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Georgakis, Marios K.; de Lemos, James A.; Ayers, Colby; Wang, Biqi; Bjorkbacka, Harry; Pana, Tiberiu A.; Thorand, Barbara; Sun, Caroline; Fani, Lana; Malik, Rainer; Dupuis, Josee; Engstrom, Gunnar; Orho-Melander, Marju; Melander, Olle; Boekholdt, S. Matthijs; Zierer, Astrid; Elhadad, Mohamed A.; König, Wolfgang; Herder, Christian; Hoogeveen, Ron C.; Kavousi, Maryam; Ballantyne, Christie M.; Peters, Annette ORCID logoORCID: https://orcid.org/0000-0001-6645-0985; Myint, Phyo K.; Nilsson, Jan; Benjamin, Emelia J. and Dichgans, Martin ORCID logoORCID: https://orcid.org/0000-0002-0654-387X (2020): Association of Circulating Monocyte Chemoattractant Protein-1 Levels With Cardiovascular Mortality A Meta-analysis of Population-Based Studies. In: Jama Cardiology, Vol. 6, No. 5: pp. 587-592 [PDF, 995kB]

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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. Question Are circulating monocyte-chemoattractant protein-1 (MCP-1) levels associated with the risk of cardiovascular disease in the general population? Findings In this meta-analysis of 7 population-based studies involving 21401 individuals who were free of overt cardiovascular disease, higher baseline circulating MCP-1 levels were associated with higher risk of cardiovascular mortality over a follow-up extending beyond 20 years. Meaning By complementing evidence from previous genetic and experimental studies, these results provide additional support for a key role of MCP-1 in cardiovascular disease development. This meta-analysis of 7 population-based cohort studies assesses the association between circulating monocyte-chemoattractant protein-1 levels and risk of cardiovascular disease and death.

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