To investigate the direct and indirect relationships between statin use, low-density lipoprotein cholesterol (LDL-C) levels, and intracerebral hemorrhage (ICH), providing new insights into this complex scientific question.

In this cohort study, UK Biobank data from 2006 to 2010 were used to construct Structural Equation Models of statin use, LDL-C, and ICH, including 414,253 participants with LDL-C data. Published Genome-Wide Association Studies data were used for drug-target Mendelian Randomization analysis.

The study included 414,253 participants, comprising 225,454 women (54.4%) with a mean age of 56.07 (8.11) years. During a median follow-up of 14.01 years, 2973 patients experienced ICH. Structural Equation Modelling showed the indirect effect (path a∗b) of statin on ICH was 0.003 (P < 0.001), the direct effect (path c') was -0.001 (P = 0.568), the total effect (path c) was 0.002 (P = 0.391), and the mediation proportion of LDL-C (a∗b/c) was 150.0%. Mendelian Randomization showed a negative association between LDL-C levels and ICH (β: -0.663, SE: 0.229, P = 0.004), with no causal relationship between statin use and ICH (β: -1.454, SE: 3.133, P = 0.643). Drug-targeted Mendelian Randomization revealed LDL-C levels, predicted by variants in or near HMGCR, PCSK9, CETP, ABCG8/5, and LAP, were negatively associated with ICH risk.

This study confirmed that statins increase the risk of ICH primarily through their LDL-C-lowering effects, rather than the direct effects of the statins themselves. LDL-C is negatively associated with ICH, an association not confined to the effects of the HMGCR loci. This advance provides evidence for the controversy between statin use, LDL-C levels, and ICH risk.

Future long-duration crewed space missions beyond Low Earth Orbit (LEO) will bring new healthcare challenges for astronauts for which pharmacological countermeasures (pharmacological countermeasures) are crucial. This paper highlights current pharmacological countermeasures challenges described in the ESA SciSpacE Roadmap, with a focus on the cardiovascular system as a model to demonstrate the potential implication of the challenges and recommendations. New pharmacological approaches and procedures need to be adapted to spaceflight (spaceflight) conditions, including ethical and reglementary considerations. Potential strategies include combining pharmacological biomarkers such as pharmacogenomics with therapeutic drug monitoring, advancing microsampling techniques, and implementing a pharmacovigilance system to gain deep insights into pharmacokinetics/pharmacodynamics (PK/PD) spaceflight alteration on drug exposure. Emerging therapeutic approaches (such as long-term regimens) or manufacturing drugs in the space environment, can address specific issues related to drug storage and stability. The integration of biobanks and innovative technologies like organoids and organ-on-a-chip, artificial intelligence (AI), including machine learning will further enhance PK modelling leading to personalized treatments. These innovative pharmaceutical tools will also enable reciprocal game-changing healthcare developments to be made on Earth as well as in space and are essential to ensure space explorers receive safe effective pharmaceutical care.

This study investigates the effects of prolonged simvastatin exposure on coenzyme Q9/10 (CoQ9/10) levels, an essential component of antioxidant defense, in cultured cardiac cells. Statins, commonly used to manage dyslipidemia and reduce cardiovascular risk, may impair mitochondrial function, but their impact on CoQ10 depletion and oxidative stress is not well understood. We examined the influence of simvastatin on mitochondrial oxidative capacity, reactive oxygen species (ROS) production, and CoQ9/10 status at concentrations of 0.3, 0.6, 1.25, 2.5, 5, 10, and 20 μM, over durations of 24, 48, and 72 h. Using an in vitro model of cultured H9c2 cardiomyoblasts, our results showed that short-term exposure (24 h) at lower concentrations (<5 μM) enhanced cytosolic and mitochondrial ROS levels without affecting mitochondrial function or CoQ9/10 status. However, prolonged exposure to higher concentrations (≥10 μM for >48 h) resulted in impaired mitochondrial oxidative capacity, indicated by increased proton leak and elevated ROS levels, which were followed by significantly reduced cell viability. These findings suggest that prolonged, high-dose simvastatin exposure may disrupt the oxidative balance of CoQ9/10, leading to myocardial injury. This research addresses a gap in understanding the long-term effects of statins on mitochondrial health and underscores the need for further studies to optimize statin therapy and minimize adverse effects on myocardial function.

Spinal cord trauma represents a significant clinical challenge, and improving patient outcomes is a main priority for many scientific teams globally. Despite advances in the understanding its pathogenesis, the overall mechanisms occurring in the spinal cord after traumatic injury remain unclear. This study explores the possible synergistic effects of a regenerative therapy that combines electrical stimulation with the anti-inflammatory drug Atorvastatin (ATR) after spinal cord injury (SCI). SCI was induced at the T9 segment under isoflurane anesthesia and applying a compression force of 40 g for 15 minutes. An oscillating field stimulator (OFS) was implanted subcutaneously, delivering a weak electric current (50 µA) that changed polarity every 15 minutes for six weeks to promote axonal growth at the injury site. Female Wistar albino rats were divided into four groups: SCI with non-functional stimulator (SCI + nOFS), SCI with functional stimulator (SCI+OFS), and two groups that received ATR together with stimulator for 7 days after injury (SCI+OFS+ATR, SCI+nOFS+ATR). Behavioral tests (hot-plate test and BBB scale) showed improvement in sensory and motor performance in animals treated with the combination therapy. The protein levels of astrocytes (GFAP), neurofilaments (NF-L), newly sprouting axons (GAP-43), and oligodendrocytes (PLP -1, CNPase) were analysed by Western blot. The results showed increased neurofilaments, newly sprouting axons and oligodendrocytes in groups receiving both individual and combination therapies, with a decrease in their concentrations in the following order: SCI+OFS+ATR, SCI+nOFS+ATR, SCI+OFS, SCI+nOFS. In addition, astrocyte protein levels were lower in the SCI+OFS+ATR group compared with others. Histological analysis showed a significant reduction in white and gray matter after SCI, but less white and gray matter volume loss was found in the groups receiving therapies (SCI+OFS+ATR, SCI+nOFS+ATR, SCI+OFS). These results suggest that the combination of Atorvastatin with OFS stimulation promotes neural recovery after SCI, highlighting the potential of combination therapies in enhancing regenerative outcomes.

Clarify the relationship between the use of statins and the risk of dementia, and further guide the clinical application of statins. This paper uses computer search Chinese and foreign language databases Pubmed, Medline, Cochrane, Embase, Web of Science, Weipu, CBM, Wanfang, CNKI, etc., to include the literature that meets the standards from the establishment of the library to December 2020, and uses Revman 5.1 software and Stata15.0 software for meta-analysis. Of the 34 included observational studies, stratified subgroup analyses were performed based on the type of clinical trial, sex of participants, presence or absence of apolipoprotein E-4 (ApoEε4) allele, and duration of use. The conclusions showed that (1) the use of statins can significantly reduce the risk of dementia; (2) There is no significant sex difference in reducing the risk of dementia; (3) Continuous use of statins for ≥ 1 year can significantly reduce the risk of dementia compared with the time of taking the drug for < 1 year; (4) Compared with subjects with negative ApoEε4 allele, the use of statins has a more significant effect on reducing the risk of dementia in subjects carrying the ApoEε4 allele.

