Interleukin-6 level is a powerful predictor of long-term cardiovascular mortality in patients with acute coronary syndrome

Vascul Pharmacol. 2020 Dec;135:106806. doi: 10.1016/j.vph.2020.106806. Epub 2020 Oct 7.


Background: The interleukin-6 (IL-6) pathway has a crucial role in the pathogenesis of atherosclerosis, the main cause of cardiovascular diseases. We aimed to characterize the predictive value of inflammatory biomarkers on long-term cardiovascular mortality in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).

Methods: This prospective observational study included 322 consecutive patients with ACS undergoing PCI. Blood-derived biomarkers IL-6 and high-sensitivity C-reactive protein (hsCRP) were assessed at the time point of ACS. Patients were followed-up for 6 years. Long-term cardiovascular mortality was our primary endpoint. Adjusted Cox-regression analysis was used for prediction of events.

Results: Elevated IL-6 values (≥3.3 pg/mL) emerged as an independent and the most powerful predictor for cardiovascular mortality: the ROC analysis showed that IL-6 was more accurate for cardiovascular mortality prediction as compared to hsCRP (IL-6: AUC = 0.72; 95%CI: 0.62-0.81; p = 0.009 vs hsCRP: AUC = 0.56; 95%CI: 0.41-0.72; p = 0.445). The positive predictive value of IL-6 for mortality was 9%, the negative predictive value 99%, sensitivity 94% and specificity 48%. The primary endpoint of long-term cardiovascular death occurred more frequently in patients with high vs low IL-6 (9.0% vs 0.5%, p = 0.001). The multivariate Cox regression analysis revealed that patients with high IL-6 (≥3.3 pg/mL) values were at 8.6-fold higher hazard to die than those with low IL-6 (<3.3 pg/mL) levels (adj. hazard ratio [HR] = 8.60, 95%CI: 1.07-69.32; p = 0.043).

Conclusion: In the setting of ACS, high IL-6 values are associated with substantial long-term cardiovascular mortality. Further, IL-6 performs as a superior predictor for cardiovascular death as compared to hsCRP.

Keywords: Acute coronary syndrome; Cardiovascular mortality; High-sensitivity C-reactive protein; Interleukin-6; Long-term; Powerful predictor.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy*
  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / mortality
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation


  • Biomarkers
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • C-Reactive Protein