Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction results of the biomarker substudy of the surgical treatment for ischemic heart failure trials

Arthur M. Feldman, Douglas L. Mann, Lilin She, Michael R. Bristow, Alan S. Maisel, Dennis M. McNamara, Ryan Walsh, Dorellyn L. Lee, Stanislaw Wos, Irene Lang, Gretchen Wells, Mark H. Drazner, John F. Schmedtje, Daniel F. Pauly, Carla A. Sueta, Michael Di Maio, Irving L. Kron, Eric J. Velazquez, Kerry L. Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background.Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. Methods and Results.In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor- receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: x 2=40.6; P<0.0001 and sTNFR-1: x2=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (x2=30.3) and sTNFR-1 (x2=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (x2=6.0; P=0.049) and sTNFR-1 (x2=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index .0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions.Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

Original languageEnglish (US)
Pages (from-to)461-472
Number of pages12
JournalCirculation: Heart Failure
Volume6
Issue number3
DOIs
StatePublished - May 1 2013
Externally publishedYes

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Receptors, Tumor Necrosis Factor, Type I
Tumor Necrosis Factor Receptors
Brain Natriuretic Peptide
Left Ventricular Dysfunction
Coronary Artery Bypass
Coronary Artery Disease
Cardiovascular Diseases
Multivariate Analysis
Heart Failure
Biomarkers
Outcome Assessment (Health Care)
Therapeutics
Hospitalization

Keywords

  • Bypass graft
  • Cardiovascular disease
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction results of the biomarker substudy of the surgical treatment for ischemic heart failure trials. / Feldman, Arthur M.; Mann, Douglas L.; She, Lilin; Bristow, Michael R.; Maisel, Alan S.; McNamara, Dennis M.; Walsh, Ryan; Lee, Dorellyn L.; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H.; Schmedtje, John F.; Pauly, Daniel F.; Sueta, Carla A.; Maio, Michael Di; Kron, Irving L.; Velazquez, Eric J.; Lee, Kerry L.

In: Circulation: Heart Failure, Vol. 6, No. 3, 01.05.2013, p. 461-472.

Research output: Contribution to journalArticle

Feldman, AM, Mann, DL, She, L, Bristow, MR, Maisel, AS, McNamara, DM, Walsh, R, Lee, DL, Wos, S, Lang, I, Wells, G, Drazner, MH, Schmedtje, JF, Pauly, DF, Sueta, CA, Maio, MD, Kron, IL, Velazquez, EJ & Lee, KL 2013, 'Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction results of the biomarker substudy of the surgical treatment for ischemic heart failure trials', Circulation: Heart Failure, vol. 6, no. 3, pp. 461-472. https://doi.org/10.1161/CIRCHEARTFAILURE.112.000185
Feldman, Arthur M. ; Mann, Douglas L. ; She, Lilin ; Bristow, Michael R. ; Maisel, Alan S. ; McNamara, Dennis M. ; Walsh, Ryan ; Lee, Dorellyn L. ; Wos, Stanislaw ; Lang, Irene ; Wells, Gretchen ; Drazner, Mark H. ; Schmedtje, John F. ; Pauly, Daniel F. ; Sueta, Carla A. ; Maio, Michael Di ; Kron, Irving L. ; Velazquez, Eric J. ; Lee, Kerry L. / Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction results of the biomarker substudy of the surgical treatment for ischemic heart failure trials. In: Circulation: Heart Failure. 2013 ; Vol. 6, No. 3. pp. 461-472.
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abstract = "Background.Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. Methods and Results.In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor- receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: x 2=40.6; P<0.0001 and sTNFR-1: x2=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (x2=30.3) and sTNFR-1 (x2=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (x2=6.0; P=0.049) and sTNFR-1 (x2=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index .0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions.Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.",
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TY - JOUR

T1 - Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction results of the biomarker substudy of the surgical treatment for ischemic heart failure trials

AU - Feldman, Arthur M.

AU - Mann, Douglas L.

AU - She, Lilin

AU - Bristow, Michael R.

AU - Maisel, Alan S.

AU - McNamara, Dennis M.

AU - Walsh, Ryan

AU - Lee, Dorellyn L.

AU - Wos, Stanislaw

AU - Lang, Irene

AU - Wells, Gretchen

AU - Drazner, Mark H.

AU - Schmedtje, John F.

AU - Pauly, Daniel F.

AU - Sueta, Carla A.

AU - Maio, Michael Di

AU - Kron, Irving L.

AU - Velazquez, Eric J.

AU - Lee, Kerry L.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Background.Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. Methods and Results.In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor- receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: x 2=40.6; P<0.0001 and sTNFR-1: x2=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (x2=30.3) and sTNFR-1 (x2=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (x2=6.0; P=0.049) and sTNFR-1 (x2=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index .0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions.Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

AB - Background.Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. Methods and Results.In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor- receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: x 2=40.6; P<0.0001 and sTNFR-1: x2=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (x2=30.3) and sTNFR-1 (x2=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (x2=6.0; P=0.049) and sTNFR-1 (x2=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index .0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions.Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

KW - Bypass graft

KW - Cardiovascular disease

KW - Heart failure

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U2 - 10.1161/CIRCHEARTFAILURE.112.000185

DO - 10.1161/CIRCHEARTFAILURE.112.000185

M3 - Article

C2 - 23584092

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VL - 6

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