Multidimensional Mechanisms of Hypertension and Advances in Diagnosis and Integrated TCM-Based Treatment: A Review

Introduction

Hypertension remains one of the most prevalent chronic cardiovascular conditions worldwide and represents a major modifiable risk factor for cardiovascular disease, stroke, and chronic kidney disease; thus imposing substantial burdens on global public health systems.¹ Recent large-scale epidemiological analyses indicated that its global prevalence continues to increase due to persistence in suboptimal awareness, treatment and control rates across both developed and developing regions, highlighting ongoing challenges in effective disease management.^1,2 In addition to traditional risk factors such as obesity, high sodium intake and physical inactivity, emerging evidence suggests that environmental determinants, including climate variability and socioeconomic transitions, further contribute to the evolving epidemiological landscape of hypertension.³

The pathophysiology of hypertension is complex and involves the interplay of numerous regulatory systems, including vascular endothelial function, the renin–angiotensin–aldosterone system (RAAS), sympathetic nervous system activation, and metabolic and inflammatory pathways.⁴ In addition, increasing attention has been directed toward molecular and genetic contributors, such as oxidative stress–related signaling pathways and gene polymorphisms, which further highlight the heterogeneity of disease mechanisms across populations.⁵ This multidimensional nature limits the effectiveness of conventional reductionist approaches that target single pathways, thereby necessitating a more integrated understanding of disease mechanisms.

Recent advances in diagnostic strategies, including 24-hour ambulatory blood pressure monitoring (ABPM), home blood pressure monitoring (HBPM), and biomarker-based risk stratification, have improved the accuracy of hypertension detection and prognostic assessment.⁶ Nevertheless, its clinical management remains largely standardized, with limited use of individualized risk profiles. Despite the availability of multiple antihypertensive agents, a substantial proportion of patients fail to achieve optimal blood pressure control, and treatment-related adverse effects further complicate long-term treatment adherence.⁷ These limitations highlight an important need for more comprehensive and personalized therapeutic strategies.

In this context, Traditional Chinese Medicine (TCM) has attracted increasing attention as a complementary and integrative approach in hypertension management.⁸ It is characterized by a holistic, multi-target therapeutic framework that has been shown to modulate key pathophysiological processes, including endothelial dysfunction, oxidative stress, neurohumoral regulation, and inflammatory responses.⁹ In addition, emerging clinical and experimental evidence suggests that TCM, particularly when combined with conventional Western therapies, may enhance therapeutic efficacy while reducing adverse effects, thereby offering a potential advantage in complex and refractory cases.¹⁰

Against this background, a comprehensive review that integrates current evidence on the epidemiology, genetic and molecular mechanisms, diagnosis, and treatment of hypertension is needed. Herein, this review presents a multidimensional overview of hypertension, with particular emphasis on the role of TCM in integrated management (Figure 1). The literature search strategy, eligibility considerations, and overall review methodology are described in the Supplementary Methods. By connecting mechanistic research with clinical practice, it aims to provide a useful reference for developing more personalized and comprehensive approaches to the prevention and treatment of hypertension.

Figure 1 Graphical abstract of the multidimensional overview of hypertension, from epidemiology, pathophysiological mechanisms and Traditional Chinese medicine-based integrated management to future research directions.

Epidemiology of Hypertension

The epidemiology of hypertension is characterized not only by its high global prevalence but also by its marked heterogeneity across populations and exposure, with insufficient control in a large proportion of patients, reflecting substantial variation in risk distribution and health system performance.¹¹ Thus, current epidemiological research is increasingly focusing on the structure of risk, highlighting the interaction between metabolic, environmental, and genetic determinants.

From a population perspective, metabolic abnormalities constitute a central component of hypertension epidemiology as they contribute to vascular dysfunction and sustained blood pressure elevation. Large-scale analyses from the Global Burden of Disease study have confirmed that elevated body mass index and dietary risks remain leading contributors to hypertension-related disease burden.¹² In addition, environmental and climatic exposures are increasingly recognized as important factors influencing hypertension risk. For instance, temperature variation may directly affect blood pressure regulation.¹³ Cold exposure can increase sympathetic nervous system activity and peripheral vasoconstriction, leading to elevated blood pressure, whereas high temperatures may cause dehydration, activation of RAAS, and hemodynamic instability.^14,15 While cold-related effects remain substantial, the health burden attributable to high temperatures has increased in recent years and is expected to continue rising under climate change scenarios.³ Of note, these effects are not evenly distributed, with older adults and individuals having pre-existing cardiovascular conditions showing greater susceptibility.¹⁶