While numerous studies have extensively documented the pleiotropic effects of statins, including their capacity to reduce inflammation, there is a lack of research estimating the anti-inflammatory effectiveness of statins among individuals with chronic diseases. This meta-analysis evaluates the effect of statin therapy on inflammatory markers and the lipid profile in patients with chronic diseases by analysing evidence from randomized controlled trials (RCTs). We conducted a systematic review and searched articles published between 1st January 1999 and 31st December 2023 in databases including PubMed, Web of Science, Scopus, and Cochrane. The meta-analysis was performed using random effects models and inverse variance. Effect measures were mean differences (MD) and 95% confidence intervals (CI). Collectively, statins significantly reduced IL-6 (MD = -0.24 ng/dL [95% CI, -0.36 to -0.13], I2 = 98.3%, p < 0.001), TNF-α (MD = -0.74 ng/dL [95% CI, -1.08 to -0.40], I2 = 98.8%, p < 0.001); and CRP (MD = -1.58 mg/L [95% CI, -2.22 to -0.94], I2 = 86.5%, p < 0.001). Notably, atorvastatin demonstrated the most significant reduction in IL-6 and TNF-α levels, while fluvastatin and rosuvastatin displayed the greatest impact on decreasing CRP and LDL-C levels, respectively. Stratification by a longer treatment duration of more than four months revealed that atorvastatin achieved the most significant reduction in IL-6 and TNF-α. In conclusion, statin therapy not only regulates the lipid profile but also reduces systemic inflammatory biomarkers. Prolonged administration of statins led to a more substantial reduction in IL-6 and TNF-α, with atorvastatin exhibiting the greatest effect in our analysis.

Chemotherapy-induced cardiomyopathy (CICM) is a critical adverse consequence associated with chemotherapeutic treatments such as anthracyclines, taxanes, and alkylating agents. Cardiac dysfunction, characterized by left ventricular systolic dysfunction, is the primary effect found in these patients. This may result in heart failure, with heart failure related to chemotherapy resulting in a 3.5-fold increased risk of mortality compared with idiopathic cardiomyopathy alone. Multiple factors, including oxidative stress, inflammation, and disruption of key cellular pathways, are involved in cardiomyocyte damage and influence CICM pathophysiology. So far, dexrazoxane is the sole FDA-approved preventive therapy, but alternative interventions, such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins, have been studied for their cardioprotective potential. Statins, beyond their cholesterol-lowering capabilities, stand out for their pleiotropic effects, including antioxidant, anti-inflammatory, and endothelial-protective actions, which counteract inflammatory effects. Multiple studies and meta-analyses suggest that statin therapy may decrease both the incidence and severity of chemotherapy-related cardiotoxicity (CTX), as evidenced by smaller declines in left ventricular ejection fraction and lower rates of heart failure in statin-treated patients. However, not all investigations confirm these protective benefits; for instance, some trials, including SPARE-HF, reported no significant differences in cardiac outcomes. While these conflicting findings underscore the need for larger randomized trials, they also reflect the heterogeneity of cancer types, chemotherapy regimens, and patient profiles. Statins show promise as a cardioprotective strategy for individuals at risk of CICM. Enhancing patient selection and specifying the timing and duration of statin therapy are essential steps for incorporating these agents into standard care. Optimizing these parameters may reduce chemotherapy-related cardiac damage, improve long-term cardiac function, and enhance overall survival in cancer survivors.

All commonly prescribed statins have been reported to cause reversible memory loss within weeks of therapy, though the exact molecular mechanism remains unknown. However, whether therapeutic concentrations of statins can directly regulate the contractility of resistance cerebral arteries that control cerebrovascular perfusion remains unexplored. Here, we examined the acute vascular effects of statins on rat cerebral arteries and the underlying molecular mechanisms. Our pressure myography data demonstrate that, at therapeutically-relevant nanomolar concentrations, statins produced a robust and rapid vasoconstriction, appearing within 2-3 min of drug application. Interestingly, such vasoconstriction was largely absent in female rat cerebral arteries. Endothelial denudation or mevalonate supplementation did not alter statin-induced vasoconstriction, suggesting an endothelium- and cholesterol-independent mechanism. In contrast, such vasoconstriction was abolished upon removal of extracellular Ca2+, pharmacological blockade of the smooth muscle cell voltage-gated Ca2+ channel, CaV1.2, or siRNA knockdown of CaV1.2 - all of which reduced [Ca2+]i, indicating that Ca2+ entry through CaV1.2 plays a critical role in cerebral artery vasoconstriction. Arterial biotinylation revealed that acute statin exposure did not alter the surface expression, distribution, or function of CaV1.2 channels. Altogether, our data unveil an unexpected role of statins in rapidly inducing constriction of resistance cerebral arteries by directly stimulating CaV1.2 in smooth muscle cells. These findings offer a plausible explanation for statin-associated reversible memory impairment, its mitigation by calcium channel blockers, and why such effects may not be observed in all subjects, particularly those concurrently taking antihypertensive agents.

High-density lipoproteins (HDLs) are heterogeneous particles with pleiotropic functions including anti-inflammatory and anti-infectious effects. In clinical studies, lower HDL-associated cholesterol (HDL-C) concentration has been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and mortality. A reduction in the number of HDL particles, particularly small ones has been observed with alterations in their protein and lipid composition impairing their functions. These observations have supported HDL supplementation with promising results in small preliminary studies. This review summarizes available evidence to better understand the two-way interaction between HDLs and Coronavirus disease 2019 (COVID-19) and guide future HDL-based therapies for preparing for the next pandemic.

The widespread use of statin therapy for hypercholesterolemia has raised concerns due to its associated risk of inducing diabetes. Biochanin-A (BA), an isoflavone, exhibits potential in preventing diabetes and hyperlipidemia, yet its efficacy in mitigating statin-induced diabetes remains unexplored. This gap prompts a crucial inquiry: Can BA reduce the risk of diabetes associated with statin therapy? The present study investigated the molecular mechanisms behind atorvastatin's diabetogenic nature and evaluated the potential of BA to counteract these effects. Insulin resistance was assessed using L6 skeletal muscle cells and pancreatic beta cell apoptosis in MIN-6 cells. Our hypothesis posits that atorvastatin exacerbates free fatty acid accumulation, leading to the downregulation of sirtuin-1 (SIRT-1) and decreased uncoupling protein (UCP) 3 expression, culminating in insulin resistance. Conversely, BA is assumed to positively modulate SIRT-1 and downregulate UCP2, thus offering a protective effect. In vitro studies using L6 and MIN-6 cells revealed that BA has increased cell viability and shown optimal protection against the toxicity induced by atorvastatin in both cell lines at different concentrations. BA effectively inhibited the reduction in glucose uptake caused by atorvastatin. Pre-treatment with BA upregulated proteins that are involved in the insulin-signaling pathway and reversed the expression levels of UCPs induced by atorvastatin. BA also enhanced insulin release, preserved mitochondrial function, and prevented atorvastatin-induced apoptosis. Furthermore, BA improved SIRT-1 expression, potentially through the nicotinamide phospho-ribosyl-transferase-nicotinamide adenine dinucleotide + SIRT1-pathway, revealing that BA may play a role in modulating cellular processes in statin-associated SIRT-1 downregulation. BA can be considered a promising molecule to counteract statin-induced diabetes, suggesting a prospective therapeutic role in enhancing the safety profile of statin therapy. This research lays the groundwork for future clinical evaluations of BA as an adjunctive treatment for patients at risk of statin-induced diabetes.

