PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT
Year: 2018
Type: article
Abstract: Background and objectives The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive BP lowering reduced the risk of cardiovascular disease, but increased eGFR decline. Serum parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) concentrations are elevated in CKD and are associated with cardiovascular disease. We evaluated whether intact PTH or intact FGF23 concentrations modify the effects of intensive BP control on cardiovascular events, heart failure, and all-cause mortality in SPRINT participants with CKD. Design, setting, participants, & measurements We measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m 2 at baseline. Cox models were used to evaluate whether serum PTH and FGF23 concentrations were associated with cardiovascular events, heart failure, and all-cause mortality, and whether PTH and FGF23 modified the effects of intensive BP control. Results The mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m 2 . Median PTH was 48 (interquartile range [IQR], 35–67) pg/ml and FGF23 was 66 (IQR, 52–88) pg/ml. There were 261 composite cardiovascular events, 102 heart failure events, and 179 deaths within the subcohort. The adjusted hazard ratio (HR) per doubling of PTH concentration for cardiovascular events, heart failure, and all-cause mortality were 1.29 (95% confidence interval [95% CI], 1.06 to 1.57), 1.32 (95% CI, 0.96 to 1.83), and 1.04 (95% CI, 0.82 to 1.31), respectively. There were significant interactions between PTH and BP arm for both the cardiovascular ( P -interaction=0.01) and heart failure ( P -interaction=0.004) end points. Participants with a PTH above the median experienced attenuated benefits of intensive BP control on cardiovascular events (adjusted HR, 1.02; 95% CI, 0.72 to 1.42) compared with participants with a PTH below the median (adjusted HR, 0.67; 95% CI, 0.45 to 1.00). FGF23 was not independently associated with any outcome and did not modify the effects of the intervention. Conclusions SPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH.
DOI: 10.2215/cjn.05390518
Authors: Charles Ginsberg, Timothy E. Craven, Michel B. Chonchol, Alfred K. Cheung, Mark J. Sarnak, Walter T. Ambrosius, Anthony A. Killeen, Kalani L. Raphael, Udayan Y. Bhatt, Jing Chen, Glenn M. Chertow, Barry I. Freedman, Suzanne Oparil, Vasilios Papademetriou, Barry M. Wall, Clinton B. Wright, Joachim H. Ix, Michael G. Shlipak
Institutions: University of California San Diego, VA San Diego Healthcare System, University of Colorado Anschutz, University of Utah, Tufts Medical Center, University of Minnesota, The Ohio State University Wexner Medical Center, The Ohio State University, Tulane University, Stanford Medicine, Stanford University, Wake Forest University Health Sciences, Wake Forest University, University of Alabama at Birmingham, UAB Medicine, Georgetown University Medical Center, Memphis VA Medical Center, University of Miami, San Francisco VA Medical Center, University of California, San Francisco
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: American Heart Association, American Society of Nephrology, University of Minnesota, University of Washington, Omron Healthcare, National Institute for Health and Care Research, National Institutes of Health, Takeda Pharmaceuticals International, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1, G1201304535, G130883262, G1346455397, G1452718737, G1534123016, G1575401839, G1815451664, Together: Transforming and Translating Discovery to Improve Health, G2244966566, The Ohio State University Center for Clinical and Translational Science (UL1), Tufts Clinical and Translational Research Institute, Kidney Tubular Damage and Dysfunction Identify a Novel Axis of Chronic Kidney Disease, G3042542605, G3182908838, G3345260134, Translational Research in Hypertension and Renal Biology, UC Davis Clinical and Translational Science Center, G3759862710, Clinical and Translational Science Institute at Children's National, UF Clinical and Translational Science Award, G4559308260, G467313275, G5068655555, G522538789, Institutional Clinical and Translational Science Award, G576625284, G5831220822, Tufts Clinical and Translation Science Institute (UL1), G5971433106, G742032275, Institutional Clinical and Translational Science Award, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G797306165, Adult and Pediatric Nephrology Clinical Investigation Training Program, The Effects of Phosphate on Microvascular Function, Clinical and Translational Science Collaborative of Cleveland, G8723760441, Clinical and Translational Science Collaborative of Cleveland, G884570035, G94668252
OpenAlex ID: W2901723277