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

Walter, Joan; Tanglay, Yunus; du Fay de Lavallaz, Jeanne; Strebel, Ivo; Boeddinghaus, Jasper; Twerenbold, Raphael; Doerflinger, Stephanie; Puelacher, Christian; Nestelberger, Thomas; Wussler, Desiree; Amrein, Melissa; Badertscher, Patrick; Todd, John; Rentsch, Katharina; Fahrni, Gregor; Jeger, Raban; Kaiser, Christoph; Reichlin, Tobias Roman; Mueller, Christian (2019). Clinical utility of circulating interleukin-6 concentrations in the detection of functionally relevant coronary artery disease. International journal of cardiology, 275, pp. 20-25. Elsevier 10.1016/j.ijcard.2018.10.029

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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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