Stroke Risk Increases With HbA1c Level in Women but Not Men

Risk for stroke shows a graded association with rising levels of HbA_1c in women with type 2 diabetes, new findings from a large prospective study show. Notably, poor control of blood sugar was found to have the strongest effect on stroke in diabetic women over 55 years of age.

The Louisiana State University Hospital-Based Longitudinal Study (LSUHLS) aimed to better understand the relationship between glycemic control and stroke and is published online February 24 in Diabetologia.

Previous research has been inconsistent, with some studies showing that type 2 diabetes may have a stronger effect on the risk for stroke in women compared with men, but one prior paper has shown a greater risk in diabetic men.

"Our study shows that diabetes poses a substantially greater increase in the risk for stroke among women than among men, which merits further investigation," study coauthor Gang Hu, MD, from Pennington Biomedical Research Center, Baton Rouge, Louisiana, told Medscape Medical News.

HbA_1c as a Continuous Variable at Baseline and Follow-up

The main findings show that after a mean follow-up of 6.7 years, a total of 1093 male and 1856 female cases of stroke were identified among 10,876 men and 19,278 women with type 2 diabetes in LSUHLS. A statistically significant association with increasing levels of HbA_1c was found in women but not men.

The multivariable-adjusted hazard ratios of stroke were assessed by levels of HbA_1c at baseline: HbA_1c less than 6.0%, 6.0%–6.9% [reference group], 7.0%–7.9%, 8.0%–8.9%, 9.0%–9.9%, and 10.0% or greater.

Levels of HbA_1c were evaluated as both a continuous variable at baseline and during follow-up, thus accounting for change in HbA_1c levels over time.

Among women, those with HbA_1c of 8.0%–8.9% were 19% more likely to have a stroke than those with normal blood sugar levels; those with levels of 9.0%–9.9% had a 32% increased risk for stroke; and those with HbA_1c above 10% a 42% higher risk (P for trend < .001). Men demonstrated a trend toward increased risk for stroke as HbA_1c increased, but this was not statistically significant.

The graded association remained true when results among women were stratified by race, whether with or without glucose-lowering agents. When stratified by age, each 1% increase in baseline HbA_1c was associated with a 2% increased risk for stroke in females aged under 55 years and a 5% higher risk in women over 55 years.

When the comparison was made between women with HbA_1c level greater than 10% and women who had normal blood glucose levels (6.0%–6.9%), the hazard ratio for risk for stroke was 1.41 in the over 55s and 1.24 in the under 55s.

Treatment Differences Between Men and Women?

The clear positive association between risk for stroke and graded increase in HbA_1c levels in women but not men has prompted researchers to suggest this may be due to a treatment bias that favors men.

Dr. Hu reflected this standpoint: "Recent studies found that men with diabetes or established cardiovascular disease are more likely to receive aspirin, statins, or antihypertensive drugs than women."

For example, one study found only 35% of women with diabetes or cardiovascular disease were prescribed a statin compared with 45% of men with similar medical histories. "I think this [is] one possible cause of the differences seen," said Dr. Hu.

"More aggressive blood sugar treatments and better control of other risk-factor levels in women with diabetes are likely to substantially reduce stroke in this subgroup," he added.

And commenting on the increased risk seen in women over the age of 55, Dr. Hu said this might be related to the role of estrogen, which declines markedly after the onset of menopause.

"The incidence of cerebrovascular disease in women increases [at menopause]. Preclinical studies have indicated that estrogen is neuroprotective and reduces stroke infarct volume, but clinical trials failed to show the benefit. There is a need for more research to clarify this association."

First author Wenhui Zhao, MD, also from Pennington Biomedical Research Center, noted that the higher number of strokes occurring among women compared with men was at least partly attributed to the longer life expectancy of women.

And "some studies have suggested that the sex difference in cardiovascular risk is mediated in large part by differences in the levels of cardiovascular risk factors, because women with diabetes have significantly higher levels of blood pressure and lipids than men with diabetes," Dr. Zhao concluded.

The authors have reported no relevant financial relationships.

Diabetologia. Published online February 24, 2014. Article

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