Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, University of Murcia, Spain.
Eur J Intern Med. 2012 Mar;23(2):169-74. doi: 10.1016/j.ejim.2011.08.022. Epub 2011 Sep 15.
The growth differentiation factor 15 (GDF-15) has been shown up-regulated in stress conditions and to have regulatory actions in myocyte hypertrophy. We hypothesized that GDF-15 could be related to disease severity and functional status in patients with hypertrophic cardiomyopathy (HCM).
We performed a study which includes 102 consecutive outpatient HCM subjects, 73% males, aged 47.1±14.6 years. A complete history and clinical examination was performed, including 12-lead electrocardiogram, echocardiography, symptom-limited treadmill exercise, 24-hour ECG-Holter monitoring, and magnetic resonance with Gadolinium. Several biomarkers, associated with myocardial remodeling and damage, were compared to GDF-15 levels. The assays were performed with commercial ELISAs or standardized methods when available. There was a significant association between GDF-15 levels and comorbidities, being higher in hypertension (p=0.001), diabetes (p=0.030), atrial fibrillation (p=0.012), dyspnea (p=0.020) and NYHA≥II functional class (p=0.037). GDF-15 levels were positively correlated with clinical variables (age, worse exercise capacity and mild renal dysfunction) and biomarkers of interstitial remodeling, such as metalloproteinase-2 (r: 0.40; p=0.009), N-terminal pro-B-type natriuretic peptide (r: 0.28; p=0.049), high-sensitivity troponin T (r: 0.30; p=0.003) and von Willebrand factor (r: 0.33; p=0.001). Multivariate analysis was assessed to estimate the involvement of these different factors in the GDF-15 levels, confirming the independent implication of severe dyspnea and functional status.
The present results show that higher levels of GDF-15 are associated to conditions of severe disease in HCM. Hence, GDF-15 is suggested as a novel marker related to the severity and could represent a further useful tool in monitoring functional capacity of HCM patients.
生长分化因子 15（GDF-15）已被证明在应激条件下上调，并在心肌细胞肥大中具有调节作用。我们假设 GDF-15 可能与肥厚型心肌病（HCM）患者的疾病严重程度和功能状态有关。
我们进行了一项研究，纳入了 102 例连续的门诊 HCM 患者，其中 73%为男性，年龄 47.1±14.6 岁。进行了完整的病史和临床检查，包括 12 导联心电图、超声心动图、症状限制跑步机运动、24 小时心电图-Holter 监测和钆增强磁共振成像。比较了几种与心肌重构和损伤相关的生物标志物与 GDF-15 水平。使用商业 ELISA 或有标准方法时使用标准化方法进行检测。GDF-15 水平与合并症之间存在显著相关性，在高血压（p=0.001）、糖尿病（p=0.030）、心房颤动（p=0.012）、呼吸困难（p=0.020）和 NYHA≥II 功能分级（p=0.037）中更高。GDF-15 水平与临床变量（年龄、运动能力更差和轻度肾功能障碍）和间质重构的生物标志物（基质金属蛋白酶-2（r：0.40；p=0.009）、N 末端 pro-B 型利钠肽（r：0.28；p=0.049）、高敏肌钙蛋白 T（r：0.30；p=0.003）和血管性血友病因子（r：0.33；p=0.001））呈正相关。进行了多变量分析以评估这些不同因素在 GDF-15 水平中的参与程度，证实严重呼吸困难和功能状态的独立影响。
目前的结果表明，较高水平的 GDF-15 与 HCM 中的严重疾病状况有关。因此，GDF-15 被认为是一种与严重程度相关的新型标志物，并可能成为监测 HCM 患者功能能力的另一个有用工具。
