Lipid-lowering Agents Research Articles

Comprehensive developmental investigation on simvastatin enriched bioactive film forming spray using the quality by design paradigm: a prospective strategy for improved wound healing

The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach. Optimised formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 – time for 80% drug release − 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within the composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.

Lipid-Lowering Medications for Managing Dyslipidemia: A Narrative Review.

Dyslipidemia refers to the change in the normal levels of one or more lipid components in the bloodstream, which include triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Dyslipidemia represents a substantial source of danger for cardiovascular disease (CVD). Effectively managing dyslipidemia involves a thorough strategy that includes changing one's lifestyle and using medications that are specifically designed to target the complex processes involved in lipid metabolism. Lipid-lowering treatments play a crucial role in this approach, providing a wide range of medications that are developed to specifically target different components of dyslipidemia. Statins are the main drug among these medications. Other drugs that are used with statin or as monotherapy include fibrates, omega-3 fatty acids (OM3FAs), ezetimibe, bile acid sequestrants, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and bempedoic acid. Using the PubMed database, we reviewed the literature about dyslipidemia, drugs used for treating dyslipidemia, their efficacy parameters, and common adverse events. We also reviewed the international guidelines for treating dyslipidemia and discussed the future of lipid-lowering medications. More trials and experiments are still required to verify the effectiveness of many lipid-lowering drugs and to know their common adverse events to be able to manage them properly.

Garlic ameliorates atherosclerosis by regulating ferroptosis pathway: an integrated strategy of network pharmacology, bioinformatic and experimental verification.

Atherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic's anti-atherosclerotic effects remain unclear. This study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis. The study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets. The integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis. Garlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

Diabetic dyslipidemia and its predictors among people with diabetes in Ethiopia: systematic review and meta-analysis

BackgroundDyslipidemia is an imbalance of lipid profiles. It increases the chance of clogged arteries and may cause heart attacks, strokes, and other circulatory disorders. Dyslipidemia affects the general population, but its severity is higher in diabetic populations. As a result, the chance of dyslipidemia-associated morbidity and mortality is highest in diabetic patients. In Ethiopia, around 2 to 6.5% of the population live with diabetes, but their lipid profiles are inconsistent across the studies. Therefore, this study aimed to estimate the pooled prevalence of diabetic dyslipidemia and its predictors among people with diabetes in Ethiopia.MethodA systematic review and meta-analysis was conducted. The searches were carried out in MEDLINE via PubMed and OVID, EBSCO, Embase, and other supplementary gateways such as Google and Google Scholar, for articles published up to June 2023. The articles were searched and screened by title (ti), abstract (ab), and full text (ft). The quality of the eligible studies was assessed by the Newcastle–Ottawa scale. The heterogeneity was detected by the Cochrane Q statistic test and the I-squared (I2) test. Then subgroup analysis and meta-regression analysis were used to identify the source of the variations. A random or fixed-effect meta-analysis model was used to estimate the overall pooled prevalence and average effects. The publication bias was assessed by the funnel plot asymmetry test and/or Begg and Mazumdar’s test for rank correlation (p-value < 0.05). The protocol has been registered in an international database, the prospective register of systematic reviews (PROSPERO), with reference number CRD42023441572.ResultA total of 14 articles with 3662 participants were included in this review. The pooled prevalence of diabetic dyslipidemia in Ethiopia was found to be 65.7% (95% confidence interval (CI): 57.5, 73.9), I2 = 97%, and p-value < 0.001. The overall prevalence of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) were found to be 51.8% (95% CI: 45.1, 58.6) and 44.2% (95% CI: 32.8, 55.7), respectively, among lipid profiles. In meta-regression analysis, the sample size (p value = 0.01) is the covariate for the variation of the included studies. Being female (adjusted odds ratio (AOR): 3.9, 95% CI: 1.5, 10.1), physical inactivity (AOR: 2.6, 95% CI: 1.5, 4.3), and uncontrolled blood glucose (AOR: 4.2, 95% CI: 1.9, 9.4) were found to be the determinants of dyslipidemia among diabetic patients.ConclusionThis review revealed that the prevalence of diabetic dyslipidemia is high among people with diabetes in Ethiopia. Being female, having physical inactivity, and having uncontrolled blood glucose were found to be predictors of dyslipidemia among people with diabetes. Therefore, regular screening of lipid profiles and the provision of lipid-lowering agents should be strengthened to reduce life-threatening cardiovascular complications. Furthermore, interventions based on lifestyle modifications, such as regular physical activity and adequate blood glucose control, need to be encouraged.

