title: Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, and mortality: A systematic review and meta-analyses.
abstract: BACKGROUND
  Low circulating levels of adiponectin, an anti-inflammatory and vasculoprotective adipokine, are associated with obesity, type 2 diabetes, and atherosclerotic disease. Presence of unstable plaques in the carotid artery is a known etiological factor causing ischemic strokes. Herein, we systematically reviewed the association between circulating adiponectin and progression of carotid atherosclerotic disease, particularly evaluating the occurrence of (1) carotid atherosclerotic plaques, (2) ischemic stroke, and (3) mortality in subjects who suffered a previous ischemic stroke.
  
  
  METHODS
  Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The effect size and 95% confidence intervals (CIs) of the individual studies were pooled using fixed-effect or random-effect models. The quality of the eligible studies was evaluated using the Newcastle-Ottawa quality assessment scale. Sensitivity, subgroup, and meta-regression analyses were performed to address the impact of various risk factors on the association between adiponectin and ischemic stroke risk.
  
  
  RESULTS
  Twelve studies fulfilled the inclusion criteria for 3 independent meta-analyses. The association of increasing circulating adiponectin levels (5μg/mL-increment) with presence of carotid plaque was not conclusive (n=327; OR: 1.07; 95% CI: 0.85-1.35; 2 studies), whereas high adiponectin levels showed a significant 8% increase in risk of ischemic stroke (n=13,683; 7 studies), with a more sizable association observed among men compared to women. HDL was observed to have a marginal effect on the association between adiponectin and ischemic stroke, while other evaluated parameters were not found to be effect modifiers. A non-significant association of adiponectin with mortality was yielded (n=663; OR: 2.58; 95% CI: 0.69-9.62; 3 studies). Although no publication bias was evident, there was significant between-study heterogeneity in most analyses.
  
  
  CONCLUSIONS
  It appears that the direction of the relationship between adiponectin and carotid atherosclerotic plaque presence is dependent on the duration, severity, and nature of the underlying disease, while increased adiponectin levels were associated with an increase in risk for ischemic stroke. Lastly, the results from the mortality meta-analysis remain inconclusive. Future properly designed studies are necessary to further elucidate the role of adiponectin on atherosclerotic plaque development, and its related outcomes.
authors.affiliation: Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. Electronic address: jessica.gorgui@umontreal.ca.
authors.forename: Jessica
authors.initials: J
authors.lastname: Gorgui
authors.affiliation: Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. Electronic address: karina.gasbarrino@mail.mcgill.ca.
authors.forename: Karina
authors.initials: K
authors.lastname: Gasbarrino
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece. Electronic address: mgeorgakis91@gmail.com.
authors.forename: Marios K
authors.initials: MK
authors.lastname: Georgakis
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece. Electronic address: marykaralexi@windowslive.com.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Karalexi
authors.affiliation: Medical Library, McGill University Health Centre, Montreal, Quebec, Canada. Electronic address: benedicte.nauche@muhc.mcgill.ca.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Nauche
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece. Electronic address: epetrid@gmail.com.
authors.forename: Eleni Th
authors.initials: ET
authors.lastname: Petridou
authors.affiliation: Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. Electronic address: stella.daskalopoulou@mcgill.ca.
authors.forename: Stella S
authors.initials: SS
authors.lastname: Daskalopoulou
mesh_terms: D052242:Adiponectin / Q000097:blood*; D002545:Brain Ischemia / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D002340:Carotid Artery Diseases / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D018570:Risk Assessment; D020521:Stroke / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin
keywords: Adiponectin; Atherosclerotic plaque; Carotid artery disease; Ischemic stroke; Mortality