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This article examines the relationship between cholesterol levels and Alzheimer's disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention. [ABSTRACT FROM AUTHOR]

AbstractStatins are the most prescribed drug for regulating the high cholesterol level in the blood, which can lead to severe complications, such as cardiovascular diseases and other health complications. A wide range of analytical techniques have been employed for the quantification of statins from various origins, including fermentation derived (lovastatin, pravastatin, and compactin), semi-synthetic (simvastatin), and synthetic (atorvastatin, rosuvastatin, and fluvastatin) routes. The presence of more than one structural form and structural analogue generated in the biosynthesis pathway, as well as reaction intermediates and macromolecules in the clinical sample, complicates the quantification of statins. Furthermore, significant concentrations of statins in environmental samples pose serious health and ecology hazards, and estimating statins in those diluted samples is extremely difficult. On the other hand, the: cost, accurate estimation of the desired one from other structural forms, sample complexity, time, limits of detection and quantification, were major criteria distinguishing the usability of each technique. As a result, the current manuscript focuses on analytical techniques such as molecular spectroscopy (normal and derivatives UV-Visible spectrophotometer), chromatography (TLC, HP-TLC, HPLC, GC, swing column, micellar, and supercritical fluid), mass spectroscopy (HPLC-MS/MS and GC-MS/MS), sequential flow injection, capillary electrophoresis, and cyclic voltammetry, as well as their: optimal operating conditions, limits of detection and quantification, advancements, and limitations. Furthermore, various online and offline sample preparations (precipitation, solid phase extraction, liquid-liquid extraction, and micellar extraction) have been highlighted as an essential pretreatment technique to avoid the interference caused by structural analogues and other macromolecules. The greener and more sustainable concepts used in analytical approaches for the quantification statins are also highlighted with current advancements. [ABSTRACT FROM AUTHOR]

Introduction: The Medication Review in the Pharmacotherapeutic Follow-up Service (PFS) seems to be an effective method to study long-term drug safety in the outpatient setting. The adverse drug reactions (ADRs) that are not immediately obvious are difficult to identify and sometimes can be confused with a more common condition. Misdiagnosis by not associating the symptoms of AMR to its pharmacological cause causes its masking and hinders its detection. Objective: Detect in the SFT service the diagnostic errors related to the non-detection of adverse reactions to statins. Material and Method: The data obtained from the medication review at the Pharmacotherapeutic Follow-up Service (PFS) were pooled for analysis. The patients who received the service were selected with the "DLGM screening" tool, an acronym "Diagnosis load Generated by Medications", that allows us to describe adverse drug reactions (ADRs), when their symptoms are attributed to a pathology, without considering medication as a possible underlying cause. Only the results of patients over 60 years of age, who after a prolonged period of statin use gradually presented musculoskeletal disorders (MSD) and other symptoms theoretically described as possible ADRs, are shown. Results: In 66 % of the cases, corresponding to 14 patients out of a total of 21 studied, the physician modified the treatment and in 92% of these cases there was improvement and a decrease of the consumption of analgesics drug, anti-inflammatory and other drugs used to treat ADR symptoms. Conclusion: DLGM screening identified hidden AMRs in 62 % of patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Numerous European countries, including Romania, are facing the concern of rapid ageing of their populations. Moreover, Romania's life expectancy ranks among the lowest in the European Union. In light of this, it is imperative that the assessment of medication-related harm be given national priority in order to secure and enhance pharmacotherapy and the medical act. In this study, we sought to describe and evaluate the under-prescribing practices among the Romanian elderly population. Methods: We conducted a cross-sectional study in urban areas of two counties in Western Romania (Timis and Arad) from November 2017 to February 2019. We collected chronic electronic prescriptions issued for elderly patients (>65 years old) with chronic conditions. The medication was prescribed by generalist or specialist physicians for periods ranging between 30 and 90 days. To assess inappropriate prescribing behaviours, a multidisciplinary team of specialists applied the Screening Tool of Older Persons' Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) v.2 criteria to the collected prescriptions. Results: Within the 1498 prescriptions included in the study, 57% were issued to females, the mean age was 74.1 ± 6.95, and the average number of medicines per prescription was 4.7 ± 1.51. The STOPP criteria most commonly identified were the (1) long treatment duration (23.6%) and (2) prescription of neuroleptics (14.6%) or zopiclone (14.0%) as medications that increase the risk of falls. According to START criteria, the following medicines were under-prescribed: (1) statins (47.4%), (2) beta-blockers (24.5%), (3) antiresorptive therapy (10.0%), and (4) β2-agonists and muscarinic antagonists for chronic obstructive pulmonary disease (COPD) (4.5%). Within our study group, the prevalence of potentially inappropriate medications was 18.58%, whereas the prevalence of potential prescribing omissions was 49.2%. Conclusions: To decrease medication-related harm and morbid-mortality, and to increase the quality of life for elderly people in Romania, immediate actions are needed from national authorities. These actions include reinforcing primary care services, providing periodic training for physicians, implementing medication review services by pharmacists, and utilising electronic health records at their full capacity. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) with preserved ejection fraction (pEF) has lacked effective treatments for reducing mortality. However, previous studies have found an association between statin use and decreased mortality in patients with HFpEF. The aim of this study was to analyse whether statin therapy is associated with a reduction in mortality in these patients and whether the effect differs according to the presence or absence of ischaemic heart disease (IHD). Methods: We analysed data from the National Registry of Heart Failure, a prospective study that included patients admitted for HF in Internal Medicine units nationwide. Patients with HFpEF were classified according to the use of statins, and the differences between the two groups were analysed. A multivariable analysis was performed using Cox regression to assess factors independently related to mortality. Results: A total of 2788 patients with HFpEF were included; 63% of them were women with a mean age of 80.1 (±7.8) years. The statin-treated group (40.2%) was younger, with better functional status, and had a more common diagnosis of vascular disease and lower frequency of atrial fibrillation. The most frequent aetiology of HF in both groups was the hypertensive one. Nevertheless, ischaemic HF was more common in those who received statins (24.8% vs. 9.6%; p < 0.001). Multivariable analysis showed lower mortality at the 1-year follow-up in statin-treated patients (OR: 0.74; 95%CI: 0.61–0.89; p = 0.002). This association was observed in patients without IHD (p < 0.001) but not in those with IHD (p = 0.11). Conclusions: Statins are associated with a decrease in total mortality in patients with HFpEF. This benefit occurs mainly in those without IHD. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests the potential of hydroxymethylglutaryl-coenzyme A (HMG-CoA, statins) as a therapeutic option for dementia. Objective: The primary objective of this study is to assess the current state of research on statins use in dementia, with a focus on identifying pivotal questions within the field. Methods: A systemic search for publications on statin use in dementia between 2007 and 2023 was conducted, utilizing the Web of Science Core Collection. The scientific output was analyzed from various perspectives through VOSviewer, CiteSpace, and the bibliometrics website (). Results: 560 articles authored by 2,977 individuals and 999 institutions across 58 countries were included, which were published in 295 periodicals and cited 21,176 references from 16,424 authors. The annual publication output remained steady, while the number of citations increased consistently. The U.S. and Mayo Clinic emerged as the most significant country and institution, respectively. B. McGuinness and D.L. Sparks were the most eminent authors. Journal of Alzheimer's Disease was the most influential journal. Three sets of keywords and the top 10 references were identified, suggesting pivotal questions within the field. Conclusions: While statins show promising potential as a treatment option for dementia, their use remains uncertain due to the reported short-term cognitive impairment events and questionable long-term protective effects against dementia. The pivotal question is to ascertain the association between statins and cognition. The mechanisms underlying the effects of statins on cognition are multifaceted. This study provides insights into the current status within the field of statin use in dementia. [ABSTRACT FROM AUTHOR]

