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.