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AimsThoracic aortic aneurysm (TAA) that progress to acute aortic dissection is often fatal and there is no pharmacological treatment that can reduce TAA progression. We aim to evaluate statins’ effects on TAA growth rate and outcomes using a meta-analysis approach.Methods and resultsA detailed search related to the effects of statins on TAA was conducted according to PRISMA guidelines. The analyses of statins’ effects on TAA growth rate were performed on 4 studies (n = 1850), while the impact on outcomes was evaluated on 3 studies (n = 2,867). Patients under statin treatment showed a reduced TAA growth rate (difference in means = −0.36 cm/year; 95%CI: −0.64, −0.08; p = 0.013) when compared to controls, patients not taking statins. Regarding the outcomes (death, dissection, or rupture of the aorta, and the need for operative repair), statins exhibited a protective effect reducing the number of events (log odds ratio = −0.56; 95%CI: −1.06, −0.05; p = 0.030). In vitro, the anti-fibrotic effect of atorvastatin was tested on vascular smooth muscle cells (VMSC) isolated from patients with TAA. Our results highlighted that, in transforming growth factor beta 1 (TGF-β1) pro-fibrotic condition, VSMC expressed a significant lower amount of collagen type I alpha 1 chain (COL1A1) when treated with atorvastatin (untreated = +2.66 ± 0.23 fold-change vs. treated = +1.63 ± 0.09 fold-change; p = 0.014).ConclusionStatins show a protective effect on TAA growth rate and adverse outcomes in patients with TAA, possibly via their anti-fibrotic properties on VSMC. Given the current lack of effective drug treatments for TAA, we believe our findings highlight the need for more in-depth research to explore the potential benefits of statins in this context.

Background and aims: Cardiovascular disease remains a leading cause of mortality, with statins widely used to reduce its risk. Despite extensive research, the nuanced impact of statin therapy on cardiorespiratory fitness, particularly the reduction in peak oxygen consumption (VO2), is still an open question. This study aims to contribute fresh insights to the ongoing discussion, highlighting the unresolved nature of this clinical matter. Methods: We retrospectively analyzed maximal cardiopulmonary exercise test (CPET) in male and female participants over 18 years of age who were under statins treatment. They were categorized as physically active or inactive according to self-report of physical activity. From 33,804 CPET, 4,941 participants (76 % men, age 42 ± 13 years; and 24 % women, age 41 ± 13 years) were included in the study. Results: The multivariate linear regression model showed that statins were associated with a significant reduction in VO2 peak (−4.2 [-4.8, −3.5] mL/kg/min, p 600 min/week: 6.9 [5.4; 8.4] mL/kg/min, all p 150 min/week). Future research should explore the mechanisms behind this interaction and identify optimal exercise regimens for individuals on statin therapy.

Background: Obesity increases risk of atrial fibrillation (AF) at least in part due to pro-inflammatory effects, but has been paradoxically associated with improved mortality. Although statins have pleiotropic anti-inflammatory properties, their interaction with obesity and clinical outcomes in AF is unknown. We explored the relationship between BMI, statin use, and all-cause mortality and AF/congestive heart failure (CHF)-related encounters, hypothesizing that statin exposure may be differentially associated with improved outcomes in overweight/obesity. Methods: This was a single center retrospective cohort study of adults with AF diagnosed between 2011–2018. Patients were grouped by body mass index (BMI) and statin use at time of AF diagnosis. Outcomes included all-cause mortality and ED or inpatient encounters for AF or CHF. Results and Conclusions: A total of 2503 subjects were included (median age 66 years, 43.4 % female, median BMI 29.8 kg/m2, 54.6 % on baseline statin therapy). Increasing BMI was associated with decreased mortality hazard but not associated with AF/CHF encounter risk. Adjusting for statin-BMI interaction, demographics, and cardiovascular comorbidities, overweight non-statin users experienced improved mortality (adjusted hazard ratio [aHR] 0.55, 95 % CI 0.35–0.84) compared to statin users (aHR 0.98, 95 % CI 0.69–1.40; interaction P-value = 0.013). Mortality hazard was consistently lower in obese non-statin users than in statin users, however interaction was insignificant. No significant BMI-statin interactions were observed in AF/CHF encounter risk. In summary, statin use was not differentially associated with improved mortality or hospitalization risk in overweight/obese groups. These findings do not support statins for secondary prevention of adverse outcomes based on overweight/obesity status alone.

Background: Statin therapy is well-established for treating hyperlipidemia and ischemic heart disease (IHD), but its role in Acute Decompensated Heart Failure (ADHF) remains less clear. Despite varying clinical guidelines, the actual utilization and impact of statin therapy initiation in patients with ADHF with an independent indication for statin therapy have not been thoroughly explored. Methods: We conducted a retrospective observational study on 5978 patients admitted with ADHF between January 1st, 2007, and December 31st, 2017. Patients were grouped based on their statin therapy status at admission and discharge. We performed multivariable analyses to identify independent predictors of short-term, intermediate-term, and long-term mortality. A sensitivity analysis was also conducted on patients with an independent indication for statin therapy but who were not on statins at admission. Results: Of the total patient cohort, 73.9% had an indication for statin therapy. However, only 38.2% were treated with statins at admission, and 56.1% were discharged with a statin prescription. Patients discharged with statins were younger, predominantly male, and had a higher prevalence of IHD and other comorbidities. Statin therapy at discharge was an independent negative predictor of 5-year all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76–0.85). The sensitivity analysis confirmed these findings, demonstrating higher mortality rates in patients not initiated on statins during admission. Conclusions: The study highlights significant underutilization of statin therapy among patients admitted with ADHF, even when there’s an independent indication for such treatment. Importantly, initiation of statin therapy during hospital admission was independently associated with improved long-term survival.

