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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.

BACKGROUND: Dyslipidemia is treated effectively with statins, but treatment has the potential to induce new-onset type-2 diabetes. Gut microbiota may contribute to this outcome variability. We assessed the associations of gut microbiota diversity and composition with statins. Bacterial associations with statin-associated new-onset type-2 diabetes (T2D) risk were also prospectively evaluated. METHODS: We examined shallow-shotgun-sequenced fecal samples from 5755 individuals in the FINRISK-2002 population cohort with a 17+-year-long register-based follow-up. Alpha-diversity was quantified using Shannon index and beta-diversity with Aitchison distance. Species-specific differential abundances were analyzed using general multivariate regression. Prospective associations were assessed with Cox regression. Applicable results were validated using gradient boosting. RESULTS: Statin use associated with differing taxonomic composition (R2, 0.02%; q=0.02) and 13 differentially abundant species in fully adjusted models (MaAsLin; q

This study aims to develop, characterize, and evaluate the best statin-loaded Collagen Silver nanoparticle-coated polycaprolactone nanofibers by electrospinning technique. The characterization and evaluation results reveal that nanofibers had shown an aligned Collagen Silver nanoparticle-coated polycaprolactone nanofibers distribution of fibers and aliment of collagen and silver nanoparticle coating material on the surface of the nanofibers. Furthermore, the electrospun nanofibers have shown no interaction between the drug and collagen and PCL polymeric material and have demonstrated controlled drug release for 360 h and significant degradation for 60 days of the study. In vitro, among the nanofiber treatment groups and the control groups, Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers have shown cell proliferation and migration of NHDF cells and blood vessel development in the CAM assay and potential anti-bacterial activity against S. aureus and E. coli. In vivo, the Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers have demonstrated improved wound recovery, reepithelization, fibroblast cell proliferation, angiogenesis, and ECM remodeling and enhanced VEGF-sprouting in the excised tissues of streptozotocin-induced diabetic rats for 7, 14, and 21 days of the study. Therefore, the developed Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers could be a promising wound-dressing platform for effectively treating and managing diabetic wounds. Highlights * Nanofiber wound dressings provide numerous structural features in biomaterials. * Polycaprolactone can release the repurposed statin molecules into the wound site in a controlled manner. * In diabetic wounds, ECM tissue remodeling stimulates repair and vessel growth. * Pravastatin has been demonstrated to improve angiogenesis and ECM secretion for wound healing in diabetic conditions. KEYWORDS diabetic wounds, electrospinning, hypoxic microenvironment, nanofibers, pro-angiogenesis, re-epithelization, wound dressing, 1 | INTRODUCTION The most prevalent cause of death in diabetic individuals is diabetic wounds. Unfortunately, the bulk of the treatment options in the market do not entirely address how [...]

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]

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]

Backgrounds and objective: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are pivotal in managing hypercholesterolemia and reducing cardiovascular risk. While rosuvastatin demonstrates superior efficacy and tolerability compared to other statins, its safety profile in elderly patients older than 75 years old with acute coronary syndrome (ACS) remains underexplored. So, the objective of this study is to evaluate the frequency of adverse reactions and investigate the efficacy of high-dose rosuvastatin on lipid profiles in elderly patients aged over 75 with ACS. Methods: In this observational study, 110 consecutive elderly ACS patients attending Modarres Hospital in Tehran, Iran, in 2019 were enrolled. The effects of high-dose rosuvastatin were assessed in elderly patients older than 75 years old by comparison of the adverse effects, lipid profile, cardiac function, and other biomarkers at the baseline and after 6 weeks of rosuvastatin therapy with a dose of 40 mg. Results: Following 6 weeks of treatment, there was a significant reduction in total cholesterol (136.2 ± 24.3 to 115.5 ± 24.0, p = 0.001) and LDL levels (72.6 ± 17.5 to 50.9 ± 18.9, p = 0.001), accompanied by a notable increase in HDL levels (38.3 ± 7.1 to 47.2 ± 7.4, p = 0.001). Cardiac function, as measured by ejection fraction (EF), significantly improved from 43.4 ± 8.8 to 48.5 ± 8.5 (p = 0.001). Adverse effects such as cramps (N = 12, p = 0.001), weakness (N = 28, p = 0.001), and anorexia (N = 12, p = 0.001) were reported but did not warrant discontinuation of therapy. Notably, no cases of jaundice were observed. Two deaths occurred due to major adverse cardiac events (MACE) during the study period, unrelated to stroke or recurrent myocardial infarction. Conclusion: Totally, high-dose rosuvastatin therapy effectively improved lipid profiles, cardiac function, and liver enzyme levels in elderly ACS patients, with manageable adverse effects. These findings underscore the importance of rosuvastatin in optimizing cardiovascular health in this vulnerable population. [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]

