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

Pubmed ID: 35713008

Pubmed Central ID: PMC9308732

Journal: Circulation research

Publication Date: July 8, 2022

Affiliation: Department of Medicine, Faculty of Medicine and Dentistry (G.C.J.), University of Alberta, Edmonton, Canada.

MeSH Terms: Humans, Male, Female, Aged, Risk Factors, Prospective Studies, Stroke, Atherosclerosis, Carotid Stenosis, Interleukin-6, Plaque, Atherosclerotic, Constriction, Pathologic, Endarterectomy, Carotid

Grants: HHSN268200800007C, HHSN268201200036C, N01 HC085085, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 AG023629, U01 HL080295, U01 HL130114, HHSN268201800001C, 75N92021D00006, RF1 AG074306, U24 NS107267, R01 MD012467, R01 NS040807, R01 AG056169, R01 NS029993, P30 AG066506, KL2 TR002737, UL1 TR002736, R56 AG056169

Authors: Polak JF, Rundek T, Kamtchum-Tatuene J, Saba L, Heldner MR, Poorthuis MHF, de Borst GJ, Kakkos SK, Chaturvedi S, Topakian R, Jickling GC

Cite As: Kamtchum-Tatuene J, Saba L, Heldner MR, Poorthuis MHF, de Borst GJ, Rundek T, Kakkos SK, Chaturvedi S, Topakian R, Polak JF, Jickling GC, Carotid Atherosclerosis and Stroke Collaboration (CASCO). Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and Progression. Circ Res 2022 Jul 8;131(2):e22-e33. Epub 2022 Jun 17.

Studies:

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 <i>P</i>&gt;0.05 for variable removal. To assess model stability, we computed the <i>E</i>-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, <i>P</i>=1.3×10<sup>-3</sup>), vulnerability (OR, 1.21 [95% CI, 1.05-1.40]; <i>P</i>=7.4×10<sup>-3</sup>, <i>E</i>-value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], <i>P</i>=9.1×10<sup>-6</sup>, <i>E</i>-value 2.24). In participants with &gt;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.