Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke : Meta-Analysis of Population-Based Studies Involving 17 180 Individuals
(2019) In Circulation Research 125(8). p.773-782- Abstract
Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and... (More)
Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.
(Less)
- author
- organization
-
- Cardiovascular Research - Cellular Metabolism and Inflammation (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Cardiovascular Research - Epidemiology (research group)
- EpiHealth: Epidemiology for Health
- Cardiovascular Research - Hypertension (research group)
- Diabetes - Cardiovascular Disease (research group)
- Cardiovascular Research - Immunity and Atherosclerosis (research group)
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- atherosclerosis, cerebrovascular disorders, chemokine CCL2, inflammation, stroke
- in
- Circulation Research
- volume
- 125
- issue
- 8
- pages
- 10 pages
- publisher
- American Heart Association
- external identifiers
-
- pmid:31476962
- scopus:85072718369
- ISSN
- 0009-7330
- DOI
- 10.1161/CIRCRESAHA.119.315380
- language
- English
- LU publication?
- yes
- id
- 2487f2ad-8be0-49c1-b3b2-9f1b72524992
- date added to LUP
- 2019-10-10 10:55:06
- date last changed
- 2024-09-19 10:55:07
@article{2487f2ad-8be0-49c1-b3b2-9f1b72524992, abstract = {{<p>Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.</p>}}, author = {{Georgakis, Marios K. and Malik, Rainer and Björkbacka, Harry and Pana, Tiberiu Alexandru and Demissie, Serkalem and Ayers, Colby and Elhadad, Mohamed A. and Fornage, Myriam and Beiser, Alexa S. and Benjamin, Emelia J. and Boekholdt, Matthijs S. and Engström, Gunnar and Herder, Christian and Hoogeveen, Ron C. and Koenig, Wolfgang and Melander, Olle and Orho-Melander, Marju and Schiopu, Alexandru and Söderholm, Martin and Wareham, Nick and Ballantyne, Christie M. and Peters, Annette and Seshadri, Sudha and Myint, Phyo K. and Nilsson, Jan and de Lemos, James A. and Dichgans, Martin}}, issn = {{0009-7330}}, keywords = {{atherosclerosis; cerebrovascular disorders; chemokine CCL2; inflammation; stroke}}, language = {{eng}}, number = {{8}}, pages = {{773--782}}, publisher = {{American Heart Association}}, series = {{Circulation Research}}, title = {{Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke : Meta-Analysis of Population-Based Studies Involving 17 180 Individuals}}, url = {{http://dx.doi.org/10.1161/CIRCRESAHA.119.315380}}, doi = {{10.1161/CIRCRESAHA.119.315380}}, volume = {{125}}, year = {{2019}}, }