Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke: Meta-Analysis of Population-Based Studies Involving 17 180 Individuals. Issue 8 (27th September 2019)

• Record Type: Journal Article
• Authors: Georgakis, Marios K.; Malik, Rainer; Björkbacka, Harry; Pana, Tiberiu Alexandru; Demissie, Serkalem; Ayers, Colby; Elhadad, Mohamed A.; Fornage, Myriam; Beiser, Alexa S.; Benjamin, Emelia J.; Boekholdt, Matthijs S.; Engström, Gunnar; Herder, Christian; Hoogeveen, Ron C.; Koenig, Wolfgang; Melander, Olle; Orho-Melander, Marju; Schiopu, Alexandru; Söderholm, Martin; Wareham, Nick; Ballantyne, Christie M.; Peters, Annette; Seshadri, Sudha; Myint, Phyo K.; Nilsson, Jan; de Lemos, James A.; Dichgans, Martin
• Is Part Of: Circulation research. Volume 125:Issue 8(2019)
• Publication Date: 2019-09-27
• Subjects: atherosclerosis -- cerebrovascular disorders -- chemokine CCL2 -- inflammation -- stroke; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.119.315380
• Languages: English
• ISSNs: 0009-7330

Abstract

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 Methods and Results: : We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations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 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. Abstract : Supplemental Digital Content is available in the text.