PMID- 31476962
OWN - NLM
STAT- MEDLINE
DCOM- 20200629
LR  - 20240517
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 125
IP  - 8
DP  - 2019 Sep 27
TI  - Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke: Meta-Analysis 
      of Population-Based Studies Involving 17 180 Individuals.
PG  - 773-782
LID - 10.1161/CIRCRESAHA.119.315380 [doi]
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      previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7+/-8.1 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.
FAU - Georgakis, Marios K
AU  - Georgakis MK
AD  - From the Institute for Stroke and Dementia Research, University Hospital (M.K.G., 
      R.M., M.D.), Ludwig-Maximilians-University, Munich.
AD  - Graduate School for Systemic Neurosciences (M.K.G.), 
      Ludwig-Maximilians-University, Munich.
FAU - Malik, Rainer
AU  - Malik R
AD  - From the Institute for Stroke and Dementia Research, University Hospital (M.K.G., 
      R.M., M.D.), Ludwig-Maximilians-University, Munich.
FAU - Bjorkbacka, Harry
AU  - Bjorkbacka H
AD  - Clinical Sciences, Malmo, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., 
      A.S., M.S., J.N.).
FAU - Pana, Tiberiu Alexandru
AU  - Pana TA
AD  - Institute of Applied Health Sciences, School of Medicine, Medical Sciences and 
      Nutrition, University of Aberdeen, Scotland (T.A.P., P.K.M.).
FAU - Demissie, Serkalem
AU  - Demissie S
AD  - Biostatistics, Boston University School of Public Health, MA (S.D., A.S.B.).
AD  - National Heart, Lung, and Blood Institute's and Boston University's Framingham 
      Heart Study, MA (S.D., A.S.B., E.J.B., S.S.).
FAU - Ayers, Colby
AU  - Ayers C
AD  - Cardiology, University of Texas Southwestern Medical Center, Dallas (C.A., 
      J.A.d.L.).
FAU - Elhadad, Mohamed A
AU  - Elhadad MA
AD  - Research Unit of Molecular Epidemiology (M.A.E.), Helmholtz Zentrum Munchen, 
      German Research Center for Environmental Health, Neuherberg.
AD  - Institute of Epidemiology (M.A.E., A.P.), Helmholtz Zentrum Munchen, German 
      Research Center for Environmental Health, Neuherberg.
AD  - German Research Center for Cardiovascular Disease, Partner site Munich Heart 
      Alliance (M.A.E., W.K.).
FAU - Fornage, Myriam
AU  - Fornage M
AD  - Brown Foundation Institute of Molecular Medicine, McGovern Medical School and 
      Human Genetics Center, School of Public Health, University of Texas Health 
      Science Center, Houston (M.F.).
FAU - Beiser, Alexa S
AU  - Beiser AS
AD  - Biostatistics, Boston University School of Public Health, MA (S.D., A.S.B.).
AD  - National Heart, Lung, and Blood Institute's and Boston University's Framingham 
      Heart Study, MA (S.D., A.S.B., E.J.B., S.S.).
AD  - Department of Neurology, Boston University School of Medicine, MA (A.S.B.).
FAU - Benjamin, Emelia J
AU  - Benjamin EJ
AD  - National Heart, Lung, and Blood Institute's and Boston University's Framingham 
      Heart Study, MA (S.D., A.S.B., E.J.B., S.S.).
AD  - Medicine, Boston University School of Medicine, MA (E.J.B., S.S.).
AD  - Epidemiology, Boston University School of Public Health, MA (E.J.B.).
FAU - Boekholdt, S Matthijs
AU  - Boekholdt SM
AD  - Amsterdam UMC, University of Amsterdam, Cardiology, the Netherlands (M.S.B.).
FAU - Engstrom, Gunnar
AU  - Engstrom G
AD  - Clinical Sciences, Malmo, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., 
      A.S., M.S., J.N.).
FAU - Herder, Christian
AU  - Herder C
AD  - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for 
      Diabetes Research at Heinrich Heine University Dusseldorf (C.H.).
AD  - German Center for Diabetes Research, Partner Dusseldorf (C.H.).
AD  - Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University 
      Dusseldorf, Germany (C.H.).
FAU - Hoogeveen, Ron C
AU  - Hoogeveen RC
AD  - Medicine, Baylor College of Medicine, Houston, TX (R.C.H., C.M.B.).
FAU - Koenig, Wolfgang
AU  - Koenig W
AD  - German Research Center for Cardiovascular Disease, Partner site Munich Heart 
      Alliance (M.A.E., W.K.).
AD  - Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Germany (W.K.).
AD  - Institute of Epidemiology and Biostatistics, University of Ulm, Germany (W.K.).
FAU - Melander, Olle
AU  - Melander O
AD  - Clinical Sciences, Malmo, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., 
      A.S., M.S., J.N.).
FAU - Orho-Melander, Marju
AU  - Orho-Melander M
AD  - Clinical Sciences, Malmo, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., 
      A.S., M.S., J.N.).
FAU - Schiopu, Alexandru
AU  - Schiopu A
AD  - Clinical Sciences, Malmo, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., 
      A.S., M.S., J.N.).
AD  - Cardiology, Skane University Hospital, Malmo, Sweden (A.S.).
FAU - Soderholm, Martin
AU  - Soderholm M
AD  - Clinical Sciences, Malmo, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., 
      A.S., M.S., J.N.).
FAU - Wareham, Nick
AU  - Wareham N
AD  - MRC Epidemiology Unit, University of Cambridge, United Kingdom (N.W.).
