Glycaemia (haemoglobin A_1c) and incident ischaemic stroke: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Individuals with diabetes have a raised risk of stroke, but it is unclear whether sustained hyperglycaemia contributes to the development of cerebrovascular disease. Haemoglobin A1c (HbA_1c), a measure of long-term glycaemia, is strongly related to retinopathy, nephropathy, and neuropathy in diabetes. We sought to assess the association between HbA _1c and stroke in people with and without diabetes. Methods: 10 886 participants without diabetes and 1635 participants with diabetes in the ARIC study, who did not have cardiovascular disease, were followed up for incident ischaemic stroke over 8-10 years. We assayed HbA_1c for all 167 stroke cases and a sample of 680 non-cases in the adults without diabetes and for the full cohort of 1635 adults with diabetes (including 89 stroke cases). We assessed the relation between HbA_1c concentrations (in tertiles specific for individuals with and without diabetes) and incident ischaemic stroke during follow-up using Cox proportional hazards models, controlling for risk factors for stroke. Findings: The adjusted relative risks of stroke increased with increasing tertile of HbA1c in both adults without diabetes (p=0·02) and with diabetes (p<0·0001). Compared with adults without diabetes in the lowest tertile of HbA1c, the adjusted relative risks of stroke by HbA_1c tertile were 1·18 (0·70-2·00) and 1·58 (0·94-2·66) in adults without diabetes and 1·75 (0·90-3·42), 2·29 (1·24-4·21), and 4·71 (2·69-8·25) in adults with diabetes. Interpretation: Raised HbA_1c could be an independent risk factor for stroke in people with and without diabetes, with relative risks similar to those previously reported for coronary heart disease.