PAD underrecognized, understudied in women

Issue: April 2012

Women with peripheral artery disease are two to three times more likely to have a stroke or MI compared with women without the disease, yet it is often underrecognized and untreated, according to a recent scientific statement released by the American Heart Association.

Michael R. Jaff, DO, a Cardiology Today Editorial Board member, said a multipronged approach is needed regarding the diagnosis and treatment of PAD.

Source: Bill Truslow

“The rate of deaths and the health care costs associated with peripheral artery disease are at least comparable to those of heart disease and stroke,” Alan T. Hirsch, MD, director of the Vascular Medicine Program at the Lillehei Heart Institute at University of Minnesota Medical School, said in a press release. “Women, in particular, suffer an immense burden from PAD, yet current data demonstrate most women still remain unaware of their risk.” The scientific statement was developed by the AHA in collaboration with the Vascular Disease Foundation and Peripheral Arterial Disease Coalition as a call to action for both health care providers and patients to raise awareness of PAD, according to Hirsch, lead author of the statement.

“PAD is clearly underrecognized, yet very common,” said Michael R. Jaff, DO, medical director of the Mass General Vascular Center and Vascular Diagnostic Laboratory and Cardiology Today Editorial Board member.

Knowledge gaps

Only about 10% of those with PAD experience the warning sign of claudication, and this pain usually goes away while resting. Many experience no symptoms at all, and as a result, few receive prompt treatment. Even so, PAD care leads to more than 1.1 million medical visits by women each year, a rate that is comparable to office visits by women for stroke care, according to the statement.

Recognized risk factors for PAD include older age (>50 years), smoking and diabetes. Hypertension, hypercholesterolemia, obesity, chronic kidney disease and family history of PAD may also increase risk.

According to the statement, PAD awareness by men and women is “strikingly low” compared with knowledge of other CVDs and general diseases.

“The main reason for the lack of recognition is that symptoms are very vague, unpredictable and are often misconstrued as due to orthopedic or musculoskeletal causes,” Jaff said.

It is suggested that women experience the consequences of PAD at rates at least as high as those observed in men.

“PAD is a major cause of CV morbidity and mortality in women,” William Hiatt, MD, professor of medicine in the division of cardiology at University of Colorado School of Medicine, told Cardiology Today. Much of this risk is modifiable if women at risk for PAD are appropriately identified using the ankle-brachial index (ABI), and risk-modification therapies are instituted.

Hiatt said the underdiagnosis of PAD was first described in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) trial published in the Journal of the American Medical Association in 2001. Hirsch, Hiatt and other researchers evaluated more than 6,900 patients aged at least 70 years or aged 50 to 69 years with history of smoking or diabetes at nearly 400 US sites in 1999. PAD (defined as ABI <0.9) was detected in 29% of patients; of those, 44% had PAD only, with no evidence of CVD. Eighty-three percent of patients with prior PAD were aware of their diagnoses, but only 49% of physicians were aware of these diagnoses. The researchers concluded: “Prevalence of PAD in primary care practices is high, yet physician awareness of the PAD diagnosis is relatively low. … These results demonstrate that underdiagnosis of PAD in primary care practice may be a barrier to effective secondary prevention of high ischemic CV risk associated with PAD.”

In addition, women with PAD have greater functional impairment and faster functional decline than men with PAD, Mary M. McDermott, MD, professor of medicine at Northwestern University Feinberg School of Medicine, told Cardiology Today. McDermott cited data from a study she and colleagues published in the Journal of the American College of Cardiology in 2011 that described a faster rate of functional decline in women with PAD. Women with PAD were more likely to become unable to continuously walk for 6 minutes, were more likely to develop mobility disability, and had greater declines in walking velocity and distance achieved during a 6-minute walk test compared with men. A 2005 American Journal of Epidemiology study by McDermott and colleagues described the higher prevalence of borderline PAD in women as compared with men.

Alan T. Hirsch

Further, ethnic-related differences in the prevalence and treatment of PAD have been documented. For example, non-white women and men fare worse than whites in terms of health status, disability and mortality.

“In reality, PAD is as common and dangerous as breast cancer or cervical cancer. It is strange that women neither demand nor do [most] clinicians offer facilitated access to what I believe are the simplest, safest and most cost-effective prevention-based diagnostic tests for women,” said Hirsch, who is also professor of medicine, epidemiology and community health at the Lillehei Heart Institute.

