医学
内科学
混淆
狭窄
优势比
逻辑回归
心脏病学
易损斑块
人口
颈动脉内膜切除术
外科
环境卫生
作者
Joseph Kamtchum‐Tatuene,Luca Saba,Mirjam Rachel Heldner,Michiel H.F. Poorthuis,G.J. de Borst,Tatjana Rundek,Stavros K. Kakkos,Seemant Chaturvedi,Raffi Topakian,Joseph F. Polak,Glen C. Jickling
标识
DOI:10.1161/circresaha.122.320877
摘要
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.
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