Incremental Value of a Metabolic Risk Score for Heart Failure Mortality: A Population-Based Study.

IF 6 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation: Genomic and Precision Medicine Pub Date : 2024-04-01 Epub Date: 2024-03-22 DOI:10.1161/CIRCGEN.123.004312

Jungnam Joo, Joseph J Shearer, Anna Wolska, Alan T Remaley, James D Otvos, Margery A Connelly, Maureen Sampson, Suzette J Bielinski, Nicholas B Larson, Hoyoung Park, Katherine M Conners, Sarah Turecamo, Véronique L Roger

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Abstract

Background: Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure.

Methods: Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed.

Results: The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%-51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9-2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3-1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno's C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP.

Conclusions: This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers.

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代谢风险评分对心力衰竭死亡率的增量价值：一项基于人群的研究

背景：心力衰竭是一种异质性综合征，死亡率居高不下。核磁共振波谱技术实现了高通量代谢组学，适用于精准表型分析。我们旨在利用靶向代谢组学得出代谢风险评分（MRS），从而改善心衰患者的死亡率风险分层：方法：利用核磁共振测量心衰社区队列血浆中的 21 种代谢物（脂蛋白亚种、支链氨基酸、丙氨酸、GlycA、酮体、葡萄糖和柠檬酸盐）。MRS 是通过 LASSO 惩罚性 Cox 回归和时间验证得出的。评估了 MRS 与死亡率之间的关系，以及与 Meta-Analysis Global Group in Chronic Heart Failure 临床风险评分和 NT-proBNP（N-末端前 B 型钠尿肽）水平相比，风险分层是否有所改善：研究共纳入 1382 名患者（中位年龄 78 岁，52% 为男性，43% 射血分数降低），5 年生存率为 48%（95% CI，46%-51%）。MRS 包括 9 种代谢物的测量。在验证数据集中，MRS 每增加 1 SD，死亡率就会增加很多（危险比为 2.2 [95% CI, 1.9-2.5]），在调整了慢性心力衰竭 Meta-Analysis Global Group 评分和 NT-proBNP 后，死亡率仍然增加（危险比为 1.6 [95% CI, 1.3-1.9]）。这些关联在射血分数上没有差异。综合分辨和净再分类指数以及Uno's C统计表明，与Meta-Analysis Global Group in Chronic Heart Failure和NT-proBNP相比，MRS的加入提高了分辨能力：结论：在心力衰竭社区队列中开发的这一 MRS 与巨大的超额死亡风险相关，并在既定风险评分和临床标记物之外改善了风险分层。

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来源期刊

Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

9.20

自引率

5.40%

发文量

144

期刊介绍： Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.