Department of Medicine, Universidad Complutense de Madrid (UCM), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Hematology Department, IML, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos, Profesor Martín Lagos s/n, 28040 Madrid, Spain.
Department of Medicine, Universidad Complutense de Madrid (UCM), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Hematology Department, IML, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos, Profesor Martín Lagos s/n, 28040 Madrid, Spain.
Int J Cardiol. 2022 Aug 15;361:91-100. doi: 10.1016/j.ijcard.2022.05.004. Epub 2022 May 6.
Heart failure with preserved ejection fraction (HFpEF) is a disorder related to patient comorbidities and aging. Whether mitochondrial dysfunction is present during HFpEF decompensation versus the stable phase is largely unknown. The aim of the present study was to identify mitochondrial and cell metabolism blood biomarkers in older patients with acute and stable HFpEF.
Peripheral blood biomarkers were investigated in a group of eight to 12 patients aged 80-96 years and diagnosed with HFpEF first when they were in decompensated phase and then at least three months later in stable phase. Their data were compared to two control groups with an equal number of participants and sex proportions. One group was age matched and the other included individuals aged between 22 and 44 years.
Decompensated patients experienced an increased mitochondrial superoxide production and mitochondrial mass, lower mitochondrial DNA copy number and LDHB expression, and higher lactate level compared to the stable stage. The stable phase was characterized by a sharp reduction in formate level. Multivariate analysis indicated that formate, lactate, and histidine can distinguish both of the HFpEF phases. Many of these parameters, including LDHB, lactate, formate, and mitochondrial mass, followed an age-related pattern, with acute HFpEF at its apex or nadir, suggesting that it represents an exacerbation of an aging-related process.
We identified distinct blood biomarkers of chronic and decompensated HFpEF phases. The data underlined the relationship between HFpEF and aging. These findings could be used to monitor patients and might be therapeutically targeted.
射血分数保留的心力衰竭（HFpEF）是一种与患者合并症和衰老相关的疾病。在 HFpEF 失代偿与稳定期是否存在线粒体功能障碍尚不清楚。本研究旨在确定急性和稳定的 HFpEF 老年患者的血液线粒体和细胞代谢生物标志物。
研究小组对 8 至 12 名 80 至 96 岁的 HFpEF 患者进行了外周血生物标志物检测，这些患者在失代偿期时首次被诊断为 HFpEF，然后至少在 3 个月后进入稳定期。他们的数据与两个对照组进行了比较，对照组的参与者数量和性别比例相同。一组是年龄匹配的，另一组包括 22 至 44 岁的个体。
与稳定期相比，失代偿患者的线粒体超氧化物产生和线粒体质量增加，线粒体 DNA 拷贝数和 LDHB 表达降低，乳酸水平升高。稳定期的特征是甲酸水平急剧下降。多变量分析表明，甲酸、乳酸和组氨酸可以区分 HFpEF 的两个阶段。包括 LDHB、乳酸、甲酸和线粒体质量在内的许多参数都遵循与年龄相关的模式，急性 HFpEF 处于顶峰或最低点，这表明它代表了与衰老相关过程的恶化。
我们确定了慢性和失代偿性 HFpEF 阶段的不同血液生物标志物。这些数据强调了 HFpEF 与衰老之间的关系。这些发现可用于监测患者，可能是治疗的靶点。
