A retrospective cohort study on the clinical efficacy of Shanhuang Jiangzhi tablets and Atorvastatin calcium tablets in the treatment of carotid atherosclerosis

Abstract

Background

The efficacy and safety of the combination therapy of Shanhuang Jiangzhi tablets and atorvastatin in treating primary hyperlipidemia and carotid atherosclerosis remain unclear and require further investigation.

Materials and methods

A retrospective cohort study was conducted using the medical records of the neurology wards from 1 January 2014 to 30 June 2022. Patients were divided into observation and control groups based on inclusion and exclusion criteria. The control group received atorvastatin calcium tablets at a dose of 20 mg per day, whereas the observation group received the same dose of atorvastatin plus Shanhuang Jiangzhi tablets at 2.4 g per day. The treatment period for both groups was 2 years. Blood lipid profiles and carotid ultrasound indicators were compared before and after treatment. All the data were statistically analysed using SPSS 26.0.

Results

This study included 319 atherosclerosis patients, with 162 in the observation group (average age 62.84 ± 11.90 years, 44.4% men) and 157 in the control group (average age 62.62 ± 10.33 years, 52.2% men). No significant differences were found in baseline characteristics between the two groups (p > 0.05). Following treatment, significant reductions in total cholesterol (4.38 ± 1.07 vs. 4.71 ± 1.11) and low-density lipoprotein cholesterol levels (2.78 ± 0.80 vs. 3.11 ± 0.92) were observed in the observation group compared with the control group (p < 0.05). Additionally, improvements in the carotid intima-media thickness (IMT) (1.63 ± 0.09 vs. 1.80 ± 0.05) and plaque scores (4.06 ± 0.26 vs. 4.17 ± 0.29) were more pronounced in the observation group (p < 0.05).

Conclusion

This study investigated the use of Shanhuang Jiangzhi tablets combined with atorvastatin calcium for carotid atherosclerosis, offering effective options for traditional Chinese medicine in managing atherosclerosis and hyperlipidaemia.

Supplementary Information

The online version contains supplementary material available at 10.1186/s41043-025-01057-0.

Background

Hyperlipidaemia is a prevalent clinical condition characterised by elevated blood lipid levels and is a major risk factor for atherosclerosis and cardiovascular events [1, 2]. The condition poses a substantial burden on both healthcare systems and public health. Therefore, controlling hyperlipidaemia is a critical priority in reducing the associated medical burden [3, 4]. At present, there are many first-line drugs for the treatment of the condition, including statins, fibrates, niacin, resins, cholesterol absorption inhibitors and protein convertase subtilisin/kexin type 9 inhibitors [5]. However, long-term use of these lipid-lowering agents can lead to various degrees of adverse reactions in the digestive, musculoskeletal, central and peripheral nervous systems. As the fundamental therapy for dyslipidaemia [6], statins are effective for most patients; however, some individuals experience statin-associated muscle symptoms, necessitating alternative treatments [7].

In ancient Chinese medical books, hyperlipidaemia does not have a specific term; however, its clinical manifestations can be categorised under ‘phlegm’ and ‘blood stasis’ syndromes [8]. Combining traditional Chinese medicine (TCM) with conventional therapies offers a holistic approach to managing hyperlipidaemia. Studies have demonstrated that TCM approaches that focus on invigorating the spleen, dissipating phlegm, promoting blood circulation and removing stasis can effectively regulate blood lipid levels in patients with hyperlipidaemia [9]. Clinical and experimental research has shown that many TCM prescriptions and classical formulas can achieve lipid-lowering effects without causing adverse reactions, even with long-term use [10, 11].