INTERASPIRE a global cross-sectional survey of secondary prevention of cardiovascular disease (CVD) across six WHO regions

Abstract Introduction This survey of secondary prevention of CVD was conducted through National Societies of Cardiology across all WHO regions and included Kenya, Nigeria, Tanzania, Argentina, Colombia, Egypt, UAE, Poland, Portugal, Indonesia, China, Malaysia, Philippines and Singapore. Purpose The overall aim of INTERASPIRE was to assess the clinical implementation of risk reduction initiatives to reduce cardiovascular risk in line with lifestyle, risk factor and therapeutic targets defined in international and national guidelines on CVD prevention. Methods A consecutive sample of patients (&amp;gt; 18 and &amp;lt; 80 years) admitted to public hospitals in selected regions within each participating country with an acute ST elevation myocardial infarction (MI), Non-ST elevation MI, acute myocardial ischaemia or for elective revascularisation was identified retrospectively from medical record systems. Patients were invited to attend a clinical visit with trained research assistants at least 6 months but not more than 2 years after their event. The assessment included self-reported smoking status validated with an expired breath carbon monoxide measurement, self-reported participation in physical activity using the Godin validated questionnaire and standardised measurements of height, weight, blood pressure, blood lipids and blood glucose including an oral glucose tolerance test. Results 4548 (21.1% women) patients attended the clinical visit. 12.6% were smoking with wide variation across countries (1.9 – 27.3%). 48% of those who were smoking at the time of hospital admission had continued to smoke. 66.5% reported being sedentary with wide variation across countries (51.3 – 90.5%). 24% were obese and 40% centrally obese with a large difference between men (32.3%) and women (69.4%). 38% achieved a blood pressure target of &amp;lt; 130/80 mmHg, 19.2% achieved an LDL-C target of &amp;lt; 1.4 mmol/l and in patients with self-reported diabetes 56% achieved a target HbA1c of &amp;lt; 53 mmol/mol (7%). In those who did not report having diabetes, a further 9.8% had undetected diabetes and 26.9% impaired glucose tolerance. 48% were prescribed all four classes of cardioprotective drugs (antiplatelets, beta blockers, ACE/ARB, lipid lowering agents) with wide variation between countries (25% - 75%) and 88.3% were prescribed both antiplatelets and lipid lowering agents. Only 1219 (26.8%) were advised to attend cardiac rehabilitation with wide variation (4.5% to 58.9%) between countries. Overall only 9.0% (men 9.1%, women 9.1%) of all patients attended cardiac rehabilitation. Figure 1 shows the distribution of the INTERASPIRE Guideline Target Score. Conclusion There is substantial room for improvement in secondary prevention in patients with coronary disease globally. It is of concern that only 9% of patients received cardiac rehabilitation despite it being a Class 1 recommendation in all prevention guidelines with wide variation in advice and uptake between countries.Figure 1

Statistical Analysis Plan for the AIRCARD Study: Individual Long-Term Air and Noise Pollution Exposure and Cardiovascular Disease Incidence and Mortality - A Prospective Cohort Study Utilizing DANCAVAS and VIVA Screening Trials.

