Jacobson Tyler A, Rahbari Kian J, Schwartz William A, Bae Yeunook, Zhang Runze, Nunes Denise A, Huang Cathelin, Issa Ramzy P, Smilowitz Karen, Yan Lily D, Hirschhorn Lisa R, Khan Sadiya S, Huffman Mark D, Miller Gregory E, Feinglass Joseph M, McDade Thomas W, Funk William E
Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL USA.
Department of Medicine Vanderbilt University Medical Center Nashville TN USA.
J Am Heart Assoc. 2025 Mar 18;14(6):e037454. doi: 10.1161/JAHA.124.037454. Epub 2025 Mar 13.
Dried blood spot sampling offers a scalable strategy to close diagnostic gaps and improve global surveillance for cardiovascular-kidney-metabolic syndrome. However, assay performance and the extent of validity vary widely between biomarkers used in cardiovascular-kidney-metabolic health assessment under different settings and have not been well described. To fill this gap, we conducted a systematic search of the literature and a narrative synthesis through April 2024 and included reports with laboratory or field validation measuring biomarkers that can be used in cardiovascular-kidney-metabolic health assessment. We categorized assays into categories based on laboratory validation: excellent performance (r>0.95 with gold standard methods and coefficients of variation <5%), very good performance (r>0.90 and coefficients of variation <10%), reasonable performance (r>0.80 and coefficients of variation <15%), and poor performance (r<0.80 or coefficients of variation >15%). The extent of validation was determined by the total number of field validation studies with strong agreement. Hemoglobin A1c has strong laboratory and field validation and should be considered for expansion into clinical testing in low-resource settings. Traditional lipid biomarkers showed poor performance in field validation studies, but apoB (apolipoprotein B), creatinine, cystatin C, and NT-proBNP (N-terminal prohormone of brain natriuretic peptide) showed promising initial laboratory validation results and deserve greater attention in field validation studies. High-sensitivity C-reactive protein has strong laboratory and field validation but has limited clinical utility. Dried blood spot assays have been developed for biomarkers that offer mechanistic insights including inflammatory and vascular injury markers, fatty acids, malondialdehyde, asymmetric dimethylarginine, trimethylamine N-oxide, carnitines, and omics.
干血斑采样提供了一种可扩展的策略，以弥合诊断差距并改善对心血管-肾脏-代谢综合征的全球监测。然而，在不同环境下用于心血管-肾脏-代谢健康评估的生物标志物之间，检测性能和有效性程度差异很大，且尚未得到充分描述。为了填补这一空白，我们对截至2024年4月的文献进行了系统检索并进行了叙述性综合分析，纳入了有关测量可用于心血管-肾脏-代谢健康评估的生物标志物的实验室或现场验证报告。我们根据实验室验证将检测分为几类：卓越性能（与金标准方法的r>0.95且变异系数<5%）、非常好的性能（r>0.90且变异系数<10%）、合理性能（r>0.80且变异系数<15%）和差的性能（r<0.80或变异系数>15%）。验证程度由具有高度一致性的现场验证研究总数确定。糖化血红蛋白具有强大的实验室和现场验证，应考虑在资源匮乏地区扩展到临床检测。传统脂质生物标志物在现场验证研究中表现不佳，但载脂蛋白B、肌酐、胱抑素C和N末端脑钠肽前体在初步实验室验证中显示出有前景的结果，值得在现场验证研究中给予更多关注。高敏C反应蛋白具有强大的实验室和现场验证，但临床应用有限。已开发出用于提供机制见解的生物标志物的干血斑检测方法，包括炎症和血管损伤标志物、脂肪酸、丙二醛、不对称二甲基精氨酸、氧化三甲胺、肉碱和组学。
