Women with diabetes face higher risk of artery disease from hormones

06/24/04

DALLAS, June 29 Postmenopausal hormone therapy can promote cardiovascular disease in women with diabetes or pre-diabetes (abnormal fasting glucose), according to a report in today's rapid access issue of Circulation: Journal of the American Heart Association.

While hormone therapy improved women's cholesterol, fasting glucose and insulin resistance, it significantly worsened artery narrowing and exacerbated inflammatory markers, such as C-reactive protein (CRP) and fibrinogen, which are linked to cardiovascular disease.

This is the first trial to use angiography, or X-rays of coronary vessels, to document the progression of atherosclerosis in postmenopausal women with diabetes or impaired glucose tolerance who take hormones.

"The big lesson here is that fixing a single risk factor does not necessary mean you fix the outcome," said the study's lead author, Barbara Howard, Ph.D., president of MedStar Research Institute, Washington D.C. "It can't be assumed that everything that lowers a risk factor, such as reducing low-density lipoproteins, will improve heart disease."

Low-density liproprotein (LDL) is "bad cholesterol" that clogs arteries.

"People once thought that hormone therapy could prevent heart disease in women, especially in women with diabetes, who have an increased risk," Howard said. "But this study provides evidence that hormone therapy should not be used to reduce cardiovascular disease risk in women with diabetes or pre-diabetes."

Researchers analyzed data from the Women's Angiographic Vitamin and Estrogen (WAVE) Study, a multicenter prospective trial that used angiography to examine women randomly assigned to PHT or placebo for three years. Of the 321 women studied, 140 had diabetes or pre-diabetes, 181 had normal glucose levels. All the women had angiographic evidence of heart disease upon study entry and received follow-up angiograms near the end of the study.

Risk factors for heart disease improved among all the women. Both groups had reduced LDL levels and increased high-density lipoproteins (HDL), the "good cholesterol." In addition, women with abnormal glucose tolerance taking hormone therapy had slight decreases in fasting glucose and insulin concentrations, although none met statistical significance.

However, hormone therapy in women with abnormal glucose tolerance had adverse effects on fibrinogen and CRP levels. Fibrinogen, a marker for clotting, increased in women taking hormones with abnormal glucose tolerance, while it dropped in women taking hormones with normal glucose tolerance.

CRP, an inflammatory marker associated with heart disease, increased in women taking hormones who had diabetes or pre-diabetes; whereas those with normal glucose tolerance had a slight decrease.

Researchers measured the effects of hormone treatment by angiography in diseased and non-diseased artery segments as change per year in minimum and average lumen (vessel opening) diameter. They found no differences when comparing the adverse effects of postmenopausal hormone therapy on minimum and average diameters on diseased segments in women with abnormal glucose versus the women with normal glucose.

"On the other hand, there were differing effects on non-diseased segments in women with diabetes or pre-diabetes," Howard said. "In these women, hormone treatment was associated with a decrease in both minimum and average lumen diameter."

Lumen decreased about .022 millimeter per year (mm/y) in women with abnormal glucose tolerance, compared to .0007 mm/yr in women with normal glucose tolerance.

"In parts of the vessel without disease at baseline, postmenopausal hormone therapy actually made the narrowing worse in women with abnormal glucose tolerance," Howard said.

The current study's findings provide "further evidence that this regimen will not be beneficial in preventing cardiovascular disease in diabetic women," researchers said.

Physicians may still consider using postmenopausal hormonal therapy in diabetic women who have serious menopausal side effects, she said. "Following FDA guidelines, hormone therapy should be used for the shortest time needed and in the lowest dose."

Previous studies found that hormone replacement therapy increases the risk of heart disease and stroke. The Women's Health Initiative (WHI) Hormone Trial found that a combination of estrogen and progestin increased the risk of heart disease, stroke and thromboembolic (blood clots) events in postmenopausal women. The Heart Estrogen Protection Study (HERS) showed that hormone therapy did not protect women from heart disease. Both studies showed that hormone therapy had an adverse effect on cardiovascular disease in women with diabetes.

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