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Plasma PCSK9 is a late biomarker of severity in patients with severe trauma injury
Maëlle Le Bras1, Antoine Roquilly, Valérie Deckert
1Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, University Hospital of Nantes, F-44000 Nantes, France.
Insights
Plasma PCSK9 levels significantly increased in patients with severe multiple trauma over 8 days. Elevated PCSK9 at day 8 correlated with illness severity, indicating its potential as a late biomarker.
Area of Science:
- Biochemistry
- Critical Care Medicine
- Molecular Biology
Background:
- Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates cholesterol homeostasis by affecting low-density lipoprotein receptor expression.
- Low plasma lipoprotein levels are linked to critical illness severity and survival in intensive care unit (ICU) patients.
Purpose of the Study:
- To investigate the regulation of plasma PCSK9 during critical illness.
- To determine the association between PCSK9, lipid parameters, and clinical severity markers.
Main Methods:
- Analysis of plasma samples from 111 severe multiple trauma patients in a surgical ICU.
- Measurement of PCSK9 concentrations by ELISA at days 0 and 8.
- Assessment of correlations with lipid profiles and clinical severity scores.
Main Results:
- Plasma PCSK9 levels doubled from day 0 to day 8 (P = .0001).
- Hydrocortisone therapy did not affect PCSK9 levels.
- Day 8 PCSK9 correlated inversely with HDL-cholesterol and positively with injury severity, ICU length of stay, mechanical ventilation, and norepinephrine duration.
Conclusions:
- Plasma PCSK9 emerges as a late biomarker for illness severity in severe multiple trauma patients.
- PCSK9 levels at day 8 reflect disease progression and patient outcomes.
Context:
PCSK9 (proprotein convertase subtilisin kexin type 9) is a secreted protease that modulates cholesterol homeostasis by decreasing low-density lipoprotein receptor expression. Low levels of plasma lipoproteins are related to severity of illness and survival in patients of intensive care units (ICU).
Objective:
The aim of the study was to investigate the regulation of plasma PCSK9 and its association with plasma lipid parameters and clinical markers of severity during critical illness.
Design And Patients:
The plasma biobank from the previously published HYPOLYTE prospective study was used to measure PCSK9 concentrations by ELISA at days 0 and 8 in 111 patients admitted to surgical ICU for severe multiple trauma. Patients were randomly assigned to hydrocortisone therapy or placebo.
Results:
Plasma PCSK9 levels were increased by 2-fold between days 0 and 8 (231 ± 116 vs 481 ± 227 ng/ml; P = .0001). Hydrocortisone therapy did not alter PCSK9 concentrations (451 ± 216 vs 511 ± 239 ng/ml in placebo group; P = .33). PCSK9 was positively associated with low-density lipoprotein-cholesterol (Pearson coefficient, 0.26; P = .007) at day 0, but not at day 8. At day 8, an inverse correlation was found between PCSK9 and high-density lipoprotein-cholesterol (β = -653; P = .004). Although baseline PCSK9 concentrations were not associated to severity scores, PCSK9 values at day 8 were related to injury severity score (β = 6.17; P = .0007), length of stay in ICU (β = 6.14; P = .0001), and duration of both mechanical ventilation (β = 8.26; P = .0001) and norepinephrine infusion (β = 18.57; P = .015).
Conclusions:
Plasma PCSK9 appears as a late biomarker of illness severity in patients with severe multiple trauma.
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