Abstract / Description of output
Interleukin-6, C-Reactive Protein and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data from 9,798 Patients.
Background and aims
RCTs of anti-inflammatory therapies for prevention after stroke are ongoing. IL-6 and high-sensitivity CRP are independently associated with major adverse cardiovascular events (MACE) post-stroke and may guide patient selection in future RCTs. Interpretation of IL-6/hsCRP levels may be confounded by the contribution of an inflammatory response to infarction. Optimal timing of hsCRP/IL-6 measurement post-stroke is unknown.
Methods
Using individual-participant data from 9,798 patients (11 studies, 19,891 person-years follow-up), we performed a time-course analysis to investigate the association between hsCRP/IL-6 and recurrence stratified by phlebotomy timing. The post-stroke dynamics of IL-6/hsCRP levels were analysed by plotting their mean concentrations within each tenth of the sampling timeframe. Acute/post-acute phases were defined separately for each marker according to the shape of this relationship.
Results
IL-6 was markedly elevated <24hrs post-event compared with basal levels (≥24hrs) (11.6pg/ml vs. 3.02pg/ml, p<0.001). HsCRP remained elevated for 10days (Fig.1). On univariate analysis, IL-6 was associated with MACE if measured ≥24hrs (Risk ratio [RR] 1.30, CI 1.19-1.41, per unit logeIL-6), but not <24hrs (RR 1.10, CI 0.98-1.25, Pheterogeneity=0.03). After adjustment for risk factors/medication, the association remained for post-acute IL-6 when analysed per logeunit (RR 1.16, CI 1.05-1.66) and per quarter increase (RR 1.55, CI 1.19-2.02, Q4 vs Q1), but not if measured <24hrs, with similar findings for recurrent stroke. There was no evidence of interaction for hsCRP.
Conclusions
The association between IL-6 and recurrence is modified by sample timing. These data will inform future RCT design incorporating biomarker-based selection of patients for anti-inflammatory therapies.
Background and aims
RCTs of anti-inflammatory therapies for prevention after stroke are ongoing. IL-6 and high-sensitivity CRP are independently associated with major adverse cardiovascular events (MACE) post-stroke and may guide patient selection in future RCTs. Interpretation of IL-6/hsCRP levels may be confounded by the contribution of an inflammatory response to infarction. Optimal timing of hsCRP/IL-6 measurement post-stroke is unknown.
Methods
Using individual-participant data from 9,798 patients (11 studies, 19,891 person-years follow-up), we performed a time-course analysis to investigate the association between hsCRP/IL-6 and recurrence stratified by phlebotomy timing. The post-stroke dynamics of IL-6/hsCRP levels were analysed by plotting their mean concentrations within each tenth of the sampling timeframe. Acute/post-acute phases were defined separately for each marker according to the shape of this relationship.
Results
IL-6 was markedly elevated <24hrs post-event compared with basal levels (≥24hrs) (11.6pg/ml vs. 3.02pg/ml, p<0.001). HsCRP remained elevated for 10days (Fig.1). On univariate analysis, IL-6 was associated with MACE if measured ≥24hrs (Risk ratio [RR] 1.30, CI 1.19-1.41, per unit logeIL-6), but not <24hrs (RR 1.10, CI 0.98-1.25, Pheterogeneity=0.03). After adjustment for risk factors/medication, the association remained for post-acute IL-6 when analysed per logeunit (RR 1.16, CI 1.05-1.66) and per quarter increase (RR 1.55, CI 1.19-2.02, Q4 vs Q1), but not if measured <24hrs, with similar findings for recurrent stroke. There was no evidence of interaction for hsCRP.
Conclusions
The association between IL-6 and recurrence is modified by sample timing. These data will inform future RCT design incorporating biomarker-based selection of patients for anti-inflammatory therapies.
| Original language | English |
|---|---|
| Pages (from-to) | 1289–1299 |
| Journal | Stroke |
| Volume | 54 |
| Issue number | 5 |
| Early online date | 19 Dec 2023 |
| DOIs | |
| Publication status | Published - 23 Jan 2024 |