Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke

Georgakis, Marios K.; Malik, Rainer und Dichgans, Martin (27. September 2019): Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke. Meta-Analysis of Population-Based Studies Involving 17 180 Individuals. In: Circulation Research, Bd. 125, Nr. 8

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Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations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

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 666881
• EU-Projekte: Horizon 2020 > RIA - Research and Innovation action > SVDs-at-target - Small Vessel Diseases from a therapeutic perspective: Targets for intervention. Affected pathways and mechanistic exploitation for prevention of stroke dementia ; Horizon 2020 > RIA - Research and Innovation action > CoSTREAM - Common mechanisms and pathways in stroke and Alzheimer's disease
• Fakultät: Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0009-7330
• Bemerkung: Vollständige Autorenliste s. Volltext
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198