Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and Progression

Abstract

BACKGROUND: IL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study). METHODS: Duplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P >0.05 for variable removal. To assess model stability, we computed the E -value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples. RESULTS: There were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β=0.09, P =1.3×10 −3 ), vulnerability (OR, 1.21 [95% CI, 1.05–1.40]; P =7.4×10 −3 , E -value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P =9.1×10 −6 , E -value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models. CONCLUSIONS: Circulating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.

High Interleukin-6 Levels Are Associated With Large-Artery Atherosclerotic Stroke

“…8,13 Some previous clinical evidence revealed that the elevation of IL-6 is associated with the severity, vulnerability, and progression of carotid atherosclerotic plaques. 14,15 Genetic studies confirmed the causal relationship between IL-6 signaling and atherosclerotic disease. 16 Basic research has found that IL-6 plays an important role in initiating and maintaining atherosclerotic plaque development and plaque destabilization in many ways, including the proliferation and migration of smooth muscle cells and the recruitment and activation of the inflammatory mediators.…”

“…13,17 In addition, a recent study demonstrated that the proatherothrombotic effect from cardiovascular risk factors at least in part by accelerating IL-6-mediated arterial inflammation and remodeling. 15 Furthermore, the atherosclerosis-protective effect of some new anti-inflammatory drugs is mediated by reducing circulating IL-6 levels. 15 Together with the present study, our findings supported the assumption that IL-6 is linked to the progression of atherosclerosis.…”

Non-Fasting Hypertriglyceridemia Burden as a Residual Risk of the Progression of Carotid Artery Stenosis

“…The findings in the present study probably reflect the results of younger patients preferring diets that raise TG values. Although symptomatic carotid stenosis was also an independent risk factor for the progression in this study, the finding may reflect the importance of local factors such as inflammation [ 10 ], which cannot be shown by degree of stenosis and SIR of plaques.…”

The role of interleukin-6 in the development of cardiovascular diseases: A review

“…У 29,2% больных наблюдалась уязвимость бляшки, у 34,0% -прогрессирование бляшки. Уровень IL-6 коррелировал с размером бляшек и их уязвимостью [отношение шансов (ОШ) 1,21; 95% доверительный интервал (ДИ) 1,05-1,40; p=7,4×10 -3 ; E-значение 1,71] и прогрессированием (ОШ 1,44; 95% ДИ 1,23-1,69) [32].…”