Peripheral Artery Disease (PAD) Research

• NHLBI’s Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) study showed that a supervised exercise program was more effective at improving treadmill walking capacity than angioplasty with or without stenting of an occluded blood vessel, or using or medicines alone. The results of CLEVER and other research studies including the Improving Functioning in Peripheral Arterial Disease trial, led the Centers for Medicare & Medicaid Services to reimburse supervised exercise training (SET) programs for symptomatic PAD.
• The Low InTensity Exercise Intervention in PAD (LITE) trial demonstrated that a home-based coaching program incorporating high-intensity but not low-intensity walking exercise improved walking performance in people with symptomatic PAD. This type of intervention does not require travel to a training center and is likely to be more accessible than traditional in-center SET programs.
• Researchers found that African Americans taking part in the Jackson Heart Study and the Atherosclerosis Risk in Communities Study had an increased risk of PAD if they smoked. Smoking was associated with PAD in a dose-dependent manner: People who smoked twice as much or for twice as long as others were twice as likely to develop PAD.

Our Division of Cardiovascular Sciences, which includes the Vascular Biology and Hypertension Branch, oversees much of the research on PAD we fund.

Current research on PAD treatments

PAD is  a challenging condition to treat because the recommended treatment — regular walking — can be painful, difficult to undertake due to other co-existing health conditions such as arthritis, and/or not practicable in the home or community environment. NIH-funded research is working on ways to increase walking endurance and circulation in the legs by using mechanical devices.

• Conventional ultrasound therapy for PAD involves using sound waves to increase blood flow in the legs. Until now, this therapy has been available only in clinical settings. NHLBI-funded researchers have developed an ultrasound device for people with PAD to wear when resting or sleeping. The device is like a sleeve worn over the legs and has its own portable power generator. Researchers hope to find out if this therapy improves blood flow in the legs.
• Participants in the INTERCEDE (INTERmittent pneumatic ComprEssion for Disability rEversal in PAD) trial wear inflatable cuffs wrapped around their feet, ankles, and calves for 2 hours every day. Every 20 seconds, the cuffs rapidly inflate and then rapidly deflate. This increases blood flow through the legs. Researchers will look at whether the device improves walking performance, how it changes leg muscles and blood flow, and whether those changes last.
• Small implantable sensors are being developed to monitor tissue oxygen levels in limbs of PAD patients during and after procedures done to restore blood flow.

Find more NHLBI-funded studies on PAD treatments at the NIH RePORTER.

Eliminating health disparities in PAD

Health disparities exist whenever a person’s membership in a racial, ethnic, age, or other type of group makes them more likely to get or develop a disease or less likely to be diagnosed or treated for a disease. Researchers have found, for example, that African American smokers are three times more likely to develop PAD than white smokers. NHLBI-funded research is working to determine what health disparities exist, what causes them, and how to address them. One fundamental way NHLBI will achieve these goals is to ensure diversity in enrollment in all PAD research studies that involve people.

• The NHLBI is funding PASOS (Peripheral Artery Disease Study of SOL, an ancillary study of the Hispanic Community Health Study/Study of Latinos). As part of the study, researchers screen more than 6,000 participants age 45 and older for early signs of PAD, including reduced blood flow in the legs. They also use fitness trackers to measure activity levels. Participants with borderline poor circulation will be followed more closely to see what factors predict who will develop PAD.
• The Variant Determinants of African American Limb Pathology in Peripheral Arterial Disease study hopes to learn more about how variants of a gene, BAG3, known to exist in both African Americans with critical limb ischemia (CLI) and with cardiomyopathy, may disrupt normal reparative links between muscle damaged by lack of oxygen and new blood vessel growth. If the hypothesis is correct, this gene may become a therapeutic target. Findings may help explain why African Americans with PAD disproportionately suffer from CLI.

Find more NHLBI-funded studies on health disparities and PAD at the NIH RePORTER.

Current research to better understand PAD

NHLBI-funded research has contributed to the understanding of the basic biology behind PAD. But there is still more to learn. This basic knowledge is what often help scientists develop future treatments.

• A large NHLBI-funded multisite clinical trial, BEST-CLI, will compare effectiveness of two standard treatment strategies for CLI treatment: Endovascular and open surgical bypass revascularization. Extensive data on clinical course, adverse events, and clinical outcomes including amputation, major reintervention, and death will be collected over a period of 2 years.
• Hematopoietic stem cells and progenitor cells are found in bone marrow and circulating blood and develop into other cells including blood cells. Researchers want to know whether giving people with PAD a protein that stimulates the release of stem cells from the bone marrow will promote the growth of blood vessels in the legs, improve circulation, and increase walking endurance.
• Sometimes, to better understand a disease, researchers build computer models based on real-life experiments they have run. These models allow them to change variables and see what the outcomes of those changes might be. NHLBI-funded researchers are doing just that to study PAD. Their state-of-the-art computer model will represent the way new blood vessels form, grow, and provide oxygen-carrying blood to the legs and feet. Researchers hope that this work will provide a better understanding of PAD and help suggest new treatments.
• Researchers believe they have worked out the details of a cellular pathway that explain the lack of circulation and oxygen in the lower extremities of patients with PAD. They now want to test their hypothesis by giving people with PAD a protein that promotes the growth of blood vessels by blocking another protein that inhibits vessel growth. The researchers hope this will improve circulation in people with PAD.

Find more NHLBI-funded studies on understanding PAD at the NIH RePORTER. 

NHLBI in the Press

Learn about research that confirms the safety of drug-coated stents and other devices used to open up blocked arteries in the legs of patients with PAD.

Our Division of Intramural Research, which includes investigators from the Translational Vascular Medicine Branch and its Experimental Atherosclerosis Laboratory, performs research on PAD.

• Researchers in the NHLBI-funded Multi-Ethnic Study of Atherosclerosis (MESA) followed a group of study participants for 10 years and found that nearly 5% of them developed PAD. However, participants who scored higher on the American Heart Association’s Life’s Simple 7 checklist for maximizing heart health were less likely to have PAD; their risk decreased about 17% for each of the Life’s Simple 7 criteria they met.
  
  Learn more about this study: Life’s Simple 7 and Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis.
• NHLBI’s Vascular Interventions/Innovations and Therapeutic Advances (VITA) Program studies and develops promising tests and treatments for blood vessel diseases, including PAD, and vascular access for hemodialysis. VITA has developed a new approach for treating people who have serious complications from PAD. One problem with angioplasty (a common treatment for PAD to open narrowed or blocked arteries) is the risk that the blood vessels will scar and re-narrow. A VITA project developed bioengineered tubes that one day could be used instead of a person’s own blood vessels or donor vessels for bypass revascularization . They are unique because the body’s immune system will not reject them as foreign.
  
  Learn more about the VITA program: Next-generation replacement blood vessels target kidney and heart disease.