TOPLINE:

After stroke, patients with atrial fibrillation (AF) had higher levels of the inflammatory markers high‑sensitivity C‑reactive protein (hsCRP) and interleukin‑6 (IL‑6) than those without AF, irrespective of stroke severity, and inflammation remained elevated beyond the acute stroke phase. Elevated hsCRP levels independently predicted the risk for major adverse cardiovascular events (MACEs), irrespective of AF status, but did not predict the risk for recurrent stroke.

METHODOLOGY:

• Researchers conducted an individual participant data meta‑analysis to determine whether elevated levels of the inflammatory markers hsCRP and IL‑6, measured after stroke, were associated with an increased risk for recurrent stroke and MACEs and differed by AF status.
• They included 11 studies identified through a systematic review (10 prospective cohort studies and one nested case-control study within a randomised controlled trial) comprising 10,080 participants (59.3% men), of whom 8574 had experienced ischaemic stroke and 2134 had AF.
• Analyses were conducted separately for participants with and without AF at baseline, defined as a history or new diagnosis of paroxysmal, persistent, or permanent AF during the treatment episode for the index stroke.
• Coprimary endpoints were any MACE (ie, any recurrent stroke, major coronary event, or death due to vascular causes) and recurrent stroke (any ischaemic, haemorrhagic, or unknown subtype); only events that occurred after biomarker measurement were counted.

TAKEAWAY:

• During 21,085 person-years of follow-up, 1677 participants experienced at least one MACE, where the first event was recurrent stroke in 1338 participants, a major coronary event in 311, or vascular death of unspecified cause in 28, and 1342 had recurrent stroke (1220 ischaemic, 111 haemorrhagic, and 11 unknown subtype).
• After stroke, patients with AF had substantially higher median levels of IL-6 (7.46 pg/mL vs 3.98 pg/mL) and hsCRP (4.17 mg/L vs 3.0 mg/L; P < .001 for both) than those without AF, irrespective of stroke severity, and this difference persisted beyond the acute stroke period.
• After multivariable adjustments, each per loge-unit increase in hsCRP level was associated with a higher risk for MACEs in patients with AF (adjusted relative risk [RR], 1.14; 95% CI, 1.04-1.25) and those without AF (adjusted RR, 1.08; 95% CI, 1.03-1.13). No significant association was observed between increased hsCRP levels and the risk for recurrent stroke in either group.
• Increased IL-6 levels were not independently associated with the risk for MACEs or recurrent stroke in patients with AF, with no evidence of interaction by AF status.

IN PRACTICE:

"This work provides a strong rationale for inclusive, biomarker-guided anti-inflammatory trials and moves the field toward a more mechanistically informed and personalized model of secondary stroke prevention," experts wrote in an editorial accompanying the article.

SOURCE:

This study was led by John J. McCabe, Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland. It was published online on February 16, 2026, in Neurology.

LIMITATIONS:

The study could not establish causality, and residual confounding likely remained because data on AF-specific predictors such as heart failure, chronic kidney disease, left atrial size, and the timing and burden of AF were unavailable. Data were pooled from studies with independent protocols that used various assays, introducing potential bias. The study may have been underpowered to detect effect modification by AF status despite formal interaction testing.

DISCLOSURES:

The authors reported receiving no targeted funding. Several authors declared receiving research grants or speaker honoraria, serving on advisory boards, and having other relationships with various pharmaceutical companies and organisations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.