Anticoagulation is frequently required for patients with systemic lupus erythematosus (SLE), given their high prevalence of cardiovascular disease and thrombosis, due to the complexity of disease pathophysiology, some overlap with antiphospholipid syndrome (APS), comorbidities, prevalent cardiovascular risk factors and treatment complications.

This article outlines the epidemiology and pathophysiology of cardiovascular disease and arterial and/or venous thrombosis in SLE, with/without APS. We discuss common cardiovascular comorbidities and thrombotic disorders that may present as a complication of SLE and/or APS and highlight recommendations in current guidelines for anticoagulation management, alongside relevant disease-specific considerations. We specifically comment on the use of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in these patients.

Assessment of cardiovascular risk and aPL profile is paramount in SLE patients. While warfarin is preferred in high-risk APS patients, DOACs can be used in a selected group of SLE and/or APS patients with VTE and no prior history of arterial thrombosis. Initiating anticoagulation in the setting of Catastrophic APS (CAPS) can be extremely challenging. Knowledge gaps remain regarding the management of patients with recurrent arterial and/or venous thrombosis despite anticoagulation. Research is needed to optimize strategies to reduce thrombotic events in APS patients.

Dementia is a heterogeneous syndrome characterized by the progressive deterioration of various brain functions, severely impacting cognitive, emotional, and social abilities. According to a World Health Organization (WHO) report, dementia represents a pressing global health concern, with the number of affected individuals projected to triple by 2050. Among its various subtypes, vascular dementia (VD) stands as the second most common form, following Alzheimer's disease (AD). Despite ongoing efforts in drug development, no pharmaceutical entity has yet received approval from the U.S. Food and Drug Administration (FDA) for the treatment of VD. Emerging evidence underscores the critical involvement of the brain's Renin-Angiotensin System (RAS) in the pathogenesis of multiple neurodegenerative disorders, including VD. The intricate roles of RAS components include regulating vascular tone, neuronal growth and survival, regulating cerebral blood flow and endothelial dysfunction, increasing neuroinflammation (by increasing release of IL-1, IL-6, TNF-α, microglial activation), oxidative stress and destruction of BBB integrity, mainly through Angiotensin II type 1 (AT1) and type 2 (AT2) receptors, are of significant interest in the pathophysiology of VD. However, disruptions in these signaling pathways are believed to contribute substantially to the progression of VD. This review addresses the limitations of current therapeutic approaches for VD while emphasizing the untapped potential of RAS-targeted interventions. We systematically explore the neurophysiological mechanisms of brain RAS, their role in promoting neuronal health, and the factors that compromise these pathways, ultimately leading to cognitive decline. By elucidating these mechanisms and challenges, the review offers novel insights into designing innovative RAS-based therapeutic strategies, paving the way for effective clinical management of VD. This work aspires to stimulate further research and development in this underexplored yet promising domain.

Although numerous drugs have been associated with cataracts, the risk for most drugs remains unclear. This study aimed to investigate the risk factors for drug-induced cataracts by analyzing large-scale data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

We used the reporting odds ratio (ROR) to evaluate reports of drug-induced cataracts in FAERS from the first quarter of 2004 to the third quarter of 2024. A univariate analysis, LASSO (least absolute shrinkage and selection operator) regression, and a multivariate regression analysis were performed to identify drug-related risk factors for cataracts, and Bonferroni correction was applied for multiple comparisons.

Multivariate logistic regression ultimately identified 15 drugs as independent risk factors, including immunomodulators (6/15), antineoplastic drugs (3/15), psychotropic drugs (1/15), respiratory drugs (1/15), gastrointestinal drugs (1/15), orthopedic drugs (1/15), metabolic regulators (1/15), and ophthalmic drugs (1/15). The median time to onset of drug-induced cataracts was 449 days (interquartile range [IQR]: 150-901 days), with approximately 75% of adverse events occurring within 747 days.

These findings may help clinicians detect drug-related cataracts at an early stage and provide valuable insights for future research on the mechanisms of drug-induced cataracts.

Statin use has been consistently associated with improved clinical outcomes (especially recurrence) in breast cancer in multiple observational studies backed by compelling preclinical evidence. The strength of this evidence warrants a clinical trial to test the efficacy of statin exposure on breast cancer recurrence.

The double-blind, phase III, randomized, placebo-controlled MASTER (MAmmary cancer STatins in ER positive breast cancer) trial includes women diagnosed with early-stage, estrogen receptor-positive (ER+) breast cancer who are candidates for systemic (neo)adjuvant therapy. Enrolled patients are given standard (neo)adjuvant therapy and additionally randomized to either atorvastatin (80 mg/day) or placebo for two years. The trial's primary outcome is invasive disease-free survival (IDFS), with a target accrual of 3360 patients in total to achieve 80% power (two-sided alpha=0.05) to detect a 25% reduction in the risk of an IDFS event comparing the statin and placebo arms. At 3-, 6-, 12-, and 24-month follow-up time points, patients will have blood drawn for biomarker studies, answer patient-reported outcome (PRO) questionnaires, and control for adverse events. Subsequently, patients will receive annual PRO-criteria for Adverse Events (CTCAE) questionnaires until the completion of their 10 years of follow-up. Secondary endpoints include additional clinical endpoints; pathological response (neo-adjuvant treated patients), recurrence-free survival, distant-recurrence-free interval, overall survival and cardiac death-free interval, co-morbidity, and health-related quality-of-life measured by PRO-CTCAE questionnaires during and beyond study medication. Translational endpoints are evaluated in collected blood- and tumor samples.

If a protective effect of statins on breast cancer recurrence is supported by evidence from the MASTER trial, then the indications for a safe, well-tolerated, and inexpensive treatment can be expanded towards improved clinical outcomes for breast cancer patients.

