Glycated Hemoglobin and Risk of Stroke in People Without Known Diabetes in the European Prospective Investigation Into Cancer (EPIC)–Norfolk Prospective Population Study: A Threshold Relationship?

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Background and Purpose—

Diabetes is a well-recognized risk factor for cardiovascular diseases. Evidence suggests a linear relationship between blood glucose and myocardial infarction, even at blood glucose concentrations below the threshold for diabetes. The relationship between blood glucose concentration and stroke in people without established diabetes has been studied less extensively.


We examined the prospective relationship between usual blood glucose level measured by glycohemoglobin (HbA1c) concentrations and incident stroke risk in a general population without diabetes and stroke at baseline assessment in the European Prospective Investigation Into Cancer (EPIC)–Norfolk.


A total of 10 489 men and women aged 40 to 79 years at baseline were followed up (mean=8.5 years). Mean age, systolic and diastolic blood pressure, body mass index, total cholesterol, triglycerides, and proportion of current smokers increased and mean high-density lipoprotein cholesterol decreased with increasing HbA1c concentrations. There were 164 incident strokes identified over 88 652 person-years. After adjustment for age, sex, and cardiovascular risk factors, the relative risks (95% CI) for stroke for participants with HbA1c concentrations 5% to 5.4%, 5.5% to 6.9%, and ≥7% were 0.78 (0.50 to 1.22), 0.83 (0.54 to 1.27), and 2.83 (1.40 to 5.74), respectively, compared with those with HbA1c <5%.


In contrast to the continuous linear relationship observed between blood glucose level and coronary heart disease risk, the association between blood glucose level and stroke risk appears to be more consistent with a threshold relationship. These observations may give insights into the differing pathogenesis of different vascular diseases.

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