Predictors of early disease in the lower limbs.

Increasing age and male gender are unavoidable risk factors for peripheral arterial occlusive disease (PAOD). A number of studies have looked at classical risk factors for atherosclerosis, such as diabetes, hypertension, lipid abnormalities, and smoking, as well as some more recently identified associations, such as plasma fibrinogen levels, impaired glucose tolerance, and hyperhomocysteinemia. However, most "risk factors" are really associations. A causal relationship may only reasonably be firmly established if a prospective controlled study shows that removing the risk factor significantly alters the course of the disease, as with smoking. Smoking is probably the strongest risk factor for intermittent claudication (IC), but hyperhomocysteinemia also appears to be strongly associated with the development of PAOD. Moderate alcohol intake and regular physical exercise appear to have a protective effect. A genetic risk factor is suggested but not as yet confirmed. The magnitude of the association varies from odds ratios of 2 to 3 for smoking and diabetes. There is insufficient evidence for hyperhomocysteinemia, but the effect may be even greater. The association with hypertension and lipid abnormalities is surprisingly inconclusive.