To evaluate the impact of statins on CHD prevention, role of CAC scoring and CCTA in guiding statin therapy for both primary and secondary prevention in ASCVD. Coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) have emerged as vital non-invasive imaging tools for refining cardiovascular risk assessment and guiding statin therapy in patients with atherosclerotic cardiovascular disease (ASCVD). CAC scoring helps stratify patients based on subclinical atherosclerosis burden, while CCTA provides detailed insights into plaque composition and distribution. Multiple studies, including the Multi-Ethnic Study of Atherosclerosis (MESA) and the CONFIRM registry, have demonstrated the utility of CAC scoring in identifying individuals at risk of major adverse cardiovascular events (MACE) and guiding personalized statin therapy. CAC scores, categorized into risk-based thresholds, enable clinicians to determine when statins should be initiated or deferred. CCTA complements CAC scoring by assessing plaque characteristics, including non-calcified plaque (NCP), calcified plaque, and high-risk features such as low-attenuation plaques, spotty calcifications, and positive remodeling. Serial CCTA imaging has further highlighted the effect of high-intensity statin therapy on plaque progression, demonstrating reductions in NCP and stabilization through increased calcification. CAC scoring effectively identifies patients with subclinical atherosclerosis who would benefit from statin therapy, particularly those with CAC scores > 100 or in the ≥ 75th percentile for age and sex. Statin therapy has been shown to promote plaque stabilization by increasing calcified plaque volume while reducing the progression of non-calcified plaques, thereby mitigating the risk of plaque rupture. CCTA provides additional value by identifying vulnerable plaque features and monitoring the impact of statin therapy over time. Studies have demonstrated significant reductions in total plaque volume and low-attenuation plaques in patients undergoing intensive lipid-lowering therapy, reinforcing the role of CCTA in guiding statin decisions for patients with established ASCVD. CAC scoring serves as a powerful tool to refine risk stratification and guide statin therapy initiation, particularly in asymptomatic individuals. CCTA enhances this approach by providing comprehensive plaque assessment and monitoring the response to statin therapy. Integrating CAC scoring and CCTA into clinical practice allows for a personalized approach to ASCVD management, improving patient outcomes through optimized statin therapy and targeted risk reduction.

There is an urgent need for antiviral compounds effective against currently known and future viral threats. The development of host-targeting antivirals (HTAs) appears as an alternative strategy to fight viral infections minimizing the potential of resistant mutant development and potentially leading to the identification of broad-spectrum antiviral agents. Among the host factors explored for HTA strategy, lipids constitute an attractive target as many viruses, even genetically diverse, hijack specific lipids during their lifecycle. Multiple repurposing efforts have been performed to analyze the antiviral properties of lipid-targeting compounds. These studies include the analysis of the effects of cholesterol lowering drugs such as statins, cholesterol transport inhibitors, sphingolipid modulators, de novo lipogenesis inhibitors blocking fatty acid synthesis, compounds targeting glycerophospholipids or drugs interfering with lipid droplet metabolism. This review is focused on the current status of lipid-based or lipid-targeting antiviral strategies and their potential for the development of antiviral therapies, with special emphasis on those studies that have reached advanced stages of development such as efficacy studies in animal models or clinical trials. Whereas there is still a long way to go, multiple proof-of-concept studies and clinical evidence reinforce the therapeutic potential of these strategies warranting their further development into effective antiviral therapies.

Non-traumatic osteonecrosis is a frequent complication in patients with autoimmune disorders, though its prevalence varies markedly depending upon the type of disorder. Understanding the causes of this difference can help uncover the underlying pathophysiology of osteonecrosis and guide the development of effective preventive and therapeutic strategies.

In this perspective study, we reviewed available databases, including PubMed, Cochrane Library, Scopus, and Web of Science, to explore why the risk of osteonecrosis varies among different autoimmune disorders. Is this variation primarily due to the disease's pathophysiology, the use of medications such as corticosteroids, or a combination of both? If both factors are involved, what is the extent of each contribution in this context?

Non-traumatic osteonecrosis is often induced by an interaction between disease pathophysiology and corticosteroid use. In patients with different autoimmune disorders but an identical history of corticosteroid use, the risk of osteonecrosis is influenced by how the underlying pathophysiology compromises bone health. In autoimmune disorders with multiple adverse effects on bone, such as SLE (systemic lupus erythematosus), there is a much higher risk of osteonecrosis compared to disorders with minimal impact on bone health, such as celiac disease and MS (multiple sclerosis).

The effect of statin therapy on kidney function among older adults is unclear.

To examine the association between statin use and changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), positive or negative, in an older adult cohort with versus without chronic kidney disease (CKD) at baseline.

This analysis included 18,056 participants aged ≥65 years with versus without CKD at baseline in a randomized trial of low-dose aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially. Outcome measures included eGFR and UACR. Linear mixed-effects models were used to estimate the associations of baseline statin use versus no use with eGFR and UACR changes over time. The inverse-probability of treatment-weighting technique was used for all analyses to address confounding by indication due to the lack of randomization in treatment assignment.

Statin use was not associated with change in eGFR, UACR, or incident CKD in participants with or without CKD at baseline (p > 0.05 for all associations). Subgroup analyses found no significant interactions between statin and age, sex, diabetes, country, and frailty status on any of the study outcomes.

Among adults ≥65 years of age, with and without CKD, statin therapy was not associated with improved or worsened kidney function. This data suggests that the decision to use versus not use statins in this population may be ideally guided by factors other than kidney health.

The triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index, calculated as TG divided by HDL-C, has been suggested as a predictor of cardiovascular disease (CVD). We investigated the association between the TG/HDL-C index and CVD events in type 2 diabetes mellitus (T2DM) patients with retinopathy and hyperlipidemia but no known CVD, enrolled in the EMPATHY study, which compared intensive and standard statin therapy (targeting LDL-C levels < 70 mg/dL and ≥ 100 to < 120 mg/dL, respectively). A total of 4665 patients were divided into high (TG/HDL-C ≥ 2.5, n = 2013) and low (TG/HDL-C < 2.5, n = 2652) TG/HDL-C index groups. During a median follow-up of 36.8 months, 260 CVD events occurred. The high TG/HDL-C index group had higher CVD risk than the low group (HR 1.89, 95% CI 1.45-2.47, p < 0.001). This association remained consistent across subgroups. A trend toward interaction between TG/HDL-C index and statin treatment allocation for CVD risk was observed (p for interaction = 0.062). Intensive statin treatment reduced CVD risk in the high TG/HDL-C group but not in the low group. In conclusion, a TG/HDL-C index ≥ 2.5 was associated with higher CVD risk in T2DM patients with retinopathy and hyperlipidemia without a history of CVD. The TG/HDL-C index may identify patients who benefit from intensive statin treatment.

Cardiovascular drugs are widely used for the prevention and treatment of various cardiac and vascular disorders. However, some of these drugs can also cause adverse effects on the kidney, leading to acute or chronic renal dysfunction, electrolyte imbalances, and increased mortality. The mechanisms of drug-induced renal toxicity vary depending on the type and class of the drug, the dose and duration of exposure, and the patient's characteristics and comorbidities. In this review, we summarize the current knowledge on the renal effects of some common cardiovascular drugs, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, antiplatelet agents, anticoagulants, and statins and proton-pump inhibitors. We also discuss the clinical implications and management strategies for preventing or minimizing drug-induced nephrotoxicity, as well as the potential role of oxidative stress in its pathogenesis.

The purpose of this study was to create a risk score for 30-day and 1-year mortality after major lower extremity amputation to facilitate clinical expectations and the identification of patients in need of heightened vigilance in longitudinal care.

