The global population aged 80 years and older will reach approximately half a billion in the coming years, and cardiovascular prevention in this group of patients will become a global health challenge. In the era of evidence-based medicine, the use of lipid-lowering therapies (LLTs) in the elderly, particularly in primary and secondary cardiovascular prevention, remains an area of active research. Although there is broad consensus on the use of LLTs in the elderly to prevent recurrent cardiovascular events in secondary prevention, there is considerable debate about their use in primary prevention. Many efforts have been made to improve cardiovascular risk stratification in patients over 75 years of age in primary prevention. In recent years, some specific risk scores have been developed, including the Systematic Coronary Risk Evaluation 2 for Older Persons (SCORE2-OP). While there are very few specific warnings to consider for LLTs in the elderly, an important challenge in this patient population is to identify the turning point at which the disutility risk outweighs the potential benefits. However, despite the widespread recognition of the importance of this issue, there is a lack of guidance on how to identify patients who should be withdrawn from therapy. The aim of this narrative review is to examine the current state of knowledge regarding the indications for LLT in elderly patients, identify outstanding issues, and discuss future developments.

REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) showed benefits of pitavastatin as preventive therapy for atherosclerotic cardiovascular disease (ASCVD) in people with HIV (PWH). In February 2024, the U.S. Department of Health and Human Services Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV (ARV Guidelines Panel) developed statin therapy recommendations for PWH. These recommendations were issued in collaboration with representatives from the American College of Cardiology (ACC), the American Heart Association (AHA), and the HIV Medicine Association (HIVMA). This synopsis summarizes the development process, the recommendations, and how they supplement the AHA/ACC/multisociety cholesterol guidelines and outlines gaps in primary prevention of ASCVD for PWH.

The ARV Guidelines Panel convened a writing group of 10 members (6 members of the Panel with expertise in HIV-related comorbid conditions, biostatistics, and pharmacology and 4 consultants representing ACC, AHA, and HIVMA with cardiometabolic and HIV management expertise). The writing group reviewed REPRIEVE trial data, other studies evaluating the use of statins in PWH, and the AHA/ACC/multisociety cholesterol guidelines to devise recommendations. Recommendations were based on scientific evidence with a rating scheme developed since the 1998 inception of the ARV guidelines. Proposed recommendations were presented to the full ARV Guidelines Panel, rated via vote, and approved by the Panel's voting members. These recommendations were then endorsed by ACC, AHA, and HIVMA.

The ARV Guidelines Panel issued a strong recommendation for initiating statin therapy among PWH with a 10-year ASCVD risk score of 5% or higher, whose absolute benefit from statins in REPRIEVE was greatest. For patients with a 10-year ASCVD risk score below 5%, the Panel favored statins but recommended patient-clinician risk discussions considering additional HIV-related factors that can increase ASCVD risk.

Hypercholesterolemia is one of the major risk factors for cardiovascular diseases. While probiotics and prebiotics show cholesterol-lowering potential, current evidence suggests limited efficacy when used alone. This study investigated the synergistic effects of oat β-glucan (OBG) and Lacticaseibacillus paracasei K56 (L. paracasei K56) against diet-induced hypercholesterolemia in mice. Hypercholesterolemic mice were treated for 12 weeks with atorvastatin (5 mg/kg/day), L. paracasei K56 (5 × 109 CFU/kg), OBG (1 g/kg/day) or their combination. The combination treatment demonstrated superior efficacy, reducing total cholesterol (TC) by 41.19 ± 7.13 % (vs model group) and low-density lipoprotein cholesterol (LDL-C) by 37.47 ± 6.55 % (vs model group), with 24.37 ± 9.18 % (vs OBG group) and 15.10 ± 10.30 % (vs K56 group) greater TC reduction. Liver histopathology showed 3.7-fold reduction in steatosis scores versus model group. Mechanistically, compared with the model group, the combination upregulated hepatic CYP7A1/CYP27A1 expression by 5.75 ± 0.51-fold and 2.34 ± 0.21-fold respectively, increased fecal bile acids and enriched bile acid producing bacteria. In summary, L. paracasei K56 and OBG synergistically regulate gut microbiota and bile acid metabolism, promoting the conversion of cholesterol into bile acids, thereby alleviating hypercholesterolemia in mice.

1.Atorvastatin Calcium (AC) is the first line lipid-lowering drug in clinical. Nowadays, the combination of AC and BBR is often used to treat hyperlipidemia in clinical. In order to determine the mechanism, we investigate the regulatory of atorvastatin combined with berberine on PI3K/Akt/FoxO1 signaling pathway in rats with hyperlipidemia.2.The hyperlipidemia rat model was constructed. Meanwhile, lipid-lowering and liver protective effects were determined by oil red O and H&E method. The expression of PI3K, Akt and FoxO1 was examined by IHC, WB and RT-pCR. The level of CK and LDH in serum was examined by ELISA.3.The results showed that the expression of PI3K, AKT increased and FoxO1 decreased in MC group compared with NC group (P < 0.01). The expression of PI3K, AKT decreased and FoxO1 increased compared with MC group (P < 0.05). The expression of FoxO1 in combination group is lower than AC group. The levels of CK and LDH in AC group increased compared with NC group (P < 0.01), but decreased significantly in AC + BBR group compared with AC group(P < 0.01).4.The combination of AC and BBR could regulate the lipid level by mediating PI3K/Akt/FoxO1, which providing a new references for the treatment of hyperlipidemia.

