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

Faheem W Guirgis, Sunita Dodani, Christiaan Leeuwenburgh, Lyle Moldawer, Jennifer Bowman, Colleen Kalynych, Victor Grijalva, Srinivasa T Reddy, Alan E Jones, Frederick A Moore, Faheem W Guirgis, Sunita Dodani, Christiaan Leeuwenburgh, Lyle Moldawer, Jennifer Bowman, Colleen Kalynych, Victor Grijalva, Srinivasa T Reddy, Alan E Jones, Frederick A Moore

Abstract

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Patient enrollment flow diagram.
Fig 1. Patient enrollment flow diagram.

References

    1. Singer M., Deutschman C., Seymour C., Shankar-Hari M., Annane D., Bauer M., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315, 801 (2016). 10.1001/jama.2016.0287
    1. Mira J. C., Gentile L., Mathias B., Efron P., Brakenridge S., Mohr A., et al. Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome. Crit. Care Med. XX, 1–10 (2016).
    1. Hotchkiss R. S., Monneret G. & Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat. Rev. Immunol. 13, 862–74 (2013). 10.1038/nri3552
    1. Boomer J. S., To K., Chang K., Takasu O., Osborne D., Walton A., et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 306, 2594–2605 (2011). 10.1001/jama.2011.1829
    1. Walton A. H., Muenzer J., Rasche D., Boomer J., Sato B., Brownstein B., et al. Reactivation of multiple viruses in patients with sepsis. PLoS One 9, e98819 (2014). 10.1371/journal.pone.0098819
    1. Chien J.-Y., Jerng J.-S., Yu C.-J. & Yang P.-C. Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit. Care Med. 33, 1688–93 (2005).
    1. Chien Y.-F., Chen C.-Y., Hsu C.-L., Chen K.-Y. & Yu C.-J. Decreased serum level of lipoprotein cholesterol is a poor prognostic factor for patients with severe community-acquired pneumonia that required intensive care unit admission. J. Crit. Care 30, 506–10 (2015). 10.1016/j.jcrc.2015.01.001
    1. Guirgis F. W., Dodani S., Moldawer L., Leeuwenburgh C., Bowman J., Kalynych C., et al. Exploring the Predictive Ability of Dysfunctional High Density Lipoprotein for Adverse Outcomes in Emergency Department Patients with Sepsis. SHOCK 1 (2017). 10.1097/SHK.0000000000000887
    1. Khovidhunkit W., Kim M., Memon R., Shigenaga J., Moser A., Feingold K., et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J. Lipid Res. 45, 1169–1196 (2004). 10.1194/jlr.R300019-JLR200
    1. Beutler B., Hoebe K., Du X. & Ulevitch R. J. How we detect microbes and respond to them: the Toll-like receptors and their transducers. J. Leukoc. Biol. 74, 479–485 (2003). 10.1189/jlb.0203082
    1. Kitchens R. L., Wolfbauer G., Albers J. J. & Munford R. S. Plasma lipoproteins promote the release of bacterial lipopolysaccharide from the monocyte cell surface. J. Biol. Chem. 274, 34116–22 (1999).
    1. Murphy A. J., Woollard K., Suhartoyo A., Stirzaker R., Shaw J., Sviridov D., et al. Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein A-I in in vitro and in vivo models of inflammation. Arterioscler. Thromb. Vasc. Biol. 31, 1333–1341 (2011). 10.1161/ATVBAHA.111.226258
    1. Guo L., Zheng Z., Ai J., Howatt D., Mittelstadt P., Thacker S., et al. Scavenger receptor BI and high-density lipoprotein regulate thymocyte apoptosis in sepsis. Arterioscler. Thromb. Vasc. Biol. 34, 966–75 (2014). 10.1161/ATVBAHA.113.302484
    1. Navab M., Hama S., Hough G., Subbanagounder G., Reddy S., Fogelman A., A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids. J. Lipid Res. 42, 1308–1317 (2001).
    1. Parrillo J. E. Pathogenetic Mechanisms of Septic Shock. N Engl J Med 328, 1471–1477 (1993). 10.1056/NEJM199305203282008
    1. Catapano A. L., Pirillo A., Bonacina F. & Norata G. D. HDL in innate and adaptive immunity. Cardiovasc. Res. (2014). cvu150 [pii]
