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Background: In persons with diabetes, chronic hyperglycemia (assessed by glyco sylated hemoglobin level) is related to the development of microvascular disease ; however, the relation of glycosylated hemoglobin to macrovascular disease is l ess clear. Purpose: To conduct a meta analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabet ic persons. Data Sources: Search of the MEDLINE database by using Medical Subjec t Heading search terms and keywords related to glycosylated hemoglobin, diabete s, and cardiovascular disease. Study Selection: Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease. Data Extraction: Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria. Data Synthesis: Adjusted relative risk e stimates 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 ef fects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved perso ns with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1 percentage point increase in glycosylate d hemoglobin level (95%CI, 1.10 to 1.26) in persons with type 2 diabetes. Resul ts in persons with type 1 diabetes were similar but had a wider CI (pooled relat ive risk, 1.15 [CI, 0.92 to 1.43]). Limitations: This review largely reflects th e limitations of the literature. Important concerns were residual confounding, t he possibility of publication bias, the small number of studies, and the heterog eneity of study results. Conclusions: Pending confirmation from large, ongoing c linical trials, this analysis shows that observational studies are consistent wi th limited clinical trial data and suggests that chronic hyperglycemia is associ ated with an increased risk for cardiovascular disease in persons with diabetes.
Background: In persons with diabetes, chronic hyperglycemia (assessed by glyco sylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to l ess clear. Purpose: To conduct a meta analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons. Data Sources: Search of the MEDLINE database by using Medical Subjec t Heading search terms and keywords related to glycosylated hemoglobin, diabete s, and cardiovascular disease. Study Selection: Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease. Data Extraction: Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria. Data Synthesis: Adjusted relative risk e stimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1 , or hemoglobin A1c levels) and car Three of the subjects involved persons with type 1 diabetes (n = 1688), and 10 studies involved perso ns with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1 percentage point increase in glycosylate d hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Resul ts in persons with type 1 diabetes were similar but had a wider CI (pooled rela t ive risk, 1.15 [CI, 0.92 to 1.43]). Limitations: This review substantially suggests th e limitations of the literature. Important concerns were residual confounding, t he possibility of publication bias, the small number of studies, and the heterog eneity of study results. Conclusions: Pending confirmation from large, ongoing cinical trials, this analysis shows that observational studies are consistent wi th limited clinical trial data and suggests that chronic hyperglycemia is associated with an increased risk for cardiovascular disease in persons with diabetes.