Statins are the most commonly used drugs worldwide. Besides a significant decrease in cardiovascular diseases (CVDs) risk, the use of statins is also connected with a broad beneficial pleiotropic effect. At the same time, it is burdened with different side effects. The most common ones are muscle issues (from mild myalgia to rhabdomyolysis). The mechanisms of many of them are still unclear. Therefore, an analytical method for the determination of simvastatin (SIM) and its main metabolite (the hydroxy acid form - SIMA) in muscle tissue was developed.

Muscle samples were homogenized with ammonium acetate buffer using the bead mill homogenizer, and then statins were extracted with a mixture of methanol and ethanol. Prepared samples were analyzed with liquid chromatography (using a reverse-phase column with a gradient elution) combined with the mass spectrometer which was operated in a multiple reaction monitoring mode.

The assay was linear over a 0.1-5 ng/mL range for both statin forms. Inter- and intra-day precision and accuracy were characterized. The method was considered precise (with the following relative standard deviation values: 6.0-6.9% for SIM, and 8.1-12.9% for SIMA) and accurate (with the following mean accuracies: 91.4-100.1% for SIM, and 102.2-115.4% for SIMA). The extraction efficiency was evaluated by recovery determination (76% for SIM, and 99% for SIMA). Moreover, the matrix effect was calculated with the following results: 87% for SIM, and 139% for SIMA. The proposed method was applied for SIM and SIMA determination in skeletal muscle tissues obtained from statin-treated patients.

The obtained results proved that the method may be a useful tool for explaining muscle effects related to statin therapy.

This study aimed to compare the lipid-lowering effect and safety of low-intensity atorvastatin (5 mg) plus ezetimibe (10 mg) combination therapy (A5E10) with monotherapy regimens-atorvastatin 5 mg [A5], ezetimibe 10 mg [E10], and atorvastatin 10 mg [A10])-in dyslipidemia patients.

A randomized, double-blind, placebo-controlled trial involving 252 dyslipidemia patients was conducted at 25 centers in South Korea (NCT05970679). Participants aged ≥ 19 years were randomized into four groups: A5E10, A5, E10, and A10. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to 8 weeks. Secondary endpoints included changes in other lipid parameters, lipid ratios, LDL-C goal achievement rates and safety assessments.

The mean age of the patients was 63 years, and 51.2% were male. The A5E10 group showed significantly greater LDL-C reduction (47.6%) compared with A5 (33.4%), E10 (19.4%), and A10 (40.1%) at 8 weeks (p < 0.0001). A5E10 also significantly reduced triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. In addition, a significant reduction in LDL-C levels was observed over the 4 weeks, with a 46.7% reduction in LDL-C levels after 4 weeks of A5E10 administration. No severe adverse events were observed in the A5E10 group.

The combination of low-intensity atorvastatin and ezetimibe was more effective than moderate-intensity atorvastatin monotherapy in lowering LDL-C levels and improving other lipid parameters. It was well-tolerated and demonstrated rapid benefits within a month, offering a promising alternative for patients with low to moderate cardiovascular risk who do not achieve adequate control with statin monotherapy.

Statins represent the first-line therapy for cholesterol management. However, for patients prone to statin side effects, unable to tolerate higher doses, or requiring additional low-density lipoprotein cholesterol (LDL-C) reduction, ezetimibe alone or in combination with statins is recommended. This meta-analysis aimed to evaluate the safety and efficacy of combining low- or moderate-intensity statins with ezetimibe compared to high-intensity statin monotherapy, yielding reliable evidence to guide clinical decision-making and personalize treatment strategies. PubMed, Embase, and Scopus were systematically searched from inception until May 2023. All randomized controlled trials (RCTs) comparing a high-intensity statin with a low/moderate-intensity statin with ezetimibe were included. The outcomes of interest comprised changes in concentrations of lipids-LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs)-and apolipoprotein (Apo) A1, Apo B, and high-sensitivity C-reactive protein (hs-CRP), along with major adverse cardiovascular events (MACE). All data were analyzed using Review Manager version 5.4. p-values less than 0.05 were considered to indicate statistical significance. Overall, 20 RCTs, with 5,412 participants, were included. A low/moderate-intensity statin combined with ezetimibe yielded a significantly greater reduction in LDL-C levels than high-intensity statin monotherapy (mean difference [MD], -6.59; 95% confidence interval [CI], -10.95, -2.24; p=0.003; I2=84%). No significant differences were observed between combination and high-intensity statin monotherapy regarding TC, TG, or HDL-C levels. However, hs-CRP levels were significantly higher with combination therapy (MD, 0.32; 95% CI, 0.01, 0.64; p=0.04; I2=0%). Combination therapy involving a low/moderate-intensity statin with ezetimibe was significantly associated with lower LDL-C levels than high-intensity statin monotherapy. No significant differences were observed for TC, TGs, HDL-C, alanine transaminase, or MACE. However, creatine phosphokinase levels significantly increased with monotherapy.

