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Jan Nilsson

Professor

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

Author

  • 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

Summary, in English

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..

Department/s

  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension

Publishing year

2020-11-04

Language

English

Publication/Series

JAMA Cardiology

Document type

Journal article

Publisher

American Medical Association

Topic

  • Cardiac and Cardiovascular Systems

Status

Epub

Research group

  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • Cardiovascular Research - Epidemiology
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 2380-6583