Blood Pressure and Pulse Pressure Effects on Renal Outcomes in the Veterans Affairs Diabetes Trial (VADT)

OBJECTIVE Blood pressure (BP) control for renal protection is essential for patients with type 2 diabetes. Our objective in this analysis of Veterans Affairs Diabetes Trial (VADT) data was to learn whether on-study systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) affected renal outcomes measured as albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS The VADT was a prospective, randomized study of 1,791 veterans with type 2 diabetes to determine whether intensive glucose control prevented major cardiovascular events. In this post hoc study, time-varying covariate survival analyses and hazard ratios (HR) were used to determine worsening of renal outcomes. RESULTS Compared with SBP 105-129 mmHg, the risk of ACR worsening increased significantly for SBP 130-139 mmHg (HR 1.88 [95% CI 1.28-2.77]; P = 0.001) and for SBP >= 140 mmHg (2.51 [1.66-3.78]; P < 0.0001). Compared with a PP range of 40-49 mmHg, PP < 40 was associated with significantly lowered risk of worsening ACR (0.36 [0.15-0.87]; P = 0.022) and PP >= 60 with significantly increased risk (2.38 [1.58-3.59]; P < 0.0001). Analyses of BP ranges associated with eGFR worsening showed significantly increased risk with rising baseline SBP and an interaction effect between SBP >= 140 mmHg and on-study A1C. These patients were 15% more likely than those with SBP <140 mmHg to experience eGFR worsening (1.15 [1.00-1.32]; P = 0.045) for each 1% (10.9 mmol/mol) A1C increase. CONCLUSIONS SBP >= 130 mmHg and PP >60 mmHg were associated with worsening ACR. The results suggest that treatment of SBP to <130 mmHg may lessen ACR worsening. The interaction between SBP >= 140 mmHg and A1C suggests that the effect of glycemic control on reducing progression of renal disease may be greater in hypertensive patients.