Ethanol (EtOH) consumption is frequently associated with acute and chronic gastrointestinal disorders. Rosuvastatin (RSV), a third-generation statin, has demonstrated certain biological functions beyond its lipid-lowering properties. This study is designed to explore the gastroprotective impact of RSV in a rat model of EtOH-induced gastric ulceration in a dose-dependent manner through the evaluation of oxidant/antioxidant biomarkers, inflammatory myeloperoxidase (MPO) enzyme activity, and prostaglandin E2 (PGE2) levels in gastric tissues, along with histopathological examination of the gastric tissues. Therefore, 40 adult male rats were randomly divided into five equal groups as control, EtOH (gastric ulcer), RSV-low dose plus EtOH and RSV-high dose plus EtOH. The EtOH rat model of gastric ulceration was achieved by intragastric administration of a single dose of EtOH. Seven days before EtOH administration, rats were orally administered either omeprazole (20 mg/kg/day) or RSV (10 mg/kg/day or 20 mg/kg/day). RSV administration enhanced the antioxidant glutathione reduced, countered oxidative malondialdehyde, augmented cytoprotective PGE2, suppressed inflammatory MPO enzyme activity in gastric tissues, decreased ulcer index scoring, increased the percentage of ulcer inhibition, and reversed the associated histological and ultrastructural abnormalities, additionally, RSV treatment resulted in weak positive nuclear staining for the inflammatory nuclear factor kappa B in a dose-dependent manner. It is concluded that RSV demonstrates gastroprotective potential, attributable at least in part, to its antioxidant and anti-inflammatory properties, as well as its ability to promote ulcer protection through the maintenance of mucosal content and PGE2 levels. Thus, RSV therapy emerges as a safe option for patients with gastric ulcers. [ABSTRACT FROM AUTHOR]

Background: Age is a major risk factor for atherosclerotic cardiovascular disease (CVD) and death, but there has been a debate about benefit-risk of statin treatment in the elderly with limited evidence on benefits for primary prevention, while there is strong evidence for its use in secondary prevention. Aim: The aim of this study was to provide an overview of statin utilization in primary and secondary prevention for patients 75–84 years and ≥ 85 years in the Swedish capital Region Stockholm in 2019. Methods: This is a cross-sectional study based on the regional healthcare database VAL containing all diagnoses and dispensed prescription drugs for all 174,950 inhabitants ≥ 75 years old in the Stockholm Region. Prevalence and incidence were analyzed by sex, age, cardiovascular risk, substance, and the intensity of treatment. Results: A total of 35% of all individuals above the age of 75 in the region were treated with statins in 2019. The overall incidence in this age group was 31 patients per 1000 inhabitants. Men, individuals 75–84 compared to ≥ 85 years of age, and those with higher cardiovascular risk were treated to a greater extent. Simvastatin was used primarily by prevalent users and atorvastatin by incident users. The majority was treated with moderate-intensity dosages and fewer women received high intensity treatment. Conclusions: Statins are widely prescribed in the elderly. Physicians seem to consider individual cardiovascular risk when deciding to initiate statin treatment for elderly patients, but here may still be some undertreatment among high-risk patients (especially women and elderly 85 + years) and some overtreatment among patients with low-risk for CVD. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion People with HIV (PWH) are at an increased risk of developing cardiovascular disease (CVD) compared to HIV‐negative individuals. We sought to evaluate the adherence to medications for CVD in PWH and identify factors associated with non‐adherence to these medications.We conducted a cross‐sectional study at the University Hospitals of Leicester NHS Trust between 16 April 2019 and 8 November 2022. We recruited consecutive PWH, who were attending a routine follow‐up outpatient appointment and were prescribed at least one medication for CVD. In addition, we included urinary adherence results of patients with samples collected as part of routine clinical care. We used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to assess if their prescribed medications (antihypertensives, diuretics, beta‐blockers, lipid‐lowering agents, antiplatelets, anticoagulants, antidiabetic medications) were present in the participant's urine sample. Multivariable models were used to identify demographic or clinical features that were associated with non‐adherence.A total of 162 PWH were included in the analysis. Median age was 55 [interquartile range (IQR): 50–61] years, 63% were male, average time living with HIV was 15 years (IQR: 11–19) and the majority (98%) had an undetectable HIV viral load. In approximately one‐third of patients (59/162), at least one prescribed medication of interest was not detected in urine. Non‐adherence to lipid‐lowering agents was common (35/88, 40%). On multivariable logistic regression, the number of prescribed cardiovascular medications, was associated with medication non‐adherence [medication non‐adherence, per one medication increase: adjusted odds ratio (95% confidence interval) = 1.78 (1.34–2.36); p < 0.001].We found sub‐optimal adherence to medications for CVD in PWH. In order to maximize the clinical benefit of statin therapy in PWH, factors requiring consideration include: improved medication adherence, awareness of polypharmacy, educational interventions and quantitative assessment of sub‐optimal adherence through chemical adherence testing. [ABSTRACT FROM AUTHOR]

In recent years, various approaches have been undertaken to eliminate lipoproteins co‐isolated with extracellular vesicles, as they were initially regarded as contaminating entities. However, novel discoveries are reshaping our perspective. In body fluids, these distinct particles not only co‐exist, but also interactions between them are likely to occur. Extracellular vesicles and lipoproteins can associate with each other, share cargo, influence each other's functions, and jointly have a role in the pathomechanisms of diseases. Additionally, their association carries important implications for therapeutic and pharmacological aspects of lipid‐lowering strategies. Extracellular vesicles and lipoprotein particles may have roles in the elimination of each other from the circulation. The objective of this minireview is to delve into these aspects. Here, we show that under certain physiological and pathological conditions, extracellular vesicles and lipoproteins are ‘partners’ rather than ‘strangers’ or ‘rivals’. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between statins and the risk of osteoarthritis through Mendelian randomization analysis using summary data from large-scale population-based genome-wide association studies (GWAS). METHODS: Firstly, single nucleotide polymorphism data related to statins were obtained from the latest 9th edition of the FinnGen database, while data of osteoarthritis, knee osteoarthritis and hip osteoarthritis were obtained from the IEU Open GWAS, UK Biobank, and ArcOGEN (Genetics of Osteoarthritis) databases, respectively. The inverse variance weighted method was used as the primary analysis approach to evaluate the causal effects. The weighted median method, simple median method, weighted mode-based method, and MR-Egger regression were used as supplementary analyses. The causal relationship between statins and the risk of osteoarthritis, knee osteoarthritis and hip osteoarthritis was assessed using odds ratios (OR) with 95% confidence intervals (CI). Sensitivity analyses were conducted to validate the reliability of the results, including the Cochran’s Q test for heterogeneity and the MR-Egger-intercept test for horizontal pleiotropy, as well as leave-one-out analysis to identify potentially influential single nucleotide polymorphisms. RESULTS AND CONCLUSION: The inverse variance weighted analysis demonstrated a negative causal relationship between genetically predicted statins and the risk of osteoarthritis (OR=0.998, 95% CI: 0.996-0.999, P=0.01), knee osteoarthritis (OR=0.964, 95% CI: 0.940-0.989, P=0.005), and hip osteoarthritis (OR=0.928, 95% CI: 0.901-0.955, P=4.28×10-7). MR-Egger intercept analysis did not detect potential horizontal pleiotropy (osteoarthritis: P=0.658; knee osteoarthritis: P=0.600; hip osteoarthritis: P=0.141). The results of this study provide evidence that statins reduce the risks of osteoarthritis, knee osteoarthritis and hip osteoarthritis as described in observational studies. Further research is needed to explore the specific mechanisms of statin treatment for osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients. Methods: In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post‐diagnosis statin use and risks of breast cancer recurrence and breast cancer–specific mortality. Results: Over a median follow‐up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post‐diagnosis statin use was 2.2 years. Statin use post‐diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91–1.21), but was associated with a reduced risk of cancer‐specific mortality (HR, 0.85; 95% CI, 0.75–0.96). The reduction was more pronounced in women with hormone receptor–positive/human epidermal growth factor receptor 2–negative breast cancer (HR, 0.71; 95% CI, 0.57–0.88). Conclusions: These findings suggest that post‐diagnosis statin use is associated with improved cancer‐specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients. Statin use after cancer diagnosis is associated with improved cancer survival in a large cohort of elderly women with breast cancer, highlighting the potential of statins as anticancer agents in improving breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Statins, the first‐line medication for dyslipidemia, are linked to an increased risk of type 2 diabetes. But exactly how statins cause diabetes is yet unknown. In this study, a developed short‐term statin therapy on hyperlipidemia mice show that hepatic insulin resistance is a cause of statin‐induced diabetes. Statin medication raises the expression of progesterone and adiponectin receptor 9 (PAQR9) in liver, which inhibits insulin signaling through degradation of protein phosphatase, Mg2+/Mn2+ dependent 1 (PPM1α) to activate ERK pathway. STIP1 homology and U‐box containing protein 1 (STUB1) is found to mediate ubiquitination of PPM1α promoted by PAQR9. On the other hand, decreased activity of hepatocyte nuclear factor 4 alpha (HNF4α) seems to be the cause of PAQR9 expression under statin therapy. The interventions on PAQR9, including deletion of PAQR9, caloric restriction and HNF4α activation, are all effective treatments for statin‐induced diabetes, while liver specific over‐expression of PPM1α is another possible tactic. The results reveal the importance of HNF4α‐PAQR9‐STUB1‐PPM1α axis in controlling the statin‐induced hepatic insulin resistance, offering a fresh insight into the molecular mechanisms underlying statin therapy. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusions To investigate the influence of statins on the survival outcomes of patients with non‐muscle‐invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette‐Guérin (BCG) immunotherapy.A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer‐specific survival (CSS), recurrence‐free survival (RFS), and progression‐free survival (PFS) were analysed between the Statins Group vs No‐Statins Group using Kaplan–Meier method and multivariable Cox regression.A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow‐up was 11.0 years. On Kaplan–Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the ‘statins before BCG’ group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514–0.716), and CSS (HR 0.571, 95% CI 0.376–0.868), but not RFS (HR 0.885, 95% CI 0.736–1.065), and PFS (HR 0.689, 95% CI 0.469–1.013).Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG. [ABSTRACT FROM AUTHOR]

