Role of gut microbiota and metabolomics in the lipid-lowering efficacy of statins among Chinese patients with coronary heart disease and hypercholesterolemia.

Background: Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy. Methods: A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the "Up to standard" (US) group and the "Below standard" (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites. Results: A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-ß-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism. Conclusions: The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

[Central sensitization and comorbid disorders in patients with coronary heart disease]. / Tsentral'naya sensitizatsiya i komorbidnye rasstroistva u patsientov s ishemicheskoi bolezn'yu serdtsa.

OBJECTIVE: Study of central sensitization (CS), insomnia and meteosensitivity in patients with coronary heart disease (CHD) admitted for a routine examination. MATERIAL AND METHODS: 67 patients (29 men and 38 women), aged 50-87 years, average age 73 [67; 85] years, with chronic forms of coronary heart disease were examined. The examination included the Russian version of the central sensitization inventory (CSI); assessment of meteosensitivity using a visual analogue scale (VAS); questionnaire for semi-quantitative assessment of subjective sleep characteristics (ASHS). Patients with the presence of CS were prescribed Anvifen 250 mg 3 times a day; in addition, patients could take the drug during the day if necessary, as well as during night or early morning awakening (without exceeding the maximum daily dose of 1500 mg). The duration of drug administration and observation of patients was 30 days. RESULTS: The severity of CS (before and after treatment): subclinical - in 14 and 20, mild - in 15 and 37, moderate - in 17 and 10, severe - in 14 and 0, critical - in 7 and 0 patients, respectively. The average CSI score was 40.5[30; 50] and 32.5[25; 37.3] (p=0.00001). The severity of meteosensitivity according to VAS before and after treatment was 70 [60; 80] and 25 [20; 30] points (p=0.00002). The average ASHS score for subjective sleep characteristics before and after treatment was 13 [12; 15] and 26 [25; 28] points (p=0.00001). CONCLUSION: Central nervous system, insomnia and meteosensitivity are common clinical conditions in patients with coronary artery disease. Inattention to them leads to insufficient effectiveness of specific therapy and worsening of the course of cardiovascular diseases. The GABAergic drug Anvifen effectively reduces CS, meteosensitivity and improves sleep. The CSI is a simple and informative tool for assessing cerebral dysfunction in patients with coronary artery disease and can be recommended for daily routine practice in order to optimize personalized medical care.

[Coronary heart disease: innovative understanding from traditional Chinese medicine and treatment by classic formulas].

Coronary heart disease is a common cardiovascular disease, attacking about 11.4 million patients in China. With increasing prevalence and mortality year by year, coronary heart disease has become a major factor threatening human health and public health. Although primary and secondary prevention, intervention, coronary artery bypass grafting and other interventions have reduced the death rate, there are drug(aspirin) resistance, secondary nitroglycerin failure, post-intervention fatigue, chest tightness, and an-xiety, and complication with a high risk of bleeding, which have become the key clinical and scientific issues needed to be resolved. Coronary heart disease belongs to the category of chest impediment and heart pain in traditional Chinese medicine(TCM). The TCM etiology of this disease includes external contraction of cold, emotional disorders, constitutional insufficiency, physical weakness, and labor injury, which are closely related to sympathetic nerve activity, state of cardiac and psychological diseases, family history, and cardiovascular metabolic disorders in modern medicine. The TCM causes of coronary heart disease include Qi depression, phlegm turbidity, blood stasis, fire-heat, cold congealing, and healthy Qi deficiency, which are associated with emotional factors such as anxiety and depression, abnormal lipid metabolism, abnormalities in blood circulation and coagulation, inflammatory responses, hyperactive immune responses, and heart failure, chronic wasting disease, or aging, respectively. Accordingly, the patients with Qi depression should be treated with Chaihu Longgu Muli Decoction, and those with phlegm turbidity should be treated with Wendan Decoction and Gualou Xiebai Banxia Decoction. Xuefu Zhuyu Decoction and Guizhi Fuling Pills are recommended for blood stasis, Xiaoxianxiong Decoction and Sanhuang Xiexin Decoction for fire-heat, Zhishi Xiebai Guizhi Decoction for cold congealing, and Renshen Decoction for healthy Qi deficiency. Due to the changes in the spectrum of diseases from ancient to modern times as well as the differences in physical constitution, the key cause of coronary heart disease has evolved from the chest Yang deficiency and cold congealing to Qi depression, phlegm turbidity, phlegm combined with stasis, and fire-heat, showing a shift from cold to heat and from deficiency to excess. The combination of classic formulas presents a pattern. That is, the core formula-syndrome correspondence of a disease often fixedly appears with other formula-syndrome correspondence, which may be related to the development of the pathophysiological mechanism of the disease. In the clinical application of modern pharmacological results, the research team has formulated the clinical principle of pathogenesis corresponding to pathological changes and medicinal nature corresponding pharmacological effects. The modern pharmacological research on classic formulas is conducive to targeted treatment. Moreover, classic formulas help to ameliorate aspirin resistance, clopidogrel resistance, post-intervention anxiety, and high risk of bleeding and address the lack of effective blockade of critical lesions in the coronary artery and the progression of post-infarction heart failure. The innovative understanding of the etiology and pathogenesis of co-ronary heart disease helps to improve the clinical efficacy of TCM and the clinical system for treating coronary heart disease with classic formulas.

