Peripheral arterial disease 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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Editors-in-Chief: C. Michael Gibson, M.D., Beth Israel Deaconess Medical Center, Boston, MA; Robert G. Schwartz, M.D. [1], Piedmont Physical Medicine and Rehabilitation, P.A.; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Risk Factors

Traditional risk factors:

• Advanced age:

  • Prevalence of PAD increases with age
  • PAD may be present in younger individuals (≤ 50 years of age), such patients represent a very small percentage of cases
  • 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.

• Individuals at risk for Lower-extremity Peripheral Arterial Disease
  • Age less than 50 years, with diabetes and one other atherosclerosis risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia)
  • Age 50 to 69 years and history of smoking or diabetes
  • Age 70 years and older

• Cigarette smoking:

  • The single most modifiable risk factor for the development of PAD and its complications:

    • Intermittent claudication
    • Critical limb ischemia

  • Smoking increases the risk of PAD fourfold and accelerates the onset of PAD symptoms by nearly a decade
  • 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
  • The association between smoking and PAD is about twice as strong as that between smoking and coronary artery disease

• 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.
  • 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
  • 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
  • Severity of diabetes plays an important role in the development of PAD

    • There is a 28% increase of PAD for every percentage-point increase in hemoglobin A1c
    • The seriousness of PAD appears to be related to both the duration of hyperglycemia and to glycemic control
    • PAD prevalence is also increased in individuals with impaired glucose tolerance

  • Diabetes is most strongly associated with the occlusive disease in the tibial arteries
  • Patients with PAD and diabetes are more likely to develop microangiography and neuropathy and to have impaired wound healing than those with PAD alone
  • PAD tends to present later in life and in a more severe and progressive form in diabetics than nondiabetics, as a result of PAD being more asymptomatic in diabetics
  • PAD patients who have diabetes also have a higher risk for ischemic ulceration and gangrene
  • Persons with diabetes are more than likely to have additional risk factors as compared to their nondiabetic counterparts:

    • Tobacco use
    • Elevated blood pressure
    • Increased levels of triglycerides, cholesterol, and other blood lipids
    • Increased vascular inflammation
    • Endothelial cell dysfunction
    • Abnormalities in vascular smooth muscle cells
    • Diabetes is also associated with increases in platelet aggregation and impaired fibrinolytic function

• Dyslipidemia

  • Increases the adjusted likelihood of developing PAD by 10% for every 10-mg/dL rise in total cholesterol
  • Elevations in total cholesterol, LDL cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides are all independent risk factors for PAD
  • 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 seen in patients with the metabolic syndrome and diabetes)

• Hypertension

  • 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 independent of other risk factors

Nontraditional risk factors:

• Race/ethnicity

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

• Elevated levels of inflammatory markers (C-reactive protein, fibrinogen, leukocytes, interleukin-6)

• Chronic kidney disease:

  • Association of PAD and chronic kidney disease appears to apply to more severe renal 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%
  • PAD patients with chronic kidney disease are at increased risk for critical limb ischemia, while those with end-stage renal disease are at increased risk for amputation
  • The association between PAD and chronic kidney disease is independent of diabetes, hypertension, ethnicity and age

    • May be related to the increased vascular inflammation and markedly elevated plasma homocysteine levels seen in chronic kidney disease

• Genetics:

  • 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

• Hypercoaguable states (altered levels of D-dimer, homocysteine, lipoprotein[a])

  • Uncommon risk factor for PAD
  • 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, evaluation of hypercoaguable condition should be considered
  • Evaluation of elevated homocysteine and lipoprotein(a) levels appears to be important in individuals with diffuse PAD who lack traditional risk factors
  • Hyperhomocysteinemia is associated with premature atherosclerosis and appears to be a stronger risk factor for PAD than for CAD.

    • Also been implicated in PAD progression and as a risk factor for failure of peripheral arterial interventions

• 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.

References

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