Statins, widely used cardiovascular drugs that lower cholesterol by inhibiting HMG-CoA reductase, have been increasingly recognized for their potential anticancer properties. This study elucidates the underlying mechanism, revealing that statins exploit Synthetic Lethality, a principle where the co-occurrence of two non-lethal events leads to cell death. Our computational analysis of approximately 37,000 SL pairs identified statins as potential drugs targeting genes involved in SL pairs with metastatic genes. In vitro validation on various cancer cell lines confirmed the anticancer efficacy of statins. This data-driven drug repurposing strategy provides a molecular basis for the anticancer effects of statins, offering translational opportunities in oncology. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. A secondary aim was to determine if there are any associations between the polypharmacological properties of the statins and their associated muscle-related side effects. Methods: The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL), was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare Products Regulatory Agency's (MHRA) Yellow Card scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation. Results: The study found no significant difference between the statins association with suspected ADRs across all organ classes (X2, p > 0.05). Fluvastatin was found to have a higher incidence of ADRs/100,000 Rx across multiple system organ classes. Conclusions: No significant difference was found between the suspected ADR incidence of the statins across all system organ classes. [ABSTRACT FROM AUTHOR]

Statins have been widely used for their cholesterol-lowering properties. Recent studies have shown that they increase survival in human infectious diseases by promoting host defense and inhibiting pathological inflammation. Infectious diseases caused by viruses have been a major challenge to public health. This review discusses potential use of statins to treat viral infection. [ABSTRACT FROM AUTHOR]

Background: Chest pain is one of the most common causes of emergency room visits and also accounts for numerous visits to the family physician's office or Outpatient Clinics of cardiology or internal medicine. Case Report: Here we present a case of a 48-year-old female patient who presented to our hospital emergency unit but refused hospital admission. She presented in our Outpatient Clinic with a complaint of typical chest pain indicating it to be of coronary origin. A computed tomography (CT) coronary angiography for the evaluation of this chest pain was indicated. While ruling out the coronary origin of this chest pain, we were surprised to have incidentally identified the presence of an esophageal tumor mass that had intimate contact with carina of the trachea. After the diagnosis of esophageal leiomyoma was made and its surgical treatment was performed, the patient was asymptomatic. Approximately one year after the surgical intervention was performed, following the cessation of antiplatelet therapy and statin, the patient returned to our Outpatient Clinic complaining of chest pain again with the same characteristics as previously presented, being terrified by the possibility of the recurrence of the esophageal leiomyoma. Upon resuming investigations, it was proven through coronary angio-CT evaluation that the etiology of the chest pain was indeed coronary this time. However, the patient still refused hospital admission and the performance of percutaneous coronary angiography with the potential implantation of a coronary stent. Conclusions: Chest pain can be due to various underlying pathologies and should not be neglected. A thorough investigation and timely management are key to treating this possible fatal symptom. In our case, the patient presented twice with the complaint of typical chest pain indicating a possible coronary event, but at the first presentation, it was due to esophageal leiomyoma, while a year later, the patient had similar pain, which was indeed this time due to coronary blockage. Hence, it is of utmost importance to think of all possible scenarios and to investigate accordingly, leaving no stone unturned. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes is associated with obesity and dyslipidemia, which are risk factors for cardiovascular disease. The Food and Drug Administration (FDA)-approved indications for statins are being broadened due to their lipid-lowering and pleiotropic effects; statins are currently among the most widely used drugs in patients with and without diabetes. Aim: To evaluate the role of atorvastatin at different doses in the development and progression of glucose intolerance or diabetes in albino rabbits. Materials and Methods: An in-vivo experimental study on rabbits was conducted over a total duration of eight months in the Department of Pharmacology at SCB Medical College, Cuttack, Odisha, India. The animals were divided into five groups of six rabbits each. Atorvastatin at 4 mg/kg and 2 mg/kg was calculated based on human doses corresponding to 80 mg and 40 mg, respectively. Both doses were administered to non diabetic rabbits, and 4 mg/kg atorvastatin was administered to alloxan-induced diabetic rabbits orally for six months daily. Diabetes was induced in two groups of rabbits by administering 100 mg/kg alloxan monohydrate in a 5% (w/v) solution in sterile saline intravenously. Rabbits with stabilised moderate diabetes, characterised by a fasting blood glucose level above 200 mg/dL (at least one month after alloxan injection), were used for the experiments. The effect of atorvastatin on glucose tolerance was assessed by determining Fasting Blood Sugar (FBS) and Glycated Haemoglobin (HbA1c) levels. The results were compared with those of normal and diabetic control rabbits and statistically analysed using Analysis of Variance (ANOVA) and Repeated Measures ANOVA (RMANOVA), followed by appropriate post-hoc analysis. Results: Atorvastatin at a high dose resulted in a 26.74% increase in FBS and a 20.50% increase in HbA1c; at the standard dose, it produced a 21.3% increase in FBS and a 17.99% increase in HbA1c, respectively. The diabetic group receiving high doses also showed a significant increase in FBS (11.7%) and HbA1c (10.25%). The increase in blood glucose parameters was significant in the high-dose group from the fourth month of statin therapy and in the standard-dose group at six months of therapy. Conclusion: The study revealed that atorvastatin at both doses significantly contributed to the initiation and progression of glucose intolerance in diabetic and non diabetic rabbits. [ABSTRACT FROM AUTHOR]

Statins, inhibitors of HMG-CoA reductase, have been shown to have potential anti-carcinogenic effects through the inhibition of the mevalonate pathway and their impact on Ras and RhoGTAases. Prior studies have demonstrated a reduction in breast tumor proliferation, as well as increased apoptosis, among women with early-stage breast cancer who received statins between the time of diagnosis and the time of surgery. The aim of this study was to evaluate the impact of short-term oral high-potency statin therapy on the expression of markers of breast tumor proliferation, apoptosis, and cell cycle arrest in a window-of-opportunity trial. This single-arm study enrolled 24 women with stage 0-II invasive breast cancer who were administered daily simvastatin (20 mg) for 2–4 weeks between diagnosis and surgical resection. Pre- and post-treatment tumor samples were analyzed for fold changes in Ki-67, cyclin D1, p27, and cleaved caspase-3 (CC3) expression. Out of 24 enrolled participants, 18 received statin treatment and 17 were evaluable for changes in marker expression. There was no significant change in Ki-67 expression (fold change = 1.4, p = 0.597). There were, however, significant increases in the expression of cyclin D1 (fold change = 2.8, p = 0.0003), p27 cytoplasmic (fold change = 3.2, p = 0.025), and CC3 (fold change = 2.1, p = 0.016). Statin treatment was well tolerated, with two reported grade-1 adverse events. These results align with previous window-of-opportunity studies suggesting a pro-apoptotic role of statins in breast cancer. The increased expression of markers of cell cycle arrest and apoptosis seen in this window-of-opportunity study supports further investigation into the anti-cancer properties of statins in larger-scale clinical trials. [ABSTRACT FROM AUTHOR]