[Meta-analysis and trial sequential analysis of Shenshao Capsules in treatment of angina pectoris in coronary heart disease].

The efficacy and safety of Shenshao Capsules in combination with conventional western medicine for the treatment of angina pectoris in coronary heart disease were systematically evaluated. Computer search of seven databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library, was conducted to identify randomized controlled trial(RCT) on Shenshao Capsules for the treatment of angina pectoris in coronary heart disease up to December 2023. According to inclusion and exclusion criteria, articles were screened, and data was extracted. Cochrane bias risk assessment tool 2.0(RoB 2.0) was used to evaluate the quality of the included articles. Meta-analysis was performed by RevMan 5.4 and Stata/SE 15.1 software, and evidence quality was rated by the GRADE system. TSA 0.9.5.10 beta software was used for the trial sequential analysis(TSA). Twelve RCTs, with a total of 1 128 participants(567 in the experimental group and 561 in the control group), were included. Meta-analysis showed that Shenshao Capsules + conventional western medicine significantly improved clinical efficacy(RR=1.20, 95%CI[1.15, 1.26], P<0.000 01) and electrocardiogram efficacy(RR=1.16, 95%CI[1.04, 1.30], P=0.01), reduced the frequency of weekly angina pectoris attacks(MD=-2.85, 95%CI[-5.27,-0.43], P=0.02), daily angina pectoris attacks(MD=-0.30, 95%CI[-0.57,-0.03], P=0.03) and the duration of angina pectoris attacks(RR=-2.28, 95%CI[-3.44,-1.12], P=0.000 1). There was no statistically significant difference in adverse reactions between the two groups(RR=1.33, 95%CI[0.71, 2.51], P=0.37). TSA indicated that the cumulative evidence for clinical efficacy exceeded the traditional boundary but did not exceed the TSA boundary, suggesting a potential false positive result. According to GRADE assessment, except for clinical efficacy, which was rated as low-quality evidence, the remaining outcomes were rated as very low-quality evidence. The results indicate that Shenshao Capsules + conventional western medicine may have certain advantages in improving clinical efficacy and electrocardiographic efficacy, reducing the frequency and duration of angina pectoris attacks. However, due to the limitations of this study, more rigorous and high-quality RCT is needed to validate its efficacy and safety.

Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial.

BACKGROUND: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. METHODS: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. RESULTS: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). CONCLUSIONS: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. TRIAL REGISTRATION: NCT: 04117763.

Dan-Lou tablets reduce inflammatory response by inhibiting the activation of NLRP3 inflammasome for coronary heart disease.

