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 wellregarding 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). Reisinger et al. Arylesterase Activity in Sepsis 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.

Soluble urokinase plasminogen activator receptor (suPAR) predicts critical illness and kidney failure in patients admitted to the intensive care unit

“…As a side note, like previous reports 45 , we were able to show that lipoproteins were significantly different between ICU survivors and non-survivors, with the latter having lower levels of HDL-C and total cholesterol. Most notably, HDL-C levels were significantly lower in patients with hemorrhagic shock or GI bleeding, moderate-severe liver disease and in sepsis patients (Supplementary Table 3).…”

Branched-Chain Amino Acids Can Predict Mortality in ICU Sepsis Patients

“…In our study, 53 patients in the sepsis and 25 patients in the control cohort were included ( Table 1 ). The median age of sepsis patients was 66 years (50–75), whereas ICU-survivors were 63 (46–76) and non-survivors 66 (53–73) years of age ( p = 0.86), as previously reported [ 5 ]. In brief, females accounted for 40% of the sepsis study population and most infections (91%) were community-acquired.…”

“…In a first step, targeted metabolomic assessment of lipoproteins using 1 H NMR spectroscopy was performed to confirm and extend our previous results [ 5 ]. One patient in the sepsis cohort had to be excluded before lipoprotein analyses were performed due to insufficient sample volume in the aliquot.…”

“…We recruited patients older than 18 years with sepsis and septic shock and ICU controls admitted to the ICU of the Department of Internal Medicine at the Medical University of Graz, Austria, as formerly published [ 5 ]. In brief, sepsis-3-criteria were applied to define sepsis patients [ 3 ], and the control group consisted of consecutive ICU patients without sepsis or bacteremia at the time of sampling.…”

“…Some inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT) were not consistently able to predict the outcome of sepsis patients, and therefore better biomarkers are needed [ 4 ]. We were recently able to show that lipoprotein functionality parameters such as the arylesterase activity of high-density lipoprotein (HDL) associated paraoxonase 1 may be useful for outcome prediction in sepsis [ 5 ]. Therefore, we aimed to validate and extend these findings using proton nuclear magnetic resonance ( 1 H NMR) spectroscopy.…”