We reported previously that in preclinical models, BMP4 is a potent inhibitor of breast cancer metastasis and that high BMP4 protein levels predict favourable patient outcomes. Here, we analysed a breast cancer xenograft with or without enforced expression of BMP4 to gain insight into the mechanisms by which BMP4 suppresses metastasis. Transcriptomic analysis of cancer cells recovered from primary tumours and phosphoproteomic analyses of cancer cells exposed to recombinant BMP4 revealed that BMP4 inhibits cholesterol biosynthesis, with many genes in this biosynthetic pathway being downregulated by BMP4. The treatment of mice bearing low-BMP4 xenografts with a cholesterol-lowering statin partially mimicked the anti-metastatic activity of BMP4. Analysis of a cohort of primary breast cancers revealed a reduced relapse rate for patients on statin therapy if their tumours exhibited low BMP4 levels. These findings indicate that BMP4 may represent a predictive biomarker for the benefit of additional statin therapy in breast cancer patients. [ABSTRACT FROM AUTHOR]

Lipid lowering, with the use of statins after an acute coronary syndrome (ACS), is a cornerstone, well-established strategy for the secondary prevention of ischemic events in this high-risk cohort. In addition to the positive effect on lipid levels, statins have also been linked to improved atherosclerotic plaque characteristics, such as plaque regression and inflammation reduction, associated with the extent of reduction in LDL-C. The recent emergence of PCSK9 inhibitors for the management of dyslipidemia and the more extensive lipid lowering provided by these agents may provide better prevention for ACS patients when initiated after the ACS event. Several trials have evaluated the immediate post-ACS initiation of PCSK9 inhibitors, which has shown, to date, beneficial results. Furthermore, PCSK9 inhibitors have been linked with positive plaque remodeling and associated mortality benefits, which makes their use in the initial management strategy of such patients appealing. Therefore, in this review, we will analyze the rationale behind immediate lipid lowering after an ACS, report the evidence of PCSK9 inhibition immediately after the ACS event and the available data on plaque stabilization, and discuss treatment algorithms and clinical perspectives for the use of these agents in this clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of tendon rupture and tendinopathies (TRT) has not been determined in a large population of patients with atherosclerotic cardiovascular disease (ASCVD). We investigated TRT prevalence among patients with ASCVD and in the general population, using data from the Symphony Health Integrated Dataverse, a large US medical and pharmacy claims database. Methods: This retrospective, observational study included patients aged ≥ 19 years from the claims database during the identification period (January 2019 to December 2020) and 12 months of continuous enrollment. The primary outcome was evidence of TRT in the 12 months following the index date (first ASCVD diagnosis in the ASCVD cohort; first claim in the claims database in the overall population). Diagnostic codes (ICD-10 and/or CPT) were used to define ASCVD and TRT diagnosis. Results: The ASCVD cohort and overall population included 5,589,273 and 61,715,843 patients, respectively. In the ASCVD cohort, use of medications with a potential or known association with TRT was identified in 67.9% (statins), 17.7% (corticosteroids), and 16.7% (fluoroquinolones) of patients. Bempedoic acid use was reported in 1556 (< 0.1%) patients. TRT prevalence during 12-month follow-up was 3.4% (ASCVD cohort) and 1.9% (overall population). Among patients with ASCVD, 83.5% experienced TRT in only one region of the body. Factors most associated with TRT in the ASCVD cohort were increasing age, most notably in those aged 45–‍64 years (odds ratio [OR] 2.19; 95% confidence interval [CI] 2.07–2.32), obesity (OR 1.51; 95% CI 1.50–1.53), and rheumatoid arthritis (OR 1.47; 95% CI 1.45–1.79). Use of statins or bempedoic acid was not associated with increased TRT risk. Conclusion: Patients with ASCVD may have greater risk of TRT than the general population, which may be driven by an increased prevalence of comorbidities and use of medications with a potential or known association with TRT. Plain Language Summary: Patients with atherosclerosis, the main cause of heart attacks, strokes, and peripheral vascular disease, typically require several drugs to control the disease. Some of the drugs used to treat atherosclerosis have been linked to a higher occurrence of tendon tears (or ruptures) or swelling/inflammation of the tendons (tendinopathies). However, there may be other factors present in these patients that increase the risk of tendon injuries that are not related to these drugs. This study used the medical records of over 5.5 million patients with atherosclerosis and over 63 million patients reflecting the general population in the United States to determine the prevalence of tendon injury. Additionally, the researchers looked at other factors that might be related to a higher risk of tendon injury in each group. Over a 12-month period, tendon injuries occurred in 3.4% of patients with atherosclerosis and 1.8% of patients in the general population. In patients with atherosclerosis, factors such as being obese, older (45–64 years), or having rheumatoid arthritis were also linked to an increased risk of tendon injuries. There was no association seen between statin or bempedoic acid use and tendon injuries. These results may help healthcare providers to determine the underlying risk of tendon injuries and guide treatment of this patient population. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of statin treatment to reduce coronary events and mortality has been hardly examined considering goals of LDL‐C. We aimed to analyse such association in secondary cardiovascular prevention. Methods: Retrospective cohort analysis of electronic health records from the SIDIAP database, Catalonia‐Spain. Recruitment period was from 2006 to 2017 and study period finished at the end of 2018. We included 54,175 people aged ≥35 years in cardiovascular secondary prevention starting statin treatment. We analysed the association of achieved LDL‐C goals after statin initiation with coronary heart disease and all‐cause mortality. Results: Mean age was 69 years and 20,146 (37.2%) were women. Coronary heart disease occurred in 5687 (10.5%) participants, and 10,676 (19.7%) persons passed away. Median follow‐up lasted 5.7 years (interquartile range, 3.4–8.1). The coronary heart disease HRs (95% CI) for the LDL‐C goals of 70–100, <70–55 and <55 mg/dL were.86 (.81–.92),.83 (.76–.9) and.8 (.72–.88), respectively. They were.89 (.83–.96) in the group with 30%–40% reduction and.86 (.8–.93) in the groups with 40%–50% and ≥50% reduction. We observed no association with mortality. We observed no relevant differences by sex or age. Conclusions: This population‐level retrospective analysis of real‐world data observed that treatment with statins is effective to achieve certain LDL‐C goals and CHD reduction. The lack of significant difference between LDL‐C goals needs confirmation in additional studies with real‐world data. The LDL‐C target should consider the magnitude of the decrease in coronary events. [ABSTRACT FROM AUTHOR]

