The common risk factors associated with PAD are older age, diabetes, tobacco smoking, hypertension, and dyslipidemia. Other associated risk factors for PAD include African American race, genetics, obesity, systemic inflammation, elevated homocysteine, metabolic syndrome, and renal disease. The relative risk of PAD by contributing risk factor is shown in Figure 2 (10).
The risk of PAD increases with age, starting at 40 years of age. People >65-70 years of age were at increased risk for the development of PAD in the Framingham Heart Study and National Health and Nutrition Examination Survey (NHANES). In NHANES, the prevalence of PAD was 2.5% between ages 50-59 years relative to 14.5% in those ≥70 years (10).
Smoking is the strongest and most common risk factor for PAD (11). Smoking increases the risk of developing PAD by 4-fold, and smokers develop PAD 10 years earlier than non-smokers. There is a significant relationship between the magnitude of smoking and risk for PAD. Pack-years of smoking correlates with progression of disease, lower patency of bypass grafts, and higher rates of amputation. Compared with nonsmokers, smokers have a higher risk of critical limb ischemia (CLI), acute limb ischemia, and amputation. Smoking is a modifiable risk factor for PAD and cessation lowers the incidence of claudication, CLI, and amputation.
Diabetes is the most common risk factor for PAD after smoking. In NHANES, diabetes was associated with a 2-3-fold higher risk of PAD (10). In the Framingham Heart Study, diabetes was associated with a 2.6-fold increased risk for symptomatic PAD (12). Furthermore, patients with diabetes and PAD are at higher risk for cardiovascular events, all-cause mortality, and amputation compared with those without diabetes.
Several studies have shown an independent association between hypertension and PAD. Among patients with PAD, hypertension is seen in 60-90% of patients. Unfortunately, hypertensive patients with PAD are less likely to receive antihypertensive therapy than those with coronary artery disease. Current clinical guidelines recommend antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers to reduce the risk of cardiovascular events in patients with PAD. However, the role of antihypertensive therapy in preventing limb events is not well known.
Dyslipidemia is an independent risk factor for PAD. In NHANES, more than half of the patients with PAD had elevated total cholesterol levels (4). In the Framingham Heart Study, there was a 1.2-fold increase in the risk of symptomatic PAD for every 40 mg/dL increase in total cholesterol levels (12). Several other lipid abnormalities, such as higher concentrations of low-density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein (a) are independently associated with an increased risk of PAD. LDL-cholesterol lowering reduces the risk of cardiovascular and limb events in patients with PAD.