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]

Background: Statin therapy is widely utilized for preventing atherosclerotic cardiovascular disease, both as a primary and secondary measure. Despite the American Association for the Study of Liver Diseases' endorsement of statin use in cirrhotic patients, practitioners exhibit hesitancy, primarily due to concerns regarding hepatotoxicity. This study aimed to evaluate statin prescription patterns in cirrhotic patients by primary care physicians (PCPs) and cardiologists through a survey. Methods: A voluntary survey via Survey Monkey with nine objective-type questions was sent to 220 PCPs and 75 cardiologists within Allegheny Health Network. Survey results were collected, and a chi square test was used to compare the two groups. A P value ≤ 0.05 was considered statistically significant. Results: A total of 64 PCPs (29.1%) and 15 cardiologists (20%) completed the survey. Overall, 12.6% did not prescribe statins for primary prevention of atherosclerotic cardiovascular disease in compensated cirrhotic patients. While all cardiologists prescribed statins for secondary prevention, over 50% preferred lower-intensity options. Conversely, 14.1% of PCPs avoided statin prescriptions for secondary prevention. Cardiologists were significantly more inclined to prescribe statins, especially for cirrhosis due to metabolic dysfunction-associated steatotic liver disease compared to PCPs (73.3% vs 45.3%, P = 0.05). Conclusions: Despite increasing evidence favoring use of statins in cirrhosis for improving portal hemodynamics and decreasing ascites, hepatic encephalopathy, the incidence of hepatocellular carcinoma, and mortality, there is still hesitation on the part of prescribers for the fear of worsening liver disease. Wider dissemination of current guidelines and education practices may help to bridge this gap. [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]

Aims: Thoracic 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 results: A 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 foldchange vs. treated = +1.63 ± 0.09 fold-change; p = 0.014). Conclusion: Statins 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. [ABSTRACT FROM AUTHOR]

Metabolic syndrome refers to the pathological state of metabolic disorder of protein, fat, carbohydrate, and other substances in the human body. It is a syndrome composed of a group of complex metabolic disorders, whose pathogenesis includes multiple genetic and acquired entities falling under the category of insulin resistance and chronic low-grade inflammationand. It is a risk factor for increased prevalence and mortality from diabetes and cardiovascular disease. Cardiovascular diseases are the predominant cause of morbidity and mortality globally, thus it is imperative to investigate the impact of metabolic syndrome on alleviating this substantial disease burden. Despite the increasing number of scientists dedicating themselves to researching metabolic syndrome in recent decades, numerous aspects of this condition remain incompletely understood, leaving many questions unanswered. In this review, we present an epidemiological analysis of MetS, explore both traditional and novel pathogenesis, examine the pathophysiological repercussions of metabolic syndrome, summarize research advances, and elucidate the mechanisms underlying corresponding treatment approaches. [ABSTRACT FROM AUTHOR]

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

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Summary: Porokeratoses are a heterogenous group of autoinflammatory keratinization disorders all characterized by the presence of a cornoid lamella. In addition to gene mutations affecting the mevalonate pathway, environmental factors such as UV radiation, immunosuppression, trauma, and infection are also thought to contribute to porokeratoses. To date, there are no management guidelines or levels of evidence for commonly used pharmacologic and non‐pharmacologic treatment options for porokeratoses. Conventional treatment strategies encompass topical and systemic drugs (e.g., salicylic acid, topical glucocorticoids, and retinoids), phototherapy, laser, and surgical interventions. Better insights into the pathogenesis of porokeratoses have paved the way for the development of novel therapeutic approaches, such as topical statins or the use of monoclonal antibodies. This narrative review aims to summarize both conventional and novel treatment options, including their level of evidence, advantages, and disadvantages. [ABSTRACT FROM AUTHOR]

