Cardiovascular Drugs Research Articles

Influence of intestinal microbiota on the metabolism of main cardiotropic drugs

The intestinal microbiota is one of the most important pathogenetic links in the development of cardiovascular diseases. Every year the world scientific community finds new interactions at the level of signaling molecules, metabolites and microorganisms, identifying more and more patterns and cause-and-effect relationships which indicate the commonality of the intestinal microbiota (GM) and cardiovascular diseases. The state of the host's intestinal community, its qualitative and quantitative composition, directly and indirectly affects the fundamental pathogenetic mechanisms of the development of cardiovascular diseases. Despite the fact that there are scientifically based methods of treatment, cardiovascular diseases remain the leading cause of death in the world. This phenomenon is partly due to wide variations in individual response to cardiovascular drugs. The pharmacological effects of cardiotropic drugs are quite different even within groups of patients comparable in age and gender. Every year intestinal microbiota is more and more evident to be responsible for this intraspecific variability. Gut microbes influence drug metabolism in several pharmacokinetic ways, and conversely, drugs can have significant effects on the microbiome and therefore pharmacodynamic processes. Drugs can alter the gut microenvironment and microbial metabolism, influence bacterial growth, thereby changing the composition and functions of the microbial community. One of the most important functions of GM, related to “intestinal-cardiovascular system”, is participation in the metabolism of major cardiotropic medications, such as digoxin, statins, ezetimibe, antithrombotic drugs, calcium channel blockers (CCBs), beta blockers (BB), gliflozins and inhibitors of the renin-angiotensin-aldosterone system (RAAS).

Abstract Su706: New risk markers of sudden cardiac death in the young : insights from machine learning on EHR data

Background: Sudden Cardiac Death (SCD) in young adults is a significant public health issue, with survival rates often less than 15%. Effective prevention is critical as many SCD cases go undetected due to nonspecific symptoms and ineffective risk stratification methods, especially among the youth. Objective: To explore risk markers specific to SCD in younger populations using Artificial Intelligence (AI) trained on systematically collected Electronic Health Records (EHR) data, and to compare these markers with those in older populations. Methods: We conducted a retrospective cohort study using data from 46,060 participants in Paris and its inner suburbs, spanning 2011 to 2020. The cohort included 1,100 SCD cases and 1,100 controls aged 40 years or younger, and 21,930 SCD cases and 21,930 controls aged over 40. A machine learning model was developed, trained, and validated on these cohorts. We used the Catboost algorithm and evaluated model performance using AUC, sensitivity, and specificity. The SHAP algorithm was employed to elucidate the relationship between variables and predicted risk. Results: The model achieved on validation sets an AUC of 0.75 (95% CI 0.67-0.83) for the younger cohort and AUC of 0.82 (95% CI: 0.70-0.83), for the older cohort. Neuropsychiatric drugs were the most influential predictors for the younger cohort, whereas age and cardiovascular drugs were most predictive for the older cohort. The results indicate that traditional cardiovascular risk factors play a secondary role in predicting SCD among younger individuals. Conclusion: In analyzing predictors of sudden death in individuals under 40, we developed a personalized SCD prediction model using EHR data tailored to this demographic. Psychiatric medications, and possibly underlying psychiatric conditions, emerged as significant predictors. Our findings emphasize the need for a multidisciplinary approach to SCD prevention, integrating neuropsychiatric and cardiovascular considerations.

Editorial Expression of Concern: Lipid-lowering therapy in patients with coronary heart disease: an Italian real-life survey. Results from the Survey on Risk FactOrs and CardiovascuLar secondary prevention and drug strategieS (SOFOCLES) in Italy.

The Editors and the Publisher have been alerted to concerns about this article (DOI: 10.4081/monaldi.2024.2972), and an investigation is in progress. In the interim, we alert readers that these concerns have been raised. This Expression of Concern will remain in place until the investigation is completed and any further needs for appropriate action have been taken.

Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French pharmacovigilance database.

Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs. This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged 18 and over. We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 [18-103] years. The most prevalent ADRs were "ILD" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). "Anti-cancer drugs" (31.2%) and "Cardiovascular drugs" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%). This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify it properly and discontinue the culprit drug urgently.