Introduction: Whole blood (WB) is associated with improved mortality while lowering blood product utilization. Furthermore, statin medications are associated with favorable outcomes in traumatic brain injury and risk reduction of venous thromboembolism. However, the use of statin medications has not been evaluated in those receiving WB. The objective of this study is to determine the effects of pre-injury statin exposure on patients receiving WB. Methods: Patients that underwent WB first resuscitation and received pre-injury statins were compared to those that did not receive pre-injury statins. Demographics as well as complication rates, blood product transfusion volumes, and mortality were evaluated. Univariate and multivariable analyses were used to determine independent predictors of mortality. Results: In the study period, 785 patients received WB as part of their resuscitation. One hundred and thirty five patients (17.3%) took statin medications prior to injury. Patients that were exposed to a pre-injury statin had a lower mortality rate than those that were not exposed (21.5% vs 32.5%, P =.01). After adjusting for imbalances, age, ISS, Glasgow Coma Scale, admission systolic blood pressures, and pre-injury statin use were independent predictors of mortality following multiple logistic regression. When evaluating outcomes based on statin intensity, the use of high-intensity statins was associated with lower mortality (OR:.37, 95% CI:.13-.93), whereas moderate and low-intensity statins were not. Conclusion: In patients resuscitated with WB, pre-injury statins use was associated with improved outcomes. Specifically, patients that received high-intensity pre-injury statins appeared to be the population that benefited. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Our objective was to describe the prevalence of cardiovascular disease (CVD) risk factors in people of African ancestry with HIV in the UK.We conducted a cross‐sectional analysis of CVD risk factors in Black people with HIV aged ≥40 years and estimated the 10‐year CVD risk using QRISK®3‐2018. Correlations between body mass index (BMI) and CVD risk factors were described using Pearson correlation coefficients, and factors associated with 10‐year CVD risk ≥5% were described using logistic regression.We included 833 Black people with HIV and a median age of 54 years; 54% were female, 50% were living with obesity (BMI ≥30 kg/m2), 61% had hypertension, and 19% had diabetes mellitus. CVD risk >5% ranged from 2% in female participants aged 40–49 years to 99% in men aged ≥60 years, and use of statins ranged from 7% in those with CVD risk <2.5% to 64% in those with CVD risk ≥20%. BMI was correlated (R2 0.1–0.2) with triglycerides and diastolic blood pressure in women and with glycated haemoglobin, systolic and diastolic blood pressure, and total:high‐density lipoprotein (HDL) cholesterol ratio in men. In both female and male participants, older age, blood pressure, diabetes mellitus, and kidney disease were strongly associated with CVD risk ≥5%, whereas obesity, total:HDL cholesterol, triglycerides, and smoking status were variably associated with CVD risk ≥5%.We report a high burden of CVD risk factors, including obesity, hypertension, and diabetes mellitus, in people of African ancestry with HIV in the UK. BMI‐focused interventions in these populations may improve CVD risk while also addressing other important health issues. [ABSTRACT FROM AUTHOR]

Background and Purpose: Statins are competitive inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase (HMGCR), and exert adverse effects on mitochondrial function, although the mechanisms underlying these effects remain unclear. We used a tamoxifen‐induced Hmgcr‐knockout (KO) mouse model, a multi‐omics approach and mitochondrial function assessments to investigate whether decreased HMGCR activity impacts key liver energy metabolism pathways. Experimental Approach: We established a new mouse strain using the Cre/loxP system, which enabled whole‐body deletion of Hmgcr expression. These mice were crossed with Rosa26Cre mice and treated with tamoxifen to delete Hmgcr in all cells. We performed transcriptomic and metabolomic analyses and thus evaluated time‐dependent changes in metabolic functions to identify the pathways leading to cell death in Hmgcr‐KO mice. Key Results: Lack of Hmgcr expression resulted in lethality, due to acute liver damage caused by rapid disruption of mitochondrial fatty acid β‐oxidation and very high accumulation of long‐chain (LC) acylcarnitines in both male and female mice. Gene expression and KO‐related phenotype changes were not observed in other tissues. The progression to liver failure was driven by diminished peroxisome formation, which resulted in impaired mitochondrial and peroxisomal fatty acid metabolism, enhanced glucose utilization and whole‐body hypoglycaemia. Conclusion and Implications: Our findings suggest that HMGCR is crucial for maintaining energy metabolism balance, and its activity is necessary for functional mitochondrial β‐oxidation. Moreover, statin‐induced adverse reactions might be rescued by the prevention of LC acylcarnitine accumulation. [ABSTRACT FROM AUTHOR]

Objective: Some observational studies have unexpectedly reported the association of cholesterol metabolism with mental and psychological disorders, but a firm conclusion has not been drawn. The aim of this study was to further investigate the effects of peripheral cholesterol traits and cholesterol-lowering therapy on depression and schizophrenia using a Mendelian randomisation approach. Methods: Instrumental variables meeting the correlation, independence and exclusivity assumptions were extracted from one genome-wide association study for predicting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and nonHDL cholesterol. Instrumental variables for total cholesterol and LDL cholesterol were also adopted to predict statin use (a type of cholesterol-lowering drug); these instrumental variables should not only satisfy the above assumptions but also be close to 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR, the target gene of statins) on the chromosome. Three methods (including inverse variance weighted) were used to conduct causal inference of the above exposures with depression and schizophrenia. Sensitivity analyses were performed to assess horizontal pleiotropy. Results: Higher levels of peripheral nonHDL cholesterol were nominally associated with a decreased risk of depression (P = 0.039), and higher levels of HMGCR-mediated total cholesterol and LDL cholesterol were nominally related to a decreased risk of depression (P = 0.013 and P = 0.028, respectively). Moreover, these cholesterol traits cannot affect the risk of schizophrenia. Sensitivity analysis did not reveal any horizontal pleiotropy. Conclusion: The study provided some interesting, but less sufficient, evidence that nonHDL cholesterol may have a protective effect on depression, and lowering cholesterol using statins might increase the risk of the disease. [ABSTRACT FROM AUTHOR]

Although free-floating thrombus (FFT) poses a significant risk of stroke or transient ischemic attack (TIA), optimal management strategies are uncertain. To determine the state-of-the-art of medical interventions for FFT, we conducted a systematic review of the efficacy of various medical interventions and factors influencing FFT resolution and recurrence. A comprehensive search of Embase, PubMed, and ScienceDirect identified 61 studies encompassing 179 patients with FFT-related stroke or TIA treated with anticoagulants, antiplatelets, or their combinations. Primary outcomes assessed were stroke recurrence and thrombus resolution. Statistical analyses (Fisher's exact test, chi-square test, Mann–Whitney test, and Kruskal–Wallis test) utilized significance set at p < 0.05. Over a median follow-up of 7 months, thrombus resolution occurred in 65% of patients, while 11.2% experienced recurrence, primarily as TIAs. Cardioembolism was significantly less common in resolved cases (p = 0.025). Combination therapy (antiplatelets, anticoagulants, and statins) significantly enhanced clot resolution (OR 11.4; 95% CI 1.436–91.91; p = 0.021) compared to monotherapies. Ulcerated plaque was a significant predictor of recurrence (OR 8.2; 95% CI 1.02–66.07; p = 0.048). These findings underscore the superiority of combination therapy in FFT management and highlight the need for targeted interventions in patients with ulcerated plaques to mitigate recurrence risk. [ABSTRACT FROM AUTHOR]

Background: People with intermediate CVD risk constitute most of the population. Within this group, the proportion of events is lower compared to the high-risk group, but they contribute with the largest absolute number of events. Atherosclerosis is a dynamic process and progression can be slowed or even reversed with medication and lifestyle changes, but adherence to prescribed treatment is crucial. Aim: To investigate the long-term effects of interventions with pictorial risk communication of cardiovascular (CVD) risk on average adherence in a group of statin users. Compare response in adherence over time between men and women after intervention. Methods: Participants on active statin treatment were followed up to 5 years after being randomly assigned to an intervention program aimed at raising CVD risk awareness among participants and their physicians. Merging prescribed medication databases with VIPVIZA study to study adherence over time. A moving average adherence was used to compare groups. Results: Generally, the average adherence to statins among the 512 participants was high. Men had a higher average adherence over time, while women had a sharper increase in adherence in conjuncture with the intervention program. Conclusions: Both men and women were receptive to pictorial information regarding CVD risk, but the intervention effect was more pronounced in women. Sex differences are important when considering risk communication strategies. Periodically repeating the intervention was beneficial for maintaining the intervention effect over time. Trial registration: The VIPVIZA study is registered with ClinicalTrials.gov, May 8, 2013, number NCT01849575. [ABSTRACT FROM AUTHOR]

• A critical literature review of case reports on statins-induced side effects in various hereditary myopathies. • Setting criteria to assess case reports of statin myotoxicity in hereditary myopathies. • Identification of myopathies with high risk for statin usage (MELAS and other mitochondrial disorders, myotonic dystrophy type 2, McArdle disease). • Suggesting practical management of hyperlipidemia in hereditary myopathies. Hyperlipidemia is not uncommon in patients with hereditary myopathies who get older and also in several conditions in which it is frequently observed. Thus, using the common cholesterol reducing medications of the stains group could be considered. However, the side effects of these drugs include myalgia, myopathy and rhabdomyolysis typically associated with high serum creatine kinase (CK). Because high CK levels are very frequently found in hereditary myopathies, physicians are reluctant to use statins in such patients. Reviewing the literature about statin side effects in hereditary myopathies does not provide a clear evidence about the true risk of these drugs. This review critically describes the reported cases of statin side effects in several genetic myopathies and suggests some guidelines for conditions that are contra indicated for statin usage (particularly in mitochondrial disorders, metabolic myopathies, myotonic dystrophy type 2). Possible solutions to the dilemma of whether to use statins in hereditary myopathies are discussed (prescribing other cholesterol lowering agents and a carefully monitored treatment initiation of statins). [ABSTRACT FROM AUTHOR]