Metabolic syndrome (MetS) is driven by a complex interplay of genetic, lifestyle, and dietary factors, leading to weight gain, insulin resistance, dyslipidemia, and chronic inflammation. Gut microbiota dysbiosis has been recently recognized as a key contributor to MetS, leading to advancements in gut microbiome-based interventions to improve health outcomes. Considering the unique challenges associated with the use of pre/probiotics, short-chain fatty acids (SCFA), also known as postbiotics, have emerged as promising therapeutic agents due to their role in modulating host metabolism and physiology. Considering this, the aim of the current study was to explore the therapeutic potential of SCFA (butyrate, propionate, and acetate) supplementation against a high-fat diet (HFD)-induced experimental model of MetS in male Wistar rats. Alterations in body weight, lipid profile, histopathology, and adipose tissue accumulation were assessed to establish SCFA-mediated amelioration of experimental MetS. Further, the enzymatic (GPx, Catalase, GR, and GST) and non-enzymatic (LPO, total ROS, and Redox ratio were evaluated. The results indicated that SCFA supplementation could effectively mitigate key features of MetS. A significant reduction in body weight gain and fasting blood glucose levels, along with markedly lowered triglycerides, total cholesterol, and LDL levels, with partial restoration of HDL levels was observed following SCFA supplementation. SCFA administration also attenuated MetS-associated hepatic damage as studied by histopathological investigation and analysis of liver function marker enzyme activities. Such ameliorative effects of SCFA against HFD-induced MetS were owed to potential redox modulation studied using enzymatic and non-enzymatic oxidative stress markers. In conclusion, the study's outcomes show that SCFA supplementation could potentially be used against managing MetS. It underscores the therapeutic potential of SCFA by placing them as a novel gut microbiome-based dietary approach to improve metabolic health and reduce the risk of MetS-associated complications. However, more detailed mechanistic explorations are warranted in the future, leading to their beneficial role in MetS contributing to holistic health outcomes.

Statins are essential for managing cardiovascular disease (CVD), but adverse effects often lead to treatment discontinuation and non-adherence, underscoring the need for personalized approaches. This study aimed to evaluate the influence of pharmacogenomic (PGx) variants and demographic factors on statin-associated adverse effects in a multiethnic cohort from the United Arab Emirates (UAE).

This sub-analysis of the EmHeart Study included 675 patients using rosuvastatin or atorvastatin. Patients were genotyped for SLCO1B1 and ABCG2 actionable variants using real-time PCR. Data on demographics, comorbidities, and statin use were extracted from electronic health records. Adverse events, including statin-associated muscle symptoms (SAMS) and liver enzyme elevation, were tracked over 12 months. Associations were analyzed using chi-square tests and logistic regression.

Rosuvastatin users carrying the ABCG2 rs2231142 variant had a threefold increased risk of liver enzyme elevation, particularly among East Asian patients (P < 0.005). Atorvastatin users with the SLCO1B1 rs4149056 variant exhibited a twofold increased risk of SAMS, with higher rates observed in females and Arabs (P < 0.05). The combination of rosuvastatin with ezetimibe further exacerbated risks of SAMS and liver enzyme elevation.

This study highlights the importance of genetic testing and demographic factors, such as ethnicity and gender, in tailoring statin therapy to minimize adverse effects. Despite extensive research on PGx-guided statin prescribing, clinical implementation remains limited. Integrating PGx testing into routine practice and enhancing physician awareness of genetic and demographic risk factors can improve the safety, efficacy, and adherence of lipid-lowering therapies in diverse populations.

Despite observational studies suggesting a link between chronic musculoskeletal pain (CMP) and increased risk of cognitive decline and dementia, the causal nature of this relationship remains uncertain due to potential confounding factors and reverse causality. We employed two-sample Mendelian Randomization (TSMR), bidirectional MR, mediation MR, drug-target MR, and colocalization analysis, along with gene set enrichment and protein-protein interaction (PPI) analyses. TSMR assessed the causal associations between CMP and the risk of dementia and its subtypes, including Alzheimer's disease (AD), vascular dementia (VaD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and Parkinson's disease (PD). Bidirectional MR evaluated reverse causality, while mediation analyses identified potential mediators, focusing on neuroimaging and cognitive phenotypes. Drug-target MR investigated the role of the SLC39A8 gene, and colocalization analysis determined shared causal genetic variants. Gene set enrichment and PPI analyses elucidated the biological pathways implicated in the CMP-dementia relationship. Robust evidence established a causal relationship between chronic low back pain (LBP) and increased risk of PD, with knee osteoarthritis identified as a partial mediator, suggesting a pathway involving chronic inflammation. Bidirectional MR analysis revealed no evidence of reverse causality, further supporting the unidirectional causal link from LBP to PD. Colocalization analysis confirmed distinct genetic architectures for LBP and PD, while drug-target MR implicated the SLC39A8 gene as a potential mediator. Gene set enrichment and PPI analyses highlighted critical biological pathways, such as purine metabolism and glutamate receptor signaling. Suggestive evidence indicated potential causal links between limb pain and overall dementia, myalgia and VaD, as well as potential protective effects of Polymyalgia Rheumatica (PMR) against AD and rheumatism against PD. This study reveals a complex causal relationship between CMP and neurodegenerative diseases, particularly the robust link between LBP and PD. The findings underscore the need for further research to elucidate the underlying mechanisms and inform targeted prevention and treatment strategies.

Atherosclerosis is characterized by the accumulation of fatty and fibrotic plaques, which preferentially develop at curvatures and branches along the arterial trees that are exposed to disturbed flow. However, the mechanisms by which endothelial cells sense disturbed flow are still unclear.

The partial carotid ligation mouse model was used to investigate disturbed flow-induced atherogenesis. In vitro experiments were performed using the ibidi system to generate oscillatory shear stress and laminar shear stress. ApoE-/- mice with endothelium-specific knockout or overexpression of 5-HT1B (serotonin receptor 1B) were used to investigate the role of endothelial 5-HT1B in atherosclerosis. RNA sequencing analysis, immunofluorescence analysis, and molecular biological techniques were used to explore the role of 5-HT1B in mechanotransduction and endothelial activation.