DESIGN, OPTIMIZATION AND EVALUATION OF RANOLAZINE FAST-DISSOLVING FILMS EMPLOYING MANGO KERNEL STARCH AS A NEW NATURAL SUPERDISINTEGRANT

Objective: The BCS class II cardiovascular medication, Ranolazine (RZN), is characterized by limited solubility and inadequate oral absorption. The objective of the current research is to develop a natural superdisintegrant in the formulation of Fast-Dissolving Films (FDFs) of Cardio Vascular Drug (CVD) RZN to enhance its dissolution rate, solubility, absorption, and therapeutic action. Methods: Mango Kernel Starch (MKS) is isolated by grinding the kernels, forming a slurry with water, filtering, and using repeated centrifugation and washing to purify the starch, which is then dried. The obtained starch is collected. Along with obtained natural superdisintegrant MKS, Maltodextrin (MDX) and Sodium Starch Glycolate (SSG) were also utilized in the fabrication of FDFs containing RZN via the solvent casting technique. A total of eight formulations (RF1 to RF8) were developed employing a 23 factorial design, using the natural superdisintegrant alone at a concentration of 5% and in combination with other superdisintegrants. Results: The prepared MKS was found to be free-flowing, fine, amorphous, insoluble in organic solvents, and exhibiting 0.17% solubility in water with a swelling index of 89.95%, indicating superdisintegrant properties. Fourier-transform infrared spectroscopy (FTIR) studies and Differential scanning calorimetry (DSC) analysis indicated that there was no drug-excipient interaction. The films prepared with a 5% concentration of the MKS showed good physical properties and resulted in an increased drug dissolution rate, with 99.78 % of the drug dissolved within 10 min, along with the lowest disintegration time of 13.45 sec. Conclusion: The research successfully isolated a new superdisintegrant, MKS and formulated FDFs of the poorly water-soluble drug RZN. The MKS was found to be an effective superdisintegrant with no drug interactions, producing films with good physical and mechanical properties, increasing the drug dissolution rate, and providing rapid disintegration with improved relative bioavailability.

Adverse Drug Reactions and Safety Profiles in Cardiovascular Drug Therapy: A Pharmacovigilance Analysis

Aims: The purpose of the study is to identify adverse drug reactions (ADRs) and evaluate patient knowledge of the disease using the Knowledge Assessment Questionnaire (KAQ). This study was designed to compare adverse effects on Cardiovascular Drug Therapy. Adverse drug reaction (ADRs) is a major cause of mortality worldwide. The objective of the present study were a) to find out the prevalence of adverse drug reaction (ADRs) in the hospitalized patient by active surveillance, b) to study the profile of ADRs detected. (3) This study was done in superspecialty hospital Netaji Subhash Chandra Bose medical college & Hospital, Jabalpur, for three month study. Methodology: This study was Pharmacovigilance group, belonging to department of cardiology at Netajisubhash Chandra bose medical college, Jabalpur M.P. (5) Total number of patients taken for study was 90 in number. Results and Conclusion: Total 90 subjects were recruited in the study. Drug used for their co morbidities to find out ADRs in which maximum ADRs found in chronic rheumatoid heart diseases, for this diseases patient took in two combination mainly Digoxin with Clopidogrel (47.36%) and another were with atorvastatin, spironolactone and warfarin (47.30% ADRs Adverse drug reactions on particular body system were mostly observed on CNS (32.14% ADRs). According to Naranjonaranjo causality assessment scale applied to this study illustrates that the maximum possible and probable adverse drug reaction were shown on Furosemide as well as for Digoxin and Spironolactone.

