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Circulating Monocyt...
Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke : Meta-Analysis of Population-Based Studies Involving 17 180 Individuals
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- Georgakis, Marios K. (author)
- University Hospital Munich,Ludwig-Maximilian University of Munich
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- Malik, Rainer (author)
- Ludwig-Maximilian University of Munich,University Hospital Munich
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- Björkbacka, Harry (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - cellulär metabolism och inflammation,Forskargrupper vid Lunds universitet,Cardiovascular Research - Cellular Metabolism and Inflammation,Lund University Research Groups
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- Pana, Tiberiu Alexandru (author)
- University of Aberdeen
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- Demissie, Serkalem (author)
- Framingham Heart Study,Boston University
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- Ayers, Colby (author)
- University of Texas Southwestern Medical Center
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- Elhadad, Mohamed A. (author)
- Helmholtz Zentrum München,German Centre for Cardiovascular Research
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- Fornage, Myriam (author)
- University of Texas Health Science Centre
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- Beiser, Alexa S. (author)
- Boston University,Framingham Heart Study
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- Benjamin, Emelia J. (author)
- Framingham Heart Study,Boston University
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- Boekholdt, Matthijs S. (author)
- Academic Medical Center of University of Amsterdam (AMC)
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- Engström, Gunnar (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups
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- Herder, Christian (author)
- Heinrich Heine University Düsseldorf
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- Hoogeveen, Ron C. (author)
- Baylor College of Medicine
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- Koenig, Wolfgang (author)
- University of Ulm,German Centre for Cardiovascular Research,Technical University of Munich
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- Melander, Olle (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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- Orho-Melander, Marju (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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- Schiopu, Alexandru (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Skåne University Hospital
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- Söderholm, Martin (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups
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- Wareham, Nick (author)
- University of Cambridge
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- Ballantyne, Christie M. (author)
- Baylor College of Medicine
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- Peters, Annette (author)
- Helmholtz Zentrum München
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- Seshadri, Sudha (author)
- University of Texas Health Science Centre,Framingham Heart Study,Boston University
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- Myint, Phyo K. (author)
- University of Aberdeen
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- Nilsson, Jan (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups
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- de Lemos, James A. (author)
- University of Texas Southwestern Medical Center
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- Dichgans, Martin (author)
- German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich,Munich Cluster for Systems Neurology
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(creator_code:org_t)
- 2019
- 2019
- English 10 s.
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In: Circulation Research. - 0009-7330. ; 125:8, s. 773-782
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- atherosclerosis
- cerebrovascular disorders
- chemokine CCL2
- inflammation
- stroke
Publication and Content Type
- art (subject category)
- ref (subject category)
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Georgakis, Mario ...
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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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Benjamin, Emelia ...
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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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Seshadri, Sudha
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Myint, Phyo K.
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Nilsson, Jan
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de Lemos, James ...
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Dichgans, Martin
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Circulation Rese ...
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