Genetic susceptibility further contributes to inter-individual and inter-population differences in hypertension prevalence. For example, recent genome-wide analyses have shown that genetic risk can be partially modified by lifestyle factors, including diet quality and physical activity, indicating that genetic predisposition is context-dependent.¹⁷ Research involving Mongolian and Han populations identified associations between single-nucleotide polymorphisms (SNPs) in PPARγ and hypertension. Specifically, rs6802898 was associated with hypertension in the Han population, while rs12633551 showed a similar association in the Mongolian population; however, these associations did not remain significant after correction for multiple testing.¹⁸ In contrast, haplotype analysis demonstrated a significant relationship between PPARγ haplotypes and hypertension risk.¹⁸ This interaction highlights the importance of integrating genetic background with modifiable exposures in epidemiological assessment.

From the perspective of TCM, these epidemiological patterns can be interpreted in a framework of systemic imbalance. For example, factors such as improper diet, emotional stress, and environmental changes are considered key drivers of “liver yang hyperactivity” (a pattern characterized by excessive upward movement of yang energy, often associated with hyperexcitability, sympathetic overactivity, and elevated blood pressure), “phlegm-dampness accumulation” (a condition involving impaired fluid metabolism and accumulation of pathological metabolites, corresponding to obesity, dyslipidemia, and metabolic dysfunction), and “yin deficiency” (a state of insufficient inhibitory and nourishing substances, often linked to chronic disease, oxidative stress, and neuroendocrine imbalance).¹⁹ Notably, recent studies have shown that TCM interventions can regulate key metabolic and inflammatory pathways involved in hypertension. For example, herbal formulations and compound prescriptions have been reported to improve lipid metabolism, reduce insulin resistance, and suppress inflammatory mediators such as TNF-α and IL-6, thereby contributing to blood pressure control and vascular protection.^20,21

As summarized in Figure 2, the epidemiology of hypertension reflects a multidimensional network of risk factors, including lifestyle-related behaviors, metabolic and inflammatory abnormalities, genetic susceptibility, environmental and climatic influences, and occupational exposures. These factors do not act independently but interact dynamically, contributing to both the development and progression of hypertension. Understanding this integrated risk structure is essential for advancing prevention strategies. In this context, TCM may serve as a useful complementary approach for hypertension because it emphasizes individualized treatment and overall body regulation, which may help address the diverse risk factors and clinical differences seen in different populations.

Figure 2 Multidimensional epidemiological risk factors contributing to hypertension. Hypertension is a multifactorial disease influenced by a range of epidemiological factors, including lifestyle-related risks, inflammatory and metabolic abnormalities, genetic susceptibility, environmental and climatic exposures, and occupational factors in specific populations. hs-CRP, high-sensitivity C-reactive protein.

Genetics of Hypertension

Hypertension has been associated with both common variants and population-specific haplotypes, which contribute to disease susceptibility. An exome-wide association study in a Japanese population identified several variants in the 12q24.1 region associated with hypertension, with the East Asian-specific haplotype CAAAA showing a protective effect.²² Similarly, polymorphisms in the Rho kinase (ROCK) pathway have been linked to vascular tone regulation, with ROCK1 (rs1481280) associated with hypertension and ROCK2 variants (rs7589629, rs978906) associated with stroke risk.²³ Mitochondrial DNA variation has also been implicated, with haplotype H associated with increased cardiovascular risk and haplotype J showing a protective effect against hypertension.²⁴ From a TCM perspective, these genetic differences may reflect individual constitutional variation (“ti zhi” [an individual’s constitutional characteristics, reflecting inherent differences in physiological function, metabolic status, and disease susceptibility]),¹⁹ which influences susceptibility to patterns such as “liver yang hyperactivity” and “yin deficiency.” Recent integrative studies suggest that genetic variation in vascular and metabolic pathways may correspond to differences in TCM syndrome distribution, supporting the biological basis of individualized treatment.²⁵

The interaction between genetic predisposition and environmental exposure is a key feature of hypertension. Evidence indicates that adherence to healthy dietary patterns, including DASH and AHEI-2010, can attenuate the effect of genetic risk on obesity and blood pressure-related traits.²⁶ Experimental studies further support this interaction. For example, p66Shc has been shown to mediate oxidative stress–related renal injury in salt-sensitive hypertension models, and its deletion improves vascular function.²⁷ These findings highlight that genetic risk is modifiable. This concept aligns with TCM theory, in which external factors such as diet and lifestyle interact with internal constitution to influence disease development, as it has been shown that TCM interventions can regulate oxidative stress and inflammatory pathways, suggesting a potential mechanism through which gene–environment interactions may be modulated.²⁸