Background: Psoriasis, a chronic autoimmune condition, imposes significant burdens on patients' well-being. While corticosteroid medications are commonly used, their prolonged use presents risks. Statins, known for their immunoregulatory and anti-inflammatory properties, have emerged as potential alternatives. Previous reviews indicated that statins might improve psoriasis symptoms but showed inconsistent results and lacked meta-analyses that generated pooled effect estimates. Therefore, this study addresses this gap by providing a comprehensive overview of the impact of statins on psoriasis severity and quality of life (QoL) for patients with psoriasis. Methods: A thorough search of four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Science Direct) was conducted for relevant studies published before April 2024. Results: Seven studies involving 369 patients were included. This meta-analysis showed a statistically significant reduction in PASI scores at week 8 with statin treatment (MD = −1.96, 95% CI [−3.14, −0.77], p = 0.001). However, no statistically significant difference was found between statins and placebo at week 12 (MD = 0.19, 95% CI [−0.18, 0.55]). Additionally, DLQI scores indicated a significant improvement in quality of life with statins compared to placebo (MD = −3.16, 95% CI [−5.55, −0.77]). Conclusions: Statins can improve disease severity and quality of life in psoriasis patients, suggesting the potential benefits of statin therapy. However, further research is needed to determine the optimal treatment duration, address outcome heterogeneity, and explore additional benefits such as cholesterol and triglyceride reduction. [ABSTRACT FROM AUTHOR]

Primary medication non-adherence describes the situation when a first prescription for a new medication is never filled. Primary non-adherence is an important, yet understudied aspect of reduced effectiveness of pharmacotherapy. This review summarizes the frequency, impact, reasons, predictors, and interventions regarding primary non-adherence to cardiovascular/cardiometabolic drugs. The current literature reveals a high prevalence of primary non-adherence. The individual risk of primary non-adherence is determined on multiple factors, e.g., primary non-adherence of lipid-lowering drugs is higher compared to antihypertensive medications. However, the overall rate of primary non-adherence is > 10%. Additionally, this review identifies specific areas for research to better understand why patients forgo evidence-based beneficial pharmacotherapy and to explore targeted interventions. At the same time, measures to reduce primary non-adherence—once proven to be effective—may represent an important new opportunity to reduce cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in patients with diabetes; limited data suggested that statins may reduce the risk of NAFLD progression. This study aimed to examine the association between statins and the development or progression of NAFLD in veterans with diabetes. In a new-user negative control design, we conducted a retrospective propensity score (PS)-matched cohort study of patients with diabetes between 2003 and 2015. After excluding patients with other causes of liver disease, we formed PS using 85 characteristics. The primary outcome was a composite NAFLD progression outcome. Primary analysis examined odds of outcome in PS-matched cohort. Post-hoc analysis included a PS-matched cohort of statin users with intensive lowering of low-density lipoprotein-cholesterol (LDL-C) vs low-intensity lowering. We matched 34,102 pairs from 300,739 statin users and 38,038 non-users. The composite outcome occurred in 8.8% of statin users and 8.6% of non-users (odds ratio (OR) 1.02, 95% confidence interval (95% CI) 0.97–1.08). In the post-hoc analysis, intensive lowering of LDL-C compared to low-intensity showed increased NAFLD progression (OR 1.21, 95% CI 1.13–1.30). This study showed that statin use in patients with diabetes was not associated with decreased or increased risk of NAFLD progression. Intensive LDL-C lowering, compared to low-intensity LDL-C lowering, was associated with an increased risk of NAFLD progression. [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]

Objective: The appropriate use of statins plays a vital role in reducing the risk of atherosclerotic cardiovascular disease (ASCVD). However, due to changes in diet and lifestyle, there has been a significant increase in the number of individuals with high cholesterol levels. Therefore, it is crucial to ensure the rational use of statins. Adverse reactions associated with statins, including liver enzyme abnormalities and statin-associated muscle symptoms (SAMS), have impacted their widespread utilization. In this study, we aimed to develop a predictive model for statin efficacy and safety based on real-world clinical data using machine learning techniques. Methods: We employed various data preprocessing techniques, such as improved random forest imputation and Borderline SMOTE oversampling, to handle the dataset. Boruta method was utilized for feature selection, and the dataset was divided into training and testing sets in a 7:3 ratio. Five algorithms, including logistic regression, naive Bayes, decision tree, random forest, and gradient boosting decision tree, were used to construct the predictive models. Ten-fold cross-validation and bootstrapping sampling were performed for internal and external validation. Additionally, SHAP (SHapley Additive exPlanations) was employed for feature interpretability. Ultimately, an accessible web-based platform for predicting statin efficacy and safety was established based on the optimal predictive model. Results: The random forest algorithm exhibited the best performance among the five algorithms. The predictive models for LDL-C target attainment (AUC = 0.883, Accuracy = 0.868, Precision = 0.858, Recall = 0.863, F1 = 0.860, AUPRC = 0.906, MCC = 0.761), liver enzyme abnormalities (AUC = 0.964, Accuracy = 0.964, Precision = 0.967, Recall = 0.963, F1 = 0.965, AUPRC = 0.978, MCC = 0.938), and muscle pain/Creatine kinase (CK) abnormalities (AUC = 0.981, Accuracy = 0.980, Precision = 0.987, Recall = 0.975, F1 = 0.981, AUPRC = 0.987, MCC = 0.965) demonstrated favorable performance. The most important features of LDL-C target attainment prediction model was cerebral infarction, TG, PLT and HDL. The most important features of liver enzyme abnormalities model was CRP, CK and number of oral medications. Similarly, AST, ALT, PLT and number of oral medications were found to be important features for muscle pain/CK abnormalities. Based on the best-performing predictive model, a user-friendly web application was designed and implemented. Conclusion: This study presented a machine learning-based predictive model for statin efficacy and safety. The platform developed can assist in guiding statin therapy decisions and optimizing treatment strategies. Further research and application of the model are warranted to improve the utilization of statin therapy. [ABSTRACT FROM AUTHOR]

