Redefining PAD with a Feminine Touch
Peripheral artery disease (PAD) affects approximately 8 million adults in the U.S., according the American Heart Association (AHA), and the disease burden may be higher in women than in men. Researchers are asking if, as in coronary heart disease (CHD), women may present differently than men. They fear PAD may go undiagnosed in women, putting them at risk of heart attacks, stroke and death. Efforts to better identify asymptomatic PAD patients may allow for earlier diagnosis and intervention.

The classic symptom of PAD is intermittent claudication, typically leg pain when walking that disappears when the activity ceases. Physicians can identify the presence of PAD by measuring the patient’s ankle-brachial index (ABI) and then proceed with a management plan that may include supervised exercise, pharmacological treatment or revascularization as well as treatment for atherosclerosis risk factors. But that requires a level of PAD awareness that is often lacking.

A landmark study designed to assess the feasibility of identifying PAD in a primary care center found that the prevalence of PAD was high and physician awareness was low (JAMA 2001;286:1317-1324). PAD was detected in 29 percent of the 6,979 patients and half of the cases were newly diagnosed. Female participants accounted for 52 percent of the overall study group. Yet, only 11 percent of the whole PAD cohort reported classic claudication.

“We have this definition of classic claudication derived primarily from men,” says Diane Treat-Jacobson, PhD, RN, of the School of Nursing at the University of Minnesota in Minneapolis. This circumstance holds parallels with angina, whose classic symptom of chest pain was found to not appear as commonly in women. Many women with CHD went undiagnosed as a consequence, and did not receive treatment to reduce the associated risk. “It is possible some women are not experiencing claudication in that classic way and because of that atypical presentation, some women may get missed more often than men. We haven’t really explored that in depth, so we don’t have data to show.”

Girl meets gap

The AHA issued a call to action this year that summarized the evidence of PAD burden in women, the associated cardiovascular risks, the efficacy of treatments and evidence gaps, including the question of subtle gender-based differences in presentation (Circulation 2012;125:1449-1472). Alan T. Hirsch, MD, chair of the writing committee and lead author of the landmark study on PAD awareness and prevalence, says that there is much gender equality in PAD but pockets of disparity still need to be addressed.

As a result, continuing to grow the evidence base remains a priority to provide solid data using a broad spectrum of the patient population. “The lack of information regarding gender-based risk, treatment outcomes or treatment preferences doesn’t provide anyone with a conclusion,” says Hirsch, a professor of medicine, epidemiology and community health at the Lillehei Heart Institute at the University of Minnesota Medical School in Minneapolis. “It is only the careful collection of robust information within clinical research investigations that provides patients, clinicians and society with conclusive information.”

Mary M. McDermott, MD, a professor of medicine at Northwestern University Feinberg School of Medicine in Chicago, is filling in some gaps. McDermott, along with Treat-Jacobson, was an author of the call to action. In her early research, she and colleagues found that while only 6.7 percent of the women had been informed by a physician that they had PAD or intermittent claudication, 35 percent had an ABI indicating PAD (Circulation 2000;101:1007-1012). Of those with significant PAD, 63 percent had no exertional leg pain.

Asymptomatic PAD was independently associated with slower walking velocity and other impaired lower extremity functions.

Debilitating consequences

Additionally, women with PAD may decline more quickly than their male counterparts. In a longitudinal observational study, McDermott and colleagues compared the rates of mobility loss and performance decline in a six-minute walking test between 180 women with PAD and 200 men with PAD (J Am Coll Cardiol 2011;57[6]:707-714). They also compared calf muscle characteristics and leg strength at baseline and at the four-year follow-up.

Their results showed women had faster rates of decline and greater mobility loss than men. They attributed the sex differences in part to a lower calf muscle area and less lower extremity strength in women compared with men at baseline.

“There are some data that women with PAD have faster decline in their functional performance than men,” McDermott says. “Despite that, we don’t have any good evidence that exercise works any differently between the two sexes. However, PAD is underdiagnosed in women. For women, making the diagnosis and implementing appropriate care should be the focus.”

Walking serves as a way to assess claudication, but supervised walking also is a treatment for claudication. Some PAD patients—men and women alike—find the pain that accompanies exercise limits their ability to train at the desired intensity or time periods. Treat-Jacobson and her colleagues developed a study to test another approach, upper extremity aerobic exercises, to intensify training without the associated leg pain.

In the pilot study, they randomized 41 patients with claudication to 12 weeks of either three hours a week of supervised training using arm exercises, treadmill walking, a combination of both or a control group (Vascular Medicine 2009;14:203-213). The primary endpoint was maximal walking distance. Maximal walking distance increased 53 percent in the arm ergometry group, 69 percent in the treadmill group and 68 percent in the combination group, all in comparison with the control group, at 12 weeks. At 12 weeks, pain-free walking distance increased 82 percent in the arm ergometry group, 54 percent in the treadmill group and 60 percent in the combination group compared with the control group.

“We had a small number of women in that study, but there was a potential signal that the women might have responded differently than men,” Treat-Jacobson says. She and colleagues hope to enroll enough women in an ongoing randomized clinical trial comparing aerobic arm exercise with treadmill training to determine whether there are differences in their response to the two methods.

The call to action authors emphasize that the most pressing challenge is increasing awareness of PAD in women to identify those at risk of the disease early to prevent its associated cardiovascular morbidity and mortality. Broadening the identification of PAD beyond intermittent claudication to encompass other symptoms may help in the effort.