title: Adiponectin and risk of stroke: prospective study and meta-analysis.
abstract: OBJECTIVE
  The favorable cardiovascular effects attributed to adiponectin may lower risk of stroke. We investigated this in a prospective study and meta-analysis.
  
  
  METHODS
  A case-cohort study nested within the Potsdam cohort of the European Prospective Investigation into Cancer was performed, with 170 incident cases of ischemic stroke and a randomly selected subcohort of 2155 participants without major cardiovascular disease at baseline. A random-effects dose-response meta-analysis was performed on prospective studies reporting on adiponectin and incident stroke in healthy populations up to April 2013, identified through MEDLINE and EMBASE.
  
  
  RESULTS
  In European Prospective Investigation into Cancer-Potsdam, after adjustment for cardiovascular risk factors, the hazard ratio of ischemic stroke per 5-µg/mL higher total-adiponectin was 1.10 (95% confidence interval, 0.89-1.37). Participants with higher total-adiponectin had higher high-density lipoprotein-cholesterol and lower high-sensitivity C-reactive protein and triglyceride levels, and had less often diabetes mellitus. Additional adjustment for these putative mediators yielded a hazard ratio of 1.31 (95% confidence interval, 1.04-1.64). Nine studies (19,259 participants, 2960 cases), including European Prospective Investigation into Cancer-Potsdam, were meta-analyzed. Pooling relative risks adjusted for cardiovascular risk factors not including putative mediators indicated moderate between-study heterogeneity (I2=52.2%). This was explained by the smallest study, and the pooled relative risk (95% confidence interval) before and after its exclusion was 1.03 (0.98-1.08) and 0.99 (0.96-1.01) per 5 µg/mL, respectively. The pooled relative risk (95% confidence interval) additionally adjusted for potential mediators was 1.08 (1.01-1.15) and 1.05 (1.00-1.11) before and after excluding the same study, respectively.
  
  
  CONCLUSIONS
  Adiponectin is not associated with risk of stroke. If anything, adiponectin relates directly to stroke risk after controlling for risk factors that favorably correlate with adiponectin.
authors.affiliation: From the Departments of Epidemiology (M.A., B.B., R.d.G., H.B., C.W.) and Molecular Epidemiology (M.B.S.), German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Nuthetal, Germany; Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany (A.F.); Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (S.W., B.I.); and Institute of Social Medicine, Epidemiology, and Health Economics, Charité University Medical Center, Berlin, Germany (C.W.).
authors.forename: Maria
authors.initials: M
authors.lastname: Arregui
authors.forename: Brian
authors.initials: B
authors.lastname: Buijsse
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Romina
authors.initials: R
authors.lastname: di Giuseppe
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Schulze
authors.forename: Sabine
authors.initials: S
authors.lastname: Westphal
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000367:Age Factors; D000704:Analysis of Variance; D015415:Biomarkers; D002545:Brain Ischemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012306:Risk; D012737:Sex Factors; D020521:Stroke / Q000097:blood* / Q000453:epidemiology*
chemical_list: D052242:Adiponectin; D015415:Biomarkers
keywords: adiponectin; meta-analysis; myocardial infarction; stroke