The data showed that human endothelial cells express a high level of 5-HT1B, which is a serotonin receptor subtype. Endothelial 5-HT1B is upregulated in atherosclerotic areas of both humans and rodents and is increased by disturbed flow both in vivo and in vitro. Endothelium-specific overexpression of 5-HT1B exacerbates, whereas knockout or knockdown of 5-HT1B in endothelium inhibits disturbed flow-induced endothelial inflammation and atherogenesis in both male and female ApoE-/- mice. We reveal a previously unknown role of 5-HT1B as a mechanosensor in endothelial cells in response to mechanical stimuli. Upon activation by oscillatory shear stress, 5-HT1B recruits β-arrestin, orchestrates RhoA (ras homolog family member A), and then activates mechanosensitive YAP (yes-associated protein), thereby enhancing endothelial inflammation and monocyte infiltration. Pharmacological blockade of 5-HT1B suppresses endothelial activation and atherogenesis via inhibition of YAP.

Taken together, these results uncover that endothelial 5-HT1B acts as a mechanosensor for disturbed flow and contributes to atherogenesis. Inhibition of 5-HT1B could be a promising therapeutic strategy for atherosclerosis.

Background and Clinical Significance: Statins are a widely used drug class associated with a plethora of muscular side effects ranging from the subclinical elevation of creatine kinase to fulminant rhabdomyolysis. Cardiac myopathy secondary to statin treatment is rare and was recently reported as a part of statin-induced necrotizing autoimmune myopathy (SINAM). Its occurrence outside of this context is still debated. Case Presentation: We present the case of a 60-year-old male who developed atorvastatin-induced rhabdomyolysis, without associated hydroxymethyl glutaryl coenzyme A reductase (HMGCR) antibodies, with clinical findings of cardiac failure and severe ECG anomalies. The symptoms slowly regressed with statin withdrawal, and the patient made a full recovery. We discuss the recently proposed statin-associated cardiomyopathy (SACM) and the possible mechanisms. We compare our case to the three other cases of statin-induced cardiac myositis found in the literature. Conclusions: We believe that in vulnerable patients, as was our case, statins can determine significant subacute cardiac toxicity. This would seem to occur in the context of severe skeletal muscle injury, probably due to higher metabolic resistance on the part of the myocardium. Also, the available evidence suggests myocardial involvement should be actively investigated in SINAM patients, preferably by cardiac MRI.

Statins, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, have been widely prescribed to lower circulating low-density lipoprotein cholesterol levels and reduce the risk of cardiovascular disease. Although statins are well tolerated, statin-associated muscle symptoms (SAMS) are the major adverse effect and cause statin intolerance. Therefore, understanding the molecular mechanisms of SAMS and developing effective strategies for its prevention are of significant clinical importance; however, both remain unclear. Here, we establish a model of statin-induced myopathy (SIM) with human induced pluripotent stem cell (hiPSC)-derived myocytes (iPSC-MCs) and investigate the effect of statins on protein homeostasis (proteostasis) that affects skeletal muscle wasting and myotoxicity. We show that treating hiPSC-MCs with statins induces atrophic phenotype and myotoxicity, establishing an hiPSC-based SIM model. We then examine whether statins impair the balance between protein synthesis and degradation. The results show that statins not only suppress protein synthesis but also promote protein degradation by upregulating the expression of the muscle-specific E3 ubiquitin ligase Atrogin-1 in a mevalonate pathway-dependent manner. Mechanistically, blocking the mevalonate pathway inactivates the protein kinase Akt, leading to the inhibition of mTOR complex 1 (mTORC1) but the activation of GSK3β and FOXO1. These changes explain the statin-induced impairment in proteostasis. Finally, we show that pharmacological blockage of FOXO1 prevents SIM in hiPSC-MCs, implicating FOXO1 as a key mediator of SIM. Taken together, this study suggests that the mevalonate pathway is critical for maintaining skeletal muscle proteostasis and identifies FOXO1 as a potential target for preventing SIM.NEW & NOTEWORTHY This work established a human induced pluripotent stem (iPS) cell-based model for statin-induced myopathy (SIM) and demonstrated that blocking the mevalonate pathway disrupts the balance between protein synthesis and degradation, leading to myopathy. Furthermore, the present study showed that pharmacological inhibition of the transcription factor FOXO1 prevents SIM in human iPS cell-derived myocytes, suggesting that FOXO1 is a key mediator of SIM and a potential target for its prevention.

High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins.

To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy.

In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70 mg/dL) within 6 months.

The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p = 0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels.

Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.

This update begins with the incidence and features of statin-associated muscle symptoms, which may often be misattributed. Articles on potential muscle mitochondria dysfunction from statins follow, along with recommendations for possibly avoiding statins in some patients with genetic myopathies. Next, autoimmune myopathies, including immune-mediated necrotizing myopathy, myositis with antimitochondrial antibodies, and overlap myositis with lupus, as well as the role of myxovirus protein A identification in muscle specimens, are addressed. The next section includes reports on the significance of elevated serum aldolase with normal creatine kinase and recommended approaches to evaluate a patient with rhabdomyolysis. A cluster of reports on muscle imaging, particularly using ultrasound and magnetic resonance imaging, are covered. They include studies of inherited and inflammatory myopathies and neck extensor myopathy on topics such as imaging features, patterns of involvement, diagnostic utility, and correlation with histopathology. Last, there are discussions on mexiletine versus lamotrigine for nondystrophic myotonias and the treatment of fatty acid oxidation disorders in adults.

