Association between Hemoglobin A1c and Stroke Risk in Patients with Type 2 Diabetes

Background and Purpose The association between hemoglobin A1c (HbA1c) and stroke risk along with its subtypes is rarely reported. We aimed to investigate the association between HbA1c and the risk of incident stroke in patients with type 2 diabetes based on real world data from three healthcare systems. Methods We performed a retrospective cohort study of 27,113 African Americans and 40,431 whites with type 2 diabetes. Demographic, anthropometric, laboratory, and medication information were abstracted from the National Patient-Centered Clinical Research Network common data model. Incident stroke events including both ischemic and hemorrhagic stroke were defined. Results During a mean follow-up period of 3.79 +/- 1.68 years, 7,735 patients developed stroke (6,862 ischemic and 873 hemorrhagic). Multivariable-adjusted hazard ratios across levels of HbA1c at baseline (<6.0%, 6.0% to 6.9% [reference group], 7.0% to 7.9%, 8.0% to 8.9%, 9.0% to 9.9%, and >= 10%) were 1.07, 1.00, 1.13, 1.23, 1.27, and 1.37 (P-trend <0.001) for total stroke, 1.02, 1.00, 1.13, 1.20, 1.24, and 1.35 (P-trend <0.001) for ischemic stroke, and 1.40, 1.00, 1.14, 1.47, 1.47, and 1.51 (P-trend=0.002) for hemorrhagic stroke. When we used an updated mean value of HbA1c, the U-shaped association of HbA1c with stroke risk did not change. This U-shaped association was consistent among patients of different subgroups. The U-shaped association was more pronounced among patients taking antidiabetic, lipid-lowering, and antihypertensive medications compared with those without these medications. Conclusions These data suggest that diabetes management may have to be individualized according to the guideline recommendations rather than intensively attempting to lower HbA1c.