Shanhuang Jiangzhi tablets are a Chinese patent medicine that is uniformly prescribed by the Internal Medicine Department of Hulunbuir Chinese and Mongolian Medicine Hospital. The preparation method is detailed in a previous report [12]. Historically, these tablets have been utilised in TCM for their ability to support digestive health and enhance the body’s metabolism. Shanhuang Jiangzhi tablets contain a variety of Chinese herbs, including Pueraria root, Gynostemma pentaphyllum, Polygonum multiflorum, Salvia miltiorrhiza, rhizoma alismati, Curcuma longa, rhubarb, Crataegus pinnatifida, Chuanxiong and Cassia seed. Previous studies have shown that the treatment has a positive effect on blood lipid regulation and can reduce atherosclerotic plaques [13]. Studies have also shown that TCMs such as Salvia miltiorrhiza [14] and rhubarb [15, 16] can effectively improve haemodynamics, regulate adhesion factors in the blood and reduce blood lipid levels. Shanhuang Jiangzhi tablets contain active ingredients from various components of Chinese medicine. The tablet form also resolves the problem of difficulty in carrying and taking decoctions [17]. The drug has been used for > 50 years since its first clinical application, with a notable lipid-lowering effect and no adverse reactions reported [18]. However, studies on their use in hyperlipidaemia management remain limited. This study systematically evaluates for the first time the clinical efficacy of Shanhuang Jiangzhi tablets combined with atorvastatin calcium in the treatment of carotid atherosclerosis. Previous studies have mostly focused on the efficacy of single drugs; however, this study, through a combined treatment plan, explores the advantages of integrating traditional Chinese and Western medicine in the treatment of hyperlipidaemia and atherosclerosis, providing new ideas and methods for clinical treatment.

Data and methods

Study design and population

The sample size was estimated using the General Power Analysis Software (3.0.10,Heinrich-Heine-Universitat DisseldorfGermmany) (Supplementary Fig. 1): The test method was selected as one way ANOVA analysis showed that the significance level (a) was set at 0.05, the test power (1-β) was set at 0.8, and the expected effect size (Cohen’s D) was 0.5. The results indicated that the minimum sample size was 128 cases to ensure sufficient statistical power. This study adopted a retrospective cohort study design. This study retrospectively reviewed the medical records of patients with hyperlipidaemia admitted to the Department of Neurology, Hulunbuir Municipal Hospital of Traditional Chinese Medicine between 1 January 2014 and 30 June 2022. The patients were divided into an observation group and a control group. Ethical approval was obtained from the Ethics Committee of Hulunbuir Zhong Meng Hospital (Approval No. 2022SZM-04).

Diagnostic criteria

(1) Hyperlipidaemia was diagnosed based on the operational definition and classification of hypercholesterolaemia, which includes fasting blood lipid levels of serum total cholesterol (TC) ≥ 5.2 mmol/L, triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein cholesterol (LDL-C) ≥ 3.4 mmol/L [19]. (2) Carotid atherosclerosis was diagnosed using criteria from the 2022 Methods and Standardised Application of Ultrasound in the Diagnosis of Carotid Atherosclerotic Plaque, which defines an IMT ≥ 1.0 mm or ≥ 1.2 mm at the bifurcation as thickening and an IMT ≥ 1.5 mm as plaque formation.

Inclusion and exclusion criteria

The inclusion criteria included (1) a definite diagnosis of carotid atherosclerosis and hyperlipidaemia and (2) complete clinical data. The exclusion criteria included (1) patients who did not adhere to treatment, (2) severe stenosis or occlusion of internal carotid artery (stenosis ≥ 70%) to avoid the confounding effect of advanced diseases and ensure the homogeneity of the study population, (3) patients with severe cardiovascular and cerebrovascular diseases in the past 12 months, (4) patients with severe liver or renal insufficiency or other critical systemic diseases, (5) dyslipidaemia secondary to nephrotic syndrome, hypothyroidism, liver disease, glycogen storage disease or systemic lupus erythematosus and (6) patients using other drugs that may affect lipid regulation (e.g. hormones, thiazide diuretics, β-blockers, erythromycin, clarithromycin, itraconazole, diltiazem, rifampicin, gemfibrozil or other TCM preparations). The study finally included 319 patients, comprising 152 men and 167 women. All data were obtained from the online database of the Hulunbuir Zhong Meng Hospital.