The identification of hypertension-related genes remains important for understanding disease mechanisms. Variants in the PPARγ gene have been associated with hypertension in different populations, with haplotype-level analysis showing more consistent associations than individual SNPs.¹⁸ In addition, ROCK signaling continues to be recognized as a key pathway linking vascular remodeling and blood pressure regulation.²³ In a TCM framework, these pathways are functionally related to processes described as “phlegm-dampness accumulation” and “qi stagnation”, which correspond to metabolic dysregulation and impaired vascular function. Emerging evidence indicates that TCM therapies may influence lipid metabolism and endothelial function, providing a biological link between traditional concepts and molecular pathways.²⁹

Monogenic forms of hypertension provide direct insight into the role of ion transport and renal regulation. Liddle syndrome, caused by mutations in epithelial sodium channel (ENaC) genes, and Gordon syndrome, associated with WNK kinase mutations, are characterized by distinct electrolyte and renin–aldosterone abnormalities.^30,31 These conditions highlight the importance of sodium handling and renal signaling in blood pressure control. From the perspective of TCM, such disorders may correspond to severe internal imbalances involving fluid metabolism and kidney function (“shen” regulation). Although TCM does not classify diseases based on single-gene defects, its emphasis on functional regulation may complement mechanistic understanding, particularly in managing symptoms and systemic imbalance.

Hypertension also demonstrates complex inheritance patterns involving both monogenic and polygenic mechanisms. Familial hyperkalemic hypertension (FHHt), caused by mutations in WNK1, WNK4, KLHL3, and CUL3, shows variable clinical severity depending on genotype.³² In contrast, polygenic hypertension is characterized by the cumulative effect of multiple variants, as demonstrated by familial aggregation studies in Chinese populations.³³ Additional associations with vascular-related genes, such as FN1 and FBN2, further support the role of extracellular matrix and vascular structure in disease development.³⁴ This heterogeneity is consistent with the TCM concept of syndrome differentiation, where similar clinical presentations may arise from different underlying mechanisms. Integrating genetic information with clinical phenotyping may therefore improve individualized treatment strategies and provide a bridge between modern precision medicine and TCM-based approaches.

Diagnosis

The diagnosis of hypertension starts with standardized blood pressure measurement, with current guidelines placing greater emphasis on confirmation outside the clinic and on overall cardiovascular risk assessment (Figure 3). For instance, the 2024 European Society of Cardiology (ESC) guideline and the 2023 European Society of Hypertension (ESH) guideline continue to define hypertension as a confirmed office blood pressure of ≥140/90 mmHg,^35,36 whereas the American Heart Association/American College of Cardiology (AHA/ACC) guideline uses the lower threshold of ≥130/80 mmHg,³⁷ emphasizeing early identification and risk-based management rather than reliance on a single diagnostic threshold.³⁸ Despite these differences, the major guidelines stress the importance of repeated measurements, validated upper-arm devices, and proper measurement technique in routine practice.

Figure 3 Diagnostic strategies for hypertension. A summary of conventional and emerging diagnostic strategies for hypertension. Conventional diagnosis is based on office blood pressure measurement, whereas newer approaches include 24-hour ambulatory blood pressure monitoring, home blood pressure monitoring, genetic testing, and biomarker assessment.

In clinical practice, screening strategies should be simple, practical, and population-oriented. The United States Preventive Services Task Force (USPSTF) recommends screening all adults ≥18 years using office blood pressure measurement, with confirmation by out-of-office measurement before a diagnosis is established.³⁹ This approach is important for reducing misclassification caused by white-coat hypertension and masked hypertension. Home blood pressure monitoring is now widely used for screening and follow-up, while ABPM remains the most established out-of-office method when confirmation is needed.⁴⁰ Moreover, risk stratification is another key part of diagnosis and should not rely on blood pressure level alone. The ESC and ESH guidelines both recommend integrating blood pressure category with cardiovascular risk factors, hypertension-mediated organ damage, diabetes, chronic kidney disease, and established cardiovascular disease.^35,36 This is important because patients with similar clinic blood pressure values may have very different long-term risks. In this setting, diagnosis moves beyond a simple threshold-based decision and becomes part of a broader evaluation of total cardiovascular risk.

