Interleukin-6, C-Reactive Protein, and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data

Area of Science:

• Biomarker analysis in cardiovascular disease
• Stroke research and epidemiology
• Inflammation and atherosclerosis

Background:

• Inflammation is a key driver of atherosclerosis.
• Current anti-inflammatory therapies lack proven benefit for post-stroke prevention.
• Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are linked to adverse cardiovascular events after stroke.

Purpose of the Study:

• To investigate the association between IL-6 and hsCRP levels and recurrent cardiovascular events after stroke.
• To determine the optimal timing for measuring IL-6 and hsCRP to predict outcomes.
• To inform patient selection for future anti-inflammatory therapy trials.

Main Methods:

• Individual-participant data from 11 studies (9798 patients) were analyzed.
• Time-course analysis examined IL-6 and hsCRP associations with recurrent major adverse cardiovascular events and stroke.
• Biomarker levels were stratified by acute (<24 hours) and postacute (≥24 hours) phases post-stroke.

Main Results:

• IL-6 levels were significantly higher in the acute phase (<24 hours) compared to the postacute phase (≥24 hours).
• Postacute IL-6 (≥24 hours) was associated with increased risk of recurrent major adverse cardiovascular events and stroke.
• Acute IL-6 measurements (<24 hours) did not show a significant association with these events.
• No time-dependent interaction was observed for hsCRP.

Conclusions:

• The timing of IL-6 measurement after stroke is critical for predicting recurrent cardiovascular events.
• Postacute IL-6 measurements are more informative than acute measurements for risk stratification.
• These findings support using IL-6 timing in future clinical trial designs for anti-inflammatory therapies in stroke survivors.