According to the American Heart Association, Peripheral Arterial Disease (PAD) affects over eight-million Americans. The risk factors for PAD are similar to those for coronary heart disease and the presence of PAD is a marker for systemic atherosclerotic disease. People with PAD have a 3.1-times higher risk for all-cause mortality and a 5.9-times higher risk for death from cardiovascular disease. The classic symptom of PAD is claudication; however, only 10% to 33% of patients with PAD exhibit it.

Dr. Mary McGrae McDermott is an Associate Professor Medicine and Preventive Medicine, Division of General Internal Medicine, Northwestern Feinberg School of Medicine. An expert on PAD, she began studying this disease during her General Internal Medicine Fellowship here at Northwestern during the 1990s. She became interested in PAD while working on a grant studying claudication. Claudication is the classic symptom of PAD.“

"As an urban teaching hospital, Northwestern offers a large and varied population to recruit for studies. Northwestern also offers researches access to the extensive range of expertise and talent available at a large, top-level university campus with outstanding facilities.”

The development of the ABI as a measure of the presence and severity of PAD has been around for more than 30 years. It was developed in part by Northwestern Professor Emeritus James Yao, MD. Dr. McDermott’s early research showed that ABI is independently associated with functional impairment and functional decline in patients with and without PAD. In one study, Dr. McDermott and colleagues developed a prospective cohort group of 676 individuals (age ≥ 55 years) with and without PAD (n=417 and n=259). They established baseline functional performance and then annually reassessed the participants’ abilities for two-years. The main outcome measures were the mean change in 6-minute walk performance and in usual-paced and fast-paced 4-m walking velocity.

Dr. McDermott found that lower baseline ABI values were associated with greater mean annual decline in 6-minute walk performance and a significantly increased odds ratio for becoming unable to walk for 6 minutes continuously. At the two-year follow-up participants with baseline ABIs of less than 0.50 who were able to walk for six minutes continuously at baseline exhibited a 13-fold increased risk of becoming unable to walk for 6 minutes continuously compared with those with ABIs of 1.10 to 1.50. She concluded that baseline ABI measurements in patients could predict the degree of functional decline they will suffer and that patients with PAD have significantly increased rates of functional decline compared to individuals without PAD.

Dr. McDermott’s work demonstrated the prognostic significance of the ABI as a measure of functional impairment and functional decline in PAD. Observational studies in the 1960s and 1970s suggested that the natural history of lower extremity disease in patients with PAD and intermittent claudication was benign. When patients were surveyed, just 15% to 30% of individuals with claudication reported symptomatic worsening over 5 – 10 years of follow-up. This lead physicians to believe that patients with intermittent claudication stabilized or improved their symptoms. However, Dr. McDermott’s results were consistent with progressive restriction in activity to adapt to functional decline. By reducing their activity, patients masked PAD-associated morbidity.

The ABI can be measured at bedside. Using Doppler ultrasonography, the pressure at the brachial artery and at the posterior tibialis and dorsalis pedis arteries are measured. The ankle systolic pressure is divided by the brachial pressure, both measured in the supine position. Normally, the ratio is more than one. In severe disease, it is less that 0.50.

Dr. McDermott began studying associations between clinical predictors and functional decline in persons with PAD. Her paper, Physical Performance in Peripheral Arterial Disease: A Slower Rate of -Decline in Patients Who Walk More (Ann Intern Med 2006 144 10 – 20), found that walking three time a week or more, even in an unsupervised exercise program, is associated with slower rates of functional decline in patients with PAD. 417 men and women with PAD were classified at baseline and annually according to the number of times they reportedly walked for exercise each week. Functional assessments (6-minute walk distance, 4-meter walking speed) were measured at baseline and annually. They found that patients who walked for exercise 3 or more times per week had a significantly smaller average annual decline in 6-minute walking distance (-48.0 feet per year compared to -56.6 feet per year for those who walked 1 to 2 times per week and -79.4 feet per year for non-exercisers). People who walked three times a week or more experienced a smaller average annual decline in the usual-paced 4-meter walking velocity (-0.014 m/s per year compared to –0.022 m/s per year for those who walked 1 to 2 times per week and -0.045 m/s per year for non-exercisers).

Having the patients engage in self-directed exercise appears important to help protect patients against functional decline. Elderly patients, who are most affected by PAD, often cannot attend supervised rehabilitative programs because they lack transportation or the treatment cost is high. In addition, many healthcare insurance plans do not cover exercise programs for patients with PAD.

Dr. McDermott feels that conducting her research here at Northwestern has many benefits. “As an urban teaching hospital, Northwestern offers a large and varied population to recruit for studies. Northwestern also offers researches access to the extensive range of expertise and talent available at a large, top-level university campus.” McDermott was able to collaborate with experts here at Northwestern including Drs. Philip Greenland, Kiang Liu, Bill Pearce, Susan Tiukinhoy, and Gary Martin. Investigators outside of Northwestern include Drs. Michael H. Criqui at U C San Diego, Jack Guralnik at the NIA and Luigi Ferrucci also at the NIA.

The referring physicians at Northwestern were extremely valuable to her in her studies, helping to recruit an accurate cross section of the population. Most of the participants come from recommendations made by the vascular lab. The General Clinical Research Center is very helpful, providing Dr. McDermott space for her equipment and activities. She is able to draw on a skilled group of medical students, residents, fellows, faculty, and MPHs to help her carry out her research.

The next step in her research is to examine the impact of strength training to improve leg function in PAD. In a current study, she is randomizing patients into one of three study groups: a supervised progressive resistance training program, an unsupervised progressive training program or a nutritionally controlled group. After six months of on-site training, participants in the exercise groups will be moved to a six-month home-based exercise program. Dr. McDermott hopes to determine whether gains made during supervised training can be maintained in a home environment.

With the help of a team of talented colleagues, excellent support facilities, and close integration with a well-respected academic/research hospital, Dr. McDermott has become a pioneer in the diagnosis and treatment of PAD. Her research has led to important information that may help improve the quality of life for thousands PAD sufferers. By demonstrating the degree of functional impairment and decline in patients with PAD and by identifying characteristics associated with less functional decline among PAD patients, Dr. McDermott has made the Department of Medicine the top research center for the study and treatment of PAD.