In the Vascular Quality Initiative, 25,150 patients were identified who underwent lower extremity amputation. Two primary outcomes were investigated: 30-day mortality after major lower extremity amputation and 1-year mortality after amputation. Univariable analysis for the 30-day and 1-year mortality analysis was conducted with χ2 analysis. Significant (P < .05) univariable factors were then included in binary logistic regression analysis to perform multivariable investigation toward the outcomes. Variables that achieved multivariable significance (P < .05) for the outcomes were then used in the respective risk scores with the regression beta coefficient being used to weigh the variables.

Overall, 7.2% of patients experienced 30-day mortality and 22.4% suffered mortality within 1 year. Variables with a significant multivariable association (P < .05) with 1-year mortality were female sex, advancing age, body mass index less than 20 kg/m2, coronary artery disease, history of coronary revascularization, congestive heart failure (CHF), chronic obstructive pulmonary disease, dialysis status at presentation, baseline renal insufficiency, anemia, lack of statin medication at presentation, being on anticoagulation at presentation, need for above-knee amputation, and need for emergent amputation. Variables that were protective vs mortality on multivariable analysis (P < .05) were body mass index greater than 30 kg/m2, history of ipsilateral amputation at a lower level, and history of ipsilateral infrainguinal bypass. Pertinent negatives included all socio-demographic variables including rural living status, insurance status, and area deprivation index home area. Variables with a statistically significant (P < .05) multivariable association with 30-day mortality were female sex, advancing age, history of coronary artery disease, history of prior coronary revascularization, history of CHF, class 3 or 4 CHF, chronic obstructive pulmonary artery disease, dialysis requirement at presentation, baseline renal insufficiency, lack of antiplatelet medication at time of presentation, lack of statin medication at time of presentation, need for above-knee amputation, acute ischemia indication, and need for emergent amputation. Variables that were protective (P < .05) vs 30-day mortality on multivariable analysis were diabetes, prior ipsilateral amputation at a lower level, prior infrainguinal bypass ipsilateral to amputation, prior ipsilateral infrainguinal endovascular revascularization (endovascular or bypass), and prior ipsilateral inflow arterial bypass. For receiver operating curve analysis, the 30-day risk score had an area under the curve of 0.715 and the 1-year risk score analysis 0.722. Hosmer-Lemeshow investigation of the multivariable regressions resulted in an overall accuracy of 92.8% for the 30-day mortality investigation (99% accurate for survival) and 78% overall accuracy on the 1-year mortality risk score (96.8% in predicting survival accurately). This indicates that these models perform far better in determining which patients will survive rather than precisely determining who will experience 1-year mortality.

Risk scores for mortality at 30 days and 1 year after major lower extremity amputation have been created that have good accuracy and steep escalation with advancing comorbidity. Variables with the most potent deleterious effect on survival were renal insufficiency, dialysis requirement, CHF, and need for emergent amputation. Patients who have already been receiving care from vascular specialists at the time of amputation have improved survival vs those without prior arterial interventions or a lower level of amputation. Social determinants of health do not impact survival among patients undergoing major lower extremity amputation at Vascular Quality Initiative centers.

The global rise in diabetes prevalence has significantly contributed to the increasing burden of atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality in this population. Diabetes accelerates atherosclerosis through mechanisms such as hyperglycemia, oxidative stress, chronic inflammation, and epigenetic dysregulation, leading to unstable plaques and an elevated risk of cardiovascular events. Despite advancements in controlling traditional risk factors like dyslipidemia and hypertension, a considerable residual cardiovascular risk persists, highlighting the need for innovative therapeutic approaches. Emerging treatments, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, epigenetic modulators, and RNA-based therapies, are showing promise in addressing the unique challenges of diabetes-associated ASCVD. Precision medicine strategies, such as nanoparticle-based drug delivery and cell-specific therapies, offer further potential for mitigating cardiovascular complications. Advances in multiomics and systems biology continue to deepen our understanding of the molecular mechanisms driving diabetes-associated atherosclerosis. This review synthesizes recent advances in understanding the pathophysiology and treatment of diabetes-related atherosclerosis, offering a roadmap for future research and precision medicine approaches to mitigate cardiovascular risk in this growing population.

Statins are known to display pleiotropic effects on the vascular system, beyond their lipid-lowering properties. Studies on isolated vascular preparations have demonstrated their acute relaxant effects on vascular tone. Considering the increased evidence in regard to the contribution of perivascular adipose tissue (PVAT) in the regulation of vascular homeostasis, we aimed to investigate the possible modulatory role of PVAT in the vascular effects of atorvastatin and rosuvastatin in isolated rat aorta.

Thoracic aortas isolated from young male Wistar rats were divided into two groups: rings with intact PVAT (+) and rings without PVAT (-), and then mounted in an isolated organ bath system. Rat aortic rings were standardized with potassium chloride (KCl, 40 mM), and then endothelium-dependent relaxation responses were checked by acetylcholine (Ach, 10-7-10-4 M). The concentration-dependent (10-7-10-4 M) effects of atorvastatin and rosuvastatin were studied on rat aortic rings precontracted submaximally with phenylephrine (Phe, 10-6-3 × 10-5 M). In addition, endothelium-independent relaxation responses were evaluated by sodium nitroprusside (SNP, 10-6 M) at the end of each experiment.

Rat aortic rings with intact PVAT (+) and without PVAT (-) displayed similar endothelium-dependent and -independent relaxations to Ach and SNP, respectively. Increasing concentrations (10-7-10-4 M) of atorvastatin and rosuvastatin directly relaxed the aortic rings with and without PVAT. The maximum relaxant effects of rosuvastatin was found significantly greater than atorvastatin.

The current study demonstrated that atorvastatin and rosuvastatin displayed prominent relaxations in rat aortic rings with intact PVAT (+) and without PVAT (-). Notably, rosuvastatin produced a greater vasorelaxant effect compared to atorvastatin in rat aortic rings with and without PVAT. Current study provides a novel evidence that PVAT does not significantly influence statin-mediated vasorelaxation under physiological conditions.

Preeclampsia (PE) is a major cause of maternal mortality and morbidity, affecting 3-6% of pregnancies worldwide and ranking among the top six causes of maternal deaths in the U.S. PE typically develops after 20 weeks of gestation and is characterized by new-onset hypertension and/or end-organ dysfunction, with or without proteinuria. Current management strategies for PE emphasize early diagnosis, blood pressure control, and timely delivery. For prevention, low-dose aspirin (81 mg/day) is recommended for high-risk women between 12 and 28 weeks of gestation. Magnesium sulfate is also advised to prevent seizures in preeclamptic women at risk of eclampsia. Emerging management approaches include antiangiogenic therapies, hypoxia-inducible factor suppression, statins, and supplementation with CoQ10, nitric oxide, and hydrogen sulfide donors. Black women are at particularly high risk for PE, potentially due to higher rates of hypertension and cholesterol, compounded by healthcare disparities and possible genetic factors, such as the APOL1 gene. This review explores current and emerging strategies for managing PE and addresses the underlying causes of health disparities, offering potential solutions to improve outcomes.

