Peripheral artery disease: An update – Harvard Health

What is peripheral artery disease?

PAD is usually caused by atherosclerosis, the same plaque-building process responsible for most coronary artery disease. Deposits containing cholesterol, fat, calcium, and other materials accumulate inside artery walls. As the passageway narrows, blood flow decreases. A leg muscle that receives enough oxygen while you are sitting may suddenly run short when you walk uphill, climb stairs, or hurry through an airport.

That is why PAD should not be viewed as merely a “leg circulation problem.” Plaque rarely respects property lines. A person with blocked arteries in the legs may also have atherosclerosis in arteries serving the heart, brain, kidneys, or other organs. Diagnosing PAD therefore creates an opportunity to protect the whole cardiovascular system, not just the calves and toes.

PAD symptoms are not always textbook-perfect

Intermittent claudication

The classic symptom is intermittent claudication: aching, tightness, burning, heaviness, weakness, or cramping that begins during physical activity and improves after several minutes of rest. Calf pain is common, although symptoms can also occur in the thighs, hips, or buttocks. The location often depends on where an artery is narrowed.

A useful clue is repeatability. If your calf starts hurting after roughly the same walking distance, settles when you stop, and returns when you resume, your leg may be following a vascular script rather than having a random bad day.

Subtle and atypical warning signs

Many people with PAD do not experience classic claudication. Some report tired legs, slower walking, poor balance, numbness, or vague discomfort. Others unconsciously reduce their activity until symptoms disappear, then conclude that nothing is wrong. According to the CDC, up to four in ten people with PAD have no leg pain.

Physical signs may include one foot feeling colder than the other, weak foot pulses, smooth or shiny skin, reduced leg hair, slow-growing toenails, skin color changes, or sores that heal poorly. Severe PAD may cause pain in the foot while resting, particularly at night. Some people find that hanging the affected foot over the side of the bed offers temporary relief because gravity assists blood flow.

Symptoms that require urgent care

Sudden severe leg pain, numbness, weakness, unusual paleness, cold skin, or loss of a pulse may indicate acute limb ischemia, a medical emergency caused by an abrupt loss of circulation. A nonhealing wound, spreading infection, blackened tissue, or persistent rest pain can indicate chronic limb-threatening ischemia. These are not “see how it looks next month” situations. Prompt vascular evaluation can help preserve tissue and, in some cases, the limb.

Who has the greatest risk?

Tobacco exposure is one of the most powerful modifiable risk factors for peripheral artery disease. Smoking injures artery walls, promotes inflammation and clotting, and accelerates plaque formation. Quitting remains one of the most valuable actions a person with PAD can take, even after decades of smoking.

Diabetes is another major risk factor because elevated blood sugar can damage both large arteries and tiny blood vessels. Diabetes may also reduce sensation in the feet, allowing blisters, cuts, or pressure injuries to worsen unnoticed. PAD plus diabetic neuropathy is an especially unfriendly partnership: one problem encourages wounds while the other makes those wounds harder to heal.

Additional risk factors include advancing age, high LDL cholesterol, high blood pressure, chronic kidney disease, obesity, physical inactivity, a family history of cardiovascular disease, and established disease in the coronary or carotid arteries. Social conditions, access to preventive care, geography, depression, and disparities affecting racial and ethnic groups can also influence diagnosis and outcomes.

How doctors diagnose peripheral artery disease

Medical history and physical examination

Evaluation begins with questions about walking distance, the location and timing of discomfort, tobacco use, diabetes, medication history, and previous cardiovascular events. A clinician may inspect the skin and feet, compare temperature and color between the legs, listen for abnormal blood-flow sounds, and check pulses in the groin, knees, ankles, and feet.

The ankle-brachial index

The ankle-brachial index, or ABI, is the cornerstone of initial PAD testing. It compares systolic blood pressure measured at the ankle with pressure measured in the arm. The test is noninvasive, generally painless, and often completed in minutes.

An ABI between approximately 1.00 and 1.40 is usually considered normal. A result of 0.90 or below supports a diagnosis of PAD. A value above 1.40 may mean the arteries are too stiff to compress, an issue seen more often in people with diabetes or chronic kidney disease. In that situation, a toe-brachial index may provide more useful information because toe arteries are less likely to be heavily calcified.

If resting results are normal or borderline despite convincing exercise-related symptoms, an exercise ABI may reveal a pressure drop after treadmill walking. Duplex ultrasound can show blood-flow patterns and locate narrowed segments. CT angiography, magnetic resonance angiography, or catheter angiography may be used when detailed anatomical planning is needed, particularly before a revascularization procedure.

