Clinical utility of circulating interleukin-6 concentrations in the detection of functionally relevant coronary artery disease. (15th January 2019) - Walter, Joan
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. Highlights: Interleukin-6 provides low diagnostic accuracy for functionally relevant CAD. Interleukin-6 provides low predictive accuracy for acute myocardial infarction. Interleukin-6 provides moderate-high predictive accuracy for (cardiovascular) death.