ST2 and mortality in non–ST-segment elevation acute coronary syndrome
Section snippets
Study population
The protocol and results of the GUSTO IV trial including 1-year follow-up data have been published previously.10, 11 This trial was a prospective multicenter study that for the first time evaluated the safety and efficacy of the glycoprotein IIb/IIIa inhibitor abciximab versus placebo on top of aspirin and unfractionated or low–molecular weight heparin as the primary treatment of NSTE-ACS. In brief, 7,800 patients were enrolled between 1999 and 2000 in GUSTO IV and randomized to 1 of 3
Patient characteristics and ST2 levels
The demographic data and clinical characteristics of the 403 patients included in the present analysis in relation to the median ST2 level at randomization are summarized in Table I. The median delay from symptom onset to randomization was 14.9 (25th-75th percentiles 9.4-19.9) hours. In total, 134 patients (33.3%) had been randomized to 24-hour treatment with abciximab, 135 patients (33.5%) to 48-hour treatment with abciximab, and 134 patients (33.3%) to placebo.
The median ST2 level at
Discussion
This is the first analysis assessing ST2 and its clinical implications in patients with NSTE-ACS. Our results demonstrate that ST2 levels are increased in NSTE-ACS and strongly predictive for mortality 1 year after the index event.
ST2 consists of a transmembrane receptor form (ST2L) restricted to the surface of T-helper type 2 cells and mast cells, and a truncated soluble receptor form (sST2). ST2L acts as a ligand for free IL-33 that exerts antihypertrophic, antifibrotic, and antiapoptotic
Conclusions
In conclusion, our results demonstrate that ST2 levels are increased in NSTE-ACS and indicate that the IL-33/ST2 system reflects a novel pathophysiologic mechanism in the setting of ischemia-related myocardial dysfunction, potentially as an on switch for downstream cardioprotective processes in the injured myocardium. Early ST2 levels were related to mortality independently of other clinical risk indicators. However, ST2 lost its predictive value after adjustment for other prognostic
Disclosures
This study was generously supported by Critical Diagnostics, providing the reagents and support for the conduction of the analyses of ST2. The GUSTO IV trial had been supported by a grant from Centocor Inc (Malvern, PA) and Eli Lilly and Company (Indianapolis, IN). None of these companies played a role in the design of study, interpretation of the data, or preparation or approval of the manuscript. None of the authors had conflicts of interest with respect to the present study.
Acknowledgements
We wish to thank James V. Snider from Critical Diagnostics for support with the conduction of the analyses of ST2 in the present study.
References (23)
- et al.
Guidelines for the diagnosis and treatment of non–ST-segment elevation acute coronary syndromes. The Task Force for the Diagnosis and Treatment of Non–ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology
Eur Heart J
(2007) - et al.
National Academy of Clinical Biochemistry laboratory medicine practice guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes
Clin Chem
(2007) - et al.
C-reactive protein and other inflammatory risk markers in acute coronary syndromes
J Am Coll Cardiol
(2003) - et al.
Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction
Circulation
(2002) - et al.
Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction
Circulation
(2004) - et al.
Complementary roles of biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction
Circulation
(2008) - et al.
Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure
J Am Coll Cardiol
(2008) - et al.
Serial sampling of ST2 predicts 90-day mortality following destabilized heart failure
J Cardiac Fail
(2008) - et al.
The IL-33/ST2 pathway: therapeutic target and novel biomarker
Nat Rev Drug Discov
(2008) - et al.
Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early revascularisation: the GUSTO IV-ACS randomised trial
Lancet
(2001)
Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina. One-year survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV–Acute Coronary Syndrome) trial
Circulation
Cited by (76)
Interleukin-33/sST2: Dynamic assessment in patients with acute coronary syndrome
2023, Advances in Medical SciencesThe value of biomarkers in diagnosis and treatment of heart failure with preserved ejection fraction retention
2023, Chinese Journal of Laboratory MedicineImpact of Myocardial Ischemia and Revascularization by Percutaneous Coronary Intervention on Circulating Level of Soluble ST2
2023, Vascular Health and Risk ManagementBiomarkers NT-PROBNP and ST2 in risk stratification of patients with acute myocardial infarction and obesity
2022, Ukrainian Journal of Cardiology