What is arteriopathy, its management, and treatment options in adults with risk factors such as hypertension, diabetes, or a history of smoking?

What is Arteriopathy?

Arteriopathy is a disease of the arteries characterized by structural and functional abnormalities of the arterial wall, most commonly caused by atherosclerosis, but also including non-atherosclerotic conditions such as inflammatory vasculitis, fibromuscular dysplasia, arterial dissection, and inherited collagen vascular disorders. 1, 2

Pathophysiology and Types

Atherosclerotic Arteriopathy (Most Common)

• Atherosclerosis is the predominant cause, involving plaque formation in arterial walls that leads to stenosis, occlusion, thromboembolism, and reduced perfusion to affected organs and limbs 1, 3

• The disease manifests through multiple mechanisms: embolism of thrombus formed on atherosclerotic plaque, atheroembolism, thrombotic occlusion from plaque rupture, and reduced perfusion from stenotic lesions 1

• Atherosclerotic arteriopathy affects multiple vascular beds simultaneously, including carotid arteries (extracranial cerebrovascular disease), peripheral arteries (lower extremity PAD), renal arteries, and mesenteric vessels 1

Non-Atherosclerotic Arteriopathies

• Inflammatory vasculitis includes conditions like Takayasu's arteritis, giant cell arteritis, Behçet's disease, and Buerger disease (particularly in young smokers) 3, 2

• Fibromuscular dysplasia primarily affects renal and carotid arteries, causing arterial stenosis without atherosclerosis 3, 2

• Inherited collagen vascular disorders such as Marfan syndrome, Ehlers-Danlos Type IV, and pseudoxanthoma elasticum cause arterial wall weakness and aneurysmal disease 2

• Dilatative arteriopathy (dolichoectasia) involves marked elongation, widening, and tortuosity of arteries with degeneration of the internal elastic lamina and smooth muscle atrophy, most commonly affecting vertebrobasilar arteries 4

• Radiation-induced arteriopathy can cause carotid stenosis and other vascular complications 1

Major Risk Factors

Smoking

• Smoking is the most powerful modifiable risk factor, increasing arteriopathy risk by 2-6 fold and affecting more than 80% of PAD patients 5, 3

• Smoking is 2-3 times more likely to cause peripheral arterial disease than coronary artery disease 5, 3

• Current smokers present with symptomatic disease at significantly younger ages and have higher rates of amputation and postoperative complications 6, 7

• Smoking progression is associated with a 50% increase in atherosclerosis progression compared to never smokers, with effects being cumulative and potentially irreversible 8

Diabetes Mellitus

• Diabetes increases arteriopathy risk by 2-4 fold, with claudication risk increased 3.5-fold in men and 8.6-fold in women 5, 3

• Diabetic patients with PAD are 7-15 times more likely to require amputation than non-diabetics 5, 3

• Diabetes causes preferential occlusion of large calf arteries (peroneal and posterior tibial), and patients more frequently present with gangrene or ulceration (>70%) rather than claudication 7

• The impact of smoking on atherosclerosis progression is greater in patients with diabetes 8

Hypertension

• Hypertension is strongly associated with carotid atherosclerosis and peripheral arterial disease in multiple epidemiological studies including ARIC, Cardiovascular Health Study, and Framingham 1

• Blood pressure lowering reduces stroke risk by 28% in patients with cerebral ischemia, even in those without baseline hypertension 1

• Hypertension is a major risk factor for peripheral arterial disease alongside diabetes and smoking 1

Other Risk Factors

• Hypercholesterolemia increases carotid stenosis risk by approximately 1.1 for every 10-mg/dL increase in total cholesterol 1

• Age, with risk increasing substantially after age 50-70 years 1, 3

• Hyperhomocysteinemia is an independent risk factor 1, 3

Clinical Manifestations by Vascular Territory

Peripheral Arterial Disease (Lower Extremity)

• Classic intermittent claudication: exertional leg muscle discomfort that consistently resolves with rest and limits exercise at reproducible distances 1

• Critical limb ischemia: chronic ischemic rest pain, non-healing ulcers, or gangrene representing severe perfusion decrease threatening limb viability 1

• Acute limb ischemia: sudden decrease in perfusion with the "five Ps" (pain, pulselessness, pallor, paresthesias, paralysis) 1

• Trophic skin changes: thin, shiny, atrophic skin; distal hair loss; hypertrophic nails; color changes (pallor with elevation, rubor with dependency); cool extremities 3

• Approximately 40% of PAD patients have no leg symptoms, making screening of high-risk patients essential 3

Extracranial Carotid and Vertebral Disease

• Transient ischemic attacks (TIA) with stroke risk as high as 13% in first 90 days and 30% within 5 years 1

• Transient monocular blindness (amaurosis fugax) from temporary reduction of blood flow to the eye 1

• Carotid bruit doubles the risk of myocardial infarction and cardiovascular death 1

Renal Arteriopathy

• Renovascular hypertension from renal artery stenosis, particularly in patients with uncontrolled blood pressure and diffuse atherosclerosis 1

• Progressive renal dysfunction and renal atrophy associated with lesion severity 1

Diagnostic Approach

Physical Examination Findings

• Pulse assessment at femoral, popliteal, dorsalis pedis, and posterior tibial sites 1, 3

• Blood pressure measurement in both arms with notation of inter-arm differences 1

