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, Kotecha, Sarah, Abdelghaffar, Mariam, Forster, Thorsten, Santos Rodrigues, Patricia Dos, Reisinger, Alexander C., White, Daniel, Hamilton, Fergus, Watkins, W. John ORCID: https://orcid.org/0000-0003-3262-6588, Griffith, David M. and Ghazal, Peter 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 , 104981. 10.1016/j.ebiom.2024.104981

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	2352-3964
Date of First Compliant Deposit:	9 February 2024
Date of Acceptance:	11 January 2024
Last Modified:	15 Feb 2024 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/165918

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