C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis

John J. McCabe; Cathal Walsh; Sarah Gorey; Katie Harris; Pablo Hervella; Ramon Iglesias-Rey; Christina Jern; Linxin Li; Nobukazu Miyamoto; Joan Montaner; Annie Pedersen; Francisco Purroy; Peter M. Rothwell; Catherine Sudlow; Yuji Ueno; Mikel Vicente-Pascual; William Whiteley; Mark Woodward; Peter J. Kelly

doi:10.1161/STROKEAHA.122.040529

C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis

John J. McCabe
, Cathal Walsh
, Sarah Gorey
, Katie Harris
, Pablo Hervella
, Ramon Iglesias-Rey
, Christina Jern
, Linxin Li
, Nobukazu Miyamoto
, Joan Montaner
, Annie Pedersen
, Francisco Purroy
, Peter M. Rothwell
, Catherine Sudlow
, Yuji Ueno
, Mikel Vicente-Pascual
, William Whiteley
, Mark Woodward
, Peter J. Kelly

Health Research Board Ireland
University College Dublin
University of Limerick
Sahlgrenska University Hospital
University of New South Wales
Health Research Institute of Santiago de Compostela
University of Gothenburg
University of Oxford
Juntendo University
Vall d'Hebron University Hospital
Hospital Universitario Virgen del Rocio
Hospital Universitario Virgen Macarena
Autonomous University of Barcelona
Hospitalt Universitari Arnau de Vilanova de Lleida
IRBLleida
University of Edinburgh
Imperial College London

Research output: Contribution to journal › Article › peer-review

Abstract

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 log_eIL-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 log_ehsCRP). 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.

Original language	English
Pages (from-to)	1289-1299
Number of pages	11
Journal	Stroke
Volume	54
Issue number	5
DOIs	https://doi.org/10.1161/STROKEAHA.122.040529
Publication status	Published - 1 May 2023
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

coronary artery disease
infarction
inflammation
ischemic stroke
thrombosis

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10.1161/STROKEAHA.122.040529

Cite this

McCabe, J. J., Walsh, C., Gorey, S., Harris, K., Hervella, P., Iglesias-Rey, R., Jern, C., Li, L., Miyamoto, N., Montaner, J., Pedersen, A., Purroy, F., Rothwell, P. M., Sudlow, C., Ueno, Y., Vicente-Pascual, M., Whiteley, W., Woodward, M., & Kelly, P. J. (2023). C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis. Stroke, 54(5), 1289-1299. https://doi.org/10.1161/STROKEAHA.122.040529

@article{d7d3b10167284399b645872571fa228b,

title = "C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis",

abstract = "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.",

keywords = "coronary artery disease, infarction, inflammation, ischemic stroke, thrombosis",

author = "McCabe, \{John J.\} and Cathal Walsh and Sarah Gorey and Katie Harris and Pablo Hervella and Ramon Iglesias-Rey and Christina Jern and Linxin Li and Nobukazu Miyamoto and Joan Montaner and Annie Pedersen and Francisco Purroy and Rothwell, \{Peter M.\} and Catherine Sudlow and Yuji Ueno and Mikel Vicente-Pascual and William Whiteley and Mark Woodward and Kelly, \{Peter J.\}",

year = "2023",

month = may,

day = "1",

doi = "10.1161/STROKEAHA.122.040529",

language = "English",

volume = "54",

pages = "1289--1299",

journal = "Stroke",

issn = "0039-2499",

number = "5",

}

McCabe, JJ, Walsh, C, Gorey, S, Harris, K, Hervella, P, Iglesias-Rey, R, Jern, C, Li, L, Miyamoto, N, Montaner, J, Pedersen, A, Purroy, F, Rothwell, PM, Sudlow, C, Ueno, Y, Vicente-Pascual, M, Whiteley, W, Woodward, M & Kelly, PJ 2023, 'C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis', Stroke, vol. 54, no. 5, pp. 1289-1299. https://doi.org/10.1161/STROKEAHA.122.040529

TY - JOUR

T1 - C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke

T2 - An Individual Participant Data Meta-Analysis

AU - McCabe, John J.

AU - Walsh, Cathal

AU - Gorey, Sarah

AU - Harris, Katie

AU - Hervella, Pablo

AU - Iglesias-Rey, Ramon

AU - Jern, Christina

AU - Li, Linxin

AU - Miyamoto, Nobukazu

AU - Montaner, Joan

AU - Pedersen, Annie

AU - Purroy, Francisco

AU - Rothwell, Peter M.

AU - Sudlow, Catherine

AU - Ueno, Yuji

AU - Vicente-Pascual, Mikel

AU - Whiteley, William

AU - Woodward, Mark

AU - Kelly, Peter J.

PY - 2023/5/1

Y1 - 2023/5/1

N2 - 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.

AB - 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.

KW - coronary artery disease

KW - infarction

KW - inflammation

KW - ischemic stroke

KW - thrombosis

UR - https://www.scopus.com/pages/publications/85153802970

U2 - 10.1161/STROKEAHA.122.040529

DO - 10.1161/STROKEAHA.122.040529

M3 - Article

C2 - 37026458

AN - SCOPUS:85153802970

SN - 0039-2499

VL - 54

SP - 1289

EP - 1299

JO - Stroke

JF - Stroke

IS - 5

ER -

C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis

Abstract

UN SDGs

Keywords

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