• Auscultation for bruits in carotid, supraclavicular, abdominal, and femoral regions 1

• Inspection of feet for color, temperature, skin integrity, ulcerations, and trophic changes 1, 3

• Assessment for edema patterns (pitting edema with hyperpigmentation suggests venous insufficiency) 3

Objective Testing

• Ankle-brachial index (ABI) is the most cost-effective screening tool, with values <0.90 indicating PAD 1, 5, 3

• Critical pitfall: arterial calcification in diabetic patients falsely elevates ABI (>1.30), requiring toe-brachial index or pulse volume recording instead 1, 3

• Exercise ABI testing when resting ABI is normal but symptoms suggest PAD 3

• Duplex ultrasound for carotid stenosis assessment, though quality varies between institutions 1

• CTA or MRA for anatomic definition, though some methods may overestimate stenosis severity 1

• Catheter-based angiography to resolve discordance between noninvasive imaging findings 1

Screening Recommendations

Screen for PAD in the following populations 1, 3:

• Age <50 years with diabetes and one other atherosclerosis risk factor
• Age 50-69 years with history of smoking or diabetes
• Age ≥70 years (all patients)
• Leg symptoms with exertion or ischemic rest pain
• Abnormal lower extremity pulse examination
• Known atherosclerotic coronary, carotid, or renal arterial disease

Management and Treatment

Risk Factor Modification (Foundation of All Treatment)

• Smoking cessation is the single most critical intervention, as it may be the most important factor in whether PAD progresses 1, 6

• Statin therapy to reduce LDL cholesterol to <100 mg/dL (optimal <70 mg/dL) reduces cardiovascular events and stroke risk 1, 6

• High-dose atorvastatin (80 mg daily) reduced absolute stroke risk by 2.2% at 5 years in patients with recent stroke or TIA 1

• Antihypertensive therapy reduces stroke and cardiovascular risk, with ACE inhibitors or ARBs preferred in PAD patients 1, 6

• Combination of perindopril and indapamide reduced recurrent ischemic events by 28% in stroke patients 1

• Aggressive diabetes management, though intensive glucose control alone (HbA1c <6.0-6.5%) did not reduce stroke risk in ACCORD and ADVANCE trials 1

• Target body mass index ≤25 kg/m² through Mediterranean diet pattern 6

Antiplatelet Therapy

• Aspirin or clopidogrel is indicated to reduce risk of myocardial infarction, stroke, and cardiovascular death in all PAD patients 6

Exercise Therapy

• Supervised exercise training is first-line therapy for intermittent claudication: at least 3 sessions per week, 30-60 minutes per session, for minimum 12 weeks 1, 6

• Structured walking programs increase pain-free and maximum walking distances 1

Pharmacotherapy for Claudication

• Antihypertensive drugs are ineffective in relieving PAD symptoms, and vasodilators (ACE inhibitors, calcium channel blockers, alpha-blockers) do not improve walking distance 1

• Beta-blockers can be used safely in PAD patients despite theoretical concerns, as recent studies show little effect on walking distance or calf blood flow, and they are beneficial for coexisting CAD or heart failure 1

Revascularization Indications

• Lifestyle-limiting claudication inadequately responsive to optimal medical therapy and supervised exercise 6

• Critical limb-threatening ischemia (CLTI) whenever feasible for limb salvage 6

• Endovascular-first strategy recommended for: short (<5 cm) aorto-iliac lesions and short (<25 cm) femoro-popliteal lesions 6

• For carotid disease, CEA within first 2 weeks after TIA/stroke reduces stroke risk, but benefit diminishes with time 1

Critical Limb-Threatening Ischemia Management

• Immediate vascular specialist consultation required for diagnostic testing strategy and therapeutic intervention planning 1

• Systemic antibiotics if skin ulceration and limb infection present 1

• Define limb arterial anatomy through noninvasive and angiographic imaging 1

• Revascularization via thrombolytic, endovascular, or surgical therapies based on: limb viability assessment, duration of ischemia, arterial anatomy, and patient comorbidities 1

Antihypertensive Drug Selection in Specific Contexts

• ACE inhibitors produce most consistent LV mass reduction in hypertensive patients with left ventricular hypertrophy 1

• Losartan-based regimen reduced LVH more than atenolol despite equivalent blood pressure lowering in the LIFE study 1

• Calcium channel blockers can be used for Raynaud's phenomenon in PAD patients 1

• No selective outcome benefit demonstrated for any individual antihypertensive class in PAD patients, so choices should be based on compelling indications 1

Critical Clinical Pitfalls

• Do not wait for symptoms to screen high-risk patients, as two-thirds of those with lower extremity disease are asymptomatic 3

• Neuropathy in diabetic patients masks ischemic pain, increasing risk of foot ulceration and limb-threatening complications 5, 3

• PAD patients have markedly increased risk for MI, stroke, and death due to coexistent coronary and cerebrovascular disease, with cardiovascular ischemic events more frequent than limb ischemic events 1, 5, 3

• All PAD patients require aggressive cardiovascular risk modification regardless of symptom severity 3, 6

• In symptomatic patients with severe carotid stenosis, the benefit versus harm of aggressive blood pressure lowering is unknown due to potential reduction in cerebral perfusion 1

• Renovascular hypertension should be strongly considered in PAD patients with uncontrolled blood pressure, especially if ACE inhibitor or ARB treatment is being considered 1