Statins Research Articles

Drug Target Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia with significant clinical implications. The potential influence of lipid-lowering therapies, specifically PCSK9 inhibitors (PCSK9i) and HMG-CoA reductase inhibitors (statins), on AF risk remains a topic of interest. This mendelian randomization (MR) study aimed to elucidate the causal relationship between genetically predicted inhibition of PCSK9 and HMG-CoA reductase and the risk of AF. Methods: Utilizing publicly available, summary-level genome-wide association study data, we employed single-nucleotide polymorphisms associated with lower LDL-C levels as instruments for gene-simulated inhibition of PCSK9 and HMG-CoA reductase. Multiple MR techniques were applied to estimate the causal effects, and sensitivity analyses were conducted to validate the results. Results: Genetically predicted inhibition of PCSK9 demonstrated a reduced risk of AF, with an odds ratio (OR) of 0.92 (95% CI: 0.85–0.99, p = 0.01) using the inverse variance-weighted (IVW) method. In contrast, the inhibition of HMG-CoA reductase did not exhibit a statistically significant association with AF risk (IVW: OR = 1.11, 95% CI: 1.00–1.22, p = 0.05). Conclusion: Our MR study suggests that genetically predicted inhibition of PCSK9, but not HMG-CoA reductase, is associated with a lower risk of AF. These findings provide evidence for a causal protective effect of PCSK9i on AF and support the use of PCSK9i for AF prevention in patients with dyslipidemia. Further studies are needed to elucidate the mechanisms underlying the differential effects of PCSK9i and statins on AF and to confirm the clinical implications of our findings.

Early statin exposure influences cardiac and skeletal development with implications for ion channel transcriptomes in zebrafish

Statins, widely prescribed for cholesterol management by inhibiting HMG-CoA reductase in the cholesterol biosynthesis pathway, may also influence vertebrate development. In this study, we investigated the developmental effects of two widely used statins, atorvastatin (ATO) and pravastatin (PRA), on zebrafish offspring. For ATO, we administered doses classified as low (1 μM), medium (5 μM), and high (10 μM), while for PRA, the corresponding concentrations were set at low (18 μM), medium (180 μM), and high (270 μM). Our results showed significant reductions in birth and hatching rates, along with decreased body length in offspring at all ATO concentrations and medium to high PRA concentrations. A notable increase in malformation rates, especially in the spine and heart, was observed across all ATO treatments and in medium and high PRA groups. Additionally, we observed reduced heart contraction rates, decreased heart size, lower bone volumes, and diminished expression of mRNA osteogenic markers. Elevated venous sinus-artery bulb (SV-BA) ratios, increased thoracic area, and abnormal cartilage development were also prominent in all ATO-treated groups. Transcriptome analysis revealed alterations in genes predominantly associated with ion channels. These findings provide insights into the potential impacts of specific concentrations of statins on offspring development and highlight potential gene interactions with statins.

Abstract 4126: The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer

Abstract Endometrial cancer (EC) is the most common gynecologic malignancy. The most common histological type is endometrioid endometrial cancer (EEC). While the majority of patients present with early-stage and low-grade EEC and have an excellent prognosis, a subset develops distant recurrence derived from EEC after initial treatment of the primary. However, the exact mechanism of distant metastasis and recurrence from EEC is still unclear. In addition, the lack of suitable pre-clinical models is a significant barrier to research for distant metastasis and recurrent cancer derived from EEC. Our preclinical EEC model, the ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/fPtenf/f; Mig-6d/dPtend/d), dramatically accelerates the development of EEC compared to single ablation of either gene. The ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/f Ptenf/f; Mig-6d/dPtend/d mice) displayed distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, the Ptend/d mice exhibited endometrial cancer without distant metastases. After hysterectomy of EEC confined to uterus, Mig-6d/dPtend/d mice exhibited recurrent EEC in abdomen and lung. To identify prognostic factors for distant metastatic and recurrent EEC, we performed transcriptomic analysis in endometrial hyperplasia, a precancerous condition, from Ptend/d and Mig-6d/dPtend/d mice. Our transcriptomic analysis identified that cholesterol biosynthesis was the most significantly activated pathway in Mig-6d/dPtend/d mice compared to Ptend/d mice. Statins, also known as HMG-CoA reductase inhibitors, are the most common cholesterol-lowering drugs. We evaluated the effect of atorvastatin on tumorigenesis and recurrence of EEC. Mig-6d/dPtend/d mice treated with atorvastatin displayed significant reduction of tumor size compared to vehicle treated group. For vehicle-treated group, our pathological analysis revealed EEC outside the uterus, therefore EEC had disseminated to involve the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, EEC was confined to the uterus in the atorvastatin treated group. Furthermore, atorvastatin treatment reduced the rate of recurrent EEC development. This data demonstrated that atorvastatin has a remarkable inhibitory effect on metastasis and recurrence of EEC in Mig-6d/d Ptend/d mice. Our results suggest that statins suppress development of distant metastasis and recurrence in mouse models of EEC with Pten and Mig-6 deficiency by inhibiting cholesterol biosynthesis. Citation Format: Keun Cheon Kim, Jung Yoon Yoo, Russell R Broaddus, Eunhee M Jeong, Mark I Hunter, Tae Hoon Kim, Jae-Wook Jeong. The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4126.