The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality. We aim to conduct a robust prospective cohort analysis assessing the cumulative and differential impacts of air and noise pollution exposure on cardiovascular disease and mortality. This study will adjust for relevant confounders, including traditional cardiovascular risk factors, socioeconomic indicators, and lipid-lowering agents. This prospective cohort study will include 27,022 male participants aged 65-74, recruited from the two large Danish DANCAVAS and VIVA trials, both population-based randomized, multicentered, clinically controlled studies. We will assess long-term exposure to air pollutants using the state-of-the-art DEHM/UBM/AirGIS modeling system and noise pollution through the Nord2000 and SoundPLAN models, covering data from 1979 to 2019. This statistical analysis plan is strictly formulated to predefine the analytical approach for all outcomes and key study variables before data access. The primary analysis will utilize Cox proportional hazards models, adjusted for confounders identified in our cohort (age, body mass index, hypertension, diabetes, smoking status, family history of heart disease, socioeconomic factors, and lipid-lowering agents). This statistical analysis plan further includes Spearman rank correlation to explore inter-pollutant associations. The AIRCARD study addresses global concerns about the impact of air and noise pollution on cardiovascular disease. This research is important for understanding how the pollutants contribute to cardiovascular disease. We aim to provide insights into this area, emphasizing the need for public health measures to mitigate pollution exposure. Our goal is to provide policymakers and healthcare professionals with information on the role of environmental factors in cardiovascular health that could influence global strategies to reduce the cardiovascular disease burden associated with pollution. The design of this SAP ensures transparency and verifiability, considering the complexities of evaluating environmental health impacts over an extended period.

The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.

Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as a major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, with statins emerging as the cornerstone treatment. These interventions play a crucial role in both primary and secondary prevention by effectively reducing cardiovascular risk through lipid profile enhancements. Beyond their primary lipid-lowering effects, extensive research indicates that these therapies exhibit pleiotropic actions, offering additional health benefits. These include anti-inflammatory properties, improvements in vascular health and glucose metabolism, and potential implications in cancer management. While statins and ezetimibe have been extensively studied, newer lipid-lowering agents also demonstrate similar pleiotropic effects, even in the absence of direct cardiovascular benefits. This narrative review explores the diverse pleiotropic properties of lipid-modifying therapies, emphasizing their non-lipid effects that contribute to reducing cardiovascular burden and exploring emerging benefits for non-cardiovascular conditions. Mechanistic insights into these actions are discussed alongside their potential therapeutic implications.

Obeticholic acid's effect on HDL function in MASH varies by diabetic status.

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro-inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid-lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro-inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre-β-HDL-the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study.

Strongylocentrotus intermedius Extract Suppresses Adiposity by Inhibiting Adipogenesis and Promoting Adipocyte Browning via AMPK Activation in 3T3-L1 Cells.

The current study aimed to determine whether Strongylocentrotus intermedius (S. intermedius) extract (SIE) exerts anti-obesity potentials employing 3T3-L1 cells as in vitro model. Herein we reported that treatment of SIE for 6 days reduced lipid accretion and triglyceride content whereas it increased the release of free glycerol. The inhibited lipid accumulation and induced lipolysis were evidenced by the downregulation of lipogenesis proteins, such as fatty acid synthase and lipoprotein lipase, and the upregulation of hormone-sensitive lipase expression. Furthermore, the downregulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1, highlights that reduced lipid accumulation is supported by lowering adipocyte differentiation. Additionally, treatment activates brown adipocyte phenotype in 3T3-L1 cells by inducing expression of brown adipose tissue-specific proteins, such as uncoupling protein 1 and peroxisome proliferator-activated receptor-γ coactivator 1α. Moreover, SIE induced the phosphorylation of AMP-activated protein kinase (AMPK). The pharmacological approach using AMPK inhibitor revealed that the restraining effect of SIE on adipogenesis and promotion of adipocyte browning were blocked. In GC-MS analysis, SIE was mainly composed of cholest-5-en-3-ol (36.71%) along with saturated and unsaturated fatty acids which have favorable anti-obesity potentials. These results reveal that SIE has the possibility as a lipid-lowering agent for the intervention of obesity.

Associations of very low Lipoprotein(a) levels with risks of new-onset diabetes and non-alcoholic liver disease