The investigation of prevalence trends of metabolic cardiovascular risk factors is important for appropriate planning of future health programs aiming to prevent cardiovascular morbidity and mortality. In a previous study, we demonstrated an increase in the prevalence of type 2 diabetes (T2D) between 2000 and 2010 in Northeast Germany. The purpose of this study is to investigate prevalence trends of T2D treatment, dyslipidemia and hepatic steatosis in Northeast Germany.

The baseline examinations of the first Study of Health in Pomerania (SHIP) project were carried out from 1997 to 2001 (SHIP-START-0, 4308 subjects). A second, independent random sample of the same region was enrolled between 2008 and 2012 (SHIP-TREND-0, 4420 subjects). All data were standardized with post-stratification weighting derived from the adult population of the German federal state of Mecklenburg-West Pomerania.

The prevalence of metformin intake increased from 2.1% to 4.1% and insulin use from 2.0% to 2.8%. While the prevalence of statin intake increased from 6.8% to 12.2%, the prevalence of dyslipidemia decreased slightly from 49.0% in SHIP-START-0 to 45.5% in SHIP-TREND-0. The prevalence of hepatic steatosis increased from 29.7% to 37.3%. This increase was most prominently observed in women and younger age groups.

T2D, dyslipidemia and hepatic steatosis are common and increasing health problems among adults in Northeast Germany. Reassuring healthy diet and controlling obesity may result in prevention of above-mentioned health problems.

Little is known about the potential benefits or harms of statins on physical function among people with human immunodeficiency virus (PWH).

REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events in PWH. Time to complete 10 chair rises, 4-m gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models.

Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female at birth; 2% transgender; and 40% Black, and 18% Hispanic. Median PREPARE follow-up was 4.7 (4.3-5.0) years. Muscle symptoms (grade ≥3 or treatment-limiting) occurred in 5% of both groups. There was no evidence of decline in chair rise rate in either treatment group and no difference in the pitavastatin group compared to placebo (estimated difference -0.10 [95% confidence interval, -.30 to 0.10] rises/min/year; P = .31). Small declines over time were observed in other physical function tests in both treatment groups, with no apparent differences between groups.

We observed minimal declines in physical function over 5 years of follow-up among middle-aged PWH, with no differences among PWH randomized to pitavastatin compared to placebo. This finding, combined with low prevalence of myalgias, supports the long-term safety of statin therapy on physical function, when used for primary prevention of major adverse cardiovascular events among PWH.

Topic modeling utilizes unsupervised machine learning to detect underlying themes within texts and has been deployed routinely to analyze social media for insights into healthcare issues. However, the inherent messiness of social media hinders the full realization of this technique's potential. As such, we hypothesized that restricting medical concepts in social media texts to specific related semantic types and applying topic modeling to these concepts could be a feasible approach to overcome the challenge of traditional topic modeling for social media texts. Therefore, we developed a semantic-type-based topic modeling pipeline to discover self-reported health-related topics. This pipeline integrated semantic type information and Systematized Medical Nomenclature for Medicine (SNOMED) precoordinated expressions into a traditional topic modeling approach to enhance effectiveness in clustering meaningful, distinct topics. Using social media texts regarding statins for illustration, we evaluated the efficacy of this new approach and validated a newly identified topic using real-world clinical data. Based on expert evaluations, this approach resulted in more novel, distinguishable, and meaningful health-related topics compared to traditional topic modeling. In addition, our electronic health record validation for a newly identified topic in two real-world clinical databases indicated that statin users had a higher prevalence of depression or anxiety compared to matched non-users. Our results indicate that this new topic modeling pipeline can improve the extraction of themes from noisy online discussions, thereby contributing to deeper insights for healthcare research.

Myasthenia gravis (MG) is a rare but serious adverse event (AE) of statins. Yet, its pharmacovigilance and clinical features remain unknown.

Data were extracted from the FDA Adverse Event Reporting System (FAERS) (2004 Q1-2023 Q4), and disproportionality analyses were conducted. Case reports on statin-associated MG dated up to 31 December 2023 were retrieved for retrospective analysis.

Data from FAERS showed 178,802 AEs of statins, with musculoskeletal disorders being the most common. Compared to other cholesterol-lowering drugs, statins exhibited a significant increase in MG, with 128 reports included, with pravastatin having the highest proportion. Sixteen cases from 12 studies demonstrated atorvastatin was the most frequently reported agent associated with MG. The median age was 58 years, with a male predominance. The main clinical symptoms were ocular muscle weakness, lasting from 1 week to 3 years. Twelve patients were acetylcholine receptor (AChR) antibody positive. All patients discontinued statins, 14 patients received treatment comprising cholinesterase inhibitors and immunosuppressive drugs. Nine patients achieved recovery, and five patients relapsed after steroid reduction or statins re-administration.

In the real-world pharmacovigilance study, statins are associated with increased reporting of MG. Early identification and timely treatment are crucial for the safe use of statins.

The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster the efficacy of azole-based treatments. Drug repurposing stands as a promising and practical avenue for advancing antifungal therapy, with the potential for swift clinical translation. This review offers a comprehensive overview of azole synergistic agents uncovered through drug repurposing strategies, alongside an in-depth exploration of the mechanisms by which these agents augment azole potency. Drawing from these mechanisms, we delineate strategies aimed at enhancing azole effectiveness, such as inhibiting efflux pumps to elevate azole concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating fungal cell resistance to azoles, and disrupting biological processes extending beyond ergosterol synthesis. This review is beneficial for the development of these potentiators, as it meticulously examines instances and provides nuanced discussions on the mechanisms underlying the progression of azole potentiators through drug repurposing strategies.

