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Clinical utility of circulating interleukin-6 concentrations in the detection of functionally relevant coronary
Joan Walter1, Yunus Tanglay2, Jeanne du Fay de Lavallaz1
1Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, University Hospital Basel, University of Basel, Switzerland; Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland.
Insights
Measuring interleukin-6 (IL-6) levels can help predict cardiovascular and all-cause death in patients with suspected coronary artery disease (CAD). While IL-6 did not strongly diagnose CAD, higher levels indicated increased mortality risk over two years.
Area of Science:
- Cardiology
- Biomarkers
- Inflammation Research
Background:
- Inflammation is a key factor in coronary artery disease (CAD) development.
- Interleukin-6 (IL-6) is a pro-inflammatory cytokine implicated in cardiovascular pathogenesis.
Purpose of the Study:
- To investigate if quantifying circulating IL-6 concentrations aids in diagnosing and predicting functionally relevant CAD.
- To assess IL-6's predictive value for cardiovascular death and all-cause mortality in patients with suspected CAD.
Main Methods:
- A cohort of 1553 patients with symptoms suggestive of CAD were studied.
- Functionally relevant CAD was adjudicated based on myocardial perfusion imaging, angiography, and 2-year mortality outcomes.
- Circulating IL-6 concentrations were measured and analyzed for diagnostic and prognostic accuracy, blinded to IL-6 levels.
Main Results:
- IL-6 concentrations were higher in patients with functionally relevant CAD but showed low-to-modest diagnostic accuracy (AUC 0.57).
- IL-6 was not an independent predictor for diagnosing functionally relevant CAD.
- IL-6 demonstrated moderate-to-high accuracy in predicting 2-year cardiovascular death (AUC 0.75) and all-cause death (AUC 0.72), remaining a significant independent predictor.
Conclusions:
- Circulating IL-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death.
- IL-6 shows significant prognostic value for mortality in patients with suspected CAD.
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.
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