The relationship between plasma cystatin C, mortality and acute respiratory distress syndrome subphenotype in the HARP-2 trial.
The relationship between plasma cystatin C, mortality and acute respiratory distress syndrome subphenotype in the HARP-2 trial.
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DOI：
10.51893/2022.3.oa4
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发表时间：
2022-09-05
期刊：
影响因子：
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通讯作者：
Taggart CC
中科院分区：
文献类型：
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作者：
McKelvey MC;Bradbury I;McDowell C;Calfee CS;Weldon S;O'Kane CM;McAuley DF;Taggart CC
目的：评价胱抑素C作为急性呼吸窘迫综合征（ARDS）患者预后和预测标志物的性能。设计、患者和环境：对HARP-2（在急性肺损伤中使用辛伐他汀抑制羟甲基戊二酰辅酶A还原酶以减少肺功能障碍）试验-一项在英国和爱尔兰的40家医院的普通重症监护室进行的多中心、2b期试验中纳入的患者的血浆样本进行了回顾性分析。采用ELISA（酶联免疫吸附试验）定量测定466例ARDS患者（在随机分配试验前）血浆中的胱抑素C浓度。结果如下：在单变量分析中，未存活超过28天的ARDS患者的血浆胱抑素C浓度显著较高（比值比[OR]，1.39 [95%CI，1.12-1.72]; P = 0.002）。在针对选定的协变量调整的多变量模型中，未存活的ARDS患者的胱抑素C浓度仍然较高，尽管这未达到统计学显著性（OR，1.28 [95%CI，0.96-1.71]; P = 0.090）。Cystatin C浓度也与高炎症性ARDS显著相关（OR，2.64 [95% CI，1.83-3.89]; P < 0.001）。在针对半胱氨酸蛋白酶抑制剂C浓度和ARDS亚表型调整的多变量模型中，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），但半胱氨酸蛋白酶抑制剂C浓度则不然（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浓度则不能预测（OR，1.10 [95%CI，0.77-1.56]; P = 0.614）。结论：CystatinC浓度与ARDS死亡率的关系可能依赖于炎症亚表型。胱抑素C浓度似乎并没有增加现有的预后或预测方法。
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.