title: Prospective Association between Diabetic Retinopathy and Cardiovascular Disease-A Systematic Review and Meta-analysis of Cohort Studies.
abstract: BACKGROUND
  Diabetic retinopathy (DR) is linked to increased risk of cardiovascular (CV) disease. However, the effect size of the association was not consistent. In this study, we performed a systematic review and meta-analysis of available cohort studies to determine the association between DR and CV disease, and to investigate the factors that influence the association.
  
  
  METHODS
  Terms related to DR and CV disease were searched from MEDLINE and EMBASE database. High-quality articles (Newcastle-Ottawa scales above 6) conducted in cohort studies reporting the association between DR and CV disease were identified. Study-specific estimates were pooled using random effects with inverse variance meta-analysis. Subgroup analysis was performed according to diabetes types. Heterogeneity of included studies was assessed using the I(2) test. The cause of the heterogeneity was examined using metaregression analyses.
  
  
  RESULTS
  A total of 13 studies representing 17,611 patients without CV disease at baseline were included. At follow-up, there were 1457 CV disease-related incidences. Overall, DR was associated with increased risk of CV disease (relative risk [RR]: 2.42, 95% confidence interval [CI]: 1.77-3.31) in diabetes. Specifically, the RR was 3.59 (95% CI: 1.79-7.20) for type 1 diabetes and 1.81 (95% CI: 1.47-2.23) for type 2 diabetes. Significant heterogeneity was found in studies with type 1 diabetes. Metaregression analysis showed that baseline systolic blood pressure was a key factor leading to the heterogeneity.
  
  
  CONCLUSIONS
  In conclusion, DR is significantly associated with CV disease incidence and CV disease-related mortality in diabetes. Patients with DR may need more intensive management to control future CV disease attacks.
authors.affiliation: Division of Biostatistics, The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; Department of Family Medicine and Primary Care, Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Vivian Yawei
authors.initials: VY
authors.lastname: Guo
authors.affiliation: Neuroscience Laboratory, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
authors.forename: Bing
authors.initials: B
authors.lastname: Cao
authors.affiliation: Division of Family Medicine and Primary Health Care, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Xinyin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of Biostatistics, The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jack Jock Wai
authors.initials: JJW
authors.lastname: Lee
authors.affiliation: Division of Biostatistics, The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; Clinical Trials and Biostatistics Lab, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. Electronic address: bzee@cuhk.edu.hk.
authors.forename: Benny Chung-Ying
authors.initials: BC
authors.lastname: Zee
mesh_terms: D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D015994:Incidence; D016017:Odds Ratio; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
keywords: Cardiovascular disease; diabetes; diabetic retinopathy; meta-analysis; systematic review