本文由小咖机器人翻译整理

期刊来源：Ann Intern Med

原文链接：https://doi.org/10.7326/M23-2328

摘要内容如下：

背景

心力衰竭（HF）是一种复杂的临床综合征，死亡率高。目前的风险分层方法缺乏精确性。高通量蛋白质组学可以提高风险预测。其在临床实践中用于指导HF患者的管理依赖于临床获益的验证和证据。

客观

开发并验证心衰患者死亡率的蛋白质风险评分。

设计

社区组群。

设置

明尼苏达州东南部。

参与者

在2003年至2012年期间登记了心衰患者，并随访至2021年。

测量

使用Somascan试验（Somalogic）测定了1351例HF患者的7289种血浆蛋白。在2003年至2007年（开发队列）和2008年至2012年（验证队列）登记的患者中，使用最小绝对收缩和选择算子回归和时间验证得出蛋白质风险评分。多变量Cox回归用于检验蛋白质风险评分与死亡率之间的关系。使用校准图、决策曲线和相对效用分析评估蛋白质风险评分预测5年死亡风险的性能，并与临床模型进行比较，包括慢性心力衰竭死亡率风险评分和N-末端B型利钠肽前体的荟萃分析全球小组。

结果

发育（n=855；中位年龄78岁；50%为妇女；29%，射血分数<40%）和验证队列（n=496；中位年龄76岁；45%为女性；33%（射血分数<40%）基本相似。在发育队列中，选择了38种独特的蛋白质用于蛋白质风险评分。独立于射血分数，蛋白风险评分显示出良好的校准，重新分类死亡风险，特别是在风险分布的极端情况下，并且与临床模型相比，显示出更大的临床实用性。

局限性

参与者主要是欧洲血统，这可能限制了研究结果对不同患者群体的可推广性。

结论

蛋白质风险评分的验证证明了良好的校准和预测益处的证据，以对心衰患者的死亡风险进行分层，优于临床方法。需要进一步的研究来前瞻性地评估评分在不同人群中的表现，并确定干预措施的风险阈值。

主要资金来源

美国国立卫生研究院国家心脏、肺和血液研究所的内部研究部门。

英文原文如下：

Abstracts

BACKGROUND  Heart failure (HF) is a complex clinical syndrome with high mortality. Current risk stratification approaches lack precision. High-throughput proteomics could improve risk prediction. Its use in clinical practice to guide the management of patients with HF depends on validation and evidence of clinical benefit.

OBJECTIVE  To develop and validate a protein risk score for mortality in patients with HF.

DESIGN  Community-based cohort.

SETTING  Southeast Minnesota.

PARTICIPANTS  Patients with HF enrolled between 2003 and 2012 and followed through 2021.

MEASUREMENTS  A total of 7289 plasma proteins in 1351 patients with HF were measured using the SomaScan Assay (SomaLogic). A protein risk score was derived using least absolute shrinkage and selection operator regression and temporal validation in patients enrolled between 2003 and 2007 (development cohort) and 2008 and 2012 (validation cohort). Multivariable Cox regression was used to examine the association between the protein risk score and mortality. The performance of the protein risk score to predict 5-year mortality risk was assessed using calibration plots, decision curves, and relative utility analyses and compared with a clinical model, including the Meta-Analysis Global Group in Chronic Heart Failure mortality risk score and N-terminal pro-B-type natriuretic peptide.

RESULTS  The development (n = 855; median age, 78 years; 50% women; 29% with ejection fraction <40%) and validation cohorts (n = 496; median age, 76 years; 45% women; 33% with ejection fraction <40%) were mostly similar. In the development cohort, 38 unique proteins were selected for the protein risk score. Independent of ejection fraction, the protein risk score demonstrated good calibration, reclassified mortality risk particularly at the extremes of the risk distribution, and showed greater clinical utility compared with the clinical model.

LIMITATION  Participants were predominantly of European ancestry, potentially limiting the generalizability of the findings to different patient populations.

CONCLUSION  Validation of the protein risk score demonstrated good calibration and evidence of predicted benefits to stratify the risk for death in HF superior to that of clinical methods. Further studies are needed to prospectively evaluate the score's performance in diverse populations and determine risk thresholds for interventions.

PRIMARY FUNDING SOURCE  Division of Intramural Research at the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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