Evaluation of multiple biomarkers of cardiovascular stress for risk prediction and guiding medical therapy in patients with stable coronary disease

Marc S. Sabatine, David A. Morrow, James A de Lemos, Torbjorn Omland, Sarah Sloan, Petr Jarolim, Scott D. Solomon, Marc A. Pfeffer, Eugene Braunwald

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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; Pinteraction=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.

Original languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalCirculation
Volume125
Issue number2
DOIs
StatePublished - Jan 17 2012

Fingerprint

Coronary Disease
Biomarkers
trandolapril
Stroke Volume
Adrenomedullin
Heart Failure
Atrial Natriuretic Factor
Endothelin-1
Therapeutics
Coronary Artery Disease
Confidence Intervals
Enzyme Therapy
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme Inhibitors
Placebos

Keywords

  • angiotensin-converting enzyme inhibitors
  • biomarkers
  • coronary disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Evaluation of multiple biomarkers of cardiovascular stress for risk prediction and guiding medical therapy in patients with stable coronary disease. / Sabatine, Marc S.; Morrow, David A.; de Lemos, James A; Omland, Torbjorn; Sloan, Sarah; Jarolim, Petr; Solomon, Scott D.; Pfeffer, Marc A.; Braunwald, Eugene.

In: Circulation, Vol. 125, No. 2, 17.01.2012, p. 233-240.

Research output: Contribution to journalArticle

Sabatine, Marc S. ; Morrow, David A. ; de Lemos, James A ; Omland, Torbjorn ; Sloan, Sarah ; Jarolim, Petr ; Solomon, Scott D. ; Pfeffer, Marc A. ; Braunwald, Eugene. / Evaluation of multiple biomarkers of cardiovascular stress for risk prediction and guiding medical therapy in patients with stable coronary disease. In: Circulation. 2012 ; Vol. 125, No. 2. pp. 233-240.
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AU - Sloan, Sarah

AU - Jarolim, Petr

AU - Solomon, Scott D.

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AB - 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; Pinteraction=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.

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