低循环总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平与脓毒症和危重病患者的死亡相关：系统评价、荟萃分析和观察性研究的观点。

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.

机构信息

Deanery of Biomedical Sciences, University of Edinburgh Medical School, Edinburgh, UK.

Department of Anaesthesia, Critical Care and Pain Medicine, NHS Lothian, Edinburgh, UK.

出版信息

EBioMedicine. 2024 Feb;100:104981. doi: 10.1016/j.ebiom.2024.104981. Epub 2024 Jan 29.

DOI:10.1016/j.ebiom.2024.104981

PMID:38290288

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10844818/

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.

FUNDING

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

摘要

背景

机制研究已经确立了固醇代谢在感染和免疫中的生物学作用，临床数据将脓毒症期间胆固醇代谢紊乱与较差的预后联系起来。在这项系统评价中，我们评估了胆固醇动态平衡的生物标志物与危重病患者死亡率之间的关系。

方法

我们通过总共搜索了七个电子数据库，从开始到 2023 年 10 月，确定了文章。前瞻性观察性队列研究纳入了那些在 ICU 入院第一天评估全身胆固醇（总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）或低密度脂蛋白胆固醇（LDL-C））水平并记录短期死亡率的患者。使用荟萃分析和荟萃回归评估幸存者和非幸存者之间血清胆固醇水平的总体平均差异。使用纽卡斯尔-渥太华量表评估研究质量。

结果

从搜索中确定的 6469 项研究中，有 24 项研究共纳入 2542 名参与者进行荟萃分析。与幸存者相比，非幸存者在 ICU 入院时的 HDL-C 明显较低-7.06mg/dL（95%CI-9.21 至-4.91，p<0.0001）。TC 也存在类似但不太显著的差异-21.86mg/dL（95%CI-31.23 至-12.49，p<0.0001）和 LDL-C-8.79mg/dL（95%CI，-13.74 至-3.83，p=0.0005）。

解释

入住重症监护病房时的全身胆固醇水平（TC、HDL-C 和 LDL-C）与死亡率呈负相关。这一发现与炎症和代谢设定点相关的观点一致，即危重病中胆固醇的适应性设定点变化与潜在的炎症过程有关。我们强调了 HDL 生物标志物作为疾病严重程度的早期预测因子的潜力，并强调未来的研究应考虑 HDL 的代谢和功能异质性。