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Georgakis, M.K.* ; de Lemos, J.A.* ; Ayers, C.* ; Wang, B.* ; Björkbacka, H.* ; Pana, T.A.* ; Thorand, B. ; Sun, C.* ; Fani, L.* ; Malik, R.* ; Dupuis, J.* ; Engström, G.* ; Orho-Melander, M.* ; Melander, O.* ; Boekholdt, S.M.* ; Zierer, A. ; Elhadad, M.A. ; Koenig, W.* ; Herder, C.* ; Hoogeveen, R.C.* ; Kavousi, M.* ; Ballantyne, C.M.* ; Peters, A. ; Myint, P.K.* ; Nilsson, J.* ; Benjamin, E.J.* ; Dichgans, M.*

Association of circulating monocyte chemoattractant protein-1 levels with cardiovascular mortality: A meta-analysis of population-based studies.

JAMA Cardiol., DOI: 10.1001/jamacardio.2020.5392 (2020)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). Results: The meta-analysis included 7 cohort studies involving 21401 individuals (mean [SD] age, 53.7 [10.2] years; 10012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P =.01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P =.02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P <.001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein. Conclusions and Relevance: Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease..
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Atherosclerosis; Mice
ISSN (print) / ISBN 2380-6591
e-ISSN 2380-6583
Zeitschrift JAMA cardiology
Verlag American Medical Association
Verlagsort Chicago, Ill.
Begutachtungsstatus Peer reviewed
Förderungen Onassis Foundation
Boston University
National Institute of Aging
National Institute of Neurological Disorders and Stroke
Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research
National Heart, Lung, and Blood Institute
Cancer Research UK
German Academic Exchange Service
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services
DonaldW. Reynolds Foundation
Medical Research Council
State of Bavaria
German Research Foundation
SVDs@target
CoSTREAM
German Research Foundation as part of the Munich Cluster for Systems Neurology
Corona Foundation
Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain)
e:Med program (e:AtheroSysMed)
European Union project CVgenes@target (project FP7/2007-2103)
European Union's Horizon 2020 research and innovation programme
Swedish Foundation for Strategic Research
Swedish Heart and Lung Foundations
University of Ulm
Federal Ministry of Health
Ministry of Innovation, Science, Research and Technology of the state North RhineWestphalia
Helmholtz Alliance "Aging and Metabolic Programming"
German Federal Ministry of Health
Ministry of Culture and Science of the State of North Rhine-Westphalia
Federal Ministry of Education and Research
Swedish Research Council
German Research Foundation as part of the Collaborative Research Center 1123