Background: There are knowledge gaps regarding the relative efficacy of statins for aneurysmal subarachnoid hemorrhage (aSAH). This study aims to examine the comparative effectiveness and determine the ranking of different statins with network meta‑analysis in patients with aSAH. Methods: MEDLINE, Embase, Pubmed, and Cochrane Central Register of Controlled Trials were searched from database inception until December 15, 2022. Outcomes included delayed cerebral ischemia (DCI), functional recovery, and mortality. Relative risk (RRs) ratios and associated 95% confidence intervals (CIs) were estimated. The values derived from surface under the cumulative ranking curve were obtained to rank the treatment hierarchy in the analysis. Results: We identified 13 trials involving 1,885 patients. Atorvastatin 20 mg (RR 0.68, 95% CI 0.53–0.86), pravastatin 40 mg (RR 0.51, 95% CI 0.31–0.77), and simvastatin 80 mg (RR 0.54, 95% CI 0.40–0.70) were superior to the placebo in preventing DCI. Additionally, simvastatin 80 mg (RR 0.60, 95% CI 0.42–0.84) and pravastatin 40 mg (RR 0.56, 95% CI 0.32–0.93) were associated with a decreased risk of DCI than simvastatin 40 mg. Comparisons across treatment durations suggested that short-term (RR 0.62, 95% CI 0.50–0.76) statin therapy reduced risk of DCI. Conclusions: Simvastatin 80 mg might be the most effective intervention in reducing DCI. Additionally, short-term therapy might provide more benefits. Further research with longer follow-up is warranted to validate the current findings in patients with aSAH who are at high risk of DCI. [ABSTRACT FROM AUTHOR]

• Anthracyclines may cause cancer therapy-related cardiovascular dysfunction. • Herein, we assessed the cardioprotective effects of statins in this setting. • Statins attenuated cancer therapy-related cardiovascular dysfunction. • Statins also improved left ventricular end-systolic volume. • Their benefits remain uncertain across the spectrum of dose of anthracyclines. Several interventions have been tested for cardio-protection against anthracycline-induced cancer therapy-related cardiovascular dysfunction (CTRCD). The role of statins in this setting remains unclear. We systematically searched PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and Web of Science for randomized controlled trials (RCTs) comparing statins versus control (placebo or no intervention) for preventing anthracycline-induced CTRCD. We applied a random-effects model to pool risk ratios (RR) and mean differences (MD) with 95 % confidence intervals (CI). We included seven RCTs comprising 887 patients with planned chemotherapy with anthracycline-based regimens, of whom 49.8 % were randomized to statins. Relative to placebo, statins significantly reduced the incidence of cardiotoxicity/CTRCD (RR 0.46; 95 % CI 0.29 to 0.72; p < 0.001). The left ventricular end-systolic volume was also lower in patients treated with statin (MD -3.12 mL; 95 % CI -6.13 to -0.12 mL; p = 0.042). There was no significant difference between groups in post-anthracycline left ventricular ejection fraction (LVEF) overall. In this meta-analysis of RCTs, statins were significantly associated with a lower incidence of anthracycline-induced CTRCD and attenuated changes in the left ventricular end-systolic volume. Thus, our findings suggest that statins should be considered as a cardio-protection strategy for patients with planned anthracycline-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background Numerous studies have linked fine particulate matter (PM2.5) to increased cardiovascular mortality. Less is known how the PM2.5-cardiovascular mortality association varies by use of cardiovascular medications. This study sought to quantify effect modification by statin use status on the associations between long-term exposure to PM2.5 and mortality from any cardiovascular cause, coronary heart disease (CHD), and stroke. Methods In this nested case-control study, we followed 1.2 million community-dwelling adults aged ≥66 years who lived in Ontario, Canada from 2000 through 2018. Cases were patients who died from the three causes. Each case was individually matched to up to 30 randomly selected controls using incidence density sampling. Conditional logistic regression models were used to estimate odds ratios (ORs) for the associations between PM2.5 and mortality. We evaluated the presence of effect modification considering both multiplicative (ratio of ORs) and additive scales (the relative excess risk due to interaction, RERI). Results Exposure to PM2.5 increased the risks for cardiovascular, CHD, and stroke mortality. For all three causes of death, compared with statin users, stronger PM2.5-mortality associations were observed among non-users [e.g. for cardiovascular mortality corresponding to each interquartile range increase in PM2.5, OR = 1.042 (95% CI, 1.032–1.053) vs OR = 1.009 (95% CI, 0.996–1.022) in users, ratio of ORs = 1.033 (95% CI, 1.019–1.047), RERI = 0.039 (95% CI, 0.025–0.050)]. Among users, partially adherent users exhibited a higher risk of PM2.5-associated mortality than fully adherent users. Conclusions The associations of chronic exposure to PM2.5 with cardiovascular and CHD mortality were stronger among statin non-users compared to users. [ABSTRACT FROM AUTHOR]

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention. [ABSTRACT FROM AUTHOR]

Background: Many observational studies have examined the association between statins and the incidence of Parkinson's disease (PD) in high‐risk populations. On the other hand, clinical trials as well as other observational studies investigated the safety and efficacy of statins in slowing disease progression in PD patients. However, the evidence has been inconclusive in both questions. To that end, we conducted this systematic review and meta‐analysis to synthesize evidence on the role of statins in decreasing the risk of PD among high‐risk populations and as a possible disease‐modifying agent for patients with PD. Methods: A comprehensive literature search of electronic databases including PubMed, Scopus, Cochrane, and Web of Science has been performed. Relevant studies were chosen and data were extracted and analyzed using RevMan software version 5.4.1. Results: Twenty‐five studies (14 cohort, 9 case–control, and 2 randomized controlled trials) have been included in the present systematic review. Of them, 21 studies reported the association between statins and PD risk. Statins were found to significantly reduce the risk of developing PD (pooled RR 0.86, 95% CI [0.77–0.95], p < 0.005). Four studies investigated statins as a disease‐modifying agent. The pooled mean difference (MD) in the UPDRS‐III from baseline to endpoint did not differ significantly between the statin and control groups (MD −1.34 points, 95% CI [−3.81 to 1.14], p = 0.29). Conclusion: Although epidemiological observational studies showed that statin use was associated with a reduced risk of PD, current evidence is insufficient to support the role of statins in slowing the progression of PD. These findings are limited by the fact that most of the included studies are observational studies which carry a high risk of confounding bias which highlights the need for future well‐designed RCTs. [ABSTRACT FROM AUTHOR]