Bioaccumulation and tissue distribution of pharmaceuticals and their transformation products in fish along the pollution gradients of a wastewater-impacted river

A field study on the occurrence and distribution of forty-three pharmaceutically active compounds (PhACs) in water and fish samples from anthropogenically impacted section of the Sava River (Croatia) was performed to estimate the importance of bioaccumulation for the environmental risk assessment of PhACs. The study was performed using a highly specific LC-MS/MS method, tailored to include the most prominent PhACs from different therapeutic categories as well as their major metabolites and/or transformation products (TPs). The results revealed a widespread occurrence of PhAC residues both in water and fish samples with a large spatial variability reflecting the distance from the dominant wastewater discharges. The most prominent PhAC categories in less polluted upstream part of the river were common psychostimulants caffeine and cotinine, therapeutic opioids and cardiovascular drugs, while in the river section affected by the local municipal and industrial wastewater inputs, antibiotic drugs became clearly predominant, especially in fish tissue samples. The apparent bioconcentration factors (BCFs) of investigated PhACs varied over several orders of magnitude, from 0.02 ± 0.01 Lkg−1 for O-desmethyl tramadol in fish muscle to 784 ± 260 Lkg−1 for terbinafine in fish liver, indicating rather large differences in their bioconcentration potential and affinity to different tissues, with the tissue-specific BCFs increasing in the following order: muscle < gills < gonads < heart < liver < kidneys. The bioconcentration potential of most of the PhACs included in this study was only low to moderate however moderately high BCFs of certain PhACs (e.g. sertraline, terbinafine, loratadine, diazepam and azithromycin) in some tissues should be taken into consideration when assessing their potential environmental risks. Moreover, it was shown that BCFs could be strongly affected by biotransformation in fish. Risk prioritization based on risk quotient (RQ) and ToxPi index, revealed antibiotics, in particular azithromycin, and therapeutic psychoactive substances as the most hazardous pharmaceutical contaminants in the Sava River.

Gut microbiome and inflammation in cardiovascular drug response: trends in therapeutic success and commercial focus.

The intricate Gut microbiome is evolving as an important system and is hypothesized to be a "metabolic organ" within the host. Alterations in Gut microbiota and inflammation associated with several diseases play acrucial role in drug transformation through microbiota-host co-metabolism, modified pharmacokinetic and pharmacodynamics profiles, and may result in the formation of toxic metabolites with interference in drug response. In recent studies, a large number of drugs are reported that are co-metabolized by the host and the Gut microbial enzymes. we summarize thedirect and indirect involvement of Gut microbiome promotion or inhibition of cardiovascular diseases, mechanisms on bioavailability, and therapeutic outcomes of cardiovascular drugs, particularly pharmacokinetics and pharmacodynamics profiles in light of AUC, Tmax, Cmax, and bioavailability and drug transportation via immune cells, inter-individual variations in intestinal microbial taxonomy, influence of drugs on diversity and richness of microflora, high lightening limitations and significance of in personalized medicine. Recent advances in target-drug delivery by nanoparticles with limitations and challenges in application are discussed. The cross-talk between Gut microbiota and cardiovascular drugs signifies abetter understanding and rationale fortargeting the Gut microbiota to improve the therapeutic outcome for cardiovascular diseases, with present-day limitations.

Bushen Huoxue Yiqi Formula Alleviates Cardiac Fibrosis in Ischemic Heart Failure through SIRT1/Notch1 Pathway-Mediated EndMT

BackgroundCardiac fibrosis plays a crucial role in the development of heart failure (HF) following myocardial infarction (MI). Endothelial-mesenchymal transition (EndMT) is one of the key drivers of cardiac fibrosis and subsequent cardiac dysfunction. The traditional Chinese medicine formula Bushen Huoxue Yiqi Formula (BHYF) is an effective prescription for treating HF, significantly improving cardiac function in patients. However, the underlying mechanisms of BHYF's efficacy remain inadequately understood. ObjectiveThis study aims to determine whether BHYF ameliorates HF by inhibiting cardiac fibrosis and to elucidate the intrinsic mechanisms involved. MethodsA post-MI HF model was established by ligating the left anterior descending coronary artery in rats, and human umbilical vein endothelial cells (HUVEC) were stimulated with hypoxia/reoxygenation (H/R) in vitro. Active compounds in BHYF were identified using HPLC. Cardiac function and morphology were assessed using echocardiography, TTC staining, HE staining, Masson's trichrome, and Sirius Red staining. The mechanism of action of BHYF was evaluated using Western blotting, immunohistochemistry, and immunofluorescence. ResultsA total of 98 compounds, including glycosides, phenolic compounds, carboxylic acids, and others, were identified or preliminarily identified. BHYF improved cardiac function and myocardial damage in rats with MI-induced HF and mitigated cardiac fibrosis by inhibiting EndMT. Mechanistically, BHYF treatment inhibited EndMT by modulating the SIRT1/Notch1 pathway, thereby exerting anti-fibrotic effects in the heart. ConclusionTargeting EndMT based on the SIRT1/Notch1 pathway, BHYF may represent a novel antifibrotic therapeutic strategy, providing a scientific basis for the development of new cardiovascular drugs.

