HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock

Objective High density lipoprotein (HDL) is important for defense against sepsis but becomes dysfunctional (Dys-HDL) during inflammation. We hypothesize that Dys-HDL correlates with organ dysfunction (sequential organ failure assessment (SOFA) score) early sepsis. Methods A prospective cohort study of adult ED sepsis patients enrolled within 24 hours. Results Eighty eight patients were analyzed. Dys-HDL (expressed as HDL inflammatory index (HII)) correlated with SOFA at enrollment (r = 0.23, p = 0.024) and at 48 hours (r = 0.24, p = 0.026) but HII change over the first 48 hours did not correlate with change in SOFA (r = 0.06, p = 0.56). Enrollment HII was significantly different in patients with most severe organ failure (2.31, IQR 1.33–5.2) compared to less severe organ failure (1.81, IQR 1.23–2.64, p = 0.043). Change in HII over 48 hours was significantly different for in-hospital non-survivors (-0.45, IQR-2.6, -0.14 p = 0.015) and for 28-day non-survivors (-1.12, IQR -1.52, 0.12, p = 0.044). In a multivariable linear regression equation (R2 = 0.13), for each unit HII increase, 48-hour SOFA increased by 0.72 (p = 0.009). Conclusion HII correlated with SOFA and predicted 48-hour SOFA score in early sepsis. Future studies are needed to delineate potential mechanisms. Trial registration NCT02370186. Registered February 24, 2015.

[1]  L. Moldawer,et al.  Exploring the Predictive Ability of Dysfunctional High-Density Lipoprotein for Adverse Outcomes in Emergency Department Patients with Sepsis: A Preliminary Investigation , 2017, Shock.

[2]  L. Moldawer,et al.  HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis: A Subanalysis of a Prospective Pilot Study , 2017, Shock.

[3]  F. Veglia,et al.  Plasma cholesterol homeostasis, HDL remodeling and function during the acute phase reaction[S] , 2017, Journal of Lipid Research.

[4]  L. Moldawer,et al.  Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome , 2017, Critical care medicine.

[5]  John P. Donnelly,et al.  Cholesterol levels and long-term rates of community-acquired sepsis , 2016, Critical Care.

[6]  K. Walley,et al.  Lipopolysaccharide Is Cleared from the Circulation by Hepatocytes via the Low Density Lipoprotein Receptor , 2016, PloS one.

[7]  R. Bellomo,et al.  The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). , 2016, JAMA.

[8]  C. Fjell,et al.  Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis , 2016, Journal of Innate Immunity.

[9]  Chong-Jen Yu,et al.  Decreased serum level of lipoprotein cholesterol is a poor prognostic factor for patients with severe community-acquired pneumonia that required intensive care unit admission. , 2015, Journal of critical care.

[10]  I. Dimopoulou,et al.  Adipose tissue lipolysis and circulating lipids in acute and subacute critical illness: effects of shock and treatment. , 2014, Journal of critical care.

[11]  M. Reilly,et al.  PCSK9 is a critical regulator of the innate immune response and septic shock outcome , 2014, Science Translational Medicine.

[12]  G. Norata,et al.  HDL in innate and adaptive immunity. , 2014, Cardiovascular research.

[13]  R. Hotchkiss,et al.  Reactivation of Multiple Viruses in Patients with Sepsis , 2014, PloS one.

[14]  C. Bonithon-Kopp,et al.  Low Preoperative Cholesterol Level Is a Risk Factor of Sepsis and Poor Clinical Outcome in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass* , 2014, Critical care medicine.

[15]  A. Remaley,et al.  Scavenger Receptor BI and High-Density Lipoprotein Regulate Thymocyte Apoptosis in Sepsis , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[16]  A. Gaggar,et al.  L-4F Inhibits Lipopolysaccharide-Mediated Activation of Primary Human Neutrophils , 2014, Inflammation.

[17]  R. Hotchkiss,et al.  Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy , 2013, Nature Reviews Immunology.

[18]  A. Gaggar,et al.  Anti-Inflammatory Mechanisms of Apolipoprotein A-I Mimetic Peptide in Acute Respiratory Distress Syndrome Secondary to Sepsis , 2013, PloS one.

[19]  Kyuseok Kim,et al.  4F, apolipoprotein AI mimetic peptide, attenuates acute lung injury and improves survival in endotoxemic rats , 2012, The journal of trauma and acute care surgery.

[20]  Z. Varghese,et al.  Inflammatory stress exacerbates hepatic cholesterol accumulation via disrupting cellular cholesterol export , 2012, Journal of gastroenterology and hepatology.

[21]  R. Hotchkiss,et al.  Immunosuppression in patients who die of sepsis and multiple organ failure. , 2011, JAMA.

[22]  D. Sviridov,et al.  Neutrophil Activation Is Attenuated by High-Density Lipoprotein and Apolipoprotein A-I in In Vitro and In Vivo Models of Inflammation , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[23]  Pan‐Chyr Yang,et al.  Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis* , 2005, Critical care medicine.

[24]  Kenneth R Feingold,et al.  Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. , 2004, Journal of lipid research.

[25]  B. Beutler,et al.  How we detect microbes and respond to them: the Toll‐like receptors and their transducers , 2003, Journal of leukocyte biology.

[26]  J. Verhoef,et al.  Lipoprotein metabolism in patients with severe sepsis , 2003, Critical care medicine.

[27]  S. Reddy,et al.  A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids. , 2001, Journal of lipid research.

[28]  R. Munford,et al.  Plasma Lipoproteins Promote the Release of Bacterial Lipopolysaccharide from the Monocyte Cell Surface* , 1999, The Journal of Biological Chemistry.

[29]  P. Vadas,et al.  Lipoproteins are substrates for human secretory group IIA phospholipase A2: preferential hydrolysis of acute phase HDL. , 1998, Journal of lipid research.

[30]  E. Edelman,et al.  Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels , 1997, Nature.

[31]  J. Parrillo Pathogenetic mechanisms of septic shock. , 1993, The New England journal of medicine.

[32]  G. Coetzee,et al.  Serum amyloid A-containing human high density lipoprotein 3. Density, size, and apolipoprotein composition. , 1986, The Journal of biological chemistry.

[33]  G. Fonarow,et al.  formation of , 2022 .