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

Guirgis, Faheem W.; Leeuwenburgh, Christiaan; Grijalva, Víctor; Bowman, Jennifer; Kalynych, Colleen; Moldawer, Lyle L.; Moore, Frederick A.; Reddy, Srinivasa T.

doi:10.1097/shk.0000000000001030

Cited by 24 publications

(28 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It does not take into account hepatic SR-BI receptor activity or expression or cholesterol ester transfer protein-mediated hepatic cholesterol transfer that are necessary for the entire process. [ 25 ] Zimetti and colleagues recently studied 59 patients with an acute phase response, of whom 37 had infections, and noted that APR patients had changes in HDL composition (specifically the displacement of ApoA-I by serum amyloid A) and reduction in cholesterol efflux (specifically due to decreased activity of SR-BI and ABCG1), going against this hypothesis. [ 26 ] Our study is different from Zimetti’s however, in that our population of severe sepsis and septic shock patients was critically ill as nearly all patients had multiple organ failure (SOFA score median 7, IQR 5–10), and the overall in-hospital and 28-day mortality were 20% and 31%, respectively.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

ObjectiveHigh 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.MethodsA prospective cohort study of adult ED sepsis patients enrolled within 24 hours.ResultsEighty 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).ConclusionHII correlated with SOFA and predicted 48-hour SOFA score in early sepsis. Future studies are needed to delineate potential mechanisms.Trial registrationNCT02370186. Registered February 24, 2015.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The cholesterol efflux assay is a quantitative assessment of HDL function and measures the ability of HDL to move lower density lipids from peripheral macrophages to the liver for clearance. HDL-mediated cellular cholesterol efflux assays will be performed to assess potential improvements in HDL function with LIE versus control as in previous studies 27. SOFA score assessment will occur prior to enrolment and 48 hours later as well as at 7 days to determine change in SOFA score over time as well as serum lactate.…”

Section: Methodsmentioning

confidence: 99%

“…Levels of very low-density lipoproteins and triglycerides increase due to adipose tissue lipolysis, which is stimulated by catecholamines, cortisol and growth hormone, possibly to meet energy needs or for bacterial toxin binding 8 24 25. Although some have attempted to demonstrate that these changes in cholesterol levels are not causal,26 there may be a direct association between cholesterol levels and poor outcomes, as both cholesterol levels and functional status are predictive of poor outcomes 22 27–29. The physiological rationale for the protective effects of cholesterol is strong, and thus we believe a pilot investigational study is warranted.…”

Section: Introductionmentioning

confidence: 99%

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock

et al. 2019

Self Cite

View full text Add to dashboard Cite

IntroductionSepsis is a life-threatening, dysregulated response to infection. Both high-density lipoprotein and low-density lipoprotein cholesterol should protect against sepsis by several mechanisms; however, for partially unknown reasons, cholesterol levels become critically low in patients with early sepsis who experience poor outcomes. An anti-inflammatory lipid injectable emulsion containing fish oil is approved by the Food and Drug Administration as parenteral nutrition for critically ill patients and may prevent this decrease in serum cholesterol levels by providing substrate for cholesterol synthesis and may favourably modulate inflammation. This LIPid Intensive Drug therapy for Sepsis Pilot clinical trial is the first study to attempt to stabilise early cholesterol levels using lipid emulsion as a treatment modality for sepsis.Methods and analysisThis is a two-centre, phase I/II clinical trial. Phase I is a non-randomised dose-escalation study using a Bayesian optimal interval design in which up to 16 patients will be enrolled to evaluate the safest and most efficacious dose for stabilising cholesterol levels. Based on phase I results, the two best doses will be used to randomise 48 patients to either lipid injectable emulsion or active control (no treatment). Twenty-four patients will be randomised to one of two doses of the study drug, while 24 control group patients will receive no drug and will be followed during their hospitalisation. The control group will receive all standard treatments mandated by the institutional sepsis alert protocol. The phase II study will employ a permuted blocked randomisation technique, and the primary endpoint will be change in serum total cholesterol level (48 hours − enrolment). Secondary endpoints include change in cholesterol level from enrolment to 7 days, change in Sequential Organ Failure Assessment score over the first 48 hours and 7 days, in-hospital and 28-day mortality, lipid oxidation status, inflammatory biomarkers, and high-density lipoprotein function.Ethics and disseminationInvestigators are trained and follow good clinical practices, and each phase of the study was reviewed and approved by the institutional review boards of each institution. Results of each phase will be disseminated through presentations at national meetings and publication in peer-reviewed journals. If promising, data from the pilot study will be used for a larger, multicentre, phase II clinical trial.Trial registration numberNCT03405870.

show abstract

“…Specifically, de la Llera et al have shown that in twenty healthy adults, an endotoxemia induced by LPS (3 ng/kg) administrated as an intravenous bolus infusion led to a reduced capacity of HDLs to efflux cholesterol in vitro [72]. Interestingly, when comparing the 10 oldest septic patients to the ten oldest healthy subjects, the cholesterol efflux was significantly reduced in septic patients (24 ± 1.2%) compared to control subjects (31.5 ± 1.0%) [84].…”

Section: Hdl Function In Inflammatory Statementioning

confidence: 98%

High-density lipoproteins during sepsis: from bench to bedside

et al. 2020

View full text Add to dashboard Cite

High-density lipoproteins (HDLs) represent a family of particle characterized by the presence of apolipoprotein A-I (apoA-I) and by their ability to transport cholesterol from peripheral tissues back to the liver conferring them a cardioprotective function. HDLs also display pleiotropic properties including antioxidant, anti-apoptotic, antithrombotic, anti-inflammatory, or anti-infectious functions. Clinical data demonstrate that HDL cholesterol levels decrease rapidly during sepsis and that these low levels are correlated with morbi-mortality. Experimental studies emphasized notable structural and functional modifications of HDL particles in inflammatory states, including sepsis. Finally, HDL infusion in animal models of sepsis improved survival and provided a global endothelial protective effect. These clinical and experimental studies reinforce the potential of HDL therapy in human sepsis. In this review, we will detail the different effects of HDLs that may be relevant under inflammatory conditions and the lipoprotein changes during sepsis and we will discuss the potentiality of HDL therapy in sepsis.

show abstract

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

Abstract: 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.

Cited by 24 publications

References 34 publications

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

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

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock

High-density lipoproteins during sepsis: from bench to bedside

Contact Info

Product

Resources

About