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

Abstract

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. Methods-We examined the prospective relationship between usual blood glucose level measured by glycohemoglobin (HbA 1c ) 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. Results-A total of 10 489 men and women aged 40 to 79 years at baseline were followed up (meanϭ8.5 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 HbA 1c 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 HbA 1c concentrations 5% to 5.4%, 5.5% to 6.9%, and Ն7% 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 HbA 1c Ͻ5%. Conclusions-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. (Stroke.

Glycated Hemoglobin and Risk of Stroke, Ischemic and Hemorrhagic, in Japanese Men and Women

“…The Atherosclerosis Risk in Communities study conducted in the USA investigated the association between HbA 1c and ischemic stroke in about 10,000 individuals without diabetes and about 1,600 with diabetes and reported that the risk of ischemic stroke incidence increased continuously with rises in HbA 1c level, from the <4.7% HbA 1c category to the ≥6.8% HbA 1c category, indicating the lack of a threshold [18]. The European Prospective Investigation into Cancer/Norfork study conducted in the UK examined the relationship between HbA 1c and all-stroke incidence in about 10,000 individuals without any diagnosed diabetes and reported that the risk of stroke incidence did not rise at <7% HbA 1c levels but increased suddenly from the ≥7% HbA 1c level, up to about 3-fold, suggesting the presence of a threshold [19]. However, the number of stroke events observed in the study was relatively small (164 events) and probably included some hemorrhagic strokes.…”

“…However, only a few trials have investigated the relationship between HbA 1c and the risk of stroke incidence in the general population [18,19,20]. A cohort study conducted in the USA evaluated the relationship between HbA 1c and ischemic stroke in individuals with and without diabetes and reported that the risk of ischemic stroke incidence rose continuously with HbA 1c level [18].…”

“…A cohort study conducted in the USA evaluated the relationship between HbA 1c and ischemic stroke in individuals with and without diabetes and reported that the risk of ischemic stroke incidence rose continuously with HbA 1c level [18]. A cohort study in a general population in the UK reported that the all-stroke risk increased suddenly from the threshold HbA 1c level of 7% [19], but another analysis in nondiabetic old women from the UK found no significant relationship [20]. Thus, the association between HbA 1c and stroke has not been fully elucidated.…”

Cortical Neurons Develop Insulin Resistance and Blunted Akt Signaling: A Potential Mechanism Contributing to Enhanced Ischemic Injury in Diabetes

“…The contributions of each component of the metabolic syndrome to stroke vary and are controversial. Studies concerning the role of hyperglycemia on stroke demonstrate conflicting results; some conclude there is increased stroke risk with chronic hyperglycemia (1,37), whereas other work finds no such relationship (45). The UK Prevention in Diabetes Study failed to demonstrate significantly reduced risk of stroke in patients treated with tight glucose control compared to conventional diet therapy (21).…”

Haemoglobin A1c levels and subsequent cardiovascular disease in persons without diabetes: a meta-analysis of prospective cohorts

“…After reading the full text, there were 26 potentially acceptable studies that were rejected at the final stage: 14 did not have appropriate data [1,[13][14][15][16][17][18][19][20][21][22][23][24][25]; four did not involve outcomes of interest [26][27][28][29]; three studied non-relevant populations [30][31][32]; three were duplicates [33][34][35]; and two were editorials/review papers [36,37]. That left seven papers for analysis [38][39][40][41][42][43][44].…”