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

Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis, and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis, and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol, and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis, and fecal-neutral steroid excretion. MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.

Dyslipidemia is a medical term used to describe an abnormal level of lipids (fats) in the blood. This can include elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high density protein lipoprotein (HDL) cholesterol and serum triglicerides. Depression, also known as depressive disorder, is a common mental illness. It is characterized by a persistent feeling of sadness, loss of pleasure, or lack of interest in activities that are present of at least two weeks and significantly impair patient everyday functioning. Dyslipidemia and depression can co-occur due to a complex interplay of shared risk factors, such as inflammation, metabolic syndrome, medication side effects, and lifestyle changes, suggesting a bidirectional relationship where each condition might contribute to the development or exacerbation of the other. Given these considerations, a comprehensive approach to managing dyslipidemia in psychiatric patients with depression is essential. This should include regular monitoring of lipid profiles and monitoring of anticholesterol and antidepressant drugs. Interestingly, simple lifestyle changes, such as a healthy diet and exercise, have an impact on the treatment of depression and dyslipidemia.

Background Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. Conclusions The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.

Real-world data on lipid levels and treatment among adults with diabetes mellitus (DM) are relatively limited. We studied lipid levels and treatment status in patients with DM across cardiovascular disease (CVD) risk groups and sociodemographic factors. In the All of Us Research Program, we categorized DM as (1) moderate risk (≤1 CVD risk factor), (2) high risk (≥2 CVD risk factors), and (3) DM with atherosclerotic CVD (ASCVD). We examined the use of statin and non-statin therapy as well as LDL-C and triglyceride levels. We studied 81,332 participants with DM, which included 22.3% non-Hispanic Black and 17.2% Hispanic. A total of 31.1% had ≤1 DM risk factor, 30.3% had ≥2 DM risk factors, and 38.6% of participants had DM with ASCVD. Only 18.2% of those with DM and ASCVD were on high-intensity statins. Overall, 5.1% were using ezetimibe and 0.6% PCSK9 inhibitors. Among those with DM and ASCVD, only 21.1% had LDL-C < 70 mg/dL. Overall, 1.9% of participants with triglycerides ≥ 150 mg/dL were on icosapent ethyl. Those with DM and ASCVD were more likely to be on high-intensity statins, ezetimibe, and icosapent ethyl. Guideline-recommended use of high-intensity statins and non-statin therapy among our higher risk DM patients is lacking, with LDL-C inadequately controlled.

Although 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors are well tolerated, a small subset of patients may develop autoimmune myopathy, classified as immune-mediated necrotizing myopathy. Statin-induced immune-mediated necrotizing myopathy can present as proximal muscle weakness and in some cases as dysphagia and respiratory distress. We present two cases of patients taking statins who developed dysphagia and muscle weakness found to have statin-induced immune-mediated necrotizing myopathy. Both patients were treated with immunosuppressive therapy: one did well clinically, while the other had an aggressive form of statin-induced immune-mediated necrotizing myopathy and succumbed to the disease. Although statin-induced immune-mediated necrotizing myopathy is rare, early treatment to induce remission of this disabling condition should be initiated to prevent morbidity and mortality.

Introduction There is insufficient evidence in statin on the treatment of Staphylococcus aureus (SA) infection, we observe and analyze the clinical outcomes and antibiotic resistance of SA bloodstream infections in patients who received statins. Material and methods A retrospective study was carried out in SA bloodstream infection of hospitalized patients from January 2018 to August 2023. The 30-day attributable mortality, 30-day all-cause mortality and clinical data of patients who received statins and non-statins were compared. Results A total of 74 patients with SA bloodstream infection were included, 32 (43.2%) patients received treatment with statins and 42 (56.8%) with non-statins. The incidence of methicillin-resistant SA (MRSA) was significantly lower in the statins group (15.6% vs. 38.1%, p = 0.034), however, no significant differences were observed in the mortality rate (p = 0.410). Conclusions This study revealed the superiority of statins in reducing incidence of MRSA among SA bloodstream infection patients, but statins do not improve the 30-day mortality rate.

Abstract Background Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. Methods The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. Results Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). Conclusions This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

Background and aims: Statin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS. We aimed to compare atorvastatin pharmacokinetics between coronary heart disease (CHD) patients with and without clinically statin intolerance and statin-dependent histopathological alterations in muscle tissue. Secondarily we aimed to assess genetic variants relevant for the observed pharmacokinetic variables. Methods: Twenty-eight patients with CHD and subjective SAMS were included in the exploratory MUSE biomarker study in 2020. Participants received atorvastatin 40 mg/day for seven weeks followed by no statins for eight weeks. Muscle biopsies and blood were collected at the end of each period. Four patients were categorized as clinically intolerant to ≥3 statins prior to study start whereas four patients had signs of muscle cell damage during treatment. Results: We found significantly lower levels of atorvastatin acids, and higher lactone/acid ratios in the statin intolerant, both in muscle and plasma. With optimal cut-off, the combination of 2-OH-atorvastatin acid and the 2-OH-atorvastatin lactone/acid ratio provided sensitivity, specificity, and predictive values of 100 %. Patients with variants in UGT1A1 and UGT1A3 had higher lactone metabolite levels than those with wild type, both in muscle and plasma. Conclusion: Atorvastatin metabolites appear promising as biomarkers for the identification of clinical statin intolerance in patients with self-perceived SAMS, but the findings have to be confirmed in larger studies.

