Risk Factors for Peripheral Artery Disease
The major risk factors for peripheral artery disease are smoking (the most powerful risk factor for PAD specifically), diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and older age, with smoking being 2-3 times more likely to cause PAD than coronary disease. 1, 2
Traditional Atherosclerotic Risk Factors
Smoking - The Dominant Risk Factor
- Smoking is exceptionally powerful for PAD, increasing risk 2-6 fold for disease development and 3-10 fold for intermittent claudication 2
- More than 80% of PAD patients are current or former smokers 2
- Smoking is 2-3 times more likely to cause lower extremity PAD than coronary artery disease 2
- Risk increases in a dose-dependent manner with both number of cigarettes per day and years smoked 2
- The 5-year mortality rate with active smoking and chronic symptomatic PAD is 40-50% 1
Diabetes Mellitus
- Increases PAD risk 2-4 fold 2
- Present in 12-20% of persons with PAD 2
- In the Framingham Heart Study, diabetes increased intermittent claudication risk by 3.5-fold in men and 8.6-fold in women 2
- Risk is proportional to both severity and duration of diabetes 2
- Diabetic patients with PAD are 7-15 times more likely to undergo major amputation than non-diabetics 2
- Among patients with diabetes: up to 20% of those >40 years, 30% >50 years, and 70% >70 years have PAD 1
Hypertension
- Most prevalent risk factor for PAD 1
- Associated with increased relative risk of 2.8 for PAD in the Limburg PAOD study 3
- Low ankle-brachial index (<0.90) associated with both increased systolic and diastolic blood pressure 3
- Uncontrolled hypertension increases risk of major adverse cardiovascular events, chronic kidney disease, and polyvascular disease 1
Dyslipidemia
- High total cholesterol and low HDL cholesterol independently increase PAD risk 3
- In the US Physicians Health Study, the ratio of total/HDL cholesterol was the lipid measure most strongly related to disease 3
- Elevated LDL cholesterol is a well-established risk factor 2
Additional Major Risk Factors
Chronic Kidney Disease (CKD)
- Up to 25% of patients with CKD have PAD 1
- CKD increases risk of composite cardiovascular death, MI, and ischemic stroke (adjusted HR: 1.45) 1
- Patients with CKD have 1.8-fold higher risk of coronary artery disease and 2.5-fold increased risk of MI 1
- Patients with CKD and PAD have higher rates of amputation than those with CKD alone 1
Age
- Prevalence increases dramatically with age 4, 5
- Approximately 10-20% of community-dwelling individuals aged ≥65 years have PAD 4
- Prevalence rises from 1.9% in those <50 years to 2.7% in those >70 years for subclavian artery stenosis 3
PAD-Related Risk Amplifiers
These factors significantly increase risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE):
Polyvascular Disease
- Defined as atherosclerotic disease involving ≥2 vascular beds (coronary, peripheral, or cerebrovascular) 1
- Common among PAD patients and recently emerged as important risk amplifier 1
- Patients have compounded cardiovascular risk including myocardial infarction and stroke 1
- The combination of polyvascular disease and diabetes is synergistic in markedly amplifying risk 1
Concomitant Microvascular Disease
- Retinopathy, neuropathy, and nephropathy associated with increased risk of major adverse limb events 1
Depression
- Prevalent comorbidity in PAD patients 1
- Associated with higher rates of MACE and MALE outcomes 1
- Linked to increased length of stay and readmission after revascularization 1
- Can be assessed using Geriatric Depression Score (GDS) or Patient Health Questionnaire (PHQ)-9 1
Emerging and Other Risk Factors
- Hyperhomocysteinemia 6, 2
- Genetic factors (possible association) 4
- C-reactive protein levels (higher in those who subsequently develop PAD) 2
- Soluble intercellular adhesion molecule-1 (independently associated with future PAD development) 2
Demographic Considerations
- No significant gender differences in overall PAD prevalence in general population 4
- However, in high-income countries, prevalence slightly higher in women than men up to age 75 years 5
- Race, ethnicity, and social determinants of health (racism, socioeconomic status) associated with greater risk of MACE and MALE 1
Clinical Significance
The presence of three or more risk factors confers a 10-fold increase in PAD risk 7. Approximately 75% of the estimated 8-12 million Americans with PAD are asymptomatic 4, making risk factor assessment critical for early detection. Over a 5-year period, 25-35% of persons with PAD will suffer myocardial infarction or stroke, and an additional 25% will die, usually from cardiovascular causes 4.