Joan Walter1, Yunus Tanglay2, Jeanne du Fay de Lavallaz1, Ivo Strebel3, Jasper Boeddinghaus1, Raphael Twerenbold3, Stephanie Doerflinger3, Christian Puelacher1, Thomas Nestelberger3, Desiree Wussler1, Melissa Amrein3, Patrick Badertscher3, John Todd4, Katharina Rentsch5, Gregor Fahrni3, Raban Jeger3, Christoph Kaiser3, Tobias Reichlin6, Christian Mueller7. 1. Cardiovascular 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. 2. Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, University Hospital Basel, University of Basel, Switzerland; Department of Anaesthesiology and Intensive Care, University Hospital Basel, University of Basel, Switzerland. 3. Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, University Hospital Basel, University of Basel, Switzerland. 4. Singulex, Alameda, CA, United States. 5. Department of Laboratory Medicine, University Hospital Basel, University of Basel, Switzerland. 6. Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, University Hospital Basel, University of Basel, Switzerland; Department of Cardiology, Inselspital, University of Bern, Switzerland. 7. Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, University Hospital Basel, University of Basel, Switzerland. Electronic address: christian.mueller@usb.ch.
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.
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.
Authors: Maros Ferencik; Thomas Mayrhofer; Michael T Lu; Daniel O Bittner; Hamed Emami; Stefan B Puchner; Nandini M Meyersohn; Alexander V Ivanov; Elizabeth C Adami; Deepak Voora; Geoffrey S Ginsburg; James L Januzzi; Pamela S Douglas; Udo Hoffmann Journal: JACC Cardiovasc Imaging Date: 2022-05-11
Authors: Jeremias Bayon; Amparo Alfonso; Sandra Gegunde; Eva Alonso; Rebeca Alvarino; Melisa Santas-Alvarez; Ana Testa-Fernandez; Ramon Rios-Vazquez; Luis Botana; Carlos Gonzalez-Juanatey Journal: Cardiol Res Date: 2020-08-01