Abstract P514: Association Between Glycemic Disorder and Acute Coronary Syndrome Among Patients With Stable Coronary Artery Disease: A Propensity Score Matching Analysis

Background: Type 2 diabetes mellitus is known as a major risk factor of acute coronary syndrome (ACS) as previous studies reported. However, the association between prediabetes and ACS is not fully investigated among patients with stable coronary artery disease (CAD). Furthermore, no study has examined whether there’s effect modification by sex, age and BMI in the association between glycemic disorder and ACS. Our study aimed to evaluate the role of glycemic disorder in ACS occurrence among patients CAD. Methods: In this cross-sectional study based on electronic medical records (EMR), participants with CAD after elective coronary artery angiography (CAG) during 2016-2020 were enrolled. Diagnosis of prediabetes was based on patients’ HbA1c level ranging from 5.7% to 6.4% or fasting plasma glucose (FPG) level between 5.6 - 6.9 mmol/L. The diabetes diagnosis was defined as HbA1c ≥6.5% or fasting plasma glucose (FPG) ≥7.0 mmol/L. Multivariable logistic regression models were built to evaluate the association between prediabetes, diabetes and ACS, adjusting for age, body mass index (BMI), hypertension, low density lipoprotein, triglyceride level, statin and anti-platelet medication use. Subjects with prediabetes were matched 1:1 to healthy controls using propensity score matching to test the robustness of the result. In the subgroup analysis, we examined the heterogeneity of age, sex and BMI in the association between glycemic disorders and ACS. Results: Among 1525 participants, 1158 were male and 367 were female. Compared to participants with no diabetes, those with prediabetic were not significantly associated ACS, after adjusting for potential confounders. The result persisted after 1:1 propensity score matching. There was effect modification by sex in the association between glycemic disorders and ACS (P glycemic disorder*sex = 0.012). Female participants with diabetes, compared to those without diabetes, were positively associated with ACS (OR 2.00, 95% CI 1.00 - 3.98). The association between glycemic disorders and ACS remained stable among those with severe coronary stenosis. Conclusions: Our finding suggested that the association between prediabetes and ACS did not differ from those with normal glycemic status and CAD. The association remained consistent among those with severe coronary stenosis. Besides, sex modifies the association, and female participants with diabetes should be paid attention to their higher risk of ACS.

Rationale and Design of the Statin Use in Intracerebral Hemorrhage Patients (SATURN) Trial

Introduction: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCEs) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes, and quality of life. Methods: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, phase III clinical trial with blinded end-point assessment. A planned total of 1,456 patients with lobar ICH will be recruited from 140 sites in the USA, Canada, and Spain. Patients presenting within 7 days of a spontaneous lobar ICH that occurred while taking a statin will be randomized (1:1) to continuation (control) versus discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a 2-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. Conclusion: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from or be harmed by statins.

