Evaluation of Multiple Biomarkers of Cardiovascular Stress for Risk Prediction and Guiding Medical Therapy in Patients with Stable Coronary Disease
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 CAD and preserved left ventricular ejection fraction (LVEF) 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 LVEF, elevated levels of MR-proANP, MR-proADM, and CT-proET-1 were independently associated with the risk of cardiovascular death or heart failure (HRs per 1-SD of log-transformed biomarker levels of 1.97, 1.48, and 1.47, respectively; P≤0.002 for each biomarker). These three 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 or more these biomarkers (HR 0.53, 95% CI 0.36-0.80), whereas there was no benefit in patients with elevated levels of 0 or 1 biomarkers (HR 1.09, 95% CI 0.74-1.59) (Pinteraction=0.012).
Conclusions—In patients with stable CAD and preserved LVEF, our results suggest 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 ACE inhibitor therapy.
- Received August 24, 2011.
- Accepted December 7, 2011.
- Copyright © 2011, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited