Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome

医学内科学肾脏疾病心肌梗塞急性冠脉综合征心脏病学

作者

Gorav Batra,Tatevik Ghukasyan Lakic,Johan Lindbáck,Claes Held,Harvey D. White,Ralph Stewart,Wolfgang Köenig,Christopher P. Cannon,Andrzej Budaj,Emil Hagström,Agneta Siegbahn,Lars Wallentin,Miguel Bustamante Labarta,Luis 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,M. 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 R F 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 Bedard,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,Jan M. Kornder,Simon Kouz,Andre Y Lainesse,Rolland Leader,Lawrence A. Leiter,Eva Lonn,Alain Milot,M Pearce,Lew Pliamm,Calvin N Powell,Barry Rose,Dennis Rupka,Anthony J. Della Siega,Peter Klinke,Eric St-Amour,P. R. Talbot,Jean‐Claude Tardif,Steven Tishler,Lawrence Title,Graham C. Wong,Christopher E. Buller,Monica Andrea Acevedo Blanco,Francisco Alarcón,Edgardo Escobar,Fernando Florenzano Urzúa,Oneglio Antonio Pedemonte Villablanca,Juan Carlos Prieto Dominguez,Patricio Sanhueza Cardemil,Paola Elena Varleta Olivares,Hong Chen,Jiyan Chen,Yugang Dong,Junbo Ge,Ben He,Yong Huo,Weimin Li,Xinli Li,Liao Yuhua,Meng Wei,Xiao-Wei Yan,Ping Ye,Zuyi Yuan,Yun Zhang,Jianhua Zhu,Ondřej Čermák,Vratislav Dedek,Lumír Francek,Hana Grünfeldová,Jan Hubac,Pavel Franc,Ivana Kellnerova,Zdeněk Klimsa,J Kroupa,Ladislav Kuchař,Aleš Linhart,Jan Malecha,Jiri Povolny,Tomáš Velimský,Roman Volf,Vladimir Jirka,Lia E. Bang,Peer Grande,Lars Frost,Steen Husted,Rikke V Laursen,Tonny Nielsen,Anu Hedman,Piibe Muda,Ülle Planken,C Barnay,Christophe Bauters,Gilles Bayet,Jacques Bonnet,Éric Bruckert,Yves Cottin,J.P. Courrèges,Nicolas Danchin,Eric Decoulx,J M Demarcq,Jean‐Luc Dubois‐Randé,Meyer Elbaz,Khalifé Khalife,Michel Krempf,Eric Maupas,Michel Ovize,José Gérald Roul,François Schiele,Jean‐Pierre Bassand,Philippe Gabríel Steg,B. Vaı̈sse,Ulrich Aigner,Udo Bavendiek,Dieter Fischer,Gisela Benedix,Hilmar Boeneke,Jochen Bott,Bernadett Brado,Marianne Buhr,Christian Butter,Steffen Fischer,Andreas Foerster,Marc Oliver Grad,Josef Großkopf,M Hanefeld,Susanne Hoeltz,Horst-Michael Frick,Gabriele Illies,Thomas Jung,Barbara Kademann,Gert Kahrmann,Alexandra Bourrat,Thomas Horacek,Regina Reusch,Gerhard Klausmann,Christiane Klein,Karl Heinz Krause,Detlev Kuesters,Klaus‐Peter Mellwig,Thomas Menke,Steve Mueller,Gerhard Neumann,Ruth Nischik,Andreas Preusche,Martin Prohaska,Stefan Franz Regner,Wilfried Rein,Reinhard Rummel,Holger Samer,Thomas Schaefer,Isabelle Schenkenberger,Ekkehard Schmidt,Norbert Schoen,Andreas Schreckenberg,U Schulze,J. Wunderlich,Hae‐Young Sohn,Volker Klauß,Nicole Toursarkissian,Jan-Gerrit Voigt,Dirk Weber,B. Winkelmann,Dirk Zuechner,Dimitrios Alexopoulos,Maria Anastasiou‐Nana,Dimitrios Kremastinos,Moses Elisaf,Parashos