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Diabetes increased incident stroke risk in women
There may be a graded association between HbA1c and the risk for incident stroke among women with type 2 diabetes, according to data published in Diabetologia.
“Several mechanisms could explain why diabetes has a greater adverse effect in women than in men. In the general population, higher numbers of strokes occurring among women than men is at least partly attributed to the longer life expectancy of women,” Wenhui Zhao, MD, of Pennington Biomedical Research Center in Baton Rouge, La., said in a press release. “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. Others suggested that the greater risk associated with diabetes seen in women may reflect a treatment bias that favors men. Recent studies found that men with diabetes or established cardiovascular disease are more likely to receive aspirin, statins, or antihypertensive drugs than women.”
Zhao and colleagues conducted a prospective study, investigating the sex-specific association between varying levels of HbA1c and the risk for incident stroke among 10,876 men and 19,278 women with type 2 diabetes and a mean follow-up of 6.7 years.
The researchers observed 2,949 incident cases of stroke. According to data, multivariable-adjusted HRs of stroke were associated with the following levels of HbA1c for men:
- <6%, HR=0.96; 95% CI, 0.8-1.14;
- 6%-6.9%, HR=1 (reference);
- 7%-7.9%, HR=1.04; 95% CI, 0.85-1.28;
- 8%-8.9%, HR=1.11; 95% CI, 0.89-1.39;
- 9%-9.9%, HR=1.1; 95% CI, 0.86-1.41; and
- ≥10%, HR=1.22; 95% CI, 0.92-1.35.
In addition, they observed the following associations for women:
- <6%, HR=1.03; 95% CI, 0.9-1.18;
- 6%-6.9%, HR=1 (reference);
- 7%-7.9%, HR=1.09; 95% CI, 0.94-1.26;
- 8%-8.9%, HR=1.19; 95% CI, 1-1.42;
- 9%-9.9%, HR=1.32; 95% CI, 1.09-1.59; and
- ≥10%, HR=1.42; 95% CI, 1.23-1.65.
Age stratification indicated that the adjusted HRs were significantly higher in women older than 55 years compared with younger women, according to researchers.
“This might suggest that poor blood glucose control is more harmful in elderly women than in younger ones,” Gang Hu, MD, MPH, PhD, FAHA, also of the Pennington Biomedical Research Center, said in a press release. “The possible explanation may point to the role for estrogen. After onset of menopause, when estrogen levels decline, the incidence of cerebrovascular disease in women increases. Pre-clinical (animal) 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.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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These sex-differences are important to try to understand. Women may have more comorbidities and CV risk factors, as we have seen previously in women with ischemic heart disease and heart failure and was seen in this study group (aside from a lower rate of smoking in women compared with men).
We could also hypothesize that there is a difference in preventive treatment strategies between the sexes. Nonetheless, it is important to note that the use of lipid-lowering agents and anti-hypertensives were used more frequently in women in this cohort when compared with men. We have no information about aspirin use in either sex. We also do not know who were on ACE-inhibitors. We also have no information about control of risk factors during the follow up period aside from HbA1c. There was a statistical difference in use of glucose-lowering medication between sexes at baseline, with women on fewer medications, particularly insulin and sulfonylureas.
When a woman has diabetes, the lower cardiac risk usually attributed to a menstruating woman (whether this be due to estrogen or other factors) appear to be erased by the presence of diabetes. With stroke, although the risk of stroke is high in all women, it appears that the risk is significantly higher in women aged 55 years and older. It may be that poor glucose control affects older women greater than younger women and heightens the risk for stroke. It could also indicate that in older women, more aggressive control of diabetes is needed to lower the risk for stroke. Certainly this association is noted but this was just an observational study and more information is still needed.
Nonetheless, this is an important study that highlights some observational sex differences in stroke that need to be studied further. This study had a good representation of women; in fact more women than men, which given the prevalence of diabetes, seems representative of the population from where it was taken. In addition, blacks were well-represented in this study. The majority in this population was uninsured but this does not take away from the importance of the findings to this population.
This study also raises so many important questions about control of diabetes and its overall CV effects, particularly its effect on stroke. But what is needed is to see how aggressively we treat all CV risk factors, including diabetes in this very high risk population and its ultimate effect on lowering the risk of both heart disease and stroke.
With the recent Guidelines for the Prevention of Stroke in Women, more focus needs to be given to women and control of their diabetes, in addition to control of all CV risk factors. Appropriate preventive strategies need to part of the management of women with diabetes to lower the risk of stroke and heart disease. This remains one of the highest risk groups for CVD, and as diabetes as become epidemic worldwide, its impact on global health remains a focus of our preventive strategies.
Editor’s Note: For more on this and other cardiometabolic topics, visit Gulati’s blog.