Background & Aims: Observational studies have linked lipid-lowering drug targets pro-protein convertase subtilisin/kexin 9 (PCSK9) and HMG-CoA reductase (HMGCR) with adverse liver outcomes; however, liver disease incidence varies across diverse populations, and the long-term hepatic impact of these lipid-lowering drugs among non-white Europeans remains largely unknown. Methods: We use single nucleotide polymorphisms (SNPs) in PCSK9 and HMGCR loci from genome-wide association study data of low-density lipoprotein cholesterol in 4 populations (East Asian [EAS], South Asian [SAS], African [AFR], and European [EUR]) to perform drug-target Mendelian randomization investigating relationships between PCSK9 and HMGCR inhibition and alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin. Results: Analyses of PCSK9 instruments, including functional variants R46L and E670G, failed to find evidence for relationships of low-density lipoprotein cholesterol lowering via PCSK9 variants and adverse effects on ALT, AST, GGT, or ALP among the cohorts. PCSK9 inhibition was associated with increased direct bilirubin levels in EUR (β = 0.089; P value = 5.69 × 10–6) and, nominally, in AFR (β = 0.181; P value = .044). HMGCR inhibition was associated with reduced AST in SAS (β = –0.705; P value = .005) and, nominally, reduced AST in EAS (β = –0.096; P value = .03), reduced ALP in EUR (β = –2.078; P value = .014), and increased direct bilirubin in EUR (β = 0.071; P value = .032). Sensitivity analyses using genetic instruments derived from circulating PCSK9 protein levels, tissue-specific PCSK9 expression, and HMGCR expression were in alignment, strengthening causal inference. Conclusions: We did not find ALT, AST, GGT, or ALP associated with genetically proxied PCSK9 and HMGCR inhibition across ancestries. We identified possible relationships in several ancestries between PCSK9 and increased direct and total bilirubin and between HMGCR and reduced AST. These findings support long-term safety profiles and low hepatotoxic risk of PCSK9 and HMGCR inhibition in diverse populations.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, accounting for 85% to 90% of cases. The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has greatly improved the prognosis of NSCLC patients. However, with prolonged drug use, the inevitable occurrence of acquired resistance leads to disease recurrence, progression, and even patient's death. Metabolic reprogramming is one of the hallmarks of malignant tumors and refers to metabolic changes in tumor cells to meet energy needs. In various cancers, lipid synthesis, distribution, and catabolism of tumor cells are altered to adapt to the lack of nutrients and oxygen in the tumor microenvironment. This paper focuses on how lipid metabolism reprogramming in NSCLC leads to resistance to EGFR-TKIs and how modulation of lipid metabolism increases the sensitivity of NSCLC to EGFR-TKIs. It summarizes and consolidates existing research progress to provide a reference for basic research and clinical treatment of EGFR-TKIs resistance in NSCLC.

Background: The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommends statin treatment for all adult kidney transplant recipients (KTRs), except those aged

Staphylococcus aureus is a causative agent of nosocomial infections and its antibiotic-resistant strains give cause for concern. Solutions are being explored to improve treatment for these infections, including repositioning drugs such as statins and using nanoparticles with antimicrobial properties. This study evaluated the antimicrobial effects of simvastatin (SIM) and biologically synthesized silver nanoparticles (bio-AgNPs) in isolate form and in combination using assays of minimum inhibitory concentration (MIC), an in vitro biofilm model, and the association of antimicrobials against clinical strains of S. aureus. Bio-AgNPs showed a 53.8 ± 1.23 nm mean diameter and standard deviation, a 0.23 polydispersity index, and a −25.66 ± 2.19 mV mean potential and standard deviation. Transmission electron microscopy confirmed the formation of nanoparticles, and the presence of Ag0 and AgCl. S. aureus strains were sensitive to bio-AgNPs and SIM, showing 31.88–187.5 and 74.66–149.32 μM concentrations, respectively. The association assay showed 2.0 fractional inhibitory concentration indices (i.e., indifferent for clinical strains) and 0.32 values for the standard ATCC 29213 strain (synergy). Biofilm inhibition assays with isolated SIM and bio-AgNPs showed decreased biofilm formation 4× to ⅛ MICs concentrations, showing no synergism in association. These findings evince that simvastatin and bio-AgNPs at subinhibitory concentrations can serve as antimicrobial agents against S. aureus biofilm.