Background and aimsWe aimed to study the association of very low serum Lipoprotein(a) [Lp(a)] concentrations with new-onset type 2 diabetes (T2D) and non-alcoholic liver disease (NAFLD) in the context of statin usage in the UK Biobank, a large prospective population cohort. MethodsUsing an extended biomarker dataset, we identified 47,362 participants with very low Lp(a) concentrations (<3.8 nmol/L) from a total of 451,479 participants. With a median follow-up of 12.3 years, we assessed the risk of new-onset cardiometabolic diseases in participants stratified by statin usage with Cox proportional hazards models. We performed two-sample Mendelian randomization MR analyses to test causal relationship between genetically predicted Lp(a) and T2D and NAFLD. ResultsTaking the participants with Lp(a) within reportable range as the reference group, the hazard ratios (HR) for T2D were 1.07 (95 % confidence interval, CI 1.01–1.13) and for NAFLD 1.30 (95 % CI 1.20–1.41) respectively for participants with very low Lp(a) (<3.8 nmol/L). The risk for new-onset T2D was higher in participants using statins (adjusted HR 1.15; 95 % CI 1.05–1.27). The risk estimates for new-onset NAFLD were comparable in the analysis stratified by statin use. There was no evidence for causal links between genetically predicted Lp(a) and T2D nor NAFLD in two-sample MR analyses. ConclusionsVery low Lp(a) was associated with higher risks of T2D and NAFLD in a prospective analysis of the UK Biobank. The association with T2D was influenced by lipid lowering medication usage. MR analyses did not support causality for these inverse associations.

Serum lipid level as a biomarker in depressive disorder: A cross-sectional case control study

Objectives: This study investigates the potential of serum lipids as markers for depression, specifically focusing on symptoms such as suicidal ideation and anhedonia. In the context of advancing psychiatric biomarker research, this study aims to identify lipid-related markers and their underlying biological connections to depression, offering valuable insights for clinical practice and patient outcomes. Material and Methods: This case-control observational study was conducted over 18 months at a tertiary care center. The study enrolled patients aged 18–60 years diagnosed with depression attending outpatient and inpatient departments, totaling 100 subjects, including 100 cases and 100 controls, with gender and body mass index (BMI)-matched controls. Inclusion criteria for cases required depression diagnosis using the International Classification of Diseases-10-Diagnostic Criteria for Research criteria, while controls comprised healthy individuals within the same age range. Exclusion criteria encompassed comorbid psychiatric illnesses, substance use disorders (except tobacco), unstable medical conditions, lipid-lowering agent use, and a BMI over 30. Clinical assessments, including the Hamilton Depression Rating Scale-17 item scale, Modified Scale for Suicidal Ideation, and Snaith-Hamilton Pleasure Scale-Clinician administered, were administered. Serum lipid parameters, including triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL)-cholesterol, were measured. Results: In a cross-sectional case-control study (n = 200), we examined serum lipids as potential depression biomarkers. Cases (n = 100) matched controls in age, BMI, and gender. Cases had lower TC (153.27 mg/dL vs. 171.34 mg/dL, P &lt; 0.01*). Serum TG and low-density lipoprotein also varied significantly with depression severity (P &lt; 0.01*). However, HDL levels remained consistent. No significant associations were found between suicidal ideation and anhedonia, and post hoc analyses revealed significant differences (P ≤ 0.05) in lipid parameters across various depression severity levels. Conclusion: These findings suggest a complex relationship between serum lipids and depression, with potential implications for understanding the biological underpinnings of depression and its severity. However, there was no such relationship that was observed between serum lipids and anhedonia or suicidal ideation. These insights could inform clinical practices and improve patient outcomes in depression management.

Benzoate glycosides from Gentiana scabra Bge. and their lipid-lowering activity

Seven undescribed benzoate glycosides (1−7) and five known ones (8−12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 μM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents.

A significant presence in atherosclerotic cardiovascular disease: Remnant cholesterol: A review.

The current first-line treatment for atherosclerotic cardiovascular disease (ASCVD) involves the reduction of a patient's low-density lipoprotein cholesterol (LDL-C) levels through the use of lipid-lowering drugs. However, even when other risk factors such as hypertension and diabetes are effectively managed, there remains a residual cardiovascular risk in these patients despite achieving target LDL-C levels with statins and new lipid-lowering medications. This risk was previously believed to be associated with lipid components other than LDL, such as triglycerides. However, recent studies have unveiled the crucial role of remnant cholesterol (RC) in atherosclerosis, not just triglycerides. The metabolized product of triglyceride-rich lipoproteins is referred to as triglyceride-rich remnant lipoprotein particles, and its cholesterol component is known as RC. Numerous pieces of evidence from epidemiological investigations and genetic studies demonstrate that RC plays a significant role in predicting the incidence of ASCVD. As a novel marker for atherosclerosis prediction, when LDL-C is appropriately controlled, RC should be prioritized for attention and intervention among individuals at high risk of ASCVD. Therefore, reducing RC levels through the use of various lipid-lowering drugs may yield long-term benefits. Nevertheless, routine testing of RC in clinical practice remains controversial, necessitating further research on the treatment of elevated RC levels to evaluate the advantages of reducing RC in patients at high risk of ASCVD.

