The association between dysfunctional high density lipoprotein and bacterial infection type in sepsis and septic shock patients
Black LP, Reddy S, Henson M, Miller T, Moore F, Guirgis F, and Jayaprakash N. The association between dysfunctional high density lipoprotein and bacterial infection type in sepsis and septic shock patients. Acad Emerg Med 2019; 26:S46.
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.