Rakesh Malhotra1, Ronit Katz2, Vasantha Jotwani3, Adhish Agarwal4, Debbie L Cohen5, William C Cushman6, Areef Ishani7, Anthony A Killeen8, Dalane W Kitzman9, Suzanne Oparil10, Vasilios Papademetriou11, Chirag R Parikh12, Kalani L Raphael4, Michael V Rocco13, Leonardo J Tamariz14, Paul K Whelton15, Jackson T Wright16, Michael G Shlipak17, Joachim H Ix18. 1. Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA. 2. Kidney Research Institute, University of Washington, Seattle, WA. 3. Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA. 4. Division of Nephrology and Hypertension, Department of Medicine, University of Utah Health, Salt Lake City, UT. 5. Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA. 6. Medical Service, Veteran Affairs Medical Center and Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN. 7. Division of Nephrology, Department of Medicine, University of Minnesota and Veteran Affairs Medical Center, Minneapolis, MN. 8. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN. 9. Division of Cardiovascular Medicine, Wake Forest School of Medicine, Winston Salem, NC. 10. Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL. 11. Division of Cardiology, Department of Medicine, Georgetown University and Veteran Affairs Medical Center, Washington, DC. 12. Division of Nephrology, Department of Medicine, John Hopkins University, Baltimore, MD. 13. Division of Nephrology, Department of Medicine, Wake Forest School of Medicine, Winston Salem, NC. 14. Department of Medicine, Miller School of Medicine at the University of Miami, Miami, FL. 15. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA. 16. Division of Nephrology and Hypertension, University Hospital Cleveland Medical Center, Cleveland, OH. 17. Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA; Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA. 18. Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA. Electronic address: joeix@ucsd.edu.
Abstract
RATIONALE AND OBJECTIVE: Although 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. This study aimed to evaluate the associations 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 ≥50 year of age with 1 or more CVD risk factors. PREDICTORS: eGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits. OUTCOMES: The SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up. ANALYTICAL APPROACH: Cox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18. RESULTS: Mean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 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 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up. LIMITATIONS: Persons with diabetes and proteinuria > 1 g/d were excluded. CONCLUSIONS: In trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events. Published by Elsevier Inc.
RATIONALE AND OBJECTIVE: Although 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. This study aimed to evaluate the associations 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 ≥50 year of age with 1 or more CVD risk factors. PREDICTORS: eGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits. OUTCOMES: The SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up. ANALYTICAL APPROACH: Cox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18. RESULTS: Mean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 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 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up. LIMITATIONS: Persons with diabetes and proteinuria > 1 g/d were excluded. CONCLUSIONS: In trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events. Published by Elsevier Inc.
Authors: Robert M Perkins; Xiaoqin Tang; Amanda C Bengier; H Lester Kirchner; Ion D Bucaloiu Journal: Kidney Int Date: 2012-08-08 Impact factor: 10.612
Authors: Walter T Ambrosius; Kaycee M Sink; Capri G Foy; Dan R Berlowitz; Alfred K Cheung; William C Cushman; Lawrence J Fine; David C Goff; Karen C Johnson; Anthony A Killeen; Cora E Lewis; Suzanne Oparil; David M Reboussin; Michael V Rocco; Joni K Snyder; Jeff D Williamson; Jackson T Wright; Paul K Whelton Journal: Clin Trials Date: 2014-06-05 Impact factor: 2.486
Authors: Tanvir C Turin; Josef Coresh; Marcello Tonelli; Paul E Stevens; Paul E de Jong; Christopher K T Farmer; Kunihiro Matsushita; Brenda R Hemmelgarn Journal: Kidney Int Date: 2013-01-23 Impact factor: 10.612
Authors: Rakesh Malhotra; Timothy Craven; Walter T Ambrosius; Anthony A Killeen; William E Haley; Alfred K Cheung; Michel Chonchol; Mark Sarnak; Chirag R Parikh; Michael G Shlipak; Joachim H Ix Journal: Am J Kidney Dis Date: 2018-10-02 Impact factor: 8.860
Authors: Ziyad Al-Aly; Sumitra Balasubramanian; Jay R McDonald; Jeffrey F Scherrer; Ann M O'Hare Journal: Kidney Int Date: 2012-08-01 Impact factor: 10.612
Authors: Ian Ford; Vladimir Bezlyak; David J Stott; Naveed Sattar; Chris J Packard; Ivan Perry; Brendan M Buckley; J Wouter Jukema; Anton J M de Craen; Rudi G J Westendorp; James Shepherd Journal: PLoS Med Date: 2009-01-20 Impact factor: 11.069