular and endothelial function. Whether risk variants are associated with blood pressure (BP) is also uncertain. Methods and Results Using linear regression, we examined cross-sectional associations of risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow-mediated dilation, n=777). Using linear mixed-effects models, we studied longitudinal associations of risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% high-risk) Black participants in MESA (Multi-Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000-2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow-mediated dilation in participants with high- versus low-risk genotypes (>0.05 for all). Over a mean follow-up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by risk status (between-group differences of -0.20, -0.14, and -0.25, respectively; >0.05 for all). Conclusions Among Black participants in MESA, high-risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.