Association of COVID-19 and influenza vaccinations and cardiovascular drugs with hospitalisation and mortality in COVID-19 and Long COVID: 2-year follow-up of 17 million individuals in England

Abstract Introduction For COVID-19 and Long COVID, determining the highest-risk subgroups, particularly in the context of compound pressures such as influenza and cardiovascular disease (CVD), may identify effective interventions to prevent adverse health outcomes, and inform public health and policy decisions. Methods Using national, linked electronic health records for England (NHS England Secure Data Environment: via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals with COVID-19 and Long COVID from January 2020 to February 2023. We compared all-cause hospitalisation and mortality in unmatched and matched cohort analyses, by prior CVD, high CVD risk (by QRISK2), COVID-19 and influenza vaccination status, and prescription of CVD preventive therapies. We investigated potential impact of targeted vaccination and CVD prevention strategies on mortality and hospitalisations by calculating population preventable fractions. Results We identified 17,373,850 individuals with COVID-19 [54.4% female; mean age 38.8 years; COVID-19 vaccination ≥2 doses:50.0%, influenza vaccination (≥1 dose):27.8%; mean follow-up 1.28 years] and 301,115 with Long Covid [61.8% female; mean age 46.0 years; COVID-19 vaccination ≥2 doses:66.4%, influenza vaccination:33.1%; mean follow-up 1.1 years]. Hospitalisation and mortality rates were 15.3% and 2.0% in COVID-19 (Long COVID rate 1.3%) and 16.8% and 1.4% in Long COVID, respectively. Adjusted risk of mortality and hospitalisation were reduced with COVID-19 vaccination ≥2 doses (COVID-19:HR 0.36, 95% CI 0.34-0.38 and 0.69, 0.68-0.69; Long COVID:0.44, 0.42-0.47 and 0.90, 0.89-0.91). With influenza vaccination, mortality was reduced, but not hospitalisation (COVID-19: 0.86, 0.85-0.86 and HR 1.01, 1.01-1.01, and Long COVID: 0.72, 0.67-0.76, and 1.05, 1.03-1.07), with greatest effect in those with prior CVD and high CVD risk. Mortality and hospitalisation were also reduced by CVD prevention in those with CVD, e.g. anticoagulants- COVID-19: 0.69, 0.69-0.70 and 0.92, 0.91-0.93; Long Covid: 0.59, 0.54-0.64, and 0.88, 0.84-0.92. COVID-19 vaccination, influenza vaccination and CVD drugs (Anticoagulants) averted 101117 of 193598, 2138 of 4017 and 16573 of 36847 preventable deaths among individuals after COVID-19, and 875 of 1189, 65 of 127 and 507 of 1007 preventable deaths among those with Long COVID, particularly in people with CVD. Conclusions Prior CVD and high CVD risk are associated with increased hospitalisation and mortality risk in people with COVID-19 and Long COVID. Targeted improvement in COVID-19 vaccination and CVD prevention, especially in those with CVD are priority interventions in pandemics to avoid excess hospitalisation and mortality.Baseline Characteristics and OutcomesHospitalisation/mortality by COVID vaccn

Prevalence and incidence of heart failure in patients with type 2 diabetes mellitus. Results of the prospective DIABET-IC study

