Peripheral Arterial Disease

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DESCRIPTION

Peripheral arterial disease (PAD) represents an atherosclerotic occlusive disease of the peripheral arteries, most commonly in the lower extremities.

  • It is an underdiagnosed form of cardiovascular disease strongly associated with health care disparities, an increased risk of amputation, myocardial infarction (MI), stroke, death, and significantly impaired functionality and quality of life.
  • Definition: (generally) lower extremity atherosclerotic arterial obstruction that occurs from the aortoiliac segments to the pedal arteries (1).
  • 4 clinical presentations:
    • Asymptomatic PAD
    • Chronic symptomatic PAD (Intermittent claudication [IC])
    • Chronic (critical) limb-threatening ischemia (CLTI)
    • Acute limb ischemia (ALI)

EPIDEMIOLOGY

  • Affects >1:20 Americans aged >50 years, >230 million people globally
  • Prevalence is equivalent between sexes or slightly higher in women (3.5%) than in men (2.5%) (1).

Prevalence

  • Uncommon in those <40 years old (4.3%), prevalence rises rapidly with ages >70 years (14.3%) and >80 years (20%)
  • Black Americans: disproportionally affected (1):
    • PAD rates are twice as high as other ethnicities at any given age
    • More advanced and severe disease (gangrene, foot sepsis) at presentation
    • 77% higher risk of major amputations
    • Less likely to be prescribed statin or antiplatelet therapy
  • Black, Hispanic, and Native Americans with PAD are less likely to undergo revascularization procedures; have 10–30% higher complication rates than white PAD patients.

ETIOLOGY AND PATHOPHYSIOLOGY

PAD begins as a complex inflammatory cascade within the intimal layer of a large lower extremity artery wall, leading to progressive lipoprotein accumulation, atherosclerosis, and eventual arterial diameter narrowing.

  • Compromised blood flow distal to arterial occlusion is unable to match muscle oxygen demand with exercise despite collateral vessel formation; producing symptoms of ischemia (see below)
  • On average, Black Americans with PAD have increased markers of vascular aging (increased arterial stiffness, oxidative stress, lower skeletal mitochondrial function) compared to white Americans with PAD.

Genetics

Several of the risk factors for PAD (as noted below) are heritable, and genome-wide association studies to isolate PAD-specific single nucleotide polymorphisms are being explored.

  • A positive family history of PAD may double the odds of PAD in family members.
  • Factor V Leiden gene mutation (most common inherited cause of venous system blood clots) may be associated with development of PAD.

RISK FACTORS

  • Conventional: smoking, diabetes, hypertension (HTN), sedentary lifestyle, increased levels of total cholesterol, LDL, lipoprotein(a) (Lp[a]) and apolipoprotein B (apoB), dyslipidemia, hypertriglyceridemia, chronic kidney disease (CKD), obesity (1)
  • Nonconventional: lead and cadmium exposure, air pollution, depression (1)
  • Risk amplifiers: race, ethnicity, geography, structural racism, implicit bias, and age (1)

GENERAL PREVENTION

Smoking abstinence or cessation, regular physical activity, heart-healthy nutrition, healthy weight, evidence-based control of blood pressure, blood sugar and lipids, preventive foot hygiene, regular foot inspections (self and professional)

COMMONLY ASSOCIATED CONDITIONS

Coronary artery disease, stroke, MI, carotid artery disease, transient ischemic attack (TIA), atrial fibrillation, congestive heart failure, HTN, diabetes, vascular dementia, cognitive decline, sleep apnea

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