Chronic subdural hematoma (CSDH) is a chronic space-occupying lesion formed by blood accumulation between the arachnoid membrane and the dura mater. Atorvastatin is of increasing clinical interest for CSDH. We performed a meta-analysis of published randomized controlled trials (RCTs) and used objective data as the primary outcomes to provide an evidence-based analysis of the efficacy of atorvastatin for CSDH treatment. Databases of MEDLINE (via PubMed), EMBASE, the Cochrane Library, Scopus, Web of Science, ScienceDirect, Chinese National Knowledge Infrastructure (CNKI), Cqvip database (CQVIP), and Wanfang database were systematically searched for RCTs reporting the use of atorvastatin for CSDH treatment. Odds ratio (OR), standard mean difference (SMD), and 95% confidence intervals (CIs) were used as summary statistics. I-square (I2) test was performed to assess the impact of study heterogeneity on the results of the meta-analysis. Nine relevant RCTs with 611 patients were identified for inclusion in this meta-analysis. Compared to controls, atorvastatin treatment had a significantly higher effectiveness (OR: 7.41, 95% CI: 3.32-16.52, P < 0.00001, I2 = 0%), lower hematoma volume (SMD: −0.46. 95% CI: −0.71 to −0.20, P = 0.0005, I2 = 0%), higher activities of daily living-Barthel Index (ADL-BI) (SMD: 2.07, 95% CI: 1.06-3.09, P < 0.0001, I2 = 92%), and smaller Chinese stroke scale (CSS) (SMD: -1.10, 95% CI: −1.72 to −0.48, P = 0.0005, I2 = 57%). In view of these findings, we conclude that the outcomes of experimental group are superior to the control group with respect to effectiveness, hematoma volume, ADL-BI, and CSS based on nine RCTs with 611 patients. Atorvastatin is beneficial to CSDH patients without surgery.

Background: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. Methods: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. Results: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). Conclusions: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings. [ABSTRACT FROM AUTHOR]

Background: Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC). Objectives: We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC. Design: Retrospective observational study. Methods: All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied. Results: Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th–75th percentile 4–10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06–12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39–2.90), PPIs (OR: 1.09, 95% CI: 0.45–2.63), SSRI (OR: 1.41, 95% CI: 0.82–2.44), or statins (OR: 0.83, 95% CI: 0.35–1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis. Conclusion: The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins. Plain language summary: The use of drugs and the odds for patients with microscopic colitis of having a second course of budesonide Microscopic colitis is a common cause of chronic diarrhea. Previous studies have shown that the use of non-steroidal anti-inflammatory drugs, acetylsalicylic acid, proton-pump inhibitors, serotonin reuptake inhibitors and statins are used more often in patients who later develop microscopic colitis. We aimed to study if these drugs also had an association to an increased risk of disease flares treated with budesonide in 183 patients with known microscopic colitis. Oral budesonide for 6-8 weeks are recommended for disease flares of microscopic colitis. In our study, 90 patients (49%) were prescribed a second course of budesonide probably due to a disease flare. We found a higher odds for being prescribed a second course of budesonide in patients with microscopic colitis who were prescribed non-steroidal anti-inflammatory drugs but no higher risk for the other 'risk drugs' for microscopic colitis. [ABSTRACT FROM AUTHOR]

Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients against developing active tuberculosis, suggesting that these drugs could help the host to control the pathogen at the initial stages of the disease. This work studies the effect of fluvastatin on the early response of healthy peripheral blood mononuclear cells (PBMCs) to inactivated Mycobacterium tuberculosis (Mtb) H37Ra. We found that in fluvastatin-treated PBMCs, most monocytes/macrophages became foamy cells that overproduced NLRP3 inflammasome components in the absence of immune stimulation, evidencing important cholesterol metabolism/immunity connections. When both fluvastatin-treated and untreated PBMCs were exposed to Mtb H37Ra, a small subset of macrophages captured large amounts of bacilli and died, concentrating the bacteria in necrotic areas. In fluvastatin-untreated cultures, most of the remaining macrophages became epithelioid cells that isolated these areas of cell death in granulomatous structures that barely produced IFNγ. By contrast, in fluvastatin-treated cultures, foamy macrophages surrounded the accumulated bacteria, degraded them, markedly activated caspase-1 and elicited a potent IFNγ/cytotoxic response. In rabbits immunized with the same bacteria, fluvastatin increased the tuberculin test response. We conclude that statins may enhance macrophage efficacy to control Mtb, with the help of adaptive immunity, offering a promising tool in the design of alternative therapies to fight tuberculosis. [ABSTRACT FROM AUTHOR]

Study design. Retrospective cohort study. Objective. To investigate the relationships of low-density lipoprotein cholesterol and statin usage with pseudarthrosis following single-level posterior or transforaminal lumbar interbody fusion (PLIF/TLIF). Summary of background data. Hypercholesterolemia can lead to atherosclerosis of the segmental arteries, which branch into vertebral bone through intervertebral foramina. According to the vascular hypothesis of disc disease, this can lead to ischemia of the lumbar discs and contribute to lumbar degenerative disease. Yet, little has been reported regarding the effects of cholesterol and statins on the outcomes of lumbar fusion surgery. Materials and Methods. TriNetX, a global federated research network, was retrospectively queried to identify 52,140 PLIF/TLIF patients between 2002 and 2021. Of these patients, 2137 had high cholesterol (= 130 mg/dL) and 906 had low cholesterol (=55 mg/dL). Perioperatively, 18,275 patients used statins, while 33,415 patients did not. One-to-one propensity score matching for age, sex, race, and comorbidities was conducted to balance the analyzed cohorts. The incidence of pseudarthrosis was then assessed in the matched cohorts within the six-month, one-year, and two-year postoperative periods. Results. After propensity score matching, high-cholesterol patients had greater odds of developing pseudarthrosis six months [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.28-2.33], one year (OR: 1.59, 95% confidence interval (CI): 1.20-2.10), and two years (OR: 1.57, 95% CI: 1.20-2.05) following a PLIF/TLIF procedure. Patients with statin usage had significantly lower odds of developing pseudarthrosis six months (OR: 0.74, 95% CI: 0.69-0.79), one year (OR: 0.76, 95% CI: 0.71-0.81), and two years (OR: 0.77, 95% CI: 0.72-0.81) following single-level PLIF/TLIF. Conclusions. The findings suggest that patients with hypercholesterolemia have an increased risk of developing pseudarthrosis following PLIF/TLIF while statin use is associated with a decreased risk. The data presented may underscore an overlooked opportunity for perioperative optimization in lumbar fusion patients, warranting further investigation in this area. [ABSTRACT FROM AUTHOR]