There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p < 0.0125 was considered significant after Bonferroni Correction. To triangulate the findings, genetic variants of whole blood-derived targets gene expression (cis-eQTL) and plasma-derived protein (cis-pQTL) levels were used to perform secondary MR analyses and data from the National Health and Nutrition Examination Survey were used for cross-sectional analysis. Genetically proxied inhibition of HMGCR was associated with higher risks of DN and DR (DN: OR = 1.79, p = 0.01; DR: OR = 1.41, p = 0.004), while no such association was found for PCSK9. Secondary MR analyses confirmed these associations. Cross-sectional analysis revealed a positive link between statin use and DR incidence (OR = 1.26, p = 0.03) and a significant negative association with glomerular filtration rate (Beta = − 1.9, p = 0.03). This study provides genetic evidence that genetically proxied inhibition of HMGCR is associated with increased risks of DN/DR, and this effect may not be attributed to their LDL-C-lowering properties. For patients with diabetic dyslipidemia, PCSK9 inhibitors may be a preferable alternative. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Clinicians and patients often face a decision to continue or discontinue statins. We examined the impact of discontinuation of statins compared with continuation on clinical outcomes (all‐cause mortality, cardiovascular [CV] mortality, CV events, and quality of life).We conducted a systematic review. Randomized controlled trials (RCTs), cohort studies, case–control studies, and quasi‐randomized studies among people ≥18 years were eligible. We searched MEDLINE, Embase, and Cochrane Central Registry (inception to August 2023). Two independent reviewers performed screening and extracted data. Quality assessment was performed by one author and verified by another. We summarized results narratively, performed meta‐analysis for a subset of studies, and used GRADE to assess certainty of evidence. We summarized findings in the subgroup of persons ≥75 years.We retrieved 8369 titles/abstracts; 37 reports from 36 studies were eligible. This comprised 35 non‐randomized studies (n = 1,708,684) and 1 RCT (n = 381). The 1 RCT was conducted among persons with life expectancy <1 year and showed there is probably no difference in 60‐day mortality (risk difference = 3.5%, 90% CI −3.5 to 10.5) for statin discontinuation compared with continuation. Non‐randomized studies varied in terms of population and setting, but consistently suggested that statin discontinuation might be associated with a relative increased risk of mortality (hazard ratio (HR) 1.92, 95% CI 1.52 to 2.44, nine studies), CV mortality (HR 1.63, 95% CI 1.27 to 2.10, five reports), and CV events (HR 1.31, 95% CI 1.23 to 1.39, eight reports). Findings in people ≥75 years were consistent with main results. There was a high degree of uncertainty in findings from non‐randomized studies due to methodological limitations.Statin discontinuation does not appear to affect short‐term mortality near end‐of‐life based on one RCT. Outside of this population, findings from non‐randomized studies consistently suggested statin discontinuation may be associated with worse outcomes, though this is uncertain. [ABSTRACT FROM AUTHOR]

Statins, known as hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) inhibitors, are primarily used to lower blood lipids, preventing and treating cardiovascular diseases. Research indicates that statins exhibit multiple effects in the prevention and treatment of colorectal cancer. They function by inhibiting the MVA pathway, suppressing inflammation, enhancing cellular immunity, and influencing the gut microbiota, positively impacting the onset and progression of colorectal cancer. Clinical studies have additionally uncovered that statin drugs can augment the effectiveness of chemotherapy, immunotherapy, and adjuvant therapies, acting as both preventive and adjunctive measures for colorectal cancer. This article critically reviews the research progress on statins in colorectal cancer, aiming to establish a theoretical foundation for exploring innovative treatment options. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to explore the correlation between statin administration in the intensive care unit (ICU) setting and the in-hospital mortality risk of patients suffering from sepsis-induced coagulopathy (SIC). Methods: Utilizing a retrospective cohort study design, this investigation collected data from the Medical Information Mart for Intensive Care (MIMIC)-IV spanning 2008 to 2019. The diagnosis of SIC was established based on a SIC score of 4 or above. Statin usage during the ICU period was extracted from the prescription records based on the keywords of statin medications. The primary endpoint analyzed was the in-hospital mortality within the ICU, characterized by any death occurring during the ICU admission. Results: During the follow-up, which had a median duration of approximately 7.28 days, 18.19% of the 4,777 SIC patients died in the ICU. Statin was linked with a decrease in the risk of in-hospital mortality for SIC patients in the ICU [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.60–0.89, P = 0.002]. Relative to rosuvastatin, the use of atorvastatin (HR: 0.54, 95% CI: 0.34–0.85, P = 0.008) or simvastatin (HR: 0.55, 95% CI: 0.33–0.92, P = 0.024), as well as combinations of multiple statins (HR: 0.36, 95% CI: 0.15–0.86, P = 0.022), was associated with a reduction in ICU in-hospital mortality risk. Subgroup analysis also suggested that the use of atorvastatin, simvastatin, or a combination of statins had an advantage over rosuvastatin in reducing ICU in-hospital mortality in SIC patients older than 65 years of age or SIC patients with respiratory failure or cardiogenic shock (all P < 0.05). Conclusion: The present study supports the potential benefits of statin use in mortality in SIC patients during ICU stays. The study encourages clinicians to consider the benefits of statins and supports the ongoing exploration of statins for enhanced outcomes in critical care settings. [ABSTRACT FROM AUTHOR]

Purpose: Statin therapy is widely used for the management of dyslipidemia and the prevention of cardiovascular diseases (CVDs). However, there is a growing concern about its potential effects on bone metabolism markers and mineral density. The aim of this systematic review and meta-analysis was to investigate the effect of statin therapy on these parameters. Methods: PubMed/MEDLINE, Scopus, and Clarivate Analytics Web of Science databases were searched from inception to August 2023, using MESH terms and keywords. Results: After screening 2450 articles, 16 studies that met the inclusion criteria were included, of which 12 randomized controlled trials (RCTs) were used for meta-analysis. The findings showed that statin therapy significantly reduced bone-specific alkaline phosphatase (B-ALP) levels (WMD=-1.1 U/L; 95% CI -2.2 to -0.07; P =0.03; I2=0%,), and bone mineral density (BMD) at different sites (WMD=-0.06 g/cm2; 95% CI -0.08 to -0.04; P <0.001;>2=97.7%, P <0.001).> Conclusion: This systematic review and meta-analysis provide evidence that statin therapy is associated with a significant reduction in B-ALP levels and BMD at different sites of the skeleton. Further studies are needed to investigate the long-term effects of statin therapy on bone health and to identify the potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the correlation between statin therapy and prognosis of esophageal cancer based on Meta-analysis. METHODS: PubMed, Web of Science, the Cochrane Library and Embase databases were systematically retrieved to collect the relevant literature of correlation between statin exposure and prognosis of esophageal cancer from the establishment of the database to Sept. 1st, 2023. Stata 17. 0 software was used to analyze prognosis indicators all-cause mortality and malignancy specific mortality. RESULTS: According to the inclusion and exclusion criteria, a total of 8 articles (26 553 patients diagnosed with esophageal cancer) were included in the Metaanalysis. The combined results showed that statin therapy was significantly associated with all-cause mortality (HR = 0. 82,95%CI = 0. 77-0. 87) and malignancy specific mortality (HR = 0. 78,95% CI = 0. 70 ~ 0. 86) in patients with esophageal cancer. In the subgroup analysis, the above significant correlations existed. Sensitivity analysis and publication bias detection supported the stability of the results. CONCLUSIONS: Current study provides preliminary evidence that statins therapy is associated with a survival benefit in patients with esophageal cancer, yet more research is needed to validate the findings. [ABSTRACT FROM AUTHOR]

Evidence suggests that inflammatory processes play a role in the pathophysiology of schizophrenia. Statins exert anti-inflammatory and antioxidant effects and may be effective in improving the symptoms of schizophrenia. This study explored whether statins, as an adjunctive therapy, can alleviate the symptoms of schizophrenia. PubMed, EMBASE, and the Cochrane Library were searched for articles published up to March 2023. The risk-of-bias tool for randomized trials was used to assess study quality. Two researchers independently assessed the risks of bias and extracted data. Pooled data on Positive and Negative Syndrome Scale (PANSS) scores were analyzed. A random-effects model was employed to calculate pooled effect sizes. Statistical heterogeneity across studies was assessed using the I 2 statistic. All analyses were performed using RevMan5 and Comprehensive Meta-Analysis software. Nine trials enrolling 533 patients in total were included. Add-on statin therapy was found to be associated with a significantly better total PANSS score [standardized mean difference (SMD) = −0.42, 95% confidence interval (CI) −0.75 to −0.09, I 2 = 72%; P = 0.01] and PANSS negative subscale score (SMD = −0.26, 95% CI −0.45 to −0.07, I 2 = 0%; P = 0.009) in comparison with placebo. However, add-on statin therapy did not appear to improve scores for the PANSS positive and general subscales at the study-defined endpoint (6–24 weeks). Our meta-analysis indicates that adjunctive statin therapy may confer benefits in ameliorating PANSS negative and total scores. It needs more solid data to confirm the results are related to clinical improvement and functioning. [ABSTRACT FROM AUTHOR]