Abstract Introduction Heart failure (HF) is one of the major health problems in our environment today. Type 2 diabetes mellitus (DM2) is an important cardiovascular risk factor and can increase the burden of HF through various mechanisms. The incidence of HF in DM2 has not been well studied. Purpose The aim of our study was to evaluate the prevalence and incidence of HF in patients with DM2 followed in hospital cardiology and endocrinology departments. Methods The DIABET-IC study is a longitudinal cohort, prospective, multicenter follow-up study that included 1,249 consecutive patients with DM2 in 2018-2019 in 30 Spanish centers in cardiology and endocrinology outpatient clinics. HF was diagnosed according to the clinical records and following the criteria of the European Society of Cardiology. The prevalence of HF at the inclusion visit was analyzed, as well as the incidence of HF (new diagnoses) during a 3-year follow-up. Results Mean age was 67.3±+9.9 years, with 31.7% of the patients being women. Cardiology clinics included 61.9% of patients and endocrinology clinics the remaining 38.1%. There was a previous history of coronary artery disease in 38.6%, hypertensive heart disease in 21% and atrial fibrillation in 31.9%. Cardiovascular and antidiabetic drugs prescribed at the baseline and 3-year visits are shown in figure 1. Figure 2 summarizes the results of the study. The prevalence of HF at the baseline visit was 39.2%, 490 cases (with reduced LVEF 17.3%, mildly reduced 8.1% and preserved 13.8%). After a follow-up of 1,935/100 persons-year of cases without baseline HF, 58 incident cases of HF were diagnosed, 7.6% (32 in the first year, 13 in the second and 13 in the third year of follow-up). The incidence rate was 3.01/100 person-years (95%CI: 2.30-3.92). Of these 58 cases, 23.7% were with reduced LVEF, 28.9% with slightly reduced LVEF and 47.4% preserved. The incidence was higher in patients followed by endocrinology (3.90 vs 2.90/100 persons-year; p=0.042). At the end of the 3-year follow-up, including baseline prevalence, 46.8% of all patients had HF. Conclusions The prevalence and incidence of HF in patients with DM2 are very high. The incidence of HF is around 3% per year, which is almost 8 times higher than the rate found in large studies in the general population. Approximately half of the new cases were HF with preserved LVEF, and the other half with LVEF &amp;lt; 50%. The use of new antidiabetic drugs, such as iSGLT2, which have been shown to reduce the incidence of HF, should be encouraged.

Epigenetic modulation of sirt1 and sirt6 in cardiovascular diseases: unraveling autophagy regulation and endothelial function

Abstract Background Heart failure (HF) and cardiovascular diseases (CVD) still represent major causes of death. Dysmetabolic conditions led by epigenetic alterations play a major role as CVD triggers, expecially those related to the modulation and control of autophagy during the remodelling in HF. Accordingly, several studies have strengthened the role of epigenetics in regulating both cardiac/endothelial phenotype and function, demonstrating how sirtuins, a well-acknowledged family of histone deacetylase, can conjunct the control of cardiac fibrosis, angiogenesis and induction of autophagy. However, this link remains to be fully clarified and explored. Thus, novel drugs targeting autophagy trough epigenetic mechanisms are considered appealing as targets from a pharmacological standpoint in CVD. Purpose This project aims to develop and test two epigenetic modulators and allosteric activators targeting SIRT1 and -6 to further elucidate their role in autophagy regulation and in cardiac/endothelial biology. Methods Chemical synthesis of SIRT1 and SIRT6 activator isoform (SRT2104 and MDL800). Evaluation of epigenetic modulation (H3 histone acetylation H3K9) of endothelial cells (HUVEC). HUVEC survival, angiogenic and autophagy activity were assessed undergo hyperglycemic or hypoxic stress, co-treatment with the selected compounds. Results The specific activator of SIRT-1 (SRT2104) and SIRT-6 (MDL800) show epigenetic activity as they induce the deacetylation of histone H3 on lysine 9. Endothelial cell viability is not influenced by the treatment with both modulators in hyperglycemia and upon hypoxic condition. In HUVEC cultures underwent to hyperglycemia-based stress, both molecules can activate autophagy with an increase in LC3 II protein (1,4-fold HG SRT2104 and 2,8-fold HG MDL800), compared to control.The treatment with SRT2104 enhances HUVEC tube formation, suggesting the increased functional angiogenic ability even in presence of high levels of glucose. Interestingly, the treatment with SRT2104 impacts the transcriptional levels of other members of the sirtuins family, by increasing SIRT-2, 3 and 5. In conclusion, the epigenetic activators SRT2104 and MDL800 have a beneficial effect on endothelial cells by enhancing the autophagic process and stimulate neoangiogenesis.The implementation of these results will attempt to understand to what extent epigenetic drugs such as sirtuin activators, could boost the more pleiotropic and less targeted effects of the current cardiovascular drugs, and to evaluate their functional and phenotype-driven drug refinement.

