Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome
Gorav Batra, Tatevik Ghukasyan Lakic, Johan Lindbäck, Claes Held, Harvey D. White, Ralph Stewart, Wolfgang Köenig, Christopher P. Cannon, Andrzej Budaj, Emil Hagström, Agneta Siegbahn, Lars Wallentin, STABILITY Investigators, Miguel Bustamante Labarta, Luis R Cartasegna, Sergio Chekherdemian, Jose L Cuello, Pedro Elías, Jorge A Giordano, Alfredo Hirschson, Miguel Hominal, Julio O Ibañez, Horacio O. Jure, Marcos Litvak, Stella M. Macı́n, Ignacio Jorge MacKinnon, Laura Maffei, Oscar Montaña, Aldo Prado, JORGELINA SALA, Vanina Gorosito, Ramiro Sánchez, David Brieger, Derek P. Chew, D. Cross, Ferdinandus J. de Looze, A. Farshid, Stephen Hall, Henry Krum, Geoff K Lane, Ernesto Oqueli Flores, John Stickland, Peter W Purnell, Gregory Szto, Peter L. Thompson, Jonathan Waites, Maged William, Christophe Beauloye, Jean Boland, Filip Charlier, Herbert JLP De Raedt, Joseph AY Dens, Karl Dujardin, Alain Friart, André Scheen, Erwin Schröder, Peter Sinnaeve, Stefan Verheye, Pascal Vranckx, JOSE ANTONIO ABRANTES, Denílson Campos de Albuquerque, Wilma Roberta Ardito, Luciano Baracioli, Marcelo Chiara Bertolami, Luiz Carlos Bodanese, Raúl D. Santos, Lília Nigro Maia, Euler RF Manenti, Roberto Luiz Marino, Clarisse Kaoru Ogawa Indio do Brasil, Maria Sanali de Oliveira Paiva, Álvaro Rabelo Alves, Salvador Rassi, Gilmar Reis, Paulo RF Rossi, José Francisco K Saraiva, Haralambi O Benov, Boryana Chompalova, Stefan Denchev, Assen Goudev, Valentina Grigorova, Atanas Mihov, Valentina M Mincheva, С. В. Петрова, Angelina Staneva, Dimitar Raev, S. Tisheva, Ronnie Aronson, Jacques Bédard, RAKESH BHARGAVA, David J. Borts, Christian Constance, Jean R. Cusson, Richard F. Davies, John Ducas, Murdo ER Ferguson, Ronald Goldenberg, François Grondin, Gábor Gyenes, Frank Halperin
Abstract
Importance: Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease. Objective: To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function. Design, Setting, and Participants: This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020. Exposures: Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs ≥2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [≥90 mL/min/1.73 m2], mildly decreased eGFR level [60-90 mL/min/1.73 m2], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m2]). Main Outcomes and Measures: Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. Results: This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (≥2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]). Conclusions and Relevance: In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.