Updated results from the Women’s Ischemia Syndrome Evaluation (WISE) Study suggest that it is vital to identify affected women because their ischemic disease often evades detection with traditional diagnostics and remains undiagnosed until it has reached a critical stage, according to a supplement of the February 7 issue of the Journal of the American College of Cardiology.

The major gender difference was described with “Functional rather than structural abnormalities of the coronary circulation may be the hallmark of the disease in women,” in a comparison of the typical male obstructive arterial lesion with the two major areas of dysfunction in women: in the coronary endothelium and in the cardiac microcirculation.

C. Noel Bairey Merz, MD, chairs the WISE study, which was launched in 1996. WISE was designed to study diagnostic testing and pathophysiology of ischemic heart disease in women and how sex hormones and other gender-specific findings influence clinical aspects of the disease. From 1996 to 2000, 936 women referred for angiograms because of chest pain and suspected ischemia were enrolled.
In the supplement, Merz and her fellow WISE researchers offer the first description of a female-specific vascular disorder, “a global pattern of dysfunction in the macro- and microcirculation.”

The supplement articles on WISE studies, accompanied by discussions by several experts in the field, provide insight on a wide variety of subjects, including the array of gender-specific factors contributing to women’s manifestation of heart disease and implications for innovative diagnostic and evaluation procedures.
One area of focus was the major roles of sex hormones in women. High estrogen levels before menopause and decreasing estrogen and progesterone levels after menopause are believed to influence ischemic heart disease in women.

Premenopausal estrogen deficiency due to ovarian dysfunction may be a significant risk factor for younger women. Women with disruption of ovulation and decreased estrogen production have a greatly increased risk of coronary artery disease.

Because women’s diffuse atherosclerosis is far less likely to be imaged with traditional catheterization, the researchers recommend use of nuclear-based heart studies. Nuclear SPECT (single-photon emission computed tomography) imaging, for example, has resulted in dramatic improvement in diagnostic accuracy for women.

Although functional capacity is one of the strongest estimators of cardiac prognosis, treadmill stress testing is not suitable or effective for many women. Tests that induce stress chemically should be considered. Also, a 12-item questionnaire, the Duke Activity Status Index (DASI), provides a valuable risk assessment using self-reported activities of daily living.

These are translated into METs (metabolic equivalents), which are used to approximate physical work capacity. Two thirds of the cardiac events in the WISE women occurred in those with an estimated capacity of less than 4.7 METs. Women with evidence of lower scores were also significantly more likely to have risk factors and obstructive coronary artery disease.

Although overweight women are more likely than normal-weight women to have coronary artery disease risk factors, researchers found that metabolic alterations associated with obesity are key factors in placing a woman at risk for coronary artery disease and cardiac events. Women with metabolic syndrome are at much higher risk of cardiac events than those with normal metabolic status. Metabolic syndrome includes insulin resistance, unhealthy cholesterol and/or triglyceride levels, hypertension, and abdominal obesity.

This new reinforcement of the realization that there are different, unique risk factors for ischemic heart disease in women ? such as inflammatory processes in the arteries, anemia, and microvascular dysfunction ? leads to the possibility that different diagnostic and prognostic tools may be employed.

Among options currently being evaluated are high-sensitivity C-reactive protein, hemoglobin monitoring, and retinal artery narrowing examinations and coronary calcification tests.