Hypertension is a major chronic non-communicable disease closely associated with metabolic disorders and characterized by significant population heterogeneity. The traditional Chinese medicine formula Chaigu Decoction (CGD) has demonstrated unique antihypertensive efficacy in patients with hypertension of liver depression and blood deficiency pattern; however, its therapeutic characteristics across different sexes, ages, and other subgroups, as well as its metabolic regulatory features, remain to be further elucidated.

To investigate the clinical efficacy of CGD combined with antihypertensive drugs in treating hypertension of liver depression and blood deficiency pattern and to explore its underlying metabolic mechanisms.

This study was designed as a prospective randomized controlled trial. Patients with hypertension of liver depression and blood deficiency pattern who visited the Department of Cardiology at Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine between April 2022 and April 2023 were enrolled. One hundred eligible patients were randomly assigned in a 1∶1 ratio to either the conventional treatment group (nifedipine controlled-release 30 mg once daily plus olmesartan medoxomil 20 mg once daily, orally) or the CGD group (conventional treatment plus CGD) for one month. Blood pressure changes and control rates (target <130/80 mmHg, 1 mmHg=0.133 kPa) were monitored, and subgroup analyses were performed. Thirty-two patients were randomly selected from each group, and 32 healthy individuals were concurrently enrolled as healthy controls. Serum samples were collected for untargeted metabolomic analysis to screen differential metabolites and perform pathway enrichment analysis.

After one month of treatment, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly from baseline in both groups (P<0.05). The CGD group exhibited greater reductions in SBP (ΔSBP) and DBP (ΔDBP) and a higher blood pressure control rate than the conventional treatment group (P<0.05). Subgroup analysis revealed that among female patients, ΔSBP was greater in the CGD group than in the conventional treatment group (P<0.001), with a significant interaction between sex and treatment on ΔSBP (P_interaction =0.022). In patients aged≥65 years, ΔSBP was also greater in the CGD group (P=0.007); however, no significant interaction was observed between age and treatment on ΔSBP (P_interaction =0.090). No significant interaction was observed between body type and treatment on ΔSBP (P_interaction =0.377). Sex, age, and body type showed no significant interactions with the reduction in DBP (ΔDBP) (P_interaction>0.05). Metabolomic analysis, with a variable importance in projection (VIP) score≥1.0 as the threshold, identified 30 potential differential metabolites, including 14 between healthy controls and hypertensive patients, involving steroid, fatty acid, bile acid, and phospholipid metabolism pathways. In the post-treatment intergroup comparison, serum levels of lysophosphatidylcholine (LPC) (16∶0/0∶0) and LPC (16∶1/0∶0) were higher in the CGD group than in the conventional treatment group (fold change=1.08 and 1.21, respectively; P<0.05), representing key differential metabolites, with LPC (16∶1/0∶0) showing a relatively greater upregulation.

CGD combined with conventional antihypertensive therapy demonstrates synergistic blood pressure–lowering effects and improves blood pressure control rates in patients with hypertension of liver depression and blood deficiency pattern. Sex showed a significant interaction with SBP reduction. Although the interaction between age and treatment was not statistically significant, patients aged≥65 years exhibited greater SBP reduction with CGD. Metabolomic findings suggest that CGD may exert vascular protective effects by regulating glycerophospholipid metabolism and promoting the conversion of LPC 16∶0 to LPC 16∶1. Female and elderly hypertensive patients may represent populations with greater therapeutic potential for CGD, providing novel evidence for precision diagnosis and treatment of hypertension based on metabolic features.

高血压是一种与代谢紊乱密切相关、具有显著人群异质性的重大慢性非传染性疾病。传统复方柴归汤在肝郁血虚型高血压患者中显示出独特的降压优势，但其对不同性别、年龄等人群的治疗特点及在代谢调控方面的作用特征仍有待进一步阐明。

探究柴归汤联合降压药治疗肝郁血虚型高血压的临床疗效及其潜在代谢机制。

本研究采用前瞻性随机对照试验，选取2022年4月—2023年4月在南京中医药大学附属无锡医院心血管科就诊的肝郁血虚型高血压患者作为研究对象。将100例肝郁血虚型高血压患者按1∶1随机分为西药组（硝苯地平控释片30 mg/次，1次/d+奥美沙坦酯片20 mg/次，1次/d，口服）和柴归组（在西药组治疗基础上加用柴归汤），治疗1个月；监测治疗期间血压变化及达标率（<130/80 mmHg，1 mmHg=0.133 kPa），并进行亚组分析。从每组随机选取32例患者，同时纳入32名健康人群作为正常对照（健康组），采集血清进行非靶向代谢组学检测，筛选差异代谢物并富集相关代谢通路。

治疗1个月后，两组患者收缩压（SBP）和舒张压（DBP）均较治疗前下降（P<0.05）。柴归组患者SBP变化量（ΔSBP）、DBP变化量（ΔDBP）及血压达标率均高于西药组（P<0.05）。亚组分析显示，女性患者中柴归组ΔSBP高于西药组（P<0.001），性别对两组ΔSBP有交互作用（P_交互=0.022）。≥65岁患者中柴归组ΔSBP高于西药组（P=0.007），但年龄对ΔSBP无交互作用（P_交互=0.090）。体型对ΔSBP无交互作用（P_交互=0.377）。性别、年龄、体型均对ΔDBP无交互作用（P_交互>0.05）。代谢组学分析以变量投影重要性（VIP）≥1.0为阈值，共筛选出30种潜在差异代谢物，其中健康组与疾病组之间存在14种差异代谢物，涉及类固醇、脂肪酸、胆汁酸和磷脂代谢等通路。治疗后组间比较，柴归组血清中溶血磷脂酰胆碱（LPC）（16∶0/0∶0）与LPC（16∶1/0∶0）表达强度高于西药组[倍数变化（FC）=1.08、1.21，P<0.05]，为关键差异代谢物，且LPC（16∶1/0∶0）上调幅度相对更大。

柴归汤联合西药在肝郁血虚型高血压患者中显示出协同降压效果，可提高血压达标率。性别对SBP有交互作用，年龄则仅呈现获益优势。代谢组学提示其可能通过调节甘油磷脂代谢、促进LPC 16∶0向LPC 16∶1转化发挥血管保护作用。女性及老年高血压患者可能是柴归汤的优势人群，为基于代谢特征的高血压精准诊疗提供了新依据。