Estimated GFR Variability and Risk of Cardiovascular Events and Mortality in SPRINT (Systolic Blood Pressure Intervention Trial)

Abstract Rationale and Objective While low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. We aimed to evaluate the association between variability in eGFR and the risk of CVD events and all-cause mortality. Study Design Longitudinal analysis of clinical trial participants. Settings and Participants 7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants aged ≥ 50 year with 1 or more CVD risk factors. Predictors eGFR variability, estimated by the coefficients of variation of eGFR measurements at the 6, 12, and 18-month study visits. Outcomes SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to end of follow-up. Analytical Approach Cox models evaluated associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria and month 18 eGFR. Results Mean age was 68±9 years, 65% were men, and 58% were white. The mean eGFR was 73±21 ml/min/1.73m2 at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio (HR) per standard deviation (SD) greater variability, 1.29; 95% confidence interval (CI) 1.14 to 1.45) but not CVD events (HR 1.05; 95% CI 0.95 to 1.16) after adjusting for albuminuria at baseline, eGFR at month 18, and other CVD risk factors. Associations were similar when stratified by treatment arm and baseline CKD status, when accounting for concurrent systolic BP changes, use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and diuretic medications during follow-up. Limitations Persons with diabetes and proteinuria > 1 g/day were excluded. Conclusions In trial participants at high risk for CVD with hypertension, greater eGFR variability was independently associated with all-cause mortality but not CVD events.