The risk factors for PAD are those that are expected for any patient population with atherosclerosis. The most potent risk factors for PAD are age, diabetes mellitus, and cigarette smoking. In addition, hyperlipidemia, hypertension, and elevations in plasma homocysteine levels play an important role in promoting peripheral atherosclerosis.
All forms of cardiovascular disease become more prevalent with age, and PAD is particularly prevalent in the elderly. In several studies, the risk of PAD increased approximately twofold for every 10-year increase in age.
Diabetes is a major risk factor for PAD; persons with diabetes were four to five times more likely to develop claudication than nondiabetics. The major risk for PAD due to diabetes appears to be the association of smoking, hypertension, and byperlipidemia with diabetes, and not the degree of glycemic control per se. Thus, diabetes is a critical risk factor in the development of PAD, particularly in conjunction with other risk factors.
Cigarette smoking is associated with an approximate three- to fourfold increase in risk for peripheral atherosclerosis. In addition, current cigarette smoking also significantly affects PAD outcomes. For example, progression from intermittent claudication to ischemic rest pain with risk of amputation occurs significantly more frequently in patients who continue to smoke than those who are abstinent.
Independent risk factors for PAD include a reduced HDL cholesterol level, and elevations of total cholesterol, LDL cholesterol, triglycerides, and lipoprotein(a). For every 10 mg/dL increase in total cholesterol concentration, the risk of PAD increases approximately 10%.
Alterations in homocysteine metabolism are a recognized independent risk factor for PAD. Homocysteine promotes the formation of oxidized LDL cholesterol, endothelial dysfunction, and the proliferation of vascular smooth muscle cells. Perhaps the most common cause of elevations in homocysteine levels are nutritional deficiencies of B vitamins, particularly folic acid and vitamins B6 and B12.
Additional Risk Factors
An elevated fibrinogen level is an independent predictor of PAD and also for the severity of claudication. Hypercoagulable states have not been extensively evaluated as risk factors in PAD. The lupus anticoagulant has been associated with peripheral atherosclerosis, as have markers of platelet activation such as increases in beta thromboglobulin levels. However, the frequency of these abnormalities is low and not fully substantiated and therefore does not warrant screening.
1. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc. 1985;33:13-18.
2. Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of Peripheral arterial disease. The San Luis Valley diabetes study. Circulation. 1995;91:1472- 1479.
3. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with Peripheral arterial disease. N Engl J Med. 1992;326:381-386.
4. Vogt MT, Cauley JA, Newman AB, Kuller LH, Hulley SB. Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA. 1993;270:465-469.
5. Newman AB, Tyrrell KS, Kuller LH. Mortality over four years in SHEP participants with a low ankle-arm index. J Am Geriatr Soc. 1997;45:1472-1478.
6. Leng GC, Fowkes FG, Lee AJ, et al. Use of ankle brachial pressure index to predict cardiovascular events and death: a cohort study. Br Med J. 1996;313:1440-1444.
7. Leng GC, Lee AJ, Fowkes FG, et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic Peripheral arterial disease in the general population. Int J Epidemiol. 1996;25:1172-1181.