Treatment methods

The control group received 20 mg of atorvastatin calcium tablets daily, whereas the observation group received the same atorvastatin dose plus Shanhuang Jiangzhi tablets at a daily dose of 2.4 g. Both groups underwent 2 years of continuous treatment.

Observation indicators

General observation

The general observation indicators included baseline data (gender, age, smoking history, drinking history, hypertension, diabetes, coronary heart disease-related history and work status), general physical examination items, blood and urine tests, liver and kidney function and electrocardiogram results before and after treatment. Observations were also made regarding whether the patients had adverse reactions during treatment. Multiple imputation was used for missing covariates.

Efficacy observation

This included taking the mean value of the bilateral IMT for statistical analysis, as well as the atherosclerotic plaque score (Crouse score) and clinical indicators (TC, TG, LDL-C and high-density lipoprotein cholesterol [HDL-C]) before and after treatment.

Clinical index detection method

The patients’ serum was tested using a semi-automatic biochemical analyser (Model: BA-88 A; Mindray, Shenzhen, China) to measure levels of TC, TG, LDL-C and HDL-C. A carotid artery ultrasound examination was performed using the MyLab™ Alpha colour Doppler ultrasound diagnostic instrument (model: EPIQ5).

Statistical methods

The statistical analysis was performed using SPSS 26.0 software. Comparison data between the two groups were described by mean ± standard deviation according to the normal distribution. Paired t-tests were used to compare the differences within the same group before and after treatment. Two independent sample t-tests were used to compare the differences between the two groups of longitudinal data before treatment. If the difference was not significant, the difference t-test was used to compare the differences between the two groups after treatment. The median (interquartile range) was used to describe the skewed distribution. The nonparametric rank sum test was used for inter-group comparisons, and the signed rank sum test was used for intra-group comparisons. The corrected chi-squared test was used for enumeration data, and the number of cases (%) was used for description. Rank data were compared via a two-sample rank sum test and described by the number of cases (%). A p-value of < 0.05 was regarded as indicating statistical significance.

Results

Comparison of baseline levels between the two groups

A total of 319 patients were included, with 162 allocated to the observation group and 157 to the control group. The average age of the observation group was 62.84 ± 11.90 years, and that of the control group was 62.62 ± 10.33 years. In the observation group, men accounted for 44.4%, and women accounted for 55.6%. In the control group, men accounted for 52.2%, and women accounted for 47.8%. The proportions of smoking history, drinking history, diabetes, hypertension and coronary heart disease were 30.2%, 26.5%, 28.4%, 75.9% and 59.3%, respectively, in the observation group and 33.1%, 25.5%, 26.8%, 70.1% and 50.3%, respectively, in the control group. The percentage of manual workers was 47.5% in the observation group and 56.7% in the control group. There were no significant differences in demographics or comorbidities between the two groups (p > 0.05), as shown in Table 1.

Table 1.

Comparison of baseline data between the two groups

	The control group(n = 157)	Observation group(n = 162)	P	χ2/t	95%CI
Age (years)	62.62 ± 10.33	62.84 ± 11.90	0.863	0.17	-2.678 ~ 2.238
Sex
Male	82(52.2)	72(44.4)	0.164	1.94	0.880 ~ 2.123
Female	75(47.8)	90(55.6)
Smoking history
Yes	52(33.1)	49(30.2)	0.581	0.30	0.712 ~ 1.831
No	105(66.9)	113(69.8)
The history of drinking
Yes	40(25.5)	43(26.5)	0.828	0.05	0.574 ~ 1.561
No	117(74.5)	119(73.5)
diabetes
Yes	42(26.8)	46(28.4)	0.743	0.11	0.563 ~ 1.505
No	115(73.2)	116(71.6)
hypertension
Yes	110(70.1)	123(75.9)	0.238	1.39	0.820 ~ 2.214
No	47(29.9)	39(24.1)
Coronary heart disease (CHD)
Yes	79(50.3)	96(59.3)	0.109	2.57	0.447 ~ 1.084
No	78(49.7)	66(40.7)
Working condition
Physical strength	89(56.7)	77(47.5)	0.102	2.68	0.929 ~ 2.246
mental	68(43.3)	85(52.5)

Comparison of clinical indicators between the two groups before and after treatment

There were no significant differences in TC, TG, HDL-C or LDL-C levels between the two groups before treatment (p > 0.05), although there were significant differences in TC (4.38 ± 1.07 vs. 4.71 ± 1.11) and LDL-C (2.78 ± 0.80 vs. 3.11 ± 0.92) after treatment (p < 0.05). The observation group had significantly better results than the control group in reducing TC and LDL-C, as shown in Table 2.

