High IL-6 Levels Linked to Carotid Plaque Severity, Progression

Kelli Whitlock Burton

May 18, 2022

Increased circulating levels of the cytokine interleukin 6 (IL-6) are associated with carotid plaque severity and progression, contributing to an increased risk of stroke, a new study suggests.

The researchers also identified an IL-6 level cutoff that might help clinicians identify patients who could benefit from specific anti-IL-6 treatments.

"One of the major conclusions that we could draw from this is that inflammation has a contribution to vulnerability or destabilization of carotid plaques and progression of carotid plaques that is independent of that of dyslipidemia," said lead researcher Joseph Kamtchum Tatuene, MD, PhD, a neurologist at the University of Alberta in Edmonton, Alberta, Canada.

"That means that adding an anti-inflammation treatment to the current best medical therapy including antiplatelet drugs and lipid lowering drugs could improve the prevention of stroke or carotid plaque progression in patients," he added.

The findings were presented May 5 at the European Stroke Organisation Conference (ESOC) 2022 Annual Meeting in Lyon, France.

A Role for IL-6 in Plaque Severity?

The study, an analysis of the large Cardiovascular Health Study, is the latest in a growing body of work that suggests a link between inflammation and stroke.

Researchers analyzed carotid plaque assessments and IL-6 levels in 4334 participants aged 65 years at baseline and again after 5 years.

Nearly 30% of patients showed plaque vulnerability at baseline, defined as irregular, ulcerated, or echolucent plaques. At 5 years, 34% had plaque progression, measured using a standardized scoring system for carotid narrowing.

IL-6 levels predicted plaque severity (P = .04), vulnerability (odds ratio [OR], 1.22; P = .006), and progression (OR, 1.44; P < .001).

Researchers also identified a cutoff level for IL-6 — 2.0 pg/mL — that helped to correctly identify plaque progression in more than 70% of patients.

For carotid plaque severity, researchers found that for each 1 standard deviation increase in the levels of IL-6, there was a 0.08 increase in the carotid plaque severity score.

They also reported a 12% increase in plaque vulnerability found on carotid ultrasound per 1 standard deviation increase in IL-6, and a 24% increase in plaque progression at 5 years per 1 standard deviation increase in the levels of IL-6 from baseline.

Unanswered Questions

The findings suggest assessing IL-6 levels may be useful in identifying patients at high risk of atherosclerotic disease progression and provides evidence in support of clinical trials to evaluate anti-IL-6 treatments as adjuvant stroke prevention strategies in clinical trials of patients with carotid atherosclerosis.

"We hope that the findings of this study will lead to the implementation of new trials and, maybe later on, new management guidelines for patients with carotid atherosclerosis," Tatuene said.

Anti-IL-6 drugs have the potential to offer novel treatments for patients with a high risk of stroke from carotid atherosclerosis who are not eligible for carotid surgery, including patients with multiple health conditions or mild or moderate carotid artery stenosis with high-risk plaque features on imaging.

Researchers could use the proposed cutoff IL-6 level to decide which patients should be included in these trials, Tatuene added.

"This is a reasonable hypothesis, but although there may be a relationship between circulating IL-6 levels and the carotid atherosclerosis, it does not necessarily mean that lowering the level will either reduce the progression of atherosclerosis or reduce the risk of stroke," said Larry B. Goldstein, MD, professor and chair of neurology and co-director of the Kentucky Neuroscience Institute at the University of Kentucky in Lexington, Kentucky, who commented on the findings for Medscape Medical News.

The potential link between circulating IL-6 levels and carotid atherosclerosis has been explored in other studies, Goldstein added, and there are questions that future work would need to answer.

"Although the authors indicate that the analysis was adjusted for stroke risk factors, it is not clear whether it was adjusted for the use of statins or PCSK9 inhibitors," he said.

Funding was not disclosed. Tatuene and Goldstein have disclosed no relevant financial relationships.

European Stroke Organisation Conference (ESOC) 2022 Annual Meeting: Abstract 765. Presented May 5, 2022.

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