The modern treatment plan: protect the person and the limb

Current care has two equally important goals. The first is to improve walking, wound healing, and day-to-day function. The second is to reduce cardiovascular events. Treating the calf while ignoring the heart would be like fixing a leaking faucet while the basement fills with water.

1. Stop tobacco exposure

Patients who smoke should be offered practical cessation support rather than a stern lecture followed by a door closing. Counseling, nicotine-replacement products, prescription medications, quitlines, and follow-up can be combined. Avoiding secondhand smoke and other tobacco products also matters.

2. Use structured walking as therapy

Regular walking is one of the most effective treatments for chronic symptomatic PAD. A typical program alternates walking with short rest periods. The patient walks until moderate leg discomfort develops, rests until it subsides, and repeats the cycle. Over time, muscles use oxygen more efficiently, walking mechanics improve, and circulation can adapt.

The important word is structured. “Try to walk more” is pleasant advice but not much of a prescription. Effective programs define frequency, duration, progression, and symptom targets. Supervised exercise therapy or a structured home- or community-based program supported by coaching and activity tracking can improve walking performance, function, and quality of life. Medicare covers qualifying supervised exercise therapy for symptomatic PAD, generally up to 36 sessions over 12 weeks under specified conditions.

3. Lower LDL cholesterol aggressively

PAD is considered a form of clinical atherosclerotic cardiovascular disease. High-intensity statin therapy is generally recommended, with the goal of reducing LDL cholesterol by at least 50%. If LDL remains elevated despite the maximum tolerated statin dose, medications such as ezetimibe or a PCSK9 inhibitor may be considered. The objective is not simply to improve a laboratory number; it is to reduce the likelihood of heart attack, stroke, and limb complications.

4. Control blood pressure and diabetes

Blood pressure treatment reduces overall cardiovascular risk. The 2024 multisociety guideline recommends a target below 130/80 mm Hg for many patients with PAD, although treatment must still be individualized.

For patients with type 2 diabetes, medication choices may provide benefits beyond glucose control. GLP-1 receptor agonists and SGLT2 inhibitors have cardiovascular advantages in appropriate patients. Good diabetes care also includes foot examinations, nutrition, kidney monitoring, eye care, and strategies to prevent dangerously low blood sugar.

5. Prevent harmful blood clots

Single antiplatelet therapy with aspirin or clopidogrel is generally recommended for symptomatic PAD to reduce major cardiovascular events. For selected patients with symptomatic PAD, including many who have undergone lower-extremity revascularization, low-dose rivaroxaban combined with low-dose aspirin can reduce cardiovascular and major limb events.

This combination also increases bleeding risk and is not appropriate for everyone. It should never be started by borrowing a relative’s tablets or improvising from an online checklist. Kidney function, bleeding history, other medications, age, and planned procedures all influence the decision. Full-dose anticoagulation is not routinely used solely for PAD unless another condition, such as atrial fibrillation, provides a separate indication.

6. Consider medication for claudication symptoms

Cilostazol may improve walking distance and leg symptoms in people with claudication. However, it should not be used in patients with congestive heart failure. Side effects and drug interactions should be reviewed before treatment. Pentoxifylline is no longer recommended as an effective claudication treatment in current U.S. guidance.

What the semaglutide research adds

A notable development is evidence involving semaglutide, a GLP-1 receptor agonist widely associated with diabetes and weight management. The 2025 STRIDE trial studied adults with type 2 diabetes and symptomatic PAD. Compared with placebo, semaglutide improved maximum walking distance, pain-free walking distance, PAD-related symptoms, and health-related quality of life over 52 weeks. Benefits were still detectable after treatment had been paused for several weeks.

The findings are intriguing because improvement was not strongly explained by weight loss alone. Semaglutide may influence inflammation, metabolism, blood-vessel function, or several pathways at once. Researchers are continuing to investigate why patients walked farther and whether similar benefits apply to people without diabetes.

This does not turn semaglutide into a magic circulation wand. It does not erase arterial plaque overnight, replace smoking cessation, eliminate the need for statins, or make structured exercise optional. It does broaden the conversation about selecting diabetes therapies that may support cardiovascular health and physical function at the same time. Treatment must be based on the patient’s medical history, safety considerations, insurance coverage, and current prescribing information.

When angioplasty, stenting, or bypass surgery is needed

Many people with intermittent claudication improve with medical treatment and structured exercise. Revascularization is considered when symptoms remain functionally limiting despite appropriate therapy or when circulation is too poor to support wound healing and tissue survival.

Endovascular treatment may involve inflating a balloon inside the narrowed artery, sometimes followed by placement of a stent or use of another specialized device. Open bypass surgery creates a new route around the blockage using a vein or synthetic graft. The best approach depends on the location and length of disease, available veins, surgical risk, expected durability, wound severity, and the patient’s goals.