Table 2.

Comparison of TC, TG, HDL-C and LDL-C between the two groups before and after treatment

		The control group	Observation group	P	t	Effect size (95%CI)
TC	Before the treatment	6.14 ± 0.7	6.22 ± 1.11	0.406	0.83	-0.086(-0.306 ~ 0.133)
	After the treatment	4.71 ± 1.11	4.38 ± 1.07	0.007	2.71	0.303(0.082 ~ 0.523)
TG	Before the treatment	3.31 ± 2.31	2.88 ± 2.76	0.710	0.37	0.169(-0.051 ~ 0.389)
	After the treatment	1.93 ± 1.07	1.84 ± 1.01	0.414	0.82	0.087(-0.133 ~ 0.306)
HDL-C	Before the treatment	1.12 ± 0.46	1.16 ± 0.48	0.436	0.78	-0.086(-0.305 ~ 0.134)
	After the treatment	1.03 ± 0.36	1.05 ± 0.38	0.624	0.50	-0.056(-0.275 ~ 0.164)
LDL-C	Before the treatment	3.86 ± 0.78	4.04 ± 0.89	0.067	1.84	-0.215(-0.435 ~ 0.005)
	After the treatment	3.11 ± 0.92	2.78 ± 0.80	0.001	3.38	0.383(0.162 ~ 0.605)

Comparison of the IMT and carotid plaque score between the two groups

There was no significant difference in the IMT and carotid plaque score between the two groups before treatment (p > 0.05), although there were significant differences in the IMT (1.63 ± 0.09 vs. 1.80 ± 0.05) (95%CI:0.15394 ~ 0.18633) and plaque score (4.06 ± 0.26 vs. 4.17 ± 0.29)(95%CI:0.04897 ~ 0.17038) after treatment (p < 0.05), as shown in Table 3.

Table 3.

Comparison of IMT and carotid plaque score between the two groups

		The control group	Observation group	P	t	95%CI
IMT(mm)	Before the treatment	1.85 ± 0.05	1.84 ± 0.05	0.159	1.41	-0.00095 ~ 0.02110
	After the treatment	1.80 ± 0.05	1.63 ± 0.09	0.001	20.31	0.15394 ~ 0.18633
Plaque score	Before the treatment	6.51 ± 0.46	6.53 ± 0.43	0.709	0.37	-0.11818 ~ 0.07792
	After the treatment	4.17 ± 0.29	4.06 ± 0.26	0.001	3.53	0.04897 ~ 0.17038