A higher adherence to perindopril-based anti-hypertensive therapy is associated with a reduced risk of cardiovascular outcomes and all-cause mortality in real clinical practice in Italy

Abstract Background Therapeutic management of hypertension is a landmark of cardiovascular (CV) risk prevention. Combined therapies with at least 2 anti-hypertensive agents are required in many patients in whom monotherapy and lifestyle interventions failed in blood pressure control. It is well-known that poor medication adherence remains a major barrier to achieving the therapeutic targets for all CV drugs, including anti-hypertensives. Purpose We evaluated the relationship between adherence to perindopril (PER)-based therapeutic regimen prescribed as single-pill combination (SPC) or free-pill and CV outcomes and all-cause mortality in a large Italian population. Methods A retrospective analysis was performed using administrative databases corresponding to around 6.7 million health-assisted residents. Hypertensive adults were first identified through hospitalization discharge diagnosis or exemption codes for hypertension between 2010 and 2021. Patients prescribed PER-based therapies were screened for all combinations of PER with amlodipine (AML) and/or indapamide (IND) (all formulations, single-pill or free-pill). Time of the first prescription of a PER-based regimen during the inclusion period was considered the index-date. The analysis included all hypertensive subjects prescribed a PER-based therapy, having available data at least 12 months before and 24 months after the index-date, respectively. Since the analysis was focused on the possible associations between adherence level and CV outcomes and all-cause mortality, adherence was assessed during the first year of follow-up on alive patients and outcomes were assessed during the second year. Adherence was assessed using the proportion of days covered (PDC) approach on 1-year follow-up, and considering a PDC&amp;lt;80% as poor-to-moderate adherence, and PDC ≥80% as good adherence. The Cox’s proportional hazard model was applied to estimate Hazard Ratio (HR) adjusting for baseline covariates, including comorbidity profile and pill burden. Results The included cohort (N=24,476) was divided into sub-groups according to adherence in poor-to-moderate (N=6,781) and good adherent patients (N=17,695) with a mean age of 64.8±13.3 and 64.6±11.9 years old, respectively. The Cox’s proportional hazard model showed that good adherence was associated with a relative risk reduction of 23% in all-cause mortality (Table 1A), 21% in all CV events (Table 1B), 17% in ischemic heart disease (Table 1C), 33% in cerebrovascular events (Table 1E), and 22% in the composite outcome of CV events/all-cause mortality (Table 1G). Conclusions The present analysis provided evidence from the Italian real clinical practice that good adherence to PER-based anti-hypertensive therapy results in significantly lower cardiovascular risk and all-cause mortality. These data further emphasize the importance of promoting cost-effective measures to increase medication adherence in patients on anti-hypertensive treatment.