An avulsion is a severe dental injury characterized by the complete displacement of a tooth from its socket, often resulting in a compromised prognosis. One of the key factors influencing the success of reimplantation is the extraoral dry time, which refers to the duration the tooth remains outside of the socket. Prolonged dry time significantly impairs the viability of the periodontal ligament cells, crucial for successful healing and reattachment. Despite various protocols and treatment strategies developed to manage avulsed teeth, no single approach addresses all treatment needs effectively, particularly in cases of delayed reimplantation. Simvastatin, an anti-lipidemic drug, has demonstrated pleiotropic effects that extend beyond cholesterol lowering. These effects include anti-inflammatory properties, promotion of bone regeneration, and enhancement of periodontal ligament cell survival. Such actions suggest that simvastatin may have a beneficial role in improving outcomes following the delayed reimplantation of avulsed teeth. This case series proposes the use of simvastatin as an adjunctive treatment for avulsed teeth along with platelet-rich fibrin and hydroxyapatite, particularly in situations where reimplantation is delayed. By mitigating inflammation and stimulating tissue regeneration, simvastatin may help counteract the damage caused by prolonged extraoral dry time. Its potential to promote periodontal ligament cell survival and enhance healing processes could improve the prognosis of reimplantation, even in cases where traditional treatment alone would be less effective. Given these promising properties, simvastatin may represent a valuable addition to the treatment protocol for avulsed teeth with extended dry times. However, further clinical studies and trials are necessary to validate its efficacy and establish a clear role in the management of delayed reimplantation.

Dyslipidemia is linked to pregnancy complications, but its causal role remains uncertain. This two-sample Mendelian Randomization (MR) study investigated the causal relationship between lipid traits and pregnancy complications and evaluated the impact of lipid-modifying drug targets.

Genetic instruments for lipid traits and targets for lipid-modifying drugs were obtained from the Global Lipids Genetics Consortium. Three pregnancy complications' summary statistics came from the FinnGen R9 database. Significant drug targets underwent further analysis using Expression Quantitative Trait Loci data, and mediation analysis identified potential mediators.

Increased high-density lipoprotein cholesterol (HDL-C) reduced the incidence of preeclampsia (OR: 0.755, 95% CI: 0.639-0.891, p=0.001, FDR=0.012) and gestational diabetes mellitus (GDM) (OR: 0.835, 95% CI: 0.741-0.942, p=0.003, FDR=0.018). Genetic proxies for cholesteryl ester transfer protein (CETP) inhibition correlated with a decreased risk of preeclampsia (OR: 0.863, 95% CI: 0.786-0.947, p=0.002, FDR=0.027), while genetic inhibition of HMG-CoA reductase (HMGCR) increased preeclampsia risk (OR: 1.700, 95% CI: 1.189-2.431, p=0.004, FDR=0.036). Genetically mimicking the enhancement of lipoprotein lipase (LPL) related to a reduced risk of GDM (OR: 0.681, 95% CI: 0.560-0.829, p=1.29×10-4, FDR=0.004). Higher LPL expression in subcutaneous adipose tissue also reduced GDM risk (OR: 0.642, 95% CI: 0.454-0.909, p=0.013). Waist circumference (4.2%) and waist-to-hip ratio adjusted by BMI (5.7%) partially mediated LPL's effect on GDM risk.

Elevated HDL-C levels help prevent preeclampsia and GDM. CETP and LPL could be therapeutic targets for preeclampsia and GDM, respectively. However, caution is advised with HMGCR-targeting drugs, as they may increase the preeclampsia risk.

Multidrug resistance (MDR) facilitates tumor recurrence and metastasis, which has become a main cause of chemotherapy failure in clinical. However, the current therapeutic effects against MDR remain unsatisfactory, mainly hampered by the rigid structure of drug-resistant cell membranes and the uncontrolled drug release. In this study, based on a sequential drug release strategy, we engineered a core-shell nanoparticle (DOX-M@CaP@ATV@HA) depleting cholesterol for reverse tumor MDR. DOX-M@CaP@ATV@HA could accurately target tumor cells due to the active targetability of hyaluronic acid (HA) toward CD44 receptors. The calcium phosphate (CaP) shell was cleaved in the lysosomal acidic environment so that the cholesterol-lowering drug atorvastatin (ATV) was rapidly released to diminish cholesterol and P-glycoprotein (P-gp) level on the membrane, thereby boosting tumor cell drug uptake. Next, doxorubicin (DOX) was gradually released from the hydrophobic core of the mPEG-DSPE micelle, inflicting irreversible DNA damage and triggering apoptosis. The nanosystem was proven both in vitro and in vivo to reverse MDR effectively and exhibited a remarkable therapeutic efficacy on drug-resistant tumors with high biosafety. In conclusion, DOX-M@CaP@ATV@HA effectively reverses MDR via cholesterol depletion, which provides an innovative strategy for tumor MDR treatment.

Cigarette smoke contributes to skeletal muscle wasting. While exercise and nutritional therapies are effective in improving skeletal muscle quantity and quality, the effect of medications on longitudinal muscle loss is unclear. We investigated whether long-term use of common medications affects longitudinal skeletal muscle changes in current and former smokers.

Using quantitative computed tomography imaging, we measured the 5-year changes in pectoralis muscle area (delta-PMA) and pectoralis muscle density (delta-PMD) of 4191 participants in the COPD Genetic Epidemiology (COPDGene®) study. We tested whether specific medications were associated with delta-PMA and/or delta-PMD using regression analyses. Propensity score matching (PSM) analysis was performed to determine the effect of the medications on longitudinal changes on delta-PMA.

Over the study period, the median delta-PMA for the entire population showed a decrease of 2.23cm2 (interquartile range: -6.52, 1.54). Regression analyses demonstrated statin use was associated with less loss of PMA, whereas, aspirin use was associated with a greater loss of PMA. Specifically, in the PSM-adjusted analysis, statin use was associated with attenuated loss of PMA (median; -1.5 versus -2.5cm2, p=0.017), while aspirin use was associated with increased loss of PMA (median; -2.5 versus -1.9cm2, p=0.040).

In current and former smokers, statin use was associated with reduced pectoralis muscle wasting, while aspirin use was associated with increased muscle loss. Additional research is needed to verify these findings. (Clinicaltrials.gov identifier NCT00608764).

