Suppression of tumorigenicity 2 in heart failure with preserved ejection fraction

Omar Abou Ezzeddine, Paul McKie, Shannon M Dunlay, Susanna R. Stevens, G. Michael Felker, Barry A Borlaug, Horng Haur Chen, Russell P. Tracy, Eugene Braunwald, Margaret May Redfield

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background-Soluble suppression of tumorigenicity 2 (sST2) receptor is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity-driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology, but data on how sST2 relates to clinical characteristics or inflammatory conditions or biomarkers in HFpEF are limited. We sought to determine circulating levels and clinical correlates of sST2 in HFpEF. Methods and Results-At enrollment, patients (n=174) from the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HFpEF had sST2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST2 levels. Median sST2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9-49.2 ng/mL; reference range 4-31 ng/mL) and 30.8 ng/mL (range 25.3-39.3 ng/mL; reference range 2-21 ng/mL), respectively. Among HFpEF patients, higher sST2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis (P < 0.05 for all). sST2 was not associated with left ventricular structure or left ventricular systolic or diastolic function. Conclusions-In HFpEF, sST2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that ST2 may be a marker of systemic inflammation in HFpEF and potentially of extracardiac origin.

Original languageEnglish (US)
Article numbere004382
JournalJournal of the American Heart Association
Volume6
Issue number2
DOIs
StatePublished - 2017

Fingerprint

Heart Failure
Biomarkers
Inflammation
Ventricular Dysfunction
Ventricular Pressure
Exercise
Comorbidity
Reference Values
Fibrosis
Necrosis
Diastolic Heart Failure
Type 5 Cyclic Nucleotide Phosphodiesterases
Atrial Fibrillation
Diabetes Mellitus
Kidney

Keywords

  • Biomarker
  • Diastolic heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Suppression of tumorigenicity 2 in heart failure with preserved ejection fraction. / Abou Ezzeddine, Omar; McKie, Paul; Dunlay, Shannon M; Stevens, Susanna R.; Felker, G. Michael; Borlaug, Barry A; Chen, Horng Haur; Tracy, Russell P.; Braunwald, Eugene; Redfield, Margaret May.

In: Journal of the American Heart Association, Vol. 6, No. 2, e004382, 2017.

Research output: Contribution to journalArticle

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abstract = "Background-Soluble suppression of tumorigenicity 2 (sST2) receptor is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity-driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology, but data on how sST2 relates to clinical characteristics or inflammatory conditions or biomarkers in HFpEF are limited. We sought to determine circulating levels and clinical correlates of sST2 in HFpEF. Methods and Results-At enrollment, patients (n=174) from the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HFpEF had sST2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST2 levels. Median sST2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9-49.2 ng/mL; reference range 4-31 ng/mL) and 30.8 ng/mL (range 25.3-39.3 ng/mL; reference range 2-21 ng/mL), respectively. Among HFpEF patients, higher sST2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis (P < 0.05 for all). sST2 was not associated with left ventricular structure or left ventricular systolic or diastolic function. Conclusions-In HFpEF, sST2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that ST2 may be a marker of systemic inflammation in HFpEF and potentially of extracardiac origin.",
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AU - Abou Ezzeddine, Omar

AU - McKie, Paul

AU - Dunlay, Shannon M

AU - Stevens, Susanna R.

AU - Felker, G. Michael

AU - Borlaug, Barry A

AU - Chen, Horng Haur

AU - Tracy, Russell P.

AU - Braunwald, Eugene

AU - Redfield, Margaret May

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AB - Background-Soluble suppression of tumorigenicity 2 (sST2) receptor is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity-driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology, but data on how sST2 relates to clinical characteristics or inflammatory conditions or biomarkers in HFpEF are limited. We sought to determine circulating levels and clinical correlates of sST2 in HFpEF. Methods and Results-At enrollment, patients (n=174) from the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HFpEF had sST2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST2 levels. Median sST2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9-49.2 ng/mL; reference range 4-31 ng/mL) and 30.8 ng/mL (range 25.3-39.3 ng/mL; reference range 2-21 ng/mL), respectively. Among HFpEF patients, higher sST2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis (P < 0.05 for all). sST2 was not associated with left ventricular structure or left ventricular systolic or diastolic function. Conclusions-In HFpEF, sST2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that ST2 may be a marker of systemic inflammation in HFpEF and potentially of extracardiac origin.

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