Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy; Magnetic Resonance Center (CERM), University of Florence, 50019 Sesto Fiorentino, Italy.
Atherothrombotic Center, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50134 Florence, Italy.
Life Sci. 2024 Aug 15;351:122796. doi: 10.1016/j.lfs.2024.122796. Epub 2024 Jun 7.
Long-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant drugs can have specific effects on the metabolism of patients. Here we characterize, for the first time, the serum metabolomic and lipoproteomic profiles of AF patients treated with anticoagulants: vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs).
Serum samples of 167 AF patients (median age 78 years, 62 % males, 70 % on DOACs treatment) were analyzed via high resolution H nuclear magnetic resonance (NMR) spectroscopy. Data on 25 metabolites and 112 lipoprotein-related fractions were quantified and analyzed with multivariate and univariate statistical approaches.
Our data provide evidence that patients treated with VKAs and DOACs present significant differences in their profiles: lower levels of alanine and lactate (odds ratio: 1.72 and 1.84), free cholesterol VLDL-4 subfraction (OR: 1.75), triglycerides LDL-1 subfraction (OR: 1.80) and 4 IDL cholesterol fractions (ORs ∼ 1.80), as well as higher levels of HDL cholesterol (OR: 0.48), apolipoprotein A1 (OR: 0.42) and 7 HDL cholesterol fractions/subfractions (ORs: 0.40-0.51) are characteristic of serum profile of patients on DOACs' therapy.
Our results support the usefulness of NMR-based metabolomics for the description of the effects of oral anticoagulants on AF patient circulating metabolites and lipoproteins. The higher serum levels of HDL cholesterol observed in patients on DOACs could contribute to explaining their reduced cardiovascular risk, suggesting the need of further studies in this direction to fully understand possible clinical implications.
长期口服抗凝是预防房颤（AF）患者发生缺血性卒中的主要治疗方法。不同类型的口服抗凝药物可能对患者的代谢产生特定的影响。在这里，我们首次描述了接受抗凝治疗的 AF 患者（维生素 K 拮抗剂（VKAs）或直接口服抗凝剂（DOACs））的血清代谢组学和脂蛋白组学特征。
对 167 例 AF 患者（中位数年龄 78 岁，62%为男性，70%接受 DOACs 治疗）的血清样本进行了高分辨率 H 核磁共振（NMR）光谱分析。通过多元和单变量统计方法对 25 种代谢物和 112 种脂蛋白相关分数进行了定量和分析。
我们的数据表明，接受 VKAs 和 DOACs 治疗的患者在其谱中有显著差异：丙氨酸和乳酸水平较低（比值比：1.72 和 1.84），VLDL-4 亚组分游离胆固醇（比值比：1.75），LDL-1 亚组分甘油三酯（比值比：1.80）和 4 个 IDL 胆固醇分数（比值比∼1.80），以及较高的 HDL 胆固醇水平（比值比：0.48），载脂蛋白 A1（比值比：0.42）和 7 个 HDL 胆固醇分数/亚分数（比值比：0.40-0.51）是 DOACs 治疗患者血清谱的特征。
我们的结果支持基于 NMR 的代谢组学用于描述口服抗凝剂对 AF 患者循环代谢物和脂蛋白的影响。在接受 DOACs 治疗的患者中观察到较高的血清 HDL 胆固醇水平可能有助于解释其降低的心血管风险，这表明需要进一步研究这一方向，以充分了解可能的临床意义。