Bone fractures are a leading cause of morbidity and healthcare expenditure globally. The complex healing process involves inflammation, cartilage formation, mineralization, and bone remodeling. Current treatments like immobilization, surgery, and bone grafting, though effective, pose significant challenges, such as prolonged recovery and high costs. Emerging therapies such as biological agents, pharmacological treatments, and physical stimulation techniques are also associated with high costs, side effects, and practical applicability limitations. There is a critical need for alternative therapies that are cost-effective, safe, and easy to use. Recent studies suggest the potential of β-caryophyllene (BCP) and statins in promoting bone healing. BCP, a naturally occurring anti-inflammatory and antioxidant compound found in essential oils, enhances osteoblast activity and inhibits osteoclastogenesis. Statins, known for their cholesterol-lowering effects, also promote bone formation and reduce bone resorption through multiple biochemical pathways. Both BCP and statins have shown promising results in preclinical studies, enhancing bone density and promoting fracture healing. This review explores the individual and potential synergistic effects of BCP and statins on bone fracture healing. It highlights the complementary mechanisms of these agents: BCP's anti-inflammatory and osteogenic properties and statins' ability to inhibit osteoclast activity and promote angiogenesis. Combining BCP and statins could offer a multifaceted approach to enhance fracture healing, reduce complications, and improve patient outcomes. While individual effects are supported preclinically, further studies investigating synergies, formulations, and clinical translation are needed to develop this promising novel therapeutic approach for improving fracture repair outcomes.

Knee osteoarthritis (OA) is a common condition that causes pain and reduces the quality of life for many people. It also leads to high health and financial costs. Managing knee OA pain requires using different methods together for the best results. This review overviews current therapeutic options for knee OA pain, focusing on their efficacy, safety, and potential roles in clinical practice. Topical treatments, such as NSAIDs and capsaicin, offer significant pain relief with minimal systemic side effects and are suitable for initial therapy, together with nonpharmacologic interventions like exercise and, when relevant, weight loss. Oral analgesics, including acetaminophen and opioids, have limited efficacy and serious side effects, making them appropriate only for short-term or rescue therapy. Intra-articular injections, such as corticosteroids, hyaluronic acid, and platelet rich plasma, demonstrate varying levels of efficacy and safety. Nutritional supplements, including curcumin, Boswellia serrata, and glucosaminechondroitin combinations, offer modest benefits and are best used as adjuncts to standart treatment. Nonpharmacological treatments, such as transcutaneous electrical nerve stimulation (TENS), acupuncture, and local heat therapy, provide variable pain relief and should be customized based on individual patient responses. Targeted biologic agents, such as antibodies to TNF-α, IL-1, and NGF, hold promise for more precise pain relief; however, further research is required to establish their routine use. Treating knee OA pain should be personalized, combining several methods. Research must continue to improve treatments and make them safer.

Statins are widely used for treating lipid disorders and cardiovascular diseases. However, the therapeutic efficiency and adverse effects of statins vary among different patients, which numerous clinical and epidemiological studies have attributed to genetic polymorphisms in statin-metabolizing enzymes and transport proteins. The metabolic processes of statins are relatively complex, involving spontaneous or enzyme-catalyzed interconversion between more toxic lactone metabolites and active acid forms in the liver and bloodstream, influenced by multiple factors, including the expression levels of many metabolic enzymes and transporters. Addressing the variable statin therapeutic outcomes is a pressing clinical challenge. Transcription factors and epigenetic modifications regulate the metabolic enzymes and transporters involved in statin metabolism and disposition and, therefore, hold promise as 'personalized' targets for achieving optimized statin therapy. In this review, we explore the potential for customizing therapy by targeting the metabolism of statin medications. The biochemical bases of adverse reactions to statin drugs and their correlation with polymorphisms in metabolic enzymes and transporters are summarized. Next, we mainly focus on the regulatory roles of transcription factors and epigenetic modifications in regulating the gene expression of statin biochemical machinery. The recommendations for future therapies are finally proposed by targeting the central regulatory factors of statin metabolism.

Atherosclerosis is a disease of large and medium arteries that can lead to life-threatening cardiovascular and cerebrovascular consequences, such as myocardial infarction and stroke. Moreover, atherosclerosis is a major contributor to cardiovascular-related mortality in individuals with diabetes mellitus. Diabetes aggravates the pathobiological mechanisms that underlie the development of atherosclerosis. Currently available anti-atherosclerotic drugs or strategies solely focus on optimal control of systemic risk factors, including hyperglycaemia and dyslipidaemia, but do not adequately target the diabetes-exacerbated mechanisms of atherosclerotic cardiovascular disease, highlighting the need for targeted, mechanism-based therapies. This Review focuses on emerging pathological mechanisms and related novel therapeutic targets in atherosclerotic cardiovascular disease in patients with diabetes.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, highlighting the critical need for effective preventive therapies. Statins, or HMG-CoA reductase inhibitors, are widely prescribed for their ability to lower low-density lipoprotein (LDL) cholesterol and reduce CV risk. This systematic review evaluates the long-term impact of statins on CV and all-cause mortality across diverse populations, including those with chronic kidney disease, chronic heart failure, and other comorbid conditions. A comprehensive search of major databases identified randomized controlled trials and large observational cohort studies with follow-up periods exceeding one year. Findings demonstrated significant reductions in CV mortality (hazard ratio (HR) range: 0.38-0.76) and all-cause mortality (HR range: 0.55-0.80) with statin therapy, particularly among high-risk groups, such as individuals with elevated LDL-C and moderate chronic kidney disease. Additional benefits were observed in preventing major adverse cardiovascular events (MACEs). Subgroup analyses revealed variations in efficacy based on age, sex, comorbidities, and statin type or dosage, with some populations, such as those with chronic heart failure and chronic obstructive pulmonary disease, showing limited benefit. Geographic and ethnic diversity were underrepresented in the included studies, and data on long-term effects in populations with advanced renal impairment or inflammatory conditions remain insufficient. These gaps underscore the need for methodologically robust studies and tailored approaches to statin therapy that account for individual patient profiles, including comorbidities and demographic factors. Practical steps include integrating statins with newer lipid-lowering agents and developing personalized treatment protocols to maximize their benefits and minimize risks. This review reinforces the critical role of statins in reducing the global burden of CVDs while emphasizing areas for future research.

Recent advancements in research have significantly enhanced our comprehension of the intricate immune components that contribute to multiple sclerosis (MS) pathogenesis. By conducting an in-depth analysis of complex molecular interactions involved in the immunological cascade of the disease, researchers have successfully identified novel therapeutic targets, leading to the development of innovative therapies. Leveraging pioneering technologies in proteomics, genomics, and the assessment of environmental factors has expedited our understanding of the vulnerability and impact of these factors on the progression of MS. Furthermore, these advances have facilitated the detection of significant biomarkers for evaluating disease activity. By integrating these findings, researchers can design novel molecules to identify new targets, paving the way for improved treatments and enhanced patient care. Our review presents recent discoveries regarding the pathogenesis of MS, highlights their genetic implications, and proposes an insightful approach for engaging with newer therapeutic targets in effectively managing this debilitating condition.

To investigate the association between triglyceride levels and major adverse cardiovascular events (MACE) in primary and secondary prevention cohorts.

This retrospective study was conducted with a nationwide health insurance claims database, which included approximately 3.8 million participants with medical checkups between January 2005 and August 2020 in Japan. The participants were classified into primary prevention (n=3,415,522) and secondary prevention (n=29,806) cohorts based on cardiovascular or cerebrovascular disease history. Each participant was categorized as having very low (triglyceride ＜50 mg/dL), low normal (50-99), high normal (100-149), or hypertriglyceridemia (≥ 150). The primary prevention cohort was further stratified into low-, intermediate-, and high-risk groups according to atherosclerotic cardiovascular diseases risk. Outcome was MACE, including acute myocardial infarction (AMI), unstable angina, ischemic stroke, and cardiac death.

Over a mean follow-up of 3.25 years, 0.3% and 2.6% MACE occurred in primary and secondary prevention, respectively. Hypertriglyceridemia was associated with high risk of MACE in the primary prevention, but not in the secondary prevention. A significant interaction was observed between prevention categories and the association of TG levels with MACE in those with TG ＜150 mg/dL and ischemic stroke in those with TG ≥ 150 mg/dL. The population-attributable fraction for hypertriglyceridemia in primary prevention was 4.1% for MACE. In primary prevention, lower risks of AMI were observed in the lower TG category compared to the current threshold.

This study suggests distinct triglyceride thresholds for MACE risk in primary and secondary prevention cohorts, requiring further prospective validation for clinical implementation.

Opioid addiction is known as a chronic relapsing disorder associated with long-lasting molecular and cellular neuroadaptations that lead to compulsive behavior. Current pharmacotherapies target the modulation of mu-opioid receptors (MOR); however, the relapse rate remains high. In this study, we evaluated the potential effect of atorvastatin, a blood-brain barrier-permeable statin, on preventing morphine relapse through both extinction-reinstatement and abstinence-reinstatement models using conditioned place preference (CPP). Adult male Wistar rats were used to establish morphine-induced CPP (5 mg/kg), followed by extinction training and subsequent priming injection of morphine (2 mg/kg, i.p.) to induce relapse-like behavior. Extinguished rats significantly reinstated their morphine-seeking behavior. In contrast, rats that received different doses of atorvastatin (0.1, 0.5, 1 mg/kg) 1 hour before each extinction training session did not show a preference for the morphine-paired chamber. Moreover, acute atorvastatin injection (1 mg/kg, i.p.) 1 h before the reinstatement test significantly prevented reinstated morphine-seeking behavior. We found that atorvastatin 1 mg/kg attenuated morphine-seeking behaviors, and this attenuation of reinstatement was partly mediated by the upregulation of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex (PFC) and hippocampus (Hipp). Furthermore, atorvastatin reversed Oprm1 upregulation (mu-opioid receptor gene) induced by relapse in the nucleus accumbens and Hipp. Moreover, treatment with atorvastatin during the extinction period alters the electrophysiological properties of the mPFC neurons following morphine priming and enhances neuronal excitability. We conclude that atorvastatin was effective in decreasing reinstatement.

Rosuvastatin and atorvastatin are the most widely prescribed moderate- to high-intensity statins. However, evidence on their efficacy and safety during actual use is limited.

To compare the real-world effectiveness and safety of rosuvastatin and atorvastatin.

Active comparator cohort study using target trial emulation.

The China Renal Data System (CRDS) and UK Biobank (UKB) databases.

Adults newly prescribed rosuvastatin or atorvastatin.

The primary outcome was all-cause mortality. Cox proportional hazards regressions were used after 1:1 multilevel propensity score matching.

Among the 285 680 eligible participants in both databases, 6-year all-cause mortality was lower for rosuvastatin than for atorvastatin (2.57 vs. 2.83 per 100 person-years in the CRDS database and 0.66 vs. 0.90 per 100 person-years in the UKB database), with differences in cumulative incidence of -1.03% (95% CI, -1.44% to -0.46%) in the CRDS database and -1.38% (CI, -2.50% to -0.21%) in the UKB database. For secondary outcomes in both databases, rosuvastatin conferred lower risks for major adverse cardiovascular events and major adverse liver outcomes. In the UKB database, the risk for development of type 2 diabetes mellitus was higher with rosuvastatin, and the 2 medications carried similar risks for development of chronic kidney disease and other statin-related adverse effects.

Possible residual confounding.

This study found differences in risks for some important outcomes associated with rosuvastatin and atorvastatin. The differences were relatively small, and many did not meet traditional standards for statistical significance. Further research is needed to understand whether these findings can be used with confidence in clinical practice.

National Key R&D Program of China and National Natural Science Foundation of China.

Cancer induced chronic inflammation and cancer drugs effects on the vascular system can lead to rapidly progressing atherosclerotic burden. Statins drugs are known to reduce atherosclerotic plaque burden and inflammation. We studied outcomes of statins for anthracycline-related cardiac dysfunction (ARCD).

We conducted an online systematic search on PubMed and Embase to identify studies assessing statins' role in alleviating ARCD. We selected 9 studies that had patients with ARCD and use of statins. We primarily focused on outcomes including incidence of heart failure (HF), mean changes in left ventricular ejection fraction (LVEF), end-diastolic volume (LVEDV), and end-systolic volume (LVESV) from baseline. Odds ratios (OR) were calculated using a random effect model in R-statistics.

Among 9 studies with a total of 2784 patients we noticed a significant reduction in the incidence of HF among patients administered statins, with an OR of 0.52 (95 % CI 0.37-0.74, p < 0.0003), indicating a substantial protective effect. However, the mean changes in EF, LVEDV, and LVESV from baseline, represented by Hedges's g of 1.09 (95 % CI -0.40 to 2.57, p = 0.15), 0.91 (95 % CI -1.69 to 3.51, p = 0.47), and 1.32 (95 % CI -2.30 to 4.94, p = 0.49) respectively, were not statistically significant. (Figure 1).

Our meta-analysis confirms statins' effectiveness in reducing risk of ARCD. However, their influence on EF, LVEDV, and LVESV remains uncertain, warranting further study.

Canine haemangiosarcoma (HSA) is a highly aggressive cancer often associated with coagulation abnormalities. Statins, inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) clinically prescribed for hypercholesterolemia, are also believed to possess antitumour and anticoagulant properties by inhibiting downstream Akt activation. Akt phosphorylation is involved in the mechanism of the antitumour and tissue factor (TF)-lowering effects of statins. In the present study, we aimed to investigate whether statins could inhibit cell viability while concurrently inducing anticoagulant properties by regulating the expression of TFs in canine HSA cells. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), we initially exclusively detected HMGCR mRNA expression in canine HSA tissues and cell lines but not in normal cephalic vein and spleen tissues. Moreover, treatment with lipophilic statins, including atorvastatin, fluvastatin, and simvastatin, inhibited cell viability in a concentration-dependent manner and decreased TF expression both at the mRNA and protein levels, as evidenced by cell viability assays, RT-qPCR, and immunoblotting, respectively. Further investigation using cell viability assays and flow cytometry revealed that simvastatin decreased Akt phosphorylation, and MK-2206, a specific Akt inhibitor, mirrored the effect of simvastatin on cell viability and cell cycle arrest. However, MK-2206 exhibited different effects on TF expression depending on the cell type, indicating that Akt phosphorylation may not consistently regulate TF expression. Overall, this study provides insights into the potential therapeutic use of statins in targeting tumour growth and coagulation abnormalities in canine HSA. Further research is warranted to fully elucidate the underlying mechanisms and clinical applications of statins in canine HSA treatment.