Procedures should not be performed merely because an imaging scan looks dramatic. In asymptomatic PAD, revascularization is not recommended solely to prevent progression. In chronic limb-threatening ischemia, however, restoring blood flow is often essential to relieve pain, heal wounds, limit tissue loss, and preserve a functional limb.

Foot care is everyday preventive medicine

Reduced circulation makes small injuries more consequential, especially when diabetes or reduced sensation is present. Patients should inspect their feet daily, including the soles and spaces between the toes. A mirror or a willing family member can help with areas that are difficult to see.

Wash and dry the feet carefully, moisturize dry skin without leaving lotion between the toes, and wear properly fitting shoes and clean socks. Avoid walking barefoot. Do not cut corns, calluses, or ingrown nails with improvised tools. A blister, crack, color change, or sore that fails to improve should be evaluated promptly. When blood flow is poor, “tiny wound” and “tiny problem” are not always synonyms.

Practical experiences: what living with PAD often teaches

Note: The following observations are composite, experience-based lessons commonly reported in PAD care. They are not quotations from a single patient and should not replace individualized medical advice.

The first lesson: people often adapt before they seek help

A common pattern begins quietly. Someone stops taking evening walks because the neighborhood suddenly seems “too hilly.” Grocery trips become shorter. The lawn is divided into two-day projects. Because the person can still complete essential tasks, the change feels like aging rather than illness.

Keeping a simple walking diary can expose the pattern. Record where discomfort begins, how long it takes to settle, which leg is affected, and whether the distance changes. Objective notes are often more useful at an appointment than saying, “My legs act weird sometimes.”

The second lesson: exercise feels backward until it starts working

Walking into discomfort can sound irrational when walking caused the discomfort in the first place. Patients frequently worry that exercise is damaging the leg. Once a vascular professional confirms that a structured program is appropriate, the walk-rest-walk method becomes easier to understand. The aim is controlled, repeatable training, not a heroic march through unbearable pain.

Progress may appear in ordinary ways: reaching the mailbox without stopping, completing a supermarket aisle, keeping pace with a spouse, or standing through a grandchild’s soccer game. These gains may matter more than an impressive treadmill statistic.

The third lesson: medication adherence is invisible work

Statins, blood pressure medicines, antiplatelet drugs, and diabetes treatments usually do not create an immediate sensation of improved circulation. That makes them easy to underestimate. Patients may be tempted to stop a medicine because they “feel the same.” Yet much of PAD treatment is designed to prevent events that have not happenedand ideally never will.

A pill organizer, synchronized refills, written medication list, and clear explanation of each drug’s purpose can turn a confusing regimen into a manageable routine. Side effects should prompt a conversation, not a silent breakup with the prescription bottle.

The fourth lesson: the feet deserve a daily meeting

Daily foot inspection may initially feel excessive. Then a patient discovers a blister caused by a folded sock or a reddened area from a tight shoe before it becomes an ulcer. The ritual takes less than two minutes and can prevent weeks of wound care.

Caregivers can help without becoming the “foot police.” Good support sounds like, “Let’s check whether that spot is improving,” rather than, “I told you those shoes were terrible.” PAD management already contains enough stress; it does not need a courtroom drama before breakfast.

The fifth lesson: improvement is usually a team project

Effective care may involve a primary care clinician, cardiologist, vascular specialist, exercise professional, diabetes team, pharmacist, podiatrist, wound-care clinician, dietitian, and smoking-cessation counselor. The patient remains the central member of that team.

Bringing an updated medication list, knowing recent blood pressure and cholesterol numbers, asking about supervised exercise, and reporting new wounds early can change the course of care. The most useful question is often not, “Can you fix this artery?” but, “What combination of steps will protect my mobility, heart, brain, and feet?”

Conclusion

Peripheral artery disease is common, frequently overlooked, and far more important than its nickname of “poor circulation” suggests. Recurring leg discomfort with walking, cold feet, weak pulses, skin changes, or slow-healing wounds deserve medical attention, particularly in people who smoke or have diabetes, high cholesterol, hypertension, kidney disease, or established cardiovascular disease.

The encouraging news is that PAD is treatable. Tobacco cessation, structured exercise, cholesterol reduction, blood pressure control, diabetes care, antithrombotic therapy, and meticulous foot protection can improve both longevity and independence. New research involving semaglutide may add another useful option for selected patients with diabetes, while modern endovascular and surgical treatments remain available when medical care alone is not enough.

The best PAD plan rarely depends on one spectacular intervention. It is usually built from consistent, unglamorous actions performed well: taking medication, checking the feet, walking on schedule, attending follow-up visits, and reporting changes early. Cardiovascular medicine may be technologically advanced, but sometimes progress still begins with a pair of comfortable shoes and a carefully planned walk.