Discussion

Utilising a retrospective cohort design, this study preliminarily verified the clinical efficacy and safety of Shanhuang Jiangzhi tablets combined with atorvastatin calcium in the treatment of hyperlipidaemia and carotid atherosclerosis. The research results show that this combined treatment plan has significant advantages in reducing blood lipids and improving atherosclerotic indicators. As an acquired or genetic disease, hyperlipidaemia leads to increased circulating levels of blood lipids and is an independent risk factor for a variety of cardiovascular and cerebrovascular diseases [20]. The prevalence of all metabolic diseases increased between 2000 and 2019, underscoring the urgency to address metabolic risk factors, such as hyperlipidaemia [21]. Statins are the most widely used cholesterol-lowering drugs, which reduce the morbidity and mortality of cardiovascular diseases. However, statin-associated muscle symptoms can often lead to treatment discontinuation, highlighting the need for alternative therapies [22]. As a new concept, the adjuvant therapy of TCM has received extensive attention in the treatment of hyperlipidaemia. Traditional Chinese medicine additive therapy can prevent and treat hyperlipidaemia by reducing cholesterol levels, and evidence has shown that it is effective and safe for hyperlipidaemia-related diseases mediated by lipid metabolism disorders [23]. According to TCM principles, Shanhuang Jiangzhi tablets are used to lower blood lipid levels. Empirical use in outpatient clinics has shown that this herbal formulation can be beneficial for hyperlipidaemia management. Shanhuang Jiangzhi tablets have the functions of invigorating the spleen, regulating qi and dissipating phlegm, promoting blood circulation and removing blood stasis. The formula contains puerarin for clearing heat, dampness and phlegm and multiflora, semen cavitae and rhuai for clearing the liver and moisturising the intestine, which can inhibit the synthesis of TG or accelerate their decomposition [24]. Salvia miltiorrhiza and Chuanxiong aid blood circulation and blood stasis, and hawthorn can achieve lipid-lowering effects and accelerated lipolysis. Alismatis and turmeric inhibit the absorption of cholesterol from food and promote the breakdown of cholesterol in the body [25]. Comparative studies, such as this one, are essential to provide robust evidence for integrating TCM into hyperlipidaemia treatment. The results of the present study confirm that Shanhuang Jiangzhi tablets, when used in combination with atorvastatin, have superior efficacy in lowering TC and LDL-C levels.

Currently, limited studies are available regarding the use of Shanhuang Jiangzhi tablets specifically for hyperlipidaemia treatment, although there is substantial research on the efficacy of individual herbs or their combinations found in the formulation. For example, Xie et al. demonstrated that 10 out of 15 commonly used Chinese herbs for hyperlipidaemia had clinical efficacy in human trials [26]. Similarly, Zhou et al. confirmed the lipid-lowering effects of herbal preparations containing hawthorn in clinical settings [27], while Xie et al. highlighted the potential of the components of Jiang-Zhi-Ning in regulating cholesterol metabolism and its promise as a new treatment for hyperlipidaemia [28]. Xu’s study on berberine further validated its therapeutic effects on hyperlipidaemia both in animal models and in clinical trials, suggesting its potential as an alternative therapy [29]. The potential mechanism of action of Shanhuang Jiangzhi tablets is multi-faceted, mainly due to the synergistic effect of its herbal components. For instance, the two key components, Salvia miltiorrhiza and rhubarb, can inhibit cholesterol synthesis and promote the excretion of bile acids, thereby reducing blood lipid levels. In addition, these herbs can improve haemodynamics and regulate adhesion factors in the blood, which is crucial for reducing the formation of atherosclerotic plaques.

In the present analysis of 319 patients with hyperlipidaemia, the observation group (which received Shanhuang Jiangzhi tablets in addition to atorvastatin) exhibited significantly better outcomes in lowering TC and LDL-C levels than the control group, indicating enhanced therapeutic effects when the two treatments are combined. Given the established link between elevated LDL-C and increased risk of atherosclerotic cardiovascular disease (ASCVD), achieving lower LDL-C levels is crucial for reducing cardiovascular events [29]. In a foreign clinical trial, 136,299 patients received intensive LDL-C-lowering therapy, and 133,989 patients received less intensive LDL-C-lowering therapy; the all-cause mortality of the former was lower than that of the latter. Another meta-regression analysis suggested that more stringent LDL-C reduction is negatively associated with acute myocardial infarction and major adverse cardiovascular events, which indirectly indicates that the mortality of patients would be lower if LDL-C levels were controlled at relatively low levels for a long period [30]. The combined treatment of TCM and Western medicine shows a synergistic effect. Clinical data on coronary heart disease show that the combination rate of TCMs for promoting blood circulation and removing blood stasis and statins reaches 67.08%, which can simultaneously improve haemorheology and inflammatory indicators [31]. Basic research has confirmed that the combination of TCM monomers and statins can regulate the p38 MAPK signalling pathway and enhance the stability of low-density lipoprotein receptors [32]. Thus, the greater reductions in TC and LDL-C observed in the Shanhuang Jiangzhi plus atorvastatin group suggest that this combination may help reduce the long-term risk of ASCVD more effectively than statin monotherapy.

