Peripheral arterial disease risk factors

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Differentiating Peripheral arterial disease from other Diseases

Epidemiology and Demographics

Risk Factors


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AHA/ACC Guidelines on Management of Lower Extremity PAD

Guidelines for Clinical Assessment of Lower Extremity PAD

Guidelines for Diagnostic Testing for suspected PAD

Guidelines for Screening for Atherosclerotic Disease in Other Vascular Beds in patients with Lower Extremity PAD

Guidelines for Medical Therapy for Lower Extremity PAD

Guidelines for Structured Exercise Therapy for Lower Extremity PAD

Guidelines for Minimizing Tissue Loss in Lower Extremity PAD

Guidelines for Revascularization of Claudication in Lower Extremity PAD

Guidelines for Management of CLI in Lower Extremity PAD

Guidelines for Management of Acute Limb Ischemial in Lower Extremity PAD

Guidelines for Longitudinal Follow-up for Lower Extremity PAD

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Rim Halaby


The risk factors associated with peripheral artery disease are similar to those associated with coronary artery disease. They can be classified as traditional and non traditional. Another way to classify the risk factors is depending on their level of risk: high risk factors (tobacco and diabetes), moderate risk factors (hypertension and hyperhomocysteinemia) and low risk factors (hypercholesterolemia). Some risk factors are modifiable, like hypertension, whereas others are not.

Risk Factors

Traditional Risk Factors

Advanced Age

  • The prevalence of PAD increases with age.
  • The risk for lower-extremity peripheral arterial disease varies with age depending on other co-existing risk factors:
  • Younger patients with PAD tend to have poorer overall long-term outcomes, as well as a higher number of failed bypass surgeries leading to amputation, compared with their older counterparts.[1]

Cigarette Smoking

  • Cigarette smoking is the single most modifiable risk factor for the development of PAD; in fact, smoking increases the risk of PAD 4-fold and accelerates the onset of PAD symptoms by nearly a decade.
    • The association between smoking and PAD is about twice as strong as that between smoking and coronary artery disease.
    • An apparent dose-response relationship exists between the pack-year history and PAD risk.
  • Compared with their nonsmoking counterparts, smokers with PAD have poorer survival rates and are more likely to progress to critical limb ischemia, and twice as likely to progress to amputation, and also have reduced arterial bypass graft patency rates.
  • Individuals who are able to stop smoking are less likely to develop rest pain and have improved survival.[1]

Diabetes Mellitus

  • Diabetes mellitus confers a 1.5-fold to 4-fold increase in the risk of developing symptomatic or asymptomatic PAD and is associated with an increased risk of cardiovascular events and early mortality among individuals with PAD.
    • Diabetes is a stronger risk factor for PAD in women than in men.
    • The prevalence of PAD is higher in African Americans and Hispanics with diabetes than in non-Hispanic whites with diabetes.
  • In patients with diabetes, the prevalence and extent of PAD also appears to correlate with the age of the individual and the duration and severity of his or her diabetes.
    • There is a 28% increase of PAD for every percentage-point increase in hemoglobin A1c.
  • PAD prevalence is also increased in individuals with impaired glucose tolerance.
The Presentation of PAD in Patients with Diabetes Mellitus
  • Late, progressive and more severe presentation as a result initial asymptomatic nature of PAD in diabetics
  • Occlusive disease in the tibial arteries
  • Impaired wound healing due to microangiopathy and neuropathy
  • Higher risk for ischemic ulceration and gangrene.[1]
Additional Risk Factors Usually Present in Patients with Diabetes Mellitus
  • Abnormalities in vascular smooth muscle cells
  • Endothelial cell dysfunction
  • Elevated blood pressure
  • Impaired fibrinolytic function
  • Increased levels of triglycerides, cholesterol, and other blood lipids
  • Increased vascular inflammation
  • Increased in platelet aggregation
  • Tobacco use


  • Elevations in total cholesterol, LDL cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides are all independent risk factors for PAD.
    • There is 10% increased risk of developing PAD for every 10-mg/dL rise in total cholesterol.
  • Elevations in high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I appear to be protective
  • The form of dyslipidemia seen most frequently in patients with PAD is the combination of a reduced HDL cholesterol level and an elevated triglyceride level (commonly present in patients with the metabolic syndrome and diabetes).[1]


  • Hypertension has been reported in as 50-92% of patients with PAD.
  • Patients with PAD and hypertension are at greatly increased risk of stroke and myocardial infarction independently of other risk factors.

Nontraditional Risk Factors


  • PAD has been shown to be disproportionately prevalent in black and Hispanic populations

Chronic Kidney Disease

  • There is an association between PAD and chronic kidney disease independently from diabetes, hypertension, ethnicity and age. This association might be related to the increased vascular inflammation and markedly elevated plasma homocysteine levels seen in chronic kidney disease.
  • The prevalence of an abnormal ABI (< 0.90) is much higher in patients with end-stage renal disease than in those with chronic kidney disease, ranging between 30% and 38%.


  • Genetic predisposition to PAD is supported by observations of increased rates of cardiovascular disease (including PAD) in "healthy" relatives of patients with intermittent claudication.
  • To date, no major gene for PAD has been detected.

Hypercoagulable States

  • Hypercoagulable state, caused by altered levels of D-dimer, homocysteine or lipoprotein a, is an uncommon risk factor for PAD.
  • Hepercoagulable state is suspected in younger persons who lack traditional risk factors, patients with a strong family history of premature atherosclerosis, and individuals in whom arterial revascularization fails for no apparent technical reason.
    • Hyperhomocysteinemia is associated with premature atherosclerosis and appears to be a stronger risk factor for PAD than for CAD.[1]

Abnormal Waist-to-Hip Ratio

  • An association between abdominal obesity and PAD has been reported, although it is unclear whether any association exists between PAD and body mass index (BMI)
  • The lack of association between PAD and BMI can be explained by the tendency of smokers (those at an increased risk for PAD) have lower BMIs than nonsmokers. Also, many of the individuals at risk for PAD are elderly males, who generally have lower BMIs as well.


  1. 1.0 1.1 1.2 1.3 1.4 Spittel P. Chapter 44. Peripheral vascular Disease. In Murphy J, Lloyd M. Mayo Clinic Cardiology Concise Textbook. Fourth edition.Mayo clinic scientific press.2013

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