Among out-of-office methods, ABPM also has a particularly important role as it provides 24-hour, daytime, nighttime, and morning blood pressure profiles, and it is useful for identifying white-coat hypertension, masked hypertension, nocturnal hypertension, and abnormal circadian blood pressure patterns.³⁹ These are clinically relevant because ambulatory blood pressure is more closely associated with hypertension-mediated organ damage and cardiovascular outcomes than office blood pressure alone. Home blood pressure monitoring is also valuable, especially for long-term follow-up and treatment adjustment, but ABPM remains central when diagnostic uncertainty exists or when more detailed blood pressure phenotyping is required.⁴¹

From the perspective of TCM, modern blood pressure measurement remains the foundation of diagnosis, and TCM concepts do not indicate that this should be replaced by syndrome differentiation. However, TCM pattern identification provides complementary clinical information in individual patients, particularly when symptoms, sleep disturbance, emotional factors, and circadian variation are considered together.⁴² Recent work has attempted to standardize syndrome-based diagnosis in hypertension, including consensus criteria for yin deficiency syndrome, which may improve consistency in future integrative studies.⁴³ Therefore, in an integrated framework, objective blood pressure phenotyping and TCM syndrome differentiation may be used in parallel for enhanced individualized treatment approaches.

Pathophysiology of Hypertension

Mechanism of Vascular Dysfunction

Vascular dysfunction is a central feature of hypertension and involves endothelial injury, abnormal contraction of vascular smooth muscle cells (VSMCs), and structural remodeling of the vessel wall.⁴⁴ Experimental studies have shown that genetic and molecular alterations contribute directly to these changes. For example, in spontaneously hypertensive rats (SHR), deletion of the p66Shc gene restores the myogenic responsiveness of renal arteries, suggesting a role for oxidative stress–related signaling in hypertensive vascular injury.²⁷ In addition, microRNA-153 has been reported to promote vasoconstriction by targeting the KCNQ4 potassium channel, thereby increasing vascular tone and contributing to elevated blood pressure.⁴⁵ These findings indicate that both genetic regulation and ion channel function are closely involved in vascular dysfunction.

Oxidative stress plays an important role in the progression of hypertension. In angiotensin II–induced models, activation of p38 mitogen-activated protein kinase (p38-MAPK) is associated with endothelial dysfunction and vascular remodeling, while inhibition of this pathway improves vascular function.⁴⁶ Vitamin D deficiency has also been linked to impaired vascular function in salt-sensitive hypertension, whereas supplementation can partially reverse these changes.⁴⁷ More broadly, excessive production of reactive oxygen species reduces nitric oxide bioavailability and promotes inflammation, further aggravating vascular damage.⁴⁸

From a TCM perspective, vascular dysfunction in hypertension is often related to patterns such as “liver yang hyperactivity” and “yin deficiency,” which are associated with dysregulated vascular tone and reduced inhibitory control. Although described differently, these patterns may correspond to mechanisms involving sympathetic overactivity, endothelial dysfunction, and oxidative stress. Recent studies suggest that certain TCM interventions can improve endothelial function and reduce oxidative stress, providing a potential link between traditional theory and modern vascular biology.²⁹ Overall, vascular dysfunction in hypertension reflects the interaction of endothelial impairment, VSMC dysregulation, oxidative stress, and structural remodeling. A better understanding of these interconnected mechanisms may provide a stronger basis for both targeted drug therapy and integrative TCM-based interventions.

Interaction Between Hypertension and the Endocrine System

Hypertension is known to be closely related to endocrine regulation, particularly through RAAS, sympathetic activity, and hormone-mediated sodium balance. Experimental studies have shown that endogenous ouabain contributes to elevated blood pressure by inhibiting Na⁺/K⁺-ATPase and altering vascular tone.⁴⁹ In clinical settings, primary aldosteronism is a well-established cause of secondary hypertension, characterized by excess aldosterone, sodium retention, and suppressed renin levels; treatment with mineralocorticoid receptor antagonists has been shown to effectively reduce blood pressure,⁵⁰ which highlights the essential role of endocrine-mediated volume expansion and vascular regulation in hypertension. From a TCM perspective, such mechanisms may correspond to disturbances in fluid metabolism and internal balance, often reflected in patterns such as “yin deficiency” or “phlegm-dampness accumulation”, which are associated with dysregulated fluid distribution and vascular tension.⁵¹