High-intensity HMG-CoA reductase inhibitors (statins) are recommended for secondary atherosclerotic cardiovascular disease (ASCVD) prevention. Solid organ transplant (SOT) recipients are at an increased risk of ASCVD events. This study evaluated if abdominal SOT recipients who experienced an ASCVD event prior to transplant received guideline-directed pharmacotherapy for secondary ASCVD prevention post-transplant.

Single-center, retrospective, cohort study that evaluated lipid-lowering therapy prescribing practices in SOT recipients transplanted at Duke University Hospital. The primary objective was the percentage of patients receiving a high-intensity statin regimen during the first year post-transplant. Secondary objectives included reason for change in statin therapy, other lipid-lowering medications prescribed, percentage of patients who had lipid panel(s) drawn, safety of statin therapy, and the incidence of recurrent ASCVD or death secondary to an ASCVD event within the first year post-transplant.

Sixty-three transplant patients were included, 46 (73%) received a kidney, 12 (19%) a liver, and 5 (7.9%) a multi-organ transplant. Twenty-four patients (38.1%) were maintained on a high-intensity statin during the first year post-transplant. Reason for statin dose change included elevated lipids (35.3%), statin-related safety event (11.8%), and undocumented reason (52.9%). Statins were well tolerated. Two (3.2%) patients experienced a recurrent myocardial infarction within the first year post-transplant.

Less than half of the abdominal transplant patients were maintained on guideline-directed high-intensity statin therapy for secondary ASCVD prevention at 1 year post-transplant. Our findings demonstrate an opportunity to optimize the prescribing practices of lipid-lowering therapy following abdominal transplant in a high cardiovascular risk population.

In patients with atherosclerotic cardiovascular disease (ASCVD), intensive lowering of low-density lipoprotein (LDL) cholesterol levels with high-intensity statins is generally recommended. However, alternative approaches considering statin-related adverse effects and intolerance are needed.

To compare the long-term efficacy and safety of an alternative LDL cholesterol-lowering strategy vs high-intensity statin strategy in patients with ASCVD in randomized clinical trials.

PubMed, Embase, and other websites (ClinicalTrials.gov, European Society of Cardiology, tctMD) were systematically searched from inception to April 19, 2024.

Randomized clinical trials comparing an alternative LDL cholesterol-lowering strategy vs a high-intensity statin strategy in patients with ASCVD, with presence of cardiovascular events as end points.

Individual patient data were obtained from randomized clinical trials that met the prespecified eligibility criteria: RACING (Randomized Comparison of Efficacy and Safety of Lipid-Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease) and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy vs Intensity-Based Statin Therapy in Patients With Coronary Artery Disease). The moderate-intensity statin with ezetimibe combination therapy in the RACING trial and the treat-to-target strategy in the LODESTAR trial were classified as alternative LDL cholesterol-lowering strategies. The primary analysis was based on a 1-stage approach.

The primary end point was a 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. The secondary end points comprised clinical efficacy and safety end points.

Individual patient data from 2 trials including 8180 patients with ASCVD (mean [SD] age, 64.5 [9.8] years; 2182 [26.7%] female; 5998 male [73.3%]) were analyzed. The rate of the primary end point did not differ between the alternative strategy and high-intensity statin strategy groups (7.5% [304 of 4094] vs 7.7% [310 of 4086]; hazard ratio, 0.98; 95% CI, 0.84-1.15; P = .82). The mean (SD) LDL cholesterol level during treatment was 64.8 (19.0) mg/dL in the alternative strategy group and 68.5 (20.7) mg/dL in the high-intensity statin strategy group (P < .001). The alternative strategy group had a lower rate of new-onset diabetes (10.2% [271 of 2658] vs 11.9% [316 of 2656]; P = .047), initiation of antidiabetic medication for new-onset diabetes (6.5% [173 of 2658] vs 8.2% [217 of 2656]; P = .02), and intolerance-related discontinuation or dose reduction of assigned therapy (4.0% [163 of 4094] vs 6.7% [273 of 4086]; P < .001).

Results of this systematic review and individual patient data meta-analysis suggest that compared with a high-intensity statin strategy, the alternative LDL cholesterol-lowering strategy demonstrated comparable efficacy regarding 3-year death or cardiovascular events in patients with ASCVD, with an associated reduction in LDL cholesterol levels and risk for new-onset diabetes and intolerance.

PROSPERO CRD42024532550.

This study aimed to evaluate the renal protective effects of black rice anthocyanins (BRAs) against renal injury in mice induced by D-galactose (D-gal).

The renal aging mouse model was established by thirteen consecutive weeks of subcutaneous injections of D-gal. The serum levels of urea nitrogen (BUN), creatinine (CRE), uric acid (UA), antioxidant enzymes (e.g., GSH-Px and SOD), and total antioxidant capacity (T-AOC), as well as the contents of inflammatory factors (IL-1β, IL-6, and TNF-α) in kidney tissues were evaluated. Additionally, the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins was examined.

BRA treatment significantly reduced serum levels of BUN, and CRE increased the concentrations of antioxidant enzymes and total antioxidant capacity in renal tissues, and reduced the levels of inflammatory factors. Furthermore, BRAs restored the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins to normal levels and promoted the recovery of the renal tissue architecture.

