Arylesterase Activity of HDL Associated Paraoxonase as a Potential Prognostic Marker in Patients With Sepsis and Septic Shock-A Prospective Pilot Study

Abstract

Background: High-density lipoprotein (HDL) plays an essential role in the immune system and shows effective antioxidative properties. We investigated correlations of lipid parameters with the sequential organ failure assessment (SOFA) score and the prognostic association with mortality in sepsis patients admitted to intensive care unit (ICU). Methods: We prospectively recruited consecutive adult patients with sepsis and septic shock, according to sepsis-3 criteria as well as non-sepsis ICU controls. Results: Fifty-three patients with sepsis (49% with septic shock) and 25 ICU controls without sepsis were enrolled. Dyslipidemia (HDL-C < 40 mg/l) was more common in sepsis compared to non-sepsis patients (85 vs. 52%, p = 0.002). Septic patients compared to controls had reduced HDL-C (14 vs. 39 mg/l, p < 0.0001), lower arylesterase activity of the antioxidative paraoxonase of HDL (AEA) (67 vs. 111 mM/min/ml serum, p < 0.0001), and a non-significant trend toward reduced cholesterol efflux capacity (9 vs. 10%, p = 0.091). We observed a strong association between higher AEA and lower risk of 28-day [per 10 mM/min/ml serum increase in AEA: odds ratio (OR) = 0.76; 95% CI, 0.61-0.94; p = 0.01) and ICU mortality (per 10 mM/min/ml serum increase in AEA: OR = 0.71, 95% CI, 0.56-0.90, p = 0.004) in the sepsis cohort in univariable logistic regression analysis. AEA was confirmed as an independent predictor of 28-day and ICU mortality in multivariable analyses. AEA discriminated well-regarding 28-day/ICU mortality in area under the receiver operating characteristic curve (AUROC) analyses. In survival analysis, 28-day mortality estimates were 40 and 69% with AEA ≥/< the 25th percentile of AEA's distribution, respectively (log-rank p = 0.0035). Conclusions: Both compositional and functional HDL parameters are profoundly altered during sepsis. In particular, the functionality parameter AEA shows promising prognostic potential in sepsis patients.

Keywords: ICU; arylesterase activity; dyslipideamia; high density lipoprotein (HDL); paraoxonase (PON); paraoxonase (PON1); sepsis.

Figure 1

Boxplots of compositional and functional lipid parameters in the sepsis (n = 53; gray box plot bars) and control cohort (n = 25; white box plot bars). (A) HDL-cholesterol levels (mg/l); (B) triglyceride levels (mg/l); (C) arylesterase activity (mM/min/ml serum); (D) cholesterol efflux capacity (%). AEA, arylesterase activity; HDL-C, high-density lipoprotein cholesterol.

Figure 2

Kaplan–Meier curves of critically ill sepsis patients in dependence of arylesterase activity [empirical cutoff at the 25th percentile of its distribution: lowest quartile (red curve) vs. higher quartiles (dashed black curve)]. AEA, arylesterase activity.