No pain, no increase in exercise for peripheral artery disease

No pain means no gain when it comes to pulling exercise benefits for people with peripheral artery disease (PAD), reports a new study in Northwestern Medicine.

The study found that people with peripheral artery disease walk for exercise at an intensity that causes ischemic leg pain (caused by restricted blood flow). The study showed that it runs at a slow pace that does not cause ischemic bone symptoms.

This randomized trial is the first to show that a home exercise program improved the walking ability in people with peripheral artery disease when exercise was performed at a high intensity that causes ischemic bone symptoms, but not when exercise with a low ischemic leg symptoms.

“We have shown that you have to walk to provoke ischemic leg pain to reap the benefits,” said Dr. Mary McDermott, professor of medicine at Northwestern University Feinberg School of Medicine, said. “It will diminish over time, and most people will eventually be able to walk further without discomfort.”

The study was published in JAMA 6 April 2021.

McDermott’s previous research suggested that pain during exercise prevented many people with PAD from walking.

While the trial did not identify the biological changes leading to gait improvement, McDermott said previous research shows that intense exercise stimulates certain biological pathways that promote enhanced mitochondrial activity, the chemical energy source of the cell.

“Perhaps for people with PAD, exercise promotes the growth of new small blood vessels in their muscles,” McDermott said.

About 8.5 million people in the United States and about 250 million people worldwide have peripheral arterial disease (PAD). People with PAD have blockages in their veins that slow or stop the blood flow to their legs. As a result, they have pain and struggle to walk even short distances. It is similar to angina for people with symptomatic heart disease. There are few therapies to treat it.

The first month consisted of weekly personal visits with the coach. These sessions helped participants learn the difference between walking at high and low intensity, enabling them to use the technology used to monitor their exercise intensity at home, and helped them get started with their exercise activity. The program then consists of phone calls and remote control by a coach.

The distance monitoring aspect is important, McDermott said. Although supervised exercise is covered by Medicare and other insurance companies, most people with PAD do not participate in supervised exercise due to the burden of traveling to the medical center three times a week for participation.

For the study, 305 people with peripheral artery disease at four medical centers were randomized to high-intensity exercise, low-intensity exercise, or a control group that received phone calls that were not about exercise. Those randomized to a training intervention were asked to walk up to 50 minutes per session five days a week. Those with high intensity were asked to walk at a pace that was fast enough to cause ischemic bone symptoms during exercise. Those who were random to low intensity were asked to walk at a comfortable pace that did not cause ischemic bone symptoms.

The intensity was monitored remotely using an ActiGraph activity monitor worn by participants during exercise. These data were uploaded to the study website and viewed by study coaches. The six-minute walk, the treadmill test, and the patient-reported outcomes were measured at baseline and after the 12-month follow-up.

Patients who participated in high-intensity exercise significantly improved the distance they could walk in six minutes compared with the low-intensity group or the control group. The high-intensity exercise group also significantly improved the length of time they were able to walk at the end of the study, compared with each of the other two groups.

“Patients with PAD should be advised to exercise at a rate that causes ischemic bone symptoms to benefit,” McDermott said. “Exercise is the most effective non-invasive therapy to improve walking in people with PAD.”

The next step in the investigation is to determine the biological explanation for the finding that ischemia of the lower limbs appears to be necessary to benefit from walking exercise in people with PAD.