Peripheral arterial disease risk factors

Risk Factors

Traditional Risk Factors:

Advanced age:

• The prevalence of PAD increases with age.
• PAD may be present in younger individuals (≤ 50 years of age); however, 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.
• The risk for lower-extremity peripheral arterial disease varies with age and other co-existing risk factors:
  • 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:

• Cigarette smoking is the single most modifiable risk factor for the development of PAD; in fact, smoking increases the risk of PAD fourfold 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

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.
• Diabetes is associated with:
  • Occlusive disease in the tibial arteries
  • Impaired wound healing due to microangiopathy and neuropathy
  • Higher risk for ischemic ulceration and gangrene
• Late, progressive and more severe presentation as a result initial asymptomatic nature of PAD in diabetics
• Patients with diabetes are more than likely to have additional risk factors as compared to their nondiabetic counterparts:
  • 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

Dyslipidemia:

• 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).

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 independently of other risk factors.

Nontraditional Risk Factors

Race/ethnicity

• 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%.
• 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

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.

Hypercoagable States

• Hypercoagable state, manifested as altered levels of D-dimer, homocysteine, lipoprotein a, is an uncommon risk factor for PAD.
• Hepercoagble 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.

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.