BACKGROUND: The activation of the NLRP3 inflammasome has recently been revealed as a novel pathological mechanism of coronary heart disease (CHD). The Dan-Lou tablets (DLT) is widely used in the clinical treatment of CHD and prescription characterized by multi-component and multi-target regulation. However, the anti-inflammatory mechanism of DLT in the treatment of CHD remains unclear. PURPOSE: This study aimed to evaluate the effect of DLT in the treatment of CHD on the priming and activation of the NLRP3 inflammasome and to investigate the underlying anti-inflammatory mechanisms. METHODS: First, CHD rats model were established by a high-fat diet combined with left anterior coronary artery ligation (LADCA) followed by DLT intervention. The therapeutic effect of DLT was evaluated according to cardiac function, lipid level, and cardiac histopathology. Next, data-independent acquisition (DIA) proteomics was used to identify the key differential proteins of DLT intervention in CHD rats, and bioinformatics analysis was performed. Finally, the differentially expressed proteins in the NOD-like signaling pathway were verified based on bioinformatics results, and the priming and activation steps of the NLRP3 inflammasome were detected. RESULTS: In this study, a high-fat diet combined with LADCA was utilized to generate a CHD model, and DLT alleviated myocardial ischemia injury by inhibiting lipid deposition and inflammatory response. Proteomic studies observed that the RNF31, TXN2, and GBP2 of the NOD-like receptor signaling pathway were verified as the key targets of DLT in inhibiting myocardial injury in CHD rats. Furthermore, DLT in the treatment of CHD rats may function through the downregulation of P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and may then reduce the release of the IL-1ß and IL-18 inflammatory factors to play an anti-myocardial injury effect. CONCLUSION: Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD. This study innovatively proposed that DLT further exerts an anti-myocardial injury effect by inhibiting P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and then downregulates the release of the IL-1ß and IL-18 inflammatory factors.

[Effect of statins on severity of coronary artery lesion and clinical prognosis in patients with coronary heart disease].

OBJECTIVE: To investigate the effect of statins on the severity of coronary artery lesion in patients with coronary heart disease, and to analyze the risk factors of clinical prognosis. METHODS: A retrospective cohort study was conducted. The clinical data of 156 patients with coronary heart disease and completed the second re-examination of coronary CT angiography (CCTA) who were admitted to the department of cardiovascular medicine of Peking University People's Hospital from January 2017 to December 2021 were collected. According to whether they took statins regularly according to the doctor's instructions after being diagnosed with coronary heart disease based on the first CCTA examination, the patients were divided into statin group and non-statin group, and the clinical characteristics of the two groups and the results of the second re-examination of CCTA were compared and analyzed. According to whether the patients had major adverse cardiovascular and cerebrovascular events (MACCE) within 3-5 years after diagnosis of coronary heart disease, the patients were divided into MACCE group and non-MACCE group, and the clinical characteristics of the two groups were compared and analyzed. Multivariate Logistic regression analysis was used to screen the risk factors related to the adverse prognosis (occurrence of MACCE) of patients with coronary heart disease. RESULTS: (1) A total of 156 patients with coronary heart disease were enrolled, including 113 patients (72.44%) in the statin group and 43 patients (27.56%) in the non-statin group. Except for low density lipoprotein (LDL) and serum creatinine (SCr), there was no significant difference in gender, age, body mass index (BMI), basic diseases, smoking history, the first CCTA display of coronary artery lesions and plaque characteristics, the interval between the two CCTA and other laboratory indicators between the two groups. Compared with the non-statin group, the statin group had a significant reduction in the overall increase rate of coronary artery stenosis score (Gensini score) in the CCTA re-examination and the incidence of MACCE [Gensini score increase rate: 25.66% (29/113) vs. 46.51% (20/43), incidence of MACCE: 9.73% (11/113) vs. 30.23% (13/43), both P < 0.05]. (2) Among 156 patients with coronary heart disease, 24 cases (15.38%) experienced MACCE within 3-5 years after diagnosis, while 132 cases (84.62%) did not experience MACCE. The proportion of patients in the MACCE group who regularly took statins after diagnosis was significantly lower than that in the non-MACCE group [45.83% (11/24) vs. 77.27% (102/132), P < 0.01], and D-dimer and glycosylated hemoglobin (HbA1c) were significantly higher than those in the non-MACCE group [D-dimer (µg/L): 148.50 (101.25, 314.75) vs. 88.10 (59.03, 132.12), HbA1c: 6.45% (6.20%, 7.93%) vs. 6.10% (5.81%, 6.92%), both P < 0.05]. Compared with the non-MACCE group, in the first CCTA examination of patients in the MACCE group, the total percentage of atheroma volume (PAV), fibrous-fat PAV, necrotic core PAV and Gensini score were significantly increased [total PAV: 43.05% (29.19%, 60.60%) vs. 24.57% (16.94%, 39.09%), fibrous-fat PAV: 18.61% (8.48%, 26.44%) vs. 6.81% (4.16%, 12.57%), necrotic core PAV: 5.96% (2.98%, 8.71%) vs. 2.29% (1.47%, 4.36%), Gensini score: 30.25 (23.50, 38.30) vs. 19.50 (13.20, 31.10), all P < 0.05]. Multivariate Logistic regression analysis showed that regular use of statins [odds ratio (OR) = 0.282, 95% confidence interval (95%CI) was 0.110-0.727, P = 0.008], D-dimer (OR = 1.011, 95%CI was 1.005-1.017, P < 0.001), necrotic core PAV (OR = 1.323, 95%CI was 1.120-1.563, P = 0.001) and Gensini score (OR = 1.038, 95%CI was 1.004-1.073, P = 0.028) were independent risk factors for MACCE within 3-5 years after diagnosis in patients with coronary heart disease. CONCLUSIONS: For patients with coronary heart disease, D-dimer, necrotic core PAV, and Gensini scores should be closely monitored. Statins can effectively alleviate the severity of coronary artery disease and reduce the occurrence of MACCE in patients with coronary artery disease.

