Association of Blood Pressure Genetic Risk Score with Cardiovascular Disease and CKD Progression: Findings from the CRIC Study

Background: In the general population, genetic risk for elevated blood pressure has been associated with cardiovascular disease but not kidney function or incident chronic kidney disease. These relationships have not been studied longitudinally in participants with chronic kidney disease. We examined whether blood pressure genetic risk predicts cardiovascular disease and kidney disease progression in patients with chronic kidney disease. Methods: We included 1,493 African and 1,581 European ancestry participants from the Chronic Renal Insufficiency Cohort who were followed for 12 years. We examined associations of blood pressure genetic risk scores with development of cardiovascular disease (myocardial infarction, congestive heart failure, or stroke) and chronic kidney disease progression (incident end stage kidney disease or halving of estimated glomerular filtration rate) using Cox proportional hazards models. Analyses were stratified by race and included adjustment for age, sex, study site, and ancestry principal components. Results: Each standard deviation increase in systolic blood pressure and pulse pressure genetic risk score conferred respective 15% [95% confidence interval: 4%, 27%] and 11% (95% confidence interval: 1%, 23%) higher risks of cardiovascular disease, with a similar marginally significant trend for diastolic blood pressure, among European ancestry participants. Among African ancestry participants, each standard deviation increase in systolic and diastolic blood pressure genetic risk score conferred 10% (95% confidence interval: 1%, 20%) and 9% (95% confidence interval: 0%, 18%) higher risk of cardiovascular disease. Higher genetic risk was not associated with chronic kidney disease progression. Conclusions: Genetic risk for elevation in blood pressure was associated with increased risk of cardiovascular disease but not chronic kidney disease progression.