Research gaps

To date, women have been underrepresented in published clinical trials to provide a clear understanding of the progression of PAD or to determine with accuracy the incidence and prevalence of PAD in women, according to the statement.

“The epidemiology of PAD would suggest that about half [or more] of the affected subjects with PAD are women, but in our trials to develop new PAD therapies, women are typically only 20% of the studied population,” Hiatt said. “Thus, a more aggressive effort to include women in clinical trials is warranted.”

According to Hirsch, although PAD affects women and men equally, “research regarding PAD in women has lagged far behind that in men.”

The statement includes a variety of recommendations to improve the knowledge base derived from research studies of PAD, particularly in women:

Funding new research to evaluate how gender may affect the rate of development of PAD.
Pooling results from previous, available data to obtain adequate sample sizes of women and provide sufficient statistical power to conduct gender-specific analyses.
More study on the response to PAD medications and potential benefits of revascularization in both men and women.
Analyses that consider demographic and comorbidity factors, procedure-related complications and procedural utilization as potential outcomes for gender-specific reporting.

Besides these recommendations, Jaff said a number of questions remain in PAD research, such as determining the most effective therapies for PAD and to better define the role of exercise vs. endovascular therapy in femoropopliteal PAD and claudication.

There are only two FDA-approved drug therapies for improving walking performance in men and women with PAD. Supervised treadmill exercise is very effective for improving walking preformance in people with PAD. However, medical insurance typically does not cover walking exercise for individuals with PAD, McDermott said in the interview. She noted that “more research is needed to better understand mechanisms of disability in PAD and identify therapies to improve walking performance and prevent mobility loss in PAD.”

“It’s discouraging but not surprising to hear of the lack of research and awareness of PAD and its risks among women because we know a gender gap exists in these areas for most heart and circulatory diseases,” Mary Ann Bauman, MD, medical director for women’s health and community relations at Integris Health in Oklahoma City, said in the press release.

Awareness gaps

Individual clinicians and women’s CV health programs are urged to incorporate PAD-specific risk messages in their current and future CV outreach efforts that are targeted to women. Women’s CV health programs could include PAD awareness campaigns and gender-relevant PAD care pathways designed to lower CV risk, as has occurred for other CVDs. Public awareness campaigns such as the AHA’s Go Red For Women may be effective in spreading knowledge about PAD.

“A multipronged approach is needed — educating physicians, nurses, nurse practitioners, physician assistants and others regarding the diagnosis of PAD,” Jaff said.

According to the statement, “A concerted effort, in clinical research, clinical care and health policy, could provide opportunities to lower this burden, with benefits to women and to the community as a whole.” The authors describe specific opportunities to improve the health of women with or at risk for PAD, including improvements in translation of current PAD knowledge to physicians and women in clinical practice.

“Clinicians should have a high awareness of the possibility of PAD in women, particularly in those with risk factors for PAD,” McDermott said.

An updated guideline for the diagnosis and management of PAD was released in November, calling more attention to the awareness of PAD. The guideline was released by the American College of Cardiology Foundation, AHA and other collaborating societies. The guideline focuses on expanding criteria for using ABI for earlier diagnosis, from 70 years or older to 65 years or older; smoking cessation and 325 mg aspirin per day for patients with lower-extremity PAD; and specific recommendations for use of open or endovascular leg artery methods of revascularization.

“We must provide a clear and highly impactful PAD message that defines the very real short-term heart attack, stroke and limb loss risk, linked to efforts to provide more proactive diagnosis and treatment pathways for both women and men, to improve PAD-related health,” Hirsch said. “Ultimately, through this effort, we will provide a major impact as we attempt to improve global CV health.” – by Katie Kalvaitis

For more information:

Hirsch AT. Circulation 2012;125:1449-1472.
Hirsch AT. JAMA. 2001;286:1317-1324.
McDermott MM. J Am Coll Cardiol. 2011;57:707-714.
McDermott MM. Am J Epi. 2005;162:33-41.
Rooke T. J Am Coll Cardiol. 2011;58:2020-2045.

Disclosure: Dr. Bauman is a volunteer for the AHA’s Go Red For Women campaign. Dr. Hirsch reports receiving research grants to the University of Minnesota from Aastrom Biosciences, Abbott Vascular and Viromed, as well as consulting for AstraZeneca, Merck, Novartis, Pozen and Shire HGT. Drs. Hiatt and Jaff report no relevant financial disclosures. Dr. McDermott is the medical director for Peripheral Artery Disease for the Foundation for Informed Medical Decision Making.