Prognostic impact of Interleukin-1 receptor antagonist in patients with documented coronary artery disease

Int J Cardiol. 2018 Apr 15;257:24-29. doi: 10.1016/j.ijcard.2018.01.055. Epub 2018 Feb 1.

Abstract

Background: IL-1β-mediated inflammation contributes to development and progression of coronary artery disease (CAD). We aimed to assess the prognostic impact of the inflammatory marker Interleukin-1 receptor antagonist (IL1-Ra), reflecting high IL-1β activity, in patients with documented CAD.

Methods: IL-1Ra levels were determined in 1337 subjects of the AtheroGene study, a prospective cardiovascular registry comprising patients with CAD as detected by coronary angiography presenting with acute coronary syndrome (ACS) or stable angina. Median follow-up was 6.4 years.

Results: Patients with IL1-Ra levels in the highest tertile presented more often with ACS (55% vs. 40% vs. 34%, p < 0.001), were more commonly treated with PCI (47% vs. 39% vs. 34%, p < 0.001), had lower left ventricular ejection fraction (LVEF) (61 ± 15% vs. 62 ± 15% vs. 65 ± 14%, p = 0.001) and higher hs-CRP levels (10.0 vs. 4.2 vs. 2.5 mg/L, p < 0.001). IL1-Ra levels at baseline were predictive for all-cause mortality in the total study cohort after adjustment for conventional cardiovascular risk factors, LVEF, hs-CRP and Troponin T (adjusted HR 1.45 (95% CI 1.16-1.82), p < 0.001). In a subgroup of patients with ACS, but not in those with stable angina, IL1-Ra was an independent predictor for cardiovascular mortality (ACS: adjusted HR 1.93 (95% CI 1.33-2.80), p < 0.001; stable angina: adjusted HR: 1.26 (95% CI 0.92-1.73), p = 0.16).

Conclusion: IL1-Ra is an independent predictor for adverse outcome in patients with documented CAD, beyond the prognostic value of hs-CRP and Troponin T in particular in the setting of ACS. For CAD patients our finding might improve both, risk assessment in secondary prevention and patient selection for anti-inflammatory treatment.

Keywords: Coronary artery disease; Inflammation; Interleukin-1 receptor antagonist.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Biomarkers / blood
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / mortality
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / blood*
  • Male
  • Middle Aged
  • Mortality / trends
  • Prognosis
  • Prospective Studies
  • Registries
  • Stroke Volume / drug effects
  • Stroke Volume / physiology

Substances

  • Biomarkers
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein