TY - JOUR
T1 - Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke
T2 - Meta-Analysis of Population-Based Studies Involving 17 180 Individuals
AU - Georgakis, Marios K.
AU - Malik, Rainer
AU - Björkbacka, Harry
AU - Pana, Tiberiu Alexandru
AU - Demissie, Serkalem
AU - Ayers, Colby
AU - Elhadad, Mohamed A.
AU - Fornage, Myriam
AU - Beiser, Alexa S.
AU - Benjamin, Emelia J.
AU - Boekholdt, Matthijs S.
AU - Engström, Gunnar
AU - Herder, Christian
AU - Hoogeveen, Ron C.
AU - Koenig, Wolfgang
AU - Melander, Olle
AU - Orho-Melander, Marju
AU - Schiopu, Alexandru
AU - Söderholm, Martin
AU - Wareham, Nick
AU - Ballantyne, Christie M.
AU - Peters, Annette
AU - Seshadri, Sudha
AU - Myint, Phyo K.
AU - Nilsson, Jan
AU - de Lemos, James A.
AU - Dichgans, Martin
PY - 2019/9/27
Y1 - 2019/9/27
N2 - 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 Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations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.
AB - 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.
KW - atherosclerosis
KW - cerebrovascular disorders
KW - chemokine CCL2
KW - inflammation
KW - stroke
UR - http://www.scopus.com/inward/record.url?scp=85072718369&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072718369&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.119.315380
DO - 10.1161/CIRCRESAHA.119.315380
M3 - Article
C2 - 31476962
AN - SCOPUS:85072718369
VL - 125
SP - 773
EP - 782
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 8
ER -