Objective: To detect muscular system adverse reaction signals of sacubitril/valsartan treatment combined with statins (atorvastatin, rosuvastatin, simvastatin) to provide a reference for clinical administration. Methods: Multiplicative and additive models were used to mine the FDA's spontaneous reports database to detect signals of drug-drug interactions between sacubitril/valsartan and statins. SAS 9.4 software was used to conduct statistical tests for suspicious signals to determine whether the signals were statistically significant. Results: A total of 8,883,870 adverse reaction reports were analyzed. The combinations "sacubitril/valsartan - simvastatin - musculoskeletal muscle pain" had statistically significant correlation signals in both models (P < 0.05). The combination "sacubitril/valsartan - atorvastatin - myopathy" and "sacubitril/valsartan-simvastatin - myopathy" had statistically significant correlation signal in the multiplicative model (P < 0.05). Conclusion: Compared with a single drug, coadministration of sacubitril/valsartan with atorvastatin may increase safety risks to myopathy, with simvastatin may increase safety risks to the musculoskeletal pain and myopathy, which should be closely monitored in clinical practice. [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: Statins are widely used in cardiovascular disease (CVD) as a common lipid-lowering drug, while quinolones are widely used for the treatment of infectious diseases. It is common to see CVD in combination with infectious diseases, therefore it is often the case that statins and quinolones are used in combination. Data suggest combinations of statin and quinolone may be associated with potentially life-threatening myopathy, rhabdomyolysis and acute hepatitis. This systematic review aims to characterize data regarding patients affected by the statin-quinolone interaction. Methods: The purpose of this systematic review was to collect and evaluate the evidence surrounding statin-quinolone drug interactions and to discuss related risk mitigation strategies. The following databases were searched: PubMed (Medline), Embase, Scopus, and Cochrane Library. The systematic electronic literature search was conducted with the following search terms. In this study, three types of search terms were used: statins-related terms, quinolones-related terms, and drug interactions-related terms. Results: There were 16 case reports that met the criteria for qualitative analysis. Patients were involved in the following adverse reactions: rhabdomyolysis (n = 12), acute hepatitis (n = 1), muscle weakness (n = 1), hip tendinopathy (n = 1), or myopathy (n = 1). In the included literature, patients vary in the dose and type of statins they take, including simvastatin (n = 10) at a dose range of 20–80 mg/d and atorvastatin (n = 4) at a dose of 80 mg/d. There were 2 patients with unspecified statin doses, separately using simvastatin and atorvastatin. The quinolones in combination were ciprofloxacin (n = 9) at a dose range of 800–1500 mg/d, levofloxacin (n = 6) at a dose range of 250–1000 mg/d, and norfloxacin (n = 1) in an unspecified dose range. 81% of the case patients were over 60 years of age, and about 1/3 had kidney-related diseases such as diabetic nephropathy, post-transplantation, and severe glomerulonephritis. Nearly two-third of the patients were on concomitant cytochrome P450 3A4 (CYP3A4) inhibitors, P-glycoprotein (P-gp) inhibitors, or organic anion transporting polypeptide 1B1 (OATP1B1) inhibitors. Conclusion: Patients treated with statin-quinolone combination should be monitored more closely for changes in aspartate aminotransferase or creatine kinase (CK) levels, and muscle symptoms, especially in patients with ciprofloxacin or levofloxacin, with simvastatin and high-dose atorvastatin, over 60 years of age, with kidney-related diseases, and on concomitant CYP3A4 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Statins were regarded as a main medication for managing hypercholesterolemia. Administration of statin therapy could reduce the incidence of cardiovascular disease in individuals diagnosed with type 2 diabetes mellitus (DM), which was recognized by multipal clinical guidelines. But previous studies had conflicting results on whether the long-term use of statins could benefit the renal function in diabetic patients. Aim: To evaluate the association between statin treatment and Chronic Kidney Disease in DM patients. Methods: This is a retrospective disproportionality analysis and cohort study based on real-world data. All DM cases reported in US Food and Drug Administration adverse event reporting system (FAERS) between the first quarter of 2004 and the fourth quarter of 2022 were included. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). We further compared the CKD odds ratio (OR) between the statins group and the other primary suspected drug group among the included diabetes mellitus cases. Results: We finally included 593647 DM cases from FAERS, 5113 (5.31%) CKD cases in the statins group and 8810 (1.77%) CKD cases in the control group. Data analysis showed that the statins group showed a significant CKD signal (ROR: 3.11, 95% CI: 3.00-3.22; IC: 1.18, 95% CI: 1.07-1.29). In case group with two or more statins treatment history, the CKD signal was even stronger (ROR: 19.56, 95% CI: 18.10-21.13; IC: 3.70, 95% CI:3.44-3.93) compared with cases with one statin treatment history. Conclusion: The impact of statin therapy on the progression of renal disease in individuals diagnosed with type 2 diabetes mellitus (DM) remains inconclusive. After data mining on the current FAERS dataset, we discovered significant signals between statin treatment and CKD in diabetic patients. Furthermore, the incidence rate of CKD was higher among DM patients who used statins compared to those who did not. [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]