FAU - Ballantyne, Christie M
AU  - Ballantyne CM
AD  - Medicine, Baylor College of Medicine, Houston, TX (R.C.H., C.M.B.).
FAU - Peters, Annette
AU  - Peters A
AD  - Institute of Epidemiology (M.A.E., A.P.), Helmholtz Zentrum Munchen, German 
      Research Center for Environmental Health, Neuherberg.
FAU - Seshadri, Sudha
AU  - Seshadri S
AD  - National Heart, Lung, and Blood Institute's and Boston University's Framingham 
      Heart Study, MA (S.D., A.S.B., E.J.B., S.S.).
AD  - Medicine, Boston University School of Medicine, MA (E.J.B., S.S.).
AD  - Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University 
      of Texas Health Sciences Center, San Antonio (S.S.).
FAU - Myint, Phyo K
AU  - Myint PK
AD  - Institute of Applied Health Sciences, School of Medicine, Medical Sciences and 
      Nutrition, University of Aberdeen, Scotland (T.A.P., P.K.M.).
FAU - Nilsson, Jan
AU  - Nilsson J
AD  - Clinical Sciences, Malmo, Lund University, Sweden (H.B., G.E., O.M., M.O.-M., 
      A.S., M.S., J.N.).
FAU - de Lemos, James A
AU  - de Lemos JA
AD  - Cardiology, University of Texas Southwestern Medical Center, Dallas (C.A., 
      J.A.d.L.).
FAU - Dichgans, Martin
AU  - Dichgans M
AD  - From the Institute for Stroke and Dementia Research, University Hospital (M.K.G., 
      R.M., M.D.), Ludwig-Maximilians-University, Munich.
AD  - Munich Cluster for Systems Neurology, Germany (M.D.).
AD  - German Centre for Neurodegenerative Diseases, Munich, Germany (M.D.).
LA  - eng
GR  - UH3 NS100605/NS/NINDS NIH HHS/United States
GR  - R01 NS017950/NS/NINDS NIH HHS/United States
GR  - R01 AG054076/AG/NIA NIH HHS/United States
GR  - RF1 AG059421/AG/NIA NIH HHS/United States
GR  - HHSN268201500001C/HL/NHLBI NIH HHS/United States
GR  - R01 AG049607/AG/NIA NIH HHS/United States
GR  - HHSN268201500001I/HL/NHLBI NIH HHS/United States
GR  - G1000143/MRC_/Medical Research Council/United Kingdom
GR  - R01 AG028321/AG/NIA NIH HHS/United States
GR  - HHSN268201700003I/HL/NHLBI NIH HHS/United States
GR  - U01 AG049505/AG/NIA NIH HHS/United States
GR  - R01 HL092577/HL/NHLBI NIH HHS/United States
GR  - HHSN268201700004C/HB/NHLBI NIH HHS/United States
GR  - MC_UU_12015/1/MRC_/Medical Research Council/United Kingdom
GR  - R01 NS087541/NS/NINDS NIH HHS/United States
GR  - MR/N003284/1/MRC_/Medical Research Council/United Kingdom
GR  - R01 HL076784/HL/NHLBI NIH HHS/United States
GR  - HHSN268201700001I/HL/NHLBI NIH HHS/United States
GR  - G0401527/MRC_/Medical Research Council/United Kingdom
GR  - U01 AG058589/AG/NIA NIH HHS/United States
GR  - HHSN268201700004I/HL/NHLBI NIH HHS/United States
GR  - P30 AG066546/AG/NIA NIH HHS/United States
GR  - U01 AG052409/AG/NIA NIH HHS/United States
GR  - HHSN268201700005C/HL/NHLBI NIH HHS/United States
GR  - HHSN268201700001C/HL/NHLBI NIH HHS/United States
GR  - HHSN268201700002C/HB/NHLBI NIH HHS/United States
GR  - 14136/CRUK_/Cancer Research UK/United Kingdom
GR  - HHSN268201700003C/HL/NHLBI NIH HHS/United States
GR  - UH2 NS100605/NS/NINDS NIH HHS/United States
GR  - N01HC25195/HL/NHLBI NIH HHS/United States
GR  - 75N92019D00031/HL/NHLBI NIH HHS/United States
GR  - G0500300/MRC_/Medical Research Council/United Kingdom
GR  - P30 AG010129/AG/NIA NIH HHS/United States
GR  - HHSN268201700002I/HL/NHLBI NIH HHS/United States
GR  - HHSN268201700005I/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Systematic Review
DEP - 20190903
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
SB  - IM
EIN - Circ Res. 2020 Jan 3;126(1):e9. PMID: 31895655
MH  - Adult
MH  - Aged
MH  - Atherosclerosis/blood/*epidemiology
MH  - Biomarkers/blood
MH  - Chemokine CCL2/*blood
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Stroke/blood/*epidemiology
PMC - PMC6763364
MID - NIHMS1538963
OTO - NOTNLM
OT  - atherosclerosis
OT  - cerebrovascular disorders
OT  - chemokine CCL2
OT  - inflammation
OT  - stroke
EDAT- 2019/09/04 06:00
MHDA- 2020/07/01 06:00
PMCR- 2020/09/27
CRDT- 2019/09/04 06:00
PHST- 2019/09/04 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2019/09/04 06:00 [entrez]
PHST- 2020/09/27 00:00 [pmc-release]
AID - 10.1161/CIRCRESAHA.119.315380 [doi]
PST - ppublish
SO  - Circ Res. 2019 Sep 27;125(8):773-782. doi: 10.1161/CIRCRESAHA.119.315380. Epub 
      2019 Sep 3.