It was demonstrated that BRAs could potentially prevent and protect against kidney injury by modulating the Nrf2 and NF-κB signaling pathways, attenuating oxidative stress and inflammatory responses, and modulating the gut microflora. These findings provide a scientific basis for the application of BRAs as a natural bioactive substance in the field of nephroprotection, especially against the renal degeneration that accompanies the aging process.

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.

Using rosuvastatin, the RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial showed the beneficial effects of combining moderate-intensity statin with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease. This study investigated whether the beneficial effects of combination lipid-lowering therapy extend to patients treated with atorvastatin, not rosuvastatin, in daily clinical practice.

Using stabilized inverse probability of treatment weighting, a total of 31 993 patients who were prescribed atorvastatin after drug-eluting stent (DES) implantation were identified from a nationwide cohort database: 6215 patients with atorvastatin 20 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 25 778 patients with atorvastatin 40-80 mg monotherapy. The primary endpoint was the 3-year composite of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or non-fatal stroke in accordance with the RACING trial design. Combination lipid-lowering therapy was associated with a lower incidence of the primary endpoint (12.9% vs. 15.1% in high-intensity atorvastatin monotherapy; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.74-0.88, P < 0.001). Compared with high-intensity atorvastatin monotherapy, combination lipid-lowering therapy was also significantly associated with lower rates of statin discontinuation (10.0% vs. 8.4%, HR 0.81, 95% CI 0.73-0.90, P < 0.001) and new-onset diabetes requiring medication (8.8% vs. 7.0%, HR 0.80, 95% CI 0.70-0.92, P = 0.002).

In clinical practice, a combined lipid-lowering approach utilizing ezetimibe and moderate-intensity atorvastatin was correlated with favourable clinical outcomes, drug compliance, and a reduced incidence of new-onset diabetes requiring medications in patients treated with DES implantation. Trial registration:  ClinicalTrial.gov (NCT04715594).

Statins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.

In this study, we conducted a comprehensive and detailed analysis of the hepatotoxicity of statins based on the data of the US Food and Drug Administration Adverse Event Reporting System database from the first quarter (Q1) of 2004 to the Q1 of 2024 and used Reporting Odds Ratios and Empirical Bayes Geometric Mean to mine the signal of adverse events.

In this study, hepatic disorder related seven statins all exhibited positive signals. Through signal mining, we identified a total of 14,511 cases of adverse events associated with hepatic disorder caused by these statin drugs, with atorvastatin, simvastatin, and rosuvastatin occurring at a higher rate. A total of 148 positive signals related to adverse events of hepatic disorder were captured. Autoimmune hepatitis and drug-induced liver injury both presented positive signals across multiple statin drugs. Notably, atorvastatin had the most significant signal strength in cholestatic pruritus and bilirubin conjugation abnormal. Fluvastatin also showed notable signal strength in autoimmune hepatitis, while simvastatin had a relatively weaker signal strength for hepatic enzyme increased.

This study discovered specific adverse event signal values, revealing potential hepatotoxic risks associated with the use of statin drugs. The results provide an important reference for the safe clinical use of drugs, help to improve the understanding of the safety of statins, and also provide a scientific basis for clinicians to make more accurate and safe decisions when making treatment plans.

Atherosclerosis (AS), an inflammatory cardiovascular disease driven by lipid deposition, presents global prevalence with high mortality. Effective anti-inflammatory or lipid removal is a promising strategy. However, current conventional drug delivery methods may face challenges in targeting disease sites and are deficient in the treatment of AS because of the nonspecific tissue distribution and uncontrollable release of the drug. In contrast, stimulus-responsive nanodrug delivery systems (NDDSs) can respond to stimulation and achieve controlled drug release rates at specific disease sites owing to the abnormal pathological microenvironment in plaques with low pH, excessive reactive oxygen species (ROS) and enzymes, and high shear stress. As a consequence, the efficacy of treatment is improved, and adverse reactions are reduced. On the other hand, NDDSs can combine exogenous stimulus responses (photothermal, ultrasound, etc.) to precisely control their function in time and space. This review for the first time focuses on the application of stimulus-responsive NDDSs in the treatment and diagnosis of AS in the last five years. In addition, its pivotal challenges and prospects are emphasized, aiming to facilitate its application for AS.

Knowledge of muscle contractile properties, physical fitness, and their associations with perceived fatigue may provide insights into mechanisms inducing fatigue and treatment targets. We aimed to identify differences in contractile properties and physical fitness between populations, and examine associations with perceived fatigue. We pooled data on perceived fatigue, physical fitness, and contractile properties from six studies, including a control group (n = 90), cancer survivors (n = 27), patients with chronic obstructive pulmonary disease (COPD; n = 16), chronic myeloid leukemia (CML; n = 20), and statin users (n = 64). We evaluated differences between populations, and associations of contractile properties and physical fitness with perceived fatigue. Compared with the control group, we found differences in contractile properties of patients with COPD (larger muscle force decline: β = -10.5%, 95% CI = -16.7; -4.2, increase in early relaxation time (Rt): β = 84.4%, 95% CI = 51.7; 117.0, increase in half Rt: β = 83.1%, 95% CI = 45.5; 120.7, muscle force rise (MFR): β = 0.2%/ms, 95% CI = 0.1; 0.3, and decrease in MFR: β = -24.3%, 95% CI = -35.7; -13.0) and statin users (early Rt: β = -5.4 ms, 95% CI = -10.0; -0.8, increase in early Rt: β = 19.8%, 95% CI = 2.5; 37.1). Associations between contractile properties and perceived fatigue varied across populations. Longer relaxation times were associated with higher perceived fatigue in hemato-oncological populations. To conclude, contractile properties were impaired in patients with COPD and statin users. Associations between contractile properties and perceived fatigue varied across populations. In hemato-oncological populations, impaired muscle relaxation was associated with higher perceived fatigue.