• Only 27% patients with Non-Alcoholic Fatty Liver Disease (NFALD) received statins. • Statin therapy was not associated with elevated liver enzyme levels. • ALT, total cholesterol, and LDL were significantly lower in statin users. • Findings demonstrate statin use in patients with NAFLD can reduce CVD risks. • Findings were generalized to the US population. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Statins are recommended for treatment of dyslipidemia to reduce the overall cardiovascular risk in patients with NAFLD. However, statin treatment was underutilized and the effect of statins on liver enzymes remained unclear in this patient population. This study aimed to provide real-world evidence of the safety and effect of statin use in patients with NAFLD. We conducted a cross-sectional survey study of adults with NAFLD using pooled data from the US NHANES database 2009–2018. NAFLD was defined by Fatty Liver Index (FLI) ≥ 60 and United States Fatty Liver Index (USFLI) ≥ 30. Multivariate regression analyses adjusted for baseline clinical and demographic characteristics were performed to compare the liver enzymes and lipid profile between statin and non-statin users. The study included 2,533 adults with NAFLD, representing 22.6 million individuals in the US, with 27% receiving statin treatment between 2009 and 2018. The mean differences of liver enzymes for AST, ALT, ALP, and GGT between statin and non-statin users were -0.86 (p=0.539), -3.49 (p=0.042), -0.25 (p=0.913), and 0.57 (p=0.901), respectively. In individuals with NAFLD and dyslipidemia, total cholesterol and LDL levels were significantly lower in statin users compared to non-statin users (mean difference, -28.9; p<0.001 and -27.7; p<0.001). The use of statins was not associated with elevated liver enzymes in patients with NAFLD. Significantly lower levels of ALT, total cholesterol, and LDL were observed in statin users compared to non-statin users. [ABSTRACT FROM AUTHOR]

Simvastatin, a semisynthetic drug widely used to lower cholesterol, is among the most prescribed statins worldwide. This study focuses on the direct production of a simvastatin-like biomolecule using alternative substrates by Aspergillus spp. strains. Two species, A. terreus UCP 1276 and A. flavus UCP 0316, were initially evaluated in synthetic media as control. Subsequently, the carbon and nitrogen sources were replaced by agro-industrial substrates, resulting in five modified media. Cultures were maintained at 28 °C, pH 6.5, at 180 rpm for 21 days. Fungal growth kinetics were evaluated and a 23 full-factorial design (FFD) was used to investigate the influence of substrate concentration on statin yield. Presence of inhibitors was confirmed by bioassay, UV–visible spectrophotometry, and thin-layer chromatography (TLC). According to the results, A. flavus UCP yielded 0.24 mg/g of statin in condition 2 of FFD (medium containing 4.5% soluble starch and saline base), suggesting it as a promising candidate for direct production of the biomolecule. Statistical analysis showed the significant effect of soluble starch on inhibitor production, making it a viable and profitable alternative substrate. Moreover, the isolated statin exhibited broad-spectrum antimicrobial activity, including efficacy against Gram-negative and Gram-positive bacteria and yeasts, indicating therapeutic potential against antimicrobial resistance. [ABSTRACT FROM AUTHOR]

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