Molecular mechanism of Danxiong Tongmai Granules in treatment of coronary heart disease.

BACKGROUND: Danxiong Tongmai Granules (DXTMG) are widely utilized in treating coronary heart disease (CHD) in China. This study aims to explore the molecular mechanisms underlying the therapeutic effects of DXTMG on CHD by employing a network pharmacology approach, complemented with experimental validation. METHODS: Traditional Chinese Medicine (TCM) compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database was used to obtain the main target genes involved in CHD. We combined disease targets with the drug targets to identify common targets. The "TCM-compound-target" network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock software. A molecular dynamics simulation was conducted on the optimal protein-small molecule complex identified through molecular docking, using Amber18 software. The rat model for myocardial ischemia was established through pre-gavage administration of DXTMG, followed by dorsal hypodermic injection of isoprenaline. Myocardial tissues from the rats were analyzed using hematoxylin and eosin (HE) staining and Masson's trichrome staining. Relevant targets were validated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system; 109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways (P < 0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. The results of molecular docking and molecular dynamics simulations demonstrated the robust binding affinity between the compounds and target proteins. Animal experiment findings indicated that, compared with the model group, the DXTMG group effectively ameliorated inflammation and fibrosis in rat myocardial tissues, reduced LDH, cTn-I, and MDA levels (P < 0.05, P < 0.01), elevated SOD and GSH-PX levels (P < 0.05), and reduced the percentage of positive area for IL-6 and TNF-α (P < 0.05). CONCLUSION: This study preliminarily suggests that DXTMG can modulate oxidative stress, inflammation response, and cardiomyocyte regulation, thereby mitigating the onset and progression of CHD.

Five-layer-funnel filtering mode discovers effective components of Chinese medicine formulas: Zhishi-Xiebai-Guizhi decoction as a case study.