Objective: Statin is well-established as a classical lipid-lowering drug, and its cost has reduced considerably in the past years. Inclisiran is a new and effective lipidlowering drug given as a subcutaneous injection at 6-month intervals. This study aims to evaluate the cost-effectiveness of the combination use of inclisiran and statin versus statin alone for dyslipidemia in the mainland China population. Methods: The Markov decision-making model was used, and the clinical data and real-world data were collected at the University of Hong Kong--Shenzhen Hospital (HKU-SZH). Patients with cardiovascular disease (CVD) and blood lipid levels above the target on statin therapy were included as the target population and analyzed for cardiovascular events, future medical expenses, and the calculation made for the total life cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted to evaluate the influence of parameter uncertainty on the basecase analysis results. Results: If inclisiran was priced at Chinese renminbi (RMB) 20,000.00 (USD 2,973.49) per injection, patients in the inclisiran and statin group would incur an incremental cost of RMB 449,233.56 (USD 66,789.60) compared with the statin group, and they would obtain 0.21 more QALYs in their life cycle. The subsequent ICER of RMB 2,127,756.78 (USD 316,343.32)/QALY was significantly higher than the willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China, which was RMB 257,094.00 (USD 38,223.33)/QALY, suggesting that the combined use of inclisiran and statin was not cost-effective. If the price of inclisiran were reduced to RMB 2,500.00 (USD 371.69)/injection, the ICER of patients in the inclisiran and statin group would become RMB 257,790.63 (USD 38,326.91)/QALY, which is slightly lower than the WTP threshold of 3 times the per capita GDP of China, indicating that the combined use of inclisiran and statin would be cost-effective. Conclusion: If inclisiran is priced at RMB 20,000.00 (USD 2,973.49)/injection, then the combined use of inclisiran and statins is not cost-effective compared with statin alone. It will be economical only if the price of inclisiran is reduced by more than 88%. [ABSTRACT FROM AUTHOR]

Aims: The use of statins has been associated with an increased risk of new-onset diabetes. The characteristics of the population could influence this association. The objective of this study was to determine the risk of new-onset diabetes with the use of statins in patients in primary prevention, with an assessment of the results according to the baseline risk of developing diabetes of the included population. Methods: We performed an updated meta-analysis including randomized trials of statin therapy in primary prevention settings that report new-onset diabetes. The rate of new cases of diabetes in the control arms was estimated for each study. The studies were classified into two groups (low rate: < 7.5 events per 1000 patients-year; high rate; ≥ 7.5 events per 1000 patients-year). The fixed-effects model was performed. Results: Eight studies (70,453 patients) were included. Globally, statin therapy was associated with an increased risk of new-onset diabetes (OR 1.1; 95% CI 1.0–1.2, I2 35%). When we analyzed the studies according to the baseline diabetes risk in the control groups, the results showed that there was a greater risk only in the studies with a high baseline rate (OR 1.2; 95% CI 1.1–1.3, I2 0%; interaction p value = 0.01). Conclusion: Globally, the use of statins in patients in primary prevention was associated with an increased risk of new-onset diabetes. In the stratified analysis, this association was observed only in the group of studies with a high baseline rate of events. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a causative agent of nosocomial infections and its antibiotic-resistant strains give cause for concern. Solutions are being explored to improve treatment for these infections, including repositioning drugs such as statins and using nanoparticles with antimicrobial properties. This study evaluated the antimicrobial effects of simvastatin (SIM) and biologically synthesized silver nanoparticles (bio-AgNPs) in isolate form and in combination using assays of minimum inhibitory concentration (MIC), an in vitro biofilm model, and the association of antimicrobials against clinical strains of S. aureus. Bio-AgNPs showed a 53.8 ± 1.23 nm mean diameter and standard deviation, a 0.23 polydispersity index, and a −25.66 ± 2.19 mV mean potential and standard deviation. Transmission electron microscopy confirmed the formation of nanoparticles, and the presence of Ag0 and AgCl. S. aureus strains were sensitive to bio-AgNPs and SIM, showing 31.88–187.5 and 74.66–149.32 μM concentrations, respectively. The association assay showed 2.0 fractional inhibitory concentration indices (i.e., indifferent for clinical strains) and 0.32 values for the standard ATCC 29213 strain (synergy). Biofilm inhibition assays with isolated SIM and bio-AgNPs showed decreased biofilm formation 4× to ⅛ MICs concentrations, showing no synergism in association. These findings evince that simvastatin and bio-AgNPs at subinhibitory concentrations can serve as antimicrobial agents against S. aureus biofilm. [ABSTRACT FROM AUTHOR]