Other endocrine disorders also contribute to hypertension through distinct pathways. Thyroid dysfunction is associated with changes in vascular resistance and cardiac output, and studies have shown that thyroid hormone replacement in hypothyroid patients can lead to reductions in blood pressure.⁵² In addition, patients with polycystic ovary syndrome (PCOS) exhibit a higher prevalence of hypertension, largely related to insulin resistance, hyperandrogenism, and metabolic imbalance.⁵³ These conditions illustrate how endocrine and metabolic factors interact to influence blood pressure regulation. In TCM, these features are often interpreted as systemic imbalance involving the liver, kidney, and spleen functions, which regulate metabolism, hormonal balance, and internal homeostasis.⁵⁴ In addition, increasing evidence suggests that TCM interventions may improve metabolic and endocrine function, thereby indirectly contributing to blood pressure control.⁵⁵

Overall, hypertension and the endocrine system are closely interconnected through mechanisms involving hormonal regulation, metabolic balance, and vascular function. Therefore, understanding these interactions provides a broader framework for identifying secondary causes of hypertension and for developing more individualized treatment strategies. In this context, integrating endocrine evaluation with TCM-based pattern differentiation may offer complementary insights for the management of complex hypertensive conditions.

Study on the Mechanism of Neural Regulation

Neural regulation is an important part of blood pressure control and mainly involves the brain and the sympathetic nervous system, with increased sympathetic activity commonly observed in hypertension and contributes to sustained elevation of blood pressure. Clinical studies on renal sympathetic denervation (RDN) have shown that this approach can lower blood pressure, although the effect varies between patients, likely due to differences in baseline sympathetic activity.⁵⁶ In addition, studies in SHR have identified changes in gene expression in the hypothalamus, involving genes related to hormone regulation, immune responses, and stress.⁵⁷ These findings suggest that changes in brain function are involved in the development of hypertension.

In the brain, several key regions directly regulate blood pressure. The hypothalamic paraventricular nucleus (PVN) plays an important role in coordinating hormonal and autonomic responses.⁵⁸ Activation of neurons expressing angiotensin II type 1A receptor (AT1aR) in this region can increase sympathetic activity and stimulate the hypothalamic–pituitary–adrenal axis, leading to higher blood pressure.⁵⁹ Another important region is the rostral ventrolateral medulla (RVLM), which helps control sympathetic outflow. Studies have shown that salusin-β can increase blood pressure and heart rate through its effects on neurotransmitter receptors and calcium channels in this region.⁶⁰ These findings show that brain-driven mechanisms are closely linked to both hormonal regulation and vascular function.

From a TCM perspective, these changes can be related to an imbalance between excitation and inhibition, often described as “liver yang hyperactivity” and “yin deficiency”.²⁵ These patterns are associated with symptoms such as irritability, dizziness, and increased vascular tension, which may reflect sympathetic overactivity and altered neuroendocrine regulation. Some studies suggest that TCM interventions may help regulate autonomic function and reduce sympathetic activity, thereby contributing to blood pressure control.^61,62 As shown in Figure 4, neural regulation does not act alone but interacts with vascular dysfunction and endocrine mechanisms to influence blood pressure. Overall, hypertension involves coordinated changes in the brain, blood vessels, and endocrine system. Understanding how these systems interact may help identify new treatment targets and support more individualized approaches, including those based on TCM.

Figure 4 Pathophysiological mechanisms of hypertension. The pathophysiology of hypertension involves the interaction of vascular dysfunction, endocrine regulation, and neural mechanisms. Understanding these interconnected processes is important for clarifying disease development and identifying potential therapeutic targets. Abbreviations: RAAS, renin–angiotensin–aldosterone system; PVN, paraventricular nucleus; Ang II, angiotensin II.

Comprehensive Treatment Strategy of TCM for Hypertension

TCM has a longstanding history in the management of hypertension, encompassing various modalities such as compound herbal formulations, individual herbs, and acupuncture. Research in a Taiwanese cohort demonstrated that TCM interventions can reduce the incidence of stroke among patients with type 2 diabetes, with Salvia miltiorrhiza identified as one of the most frequently used single herbs.⁶³ Furthermore, experimental studies using SHR models have shown that herbal decoctions, including Xuefu Zhuyu Decoction (XFZYD), Tianma Gouteng Decoction (TMGTY), and Wendan Decoction (WDD), can ameliorate myocardial fibrosis, with XFZYD exhibiting the most pronounced effect.⁶⁴

Chinese herbs also play an important role in hypertension management. For example, genipin has been shown to mitigate hypertension-induced renal damage by inhibiting the Ang II–Toll-like receptor/MyD88/MAPK signaling pathway.⁶⁵ In addition, Qingxuan Jiangya Decoction (QXJYD) has been reported to improve vascular remodeling by promoting apoptosis in vascular smooth muscle cells in SHR models.⁶⁶ These findings suggest that TCM exerts therapeutic effects through multiple targets and pathways.

