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Circulating Monocyt...
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Georgakis, Marios K.University Hospital Munich,Ludwig-Maximilian University of Munich
(author)
Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke : Meta-Analysis of Population-Based Studies Involving 17 180 Individuals
- Article/chapterEnglish2019
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LIBRIS-ID:oai:lup.lub.lu.se:2487f2ad-8be0-49c1-b3b2-9f1b72524992
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https://lup.lub.lu.se/record/2487f2ad-8be0-49c1-b3b2-9f1b72524992URI
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https://doi.org/10.1161/CIRCRESAHA.119.315380DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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 Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations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.
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Malik, RainerUniversity Hospital Munich,Ludwig-Maximilian University of Munich
(author)
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Björkbacka, HarryLund University,Lunds universitet,Kardiovaskulär forskning - cellulär metabolism och inflammation,Forskargrupper vid Lunds universitet,Cardiovascular Research - Cellular Metabolism and Inflammation,Lund University Research Groups(Swepub:lu)medf-hbj
(author)
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Pana, Tiberiu AlexandruUniversity of Aberdeen
(author)
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Demissie, SerkalemFramingham Heart Study,Boston University
(author)
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Ayers, ColbyUniversity of Texas Southwestern Medical Center
(author)
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Elhadad, Mohamed A.German Centre for Cardiovascular Research,Helmholtz Zentrum München
(author)
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Fornage, MyriamUniversity of Texas Health Science Centre
(author)
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Beiser, Alexa S.Framingham Heart Study,Boston University
(author)
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Benjamin, Emelia J.Boston University,Framingham Heart Study
(author)
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Boekholdt, Matthijs S.Academic Medical Center of University of Amsterdam (AMC)
(author)
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Engström, GunnarLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups(Swepub:lu)smi-gen
(author)
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Herder, ChristianHeinrich Heine University Düsseldorf
(author)
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Hoogeveen, Ron C.Baylor College of Medicine
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Koenig, WolfgangUniversity of Ulm,German Centre for Cardiovascular Research,Technical University of Munich
(author)
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Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome
(author)
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Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor
(author)
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Schiopu, AlexandruLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-asc
(author)
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Söderholm, MartinLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups(Swepub:lu)med-ms8
(author)
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Wareham, NickUniversity of Cambridge
(author)
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Ballantyne, Christie M.Baylor College of Medicine
(author)
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Peters, AnnetteHelmholtz Zentrum München
(author)
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Seshadri, SudhaBoston University,University of Texas Health Science Centre,Framingham Heart Study
(author)
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Myint, Phyo K.University of Aberdeen
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Nilsson, JanLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups(Swepub:lu)medf-jni
(author)
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de Lemos, James A.University of Texas Southwestern Medical Center
(author)
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Dichgans, MartinGerman Center for Neurodegenerative Diseases (DZNE), Bonn,Munich Cluster for Systems Neurology,University Hospital Munich
(author)
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University Hospital MunichLudwig-Maximilian University of Munich
(creator_code:org_t)
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In:Circulation Research125:8, s. 773-7820009-7330
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Malik, Rainer
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Björkbacka, Harr ...
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Pana, Tiberiu Al ...
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Demissie, Serkal ...
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Ayers, Colby
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Elhadad, Mohamed ...
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Fornage, Myriam
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Beiser, Alexa S.
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Boekholdt, Matth ...
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Engström, Gunnar
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Herder, Christia ...
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Hoogeveen, Ron C ...
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Koenig, Wolfgang
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Melander, Olle
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Orho-Melander, M ...
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Schiopu, Alexand ...
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Söderholm, Marti ...
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Wareham, Nick
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Ballantyne, Chri ...
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Peters, Annette
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