Geleris,Ioannis Kallikazaros,Athanasios Kranidis,Athanasios Manolis,Ioannis Mantas,Christoforos Olympios,Dimitrios Tziakas,Vassilis Voudris,Y.Y. Lam,Wai Kwok Gabriel Yip,Chung‐Wah Siu,Béla Benczúr,Andrea Hornyik,Zoltan László,András Papp,Anikó Papp,Zsolt Plés,Annamária Piros,I Szakál,T Turi,Mátyás Sereg,András Vértes,Sunitha Abraham,Darshan Banker,Prakash Chandwani,Rajeev Kumar Gupta,Jagdish Hiremath,Santhosh M. Jayadev,Stigimon Joseph,Jaideep Menon,C Keshavamurth,Arun Srinivas,Keyur Parikh,Ramesh Babu Pothineni,Shireesh Sathe,Jitendra P Sawhney,Sumeet Sethi,Praveen Kumar Chandra,Sudhir Varma,Diego Ardissino,Marco Bobbio,Angelo Sante Bongo,Francesco Cipollone,Andrea Mezzetti,Furio Colivicchi,Massimo Santini,Giovanni Esposito,Massimo Chiariello,Mario Marzilli,Piera Angelica Merlini,Luciano Moretti,Zoran Olivari,Giampiero Patrizi,Marco Valgimigli,Hiroshi Amemiya,Kenji Andò,Masashi Iwabuchi,Masahiro Endo,Hirotaka Nagashima,Ryosuke Kametani,Akihiro Koike,Takehiko Kuramochi,Yuichiro Nakamura,Koji Oku,Masaaki Okutsu,Atsushi Sueyoshi,Wataru Takahashi,Yasuyuki Sasaki,Jun Tanabe,Hideki Tanaka,Katsuro Kashima,Yutaka TANAKA,Satoshi Takeshita,Jun‐ichi Teranishi,Tetsuo Betsuyaku,Takashi Yamamoto,Seiji Yamazaki,Shoji Yano,Kazuro Yoshida,Jei–Keon Chae,Shung-Chull Chae,Myeong-Chan Cho,Donghoon Choi,Dong‐Ju Choi,Taek-Jong Hong,Hui-Kyung Jeon,Myung‐Ho Jeong,Hyo‐Soo Kim,Hyun Joong Kim,Kyu-Hyung Ryu,Woo-Shik Kim,Kwon-Sam Kim,Sanghoon Lee,Do‐Sun Lim,Seong‐Wook Park,Ki‐Bae Seung,Jose-Luis Cervantes-Escárcega,Ismael Hernández-Santamaría,Carlos Sanchez-Diaz,Marittza-Arasely Uribe-Rios,Ricardo Alvarado-Ruiz,Robbert J. de Winter,René Dijkgraaf,Rutger M.G Jansen,N. M. J. Knufman,J. Frederiks,Adrianus F.M Kuijper,Johannes C. Post,H. R. Michels,H.W.O. Roeters van Lennep,Anho AH Liem,Pieter C. Smits,H. Swart,Adrianus J Van Boven,M E van Daele,Coenraad Van der Zwaan,Clemens von Birgelen,I. C. D. Westendorp,Laura Davidson,Gerard Devlin,John Elliott,Andrew Hamer,N. A. Harrison,Richard J Rankin,Hamish Hart,Matthew J. Hills,Timothy J O'Meeghan,Douglas Scott,Jonathan G Tisch,Michael Williams,V. Chen,Christ Berge,Helge Istad,Terje R. Pedersen,Per Anton Sirnes,Bashir Hanif,Riaz Ishaq,Azhar Mahmood Kayani,Muhammad Bilal Ahsan Qureshi,Saulat Siddique,Zia Yaqub,Rafael Doig,F S de Britto,Pedro Yanac,Manuel Horna,J. Valdivia,Mario Cesar Zubiate,Nelson S Abelardo,Maria Teresa B. Abola,John C Añonuevo,Alberto A Atilano,Federick C Cheng,Emma Y Gaspar-Trinidad,Jorge Sison,DENNIS JOSE SULIT,Rody G. Sy,Norbert Lingling D. Uy,Arkadiusz Chmielinski,Aleksandra Czepiel,Ewa M Guzniczak,Tomasz Siminiak,Grzegorz Kania,Krzysztof Kincel,Jerzy Kopaczewski,Jacek Kubica,Roman Lysek,Paweł Miękus,Adam Młodziankowski,Piotr Napora,F Prochaczek,Teresa