Dyslipidemia plays a fundamental role in the development and progression of atherosclerosis. Current guidelines for treating dyslipidemia focus on low-density lipoprotein–cholesterol (LDL-C). Despite advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease—statins—remain insufficient in the primary or secondary prevention of acute myocardial infarction. Advancing therapy for hypercholesterolemia with emerging new drugs, either as monotherapy or in combination, is expected to improve cardiovascular outcomes. An emerging field in dyslipidemia pharmacotherapy is research on genetic therapies and genetic modulation. Understanding the genetic mechanisms underlying lipid alterations may lead to the development of personalized treatments that directly target the genetic causes of dyslipidemia. RNA messenger (mRNA)-based therapies are also being explored, offering the ability to modulate gene expression to normalize lipid levels. Furthermore, nanotechnology raises new possibilities in drug delivery for treating dyslipidemia. Controlled-release systems, nanoparticles, and liposomes can enhance the effectiveness and safety of medications by providing more precise and sustained release. This narrative review summarizes current and emerging therapies for the management of patients with dyslipidemia. [ABSTRACT FROM AUTHOR]

Noonan syndrome belongs to the family of RASopathies, a group of multiple congenital anomaly disorders caused by pathogenic variants in genes encoding components or regulators of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway. Collectively, all these pathogenic variants lead to increased RAS/MAPK activation. The better understanding of the molecular mechanisms underlying the different manifestations of NS and RASopathies has led to the identification of molecular targets for specific pharmacological interventions. Many specific agents (e.g. SHP2 and MEK inhibitors) have already been developed for the treatment of RAS/MAPK-driven malignancies. In addition, other molecules with the property of modulating RAS/MAPK activation are indicated in non-malignant diseases (e.g. C-type natriuretic peptide analogues in achondroplasia or statins in hypercholesterolemia). Conclusion: Drug repositioning of these molecules represents a challenging approach to treat or prevent medical complications associated with RASopathies. What is Known: • Noonan syndrome and related disorders are caused by pathogenic variants in genes encoding components or regulators of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway, resulting in increased activation of this pathway. • This group of disorders is now known as RASopathies and represents one of the largest groups of multiple congenital anomaly diseases known. What is New: • The identification of pathophysiological mechanisms provides new insights into the development of specific therapeutic strategies, in particular treatment aimed at reducing RAS/MAPK hyperactivation. • Drug repositioning of specific agents already developed for the treatment of malignant (e.g. SHP2 and MEK inhibitors) or non-malignant diseases (e.g. C-type natriuretic peptide analogues in achondroplasia or statins in hypercholesterolaemia) represents a challenging approach to the treatment of RASopathies. [ABSTRACT FROM AUTHOR]

Objective: The effective administration of lipid-lowering treatment is of utmost importance in mitigating cardiovascular (CV) risk in patients who are undergoing secondary prevention. High-dose statins, ezetimibe, and the relatively newer PCSK9 inhibitors (PCSK9i) have shown effectiveness in achieving low density lipoprotein cholesterol(LDL-C) treatment targets for these patients. However, despite substantial evidence supporting their efficacy, these interventions remain significantly underutilized, primarily due to poor levels of patient adherence. Moreover, there is limited data available on the overall effectiveness of cholesterol-lowering treatment and the proportion of secondary prevention patients who have achieved a well-regulated lipid profile. In light of these factors, the principal aim of this investigation was to evaluate the present status of lipid-lowering medication within this specific group of individuals. Methods: The study was conducted at Mardin Artuklu University, Mardin Training and Research Hospital between April 2021 and March 2023, focusing on patients with a history of secondary prevention of CVD. The study investigated prescribed cholesterol-lowering drugs, factors contributing to statin underuse, and lipid profile disclosure. Results: 872 patients were included. 86.8% received statins, 5.2% ezetimibe, and 3.4% fibrates, while 13.2% received no lipidlowering therapy. 64% of those on statins were on high doses. LDL-C values were assessed in 452 patients, with only 30% below the recommended cutoff of 70 mg/dL. Conclusion: In this investigation involving secondary prevention patients, slightly over half of the participants received highdose statins, while a negligible proportion received ezetimibe treatment. Alarmingly, over two-thirds of the patients demonstrated LDL-C values that deviated significantly from the therapeutic range, indicating a considerable gap between their lipid profiles and the recommendations set forth by clinical guidelines. [ABSTRACT FROM AUTHOR]

The high cardiovascular disease burden globally and in Australia necessitates attention on statin expenditure, the primary pharmacological intervention for cardiovascular disease risk factors. The Pharmaceutical Benefits Scheme (PBS) subsidies approved statins for Australians. Managing PBS government expenditure occurs through price control strategies of statutory price decreases upon first generic entry and price disclosure. This study investigates the impact price control measures had on statin price evolution and government expenditure between 2010 and 2022. Prescription and pricing data were obtained from Services Australia Medicare Statistics, and price reduction strategies from the PBS. Summary statistics compared and described statin price, prescription, number of brands, market share, and government expenditure to atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin price control timelines. Statin prices exposed to price control measures decreased irrespective of dosage and correlated with reductions in government expenditure, with a comparison of 2010 and 2022 showing annual statin expenditure declined by AU$833.5 million (83.25%) whereas prescriptions reduced by 3.0 million (15.7%). Effects of price disclosure on atorvastatin and rosuvastatin market share suggest industry-prompted price reductions may arise from market share loss, whereas reasons external to pricing prompted rosuvastatin to gain market share. Limited publications on contemporary effects of statin price control measures exist. This investigation found these measures reduced government expenditure for statins by AU$949.1 million, with the price reduction correlating with price control measures. In addition to affirming price control mechanisms remain effective in contemporary times, this investigation provides data for key insights into the Australian statin industry. • The high burden of cardiovascular disease globally and in Australia necessitates attention on managing statin expenditure. The price control measures described in this article have primarily been investigated internationally, with very limited publications existing on contemporary effects on statin expenditure within the Australian healthcare system. • This article contributes to this discussion by illustrating not only the reduction in expenditure upon price control application but also a plateau phase where additional cycles of price control measures are inefficient. Furthermore, this article is the first to collate the prescription number, cost, brand number, and market share by statin and dose for all Pharmaceutical Benefits Scheme subsidized statins, allowing future publications to have a complete data set. • The impact of price control measures on government expenditure for statins listed under the national Australian medication insurance scheme was analyzed between 2010 and 2022. The evaluated price control mechanisms correlated with a reduction in government statin expenditure to an estimated AU$949.1 million. This provides insight into the continued application of government mandated price control measures as a mechanism for reducing costs associated with Australia's aging population and large burden of cardiovascular disease health. [ABSTRACT FROM AUTHOR]

