The relationship between plasma cystatin C, mortality and acute respiratory distress syndrome subphenotype in the HARP-2 trial

IF 1.4 4区医学 Q3 CRITICAL CARE MEDICINE

Critical Care and Resuscitation Pub Date : 2022-09-05 DOI:10.51893/2022.3.OA4

Michael C. McKelvey , Ian Bradbury , Cliona McDowell , Carolyn S. Calfee , Sinead Weldon , Cecilia M. O'Kane , Daniel F. McAuley , Clifford C. Taggart

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引用次数: 0

Abstract

Objective: To evaluate the performance of cystatin C as a prognostic and predictive marker in a trial of patients with acute respiratory distress syndrome (ARDS).

Design, patients and setting: A retrospective analysis was performed on plasma samples from patients included in the HARP-2 (hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction) trial — a multicentre, phase 2b trial carried out in general intensive care units across 40 hospitals in the United Kingdom and Ireland. Cystatin C concentrations in plasma obtained from 466 patients with ARDS (before they were randomly assigned in the trial) were quantified by ELISA (enzyme-linked immunosorbent assay).

Results: In a univariate analysis, plasma cystatin C concentrations were significantly higher in patients with ARDS who did not survive past 28 days (odds ratio [OR], 1.39 [95% CI, 1.12–1.72]; P = 0.002). In a multivariate model adjusted for selected covariates, cystatin C concentrations remained higher among patients with ARDS who did not survive, although this did not reach statistical significance (OR, 1.28 [95% CI, 0.96–1.71]; P = 0.090). Cystatin C concentration was also significantly associated with hyperinflammatory ARDS (OR, 2.64 [95% CI, 1.83–3.89]; P < 0.001). In multivariate models adjusted for both cystatin C concentration and ARDS subphenotype, hyperinflammatory ARDS was prognostic for mortality (OR, 2.06 [95% CI, 1.16–3.64]; P = 0.013) but cystatin C concentration was not (OR, 1.16 [95% CI, 0.85–1.57]; P = 0.346). In a multivariate analysis, hyperinflammatory ARDS was predictive of a beneficial effect of simvastatin on mortality (OR, 2.05 [95% CI, 1.16–3.62]; P = 0.014) but cystatin C concentration was not (OR, 1.10 [95% CI, 0.77–1.56]; P = 0.614).

Conclusion: The association between cystatin C concentration and mortality in ARDS may be dependent on inflammatory subphenotype. Cystatin C concentration does not appear to add to existing prognostic or predictive approaches.

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HARP-2试验中血浆胱抑素C、死亡率与急性呼吸窘迫综合征亚表型的关系

目的:评价胱抑素C作为急性呼吸窘迫综合征(ARDS)患者预后和预测指标的作用。设计、患者和环境:对HARP-2(辛伐他汀抑制急性肺损伤羟甲基戊二酰辅酶A还原酶以减少肺功能障碍)试验中患者的血浆样本进行了回顾性分析。HARP-2是一项多中心2b期试验，在英国和爱尔兰40家医院的普通重症监护室进行。采用酶联免疫吸附测定法(ELISA)对466例急性呼吸窘迫综合征患者血浆胱抑素C浓度进行定量分析。结果:在单因素分析中，急性呼吸窘迫综合征(ARDS)患者存活时间超过28天的血浆胱抑素C浓度显著较高(优势比[OR]， 1.39 [95% CI, 1.12-1.72];P = 0.002)。在对所选协变量进行调整的多变量模型中，未存活的ARDS患者胱抑素C浓度仍然较高，尽管这没有达到统计学意义(OR, 1.28 [95% CI, 0.96-1.71];P = 0.090)。胱抑素C浓度也与高炎症性ARDS显著相关(OR, 2.64 [95% CI, 1.83-3.89];P & lt;0.001)。在调整了胱抑素C浓度和ARDS亚表型的多变量模型中，高炎症性ARDS是死亡率的预后因素(OR, 2.06 [95% CI, 1.16-3.64];P = 0.013)，但胱抑素C浓度无统计学意义(OR, 1.16 [95% CI, 0.85-1.57];P = 0.346)。在多变量分析中，高炎症性ARDS可预测辛伐他汀对死亡率的有益影响(OR, 2.05 [95% CI, 1.16-3.62];P = 0.014)，但胱抑素C浓度无统计学意义(OR, 1.10 [95% CI, 0.77-1.56];P = 0.614)。结论:急性呼吸窘迫综合征(ARDS)患者胱抑素C浓度与死亡率的关系可能与炎症亚表型有关。胱抑素C浓度似乎不会增加现有的预后或预测方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Critical Care and Resuscitation CRITICAL CARE MEDICINE-

CiteScore

7.70

自引率

3.40%

发文量

审稿时长

>12 weeks

期刊介绍： ritical Care and Resuscitation (CC&R) is the official scientific journal of the College of Intensive Care Medicine (CICM). The Journal is a quarterly publication (ISSN 1441-2772) with original articles of scientific and clinical interest in the specialities of Critical Care, Intensive Care, Anaesthesia, Emergency Medicine and related disciplines. The Journal is received by all Fellows and trainees, along with an increasing number of subscribers from around the world. The CC&R Journal currently has an impact factor of 3.3, placing it in 8th position in world critical care journals and in first position in the world outside the USA and Europe.