Ruscika,Janusz Tarchalski,Wiesława Tracz,Bożena Wrzosek,Gheorghe V Basarab,Imre Benedek,Mircea Cinteză,Madalina I Cristea,Doina R Dimulescu,Daniela Dragusin,Iulia Gabor,C Ginghina,Cezar Macarie,Crina Sinescu,Gabriel Tatu-Chitoiu,Dragoș Vinereanu,Natalya A Andryushina,Svetlana R Baum,М. В. Архипов,О. Л. Барбараш,С. А. Болдуева,Mikhail Boyarkin,Arkady P Demko,Marina S Freydlin,Sergei P. Golitsyn,И. Г. Гордеев,N.A. Gratsiansky,Yuri A Karpov,Zhanna Kobalava,В. О. Константинов,Andrey D Kuimov,В. В. Кухарчук,A. V. Panov,Mikhail Y Ruda,S. A. Sayganov,В. И. Симаненков,O. G. Smolenskaya,Л. П. Цыба,Alexander Y Vishnevsky,Polina K Yakhontova,S. S. Yаkushin,D. A. Zateyshchikov,Ľudovít Gašpar,Marián Hranai,Martin Kokles,Daniel Pella,Aysha Badat,Karen Sliwa‐Hahnle,Suzanne Blignaut,Lesley Burgess,Anthony J. Dalby,Saleem Dawood,Thomas Gray,Adrian Horak,Thomas Mabin,Pravin Manga,Rajendran Moodley,Maria M Pretorius,F. S. Hough,Andre Roodt,Jan A. Saaiman,Hendrik du Toit Theron,R. Alonso Karlezi,Pedro. Mata López,Pedro Aranda Granados,José R. Fernández,Daniel Carnevali Ruiz,Almudena Castro Conde,José Ma Cruz Fernández,Eduardo de Teresa Galván,L. de Teresa Parreño,Isabel Díaz Buschmann,José Ramón Domínguez Escribano,Juan Puig,Blas Gil Extremera,Jorge Gómez Cerezo,Carlos Miguel Macaya,José Ma Mostaza Prieto,Roberto Muñoz Aguilera,Carlos Pérez Muñoz,Ramón Querejeta Iraola,José Antonio Romero Hinojosa,L.M. Ruilope Urioste,J. Ruiz,J. Sobrino Martínez,Enma Concepción Suárez Suárez,Íñigo Lozano,Faris Al-Khalili,Stellan Bandh,Marie Bennermo,Mikael Dellborg,Johan Herlitz,Per Johanson,Lars Hjelmaeus,Karl Landergren,Carina Linderfalk,Carl-Johan Lindholm,Krister Lindmark,Thomas Mooe,Jan Nilsson,Peter Wodlin,Yi‐Lwun Ho,Charles Jia‐Yin Hou,Chien‐Hsun Hsia,Shing‐Jong Lin,Liang‐Miin Tsai,Kuo‐Yang Wang,Chunhakasem Chotinaiwattarakul,Srun Kuanprasert,Nakarin Sansanayudh,Piyamitr Sritara,Taworn Suithichaiyakul,Svitlana Andriyevska,Andriy Y Basylevych,V. I. Denesiuk,L. Kononenko,Oleksii Korzh,Volodymyr M. Kovalenko,Igor Kraiz,Viktoriia Y Lishnevska,M. І. Lutay,Oleksandr Parkhomenko,Leonid Rudenko,Zinaida Y Telyatnikova,Vira Tseluyko,Mykola Vatutin,Vadym Vizir,Ameet Bakhai,Harbal S Bijral,Edmund Stewart,Henry Dargie,M. Barlow,David P. Dutka,Iain Findlay,Michael B. Fisher,Diana A. Gorog,Adam Jacques,Ian Beeton,Brian Logie,John Pepper,Marcus Flather,Ian Purcell,William Scullion,James F. Thompson,Roxy Senior,David Simpson,Simon Thackray,Mohammed F Alamgir,John Wilding,Yuk-ki Wong,Abdel M Ahmed,Mark C Antonishen,Keith Atassi,José Azócar,Eric Ball,Christie M. Ballantyne,Harold Bays,Jill E Beavins,Sabrina A Benjamin,Mark R Benson,Peter B. Berger,Jeremy W Buckley,William R Betz,Robert W.W. Biederman,Edward W. Bisher,Vera Bittner,Cristian F Breton,Salvatore