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Circ Res. 2019 Sep 27;125(8):773-782. doi: 10.1161/CIRCRESAHA.119.315380. Epub 2019 Sep 3.

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

Author information

1
From the Institute for Stroke and Dementia Research, University Hospital (M.K.G., R.M., M.D.), Ludwig-Maximilians-University, Munich.
2
Graduate School for Systemic Neurosciences (M.K.G.), Ludwig-Maximilians-University, Munich.
3
Clinical Sciences, Malmö, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., A.S., M.S., J.N.).
4
Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Scotland (T.A.P., P.K.M.).
5
Biostatistics, Boston University School of Public Health, MA (S.D., A.S.B.).
6
National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, MA (S.D., A.S.B., E.J.B., S.S.).
7
Cardiology, University of Texas Southwestern Medical Center, Dallas (C.A., J.A.d.L.).
8
Research Unit of Molecular Epidemiology (M.A.E.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg.
9
Institute of Epidemiology (M.A.E., A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg.
10
German Research Center for Cardiovascular Disease, Partner site Munich Heart Alliance (M.A.E., W.K.).
11
Brown Foundation Institute of Molecular Medicine, McGovern Medical School and Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston (M.F.).
12
Department of Neurology, Boston University School of Medicine, MA (A.S.B.).
13
Medicine, Boston University School of Medicine, MA (E.J.B., S.S.).
14
Epidemiology, Boston University School of Public Health, MA (E.J.B.).
15
Amsterdam UMC, University of Amsterdam, Cardiology, the Netherlands (M.S.B.).
16
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf (C.H.).
17
German Center for Diabetes Research, Partner Düsseldorf (C.H.).
18
Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany (C.H.).
19
Medicine, Baylor College of Medicine, Houston, TX (R.C.H., C.M.B.).
20
Deutsches Herzzentrum München, Technische Universität München, Germany (W.K.).
21
Institute of Epidemiology and Biostatistics, University of Ulm, Germany (W.K.).
22
Cardiology, Skåne University Hospital, Malmö, Sweden (A.S.).
23
MRC Epidemiology Unit, University of Cambridge, United Kingdom (N.W.).
24
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio (S.S.).
25
Munich Cluster for Systems Neurology, Germany (M.D.).
26
German Centre for Neurodegenerative Diseases, Munich, Germany (M.D.).

Abstract

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:

atherosclerosis; cerebrovascular disorders; chemokine CCL2; inflammation; stroke

PMID:
31476962
PMCID:
PMC6763364
[Available on 2020-09-27]
DOI:
10.1161/CIRCRESAHA.119.315380

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