Circulating Levels of IL-6 Receptor and gp130 and Long-Term Clinical Outcomes in ST-Elevation Myocardial Infarction

Vibeke N Ritschel, Ingebjørg Seljeflot, Harald Arnesen, Sigrun Halvorsen, Jan Eritsland, Morten W Fagerland, Geir Ø Andersen, Vibeke N Ritschel, Ingebjørg Seljeflot, Harald Arnesen, Sigrun Halvorsen, Jan Eritsland, Morten W Fagerland, Geir Ø Andersen

Abstract

Background: Reports on soluble interleukin-6 (IL-6) receptor (sIL-6R) and glycoprotein 130 (sgp130) in ST-elevation myocardial infarction (STEMI) are few and include a small number of patients. The aim of this study was to investigate the possible association between levels of these biomarkers in the acute phase of STEMI and future cardiovascular events.

Methods and results: Circulating IL-6, sgp130, sIL-6R, and C-reactive protein (CRP) were measured in 989 STEMI patients during 2007-2011, and cardiovascular events were recorded during follow-up. The primary endpoint was composite of all-cause mortality, myocardial infarction, stroke, unscheduled revascularization, or rehospitalization for heart failure. Cox regression models were used to estimate hazard ratios (HRs) for cardiovascular events in relation to biomarker levels. Median levels of sIL-6R, sgp130, IL-6, and CRP measured 24 hours (median) after symptom onset were 39.2 ng/mL, 240 ng/mL, 18.8 pg/mL, and 13.7 mg/L, respectively. During a median follow-up time of 4.6 years, 200 patients (20.2%) experienced a primary endpoint, and 82 patients (8.3%) died. Patients with sIL-6R levels in the upper quartile (>47.7 ng/mL) had significantly higher risk of future adverse events (primary endpoint) and mortality compared to patients with lower levels (adjusted HR, 1.54 [1.08, 2.21]; P=0.02 and 1.81 [1.04, 3.18]; P=0.04, respectively). Neither IL-6 nor sgp130 levels were related to future events, but patients with CRP levels in the upper quartile (>31.5 mg/L) had higher risk of death.

Conclusion: High levels of sIL-6R were associated with future cardiovascular events and mortality in STEMI patients, suggesting an important role of the IL-6 signaling system.

Keywords: inflammation; interleukins; myocardial infarction; prognosis.

© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Time‐to‐event curves for the highest quartile (Q4) of soluble interleukin‐6 receptor (sIL‐6R) vs the 3 lowest quartiles (Q1–Q3) measured in 989 STEMI patients according to the primary endpoint. The log rank test was used to compare the survival curves. STEMI indicates ST‐elevation myocardial infarction.
Figure 2
Figure 2
Time‐to‐event curves for the highest quartile (Q4) of soluble interleukin‐6 receptor (sIL‐6R) vs the 3 lowest quartiles (Q1–Q3) measured in 989 STEMI patients according to the secondary endpoint. The log rank test was used to compare the survival curves. STEMI indicates ST‐elevation myocardial infarction.

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