    1. Topchiy E., Cirstea M., Kong H., Boyd J., Wang Y., Russell J., et al. Lipopolysaccharide Is Cleared from the Circulation by Hepatocytes via the Low Density Lipoprotein Receptor. PLoS One 11, e0155030 (2016). 10.1371/journal.pone.0155030
    1. Boyd J. H., Fjel l C., Russell J., Sirounis D., Cirstea M., Walley K. Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis. J. Innate Immun. 8, 211–20 (2016). 10.1159/000442976
    1. Walley K. R., Thain K., Russell J., Reilly M., Meyer N., Ferguson J., et al. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci. Transl. Med. 6, 258ra143 (2014). 10.1126/scitranslmed.3008782
    1. Guirgis F. W., Donnelly J., Dodani S., Howard G., Safford M., Levitan E., et al. Cholesterol levels and long-term rates of community-acquired sepsis. Crit. Care 20, 408 (2016). 10.1186/s13054-016-1579-8
    1. Navab M., Hama S., Anantharamaiah G., Hassan K., Hough G., Watson A., et al. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3. J. Lipid Res. 41, 1495–1508 (2000).
    1. Lagrost L., Girard C., Grosjean S., Masson D., Deckert V., Gautier T., et al. Low preoperative cholesterol level is a risk factor of sepsis and poor clinical outcome in patients undergoing cardiac surgery with cardiopulmonary bypass. Crit. Care Med. 42, 1065–73 (2014). 10.1097/CCM.0000000000000165
    1. Kozarsky K. F., Donahee M., Rigotti A., Iqbal S., Edelman E., Krieger M. Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 387, 414–417 (1997). 10.1038/387414a0
    1. van Leeuwen H. J., Heezius E., Dallinga G., van Strijp J., Verhoef J., van Kessel K. Lipoprotein metabolism in patients with severe sepsis. Crit. Care Med. 31, 1359–1366 (2003). 10.1097/01.CCM.0000059724.08290.51
    1. Guirgis F. W., Leeuwenburgh C., Grijalva V., Bowman J., Kalynych C., Moldawer L., et al. HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis. SHOCK 1 (2017). 10.1097/SHK.0000000000001030
    1. Zimetti F., De Vuono S., Gomaraschi M., Adorni M., Favari E., Ronda N., et al. Plasma cholesterol homeostasis, HDL remodeling and function during the acute phase reaction. J. Lipid Res. 58, 2051–2060 (2017). 10.1194/jlr.P076463
    1. Ilias I., Vassiliadi D., Theodorakopoulou M., Boutati E., Maratou E., Mitrou P., et al. Adipose tissue lipolysis and circulating lipids in acute and subacute critical illness: Effects of shock and treatment. J. Crit. Care 29, 1130.e5–1130.e9 (2014).
    1. Chen Y., Chen Y., Zhao L., Chen Y., Mei M., Li Q., et al. Inflammatory stress exacerbates hepatic cholesterol accumulation via disrupting cellular cholesterol export. J. Gastroenterol. Hepatol. 27, 974–984 (2012). 10.1111/j.1440-1746.2011.06986.x
    1. Pruzanski W., Stefanski E., de Beer F., de Beer M., Vadas P., Ravandi A., et al. Lipoproteins are substrates for human secretory group IIA phospholipase A2: preferential hydrolysis of acute phase HDL. J. Lipid Res. 39, 2150–60 (1998).
    1. Coetzee G. A., Strachan A., van der Westhuyzen D., Hoppe H., Jeenah M., de Beer F. Serum amyloid A-containing human high density lipoprotein 3. Density, size, and apolipoprotein composition. J. Biol. Chem. 261, 9644–51 (1986).
    1. Kwon W. Y., Suh G. J., Kim K. S., Kwak Y. H. & Kim K. 4F, apolipoprotein AI mimetic peptide, attenuates acute lung injury and improves survival in endotoxemic rats. J. Trauma Acute Care Surg. 72, 1576–83 (2012). 10.1097/TA.0b013e3182493ab4
    1. Sharifov O. F., Xu X., Gaggar A., Tabengwa E., White C., Palgunachari M., et al. L-4F Inhibits Lipopolysaccharide-Mediated Activation of Primary Human Neutrophils. Inflammation 37, 1401–1412 (2014). 10.1007/s10753-014-9864-7
    1. Sharifov O. F., Xu X., Gaggar A.,Grizzle W., Mishra V., Honavar J., et al. Anti-inflammatory mechanisms of apolipoprotein A-I mimetic peptide in acute respiratory distress syndrome secondary to sepsis. PLoS One 8, e64486 (2013). 10.1371/journal.pone.0064486

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