The association between dysfunctional high density lipoprotein and bacterial infection type in sepsis and septic shock patients

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Conference Proceeding

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Acad Emerg Med


Background: High density lipoprotein (HDL-C) should be anti-inflammatory in sepsis, with protective functions including the ability to clear bacterial toxins, protect against inflammation, and provide substrate for steroid synthesis. However, when HDL-C becomes oxidized, it becomes dysfunctional and proinflammatory (Dys-HDL). We have previously shown that Dys-HDL is predictive of organ failure in sepsis and wished to investigate the association between Dys-HDL and bacterial infection type. We hypothesized that there would be a significant difference in Dys-HDL between gram positive and negative infections due to differences in lipoteichoic acid (LTA) and lipopolysaccharide (LPS) mediated inflammation. Methods: Adult (>18 years) patients with sepsis or septic shock were prospectively enrolled within 24 hours of presenting to the Emergency Department. Inclusion criteria were: a) suspected infection and ≥ 2 SIRS criteria, b) lactate ≥ 2, c) SOFA score ≥ 4. Dys-HDL was quantified using a cell-free assay and expressed as HDL Inflammatory Index (HII). Results: Data from 97 patients was analyzed (109 initially enrolled, 12 were excluded from analysis after adjudication for sepsis). 28 day mortality was 31%. Median SOFA score at baseline was 7 (IQR 5-10) and at 48 hours was 5 (IQR 1-7.5). Age was similar between patients with gram positive (mean 64, SD 15) and gram negative (mean 64, SD 13) infections (p = 0.431). Baseline SOFA scores were higher in gram positive (median 9, IQR 6-11) compared to gram negative (7, IQR 5-11) infections (p=0.020). 48 hour SOFA scores were similar between gram positive (median 5.5, IQR 1.5-7.5) and gram negative (5, IQR 1-7.5) infections (p=0.364). The median HII at enrollment was significantly higher in gram positive (2.22; IQR 1.59-3.25) compared to gram negative (1.62; IQR 1.16-2.61) infections (p=0.006). Similarly, the median HII at 48 hours was significantly higher in gram positive (2.13, IQR 1.35-3.27) compared to gram negative (1.60, 1.00-2.18) infections (p=0.003). Change in HII from baseline to 48 hours was not statistically significant between types of bacterial infections (p=0.337). Conclusion: Dys-HDL is significantly elevated in patients with sepsis due to gram positive infections compared to gram negative infections. Further studies are needed to determine the pathophysiologic mechanisms underlying these differences.



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