Author + information
- Received July 2, 2020
- Revision received August 12, 2020
- Accepted August 12, 2020
- Published online October 5, 2020.
- Johanne Silvain, MD, PhDa,b,∗@docjohanne@actioncoeur,
- Mathieu Kerneis, MDa,b,∗,
- Michel Zeitouni, MDa,b,
- Benoit Lattuca, MD, PhDa,b,
- Sophie Galier, BSb,
- Delphine Brugier, PhDa,b,
- Emilie Mertens, MDa,
- Niki Procopi, MDa,
- Gaspard Suc, MDa,
- Tomy Salloum, MDa,
- Eric Frisdal, PhDb,
- Wilfried Le Goff, PhDb,
- Jean-Philippe Collet, MD, PhDa,b,
- Eric Vicaut, MD, PhDc,
- Philippe Lesnik, PhDb,
- Gilles Montalescot, MD, PhDa,b,∗ ( and )
- Maryse Guerin, PhDb
- aSorbonne Université, ACTION Study Group, INSERM UMRS1166, ICAN - Institute of CardioMetabolism and Nutrition Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
- bINSERM UMRS1166 Hôpital de la Pitié, Paris, France, Sorbonne Université, Paris, France, ICAN - Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France
- cUnité de Recherche Clinique, ACTION Study Group, Hôpital Fernand Widal (AP-HP), Paris, France
- ↵∗Address for correspondence:
Dr. Gilles Montalescot, ACTION Study Group, Bureau 1, 2ème étage Institut de Cardiologie, Pitié-Salpêtrière Hospital, 47-83 bld de l'Hôpital, 75013 Paris, France.
Background Inhibition of the interleukin (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 This study assessed the association between IL-1β level with all-cause mortality in patients with acute ST-segment elevation MI who underwent 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 in 1,398 patients with ST-segment elevation MI who enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90 days and 1 year using multivariate Cox proportional regression analysis. Major adverse cardiovascular events (MACEs) 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 1 SD increase; 95% confidence interval [CI]: 1.16 to 1.87; p < 0.002). The relation was nonlinear, and the highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; 95% CI: 1.61 to 4.79; p = 0.0002) and at 1 year (adjHR: 1.93; 95% CI: 1.21 to 3.06; p = 0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACEs at 90 days (adjHR: 2.42; 95% CI: 1.36 to 4.28; p = 0.002, and adjHR: 2.29; 95% CI: 1.31 to 4.01; p = 0.004, respectively) and at 1 year (adjHR: 2.32; 95% CI: 1.36 to 3.97; p = 0.002, and adjHR: 2.35; 95% CI: 1.39 to 3.96; p = 0.001, respectively).
Conclusions IL-1β measured at admission in patients with acute MI was independently associated with the risk of mortality and recurrent MACEs.
↵∗ Drs. Silvain and Kerneis contributed equally to this work as first authors.
This work was supported by the ACTION Coeur study group, 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. Dr. Silvain has received 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, and Abbott Medical France SAS; and holds stock in Pharmaseeds. Dr. Kerneis has received research grants from Institut Servier, Federation Francaise de Cardiologie, and Sanofi; and has received consulting fees from Bayer, Sanofi, and Servier. Dr. Zeitouni has received research grants from Servier and the Fédération Francaise de Cardiologie. Dr. Lattuca has received research grants from Daiichi-Sankyo and the Fédération Francaise de Cardiologie; has received consultant fees from Daiichi-Sankyo and Eli Lilly; and has received lecture fees from AstraZeneca. Dr. Vicaut has received consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards, Pfizer, Sanofi, and Novartis. Dr. Collet has received research grants or honorarium from AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Eli Lilly, the Fédération Francaise de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi, and WebMD, all outside of the submitted work. Dr. 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, the Fédération Francaise de Cardiologie, Fondazione Anna Maria Sechi per il Cuore, Gilead, ICAN, Janssen, Lead-Up, Menarini, Medtronic, MSD, Pfizer, Sanofi, Servier, The Medicines Company, TIMI Study Group, and WebMD, all outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Paul M Ridker, MD, MPH, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received July 2, 2020.
- Revision received August 12, 2020.
- Accepted August 12, 2020.
- 2020 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.