Buttaci,Mahesh Changlani,John B. Patterson,Leroy J Byrd,Donald B Canaday,W.Richard Cashion,Harish Chandna,Anna Chang,John Chin,Harry P Claybrook,Frederick A Martin,Ken Cohen,David Colan,Gregg Coodley,Marshall A. Corson,Robert H. Knopp,Pathmaja Paramsothy,Richard A. Cottiero,Paresh Dandona,Michael H. Davidson,Kent T Kamaradt,Ashwini K Davuluri,Vikas S Desai,G. David Garson,Cara East,Ramin Ebrahimi,Howard Ellison,Bernard R Erickson,Valerian Fernandes,Angel R. Flores,Steven Folkerth,Robert E. Foster,Raul Gaona,Timothy J. Gardner,William H. George,C. Gessler,Santosh K Gill,Alan S. Go,Anne C. Goldberg,Marc Goldschmidt,Timothy A Gorman,Donald F Brautigam,John R. Guyton,Thomas A. Haffey,Sheldon D. Henry,Paul R Hermany,John A. Hoekstra,Michael Hudson,Bruce Iteld,David Jack,Frank P Johnson,B.C. Joswig,Amy J Kaissar,Adam Karns,R. Karns,S. Kaster,Boris Kerzner,Mohammad S. Khan,Ismail S Ahmed,Joshua Kieval,Edward Kim,Leslie J. Klaff,E. Klein,Michael Koren,Edward Kosinski,Razmig Krumian,Elizabeth Portnoy,Jeffrey T. Kuvin,Michael M Langer,Dustin Letts,Robert Lipetz,William J. Long,Ignatius Thomas,Maria F. Lopes‐Virella,Barry C. Lubin,Richard A. Martin,Bassem Masri,George Matthews,John Corbelli,Kevin J. McCullum,Alan W Meholick,Jerry R. Mitchell,Fariba Modares,Emile R. Mohler,Charle N Morcos,David K. Murdock,Puneet Narayan,Mandeep S Oberoi,Thomas M. O'Connor,Robert J Schnecker,Philip J. O’Donnell,Stephen T Ong,Pirouz Parang,John Pasquini,Rajesh Patel,Raghotham Patlola,W J Penny,Carl J. Pepine,Charles H. Pierce,Evan A. Stein,Larry Popeil,S. Pratt,Robert Price,Marina Raikhel,R. Ravi,Donald Cho,James M. Rhyne,Mark Richards,Ernesto Rivera,Jennifer G. Robinson,Eli M. Roth,CARL RUBENSTEIN,Jessica L. Sandoval,RENEE SANGRIGOLI,Erichn L Schramm,Arthur Schwartzbard,Gregory T Serfer,Dhiren H Shah,Marc S Shalek,Jeffrey G. Shanes,Marigene S Sharma,Elizabeth M Bretton,Zafar Iqbal Sheikh,Neal L. Sklaver,Maria Del Pilar Solano,Ronald Goldberg,Nalin Srivastava,Cezar Staniloae,Jonathan S Staub,Michael Stillabower,Damodhar P Suresh,Ireneusz Szulawski,Paul M. Thompson,Donna M. Polk,Jodi Tinkel,Utpal Pandya,Phillip T Toth,Mourhaf Traboulssi,Edward Tuohy,K Uusinarkaus,Nampalli K Vijay,Stephen Voyce,William Wainwright,Holly RHancock,James S. Walder,Tracy Wang,Stanley P. Watkins,Robert Weiss,Edwin J. Whitney,William Wickemeyer,John Willis,Dennis F Wilson,Cyril Abrams,Alan Wiseman,Eric Wolfson,David Wright,Edward T. Zawada,Suneet Verma

出处

期刊：JAMA Cardiology [American Medical Association]
日期：2021-08-25 卷期号：6 (12): 1440-1440 被引量：68

链接

jamanetwork.com hal.science nih.gov nih.govdoi.org

标识

DOI：10.1001/jamacardio.2021.3079

摘要

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.

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