Hyperlipidaemia remains one of the most important risk factors for cardiovascular diseases, especially atherosclerosis [33, 34]. With lifestyle changes and dietary shifts, hyperlipidaemia is becoming more prevalent among middle-aged and elderly populations in China. Disrupted lipid metabolism, particularly elevated TC and LDL-C levels, plays a central role in atherosclerosis development [35]. In one study, 114 patients with coronary atherosclerotic heart disease were examined via carotid ultrasound. Through the observation and analysis of the carotid IMT and carotid plaque occurrence, it was concluded that there was a close relationship between carotid atherosclerosis and cardiac coronary atherosclerosis [36, 37]. The improved lipid profiles and carotid IMT observed in the study hold substantial clinical significance. The reduction in TC and LDL-C levels, as well as the improvement in the IMT, are indicative of a positive therapeutic effect on atherosclerosis and hyperlipidaemia. Lowering TC and LDL-C is crucial for reducing the risk of cardiovascular events, as elevated levels of these lipids are major risk factors for ASCVD. The observed improvements in the IMT suggest a potential reduction in the progression of carotid atherosclerosis, which is a significant predictor of cardiovascular events such as stroke and myocardial infarction. These findings support the clinical application of Shanhuang Jiangzhi tablets in combination with atorvastatin as an effective and safe treatment option for managing hyperlipidaemia and atherosclerosis, potentially offering a more comprehensive therapeutic approach than atorvastatin monotherapy.

In summary, this study demonstrates that the combination of Shanhuang Jiangzhi tablets and atorvastatin not only effectively reduces blood lipid levels but also improves atherosclerosis indicators. The findings support the potential for TCM as an adjunct to conventional therapies, warranting further research to validate these results in larger, randomised clinical trials. This will provide clinicians with a more comprehensive and effective treatment option, especially suitable for patients who are intolerant to statin monotherapy or need more optimised lipid control.

This study was based on a hospital database and had several limitations. First, since this was a retrospective study, there may be selection bias and information bias. Compared with prospective randomised controlled trials, retrospective studies may not be able to control all confounding factors fully. Future research should prioritise the conduct of large-scale, randomised controlled trials to validate these preliminary findings. Second, the study sample included only 319 patients, and although this provided a certain statistical power, the relatively small sample size may limit the extrapolation and statistical power of the results. In addition, the total treatment period of the study was 2 years, which may not be sufficient for evaluating long-term efficacy and safety, especially in terms of chronic diseases, such as hyperlipidaemia and atherosclerosis. Furthermore, this study did not compare the adverse reactions of Shanhuang Jiangzhi tablets and atorvastatin, which we will further explore in subsequent studies.

Conclusion

This study suggests that the combination of Shanhuang Jiangzhi tablets and atorvastatin may be associated with improvements in HDL-C levels and reductions in TC and LDL-C levels compared with atorvastatin alone. The combined treatment appears to be related to better management of hyperlipidaemia and potential anti-atherosclerotic effects. These findings indicate that Shanhuang Jiangzhi tablets could serve as a promising adjunctive therapy, offering potential clinical value in lipid-lowering treatment and atherosclerosis prevention. However, given the observational nature of this study, further large-scale randomised controlled trials are required to confirm these associations and to determine the clinical application value of this combination therapy.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

The authors confirm their contribution to the paper: study conception and design: YW. Chang, Y. Zhang, HF. He; data collection: L. Fan, CY. Yang; analysis and interpretation of results: YW. Chang, GT. Sun, XW. Liang; draft manuscript: YW. Chang, Y. Zhang, HF. He. All authors reviewed the results and approved the final version of the manuscript.

Funding

Clinical medical research and clinical new technology promotion project of Inner Mongolia Medical Association in 2024 (YSXH2024KYF099); The Science and technology Program of Hulunbuir (No. SF2023017).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Hulunbuir Zhong Meng Hospital (Approval No. 2022SZM-04). The latter waived written informed consent because of the retrospective nature of our study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.