Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies

Rory Taylor; Chengyuan Zhang; Deslit George; Sarah Kotecha; Mariam Abdelghaffar; Thorsten Forster; Patricia Dos Santos Rodrigues; Alexander C Reisinger; Daniel White; Fergus Hamilton; W John Watkins; David M Griffith; Peter  Ghazal

doi:10.1016/j.ebiom.2024.104981

Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies

Rory Taylor^*, Chengyuan Zhang, Deslit George, Sarah Kotecha, Mariam Abdelghaffar, Thorsten Forster, Patricia Dos Santos Rodrigues, Alexander C Reisinger, Daniel White, Fergus Hamilton, W John Watkins, David M Griffith, Peter Ghazal^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background
Mechanistic studies have established a biological role of sterol metabolism in infection and immunity with clinical data linking deranged cholesterol metabolism during sepsis with poorer outcomes. In this systematic review we assess the relationship between biomarkers of cholesterol homeostasis and mortality in critical illness.

Methods
We identified articles by searching a total of seven electronic databases from inception to October 2023. Prospective observational cohort studies included those subjects who had systemic cholesterol (Total Cholesterol (TC), HDL-C or LDL-C) levels assessed on the first day of ICU admission and short-term mortality recorded. Meta-analysis and meta-regression were used to evaluate overall mean differences in serum cholesterol levels between survivors and non-survivors. Study quality was assessed using the Newcastle–Ottawa Scale.

Findings
From 6469 studies identified by searches, 24 studies with 2542 participants were included in meta-analysis. Non-survivors had distinctly lower HDL-C at ICU admission −7.06 mg/dL (95% CI −9.21 to −4.91, p < 0.0001) in comparison with survivors. Corresponding differences were also seen less robustly for TC −21.86 mg/dL (95% CI −31.23 to −12.49, p < 0.0001) and LDL-C −8.79 mg/dL (95% CI, −13.74 to −3.83, p = 0.0005).

Interpretation
Systemic cholesterol levels (TC, HDL-C and LDL-C) on admission to critical care are inversely related to mortality. This finding is consistent with the notion that inflammatory and metabolic setpoints are coupled, such that the maladaptive-setpoint changes of cholesterol in critical illness are related to underlying inflammatory processes. We highlight the potential of HDL-biomarkers as early predictors of severity of illness and emphasise that future research should consider the metabolic and functional heterogeneity of HDLs.

Original language	English
Article number	104981
Number of pages	17
Journal	EBioMedicine
Volume	100
DOIs	https://doi.org/10.1016/j.ebiom.2024.104981
Publication status	Published - 29 Jan 2024

Keywords / Materials (for Non-textual outputs)

Sepsis
Critical illness
Lipids
Cholesterol
Immunometabolism

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MicroRNA coupling of the sterol metabolic network to the antiviral immune response
Ghazal, P.
BBSRC
1/07/13 → 31/08/16
Project: Research

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Taylor, R., Zhang, C., George, D., Kotecha, S., Abdelghaffar, M., Forster, T., Dos Santos Rodrigues, P., Reisinger, A. C., White, D., Hamilton, F., Watkins, W. J., Griffith, D. M., & Ghazal, P. (2024). Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies. EBioMedicine, 100, Article 104981. https://doi.org/10.1016/j.ebiom.2024.104981

@article{6f7a223adf824c46bcd6a338aeb99558,

title = "Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies",

abstract = "BackgroundMechanistic studies have established a biological role of sterol metabolism in infection and immunity with clinical data linking deranged cholesterol metabolism during sepsis with poorer outcomes. In this systematic review we assess the relationship between biomarkers of cholesterol homeostasis and mortality in critical illness.MethodsWe identified articles by searching a total of seven electronic databases from inception to October 2023. Prospective observational cohort studies included those subjects who had systemic cholesterol (Total Cholesterol (TC), HDL-C or LDL-C) levels assessed on the first day of ICU admission and short-term mortality recorded. Meta-analysis and meta-regression were used to evaluate overall mean differences in serum cholesterol levels between survivors and non-survivors. Study quality was assessed using the Newcastle–Ottawa Scale.FindingsFrom 6469 studies identified by searches, 24 studies with 2542 participants were included in meta-analysis. Non-survivors had distinctly lower HDL-C at ICU admission −7.06 mg/dL (95% CI −9.21 to −4.91, p < 0.0001) in comparison with survivors. Corresponding differences were also seen less robustly for TC −21.86 mg/dL (95% CI −31.23 to −12.49, p < 0.0001) and LDL-C −8.79 mg/dL (95% CI, −13.74 to −3.83, p = 0.0005).InterpretationSystemic cholesterol levels (TC, HDL-C and LDL-C) on admission to critical care are inversely related to mortality. This finding is consistent with the notion that inflammatory and metabolic setpoints are coupled, such that the maladaptive-setpoint changes of cholesterol in critical illness are related to underlying inflammatory processes. We highlight the potential of HDL-biomarkers as early predictors of severity of illness and emphasise that future research should consider the metabolic and functional heterogeneity of HDLs.",

keywords = "Sepsis, Critical illness, Lipids, Cholesterol, Immunometabolism",

author = "Rory Taylor and Chengyuan Zhang and Deslit George and Sarah Kotecha and Mariam Abdelghaffar and Thorsten Forster and {Dos Santos Rodrigues}, Patricia and Reisinger, {Alexander C} and Daniel White and Fergus Hamilton and Watkins, {W John} and Griffith, {David M} and Peter Ghazal",

note = "EU-ERDF-Welsh Government Ser Cymru programme, BBSRC, and EU-FP7 ClouDx-i project (PG)",

year = "2024",

month = jan,

day = "29",

doi = "10.1016/j.ebiom.2024.104981",

language = "English",

volume = "100",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier",

}

Taylor, R, Zhang, C, George, D, Kotecha, S, Abdelghaffar, M, Forster, T, Dos Santos Rodrigues, P, Reisinger, AC, White, D, Hamilton, F, Watkins, WJ, Griffith, DM & Ghazal, P 2024, 'Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies', EBioMedicine, vol. 100, 104981. https://doi.org/10.1016/j.ebiom.2024.104981

Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies. / Taylor, Rory; Zhang, Chengyuan; George, Deslit et al.
In: EBioMedicine, Vol. 100, 104981, 29.01.2024.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness

T2 - Systematic review, meta-analysis, and perspective of observational studies

AU - Taylor, Rory

AU - Zhang, Chengyuan

AU - George, Deslit

AU - Kotecha, Sarah

AU - Abdelghaffar, Mariam

AU - Forster, Thorsten

AU - Dos Santos Rodrigues, Patricia

AU - Reisinger, Alexander C

AU - White, Daniel

AU - Hamilton, Fergus

AU - Watkins, W John

AU - Griffith, David M

AU - Ghazal, Peter

N1 - EU-ERDF-Welsh Government Ser Cymru programme, BBSRC, and EU-FP7 ClouDx-i project (PG)

PY - 2024/1/29

Y1 - 2024/1/29

N2 - BackgroundMechanistic studies have established a biological role of sterol metabolism in infection and immunity with clinical data linking deranged cholesterol metabolism during sepsis with poorer outcomes. In this systematic review we assess the relationship between biomarkers of cholesterol homeostasis and mortality in critical illness.MethodsWe identified articles by searching a total of seven electronic databases from inception to October 2023. Prospective observational cohort studies included those subjects who had systemic cholesterol (Total Cholesterol (TC), HDL-C or LDL-C) levels assessed on the first day of ICU admission and short-term mortality recorded. Meta-analysis and meta-regression were used to evaluate overall mean differences in serum cholesterol levels between survivors and non-survivors. Study quality was assessed using the Newcastle–Ottawa Scale.FindingsFrom 6469 studies identified by searches, 24 studies with 2542 participants were included in meta-analysis. Non-survivors had distinctly lower HDL-C at ICU admission −7.06 mg/dL (95% CI −9.21 to −4.91, p < 0.0001) in comparison with survivors. Corresponding differences were also seen less robustly for TC −21.86 mg/dL (95% CI −31.23 to −12.49, p < 0.0001) and LDL-C −8.79 mg/dL (95% CI, −13.74 to −3.83, p = 0.0005).InterpretationSystemic cholesterol levels (TC, HDL-C and LDL-C) on admission to critical care are inversely related to mortality. This finding is consistent with the notion that inflammatory and metabolic setpoints are coupled, such that the maladaptive-setpoint changes of cholesterol in critical illness are related to underlying inflammatory processes. We highlight the potential of HDL-biomarkers as early predictors of severity of illness and emphasise that future research should consider the metabolic and functional heterogeneity of HDLs.

AB - BackgroundMechanistic studies have established a biological role of sterol metabolism in infection and immunity with clinical data linking deranged cholesterol metabolism during sepsis with poorer outcomes. In this systematic review we assess the relationship between biomarkers of cholesterol homeostasis and mortality in critical illness.MethodsWe identified articles by searching a total of seven electronic databases from inception to October 2023. Prospective observational cohort studies included those subjects who had systemic cholesterol (Total Cholesterol (TC), HDL-C or LDL-C) levels assessed on the first day of ICU admission and short-term mortality recorded. Meta-analysis and meta-regression were used to evaluate overall mean differences in serum cholesterol levels between survivors and non-survivors. Study quality was assessed using the Newcastle–Ottawa Scale.FindingsFrom 6469 studies identified by searches, 24 studies with 2542 participants were included in meta-analysis. Non-survivors had distinctly lower HDL-C at ICU admission −7.06 mg/dL (95% CI −9.21 to −4.91, p < 0.0001) in comparison with survivors. Corresponding differences were also seen less robustly for TC −21.86 mg/dL (95% CI −31.23 to −12.49, p < 0.0001) and LDL-C −8.79 mg/dL (95% CI, −13.74 to −3.83, p = 0.0005).InterpretationSystemic cholesterol levels (TC, HDL-C and LDL-C) on admission to critical care are inversely related to mortality. This finding is consistent with the notion that inflammatory and metabolic setpoints are coupled, such that the maladaptive-setpoint changes of cholesterol in critical illness are related to underlying inflammatory processes. We highlight the potential of HDL-biomarkers as early predictors of severity of illness and emphasise that future research should consider the metabolic and functional heterogeneity of HDLs.

KW - Sepsis

KW - Critical illness

KW - Lipids

KW - Cholesterol

KW - Immunometabolism

U2 - 10.1016/j.ebiom.2024.104981

DO - 10.1016/j.ebiom.2024.104981

M3 - Article

SN - 2352-3964

VL - 100

JO - EBioMedicine

JF - EBioMedicine

M1 - 104981

ER -

Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: Systematic review, meta-analysis, and perspective of observational studies

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

MicroRNA coupling of the sterol metabolic network to the antiviral immune response

Cite this