Srinivasan Beddhu1,2, Jincheng Shen3, Alfred K Cheung4,2, Paul L Kimmel5, Glenn M Chertow6, Guo Wei4, Robert E Boucher4, Michel Chonchol7, Farid Arman8, Ruth C Campbell9, Gabriel Contreras10, Jamie P Dwyer11, Barry I Freedman12, Joachim H Ix13,14, Kent Kirchner15, Vasilios Papademetriou16, Roberto Pisoni9,17, Michael V Rocco12, Paul K Whelton18, Tom Greene3. 1. Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; Srinivasan.beddhu@hsc.utah.edu. 2. Division of Nephrology and Hypertension, Department of Internal Medicine, and. 3. Division of Biostatistics, Departments of Population Health Sciences and Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah. 4. Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. 5. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 6. Division of Nephrology, Stanford University School of Medicine, Palo Alto, California. 7. Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado. 8. Division of Nephrology, University of California, Los Angeles, Los Angeles, California. 9. Division of Nephrology, Medical University of South Carolina, Charleston, South Carolina. 10. Division of Nephrology, University of Miami, Miami, Florida. 11. Division of Nephrology and Hypertension, Vanderbilt University, Nashville, Tennessee. 12. Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina. 13. Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, San Diego, California. 14. Nephrology Section, Medical Service, Veterans Affairs San Diego Healthcare System, San Diego, California. 15. Division of Nephrology, G.V. (Sonny) Montgomery Veteran Affairs Medical Center, Jackson, Mississippi. 16. Division of Cardiology, Veterans Administration Medical Center, Washington, DC. 17. Medical Service, Ralph H. Johnson Veteran Affairs Medical Center, Charleston, South Carolina; and. 18. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.
Abstract
BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.
BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.
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