Exploring the Perceptions and Behaviours of UK Prescribers Concerning Novel Lipid-Lowering Agent Prescriptions: A Qualitative Study.

Reducing low-density lipoprotein cholesterol levels lowers the risk of atherosclerotic cardiovascular disease. With the current and future portfolios of emerging lipid-lowering therapies included in various national and international guidelines, the objectives of this study were (i) to investigate the perceptions of UK prescribers', including doctors, pharmacists, and nurses, on current lipid management for cardiovascular diseases and prescriptions of novel lipid-lowering therapies, and (ii) to explore the challenges and facilitating factors of prescribing novel lipid-lowering therapies through qualitative interviews. Qualitative semi-structured interviews with twelve medical and non-medical prescribers were conducted, around 20-30 min in length. The interviews were audio-recorded and transcribed on an online platform. A thematic analysis was deployed. Four major themes emerged from the analysis: (1) prescribing barriers; (2) prescribing enablers; (3) inter-profession variability; and (4) health literacy. These themes highlighted the contrast between the need for optimal shared decision making and the various constraints in practice. Participants expressed their inexperience with novel lipid-lowering therapies and acknowledged the requirement and importance of these agents for primary cardiovascular disease prevention. Participants recognised confidence and competence as key drivers for prescribing therapies and welcomed further education and training to enhance their skillset. Patients' misconceptions towards current lipid-lowering therapies contributed to their refusal of newer agents, highlighting a requirement to improve patient education. Targeting communities through awareness campaigns was identified as a viable solution.

Repurposing lipid-lowering drugs on asthma and lung function: evidence from a genetic association analysis

ObjectiveTo explore the correlation between asthma risk and genetic variants affecting the expression or function of lipid-lowering drug targets.MethodsWe conducted Mendelian randomization (MR) analyses using variants in several genes associated with lipid-lowering medication targets: HMGCR (statin target), PCSK9 (alirocumab target), NPC1L1 (ezetimibe target), APOB (mipomersen target), ANGPTL3 (evinacumab target), PPARA (fenofibrate target), and APOC3 (volanesorsen target), as well as LDLR and LPL. Our objective was to investigate the relationship between lipid-lowering drugs and asthma through MR. Finally, we assessed the efficacy and stability of the MR analysis using the MR Egger and inverse variance weighted (IVW) methods.ResultsThe elevated triglyceride (TG) levels associated with the APOC3, and LPL targets were found to increase asthma risk. Conversely, higher LDL-C levels driven by LDLR were found to decrease asthma risk. Additionally, LDL-C levels (driven by APOB, NPC1L1 and HMGCR targets) and TG levels (driven by the LPL target) were associated with improved lung function (FEV1/FVC). LDL-C levels driven by PCSK9 were associated with decreased lung function (FEV1/FVC).ConclusionIn conclusion, our findings suggest a likely causal relationship between asthma and lipid-lowering drugs. Moreover, there is compelling evidence indicating that lipid-lowering therapies could play a crucial role in the future management of asthma.

PCSK9 Inhibitors and Infection-Related Adverse Events: A Pharmacovigilance Study Using the World Health Organization VigiBase.

