Kirichenko Yu Yu, Varsieva V G, Shestakova K M, Chernichkina A D, Palienko A V, Buduscheva O I, Khabarova N V, Baskhanova S N, Belenkov Yu N, Ilgisonis I S, Appolonova S A
Sechenov First Moscow State Medical University, Moscow.
Kardiologiia. 2025 Jul 7;65(6):3-11. doi: 10.18087/cardio.2025.6.n2936.
Aim To determine the array of metabolomic profiles and structural and functional parameters of the vascular wall associated with the risk of cardiovascular toxicity of antitumor therapy (ATT) in oncohematological patients.Material and methods This study included 59 patients, among them 34 patients with lymphomas (non-Hodgkin and Hodgkin lymphoma) and 25 with multiple myeloma. Before and after 3 courses of ATT (anthracyclines, proteasome inhibitors), finger photoplethysmography and transthoracic echocardiography were performed as well as metabolomic profiling (98 metabolites) by high-performance liquid chromatography in combination with tandem mass spectrometry. Statistical analysis of the results included parametric and nonparametric tests, logistic regression, and cross-validation.Results The study showed that even before the initiation of ATT, cancer patients had signs of endothelial dysfunction and increased vascular wall stiffness (increased aSI, RI, and IO indices), which significantly worsened after the specific treatment. Metabolomic profiling identified a set of metabolites associated with the risk of cardiovascular toxicity, including increased concentrations of amino acids (asparagine, serine, glutamate, glutamine, taurine, citrulline), short-chain acylcarnitines (C18:1 OH-carnitine, C16:1 OH-carnitine, C14OH-carnitine, C2 carnitine), choline metabolism intermediates (TMAO, dimethylglycine, choline), tryptophan metabolites (hydroxyindoleacetic acid, kynurenic acid). Additionally, a logistic regression model was developed based on the analysis of the metabolomic profile, which showed a high prognostic power (AUC = 0.84) for predicting cardiovascular toxicity of ATT.Conclusion The study identified key metabolites and structural and functional parameters of blood vessels that allow detection of an increased risk of cardiovascular complications of ATT in patients with lymphomas and multiple myeloma before the initiation of a specific treatment. Increased concentrations of amino acids, acylcarnitines, and choline metabolites may serve as an additional risk factor for the onset/progression of cardiovascular complications. The proposed integrative approach, including both metabolomic profiling and non-invasive assessment of the vascular wall condition, opens broad prospects for personalized cardioprotection of cancer patients and more accurate monitoring of the cardiovascular status during ATT.
确定与肿瘤血液学患者抗肿瘤治疗（ATT）心血管毒性风险相关的代谢组学特征以及血管壁的结构和功能参数。
本研究纳入59例患者，其中34例淋巴瘤患者（非霍奇金淋巴瘤和霍奇金淋巴瘤）和25例多发性骨髓瘤患者。在3个疗程的ATT（蒽环类药物、蛋白酶体抑制剂）治疗前后，进行手指光电容积描记法和经胸超声心动图检查，并通过高效液相色谱结合串联质谱法进行代谢组学分析（98种代谢物）。结果的统计分析包括参数检验和非参数检验、逻辑回归和交叉验证。
研究表明，即使在开始ATT治疗之前，癌症患者就已经出现内皮功能障碍和血管壁硬度增加的迹象（aSI、RI和IO指数升高），在进行特定治疗后这些情况明显恶化。代谢组学分析确定了一组与心血管毒性风险相关的代谢物，包括氨基酸（天冬酰胺、丝氨酸、谷氨酸、谷氨酰胺、牛磺酸、瓜氨酸）、短链酰基肉碱（C18:1 OH-肉碱、C16:1 OH-肉碱、C14OH-肉碱、C2肉碱）、胆碱代谢中间体（氧化三甲胺、二甲基甘氨酸、胆碱）、色氨酸代谢物（羟基吲哚乙酸、犬尿酸）浓度升高。此外，基于代谢组学分析建立了一个逻辑回归模型，该模型在预测ATT的心血管毒性方面显示出较高的预测能力（AUC = 0.84）。
该研究确定了关键代谢物以及血管的结构和功能参数，这些参数能够在特定治疗开始前检测淋巴瘤和多发性骨髓瘤患者发生ATT心血管并发症的风险增加。氨基酸、酰基肉碱和胆碱代谢物浓度升高可能是心血管并发症发生/进展的额外危险因素。所提出的综合方法，包括代谢组学分析和血管壁状况的非侵入性评估，为癌症患者的个性化心脏保护以及在ATT期间更准确地监测心血管状态开辟了广阔前景。
