Abstract 287: Plasma PCSK9 Concentrations in Critically Ill Patients

Abstract

Objective. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that impairs LDL clearance by promoting the LDL receptor (LDLR) degradation. Plasma lipid parameters (LDL-C and HDL-C) are related to severity of illness and survival in intensive care patients. Here, we aimed to determine whether circulating PCSK9 concentrations were correlated to the severity of illness in patients with multiple trauma. Methods/Results. Plasma PCSK9 were measured, at day 0 and 8 after admission, by ELISA in 111 patients hospitalized in ICU for severe trauma. Patients were included in the HIPOLYTE study and were randomly assigned to hydrocortisone therapy or placebo. Plasma PCSK9 levels were significantly increased by 161% at day 8 compared to day 0 (481 ± 227 vs 231 ± 117 ng/ml, P=0.0001). Hydrocortisone therapy did not alter PCSK9 concentrations at day 8 compared to placebo (451 ± 216 vs 511 ± 239ng/ml, P=0.33). In the whole population of the study, PCSK9 was positively associated with LDL-C (Pearson coefficient : 0.26, p=0.007) at day 0, but not with markers of severity illness. At day 8, an inverse correlation was found between PCSK9 and HDL-C (β =-653 ; P=0.004). Interestingly, PCSK9 concentrations at day 8 were related to markers of severity illness as injury severity score (β =6.17 ; P=0.0007), length of stay in ICU (β =6.14 ; P=0.0001), duration of both mechanical ventilation (β =8.26 ; P=0.0001) and cathecolamines infusion (β =18.57; P=0.015). Conclusion. PCSK9 appears as a late biomarker of severity illness in patients hospitalized for multiple trauma in ICU. These results open new perspectives for a role of PCSK9 in critical illness.