Evaluation of the clinical efficacy of TCM remains an important area of research. A systematic review and meta-analysis in elderly patients with isolated systolic hypertension showed that TCM combined with conventional therapy significantly reduced systolic blood pressure and pulse pressure without increasing adverse events.⁶⁷ Similarly, a clinical study of Jingui Shenqi Pill combined with nifedipine in elderly hypertensive patients with spleen–kidney yang deficiency demonstrated improvements in blood pressure, lipid profiles, and TCM syndrome scores.⁶⁸

Non-pharmacological TCM therapies have also been increasingly studied. A systematic review and meta-analysis reported that acupoint application therapy can effectively reduce blood pressure with a favorable safety profile.⁶⁹ In addition, auricular acupuncture has been shown to improve depressive symptoms and lower blood pressure in patients with comorbid depression and hypertension.⁷⁰ These findings indicate that acupuncture-related therapies may provide additional benefit, either alone or in combination with herbal treatment.

The integration of TCM and Western medicine has shown potential advantages in hypertension management. Combined treatment strategies may enhance blood pressure control while reducing adverse effects. For example, conventional fixed-dose combinations such as nifedipine controlled-release tablets with candesartan cilexetil, or amlodipine with valsartan, have demonstrated good efficacy and tolerability.⁷¹ When used alongside TCM interventions, these approaches may provide complementary benefits in selected patient populations.

However, several challenges remain, such as the lack of standardized diagnostic criteria, inconsistent outcome measures, and variable quality of clinical studies. A systematic review of integrated approaches reported generally low methodological quality and a lack of large-scale randomized controlled trials.⁷² Although some studies have shown significant blood pressure reduction with integrated therapy, further optimization of treatment protocols and improvement in study design are still needed.⁷³ As summarized in Figure 5, TCM treatment strategies for hypertension can be broadly categorized into three main approaches: herbal therapy (including compound formulas and single herbs), acupuncture and acupoint-based therapies, and integrated TCM–Western medicine. These approaches act through multiple mechanisms and may be used alone or in combination. Overall, TCM offers a multi-component approach to hypertension management; however, future research should focus on improving methodological quality, standardizing evaluation systems, and strengthening evidence from high-quality clinical trials.

Figure 5 Traditional Chinese medicine treatment strategies for hypertension. This figure summarizes the main TCM treatment strategies for hypertension, including compound herbal formulas and single-herb therapies, acupuncture and acupoint-based interventions, and integrated TCM–Western medicine approaches. It also illustrates the proposed mechanisms by which Tianma Gouteng Decoction (TMGTY) and Jiawei Banxia Baizhu Tianma Decoction (JBBTD) may improve hypertension. Acupuncture and acupoint-based therapies may be used alone or in combination with herbal treatment. Although integrated TCM–Western medicine approaches have shown potential benefit in blood pressure control, further methodological improvement and stronger quality control are still needed in future research and clinical application.

Clinical Practice of TCM in the Treatment of Hypertension

In a randomized controlled trial, the effects of Tianma Gouteng Decoction on glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity were evaluated in patients with gestational hypertension and liver yang hyperactivity syndrome.^74,75 Patients with pregnancy-induced hypertension were randomly assigned to either the observation group or the control group and both groups received standard baseline treatment after admission. The control group was treated with intravenous magnesium sulfate, whereas the observation group received Tianma Gouteng Yin in addition to the control treatment. The intervention lasted 14 days. Blood pressure, plasma renin activity (PRA), angiotensin II (Ang II), GSH-Px, SOD, and malondialdehyde (MDA) were measured before treatment and one week after treatment. In addition, Ang II, plasma aldosterone concentration (PAC), maternal and fetal pregnancy outcomes, and adverse drug reactions were recorded. The results suggested that Tianma Gouteng Decoction combined with conventional Western medicine improved blood pressure control and maternal and neonatal outcomes in patients with gestational hypertension and liver yang hyperactivity syndrome, possibly through regulation of oxidative stress and the RAAS.

