Association between Serum Levels of Interleukin-6 and Stroke, Cardiovascular Events, and Alzheimer’s Disease Dementia

Abstract

Aims: The blood inflammatory marker interleukin 6 (IL-6) has been shown to predict future stroke, major adverse cardiovascular events (MACEs), and dementia. However, no study has yet examined this relationship in the same population. The present study compared the predictive utility of IL-6 levels in stroke, MACEs, and Alzheimer’s disease (AD) dementia.

Methods: In this post-hoc analysis, we derived data from a Japanese observational registry in which 1011 patients with evidence of cerebral vessel disease were enrolled. After excluding patients who required assistance with daily tasks, were suspected of having dementia, and lacked IL-6 measurement, 471 patients were included. The patients were followed up until March 2023. The outcomes were incident stroke, MACEs, and AD dementia.

Results: During a median follow-up period of 4.6 years, stroke, MACEs, and AD dementia occurred in 24, 36, and 21 patients, respectively. Serum IL-6 levels are associated with age, sex, and vascular factors. A Cox proportional hazard analysis revealed that the highest IL-6 tertile (≥ 2.5 pg/mL) was associated with a significantly higher risk of stroke and MACEs than the lowest IL-6 tertile after adjusting for confounding factors (stroke, adjusted hazard ratio 4.84 [95% confidence interval, 1.02-23.05], P = 0.048; MACEs, adjusted hazard ratio 3.68 [95% confidence interval, 1.01-13.51], P = 0.049). However, no association was found between IL-6 tertile groups and AD dementia.

Conclusion: Serum IL-6 levels predicted stroke and cardiovascular events but not AD dementia in patients with vascular risk factors. The involvement of low-grade systemic inflammation appears to be significantly greater in atherothrombotic events than that in AD dementia.