Short-term test for the toxicogenomic assessment of ecotoxic modes of action in Myriophyllum spicatum

In environmental risk assessment of substances, the 14-day growth inhibition test following OECD test guideline 239 is employed to assess toxicity in the macrophyte Myriophyllum spicatum. Currently, this test evaluates physiological parameters and does not allow the identification of the mode of action (MoA) by which adverse effects are induced. However, for an improved ecotoxicity assessment of substances, knowledge about their ecotoxic MoA in non-target organisms is required. It has previously been suggested that the identification of gene expression changes can contribute to MoA identification. Therefore, we developed a shortened three-day assay for M. spicatum including the transcriptomic assessment of global gene expression changes and applied this assay to two model substances, the herbicide and photosynthesis inhibitor bentazone and the pharmaceutical and HMG-CoA reductase inhibitor atorvastatin. Due to the lack of a reference genome for M. spicatum we performed a de novo transcriptome assembly followed by a functional annotation to use the toxicogenomic results for MoA discrimination. The gene expression changes induced by low effect concentrations of these substances were used to identify differentially expressed genes (DEGs) and impaired biological functions for the respective MoA. We observed both concentration-dependent numbers and differentiated patterns of DEGs for both substances. While bentazone impaired genes involved in the response to reactive oxygen species as well as light response, and also genes involved in developmental processes, atorvastatin exposure led to a differential regulation of genes related to brassinosteroid response as well as potential metabolic shifts between the mevalonate and methyl erythritol 4-phosphate pathway. Based on these responses, we identified biomarker candidates for the assessment of MoA in M. spicatum. Utilizing the shortened assay developed in this study, the investigation of the identified biomarker candidates may contribute to the development of future MoA-specific screening approaches in the ecotoxicological hazard prediction using aquatic non-standard model organisms.

The Association between Statin Medication Use and Intracranial Aneurysm Risk: A Two- Way Mendelian Randomization Study

Recent observational studies have identifi ed a potential link between statin medication use and the risk of intracranial aneurysms (IAs). However, the causal relationship between these factors is not yet clear.Methods:We used a two-way Mendelian randomization approach to examine the relationship between genetically predicted statin medication use and the risk of IAs, as well as the reverse association. We incorporated data from genome-wide association studies of statin medication and IAs in a European population. Our analysis relied on random-effects inverse variance weighted estimation as the primary statistical method.Results:Neither statin medication use nor IA risk was signifi cantly associated with the other, according to ourfindings. The odds ratio (OR) for statin medication was 1.551 (95% confi dence interval [CI]: 0.895–2.685,P = 0.117), and the OR for IA risk was 1.020 (95% CI: 0.984–1.059, P = 0.281). Our results were consistent across different analytical methods, including MR-Egger regression and weighted median.Conclusions:These fi ndings suggest that there is no causal relationship between statin medication use and IA risk.

Effect of sodium-glucose cotransporter 2 inhibitors on serum low-density lipoprotein cholesterol in Japanese patients with type 2 diabetes mellitus.

We aimed to evaluate factors that influence changes in blood low-density lipoprotein cholesterol (LDL-C) levels after treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors in Japanese patients with type 2 diabetes. We retrospectively analyzed clinical data of outpatients newly initiated on SGLT2 inhibitors (n = 176) and other oral antidiabetic drugs (n = 227). The patients were classified into four subgroups according to statin administration and baseline LDL-C levels (<120 or ≥120 mg/dL). Clinical characteristics were compared among the subgroups. Multivariate analysis was carried out to identify factors contributing to changes in LDL-C. The median follow-up period was 13.0 weeks (range 11.9-14.1 weeks, min 8 weeks, maximum 16 weeks) in the SGLT2i group, and 12.0 weeks (range 10.0-14.0 weeks, min 8 weeks, maximum 16 weeks) in the control group. Both groups showed a significant decrease in LDL-C (SGLT2i group -3.8 ± 24.7 mg/dL, control group -3.4 ± 15.0 mg/dL). Multivariate regression analyses showed that in both groups, the change in LDL-C depended on statin use and baseline LDL-C levels. Stratified analyses showed that LDL-C level was significantly decreased in statin users with baseline LDL-C ≥120 mg/dL (from 148.9 ± 33.5 to 109.3 ± 17.9 mg/dL, P = 0.002), and significantly increased in statin non-users with baseline LDL-C <120 mg/dL (from 96.3 ± 27.3 to 104.7 ± 24.8 mg/dL, P = 0.002). These changes were more characteristic for SGLT2 inhibitors than for other oral antidiabetic drugs (P for interaction = 0.010 and <0.001, respectively). LDL-C levels and statin medication at baseline influence changes in LDL-C after SGLT2 inhibitors treatment in Japanese patients with type 2 diabetes.

Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study.

Previous research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics. We used genetic instruments as proxies to the exposure of lipid-lowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy. The analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available. The drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition.

Relationship Between Social Support and Clinical Outcomes: An Evaluation of Participant-Nominated Treatment Supporters in the HOPE 4 Intervention.

The HOPE 4 trial (Heart Outcomes Prevention and Evaluation 4) investigated the effectiveness of a comprehensive, collaborative model of care, implemented in Colombia and Malaysia, which aimed to reduce cardiovascular disease risk in individuals with hypertension. One component of this intervention was the nomination of a treatment supporter, where participants could select a family member or friend to assist them with their care. The purpose of this study was to investigate the impact of these individuals on participant outcomes, as well as the relationship dynamics between participants and their treatment supporter. Participants in the HOPE 4 intervention group with baseline and 12 months of follow-up were included for analysis. They were divided into Every Visit (n=339) and <Every Visit (n=268) groups based on whether they had a treatment supporter for all 5 or for <5 follow-up visits, respectively. Outcomes were stratified between groups and tested for significance using a generalized linear mixed-effects model. A survey investigating participant satisfaction with their treatment supporter was administered at 12 months. Groups were majority female (53% versus 62%) with a mean age of 63 and 66 years. Country of origin differed between groups (22% versus 86%; Colombia). A 15.5% ([95% CI, 6.2%-24.8%] P=0.004) greater increase in statin medication use was reported in the Every Visit group at 12 months compared with the <Every Visit group. Sixty-one percent versus 48.2% of participants reported high medication adherence at 12 months (P<0.003). The difference in change in systolic blood pressure between groups was not found to be significant at 12 months, though it favored the Every Visit group (-2.3 [95% CI, -6.1 to 1.5]; P=0.045). The majority of survey respondents from either study group strongly agreed that having a treatment supporter positively influenced their health. Long-term support from a nominated treatment supporter was associated with improved adherence, risk factor management, and medication use among individuals with hypertension. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01826019.

Beyond Statins: Novel Lipid-Lowering Agents for Reducing Risk of Atherosclerotic Cardiovascular Disease

Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials.

EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Evidence for clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications among adults with peripheral artery disease: protocol for a systematic review and meta-analysis

IntroductionInternational guidelines recommend that adults with peripheral artery disease (PAD) be prescribed antiplatelet, statin and antihypertensive medications. However, it is unclear how often people with PAD are underprescribed these drugs,...

THE EFFECTS OF ROSUVASTATIN EFFECT ON THE KIDNEY IN MALE ALBINO RATS

Background and Aim: Rosuvastatin is known to competitively inhibit HMG-CoA reductase, selectively and reversibly, this enzyme converts HMG-CoA to mevalonic acid in the cholesterol biosynthesis pathway, which is the rate-limiting step in cholesterol synthesis. Rosuvastatin is one of the most important cholesterol-lowering stanins that has been on the market by AstraZeneca since 2003, with unique pharmacokinetic and pharmacodynamic properties. There are some studies that dealt with the effect of rosuvastatin on the kidneys and were contradictory in their results. Therefore, the aim of the current study was to evaluate the effect of rosuvastatin (pharma science Incorporated company - Montreal/ Canada) on the physiological and histopathological parameters in the kidneys of male albino rats. Material and Methods: Forty adult of albino rats were used in the study. After acclimation, the rats were randomly divided into four groups (8 rats in each group) as follows: The first control group: was given normal saline solution (NS), the second group 10 mg/kg rosuvastatin, the third group was given 20 mg/kg rosuvastatin, while the fourth group was given 40 mg/kg rosuvastatin. The dose was continued for 60 days in a once-daily dosing regimen. After the end of the experiment, chemical analyzes were performed for kidney function, including cystatin C and vitamin D3. Then the rats were dissected, and kidney tissues were taken for histological study

Mild untreated hypercholesterolaemia affects mechanical properties of the Achilles tendon but not gastrocnemius muscle