In another randomized controlled trial, the relationship between hypertension duration and the severity of cerebral microbleeds was examined, and the clinical efficacy of Qianyang Yuyin Granule in improving cognitive impairment in hypertensive patients with cerebral microbleeds was evaluated.⁷⁶ The systematic review and meta-analysis, including 21 randomized controlled trials with a total of 1,419 patients, was conducted to evaluate the efficacy and safety of Qianyang Yuyin Granules in mild-to-moderate essential hypertension with vascular damage. Across the included studies, the control groups received basic conventional treatment, whereas the experimental groups received Qianyang Yuyin Granules in addition to conventional therapy. The pooled results showed that the addition of Qianyang Yuyin Granules improved pulse wave velocity, reduced inflammatory markers such as C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α), and further lowered systolic and diastolic blood pressure without increasing adverse reactions. Overall, current evidence suggests that Qianyang Yuyin Granules may provide additional benefit in mild-to-moderate essential hypertension with vascular damage by improving vascular function, reducing inflammatory responses, and further lowering blood pressure without increasing adverse effects; however, these findings still require confirmation in larger, rigorously designed studies.

The effects of acupuncture combined with modified Zhengan Xifeng Decoction on early clinical manifestations and oxidative stress were also assessed in patients with hypertensive intracerebral hemorrhage (HICH) and liver–kidney yin deficiency syndrome.⁷⁷ In this randomized controlled trial, 60 patients were randomly assigned to either the control group or the observation group, with 30 patients in each group. The control group received symptomatic treatment, routine rehabilitation, and modified Zhengan Xifeng Decoction, whereas the observation group received additional acupuncture therapy. The treatment period was one month. The evaluated outcomes included clinical efficacy, TCM syndrome scores, motor and neurological function assessed by the Activity of Daily Living Scale (ADL), National Institutes of Health Stroke Scale (NIHSS), modified Ashworth Scale (MAS), and simplified Fugl–Meyer Assessment (FMA), as well as hematoma absorption, fractional anisotropy (FA) ratio, and serum levels of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2). The results indicated that acupuncture combined with Zhengan Xifeng Decoction significantly improved early clinical symptoms, reduced oxidative stress, and promoted neurological and motor function recovery in patients with acute HICH and liver–kidney yin deficiency syndrome, compared with conventional treatment alone.

A randomized controlled trial also examined the effects of Huoxue Qianyang Qutan Fang combined with auricular point therapy on blood pressure circadian rhythm and carotid intima–media thickness (IMT) in patients with non-dipping nocturnal hypertension and blood stasis, yang hyperactivity, and phlegm turbidity syndrome.⁷⁸ Sixty-two patients were randomly divided into a treatment group and a control group, with 31 patients in each group. The study compared antihypertensive efficacy, changes in blood pressure rhythm, and vascular health indicators, including IMT, vascular function, carotid plaque score, and plaque classification. The findings demonstrated that the combined intervention effectively regulated circadian blood pressure rhythm, improved vascular function, and enhanced sleep quality in patients with non-dipping nocturnal hypertension.

The clinical efficacy of Jiawei Banxia Baizhu Tianma Decoction was further evaluated in patients with obesity-related hypertension.⁷⁹ In this randomized controlled trial, 86 patients were randomly assigned to either the control group or the observation group, with 43 patients in each group. The control group received benazepril hydrochloride tablets, whereas the observation group received additional Jiawei Banxia Baizhu Tianma Decoction for eight weeks. The assessed outcomes included clinical efficacy, TCM syndrome scores, ambulatory blood pressure and blood pressure variability, including 24-hour systolic blood pressure, 24-hour diastolic blood pressure, and their variability, as well as expression of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway proteins, adipokine levels including leptin and adiponectin, Ang II, endothelial function markers including nitric oxide and endothelin, body mass index (BMI), waist-to-hip ratio, and safety indices. The results indicated that Jiawei Banxia Baizhu Tianma Decoction can safely and effectively reduce blood pressure, improve blood pressure variability, protect endothelial function, regulate adipokine profiles, and reduce body weight in patients with obesity-related hypertension, possibly through inhibition of the JAK2/STAT3 signaling pathway.

Overall, these clinical studies suggest that TCM interventions, including herbal formulas, acupuncture, and combined treatment approaches, may provide benefit in different hypertensive conditions and related complications. However, most of the available studies are still limited by relatively small sample sizes and single-center designs. Further high-quality studies are needed to better define their clinical value and mechanisms of action.

