Author + information
- Johanne Silvain, MD, PhD1,2,∗,
- Mathieu Kerneis, MD1,2,∗,
- Michel Zeitouni, MD1,2,
- Benoit Lattuca, MD, PhD1,2,
- Sophie Galier2,
- Delphine Brugier1,2,
- Emilie Mertens1,
- Niki Procopi1,
- Gaspard suc1,
- Tomy Salloum1,
- Eric Frisdal, PhD2,
- Wilfried Le Goff, PhD2,
- Jean-Philippe Collet, MD, PhD1,2,
- Eric Vicaut, MD, PhD3,
- Philippe Lesnik, PhD2,
- Gilles Montalescot, MD, PhD1,2,‡ ( and )
- Maryse Guerin, PhD2
- 1Sorbonne Université, ACTION Study Group, INSERM UMRS1166, ICAN - Institute of CardioMetabolism and Nutrition Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
- 2INSERM UMRS1166 Hôpital de la Pitié, Paris, Franc, Sorbonne Université, Paris, France, ICAN - Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France
- 3Unité de Recherche Clinique, ACTION Study Group, Hôpital Fernand Widal (AP-HP), Paris, France. SAMM - Statistique, Analyse et Modélisation Multidisciplinaire EA 4543, Université Paris, 1 Panthéon Sorbonne, France
- ↵‡Corresponding Author. Professor Gilles Montalescot ACTION Study Group, www.action-cœur.org. Bureau 1, 2ème étage Institut de Cardiologie, Pitié-Salpêtrière Hospital, 47-83 bld de l'Hôpital, 75013 Paris Telephone: +33 142163001 Fax: +33 142162931 Twitter handle: @docjohanne
Background Inhibition of the interleukin-1β (IL-1β) innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high sensitivity C-reactive protein (hs-CRP).
Objectives: to assess the association between IL-1β level with all-cause mortality in patients with acute ST segment elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death.
Methods IL-1β concentration was measured among 1398 ST segment elevation MI patients enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90-days and one-year using a multivariate-cox proportional regression analysis. Major cardiovascular events (MACE) were analyzed.
Results IL-1β concentration measured at admission was associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR], 1.47 per 1SD increase; 95% CI, 1.16 to 1.87; p<0.002). The relation was nonlinear, and highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; 95%CI: 1.61-4.79, p=0.0002) and one-year (adjHR: 1.93; 95%CI: 1.21-3.06, p=0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACE at 90 days (adjHR: 2.42; 95% CI: 1.36-4.28, p=0.002 and 2.29; 95% CI: 1.31-4.01, p=0.004, respectively) and at one year (adjHR: 2.32; 95% CI: 1.36-3.97, p=0.002 and 2.35; 95% CI: 1.39-3.96, p=0.001, respectively).
Conclusion IL-1β measured at admission in acute MI patients is independently associated with the risk of mortality and recurrent MACE.
Condensed Abstract In this observational prospective cohort study that included 1398 patients with ST segment elevation myocardial infarction, IL-1β concentration measured at admission was independently associated with all-cause mortality (adjusted hazard ratio [adjHR], 1.47 per 1SD increase; 95% CI, 1.16 to 1.87; p<0.002) and major cardiovascular event at 90 days and one year. The relation was nonlinear, and highest tertile of IL-1β was markedly associated with higher mortality rates at 90 days (adjHR: 2.78; 95%CI: 1.61-4.79, p=0.0002) and one-year (adjHR: 1.93; 95%CI: 1.21-3.06, p=0.005), regardless of the hs-CRP concentration.
↵∗ Dr Silvain and Dr Kerneis contributed equally to this work as first authors
Sources of Funding: This work was supported by the ACTION Coeur study group (www.action-coeur.org), the Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne University, the Institute of CardioMetabolism and Nutrition (ICAN), and by the French National Agency through the national program Investissements d’Avenir Grant ANR-10-IAHU-05.
Disclosures: Johanne SILVAIN reports during the past 2 years the following disclosures: Consulting Fees or Lecture Fees or Travel Support from AstraZeneca, Bayer HealthCare SAS, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Terumo France SAS, Abbott Medical France SAS, Stockholder of Pharmaseeds. Mathieu KERNEIS received Research Grants from Institut Servier, Federation Francaise de Cardiologie, Sanofi, Consulting fees from Bayer, Sanofi, Servier. Michel ZEITOUNI has received research grants from Servier and Fédération Francaise de Cardiologie. Benoit LATTUCA has received research grants from Daiichi-Sankyo and Fédération Francaise de Cardiologie; consultant fees from Daiichi-Sankyo and Eli Lilly; and lecture fees from AstraZeneca. Eric VICAUT reports consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards, Pfizer, Sanofi And Novartis. Jean-Philippe COLLET has received research grants or honorarium from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli-Lilly, Fédération Francaise de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, WebMD all outside of the scope of this study. Gilles MONTALESCOT has received research grants or honorarium from ADIR, Amgen, AstraZeneca, Bayer, Berlin Chimie AG, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Cardiovascular Research Foundation, Celladon, CME Resources, Daiichi-Sankyo, Eli-Lilly, Europa, Elsevier, Fédération Francaise de Cardiologie, Fondazione Anna Maria Sechi per il Cuore, Gilead, ICAN, Janssen, Lead-Up, Menarini, Medtronic, MSD, Pfizer, Sanofi-Aventis, Servier, The Medicines Company, TIMI Study Group, WebMD all outside of the scope of this study. The remaining authors have nothing to disclose
Data Sharing: Data sharing including for biological analyses require specific authorizations of the Hospital and Ethics committee on the basis of any new study proposal and will therefore not be made available to others without these approvals.
- Received July 2, 2020.
- Revision received August 12, 2020.
- Accepted August 12, 2020.
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