Tendon xanthoma and altered mechanical properties have been demonstrated in people with familial hypercholesterolaemia. However, it is unclear whether mild, untreated hypercholesterolaemia alters musculotendinous mechanical properties and muscle architecture. We conducted a case-control study of adults aged 50 years and over, without lower limb injury or history of statin medication. Based on fasting low-density lipoprotein (LDL) cholesterol levels, 6 participants had borderline high LDL (>3.33 mmol/L) and 6 had optimal LDL cholesterol (<2.56 mmol/L). Using shear wave elastography, shear wave velocity (SWV) of the Achilles tendon and gastrocnemius medialis muscle (a proxy for stiffness), along with muscle fascicle length and pennation angle were measured under four passive tensile loads (0, 0.5, 1.0, 1.5 kg) applied via a pulley system. Differences between groups were found for tendon SWV but not muscle SWV, fascicle length or pennation angle. Participants with hypercholesterolaemia showed greater SWV (mean difference, 95 % CI: 2.4 m/s, 0.9 to 4.0, P = 0.024) compared to the control group across all loads. These findings suggest that adults with mild hypercholesterolaemia have increased tendon stiffness under low passive loads, while muscle was not affected. Future research is needed to confirm findings in a larger cohort and explore the impact of hypercholesterolaemia on tendon fatigue injury and tendinopathy.

Drug Interactions in the Treatment of Chronic Heart Failure: Analysis of Clinical Guidelines

Background. According to Russian epidemiological studies, the prevalence of chronic heart failure (CHF) in the general population is high and amounts to 7–10%. Therapy of any disease, and especially chronic disease, is associated with the prescription of drugs. With the development of evidence-based medicine and implementation of its achievements in real clinical practice all over the world there is an increase in the number of prescribed drugs. This explains the high relevance of the problem of drug-drug interactions. Aims — analysis of interactions of drugs recommended for prescription to patients suffering from CHF. Methods. Based on the Clinical Guidelines (CG), all possible interdrug interactions of recommended medicinal products were analysed. Information on potential drug-drug interactions was obtained from the specialised website Drugs.com. Know more. Be sure (https://www.drugs.com/interactions/list/). Results. ACE inhibitors / ARA II / valsartan+sacubitril, beta-adrenoblockers and aldosterone antagonists are recommended as part of combination therapy for treatment according to CG for all patients with symptomatic heart failure (class II–IV) and reduced LV ejection fraction 40%. Amiodarone, verapamil and diltiazem are among the drugs not recommended for use in patients with the diagnosis of CHF. Also, according to clinical guidelines, HMG-CoA reductase inhibitors (atorvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin, fluvastatin), direct renin inhibitors (heparin), COX-2 inhibitors (parecoxib, polmacoxib, celecoxib, etoricoxib) are among the unrecommended drugs in chronic heart failure.For ACE inhibitors, no adverse effects from interaction with beta-blockers have been identified. This combination is widely used and recommended by the CG. According to the “Major” type for ACE inhibitors with drugs indicated for use in CHF according to CG, 4 potential interactions were identified: with valsartan-sacubitril; angiotensin II receptor antagonists; with aldosterone antagonist (spironolactone); with loop and thiazide diuretics. Therefore, the appointment of angiotensin II receptor antagonists is carried out in case of ineffectiveness of initial therapy with ACE inhibitors, when changing the treatment tactics. These drugs are not used in combination with each other due to the risk of hyperkalemia. The prescription and use of diuretics while taking ACE inhibitors should be controlled by a physician also due to the risk of hyperglycaemia. In Moderate type, potential interactions with dapagliflozin, eplerenone, cardiac glycosides and heparin have been identified for ACE inhibitors. For beta-blockers, no potential Major-type interactions were identified with drugs from CG. Combinations with dapagliflozin, loop and thiazide diuretics, cardiac glycosides, spironolactone and ivabradine require special attention. It is recommended to avoid the combination of beta-blockers with valsartan. Of the recommended angiotensin II receptor antagonists, no risk of potential interactions with beta-blockers has been identified for candesartan and losartan.

