Association of Circulating Monocyte Chemoattractant Protein-1 Levels With Cardiovascular Mortality: A Meta-analysis of Population-Based Studies.

Marios K Georgakis, James A de Lemos, Colby Ayers, Biqi Wang, Harry Björkbacka, Tiberiu A Pana, Barbara Thorand, Caroline Sun, Lana Fani, Rainer Malik, Josée Dupuis, Gunnar Engström, Marju Orho-Melander, Olle Melander, S Matthijs Boekholdt, Astrid Zierer, Mohamed A Elhadad, Wolfgang Koenig, Christian Herder, Ron C Hoogeveen, Maryam Kavousi, Christie M Ballantyne, Annette Peters, Phyo K Myint, Jan Nilsson, Emelia J Benjamin, Martin Dichgans

Journal: JAMA cardiology 2022;6(5):587-592

PMID: 33146689

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Abstract

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 21 401 individuals (mean [SD] age, 53.7 [10.2] years; 10 012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326 392 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.

Address: Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilians-University, Munich, Germany.; Graduate School for Systemic Neurosciences, Ludwig-Maximilians-University, Munich, Germany.; Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.; Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.; Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, United Kingdom.; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; German Center for Diabetes Research, München-Neuherberg, Germany.; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilians-University, Munich, Germany.; Amsterdam UMC, University of Amsterdam, Department of Cardiology, Amsterdam, the Netherlands.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; German Research Center for Cardiovascular Disease, Partner Site of Munich Heart Alliance, Munich, Germany.; German Research Center for Cardiovascular Disease, Partner Site of Munich Heart Alliance, Munich, Germany.; Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.; German Center for Diabetes Research, München-Neuherberg, Germany.; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; German Center for Diabetes Research, München-Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; German Research Center for Cardiovascular Disease, Partner Site of Munich Heart Alliance, Munich, Germany.; Institute of Medical Information Sciences, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany.; Section of Cardiovascular Medicine and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.; Framingham Heart Study, National Heart, Lung, and Blood Institute and Boston University, Framingham, Massachusetts.; Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilians-University, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; German Centre for Neurodegenerative Diseases, Munich, Germany.

DOI: 10.1001/jamacardio.2020.5392