title: Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus.
abstract: BACKGROUND
  In persons with diabetes, chronic hyperglycemia (assessed by glycosylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to macrovascular disease is less clear.
  
  
  OBJECTIVE
  To conduct a meta-analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons.
  
  
  METHODS
  Search of the MEDLINE database by using Medical Subject Heading search terms and key words related to glycosylated hemoglobin, diabetes, and cardiovascular disease.
  
  
  METHODS
  Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease.
  
  
  METHODS
  Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria.
  
  
  RESULTS
  Adjusted relative risk estimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1, or hemoglobin A1c levels) and cardiovascular disease events (coronary heart disease and stroke) were pooled by using random-effects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved persons with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1-percentage point increase in glycosylated hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Results in persons with type 1 diabetes were similar but had a wider CI (pooled relative risk, 1.15 [CI, 0.92 to 1.43]).
  
  
  CONCLUSIONS
  This review largely reflects the limitations of the literature. Important concerns were residual confounding, the possibility of publication bias, the small number of studies, and the heterogeneity of study results.
  
  
  CONCLUSIONS
  Pending confirmation from large, ongoing clinical trials, this analysis shows that observational studies are consistent with limited clinical trial data and suggests that chronic hyperglycemia is associated with an increased risk for cardiovascular disease in persons with diabetes.
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.forename: Spyridon
authors.initials: S
authors.lastname: Marinopoulos
authors.forename: Gail
authors.initials: G
authors.lastname: Berkenblit
authors.forename: Tejal
authors.initials: T
authors.lastname: Rami
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Brancati
authors.forename: Neil R
authors.initials: NR
authors.lastname: Powe
authors.forename: Sherita Hill
authors.initials: SH
authors.lastname: Golden
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D003925:Diabetic Angiopathies / Q000097:blood*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans
chemical_list: D006442:Glycated Hemoglobin