Baseline hsCRP may improve risk stratification in ICAS-related stroke by identifying residual inflammatory risk beyond conventional risk factors, while the prognostic value of IL-6 was less robust and requires further investigation.
Key Findings
Results
Among patients with ICAS, elevated IL-6 and hsCRP were each associated with significantly higher 1-year MACE rates compared to those with lower levels.
942 patients with ischemic stroke enrolled within 1 week of onset; 262 (27.8%) had ICAS defined as ≥50% stenosis/occlusion
IL-6 ≥4.2 pg/mL associated with MACE rate of 28.8% versus 15.4% in those with lower IL-6 (log-rank P=0.012)
hsCRP ≥2.0 mg/L associated with MACE rate of 28.5% versus 15.9% in those with lower hsCRP (log-rank P=0.015)
Median cutoffs of ≥4.2 pg/mL for IL-6 and ≥2.0 mg/L for hsCRP were used to define elevated levels
Primary endpoint was 1-year major adverse cardiovascular events (MACE), including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death
Results
After multivariate adjustment, hsCRP ≥2.0 mg/L remained independently associated with MACE in ICAS patients, while the association for IL-6 was attenuated and no longer statistically significant.
IL-6 ≥4.2 pg/mL: HR 1.75 (95% CI, 0.95–3.23) after multivariate adjustment, with the confidence interval crossing 1.0
The attenuation of IL-6's association suggests confounding by other clinical variables
Study design was prospective observational
Results
ROC-derived optimal cutoffs of 5.0 pg/mL for IL-6 and 2.9 mg/L for hsCRP independently predicted MACE in ICAS patients.
IL-6 cutoff of 5.0 pg/mL: HR 2.02 for MACE prediction
hsCRP cutoff of 2.9 mg/L: HR 2.86 for MACE prediction
These ROC-derived cutoffs were higher than the median-based cutoffs used in primary analyses (4.2 pg/mL and 2.0 mg/L, respectively)
Both biomarkers independently predicted MACE at these ROC-derived thresholds
Results
Both IL-6 and hsCRP were associated with MACE among ICAS patients who achieved low-density lipoprotein cholesterol <100 mg/dL.
This finding suggests that inflammatory biomarkers identify residual risk even in patients meeting LDL-cholesterol targets
LDL-C <100 mg/dL is a standard secondary prevention target consistent with guideline-based therapy
The association in this subgroup implies that inflammation contributes to risk beyond lipid control
Methods
ICAS was present in 27.8% of ischemic stroke patients enrolled within 1 week of onset.
262 of 942 patients had ICAS (27.8%)
Mean age of the full cohort was 71.2 years; 61.3% were men
ICAS was defined as ≥50% stenosis or occlusion of intracranial arteries
The study enrolled patients within 1 week of ischemic stroke onset
Background
Intracranial atherosclerotic stenosis carries a high recurrence risk despite guideline-based secondary prevention, and inflammation may contribute to this residual risk.
ICAS is described as 'a major cause of ischemic stroke with a high recurrence risk despite guideline-based secondary prevention'
The prognostic roles of IL-6 and hsCRP in ICAS-related stroke were previously unclear
The study was designed as a prospective observational study to address this knowledge gap
What This Means
This research suggests that inflammation—measured by two blood markers called interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)—can help predict which stroke patients with a particular type of artery narrowing in the brain (intracranial atherosclerotic stenosis, or ICAS) are at higher risk of having another serious cardiovascular event within a year. Among 942 stroke patients, about 28% had ICAS, and in this group, those with elevated levels of either marker had nearly double the rate of major cardiovascular events (such as another stroke, heart attack, or vascular death) compared to those with lower levels.
After accounting for other risk factors statistically, hsCRP remained a strong independent predictor of these serious outcomes, while IL-6's predictive value became less certain. Importantly, both markers were still associated with higher risk even among patients who had achieved good cholesterol control (LDL below 100 mg/dL), suggesting that inflammation represents a separate, additional source of risk that standard cholesterol-lowering treatment does not fully address.
This research suggests that measuring inflammation markers—particularly hsCRP—at the time of an ICAS-related stroke could help doctors identify patients who remain at high risk despite standard treatments, potentially opening the door to targeting inflammation as part of stroke prevention strategies. The findings also suggest that slightly higher cutoff values (5.0 pg/mL for IL-6 and 2.9 mg/L for hsCRP) may be more useful thresholds for identifying high-risk patients than simple median-based cutoffs.
Hoshino T, Mizuno T, Arai S, Hosoya M, Takahashi S, Wako S, et al.. (2026). Prognostic Value of Interleukin-6 and High-Sensitivity C-Reactive Protein in Stroke Associated With Intracranial Atherosclerotic Stenosis.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.050279