Interleukin-6 and Cardiovascular Events in Healthy Adults

Muhammad Shahzeb Khan, MD, MSc; Khawaja M. Talha, MBBS; Muhammad Haisum Maqsood, MD; Jennifer A. Rymer, MD, MBA; Barry A. Borlaug, MD; Kieran F. Docherty, MD; Ambarish Pandey, MD; Florian Kahles, MD; Maja Cikes, MD; Carolyn S.P. Lam, MD; Anique Ducharme, MD; Adrian A. Voors, MD; Adrian F. Hernandez, MD; A. Michael Lincoff, MD; Mark C. Petrie, MD; Paul M. Ridker, MD, MPH; Marat Fudim, MD, MHS

JACC: Advances (Aug 2024)

Interleukin-6 and Cardiovascular Events in Healthy Adults

Muhammad Shahzeb Khan, MD, MSc,
Khawaja M. Talha, MBBS,
Muhammad Haisum Maqsood, MD,
Jennifer A. Rymer, MD, MBA,
Barry A. Borlaug, MD,
Kieran F. Docherty, MD,
Ambarish Pandey, MD,
Florian Kahles, MD,
Maja Cikes, MD,
Carolyn S.P. Lam, MD,
Anique Ducharme, MD,
Adrian A. Voors, MD,
Adrian F. Hernandez, MD,
A. Michael Lincoff, MD,
Mark C. Petrie, MD,
Paul M. Ridker, MD, MPH,
Marat Fudim, MD, MHS

Affiliations

Muhammad Shahzeb Khan, MD, MSc: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina, USA; Address for correspondence: Dr Muhammad Shahzeb Khan, Duke University Medical Center and Duke Clinical Research Institute, 2301 Erwin Road, Durham, North Carolina 27710, USA.
Khawaja M. Talha, MBBS: Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
Muhammad Haisum Maqsood, MD: Department of Cardiology, DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas, USA
Jennifer A. Rymer, MD, MBA: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina, USA
Barry A. Borlaug, MD: Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
Kieran F. Docherty, MD: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
Ambarish Pandey, MD: Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Florian Kahles, MD: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany
Maja Cikes, MD: University of Zagreb School of Medicine, University Hospital Centre, Zagreb, Croatia
Carolyn S.P. Lam, MD: Duke-NUS Medical School, Singapore, Singapore
Anique Ducharme, MD: Institut de Cardiologie, de Montréal, Université de Montréal, Montréal, Québec, Canada
Adrian A. Voors, MD: Department of Cardiology, University Medical Center of Groningen, University of Groningen, Groningen, the Netherlands
Adrian F. Hernandez, MD: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina, USA
A. Michael Lincoff, MD: Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA
Mark C. Petrie, MD: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
Paul M. Ridker, MD, MPH: Center for Cardiovascular Disease Prevention, Division of Preventive Medicine and the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
Marat Fudim, MD, MHS: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina, USA; Dr Marat Fudim, Duke University Medical Center and Duke Clinical Research Institute, 2301 Erwin Road, Durham, North Carolina 27710, USA.

Journal volume & issue: Vol. 3, no. 8
p. 101063

Abstract

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Background: Elevated interleukin (IL)-6 levels have been linked to adverse outcomes in patients with and without baseline cardiovascular disease (CVD). Objectives: The purpose of this study was to examine the association between circulating IL-6 levels and CVD events without baseline CVD across racial and ethnic groups. Methods: We conducted an observational analysis utilizing the MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter, prospective community-based study of CVD at baseline from four racial and ethnic groups. IL-6 levels were measured at the time of enrollment (visit 1) and were divided into 3 terciles. Patient baseline characteristics and outcomes, including all-cause mortality, CV mortality, heart failure, and non-CV mortality, were included. Cox proportional hazard regression models were used to assess associations between IL-6 levels and study outcomes with IL-6 tercile 1 as reference. Results: Of 6,622 individuals, over half were women (53%) with a median age of 62 (IQR: 53-70) years. Racial and ethnic composition was non-Hispanic White (39%) followed by African American (27%), Hispanic (22%), and Chinese American (12%). Compared to tercile 1, participants with IL-6 tercile 3 had a higher adjusted risk of and all-cause mortality (HR: 1.98 [95% CI: 1.67-2.36]), CV mortality (HR: 1.55 [95% CI: 1.05-2.30]), non-CV mortality (HR: 2.05 [95% CI: 1.65-2.56]), and heart failure (HR: 1.48 [95% CI: 0.99-2.19]). When tested as a continuous variable, higher levels of IL-6 were associated with an increased risk of all individual outcomes. Compared to non-Hispanic White participants, the unadjusted and adjusted risk of all outcomes across all races and ethnicities was similar across all IL-6 terciles. Conclusions: High levels of circulating IL-6 are associated with worse CV outcomes and increased all-cause mortality consistently across all racial and ethnic groups.

Published in JACC: Advances

ISSN: 2772-963X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://www.sciencedirect.com/journal/jacc-advances

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