a Division of Medicine , Akershus University Hospital , Lørenskog , Norway.
b Center for Heart Failure Research , University of Oslo , Oslo , Norway.
Crit Rev Clin Lab Sci. 2019 Jan;56(1):33-60. doi: 10.1080/10408363.2018.1525335. Epub 2018 Nov 20.
Measurement of biomarkers has revolutionized the work-up of patients with suspected cardiovascular disease. The most widely used contemporary cardiovascular biomarkers are the natriuretic peptides in the diagnosis and prognosis of heart failure and cardiac troponins in the diagnosis of acute myocardial infarction. Numerous other biomarkers pertaining to diagnosis, prognosis, and risk prediction have been identified, but few have made their way to clinical practice. In this review, we will initially describe the fundamental approach to evaluate a novel biomarker. Before implementation of a biomarker into clinical practice, several stringent criteria related to its clinical utility are required. Essential statistical metrics such as discrimination, calibration, and reclassification are required to properly evaluate prediction models. We will then discuss the biomarkers according to main groups of cardiovascular pathology:1. myocardial injury (cardiac troponins, heart-type fatty acid-binding protein, cardiac myosin binding protein-C);2. myocardial stress (A-type and B-type natriuretic peptides, mid-regional pro-adrenomedullin, copeptin); 3. inflammation (C-reactive protein, interleukin 6, growth differentiation factor 15, soluble suppressor of tumorigenicity 2, galectin-3);4. platelet activation (soluble CD40 ligand, P-selectin);5. plaque instability (lipoprotein-associated phospholipase A, matrix metalloproteinase-9);6. systemic stress (catecholamines, granin proteins);7. calcium homeostasis (secretoneurin). Finally, we will discuss novel applications of cardiovascular biomarkers, more specifically prediction of ventricular arrhythmias, and the use of biomarkers in composite risk prediction models.
生物标志物的测量方法极大地改变了疑似心血管疾病患者的检查方式。目前应用最广泛的当代心血管生物标志物包括心力衰竭诊断和预后的利钠肽和急性心肌梗死诊断的心肌肌钙蛋白。还发现了许多其他与诊断、预后和风险预测相关的生物标志物,但很少有标志物能进入临床实践。在这篇综述中,我们将首先描述评估新型生物标志物的基本方法。在将生物标志物应用于临床实践之前,需要满足与其临床应用相关的几个严格标准。需要必要的统计指标,如区分度、校准度和重新分类,以正确评估预测模型。然后,我们将根据心血管病理学的主要组别讨论生物标志物:1. 心肌损伤(心肌肌钙蛋白、心脏型脂肪酸结合蛋白、肌球蛋白结合蛋白-C);2. 心肌应激(A 型和 B 型利钠肽、中段 pro-肾上腺髓质肽、 copeptin);3. 炎症(C 反应蛋白、白细胞介素 6、生长分化因子 15、可溶性肿瘤抑制物 2、半乳糖凝集素-3);4. 血小板激活(可溶性 CD40 配体、P 选择素);5. 斑块不稳定(脂蛋白相关磷脂酶 A、基质金属蛋白酶-9);6. 全身应激(儿茶酚胺、颗粒蛋白);7. 钙稳态(分泌酶神经肽)。最后,我们将讨论心血管生物标志物的新应用,特别是预测室性心律失常以及生物标志物在复合风险预测模型中的应用。