Clinical utility of circulating interleukin-6 concentrations in the detection of functionally relevant coronary artery disease

Int J Cardiol. 2019 Jan 15;275:20-25. doi: 10.1016/j.ijcard.2018.10.029. Epub 2018 Oct 12.

Abstract

Background: Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD).

Methods: We hypothesized, that quantifying inflammation by measuring circulating interleukin-6 concentrations help in the diagnosis and/or prediction of functionally relevant CAD. Among consecutive patients with symptoms suggestive of CAD, functionally relevant CAD was adjudicated in two domains: first, diagnosis according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, cardiovascular death and all-cause death during 2-years follow-up. Adjudication was done blinded to the interleukin-6 concentrations.

Results: Among 1553 patients, symptoms were adjudicated to be causally related to CAD in 43% (665/1553). Interleukin-6 concentrations were higher in patients with functionally relevant CAD as compared to those without (1.56 pg/mL versus 1.30 pg/mL, p < 0.001), but overall had only low-to-modest diagnostic accuracy (area under the curve [AUC]: 0.57, 95%CI 0.55-0.61) and were no independent predictor of functionally relevant CAD after multivariable adjustment (p = 0.068). Interleukin-6 concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.75, 95%CI 0.69-0.82) and all-cause death (AUC 0.72, 95%CI 0.66-0.78) at 2-years, and remained a significant predictor after multivariable adjustment (p < 0.001). Compared to patients with interleukin-6 concentrations below the median (1.41 pg/mL), patients with concentrations above the median had a significantly higher cumulative incidence of cardiovascular death (1% vs. 4%, log-rank p < 0.001) and all-cause death (2% vs. 8%, log-rank p < 0.001) at 2 years.

Conclusion: Interleukin-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death.

Keywords: Coronary artery disease; Exercise-induced myocardial ischemia; Interleukin-6; Myocardial ischemia.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cause of Death / trends
  • Coronary Angiography
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / mortality
  • Early Diagnosis*
  • Exercise Test
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoassay
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Multidetector Computed Tomography
  • Predictive Value of Tests
  • Prospective Studies
  • Reproducibility of Results
  • Survival Rate / trends
  • Switzerland / epidemiology
  • Tomography, Emission-Computed, Single-Photon / methods

Substances

  • Biomarkers
  • Interleukin-6