Diabetes, renal dysfunction, inflammation, and anemia: the deadly quartet in peripheral artery disease

The article reviews the burden of peripheral artery disease (PAD) and its association with diabetes, renal dysfunction, inflammation, and anemia. PAD is a marker of advanced atherosclerotic disease and is associated with a poor quality of life, ischemic events, and mortality. Polyvascular involvement is often observed in PAD patients (pts), and contributes to the greater risk of all-cause and cardiovascular mortality. Diabetes is a major risk factor for PAD, and the presence of PAD in diabetic pts is associated with unfavorable cardiovascular outcomes. In comparison to nondiabetic PAD pts, diabetic pts often have severe forms of PAD such as foot ulcers and gangrene, and more often have involvement of the distal extremities. Diabetes is often accompanied by anemia, particularly in the presence of impaired renal function. Chronic kidney disease and PAD share some common risk factors and frequently coexist. In PAD pts, renal dysfunction has been associated with an increased risk of major adverse cardiovascular events and mortality. Anemia is quite prevalent in PAD pts, especially in those with critical limb ischemia. The severity of anemia has been identified as an independent predictor of limb loss and mortality. C-reactive protein (CRP) is associated with the development of PAD and diabetes. Increased levels of CRP in diabetic pts intensify the risk for PAD development. Data regarding the prognostic role of CRP in PAD pts suggest that CRP is a better prognostic marker for short-term rather than long-term mortality. Considering the close relationship between diabetes, renal dysfunction, inflammation, and anemia in PAD pts, a multidisciplinary approach is needed in order to improve quality of life and prevent ischemic events and fatal outcomes.