• Post hoc study using pooled data from two phase 3 bempedoic acid clinical trials. • Patients with and without heterozygous familial hypercholesterolemia were included. • In both groups, bempedoic acid lowered LDL-C and other lipid parameters vs. placebo. • Bempedoic acid was generally well tolerated in both patient groups. • No new safety findings in patients with heterozygous familial hypercholesterolemia. Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy. To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH. Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety. A total of 217 (bempedoic acid, 146; placebo, 71) patients with HeFH and 2,792 (bempedoic acid, 1,864; placebo, 928) without HeFH were included (mean baseline LDL-C, 172.8 mg/dL and 102.6 mg/dL, respectively). Bempedoic acid significantly lowered LDL-C at week 12 vs. placebo regardless of HeFH status (with HeFH, −21.2%; without HeFH, −18.2% [both P <0.0001]). Bempedoic acid significantly reduced other lipid parameters and high-sensitivity C-reactive protein vs. placebo regardless of HeFH status (all P ≤0.01). Among patients with HeFH treated with bempedoic acid, 32% and 27% achieved LDL-C <100 mg/dL at weeks 12 and 52, respectively. Overall treatment-emergent adverse event incidence was comparable across all four groups (74.7–77.5%). Bempedoic acid significantly lowered LDL-C levels vs. placebo and was generally well tolerated in all patients, with no new safety findings in patients with HeFH, despite more intensive lipid-lowering therapy in patients with vs. without HeFH. [Display omitted] [ABSTRACT FROM AUTHOR]

INTRODUCTION: We tested the effect of statins on C‐reactive protein (CRP) and apolipoprotein E (APOE)'s associations with dementia severity. METHODS: A total of 1725 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assigned from 12‐month follow‐up data into the following groups: (1) ε4 (–)/statin (–), (2) ε4 (–)/statin (+), (3) ε4 (+)/statin (–), and (4) ε4 (+)/statin (+). Dementia severity was assessed by a δ homolog: "dHABS." A mediation model was stratified on statin use and moderation effects tested by a chi‐square difference. RESULTS: Plasma CRP level decreased with ε4 allelic dose. Statins had no effect on the dHABS d‐score in non‐carriers but were associated with better scores in carriers. Treated carriers did not have more severe dementia than non‐carriers. Statin use moderated the mutual adjusted effects of APOE and CRP. CRP was not a mediator of APOE's effect. DISCUSSION: Statins may provide a protective effect on the dementia severity of ε4 carriers. Highlights: δ is a dementia‐specific phenotype related to general intelligence "g" and is assessed via a "d‐score."Apolipoprotein E (APOE) and plasma C‐reactive protein (CRP) are independently associated with δ.Plasma CRP decreases with ε4 allelic dose.Statins were associated with better (less demented) d‐scores in ε4 carriers but had no effect in non‐ε4 carriers.Treated ε4 carriers did not have more severe dementia than non‐carriers.Statin use moderated the effects of APOE and CRP on δ.CRP was not a mediator of APOE's effect on δ. [ABSTRACT FROM AUTHOR]

