FP636
LIPOPROPTEIN-ASSOCIATED PHOSPHOLIPASE A2 PREDICTS THE LOWER LIMB ISCHEMIA IN DIALYZED PATIENTS

INTRODUCTION: Hemodialyzed patients (HDP) have high prevalence of peripheral artery disease: chronic lower limb ischemia and foot ulcers account for about 30% and 15% respectively, until 80 and 40% in the soubgroup of diabetic- HDP. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a lipase associated with LDL, that increases the oxidative stress in atherosclerotic plaques, making them instable. In general, cardiac and renal population Lp-PLA2 is correlated with the risk of acute cardiovascular morbidity and mortality. Lp-PLA2 is also recognized as a useful stratification tool, in order to optimizing the lipid lowering therapy, and studies on Lp-PLA2 inhibitors are ongoing. Finally, Lp-PLA2 is associated with peripheral artery disease in general population, but no data are available for renal subjects.The aim of our study was to evaluate the relationship between Lp-PLA2 and lower limb ischemia among HDP.

METHODS: 102 HDP were enrolled in June 2013, 64 (62%) male, age (median, IQR) 71ys, 59-88; BMI 23.9, 21.0-26.5; dialytic age 29 months, 13-53. Prevalence of diabetes, hypertension and history of coronary artery disease (CAD) were respectively 35%, 54% and 40%. They were investigated for lipoprotein plasma profile. Lp-PLA2 activity was measured as enzymatic assay. The occurrence of chronic foot ulcers, defined as the interruption of epithelium, with or without soft tissue infection, ischemia or gangrene of lower limb extremity upon or below the malleoli, was detected in the subsequent 5 ys follow-up.

RESULTS: The median (IQR) levels of Lp-PLA2, hs-CRP, Total-, HDL-, LDL-cholesterol, Triglycerides (TG) and apoB/apoA-I ratio were 184 nmol/min/ml (156.5-214.5), 0.4 mg/L (0.1-0.9), 158 mg/dL (127-191), 41 mg/dL (33-51), 79 mg/dL (63-102), 139 mg/dL (92-205) and 0.72 (0.58-0.89), respectively.The 43 HDP with Lp-PLA2 higher than the normal levels (194 nmol/min/ml) had higher median levels of total cholesterol (171 vs 142 mg/dl, p=0.018), LDL- cholesterol (92 vs 67 mg/dl, p<0.0005), ApoB/A1 ratio (0.83 vs 0.61, p<0.005) and higher incidence of de novo foot ulcers during the follow up (44% vs 17%, p=0.003). In univariate logistic regression analysis, age (p=0.0027), Lp-PLA2 (p=0.001), LDL-cholesterol (p=0.044), apoB/apoA-I ratio (p<0.0005), diabetes (p<0.0005), and CAD (p=0.021) were significantly associated with foot ulcers. In multivariate analysis Lp-PLA2 (p=0.018) and diabetes (p<0.0005) remained independently associated with lower foot ulcers.

CONCLUSIONS: Our study demonstrated that Lp-PLA2 is correlated with advanced stage of peripheral artery disease and foot ulcers among dialyzed subjects. As new Lp-PLA2 inhibitors will be available, further studies are required to confirm our findings and eventually to extend these therapies to renal patients.