期刊
CIRCULATION
卷 125, 期 2, 页码 233-U137出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.111.063842
关键词
angiotensin-converting enzyme inhibitors; biomarkers; coronary disease
资金
- National Heart, Lung, and Blood Institute (NHLBI) [N01 HC65149, R01 HL094390]
- Knoll Pharmaceuticals
- Abbott Laboratories
- Accumetrics
- Amgen
- AstraZeneca
- Beckman Coulter
- BG Medicine
- B. R. A. H. M. S. GmbH
- Bristol-Myers Squibb
- CV Therapeutics
- Daiichi Sankyo Co Ltd
- diaDexus
- Eli Lilly and Co
- Genentech
- GlaxoSmithKline
- Integrated Therapeutics
- Johnson Johnson
- Merck and Co
- Nanosphere
- Novartis Pharmaceuticals
- Nuvelo
- Ortho-Clinical Diagnostics
- Pfizer
- Roche Diagnostics
- Sanofi-aventis
- Siemens
- Singulex
- Roche
- Alere, Inc
- Alere
- Johnson & Johnson Roche Diagnostics
- Tethys Biomedical
- Beckman-Coulter
- Ortho Clinical Diagnostics
- Siemens Healthcare Diagnostics
- T2 Biosystems
- Novartis
- Anthera
- Boehringer Ingelheim
- Boston Scientific
- Cerenis
- Eleven Biotherapeutics
- Hamilton Health Sciences
- Karo Bio
- Salutria
- Sanofi Aventis
- Servier
- University of Oxford
Background-Circulating biomarkers can offer insight into subclinical cardiovascular stress and thus have the potential to aid in risk stratification and tailoring of therapy. Methods and Results-We measured plasma levels of 4 cardiovascular biomarkers, midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and copeptin, in 3717 patients with stable coronary artery disease and preserved left ventricular ejection fraction who were randomized to trandolapril or placebo as part of the Prevention of Events With Angiotensin Converting Enzyme (PEACE) trial. After adjustment for clinical cardiovascular risk predictors and left ventricular ejection fraction, elevated levels of MR-proANP, MR-proADM, and CT-proET-1 were independently associated with the risk of cardiovascular death or heart failure (hazard ratios per 1-SD increase in log-transformed biomarker levels of 1.97, 1.48, and 1.47, respectively; P <= 0.002 for each biomarker). These 3 biomarkers also significantly improved metrics of discrimination when added to a clinical model. Trandolapril significantly reduced the risk of cardiovascular death or heart failure in patients who had elevated levels of >= 2 biomarkers (hazard ratio, 0.53; 95% confidence interval, 0.36-0.80), whereas there was no benefit in patients with elevated levels of 0 or 1 biomarker (hazard ratio, 1.09; 95% confidence interval, 0.74-1.59; P-interaction = 0.012). Conclusions-In patients with stable coronary artery disease and preserved left ventricular ejection fraction, our results suggest that elevated levels of novel biomarkers of cardiovascular stress may help identify patients who are at higher risk of cardiovascular death and heart failure and may be useful to select patients who derive significant benefit from angiotensin-converting enzyme inhibitor therapy. (Circulation. 2012;125:233-240.)
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