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Background and Objectives: Periodontitis is marked by the destruction of alveolar bone. Sclerostin (SOST) and dickkopf-1 (DKK-1) act as inhibitors of the Wingless-type (Wnt) signaling pathway, a key regulator of bone metabolism. Recent studies have suggested that statins play a role in bone resorption and formation by influencing Wnt signaling. The aim of this study was to determine the levels of SOST and DKK-1 in periodontal patients with and without peroral statins treatment in their therapy. Materials and Methods: A total of 79 patients with diagnosed periodontitis were divided into two groups: 39 patients on statin therapy (SP group) and 40 patients without statin therapy as a control group (P group). The periodontal clinical examination probing (pocket) depth (PD) and gingival recession (GR) were measured, and approximal plaque was detected, while vertical and horizontal bone resorption was measured using a panoramic radiograph image. Clinical attachment loss (CAL) values were calculated using PD and GR values. Gingival crevicular fluid (GCF) was collected and used for measuring SOST and DKK-1 levels. A questionnaire was used to assess lifestyle habits and statin intake. Patients' medical records were used to obtain biochemical parameters. Results: There was no significant difference in sclerostin concentration between the SP and P group. DKK-1 values were significantly higher in the SP group compared to the control group (p = 0.04). Also, PD (p = 0.001) and GR (p = 0.03) were significantly higher in the SP group. The level of DKK-1 had a positive relationship with the PD, the greater the PD, the higher the level of DKK-1 (Rho = 0.350), while there was no significant association with other parameters. Conclusions: Peroral statins in periodontal patients are associated with GCF levels of DKK-1 but not with sclerostin levels. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion The link between the pre‐diagnostic use of statins and testosterone replacement therapy and their impact on hormone‐related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone‐related cancer survival outcomes.To examine the independent and joint effects of pre‐diagnostic use of statins and testosterone replacement therapy on the risk of all‐cause and cause‐specific mortality among older men diagnosed with hormone‐related cancers, including prostate cancer, colorectal cancer, and male breast cancer.In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results‐Medicare 2007–2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre‐diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable‐adjusted Cox proportional hazards and competing‐risks (Fine‐Gray subdistribution hazard) models were conducted.No significant associations were found in Cox‐proportional hazard models for hormone‐related cancers. However, in the Fine‐Gray competing risk models among high‐grade hormone‐related cancers, statins alone had an 11% reduced risk of hormone‐related cancer‐specific death (hazard ratio: 0.89; 95% confidence interval: 0.81–0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all‐cause death (hazard ratio: 0.76; 95% confidence interval: 0.59–0.97; p 0.0325) and a 57% lower risk of prostate cancer‐specific death (hazard ratio: 0.43; 95% confidence interval: 0.24–0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub‐groups.Pre‐diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high‐grade hormone‐related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow‐up periods are needed to substantiate these findings. [ABSTRACT FROM AUTHOR]

The modern history of cholesterol-lowering drugs started in 1972 when Dr. Akira Endo identified an active compound (compactin) that inhibited cholesterol biosynthesis from the culture broth of blue–green mold (Penicillium citrinum Pen-51). Since 1987, statins have represented the milestone for the treatment of atherosclerotic cardiovascular disease. A new therapy for the treatment of hypercholesterolemia since the discovery of statins is ezetimibe, the first and only agent inhibiting intestinal cholesterol absorption. Ezetimibe was approved by the FDA in October 2002. A year later, the association between gain-of-function PCSK9 genetic mutations and hypercholesterolemia was reported, and this discovery opened a new era in lipid-lowering therapies. Monoclonal antibodies and small-interfering RNA approaches to reduce PCSK9 were developed and approved for clinical use in 2015 and 2022, respectively. Finally, the newly approved bempedoic acid, an oral adenosine triphosphate citrate lyase inhibitor that lowers LDL-C, is able to reduce major adverse cardiovascular events in both primary and secondary prevention. In the present narrative review, we summarize the pharmacological properties and the clinical efficacy of all these agents currently used for a tailored therapy of hypercholesterolemia in patients with atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Statins, widely prescribed for lipid disorders, primarily target 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase competitively and reversibly, resulting in reduced low-density lipoprotein cholesterol (LDL-C). This mechanism proves effective in lowering the risk of lipid-related diseases such as ischemic cerebrovascular and coronary artery diseases. Beyond their established use, statins are under scrutiny for potential applications in treating bone diseases. The focus of research centers mainly on simvastatin, a lipophilic statin demonstrating efficacy in preventing osteoporosis and aiding in fracture and bone defect healing. Notably, these effects manifest at elevated doses (20 mg/kg/day) of statins, posing challenges for systematic administration due to their limited bone affinity. Current investigations explore intraosseous statin delivery facilitated by specialized carriers. This paper outlines various carrier types, characterizing their structures and underscoring various statins' potential as local treatments for bone diseases. [ABSTRACT FROM AUTHOR]

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa. [ABSTRACT FROM AUTHOR]

The employment of 2-deoxyribose-5-phosphate aldolase (DERA) stands as a prevalent biocatalytic route for synthesizing statin side chains. The main problem with this pathway is the low stability of the enzyme. In this study, mesocellular silica foam (MCF) with different pore sizes was used as a carrier for the covalent immobilization of DERA. Different functionalizing and activating agents were tested and kinetic modeling was subsequently performed. The use of succinic anhydride as an activating agent resulted in an enzyme hyperactivation of approx. 140%, and the stability almost doubled compared to that of the free enzyme. It was also shown that the pore size of MCF has a decisive influence on the stability of the DERA enzyme. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% of primary liver cancer. The advent of immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized the treatment of HCC in late-stage and unresectable HCC, as ICIs alone were disappointing in treating HCC. In addition to the altered immune microenvironment, abnormal lipid metabolism in the liver has been extensively characterized in various types of HCC. Stains are known for their cholesterol-lowering properties and their long history of treating hypercholesterolemia and reducing cardiovascular disease risk. Apart from ICI and other conventional therapies, statins are frequently used by advanced HCC patients with dyslipidemia, which is often marked by the abnormal accumulation of cholesterol and fatty acids in the liver. Supported by a body of preclinical and clinical studies, statins may unexpectedly enhance the efficacy of ICI therapy in HCC patients through the regulation of inflammatory responses and the immune microenvironment. This review discusses the abnormal changes in lipid metabolism in HCC, summarizes the clinical evidence and benefits of stain use in HCC, and prospects the possible mechanistic actions of statins in transforming the immune microenvironment in HCC when combined with immunotherapies. Consequently, the use of statin therapy may emerge as a novel and valuable adjuvant for immunotherapies in HCC. [ABSTRACT FROM AUTHOR]

Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1β and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases. [ABSTRACT FROM AUTHOR]