Gender Disparities Persist with CAD
Coronary artery disease (CAD) is the leading cause of death in women in the U.S., according to the Centers for Disease Control and Prevention. It takes the life of more than 300,000 women annually, nearly 10 times that of breast cancer. Yet, imaging—often the bedrock for first diagnosis and then treating cardiac disease in women—remains inconsistent from the treatment of their male counterparts. Understanding gender differences in the physiology, symptoms and risk factors may help to reduce the gender gap and improve care.

The conundrum

Previously thought of as a "man's disease," there's been more acknowledgment in recent years of the serious risks of heart disease in women. CAD is more prevalent in men—8.3 percent of adult men live with the condition compared with 6.1 percent of adult women, according to the American Heart Association (AHA) 2011 Statistical Update. But women are more likely to die from a first MI and also experience more long-term disability.

Certain populations of women are at a higher risk. Risk increases for obese women and doubles for post-menopausal women. Estimated 10-year CAD risk is twice as high in diabetic women as non-diabetic women, and more than three times as high in diabetic women who smoke, according to the AHA. Also, women are less likely to undergo PCI and CABG than men.

Differences in treatment may be due to gaps in knowledge about symptom presentation and risk factors, with some physicians unaware of gender-specific care. Physicians often rely on long-standing beliefs that have proven to be effective ways of practicing medicine, says Leslee J. Shaw, PhD, co-director of the Emory Clinical Cardiovascular Research Institute at Emory University School of Medicine in Atlanta. "When you have populations that are changing and the risk is different from what you would have perceived in another era, that's tough for medical practice to keep up with," she adds.

Shaw says another issue could be the differences in symptom presentation such as shortness of breath, angina that is stress-triggered as opposed to exertion-related and atypical symptoms such as indigestion, nausea and discomfort in the elbow or jaw. "We don't have a female-specific description of anginal symptoms," Shaw says. "Many of the women who present with angina symptoms are classified as more atypical because they are not exertionally related … and don't present with those typical heart attack stories, such as shoveling snow or mowing the lawn."

Underused and unnecessary?

Over the last few decades, the use of myocardial perfusion imaging (MPI) to diagnose CAD has increased threefold, with a rate of utilization among Medicare beneficiaries of 8,467 per 100,000 in 2008 (AJR 2011;196:862-867). After examining these data on nuclear imaging exams, researchers have come across a new disparity: a higher percentage of women receive tests that don't meet appropriate use criteria. Aarti Gupta, MD, a cardiology fellow at Miriam Hospital in Providence, R.I., and colleagues conducted a study of 314 consecutive MPIs and found women accounted for 68 percent of the inappropriate tests and 82 percent of the uncertain tests.

This presents a fine line for physicians. On the one hand, women are under-tested, but on the other, a higher percentage of unnecessary tests occur in women referred for MPI.

"It's not always clear," says Gupta. "Our study shows that we are testing more women with nuclear stress tests than perhaps need the test, but, at the same time, we don't want to miss women with heart attacks as again, women can present with atypical symptoms."

Another finding of Gupta et al was that cardiologists were more likely than primary care physicians to order tests classified as appropriate at rates of 86 percent to 71 percent, respectively. She says uniformly applying the guidelines of the American College of Cardiology for appropriate use of nuclear stress testing would help, because they are not being referenced enough by physicians.

"This document has been circulating in the cardiology community since 2005, but it has not become very prevalent in the primary care community," says Gupta. "We need to do more to educate primary care physicians to help them select patients for testing more appropriately."

Sticking to guidelines

Disparate treatments may result in varied disease states between the sexes. William E. Boden, MD, of the University at Buffalo School of Medicine and Public Health in Buffalo, N.Y., theorizes that women have a different syndrome that causes ischemia. Rather than a narrowing or blockage of the epicardial coronary artery, women are likely to have microvascular angina involving microvessels that are not delineated with a coronary angiogram. Evidence of ischemia may be on an initial ECG, but a report from the cath lab shows normal coronary arteries.

"I'm not really sure it's a false positive," says Boden. "It may be a true positive, but it's not due to narrowed epicardial coronary arteries. It may be due to microvascular angina."

Recent studies have looked into the theory that some MIs are triggered by different mechanisms in women. Researchers at the Cardiac & Vascular Institute at NYU Langone Medical Center in New York City, using intravascular ultrasound and cardiac MRI, discovered that 38 percent of MIs in women with normal angiograms were linked to plaque disruption that could not be seen on an angiogram (Circulation 2011;124:1414-1425).

To avoid false positives that result from these unusual forms of ischemic heart disease, some physicians may be inclined to skip over the ECG, which guidelines suggest as an initial test, and proceed straight to MPI. To contrast the benefits of the different approaches, Boden, Shaw and others conducted the WOMEN trial that examined the benefits of MPI over traditional ECG exercise treadmill testing. Prior to the trial, most researchers believed MPI combined with a treadmill test would be better than treadmill alone.

"We were not able to demonstrate that in women who were at intermediate risk for having coronary disease," says Boden. "It turns out that the treadmill exercise testing was as good as MPI and it was far less costly. Perfusion imaging was not superior to standard treadmill exercise in terms of predicting events at follow-up."

A total of 824 women were randomized to either a standard treadmill test or an exercise MPI. ECG results on the treadmill test were normal for 64 percent of women, indeterminate for 16 percent and abnormal for 20 percent. In comparison, MPI results were normal in 91 percent, mildly abnormal in 3 percent and moderate to severely abnormal in 6 percent. At two years post-test, there was no difference in major adverse cardiac events.

In the WOMEN trial, patients randomized to the standard treadmill test had diagnostic costs 48 percent lower than the exercise MPI group. If more women who are at low and intermediate risk of CAD were given standard exercise treadmill tests as an initial diagnostic test, it could result in considerable cost savings, considering an estimated two million to three million women undergo exercise MPI annually.

Boden says the findings should reinforce current guidelines and could save money if followed, though hospitals may feel pressured to order more tests to justify the purchase of expensive equipment. Plus, as long as Medicare and other payors keep paying, there's no disincentive to conduct fewer tests.

"What we should start with is applying evidence-based medicine," says Boden. "We all worship at the altar of evidence-based medicine, but we practice it selectively. We don't practice what we preach."