Background: Effective shared decision-making (SDM) tools for use during clinical encounters are available, but, outside of study settings, little is known about clinician use of these tools in practice. Objective: To describe real-world use of an SDM encounter tool for statin prescribing, Statin Choice, embedded into the workflow of an electronic health record. Design: Cross-sectional study. Participants: Clinicians and their statin-eligible patients who had outpatient encounters between January 2020 and June 2021 in Cleveland Clinic Health System. Main Measures: Clinician use of Statin Choice was recorded within the Epic record system. We categorized each patient's 10-year atherosclerotic cardiovascular disease risk into low (< 5%), borderline (5–7.5%), intermediate (7.5–20%), and high (≥ 20%). Other patient factors included age, sex, insurance, and race. We used mixed effects logistic regression to assess the odds of using Statin Choice for statin-eligible patients, accounting for clustering by clinician and site. We generated a residual intraclass correlation coefficient (ICC) to characterize the impact of the clinician on Statin Choice use. Key Results: Statin Choice was used in 7% of 68,505 eligible patients. Of 1047 clinicians, 48% used Statin Choice with ≥ 1 patient, and these clinicians used it with a median 9% of their patients (interquartile range: 3–22%). In the mixed effects logistic regression model, patient age (adjusted OR per year: 1.04; 95%CI 1.03–1.04) and 10-year ASVCD risk (aOR for 5–7.5% versus < 5% risk: 1.28; 95%CI: 1.14–1.44) were associated with use of Statin Choice. Black versus White race was associated with a lower odds of Statin Choice use (aOR: 0.83; 95%CI: 0.73–0.95), as was female versus male sex (aOR: 0.83; 95%CI: 0.76–0.90). The model ICC demonstrated that 53% of the variation in use of Statin Choice was clinician-driven. Conclusions: Patient factors, including race and sex, were associated with clinician use of Statin Choice; half the variation in use was attributable to individual clinicians. [ABSTRACT FROM AUTHOR]

Objective: Naringenin, a major flavonoid found in citrus juice, has been shown to inhibit human ether-a-go-go-related gene (HERG) channels and cause QT prolongation. Statins, the most commonly used class of cholesterol reducing drugs, have also been reported to inhibit HERG channels and prolong QT interval in patients using these drugs. However, the interaction between naringenin and statins on the function of HERG channels has not been studied. Materials and Methods: In the present study, we expressed HERG channels in Xenopus oocytes, tested the effects of naringenin and statins separately, and combined on HERG channels. Results: When 30 µm naringenin was added to statins (1 µm rosuvastatin or 3 µm atorvastatin), significantly greater inhibition of HERG was demonstrated, compared to the inhibition caused by statins alone. Conclusions: The results indicate that an additive interaction occurs between naringenin and statins; this could pose an increased risk of arrhythmias by decreasing repolarization reserve. Highlights of the Study: Naringenin, abundantly found in citrus juice, causes QT prolongation in electrocardiograms of healthy volunteers. Statins, cholesterol-reducing drugs, have also been reported to inhibit human ether-a-go-go-related gene (HERG) channels and to prolong QT interval. Naringenin and statins inhibit HERG channels in an additive manner highlighting the increased risk of QT prolongation in patients consuming statins and citrus juice concomitantly. [ABSTRACT FROM AUTHOR]

Statins are cholesterol-lowering drugs with a mechanism of inhibiting 3-hydroxy-3- methylglutaryl-CoA reductase, but long-term use can cause side effects. An example of a plant capable of reducing cholesterol levels is Angelica keiskei (ashitaba). Therefore, this study aimed to obtain suitable compounds with inhibitory activity against the HMG-CoA reductase enzyme from ashitaba through in silico tests. The experiment began with screening and pharmacophore modeling, followed by molecular docking on ashitaba’s compounds, statins groups, and the native ligand was (3R,5R)-7-[4-(benzyl carbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-imidazole1-yl]-3,5-dihydroxyheptanoic acid (4HI). Based on the results of the molecular docking simulations, 15 hit compounds had a small binding energy (∆G). Pitavastatin, as the comparator drug (∆G = −8.24 kcal/mol; Ki = 2.11 µM), had a lower ∆G and inhibition constant (Ki) than the native ligand 4HI (∆G = −7.84 kcal/mol; Ki = 7.96µM). From ashitaba’s compounds, it was found that 4′ -O-geranylnaringenin, luteolin, isobavachalcone, dorsmannin A, and 3′ -carboxymethyl-4,2′ - dihydroxy-4′ -methoxychalcone have low ∆G of below −6 kcal/mol. The lowest ∆G value was found in 3′ -carboxymethyl-4,2′ -dihydroxy-4′ -methoxy chalcone with a ∆G of −6.67 kcal/mol and Ki value of 16.66 µM, which was lower than the ∆G value of the other comparator drugs, atorvastatin (∆G = −5.49 kcal/mol; Ki = 1148.17 µM) and simvastatin (∆G = −6.50 kcal/mol; Ki = 22.34 µM). This compound also binds to the important amino acid residues, including ASN755D, ASP690C, GLU559D, LYS735D, LYS691C, and SER684C, through hydrogen bonds. Based on the results, the compound effectively binds to six important amino acids with good binding affinity and only requires a small concentration to reduce half of the enzyme activity [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the main causes of death, and statins can reduce the risk of major vascular events. Lithuania is among the European countries with the highest cardiovascular mortality despite a rapidly increasing use of statins. Previous reviews have shown the problem of poor patient adherence, but there are limited studies from Eastern European countries. The aim of this study was to evaluate treatment persistence in new users of statins in Lithuania and to investigate factors associated with persistence. Dispensed prescriptions from patients aged >18 years old initiated on statins in 2018–2019 were included, and data were obtained from a national health insurance fund. Persistence was assessed by the proportion of patients who still had statins dispensed 1 year after the first dispensing. Factors associated with persistence were assessed using logistic regression. A total of 104 726 patients (41.3% men) were initiated on statin treatment. Only 41% of them continued statin use 1 year after initiation. Factors associated with higher persistence rate were older age, higher dose of statin, use of other medicines and use of statins as secondary prevention. Low persistence to statin therapy needs to be recognized by healthcare workers, pharmacists and policy makers to address this problem. [ABSTRACT FROM AUTHOR]

Anthracyclines are associated with enhanced oxidative stress responsible for adverse events in patients with breast cancer. However, no study has investigated the potential anti-inflammatory role of statins in counteracting anthracycline toxicity. In this retrospective study utilizing a federated health network (TriNetX), patients with breast cancer (ICD code C50) treated with anthracyclines were categorized into two groups: statin users (for at least 6 months); and statin non-users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the risk of myocardial infarction, stroke, atrial fibrillation, ventricular arrhythmias, heart failure, and pulmonary embolism. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). We identified 3,701 statin users (68.8 ± 10.4 years) and 37,185 statin non-users (59.6 ± 12.8 years). After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.82, 95% CI 0.74–0.91) compared to statins non-users. Analyzing the risk for secondary outcomes, only the risk of stroke was significantly increased in statin users (HR 1.27, 95% CI 1.01–1.61), while no associations were found for the other cardiovascular events. The risk of all-cause death in statin users was the lowest during the first year after the anthracycline's initiation. No significant difference was found between lipophilic and hydrophilic statins. In patients with breast cancer treated with anthracyclines, statin use is associated with a reduced risk of all-cause death. Prospective studies are needed to investigate the potential beneficial effect of statin initiation in cancer patients without other indications. [ABSTRACT FROM AUTHOR]

The combination of aspirin (ASP) and clopidogrel (CLD) has demonstrated efficacy in managing coronary syndromes, including unstable angina and myocardial infarction. This regimen prevents clotting and effectively reduces the risk of vascular events by inhibiting both adenosine diphosphate and the cyclooxygenase pathway. Furthermore, cholesterol-lowering agents such as statins are also employed as a preventive measure for patients with acute coronary syndromes (ACS). This article reviews the current analytical methods for the quantitative determination of aspirin in combination with clopidogrel, or the combination of the two drugs with one of the statins, in various marketed formulations in the period of 2005 -2024. The most commonly used methods for determining these combinations include chromatographic techniques such as high-pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC), as well as spectrophotometric methods. Recent trends in the analysis of these combination samples show a preference for HPLC (60%), thin-layer chromatography (TLC) (22.5%) and spectrophotometric methods (17.5%) reflecting a general shift towards more sensitive methods with higher resolution capabilities. These methods also offer the advantages of requiring smaller quantities of samples and reagents and shorter analysis times. [ABSTRACT FROM AUTHOR]