Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Hypertens Res. 2022 Mar;45(3):464-473. doi: 10.1038/s41440-021-00825-9. Epub 2021 Dec 24.
This study aimed to identify the metabolomic alterations associated with hypertension (HTN) and the response of blood pressure (BP) to thiazide diuretics. A total of 50 participants previously untreated for HTN were prospectively recruited. After a 2-week lifestyle adjustment, 30 participants with systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg were classified into the HTN group and prescribed hydrochlorothiazide (HCTZ) at 50 mg per day for 2 weeks. The remaining 20 participants, who had relatively normal BP, were assigned to the normotension group. Metabolomic profiles related to the response of BP to thiazide diuretics were analyzed. A total of 73 differential metabolites were found to be associated with HTN, and 27 metabolites were significantly changed upon HCTZ treatment (HCTZ-sensitive metabolites). Among the identified metabolites, 7 (aspartate, histidine, C5-DC, C5-M-DC, C14:1, phosphatidylcholine ae C34:1, and phosphatidylcholine ae C34:3) were positively associated with HTN and decreased in abundance upon HCTZ treatment (HCTZ-reduced/HTN-associated metabolites). Moreover, multivariate analysis of 20 metabolites whose baseline levels were associated with the response of BP revealed that aspartate, glutamate, lysophosphatidylcholine C16:0, lysophosphatidylcholine C20:3, and sphingomyelin C24:1 were independently related to systolic BP reduction, and lysophosphatidylcholine C20:3 was independently associated with diastolic BP reduction. In conclusion, we identified 5 metabolites independently related to BP changes with HCTZ treatment. An advanced biomarker profile of thiazide-induced metabolomic changes may provide a clue with which to further explore the complex and mixed effects of thiazide treatment in a clinical setting.
这项研究旨在确定与高血压（HTN）相关的代谢组学改变，以及噻嗪类利尿剂对血压（BP）的反应。共有 50 名未经 HTN 治疗的参与者前瞻性招募。经过 2 周的生活方式调整，30 名收缩压≥140mmHg 和/或舒张压≥90mmHg 的参与者被分类为 HTN 组，并每天服用 50mg 氢氯噻嗪（HCTZ）治疗 2 周。其余 20 名血压相对正常的参与者被分配到正常血压组。分析了与噻嗪类利尿剂对 BP 反应相关的代谢组学特征。发现 73 个差异代谢物与 HTN 相关，27 个代谢物在 HCTZ 治疗时发生显著变化（HCTZ 敏感代谢物）。在鉴定出的代谢物中，有 7 种（天冬氨酸、组氨酸、C5-DC、C5-M-DC、C14:1、磷脂酰胆碱 ae C34:1 和磷脂酰胆碱 ae C34:3）与 HTN 呈正相关，并且在 HCTZ 治疗时丰度降低（HCTZ 减少/HTN 相关代谢物）。此外，对与 BP 反应相关的 20 种基线水平代谢物进行多元分析表明，天冬氨酸、谷氨酸、溶血磷脂酰胆碱 C16:0、溶血磷脂酰胆碱 C20:3 和神经鞘磷脂 C24:1 与收缩压降低独立相关，而溶血磷脂酰胆碱 C20:3 与舒张压降低独立相关。总之，我们确定了 5 种与 HCTZ 治疗后 BP 变化独立相关的代谢物。噻嗪类诱导的代谢组学变化的先进生物标志物谱可能为进一步探索噻嗪类治疗在临床环境中的复杂和混合效应提供线索。
