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

Georgakis, Marios K. ; De Lemos, James A. ; Ayers, Colby ; Wang, Biqi ; Björkbacka, Harry LU orcid ; Pana, Tiberiu A. ; Thorand, Barbara ; Sun, Caroline ; Fani, Lana and Malik, Rainer , et al. (2021) In JAMA Cardiology 6(5). p.587-592
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JAMA Cardiology
volume
6
issue
5
pages
6 pages
publisher
American Medical Association
external identifiers
  • pmid:33146689
  • scopus:85095884541
ISSN
2380-6583
DOI
10.1001/jamacardio.2020.5392
language
English
LU publication?
yes
id
48d32f75-e426-4b65-ba7e-0531aa8e8b51
date added to LUP
2020-11-27 11:03:39
date last changed
2024-04-17 19:47:20
@article{48d32f75-e426-4b65-ba7e-0531aa8e8b51,
  abstract     = {{<p>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 &lt;.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..</p>}},
  author       = {{Georgakis, Marios K. and De Lemos, James A. and Ayers, Colby and Wang, Biqi and Björkbacka, Harry and Pana, Tiberiu A. and Thorand, Barbara and Sun, Caroline and Fani, Lana and Malik, Rainer and Dupuis, Josée and Engström, Gunnar and Orho-Melander, Marju and Melander, Olle and Boekholdt, S. Matthijs and Zierer, Astrid and Elhadad, Mohamed A. and Koenig, Wolfgang and Herder, Christian and Hoogeveen, Ron C. and Kavousi, Maryam and Ballantyne, Christie M. and Peters, Annette and Myint, Phyo K. and Nilsson, Jan and Benjamin, Emelia J. and Dichgans, Martin}},
  issn         = {{2380-6583}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{587--592}},
  publisher    = {{American Medical Association}},
  series       = {{JAMA Cardiology}},
  title        = {{Association of Circulating Monocyte Chemoattractant Protein-1 Levels with Cardiovascular Mortality : A Meta-analysis of Population-Based Studies}},
  url          = {{http://dx.doi.org/10.1001/jamacardio.2020.5392}},
  doi          = {{10.1001/jamacardio.2020.5392}},
  volume       = {{6}},
  year         = {{2021}},
}