Background and Aims Interleukin-6 (IL-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy could be 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 Cardiovascular Health Study.

Methods Carotid ultrasound was performed at baseline and 5 years. Plaque severity was scored 0 to 5 based on NASCET grade of stenosis. Plaque vulnerability at baseline was the presence of irregular, ulcerated or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. Relationship of 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.

Results In 4334 participants with complete data (58.9% women, 72.7 ± 5.1 years). There were 1267 (29.2%) participants with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β = 0.09, p=0.04), vulnerability (OR = 1.22, 95% CI: 1.06-1.40, p=0.006) and progression (OR = 1.44, 95% CI: 1.23-1.69, p<0.001). In participants with >50% probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect performance of regression models.

Conclusions Plasma IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cut-off could help select individuals that would benefit from anti-IL-6 drugs for stroke prevention.