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C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis
John J McCabe1,2,3, Cathal Walsh1,4, Sarah Gorey1,2,3
1Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI), Dublin, Ireland (J.J.M., C.W., S.G., P.J.K.).
Insights
Inflammatory markers like high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) are linked to recurrent vascular events after ischemic stroke. This finding supports further research into anti-inflammatory therapies for stroke secondary prevention.
Area of Science:
- Neurology
- Cardiology
- Immunology
Background:
- Conflicting findings exist regarding blood inflammatory markers and vascular recurrence post-stroke.
- This uncertainty impacts the use of anti-inflammatory therapies and marker measurement in stroke management.
Approach:
- The study analyzed individual participant data from 10 prospective studies, involving 8420 patients with ischemic stroke or transient ischemic attack.
- Multivariable regression and random-effects meta-analysis were used to assess the association between hsCRP, IL-6, and recurrent major adverse cardiovascular events (MACE) and stroke.
Key Points:
- Elevated hsCRP and IL-6 levels were independently associated with increased risk of MACE and recurrent stroke after ischemic stroke.
- Higher levels of IL-6 and hsCRP were linked to a greater likelihood of recurrent cardiovascular events and stroke.
Conclusions:
- Blood inflammatory markers are independently associated with vascular recurrence following stroke.
- These findings provide a rationale for clinical trials investigating anti-inflammatory treatments for secondary stroke prevention.
Background:
Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines.
Methods:
We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis.
Results:
During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9-17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4-14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10-1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05-1.32]), per unit increase logeIL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09-1.29]; recurrent stroke RR, 1.12 [95% CI, 1.04-1.21], per unit increase logehsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04-1.21]; hsCRP, RR, 1.09 [95% CI, 1.04-1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00-1.19]; hsCRP, RR, 1.05 [95% CI, 1.00-1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09-1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07-1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08-1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93-1.43]).
Conclusions:
Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.
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