How common is Peripheral Artery Disease (PAD) to present unilaterally in an older patient with Critical Limb Ischemia (CLI) and comorbidities such as smoking, diabetes, hypertension, and hyperlipidemia, who is facing a likely lower limb amputation?

Unilateral PAD Presentation in Critical Limb Ischemia

While PAD is fundamentally a systemic atherosclerotic disease affecting multiple vascular beds bilaterally, CLI can and frequently does present with asymmetric or predominantly unilateral symptoms, particularly when acute thrombotic events or focal disease progression occurs in one limb. 1, 2

Understanding the Bilateral Nature of PAD

PAD is inherently a bilateral disease process because atherosclerosis affects the arterial system diffusely. However, the clinical manifestations—particularly CLI—often appear asymmetrically or in only one limb at presentation. 1

Key points about disease distribution:

• Atherosclerotic disease is typically bilateral even when symptoms appear unilateral, as PAD represents systemic atherosclerosis affecting coronary, cerebrovascular, and peripheral arterial beds simultaneously 1

• 60-80% of patients with lower extremity PAD have significant coronary artery disease, and approximately 12-25% have hemodynamically significant carotid stenosis, underscoring the systemic nature of atherosclerosis 1

Why CLI Often Presents Unilaterally

Despite bilateral disease, CLI frequently manifests in one limb first due to several mechanisms:

Thrombotic occlusion is the primary culprit:

• Chronic luminal thrombi with or without significant underlying atherosclerosis account for approximately 73% of severe stenoses in CLI patients 2

• Thrombotic luminal occlusion associated with insignificant atherosclerosis is commonly observed in CLI, particularly in infrapopliteal arteries (OR: 16.7 for chronic thrombi in arteries with insignificant atherosclerosis) 2

• Atherothromboembolic disease can cause acute-on-chronic deterioration in one limb, triggered by plaque rupture, in situ thrombosis, or embolization from proximal aneurysms 1, 2

Anatomic and pathologic factors:

• Infrapopliteal arteries show different pathology than femoral-popliteal segments, with more frequent thrombotic occlusion despite less severe atherosclerosis (OR: 2.14 for chronic thrombi in infrapopliteal vs. femoral-popliteal arteries) 2

• Focal disease progression, local plaque rupture, and inflammatory factors may precipitate CLI in one limb while the contralateral limb remains compensated 1

Precipitating local factors:

• Trauma, infection, or skin ulceration can trigger the transition from compensated PAD to CLI in one limb 1

• Diabetes, severe renal failure, and smoking increase microvascular dysfunction and reduce collateral flow capacity, potentially affecting limbs asymmetrically 1, 3

Clinical Implications for Your Patient

For your patient facing amputation:

• The contralateral limb is at significant risk and requires immediate comprehensive vascular assessment with ABI measurement (or toe-brachial index if vessels are non-compressible due to diabetes) 1, 4

• Approximately 11-20% of patients with known PAD develop CLI, and once one limb is affected, the risk to the contralateral limb increases substantially 1

• Patients with diabetes have a 7-15 fold increased risk of major amputation compared to non-diabetics with PAD, making bilateral surveillance critical 1, 4

Critical Assessment Steps

Evaluate the contralateral limb immediately:

• Measure ABI bilaterally; values ≤0.50 indicate severe PAD, and absolute ankle pressure ≤50 mmHg or toe pressure ≤30 mmHg suggest high amputation risk without revascularization 1

• Perform complete pulse examination (femoral, popliteal, dorsalis pedis, posterior tibial) and document numerically (0=absent, 1=diminished, 2=normal, 3=bounding) 1

• Inspect both feet with shoes and socks removed, looking for trophic changes, hair loss, skin integrity, ulcerations, and color changes 1, 4

Screen for atheroembolism sources:

• Patients presenting with CLI should be evaluated for proximal aneurysmal disease (abdominal aortic, popliteal, or common femoral aneurysms) that could cause future embolic events to either limb 1

Common Pitfalls to Avoid

Never assume the contralateral limb is unaffected simply because it is currently asymptomatic:

• 40% of PAD patients are asymptomatic yet at high cardiovascular risk, and neuropathy in diabetic patients can mask ischemic symptoms entirely 4, 5

• Medial calcification was present in 71% of arteries in CLI patients, which can falsely elevate ABI readings (>1.30), necessitating toe-brachial index or pulse volume recording instead 2, 4

Do not delay vascular imaging of the symptomatic limb:

• Patients with CLI require prompt vascular specialist evaluation within 24 hours to assess revascularization options before irreversible tissue loss occurs 4

• The distinction between acute and chronic CLI affects urgency; relatively rapid symptom progression suggests semi-urgent revascularization is needed 1

Recognize that CLI represents end-stage disease with poor prognosis:

• 1-year mortality in CLI patients is approximately 25%, rising to 45% in those undergoing amputation 1

• The 5-year mortality rate for PAD patients is 50% due to coexistent coronary and cerebrovascular disease, emphasizing the need for aggressive cardiovascular risk factor management 4