Future Outlook

Recent advances in hypertension research are increasingly driven by multi-omics approaches, including genomics, transcriptomics, proteomics and metabolomics, as they allow a more detailed understanding of disease mechanisms beyond single-gene effects. For example, large-scale genomic studies have identified loci associated with blood pressure regulation, while transcriptomic analyses have revealed gene expression changes related to neuroendocrine regulation and vascular function.⁸⁰ The integration of multi-omics data further enables the identification of molecular subtypes of hypertension, which may support more targeted interventions.⁸¹ From a TCM perspective, this systems-level approach is conceptually consistent, where multiple pathways are considered together rather than in isolation. Recent studies suggest that TCM formulations may exert effects through multi-target and multi-pathway mechanisms, which aligns with multi-omics findings.⁸²

Digital health technologies are also reshaping hypertension management. Wearable blood pressure monitoring devices and mobile health platforms now allow continuous or frequent measurement outside the clinical setting. They improve the detection of blood pressure variability and enhance long-term monitoring and adherence. In addition, remote monitoring supports early identification of high-risk individuals and facilitates individualized management. This trend may complement TCM practice, where longitudinal observation of symptoms and functional changes is emphasized, allowing integration of objective monitoring with individualized assessment.⁸³

Artificial intelligence (AI) and machine learning are increasingly used to predict hypertension risk and identify clinically relevant patterns. AI-based models can integrate clinical, imaging, and biomarker data to improve risk prediction and early detection.⁸⁴ Machine learning has also been applied to identify novel biomarkers related to inflammation and metabolism, which are closely linked to hypertension development.⁸⁵ These approaches may provide a quantitative framework for TCM syndrome differentiation, helping to standardize pattern classification and improve reproducibility in integrative research.

Precision medicine represents an important future direction in hypertension care. Genetic testing is already used in selected cases to identify monogenic hypertension, such as Liddle syndrome and Gordon syndrome.⁸⁶ In addition, pharmacogenomic studies suggest that genetic variation may influence response to antihypertensive drugs, including ACE inhibitors and angiotensin receptor blockers.⁸⁷ Device-based therapies, such as renal denervation, also show variable efficacy depending on patient characteristics, particularly sympathetic nervous system activity.⁸⁸ In TCM, individualized treatment based on syndrome differentiation shares similar principles with precision medicine, although based on different theoretical frameworks. Therefore, integrating genetic and clinical data with TCM pattern identification may provide a more comprehensive approach to personalized care.

Despite these advances, several controversies remain. Differences in diagnostic thresholds and treatment targets between guidelines, particularly between AHA/ACC and ESC/ESH, continue to generate debate regarding optimal blood pressure control. In addition, the balance between intensive and standard blood pressure targets remains an area of ongoing research, although large trials such as SPRINT have provided important evidence supporting lower targets in selected populations.⁸⁹ Future progress will depend on well-designed, large-scale studies and better integration of emerging technologies into clinical practice. In this context, combining modern biomedical approaches with TCM-based individualized strategies may offer additional value in addressing the heterogeneity of hypertension.

Lastly, several methodological limitations should be considered when interpreting current evidence. Numerous TCM clinical trials are often characterized by relatively small sample sizes, single-center designs, and insufficient reporting of randomization, blinding, and allocation concealment, which may introduce potential bias and limit reproducibility. Furthermore, substantial variability in herbal formulations, dosing regimens, and syndrome differentiation criteria may lead to clinical heterogeneity and challenges comparability across studies. Moreover, the lack of internationally standardized diagnostic frameworks and outcome measures further restricts the generalizability of findings beyond specific populations. Therefore, future studies should prioritize rigorous trial design, standardized protocols, and multicenter validation to strengthen the evidence base for TCM in hypertension.

Conclusion

Hypertension is a complex disease that cannot be fully explained or managed through a single mechanism or a single treatment approach. Current evidence suggests that TCM may serve as a useful complementary option in hypertension management, especially when combined with conventional treatment, as it may help improve blood pressure control, protect vascular function, and relieve related symptoms. However, the existing evidence is still limited by uneven study quality, inconsistent diagnostic standards, and a lack of large high-quality clinical trials. Therefore, future research should place greater emphasis on better study design, clearer evaluation standards, and closer integration of modern medicine with TCM, in order to provide a stronger basis for more comprehensive and individualized hypertension management.