Ischemic Heart Disease as an Important Risk Factor for Depression—A Case Report

The link between the mind and cardiac disease has been studied throughout the ages. Patients diagnosed with ischemic heart disease may develop psychological and psychiatric symptoms such as depressed mood, anxiety, and insomnia that can drastically affect life quality. Unfortunately, during cardiac rehabilitation, there is a lack of psychiatric care. To improve a patient’s quality of life, this intriguing relationship between ischemic heart disease and depression must be closely monitored, because risk factors and pathophysiological mechanisms may be common. This case report article is about a 47-year-old Romanian woman with acute coronary syndrome revascularized with angioplasty and stent implantation 3 months ago, admitted to the Arad Emergency County Clinical Hospital, Psychiatric Department, with depressive symptoms. Our patient was treated with an antidepressant, an anxiolytic, a mood stabilizer, a hypnotic, a nootropic, aspirin, dual platelet inhibition, a beta-blocker, a converting enzyme inhibitor, a statin, and oral antidiabetics medication, as well as having psychotherapy sessions. The treatment was well tolerated, with an improvement in the social and professional functionality of the patient. In conclusion, people with ischemic heart disease have a higher risk of developing depression, but patients with depression also have a higher risk of developing ischemic heart disease. This confirms the importance of an individualized multidisciplinary approach to management because the collaboration between psychiatrists and cardiologists can be an additional benefit to patients. This article may pave the way for further research into the association between ischemic heart disease and depressive disorders, which could provide significant advantages to patients. Interdisciplinarity contributes to the development of innovative techniques of prevention and treatment, reducing worldwide morbidity and mortality.

Impact of statins in the liver: A bane or a boon?

Treatment of hypercholesterolemia with statins is considered one of the cornerstones in the management of atherosclerotic cardiovascular diseases. Statins exert their hypolipidemic effects by inhibiting HMG-CoA reductase, the key enzyme in cholesterol biosynthesis. Beyond cholesterol reduction, statins exhibit pleiotropic effects, including anti-inflammatory, antioxidant, and antiproliferative actions, making them valuable in mitigating atherosclerotic and non-atherosclerotic diseases. Though concerns of hepatotoxicity have been associated with the use of statins, extensive evidence suggests that the risk of statin-induced liver injury (SILI) is rare, with an incidence of &lt;1%. Hepatic adverse effects include reversible asymptomatic transaminase elevation (most frequent), hepatitis, cholestasis, and rarely acute liver failure. While hepatotoxicity concerns should not be dismissed, the evidence overwhelmingly supports the safety of statins. Contrary to the myth of statin hepatotoxicity, real-world data and extensive research emphasize the safety and benefits of statins. They are therapeutic in various liver-related conditions, mainly non-alcoholic fatty liver disease. This scientific review aims to provide a comprehensive overview of statins, shedding light on their mechanism of action, hepatotoxicity concerns, and therapeutic potential in various liver-related conditions.

In vitro and in silico studies of the potential cytotoxic, antioxidant, and HMG CoA reductase inhibitory effects of chitin from Indonesia mangrove crab (Scylla serrata) shells

This study aimed to characterize chitin extracted from Indonesia mangrove crab (Scylla serrata) shells, as well as to assess its in vitro cytotoxic, antioxidant, and HMG CoA reductase inhibitory potentials. In silico molecular docking, molecular dynamic, and ADMET prediction analyses were also carried out. Chitin was extracted from mangrove crab shells using deproteination and demineralization processes, Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) characterization are then performed. The MTT method was further tested in a study of cell viability, while in vitro method was used to assess HMG CoA reductase inhibitory and antioxidant activities. The extracted chitin was found to have a moderate level of cytotoxic and antioxidant activities. In vitro studies showed that it has an IC50 of 36,65 ± 0,082 μg/mL as an HMG CoA reductase inhibitor, and decreased enzyme activity by 68.733 % at 100 μg/mL as a concentration. Furthermore, in the in silico study, chitin showed a strong affinity to several targets, including HMG CoA reductase, HMG synthase, LDL receptor, PPAR-alfa, and HCAR-2 with binding energies of −5.7; −5.8; −3.6; −5.6; −4.6 kcal/mol, respectively. Based on the ADMET properties, it had non-toxic molecules, which were absorbed and distributed across the blood-brain barrier. The molecular dynamics (MD) simulation also showed that it remained stable in the active sites of HMG CoA reductase receptor for 100 ns. These results indicated that chitin from Indonesian mangrove crab shells can be used to develop more potent HMG CoA reductase inhibitor with antioxidant and cytotoxic activities for effective dyslipidemia therapy.

Association Between Pharmacy Proximity With Cardiovascular Medication Use and Risk Factor Control in the United States.

Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort. A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses. Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.