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Review
. 2024 Nov 26;27(1):12.
doi: 10.1007/s11883-024-01259-7.

IL-6 and Cardiovascular Risk: A Narrative Review

Nehal N Mehta  1 , Emil deGoma  2 , Michael D Shapiro  3
Affiliations
Review

IL-6 and Cardiovascular Risk: A Narrative Review

Nehal N Mehta et al. Curr Atheroscler Rep. .

Abstract

Purpose of review: The objective of this narrative review is to summarize data from recently published prospective observational studies that analyze the association between circulating interleukin-6 (IL-6) levels and cardiovascular clinical or imaging endpoints.

Recent findings: Higher levels of IL-6 are associated with a higher risk of cardiovascular death, major adverse cardiovascular events, myocardial infarction, stroke, peripheral artery disease, and heart failure. Imaging studies have also shown an association between IL-6 and carotid intima-media thickness progression, carotid plaque progression, severity, and vulnerability. These observations have been consistent across a wide range of study populations and after adjusting for traditional and emerging risk factors including high-sensitivity C-reactive protein. Robust epidemiologic evidence supports IL-6 as a central mediator of cardiovascular risk along with human genetic studies and mechanistic experiments. Ongoing clinical studies are testing the therapeutic hypothesis of IL-6 inhibition in patients with atherosclerotic cardiovascular disease or heart failure.

Keywords: Atherosclerosis; Cardiovascular outcomes; Hs-CRP; Inflammation; Interleukin-6; Risk prediction.

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Conflict of interest statement

Declarations. Conflict of Interest: NNM has served as a consultant for receiving and received grants/other payments from AbbVie, Celgene, Janssen Pharmaceuticals, Novartis, AMGEN, Astra Zeneca, Abcentra, Tourmaline, Bristol Meyers Squibb, Sun Pharmaceuticals and Celgene. EdG is an employee of Tourmaline Bio, Inc. MDS is supported by institutional grants from Amgen, Arrowhead, Boehringer Ingelheim, 89Bio, Esperion, Novartis, Ionis, Merck, New Amsterdam, and Cleerly. MDS has participated in Scientific Advisory Boards with Amgen, Agepha, Ionis, Novartis, New Amsterdam, and Merck. MDS has also served as a consultant for Ionis, Novartis, Regeneron, Aidoc, Shanghai Pharma Biotherapeutics, Kaneka, Novo Nordisk, Arrowhead, and Tourmaline. Human and Animal Rights and Informed Consent: No human or animal subjects by the authors were used in this study.

Figures

Fig. 1
Fig. 1
ASCVD mechanism of disease. Figure created with Biorender.com
Fig. 2
Fig. 2
Landmark epidemiological studies of IL-6 levels and cardiovascular outcomes. A The first report of an association between IL-6 and cardiovascular outcomes was published by Ridker at al. [29] in 2000 and showed a 38% increase in risk of myocardial infarction per quartile increase in IL-6. (B). A landmark meta-analysis of 29 prospective studies published by Kaptoge et al. [14] in 2014 showed a 25% increased risk of nonfatal myocardial infarction or coronary heart disease death per 1-SD higher level of IL-6
Fig. 3
Fig. 3
Patients with high IL-6 experience higher risk of cardiovascular events, irrespective of hs-CRP levels
See this image and copyright information in PMC

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