期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 63, 期 22, 页码 2421-2428出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2014.03.026
关键词
angiotensin-converting enzyme inhibitors; biomarkers; coronary artery disease; fibroblast growth factor-23; kidney
资金
- National Heart, Lung, and Blood Institute(NHLBI) [N01HC65149]
- Knoll Pharmaceutical
- Abbott Laboratories
- Postdoctoral Research Fellowship
- Canadian Institutes for Health Research (CIHR
- Ottawa, Canada)
- Canadian Foundation for Women's Health (Ottawa, Canada)
- National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL094390]
- Amgen
- AstraZeneca, Athera, Beckman Coulter, BG Medicine, Bristol-Myers Squibb, Buhlmann Laboratories
- Daiichi Sankyo Co Ltd
- Eli Lilly and Co
- Esai
- GlaxoSmithKline
- Johnson Johnson
- Merck and Co.
- Nanosphere
- Novartis Pharmaceuticals
- Ortho-Clinical Diagnostics
- Pfizer
- Randox
- Roche Diagnostics
- Sanofi-Aventis
- Siemens
- Singulex
- Abbott Diagnostics
- BG Medicine
- Eli Lilly
- Gilead
- Novartis
- Critical Diagnostics
- Genentech
- Instrumentation Laboratory
- Konica-Minolta
- Servier
- Siemens Healthcare
Objectives This study sought to test 2 hypotheses: 1) fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent of clinical factors, renal function, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from angiotensin-converting enzyme inhibitor therapy. Background FGF-23 is an endocrine regulator of mineral metabolism and markedly elevated levels are associated with cardiovascular events in patients with chronic kidney disease. Data in patients with SIHD are more sparse. Methods FGF-23 levels were measured in 3,627 patients with SIHD randomly assigned to trandolapril or placebo within the PEACE (Prevention of Events With Angiotensin-Converting Enzyme) trial and followed up for a median of 5.1 years. Results After adjustment for clinical risk predictors, left ventricular ejection fraction, markers of renal function, and established cardiovascular biomarkers, FGF-23 concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (quartile 4 hazard ratio: 1.73; 95% confidence interval, 1.09 to 2.74; p= 0.02) and significantly improved metrics of discrimination. Furthermore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced cardiovascular death or incident heart failure (hazard ratio: 0.45; 95% confidence interval: 0.28 to 0.72), whereas there was no clinical benefit in the remaining patients (hazard ratio: 1.07; 95% confidence interval: 0.75 to 1.52; p interaction=0.0039). This interaction was independent of and additive to stratification based on renal function. Conclusions Elevated levels of FGF-23 are associated with cardiovascular death and incident heart failure in patients with SIHD and identify patients who derive significant clinical benefit from angiotensin-converting enzyme inhibitor therapy regardless of renal function. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy [PEACE]: NCT00000558) (J Am Coll Cardiol 2014; 63: 2421-8) (C) 2014 by the American College of Cardiology Foundation
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