Plasma NAP-2 levels are associated with critical limb ischemia in peripheral arterial disease patients

Our study evaluates the relationship between plasma neutrophil-activating peptide-2 (NAP-2) levels and critical limb ischemia (CLI); 189 subjects were enrolled in this study: 59 subjects with CLI and type 2 diabetes mellitus (T2DM), 45 subjects with CLI and no T2DM, 43 patients with T2DM and no CLI, and 42 without both T2DM and CLI. Subjects with CLI had higher plasma levels of NAP-2 than those of the healthy group (2.04 +/- 0.06 ng/mL vs. 1.75 +/- 0.09 ng/mL, P = 0.011). Subjects with CLI and T2DM had higher plasma levels of NAP-2 than those of the T2DM group (2.08 +/- 0.08 ng/mL vs. 1.73 +/- 0.10 ng/mL, P = 0.007). However, subjects with CLI including CLI and T2DM+CLI had higher plasma levels of NAP-2 than those of the non-CLI group including healthy and T2DM group (2.06 +/- 0.05 ng/mL vs. 1.74 +/- 0.07 ng/mL, P < 0.001). The ankle brachial index (ABI) and total cholesterol (TC) were significantly and negatively correlated with plasma NAP-2 levels (rho = -0.250, P = 0.001; rho = -0.162, P = 0.026, respectively). Systolic blood pressure (SBP) positively correlated with plasma NAP-2 levels (rho = 0.187, P = 0.010). When adjusting for the factors, plasma NAP-2 levels were still significantly correlated with CLI (odds ratio = 11.543, 95% confidence intervals: 1.327-100.403, P = 0.027). The area under the curve (AUC) of NAP-2+confounders was 0.992 (95% confidence intervals 0.981 to 1.003, P < 0.001) and it was higher than those of NAP-2 alone (95% confidence intervals 0.241 to 0.407, P < 0.001) and confounders alone (AUC = 0.990, 95% confidence intervals -0.013 to 0.018, P = 0.797). In conclusion, elevated plasma NAP-2 was independently associated with CLI, but it was not correlated with T2DM. Plasma NAP-2 levels might be an early CLI diagnostic biomarker and might provide a novel target for CLI treatment. Impact statement Critical limb ischemia (CLI) is a serious arterial obstruction, resulting in serious reduction of blood flow to the extremities. CLI is a symptomatic disorder and is frequently not diagnosed in time. This results in a high mortality and elevated risk of limb amputation. Serum or plasma biomarkers play important roles in disease prevention, diagnosis, and prognosis. Elevated plasma neutrophil-activating peptide-2 (NAP-2) was found independently associated with CLI, but not with T2DM. Plasma NAP-2 levels might be an early CLI diagnostic biomarker and might provide a novel target for CLI treatment.