BACKGROUND: How to screen and identify the effective components in the complex substance system is one of the core issues in achieving the modernization of traditional Chinese medicine (TCM) formulas. However, it is still challenging to systematically screen out the effective components from the hundreds or thousands of components in a TCM formula. PURPOSE: An innovative five-layer-funnel filtering mode stepwise integrating chemical profile, quantitative analysis, xenobiotic profile, network pharmacology and bioactivity evaluation was successfully presented to discover the effective components and implemented on a case study of Zhishi-Xiebai-Guizhi decoction (ZXG), a well-known TCM formula for coronary heart disease (CHD). METHODS: Initially, the chemical profile of ZXG was systemically characterized. Subsequently, the representative constituents were quantitatively analyzed. In the third step, the multi-component xenobiotics profile of ZXG was systemically delineated, and the prototypes absorbed into the blood were identified and designated as the primary bioavailable components. Next, an integrated network of "bioavailable components-CHD targets-pathways-therapeutic effects" was constructed, and the crucial bioavailable components of ZXG against CHD were screened out. Lastly, the bioactivities of crucial bioavailable components were further evaluated to pinpoint effective components. RESULTS: First of all, the chemical profile of ZXG was systemically characterized with the detection of 201 components. Secondly, 37 representative components were quantified to comprehensively describe its content distribution characteristics. Thirdly, among the quantified components, 24 bioavailable components of ZXG were identified based on the multi-component xenobiotic profile. Fourthly, an integrated network led to the identification of 11 crucial bioavailable components against CHD. Ultimately, 9 components (honokiol, magnolol, naringenin, magnoflorine, hesperidin, hesperetin, naringin, neohesperidin and narirutin) exhibiting myocardial protection in vitro were identified as effective components of ZXG for the first time. CONCLUSION: Overall, this innovative strategy successfully identified the effective components of ZXG for the first time. It could not only significantly contribute to elucidating the therapeutic mechanism of ZXG in the treatment of CHD, but also serve as a helpful reference for the systematic discovery of effective components as well as ideal quality markers in the quality assessment of TCM formulas.

[Clinical comprehensive evaluation of Shexiang Tongxin Dropping Pills].

Based on literature and questionnaire research, related evidence and related data on Shexiang Tongxin Dropping Pills were collected in terms of safety, effectiveness, economy, innovation, suitability, and accessibility. In addition, multi-criteria decision analysis(MCDA) model was used to comprehensively evaluate the clinical value of Shexiang Tongxin Dropping Pills. Quality control was carried out strictly based on evidence-based medicine evaluation. Shexiang Tongxin Dropping Pills were recommended for stable fatigue angina of coronary heart disease with Qi deficiency and blood stasis by guidelines and experts. The conventional treatment of western medicine adds Shexiang Tongxin Dropping Pills to reduce the frequency of angina attacks, shorten the duration, improve exercise tolerance, and improve the quality of life and Chinese symptoms, and the effectiveness is rated as grade A. Adverse reactions are mostly general adverse reactions, and no serious adverse reactions have been reported, consistent with the known risks listed in the instruction for adverse events, contraindications, and precautions. The safety is rated as grade A, and the daily cost is 7.74 yuan. The cost-effectiveness shows that it is a treatment regimen with pharmacoeconomic advantages, and the economic performance is rated as grade A. According to specialist research, Shexiang Tongxin Dropping Pills have good clinical innovation and service innovation, and innovation is rated as grade A. There are no special storage conditions, medicinal material ingredients, or other restrictions, and the clinical use meets the specifications of the medication guidelines. The suitability is rated as grade A. The price level, availability, and affordability of drugs are generally good, and the accessibility is rated as grade A. The clinical value of Shexiang Tongxin Dropping Pills is great.

Image testing based on biomedical drug loading in cardiovascular drug care simulation for coronary heart disease.

