Inflammatory mediators are associated with 1-year mortality in critical limb ischemia

The atherosclerotic process has inflammatory features. Patients with peripheral atherosclerosis and critical limb ischemia have a poor prognosis. This study evaluated the hypothesis that inflammatory markers are associated with mortality among patients admitted to the hospital because of critical limb ischemia.

This was a prospective, single-center, 1-year, follow-up study of 259 consecutive patients with critical limb ischemia who were admitted to a secondary referral center of vascular diseases. Interventions included evaluation of intercurrent disease, ankle and arm blood pressures, plasma glucose and lipid levels, plasma homocysteine, cardiolipin antibodies, resistance to activated protein C, plasma endothelin-1, and the inflammatory mediators tumor necrosis factor-alpha, interleukin-6, neopterin, high-sensitivity C-reactive protein, CD40 ligand, and 8-iso-prostaglandin F alpha in plasma. The main outcome measure was total mortality and causes of death assessed 1 year after admission.

During the first year after admission, 61 patients (24%) died. These patients were older (P < .0001), showed a higher leukocyte count (P = .0011) and levels of serum creatinine (P < .0001), lower levels of high-density lipoprotein (HDL) cholesterol (P = .003) and frequency of active treatment (P = .014) than the 198 (76%) survivors. More nonsurvivors had gangrene (P < .0001), and fewer (P = .004) had lipid-lowering treatment. The plasma levels of interleukin-6 (P < .0001), tumor necrosis factor-alpha (P < .0001), neopterin (P < .0001), and high-sensitivity C-reactive protein (P = .002) at admission for critical limb ischemia were all significantly lower in the survivors, whereas there was no difference concerning CD40 ligand. In logistic regression adjusted for age, sex, lipid-lowering therapy, active treatment, gangrene, leukocyte count, creatinine, and serum HDL cholesterol, the inflammatory mediators tumor necrosis factor-alpha (P = .0084), neopterin (P = .0035), but not interleukin-6 (P = .585) or high-sensitivity C-reactive protein (P = .314) were independent risk variables of death within 1 year.

Increased age, leukocyte count, creatinine, and inflammatory mediators, together with gangrene, were associated with 1-year mortality despite intervention in critical limb ischemia. For tumor necrosis factor-alpha and neopterin in plasma, this association was independent of the other parameters.