Cardiology
META ANALYSIS
● Meta-analysis
Inflammation Linked to Recurrence After AF-Related Stroke: Meta-Analysis
Neurology
Published March 27, 2026
McCabe John J, Harris Katie, Gorey Sarah, Walsh Cathal, Arnold Markus, De Marchis Gian Marco, Hervel…
PubMed ↗
DOI ↗
This individual participant data meta-analysis included 11 prospective studies with a total of 10,080 patients, of which 2,134 had atrial fibrillation (AF). The study aimed to evaluate the association between inflammatory markers (IL-6 and hsCRP) and vascular recurrence post-stroke, stratified by AF status. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), including fatal or nonfatal recurrent stroke or major coronary events. During 21,080 person-years of follow-up, 1,677 patients experienced MACEs and 1,342 had recurrent strokes. Elevated hsCRP levels were associated with an increased risk of MACEs in both AF (adjusted risk ratio [aRR] 1.14, 95% CI 1.04-1.25) and non-AF patients (aRR 1.08, 95% CI 1.03-1.13), with no significant difference between groups (P=0.30). However, hsCRP was not associated with recurrent stroke in either group. IL-6 showed no interaction with AF status for MACEs (P=0.57) or recurrent stroke (P=0.82), with aRRs for MACEs being 1.17 (95% CI 1.07-1.27) in non-AF patients and 1.10 (95% CI 0.91-1.34) in AF patients. For recurrent stroke, aRRs were 1.15 (95% CI 1.05-1.25) in non-AF patients and 1.12 (95% CI 0.91-1.37) in AF patients. No safety or adverse events were reported in this analysis. These findings underscore the role of inflammation in vascular recurrence and suggest that future trials of anti-inflammatory therapies should consider including AF patients and stratifying by inflammatory marker levels.
AI Accuracy Review: 9/10
· Auto-published
This study focuses on patients who have had a stroke related to atrial fibrillation, a condition where the heart beats irregularly. Researchers looked at data from many studies to see how certain inflammation markers in the blood relate to the risk of having another stroke or serious heart problems. They discovered that higher levels of inflammation were connected to an increased risk of these issues, whether or not patients had atrial fibrillation. This suggests that inflammation plays a significant role in the chances of having another stroke or heart event. For patients, this means that managing inflammation might be important in reducing their risk of future strokes or heart problems. However, it's important to note that more research is needed to understand how best to treat inflammation in these patients, especially since many recent treatments did not include those with atrial fibrillation.
What this means for you: Managing inflammation may help reduce the risk of future strokes for patients with heart rhythm issues.
View Original Abstract ↓
BACKGROUND AND OBJECTIVES: The residual recurrence risk after atrial fibrillation (AF)-related stroke is high despite anticoagulation, thereby necessitating new therapies. The importance of inflammation in AF is increasingly recognized. However, patients with AF-related stroke were excluded from recent trials of anti-inflammatory therapies. It is uncertain whether associations between IL-6/high-sensitivity C-reactive protein (hsCRP) and poststroke recurrence are modified by AF status. In this study, we aimed to analyze the association between IL-6/hsCRP and recurrence according to AF history.
METHODS: We leveraged individual participant data from studies identified by systematic review. We analyzed associations between IL-6/hsCRP and recurrent stroke/major adverse cardiovascular events (MACEs) (defined as fatal or nonfatal recurrent stroke or major coronary events) using multivariable Cox regression analyses (conditional logistic regression for 1 study) adjusted for age, sex, index event, cardiovascular risk factors, and medication use, stratified by AF status.
RESULTS: Data from 11 prospective studies with 10,080 patients (2,134 with AF, mean age 70 years, 59.3% male) were included. During 21,080 person-years of follow-up, 1,677 patients had MACEs and 1,342 had recurrent stroke. Inflammatory markers were higher in patients with AF, irrespective of stroke severity and timing of measurement, with elevated levels persisting well beyond the acute phase. hsCRP was associated with recurrent MACEs in patients with AF (adjusted risk ratio [aRR] 1.14, 95% CI 1.04-1.25, per log-unit increase) and without AF (aRR 1.08, 1.03-1.13) (P 0.30). There were similar associations on per-quarter analysis in patients with AF (aRR 1.51, 1.04-2.18) and without AF (aRR 1.32, 1.10-1.59) (Q4 vs Q1). No association was observed between hsCRP and recurrent stroke in either group. For IL-6, there was no evidence of interaction according to AF status for MACEs (P 0.57) or recurrent stroke (P 0.82). The aRR per log unit for MACE was 1.17 (1.07-1.27) in patients without AF and 1.10 (0.91-1.34) in those with AF. The corresponding aRR for recurrent stroke was 1.15 (1.05-1.25) and 1.12 (0.91-1.37) in patients without and with AF, respectively.
DISCUSSION: These data highlight the importance of inflammatory mechanisms in vascular recurrence irrespective of AF, provide rationale for the inclusion of patients with AF in trials of anti-inflammatory therapy, and support a selection approach in future trials based on elevated inflammatory marker levels, rather than stroke etiology alone.