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Research ArticleGeneral Clinical Chemistry

Endothelin-1 Measurement in Patients Undergoing Diagnostic Coronary Angiography—Results from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study

Nasrien E. Ibrahim, Rajat Gupta, Asya Lyass, Yiwei Li, Shreya Shrestha, Cian P. McCarthy, Hanna K. Gaggin, Roland R.J. van Kimmenade, Joseph M. Massaro, Ralph B. D’Agostino, James L. Januzzi
DOI: 10.1373/clinchem.2017.286385 Published September 2018
Nasrien E. Ibrahim
Cardiology Division, Massachusetts General Hospital, Boston, MA;Harvard Medical School, Boston, MA;
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Rajat Gupta
Cardiology Division, Massachusetts General Hospital, Boston, MA;Harvard Medical School, Boston, MA;
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Asya Lyass
Baim Institute for Clinical Research, Boston, MA;Department of Mathematics and Statistics, Boston University, Boston, MA;
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Yiwei Li
Baim Institute for Clinical Research, Boston, MA;
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Shreya Shrestha
Cardiology Division, Massachusetts General Hospital, Boston, MA;
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Cian P. McCarthy
Cardiology Division, Massachusetts General Hospital, Boston, MA;
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Hanna K. Gaggin
Cardiology Division, Massachusetts General Hospital, Boston, MA;Harvard Medical School, Boston, MA;
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Roland R.J. van Kimmenade
Cardiology Division, Radboud UMC and Cardiology Division, Maastricht UMC, Nijmegen, the Netherlands;
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Joseph M. Massaro
Department of Biostatistics, Boston University, Boston, MA.
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Ralph B. D’Agostino
Baim Institute for Clinical Research, Boston, MA;Department of Mathematics and Statistics, Boston University, Boston, MA;
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James L. Januzzi
Cardiology Division, Massachusetts General Hospital, Boston, MA;Harvard Medical School, Boston, MA;Baim Institute for Clinical Research, Boston, MA;
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  • For correspondence: jjanuzzi@partners.org
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Abstract

Background: Endothelin-1 (ET-1) is a vasoconstrictor produced by vascular endothelial cells and may play a role in risk for development of coronary artery disease (CAD) and heart failure (HF). In a cohort of 1084 patients referred for coronary angiography, we investigated cross-sectional associations between ET-1 concentrations and prevalent CAD, as well as value of ET-1 for prognostication of future cardiovascular events.

Methods: Associations between ET-1 and presence/ severity of CAD were assessed. Patients were followed for a median of 4 years for outcomes including incident HF, myocardial infarction (MI), cardiovascular mortality, and all-cause mortality.

Results: The median concentration of ET-1 was 2.57 ng/L. Patients with ET-1 concentrations above the median were more likely to have higher risk clinical features. Among those without prevalent MI at presentation, ET-1 concentrations were not associated with presence or severity of CAD. In adjusted Cox proportional hazards analyses, log-transformed ET-1 concentrations predicted incident HF [hazard ratio (HR) = 1.51 per increase in log-SD; 95% CI, 1.06–2.15; P = 0.02] and all-cause mortality (HR = 1.61 per increase in log-SD; 95% CI, 1.03–2.53; P = 0.04). Concentrations of ET-1 above the median were associated with shorter time to incident HF, MI, cardiovascular mortality, all-cause mortality, and the composite of incident HF/MI/cardiovascular mortality (all log-rank P < 0.001).

Conclusions: Despite epidemiologic links to CAD, we found no cross-sectional association between biologically active ET-1 and prevalent coronary atherosclerosis in an at-risk population referred for coronary angiography. Increased ET-1 concentrations independently predict incident HF and death and are associated with more near-term cardiovascular events.

  • Received for publication January 10, 2018.
  • Accepted for publication July 30, 2018.
  • © 2018 American Association for Clinical Chemistry

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Clinical Chemistry: 65 (2)
Vol. 65, Issue 2
February 2019
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Endothelin-1 Measurement in Patients Undergoing Diagnostic Coronary Angiography—Results from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study
Nasrien E. Ibrahim, Rajat Gupta, Asya Lyass, Yiwei Li, Shreya Shrestha, Cian P. McCarthy, Hanna K. Gaggin, Roland R.J. van Kimmenade, Joseph M. Massaro, Ralph B. D’Agostino, James L. Januzzi
Clinical Chemistry Jan 2018, clinchem.2017.286385; DOI: 10.1373/clinchem.2017.286385
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Endothelin-1 Measurement in Patients Undergoing Diagnostic Coronary Angiography—Results from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study
Nasrien E. Ibrahim, Rajat Gupta, Asya Lyass, Yiwei Li, Shreya Shrestha, Cian P. McCarthy, Hanna K. Gaggin, Roland R.J. van Kimmenade, Joseph M. Massaro, Ralph B. D’Agostino, James L. Januzzi
Clinical Chemistry Jan 2018, clinchem.2017.286385; DOI: 10.1373/clinchem.2017.286385

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