title: Associations of coeliac disease with coronary heart disease and cerebrovascular disease: A systematic review and meta-analysis.
abstract: OBJECTIVE
  Clinical experience suggests that atherosclerotic disease is common in individuals with coeliac disease, but epidemiological studies have had contradicting findings. To summarise the currently available evidence, we systematically reviewed and analysed observational studies of the association of coeliac disease or dermatitis herpetiformis with coronary heart disease (CHD) or stroke.
  
  
  RESULTS
  We searched for studies comparing CHD or stroke outcomes with individuals with and without coeliac disease or dermatitis herpetiformis. Three investigators independently searched electronic databases, identified relevant studies and extracted data. Study-specific results were combined in random-effects meta-analyses, and heterogeneity was quantified using the I(2) statistic and meta-regression. Twenty-one studies were included in our systematic review and 18 in the meta-analyses. For CHD, the pooled hazard ratio for incident disease was 1.05 (95% confidence interval (CI): 0.93, 1.19) and the overall standardised mortality ratio was 1.21 (0.99, 1.49). For stroke and brain haemorrhage, the corresponding estimates were 1.10 (95% CI: 1.00, 1.21) and 1.43 (0.97, 2.10), respectively. There was moderate to considerable heterogeneity among the study-specific estimates. In addition, many estimates were based on small numbers of outcomes and they had limitations in terms of adjustment for potential confounders.
  
  
  CONCLUSIONS
  Our meta-analyses lend some support to an association between coeliac disease and CHD or cerebrovascular disease, but the evidence base was heterogeneous and had limitations. Our systematic review highlighted a need in this area for adequately powered prospective studies with appropriate adjustment for potentially confounding factors.
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland. Electronic address: katriina.heikkila@uta.fi.
authors.forename: K
authors.initials: K
authors.lastname: Heikkilä
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; City of Tampere Health and Welfare Services, Tampere, Finland.
authors.forename: O A
authors.initials: OA
authors.lastname: Koskinen
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada; Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Arnav
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Department of Urology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: K A O
authors.initials: KAO
authors.lastname: Tikkinen
authors.affiliation: Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Mäki
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Kaukinen
mesh_terms: D002446:Celiac Disease / Q000150:complications / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000150:complications / Q000503:physiopathology*; D016208:Databases, Factual; D003874:Dermatitis Herpetiformis / Q000150:complications / Q000503:physiopathology; D006801:Humans; D012307:Risk Factors
keywords: Cerebrovascular disease; Coeliac disease; Coronary heart disease; Dermatitis herpetiformis; Meta-analysis; Stroke; Systematic review