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Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke : Meta-Analysis of Population-Based Studies Involving 17 180 Individuals

Author:
  • Marios K. Georgakis
  • Rainer Malik
  • Harry Björkbacka
  • Tiberiu Alexandru Pana
  • Serkalem Demissie
  • Colby Ayers
  • Mohamed A. Elhadad
  • Myriam Fornage
  • Alexa S. Beiser
  • Emelia J. Benjamin
  • Matthijs S. Boekholdt
  • Gunnar Engström
  • Christian Herder
  • Ron C. Hoogeveen
  • Wolfgang Koenig
  • Olle Melander
  • Marju Orho-Melander
  • Alexandru Schiopu
  • Martin Söderholm
  • Nick Wareham
  • Christie M. Ballantyne
  • Annette Peters
  • Sudha Seshadri
  • Phyo K. Myint
  • Jan Nilsson
  • James A. de Lemos
  • Martin Dichgans
Publishing year: 2019
Language: English
Pages: 773-782
Publication/Series: Circulation Research
Volume: 125
Issue: 8
Document type: Journal article
Publisher: American Heart Association

Abstract english

Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.

Keywords

  • Cardiac and Cardiovascular Systems
  • Neurology
  • atherosclerosis
  • cerebrovascular disorders
  • chemokine CCL2
  • inflammation
  • stroke

Other

Published
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 0009-7330
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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