Coronary heart disease is a common cardiovascular disease, and its therapeutic effect is affected by the distribution and absorption of drugs in the body. Biomedical drug-carrying image testing technology can provide a quantitative assessment of drug distribution and absorption in the body. This study aims to explore the application of biomedical drug-carrying image testing technology in the simulation of cardiovascular drug care in coronary heart disease, so as to provide reference for the optimization of drug treatment plan and individualized treatment. The study collected clinical data and medication regiments of patients with coronary heart disease. Then, the imaging examination of patients was carried out by selecting appropriate drug loading markers using the biomedical drug loading image examination technology. Then quantitative analysis was used to process the image data to quantitatively evaluate the distribution and absorption of drugs in the cardiovascular system. The quantitative data of drug distribution and absorption in patients with coronary heart disease have been obtained successfully by means of biomedical imaging. These data reveal the dynamic changes of drugs in the cardiovascular system, and help doctors optimize drug therapy, improve treatment effectiveness, and achieve personalized treatment.

Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCß], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCß, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

Treatment patterns and adherence to lipid-lowering drugs during eight-year follow-up after a coronary heart disease event.

BACKGROUND AND AIMS: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event. METHODS: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment. RESULTS: Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure. CONCLUSIONS: In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions.

Sex differences in cardiologic medication provision for adults with coronary heart disease: an analysis of health claims data from 2018 to 2020 in Saxony-Anhalt, Germany.

BACKGROUND: Coronary heart diseases (CHDs) have experienced the largest increase worldwide as a cause of death, accounting for 16% of all deaths. In Saxony-Anhalt, a federal state in Germany, both CHD morbidity and acute myocardial infarction mortality rates are particularly high. Several risk factors associated with CHDs have been studied in Saxony-Anhalt, but sex differences in service use and medication have not been investigated. This study therefore aimed to investigate sex differences in the quality and quantity of cardiological care provided to adults with CHD. METHODS: This study used health claims data from 2018 to 2020 to analyse the utilisation of healthcare services and adherence to medication-related guideline recommendations in primary and specialist care. The sample included 133,661 individuals with CHD from a major statutory health insurance company (Germany). RESULTS: Almost all CHD patients (> 99%) received continuous primary care. Continuous cardiologist utilisation was lower for females than for males, with 15.0% and 22.2%, respectively, and sporadic utilisation showed greater differences, with 33.5% of females and 43.4% of males seeking sporadic cardiologist consultations. Additionally, 43.1% of the identified CHD patients participated in disease management programmes (DMPs). The study also examined the impact of DMP participation and cardiologist care on medication uptake and revealed that sex differences in medication uptake, except for statin use, were mitigated by these factors. Statins were prescribed to 42.9% of the CHD patients eligible for statin prescription in accordance with the QiSA indicator for statin prescription eligibility. However, there were significant sex differences in statin utilisation. Female CHD patients were less likely to use statins (35.2%) than male CHD patients were (50.1%). The difference in statin utilisation persisted after adjustment for DMP participation and cardiologist consultation. CONCLUSIONS: This study highlights sex differences in the utilisation of cardiological healthcare services for patients with CHD in the Saxony-Anhalt cohort. These findings underscore the continuing need for interventions to reduce sex inequalities in accessing healthcare and providing health care for patients with CHD. Factors at the health care system, patient, and physician levels should be further investigated to eventually improve statin prescription in people with CHD, especially women.

The Impact of Home Cardiac Rehabilitation on Quality of Life and Psychological Well-Being in Patients with Coronary Heart Disease: A Randomized Controlled Study.

BACKGROUND Percutaneous coronary intervention (PCI), a therapeutic approach to coronary heart disease, significantly alleviates symptoms of coronary heart disease (CHD) and substantially improves quality of life. This study aimed to investigate the effect of home cardiac rehabilitation (HCR) on patients after PCI. MATERIAL AND METHODS We randomly divided 106 patients after PCI into an Intervention group (n=52) and a Control group (n=53). Left ventricular ejection fraction (LVEF), blood pressure, blood glucose, and low-density lipoprotein were measured in both groups before hospital discharge and after 3 months of engaging in the intervention. Patients were assessed using the short-form health survey (SF-12) scale and Hospital Anxiety and Depression Scale (HADS) scale. RESULTS After 3 months of HCR intervention, SF-12 scores of patients in the Intervention group were significantly higher compared to patients in the Control group (physical component summary (PCS): 47.46±9.86 vs 43.28±8.21; and Mental Component Summary (MCS): 50.68±9.82 vs 48.26±9.69) (P.

