Glycated hemoglobin and risk of stroke, ischemic and hemorrhagic, in Japanese men and women

Background: The relationship between glycated hemoglobin A_1c (HbA_1c) and stroke has not been fully elucidated. In addition, there have been few reports from Asia, and few trials have been conducted for each stroke subtype. Methods: A prospective cohort study was performed involving 32,726 participants (9,558 men and 23,168 women) aged 40-79 years at baseline with approximately 6 years of follow-up in a general population of Japan. The end points included the incidence of all, ischemic and hemorrhagic strokes. Multivariate-adjusted hazard ratios by 6 HbA_1c categories were calculated using a Cox proportional hazard model. Results: During the follow-up, 393 participants developed a stroke, including 240 ischemic and 139 hemorrhagic stroke cases. The adjusted hazard ratios of all strokes and ischemic stroke showed tendencies to increase with HbA_1c level, and the relationships were independent of other confounders. The adjusted hazard ratios of ischemic stroke incidence showed an apparent and graded increase from a relatively mild HbA_1c level (≥6.0%); the HRs (95% CI) were 1.79 (1.10-2.93) for HbA_1c 6.0-6.4%, 2.20 (1.21-4.00) for HbA_1c 6.5-6.9% and 2.91 (1.91-4.44) for HbA_1c ≥7.0% compared with the category of HbA_1c 5.0-5.4%. For hemorrhagic stroke incidence, no significant increase due to rises in HbA_1c level was observed. Conclusions: The relationship of the risk of stroke, especially ischemic stroke, to HbA _1c in the general population appears to be graded without any apparent threshold. The ischemic stroke risk would increase from a relatively mild HbA_1c level of ≥6.0%.