Ovarian cancer contributed to 13,270 patient deaths in the United States during 2023 and is considered the most aggressive gynecologic malignancy. While surgery, chemotherapy and targeted medications have improved ovarian cancer patient outcomes, novel therapies that further bolster treatment efficacy without compromising toxicity represent an unmet clinical need.

In the current review, we assessed the reported studies involving statin use and ovarian cancer outcomes; a preponderance of the evidence indicated that statins confer a survival benefit in ovarian cancer, especially for patients who underwent treatment post-diagnosis and for a prolonged interval.

The evidence involving a potential survival benefit from statin use in ovarian cancer remains controversial, especially with hydrophilic statins (e.g. pravastatin). While statin users may exhibit better ovarian cancer survival outcomes than non-statin users, additional research should evaluate the putative clinical benefits of statins in ovarian cancer via randomized controlled trials.

Statins are the mainstay of cholesterol treatment to prevent atherosclerotic cardiovascular disease. However, significant barriers, including physician and patient factors, prevent the optimal use of this drug class. In this article, we provide 10 clear and simple tips for clinicians when prescribing statins. The tips are based on the current guidelines, an extensive review of the literature, and decades of clinical practice of the senior author. Within the tips, we discuss key components of the guidelines, assessing cardiovascular risk profiles, evaluating drug-drug interactions, addressing adverse effects, and developing treatment plans that include statins and nonstatins. The tips will be useful for primary and specialty clinicians, such as cardiologists, endocrinologists, and nephrologists.

To consolidate key information on the efficacy and safety of ezetimibe, with a focus on the latest evidence.

While ezetimibe has long been used alongside statins to help achieve lipid goals when statins are insufficient or in statin-intolerant patients, recent studies confirm and extend its benefits. Ezetimibe, when added to statins, is now recognized as an effective option for high-risk cardiovascular patients. Additionally, for those intolerant to statins, it can be combined with bempedoic acid, offering significant LDL cholesterol reduction. Ezetimibe's favourable tolerability, with fewer side effects than statins, along with the availability of fixed-dose combinations, enhances both treatment efficacy and patient adherence. Overall, this review underscores ezetimibe's evolving role in lipid management, providing valuable guidance for optimizing cardiovascular risk reduction strategies.

Statins are first-line pharmacotherapy for the treatment of elevated low-density lipoprotein cholesterol and are generally well-tolerated. However, some patients may experience statin-associated muscle symptoms (SAMS). This paper reviews recommendations for identification and management of patients with SAMS.

The National Lipid Association and other professional societies have issued guidance to assist clinicians in identifying and managing patients with partial or complete statin intolerance. The most common reason for intolerance is SAMS. This review discusses strategies to achieve therapeutic objectives for atherogenic lipoprotein management in patients with SAMS. Many patients who experience SAMS can tolerate some degree of statin therapy and non-statin medications are available as adjunctive or alternative treatments. With a thorough clinician-patient discussion and shared decision-making, a treatment plan can be identified to achieve therapeutic objectives and reduce the risk of atherosclerotic cardiovascular disease.

High-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI.

Data was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM).

A total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89-1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73-0.97, P = 0.02).

In patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI.

Blood lipid levels play a critical role in the progression of atherosclerosis. However, even with adequate lipid reduction, significant residual cardiovascular risk remains. Therefore, it is necessary to seek novel therapeutic strategies for atherosclerosis that can not only lower lipid levels but also inhibit inflammation simultaneously.

The fusion protein FD03-IL-1Ra was designed by linking the Angiopoietin-like 3 (ANGPTL3) nanobody and human interleukin-1 receptor antagonist (IL-1Ra) sequences to a mutated human immunoglobulin gamma 1 (IgG1) Fc. This construct was transfected into HEK293 cells for expression. The purity and thermal stability of the fusion protein were assessed using SDS-PAGE, SEC-HPLC, and differential scanning calorimetry. Binding affinities of the fusion protein to ANGPTL3 and IL-1 receptor were measured using Biacore T200. The biological activity of the fusion protein was validated through in vitro experiments. The therapeutic efficacy of the fusion protein was evaluated in an ApoE-/- mouse model of atherosclerosis, including serum lipid level determination, histological analysis of aorta and aortic sinus sections, and detection of inflammatory and oxidative stress markers. ImageJ software was utilized for quantitative image analysis. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post hoc test.

The FD03-IL-1Ra fusion protein was successfully expressed, with no polymer formation detected, and it demonstrated good thermal and conformational stability. High affinity for both murine and human ANGPTL3 was exhibited by FD03-IL-1Ra, and it was able to antagonize hANGPTL3's inhibition of LPL activity. FD03-IL-1Ra also showed high affinity for both murine and human IL-1R, inhibiting IL-6 expression in A549 cells induced by IL-1β stimulation, as well as suppressing IL-1β-induced activity inhibition in A375.S2 cells. Our study revealed that the fusion protein effectively lowered serum lipid levels and alleviated inflammatory responses in mice. Furthermore, the fusion protein enhanced plaque stability by increasing collagen content within atherosclerotic plaques.

These findings highlighted the potential of bifunctional interleukin-1 receptor antagonist and ANGPTL3 antibody fusion proteins for ameliorating the progression of atherosclerosis, presenting a promising novel therapeutic approach targeting both inflammation and lipid levels.