Wimalanathan Thakshani, Paus Michael Fredrik, Brox Skranes Julia, Berge Trygve, Tveit Arnljot, Røsjø Helge, Omland Torbjørn, Lyngbakken M N, Lagethon Heck Siri
Department of Diagnostic Imaging, Division of Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway.
K.G. Jebsen Center for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
J Appl Lab Med. 2025 Mar 3;10(2):392-405. doi: 10.1093/jalm/jfae145.
Myocardial fibrosis is associated with a poor outcome for patients with cardiovascular disease (CVD). Growth differentiation factor 15 (GDF-15) concentrations predict the risk of death in patients with CVD, but the underlying pathophysiological mechanisms are poorly understood. We aimed to assess the associations between biomarkers of cellular stress and inflammation (GDF-15), cardiac injury (cardiac troponin T [cTnT]), and stretch (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), and subsequent focal and diffuse myocardial fibrosis assessed by cardiac magnetic resonance (CMR) imaging.
We measured GDF-15, cTnT, and NT-proBNP in 200 study participants without known coronary artery disease or renal dysfunction from the population-based Akershus Cardiac Examination 1950 Study at baseline in 2012 to 2015. Focal myocardial scars and diffuse fibrosis were assessed by late gadolinium enhancement imaging and septal extracellular volume fraction (ECV) by CMR 4 to 7 years later. The relationships between cardiac biomarkers and CMR parameters were assessed by logistic regression analysis adjusted for common cardiovascular risk factors.
The median age was 63.9 (interquartile range 63.4-64.5) years and 49% were women. GDF-15 (adjusted odds ratio [aOR] 4.40, 95% CI 1.09-17.72) and cTnT (aOR 1.59, 95% CI 1.01-2.50) were associated with nonischemic scars in the fully adjusted model. cTnT (aOR 2.45, 95% CI 1.41-4.25) and NT-proBNP (aOR 3.12, 95% CI 1.55-6.28) were associated with ischemic scars. None of the biomarkers were significantly associated with elevated ECV.
In a general population cohort, GDF-15, an emerging biomarker of cellular stress and inflammation, associates with nonischemic scars. Biomarkers of myocardial injury and stretch associate with ischemic scars, while no biomarker was associated with diffuse fibrosis as assessed by CMR.
心肌纤维化与心血管疾病（CVD）患者的不良预后相关。生长分化因子15（GDF - 15）浓度可预测CVD患者的死亡风险，但其潜在的病理生理机制尚不清楚。我们旨在评估细胞应激和炎症生物标志物（GDF - 15）、心脏损伤（心肌肌钙蛋白T [cTnT]）及牵张（N末端B型利钠肽原[NT - proBNP]）与随后通过心脏磁共振（CMR）成像评估的局灶性和弥漫性心肌纤维化之间的关联。
我们在2012年至2015年基线时，对基于人群的阿克什胡斯心脏检查1950研究中200名无已知冠状动脉疾病或肾功能不全的研究参与者测量了GDF - 15、cTnT和NT - proBNP。4至7年后通过CMR的钆延迟增强成像评估局灶性心肌瘢痕和弥漫性纤维化，并通过间隔细胞外容积分数（ECV）进行评估。通过对常见心血管危险因素进行校正的逻辑回归分析评估心脏生物标志物与CMR参数之间的关系。
中位年龄为63.9（四分位间距63.4 - 64.5）岁，49%为女性。在完全校正模型中，GDF - 15（校正比值比[aOR] 4.40，95%置信区间[CI] 1.09 - 17.72）和cTnT（aOR 1.59，95% CI 1.01 - 2.50）与非缺血性瘢痕相关。cTnT（aOR 2.45，95% CI 1.41 - 4.25）和NT - proBNP（aOR 3.12，95% CI 1.55 - 6.28）与缺血性瘢痕相关。没有一种生物标志物与升高的ECV显著相关。
在一个普通人群队列中，GDF - 15作为一种新出现的细胞应激和炎症生物标志物，与非缺血性瘢痕相关。心肌损伤和牵张的生物标志物与缺血性瘢痕相关，而没有生物标志物与CMR评估的弥漫性纤维化相关。
