WISE data show need for new diagnostic methods in women

Unlike men, women do not present with large arterial blockages early in their disease and it is often not easily diagnosed with traditional imaging.

Diagnostic coronary angiography designed to show large coronary artery stenosis is not very useful in women in the early phases of their disease where the plaque appears more likely to spread evenly through the artery wall, according to a report from the Women’s Ischemia Syndrome Evaluation.

“Coronary angiography alone might be missing a sizeable portion of women in terms of estimating the risk. Certainly some noninvasive modalities might be helpful, including CT and MR,” said Leslee Shaw, PhD, associate professor of medicine at Cedars-Sinai Medical Center.

Shaw is an editorial board member of Cardiology Today’s Health Policy, Patient and Practice Issues section and was one of the researchers on the WISE project, which was funded by the National Institutes of Health.

Leslee Shaw, PhD

CT and MR may not provide the necessary information either, Carl J. Pepine, MD, said. “We suggested 64-slice MDCT and MR because they are new techniques, but we really don’t know how well they are going to perform,” said Pepine, chief medical editor of Cardiology Today. “MR has tremendous promise and the potential to even assess myocardial perfusion, but it also has limitations. I am not certain CT is going to be the answer either. Women have high heart rates, smaller vessels and calcification that are likely to present problems for CT.”

Carl J. Pepine, MD

In a special 71-page supplement, The Journal of the American College of Cardiology has published many of the major findings from WISE along with editorial commentary from the researchers involved.

“This was a great opportunity for all of us to put forth our theoretical perspectives,” Shaw said. “We received a lot of latitude to explore different options, and that is the perspective that is going to be needed in women’s health.”

Diagnostic modalities

Shaw was the lead author on a paper that observed gender differences in traditional risk factors like cholesterol and obesity.

“If you ask anyone in the United States what they think the traditional risk factors are, you’ll hear the usual, such as smoking, high blood pressure, etc. What we’re seeing is that when you take a measure of global risk that includes all of those risk factors it really underestimates the risk in women. There are so many other factors that are perhaps contributing more prominently to risk in women and a lot of those are more closely aligned with the metabolic syndrome.”

Shaw’s paper suggested that intermediate to high-risk asymptomatic women, defined as having a Framingham Risk Score of 6% to 20% 10-year risk of CHD death or MI, should be given the following tests to measure subclinical disease: ankle-brachial index, brachial artery reactivity, carotid intima-media thickness, retinogram and CT coronary calcium.

“The idea of a retinogram is something that may not have been considered before, but it appears that retinal artery narrowing is predictive of cardiac death or MI in women, but not in men. Ophthalmologists have seen that, but it has never been shown in the cardiology literature until now,” Shaw said.

Vascular disease differences

Pepine’s article outlined issues related to vasculopathy of women with ischemic heart disease. Women, he said, develop a more severe or somewhat different form of vascular disease than men.

“If you wait until women present with findings like those we regularly see in men, such as unstable angina, MI or need for revascularization or heart failure, their mortality rate is approximately double that of men,” Pepine said. “So that suggests to me that one way to approach this problem is to try and look at the earlier phases of the disease.”

The challenge, Pepine said, is to develop the tools to identify their disease in the early phases.

“We know that women seem to have a lot of chest symptoms that are not what we call typical angina or male-pattern angina. We know that they have a much lower frequency of obstructive disease in the large vessels. We also know that they are more likely to have noninvasive test findings suggesting ischemia compared to men. We know that about half or more of the women who present with findings suggesting ischemia have dysfunction at the coronary microvascular level, and this dysfunction appears to be linked to adverse outcomes,” Pepine said.

Pepine said the greatest challenge for the WISE program is to determine its further applications.

“What we need is more data like the current WISE to, first of all, replicate findings that we saw in the current program, and then we need to extend our work to studies that will let us better understand the disease in its early phase,” Pepine said. – by Jeremy Moore

For more information:

• WISE Investigators. Challenging existing paradigms in ischemic heart disease: the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE). J Am Coll Cardiol. 2006;47:1S-71S.