Drug-gene interactions in older patients with coronary artery disease

BackgroundOlder patients with coronary artery disease (CAD) are particularly vulnerable to the efficacy and adverse drug reactions, and may therefore particularly benefit from personalized medication. Drug–gene interactions (DGIs) occur when an individual’s genotype affects the pharmacokinetics and/or pharmacodynamics of a victim drug.ObjectivesThis study aimed to investigate the impact of cardiovascular-related DGIs on the clinical efficacy and safety outcomes in older patients with CAD.MethodsHospitalized older patients (≥ 65 years old) with CAD were consecutively recruited from August 2018 to May 2022. Eligible patients were genotyped for the actionable pharmacogenetic variants of CYP2C9, CYP2C19, CYP2D6, CYP3A5, and SLCO1B1, which had clinical annotations or implementation guidelines for cardiovascular drugs. Allele frequencies and DGIs were determined in the cohort for the 5 actionable PGx genes and the prescribed cardiovascular drugs. All patients were followed up for at least 1 year. The influence of DGIs on the cardiovascular drug-related efficacy outcomes (all-cause mortality and/or major cardiovascular events, MACEs) and drug response phenotypes of “drug-stop” and “dose-decrease” were evaluated.ResultsA total of 1,017 eligible older patients with CAD were included, among whom 63.2% were male, with an average age of 80.8 years old, and 87.6% were administrated with polypharmacy (≥ 5 medications). After genotyping, we found that 96.0% of the older patients with CAD patients had at least one allele of the 5 pharmacogenes associated with a therapeutic change, indicating a need for a therapeutic change in a mean of 1.32 drugs of the 19 cardiovascular-related drugs. We also identified that 79.5% of the patients had at least one DGI (range 0–6). The median follow-up interval was 39 months. Independent of age, negative association could be found between the number of DGIs and all-cause mortality (adjusted HR: 0.84, 95% CI: 0.73–0.96, P = 0.008), and MACEs (adjusted HR: 0.84, 95% CI: 0.72–0.98, P = 0.023), but positive association could be found between the number of DGIs and drug response phenotypes (adjusted OR: 1.24, 95% CI: 1.05–1.45, P = 0.011) in the elderly patients with CAD.ConclusionsThe association between cardiovascular DGIs and the clinical outcomes emphasized the necessity for the integration of genetic and clinical data to enhance the optimization of cardiovascular polypharmacy in older patients with CAD. The causal relationship between DGIs and the clinical outcomes should be established in the large scale prospectively designed cohort study.

Cardiovascular management of patients undergoing noncardiac surgery

The risk assessment of patients with cardiovascular diseases before noncardiac surgery (NCS) is particularly relevant in cardiology because of the frequency and the involvement of different disciplines. The risk is determined by the operation itself and the disease or risk profile, including the patient's age. Specialist preoperative consultation can therefore remain limited if the surgery-related risk is low. The subjective symptoms (exercise tolerance) and also the determination of the cardiac biomarkers N‑terminal pro-brain natriuretic peptide (NT-proBNP) and troponin are particularly relevant for assessing the indications for an instrumental or specialist examination. Cardiovascular drug treatment should predominantly be continued perioperatively but not initiated just for the operation. There are practical guidelines for pausing oral anticoagulation, whereby a general heparin bridging is no longer recommended.

Development of a new micellar formulation of carvedilol and curcumin to enhance blood pressure reduction in a spontaneously hypertensive rat model.

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, requiring innovative therapeutic strategies. This project explores a nano-pharmaceutical approach to enhance the efficacy of cardiovascular drugs, focusing on carvedilol and curcumin. These agents, known for their potential cardiovascular benefits, are encapsulated within Soluplus® micelles to form a novel drug delivery system. The novelty of this formulation lies in its ability to significantly improve the solubility of both carvedilol and curcumin, which have traditionally been limited by their hydrophobic nature. By utilizing Soluplus® micelles, we have developed a unique delivery system that optimizes the therapeutic potential of both drugs. The nanomicelles were meticulously characterized for drug loading, size distribution, and morphological features. The carvedilol and curcumin release patterns were investigated, revealing sustained and controlled release profiles. Additionally, the antioxidant capacity of the micellar formulation was evaluated, demonstrating the preservation of curcumin's antioxidative properties. In vivo studies using spontaneously hypertensive male rats explored the pharmacokinetics and hemodynamic effects of the nanomicellar system. These results indicated successful encapsulation of both drugs without altering their plasma profiles. Furthermore, the administration of carvedilol and curcumin micelles exhibited a more significant reduction in mean arterial pressure compared to individual drug administration, suggesting a potential synergistic effect. In conclusion, this nano-pharmaceutical approach offers a promising avenue for cardiovascular therapy, providing a platform for combined drug delivery and potential synergistic effects. The optimized formulation could lead to improved patient outcomes and enhanced cardiovascular health.