Study on the Therapeutic Value of Shexiang Tongxin Dropping Pills in Patients with Stable Angina Pectoris of Coronary Heart Disease Complicated with Cognitive Impairment.

BACKGROUND: There is a pressing need to identify pharmaceuticals that are both safe and efficacious, with lower toxicity, for the treatment of stable angina pectoris in individuals suffering from coronary heart disease. The aim of this paper is to explore the therapeutic value of Shexiang Tongxin Dropping Pills in patients with stable angina pectoris of coronary heart disease complicated with cognitive impairment. METHODS: 200 patients with stable angina pectoris combined with cognitive dysfunction and coronary heart disease admitted to our hospital from January 2022 to June 2023 were retrospectively selected as the study objects. According to the treatment method, the subjects were divided into a control group and a study group, with 100 cases in each group. The control group received conventional oral Western medicine, and the study group underwent treatment with Shexiang Tongxin Dropping Pills in addition to traditional Western medicine. The course of treatment was eight weeks. The enhancement in angina pectoris, cognitive function level, self-care ability, and clinical efficacy of both groups were assessed by comparing the conditions before and after the treatment. RESULTS: After treatment, the frequency and duration of angina pectoris attacks in both groups were significantly lower than before, and the study group was lower than the control group (p < 0.05). The Montreal Cognitive Assessment (MoCA) score of both groups was higher than before, and the score of the study group was significantly higher than that of the control group (p < 0.05). Neuropsychiatric Inventory (NPI) scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). Traditional Chinese Medicine (TCM) syndrome scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). After treatment, the total effective rate of the control group and the study group was 81.00% and 93.00%, respectively, and the total clinical effective rate of the study group was significantly higher than that of the control group (p < 0.05). CONCLUSION: Shexiang Tongxin Dropping Pills can effectively reduce the incidence of angina pectoris in patients with stable angina pectoris complicated with coronary heart disease and cognitive dysfunction. It can also regulate the patient's neurological function, improve their cognitive level, and significantly improve clinical efficacy.

[Network Meta-analysis of Chinese patent medicines in treatment of coronary heart disease complicated with heart failure].

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.

Unraveling the pharmacodynamic substances and possible mechanism of Trichosanthis Pericarpium in the treatment of coronary heart disease based on plasma pharmacochemistry, network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. AIM OF THE STUDY: The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. MATERIALS AND METHODS: The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H2O2-induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. RESULTS: The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1ß, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1ß, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H2O2-induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. CONCLUSION: Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1ß, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP.

Chinese Herbal Medicines for Coronary Heart Disease: Clinical Evidence, Pharmacological Mechanisms, and the Interaction with Gut Microbiota.

Coronary heart disease (CHD) is a common type of cardiovascular disease (CVD) that has been on the rise in terms of both incidence and mortality worldwide, presenting a significant threat to human health. An increasing body of studies has shown that traditional Chinese medicine (TCM), particularly Chinese herbal medicines (CHMs), can serve as an effective adjunctive therapy to enhance the efficacy of Western drugs in treating CHD due to their multiple targets and multiple pathways. In this article, we critically review data available on the potential therapeutic strategies of CHMs in the intervention of CHD from three perspectives: clinical evidence, pharmacological mechanisms, and the interaction with gut microbiota. We identified 20 CHMs used in clinical practice and it has been found that the total clinical effective rate of CHD patients improved on average by 17.78% with the intervention of these CHMs. Subsequently, six signaling pathways commonly used in treating CHD have been identified through an overview of potential pharmacological mechanisms of these 20 CHMs and the eight representative individual herbs selected from them. CHMs could also act on gut microbiota to intervene in CHD by modulating the composition of gut microbiota, reducing trimethylamine-N-oxide (TMAO) levels, increasing short-chain fatty acids (SCFAs), and maintaining appropriate bile acids (BAs). Thus, the therapeutic potential of CHMs for CHD is worthy of further study in view of the outcomes found in existing studies.