What is Peripheral Artery Disease (PAD)?
Peripheral artery disease (PAD) is an atherosclerotic condition causing stenosis, occlusion, or aneurysmal dilation of the aorta and its branch arteries (excluding coronary arteries), most commonly affecting the lower extremities and resulting in reduced blood flow that can manifest as claudication, limb-threatening ischemia, or remain asymptomatic. 1
Core Definition and Pathophysiology
PAD encompasses vascular diseases caused primarily by atherosclerosis and thromboembolic processes that alter the normal structure and function of the aorta, its visceral arterial branches, and lower extremity arteries. 1 The disease affects an estimated 8.5 million individuals in the United States and over 220 million people worldwide, with prevalence increasing due to population aging. 1, 2
Atherosclerosis remains the dominant pathological process, though PAD can result from various mechanisms including degenerative disorders affecting arterial wall integrity and thromboangiitis obliterans (Buerger's disease), particularly in young smokers. 3
Clinical Subsets and Presentations
The 2024 ACC/AHA guidelines establish four distinct clinical subsets: 1
- Asymptomatic PAD: No leg symptoms despite objectively proven arterial disease (affects up to 50% of patients) 3, 4
- Chronic symptomatic PAD: Characterized by intermittent claudication—reproducible muscle fatigue, cramping, aching, or pain consistently induced by walking and relieved within approximately 10 minutes of rest 1, 5
- Chronic limb-threatening ischemia (CLTI): Chronic (>2 weeks) ischemic rest pain, nonhealing wounds/ulcers, or gangrene with objectively proven arterial occlusive disease, representing extreme pain at rest and amputation risk 1
- Acute limb ischemia (ALI): Acute (≤2 weeks) limb hypoperfusion characterized by the "6 Ps"—pain, pallor, pulselessness, poikilothermia, paresthesias, and/or paralysis 1
Anatomic Distribution
PAD is classified by anatomic level: 1
- Aortoiliac: Infrarenal abdominal aorta, common iliac, external and internal iliac arteries
- Femoropopliteal: Common femoral, profunda femoris, superficial femoral, and popliteal arteries
- Infrapopliteal: Tibial-peroneal trunk, anterior/posterior tibial arteries, peroneal artery, and pedal vessels
Patients frequently have multilevel disease across multiple segments. 1
Epidemiology and Risk Factors
PAD prevalence is approximately 12% in the general adult population, rising to nearly 20% in adults over 70 years and 29% in those over 70 years or aged 50-69 years with diabetes or significant smoking history. 1, 4 Major risk factors include smoking, diabetes mellitus, hypertension, hyperlipidemia, family history, and postmenopausal status. 3, 6
Clinical Significance
Only 10% of PAD patients present with classic intermittent claudication symptoms. 5, 4 The majority have atypical leg symptoms (heaviness, discomfort) or remain asymptomatic, leading to significant underdiagnosis—over 70% of primary care providers in the PARTNERS study were unaware their patients had PAD. 1
PAD serves as a marker of systemic atherosclerosis and is associated with a 2- to 4-fold increased risk for cardiovascular events and all-cause mortality, classifying patients at very high cardiovascular risk. 4, 6 CLTI carries the worst prognosis for both limb and life among PAD subsets. 1
Pain Characteristics
Pain in PAD involves nociceptive, inflammatory, and neuropathic mechanisms and can present as intermittent claudication, atypical leg pain, ischemic rest pain, neuropathic pain, or phantom limb pain post-amputation. 1 This chronic pain results in severe disability and frequently co-presents with depression, anxiety, and opioid-related complications. 1
Important Clinical Pitfall
In patients with diabetic neuropathy, typical ischemic pain may be absent despite severe disease, and skin discoloration may be the only presenting sign in elderly patients with multiple comorbidities, leading to delayed recognition of critical ischemia. 7