HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis: A Subanalysis of a Prospective Pilot Study

Background: Proper functioning of high-density lipoprotein (HDL) is necessary for protection against sepsis. However, previous work has demonstrated that HDL becomes oxidized and dysfunctional (Dys-HDL) during sepsis. Older (aged >65 years) patients are at particularly high risk of sepsis and poor outcomes from sepsis. Study objective: The aim of the study was to compare functional properties of HDL (cholesterol efflux capacity and paraoxonase enzyme 1 [PON-1] activity) and Dys-HDL between older (aged >65 years) sepsis patients and older healthy volunteers. Methods: This was a subanalysis of a prospective study in which patients with sepsis were prospectively enrolled from the emergency department within the first 24 h. Serum and plasma samples were drawn from septic patients and age- and sex-matched control subjects. Percent cholesterol efflux, HDL inflammatory index, and PON1 activity were measured. Data were analyzed using Student t test or Wilcoxon rank-sum test. Results: Ten sepsis and 10 healthy controls were analyzed. Mean age of sepsis patients (80 ± 2 years [SD]) and control subjects (77 ± 2 years) was similar (P = 0.31). Mean systolic blood pressures were significantly different in sepsis patients (113 ± 8 mmHg) compared with controls (133 ± 6 mmHg) (P = 0.049). Median SOFA scores for sepsis patients were 5.5 (interquartile range [IQR] 4–9). Mean percent cholesterol efflux was significantly reduced in sepsis (24.1 ± 1.2%) compared with controls (31.5 ± 1.0%) (P < 0.001). HDL inflammatory index was also significantly elevated in septic patients (1.63, IQR 1.3–2.34) compared with controls (0.62, IQR 0.56–0.67) (P < 0.001). However, PON1 activity was not significantly different between septic patients (70.3 ± 16.3 nmol/min/mL) and control subjects (88.8 ± 18.3 nmol/min/mL). Conclusions: Cholesterol efflux capacity seems to be significantly impaired in sepsis patients who also exhibited a higher index of Dys-HDL. The findings suggest that HDL function may be impaired in older individuals with sepsis.

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