New WISE observations underscore different vascular pathology in women

Shelley Wood

February 02, 2006

Bethesda, MD - A host of new observations from the Women's Ischemia Syndrome Evaluation (WISE) study help explain key differences in the pathogenesis of vascular disease in women and men and improve CVD prevention, diagnosis, and ultimately survival in women, experts say.

The publication of the WISE papers this week in a special supplement of the Journal of the American College of Cardiology coincides with National Wear Red Day, a US campaign to raise awareness about women's heart disease.

Authors of these latest reviews, combining new observations from WISE with other published reports, conclude that the vasculopathy in women leading to ischemic heart disease stems from a variety of factors unique to women—namely, smaller coronary vessels, more diffuse atherosclerosis, stiffer aortas, and more frequent microvascular dysfunction.

In one of the review papers, Dr C Noel Bairey Merz (Cedars-Sinai Medical Center, Los Angeles) and colleagues observe that the "typical" female symptoms of ischemic disease are more multifactorial than those of men and that additional risk assessment of inflammatory markers, evidence of plaque burden, and evidence of ischemia may be "of relatively greater importance in women." Responses to conventional risk factors may also be different in men and women, with differences in inflammatory response—possibly mediated by estrogen—probably playing a more important role in women.

Elsewhere in the supplement, Drs Amir Lerman (Mayo Clinic, Rochester, MN) and George Sopko (National Heart, Lung and Blood Institute, Bethesda, MD) write that metabolic syndrome is probably a more important risk factor in women than in men and that microvascular disease and endothelial dysfunction may be the major mechanistic factors underpinning ischemia in women. "The diagnoses of coronary microvascular dysfunction or endothelial dysfunction should be considered in women with chest pain who do not have obstructive coronary artery disease," they write. Testing for this type of dysfunction may help diagnose CAD in women when conventional tests are nondiagnostic, they add.

The missing link, writes AHA immediate past president Dr Alice Jacobs, "is a clear understanding of the relationship between symptoms and microvascular ischemia, of the gender differences in novel risk factors and particularly how they relate to the pathophysiology of acute coronary syndromes, of the independent relationship between heart failure and mortality following revascularization, and of the small but persistent gender difference in (adjusted) outcomes following both CABG and PCI."

In an interview with heart wire , Bairey Merz emphasized the need for ongoing research, like WISE, to better appreciate the unique presentation of ischemic disease in women. "At least as many as half of women with evidence of ischemia and open arteries have problems related to insufficient dilation of the arteries," she commented. "We need to do further testing in these women, including provocative coronary testing. . . . We are not clear about the mechanisms, but this abnormality of arterial dilation appears to be more prevalent in women [and] appears to be related to atherosclerosis and possibly sex differences in plaque [deposition]," she explained.

Risk-prediction tools in women

While the bulk of the WISE publications this week are review papers, three papers provide new data analyses from the WISE cohort. In one, Dr Leslee J Shaw (Cedars-Sinai Medical Center) and colleagues used the Duke Activity Status Index (DASI), a questionnaire-based measure of functional capacity, in the WISE women. Like an exercise stress test, the DASI can be used as a measure of functional capacity based on estimated metabolic equivalents (METS). Shaw et al report average DASI-estimated functional capacity was similar to estimates achieved through exercise testing—an important finding, since exercise testing is frequently inconclusive in women, they note. In women with suspected myocardial ischemia, functional impairment as estimated by the DASI correlated with indeterminate exercise test results and adverse prognosis.

"Use of the DASI before exercise testing can risk-stratify symptomatic women and may improve identification of higher-risk, functionally impaired subjects who would benefit from pharmacologic stress imaging" and could be targeted for more aggressive risk management, they conclude.

In the second paper, Dr Eileen Handberg (University of Florida College of Medicine, Gainesville) and colleagues also focus on functional capacity using the DASI and report finding a significant relationship between DASI score and vascular reactivity as measured by coronary flow response to adenosine in women with suspected ischemic heart disease. The findings offer "one possible link" explaining impairment of functional capacity in women, they suggest. "The DASI may be a simple and easy-to-use tool that contributes to the global risk assessment," Handberg et al conclude.

A third paper examines the link between high blood pressure, other cardiac risk factors, and coronary disease as it relates to age and menopausal status. As Dr Gretchen L Gierach (University of Pittsburgh, PA) et al report, elevated systolic blood pressure and elevated pulse pressure appear to be key risk factors for CAD in premenopausal women, but not in postmenopausal women undergoing angiography for suspected ischemia. "The results suggest that identification of hypertension in premenopausal women [warrants] additional CAD risk-factor assessment and management," they write.



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