4.7 Article

Accelerating Biomarker Discovery Through Electronic Health Records, Automated Biobanking, and Proteomics

期刊

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 73, 期 17, 页码 2195-2205

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2019.01.074

关键词

biomarkers; electronic health records; heart failure; proteomics

资金

  1. Vanderbilt Institute for Clinical and Translational Research (VICTR)
  2. National Institutes of Health (NIH) [K12 HL109019, K23 HL128928-01A1, R01HL133870-01A1, R01HL132320-01, UL1TR000dd5, R01HL140074]
  3. Vanderbilt University Medical Center institutional instrumentation awards [1S10OD017985-01, R-1306-0d869]
  4. European Research Council
  5. Swedish Heart-Lung Foundation
  6. Wallenberg Center for Molecular Medicine at Lund University
  7. Swedish Research Council
  8. Crafoord Foundation

向作者/读者索取更多资源

BACKGROUND Circulating biomarkers can facilitate diagnosis and risk stratification for complex conditions such as heart failure (HF). Newer molecular platforms can accelerate biomarker discovery, but they require significant resources for data and sample acquisition. OBJECTIVES The purpose of this study was to test a pragmatic biomarker discovery strategy integrating automated clinical biobanking with proteomics. METHODS Using the electronic health record, the authors identified patients with and without HF, retrieved their discarded plasma samples, and screened these specimens using a DNA aptamer-based proteomic platform (1,129 proteins). Candidate biomarkers were validated in 3 different prospective cohorts. RESULTS In an automated manner, plasma samples from 1,315 patients (31% with HF) were collected. Proteomic analysis of a 96-patient subset identified 9 candidate biomarkers (p < 4.42 x 10(-5)). Two proteins, angiopoietin-2 and thrombospondin-2, were associated with HF in 3 separate validation cohorts. In an emergency department-based registry of 852 dyspneic patients, the 2 biomarkers improved discrimination of acute HF compared with a clinical score (p < 0.0001) or clinical score plus B-type natriuretic peptide (p = 0.02). In a community-based cohort (n = 768), both biomarkers predicted incident HF independent of traditional risk factors and N-terminal pro-B-type natriuretic peptide (hazard ratio per SD increment: 1.35 [95% confidence interval: 1.14 to 1.61; p = 0.0007] for angiopoietin-2, and 1.37 [95% confidence interval: 1.06 to 1.79; p = 0.02] for thrombospondin-2). Among 30 advanced HF patients, concentrations of both biomarkers declined (80% to 84%) following cardiac transplant (p < 0.001 for both). CONCLUSIONS A novel strategy integrating electronic health records, discarded clinical specimens, and proteomics identified 2 biomarkers that robustly predict HF across diverse clinical settings. This approach could accelerate biomarker discovery for many diseases. (C) 2019 by the American College of Cardiology Foundation.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据