Rapid detection of drugs in blood using “molecular hook” surface-enhanced Raman spectroscopy and artificial intelligence technology for clinical applications

Accurate detection of cardiovascular drugs in blood is complicated by interference from serum biomolecules. This study introduces a novel surface-enhanced Raman spectroscopy (SERS) platform incorporating “molecular hooks” to capture small drug molecules while excluding larger biomolecules selectively. The self-assembled nanoparticles with the A13 molecule enhance Raman signals by creating dense electromagnetic “hotspot” regions, achieving detection limits of 10 pg/mL for dobutamine hydrochloride and 10 ng/mL for milrinone-substantially below therapeutic thresholds. Artificial intelligence (AI) integration enables automated spectral analysis, allowing rapid and precise drug detection in clinical blood samples. This approach offers a transformative solution for real-time diagnostics, significantly advancing personalized treatment strategies in clinical settings.

Association of positive airway pressure termination with mortality and non-fatal cardiovascular events in patients with obstructive sleep apnoea

Background and aimsThe recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether...

Pharmacological activity, phytochemistry, and organ protection of lithospermic acid.

Lithospermic acid (LA) is a water-soluble phenolic acid compound extracted and separated from the dried root and the rhizome of Salviamiltiorrhiza Bge (Labiatae), possessing multiple biological activities. Firstly, in terms of pharmacological activities, LA has been proven to possess anti-inflammatory, antioxidant, autophagy activation, and antiapoptotic properties. Secondly, the pharmacokinetic characteristics of LA show rapid and extensive distribution in various tissues after intravenous administration, followed by rapid elimination and excretion. Additionally, potential therapeutic effects of LA have been found in various diseases such as thrombosis, Parkinson's disease, hepatitis B, diabetes, and psoriasis, among others. Particularly, LA has shown promising prospects in the treatment of clinical heart diseases and has been included in new drug formulations for the treatment of chronic angina, demonstrating superior efficacy compared to current cardiovascular drugs. In conclusion, this review comprehensively introduces the pharmacological mechanisms, pharmacokinetics, and protective effects in diseases of LA. These information can lay a theoretical foundation for the future development and new clinical applications of LA.

Simple simultaneous analysis of various cardiovascular drug mixtures with vincamine: comparative eco-friendly assessment

The development of two eco-friendly analytical methods for the simultaneous determination of eight cardiovascular drugs; hydrochlorothiazide (HCT), captopril (CPL), lisinopril (LSP), valsartan (VAL), atorvastatin (ATR), bisoprolol (BSL), amlodipine (AML) and carvedilol (CVL); alongside with the nutraceutical vincamine (VIC) is essential for sustainable pharmaceutical analysis. This study explores the application of Micellar Electro Kinetic Chromatography (MEKC) and High-Performance Liquid Chromatography (HPLC) for this purpose. In MEKC method, the separation was done using fused silica capillary (41.5 cm × 50 µm id) and a back ground electrolyte consisting of 50 mM borate buffer (pH 9) containing 50 mM sodium lauryl sulphate (SLS) and 10% organic modifier (Acetonitrile). In HPLC method, separation was performed on a ZORBAX Extend-C18 (4.6 × 250 mm, 5 µm) column, using a gradient mobile phase consisting of 50 mM phosphate buffer pH 3 and methanol. Both methods attained good linearity (r ≥ 0.9996) with low values of LOD and LOQ. Both methods were successfully applied in the determination of co-administered single, binary and ternary dosage form of the studied drugs. Moreover, application of various combinations of co-administered dosage forms was achieved in rat plasma, confirming the applicability of these methods in different matrices. The use of micellar solutions in MEKC enhances separation efficiency while reducing the need for organic solvents, aligning with green chemistry principles. HPLC methods were optimized using environmentally benign solvents, ensuring reduced toxicity and waste production. The methodologies were evaluated through green, white, and blue metrics to ensure comprehensive sustainability, considering ecological impact, safety, and practical efficiency. These methods were not only cost-effective and time-saving but achieved high efficiency, sensitivity, and reproducibility making them ideal for routine use in pharmaceutical analysis.