Protein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are novel lipid-lowering agents used in patients with cardiovascular disease. Despite reassuring safety data from pivotal trials, increasing evidence from real-world studies suggests that PCSK9i increase the risk of bacterial and viral infections. Therefore, this study aimed to identify signals of infection-related adverse events (AEs) associated with PCSK9i. We performed an observational pharmacovigilance study using the World Health Organization's VigiBase, recorded up to December 2022. We included individual case safety reports (ICSRs) of PCSK9 inhibitors, alirocumab and evolocumab, and compared them with those of other drugs. Infection-related ICSRs were retrieved from the Medical Dictionary for Regulatory Activities System Organ Class 'infections and infestations.' Among 114,293 reports (258,099 drug-AE pairs) related to PCSK9 inhibitors, 54% included female patients, 41% included patients aged ≥65 years, and 82% included patients who received evolocumab. Additionally, beyond AEs recognized by regulatory authorities, organ infections such as influenza (reporting odds ratio [ROR] 2.89, 95% confidence interval [CI] 2.74-3.05), gastric infections (ROR 2.47, 95% CI 1.63-3.75), and kidney infections (ROR 1.36, 95% CI 1.06-1.73) were observed. Sensitivity analysis indicated a heightened risk of infection-related AEs associated with PCSK9i regardless of the specific drug type. In addition to the labelled respiratory infections, six infection-related symptoms in the gastrointestinal, urinary, and renal organs were identified. Our findings support the need for systematic surveillance of infections among PCSK9i users.

Scoping Review on Associations Between Dietary Intake and Lipid-Lowering Medication Use

Scoping Review on Associations Between Dietary Intake and Lipid-Lowering Medication Use

Meniere's Disease and Statins: Is There an Association? A Single Institution Study.

Meniere's disease (MD) is a complex inner ear disease related to endolymphatic hydrops and with multiple other etiologies suggested including autoimmunity and vascular insufficiency. Statins are lipid-lowering medications with additional effects including reduction of oxidative stress and inflammation. We performed a cross-sectional study comparing patients with MD on statins to those not on statins to see if there is any difference in disease activity (major vertigo spells) and hearing stage utilizing linear and logistic regression. Our analysis showed no difference in the average number of major vertigo spells per month (β = .07, P = .9) between statin users and nonusers; however, statin users were found to have lower odds of worse hearing (odds ratio = 0.46, P = .047). Further studies are needed to confirm our results.

Assessment of bone tissue cytoarchitectonics by 2D 1H NMR relaxometry maps

Bone is a complex tissue that fulfills the role of a resistance structure. This quality is most commonly assessed by bone densitometry, but bone strength may not only be related to bone mineral density but also to the preservation of bone cytoarchitectonics. The study included two groups of rats, ovariectomized and non-ovariectomized. Each group was divided into three batches: control, simvastatin-treated, and fenofibrate-treated. In the ovariectomized group, hypolipidemic treatment was instituted at 12 weeks post ovariectomy. One rat from each of the 6 batches was sacrificed 8 weeks after the start of treatment in the group. The experimental study was performed using a Bruker Minispec mq 20 spectrometer operating at a frequency of 20 MHz, subsequently also performed by 1H T2-T2 molecular exchange maps. The results were represented by T2-T2 molecular exchange maps that showed, comparatively, both pore size and their interconnectivity at the level of the femoral epiphysis, being able to evaluate both the effect of estrogen on bone tissue biology and the effect of the lipid-lowering medication, simvastatin, and fenofibrate, in both the presence and absence of estrogen. T2-T2 molecular exchange maps showed that the absence of estrogen results in an increase in bone tissue pore size and interconnectivity. In the presence of estrogen, lipid-lowering medication, both simvastatin and fenofibrate alter bone tissue cytoarchitectonics by reducing pore interconnectivity. In the absence of estrogen, fenofibrate improves bone tissue cytoarchitectonics, the T2-T2 molecular exchange map being similar to that of non-osteoporotic bone tissue.

Burden of Disease in Refugee Patients with Diabetes on the Island of Lesvos-The Experience of a Frontline General Hospital.

We sought to evaluate the degree of hyperglycaemia in refugees with known or recently diagnosed diabetes, to assess cardiovascular comorbidities and diabetes complications, to review and provide available therapeutic options, and to compare, if possible, the situation in Lesvos with other locations hosting refugee populations, thus raising our awareness towards barriers to accessing healthcare and managing diabetes in these vulnerable populations and to propose follow-up strategies. We retrospectively studied 69 refugee patients (68% of Afghan origin, 64% female) with diabetes mellitus (81% with type 2 diabetes), who were referred to the diabetes outpatient clinics of the General Hospital of Mytilene, Lesvos, Greece, between June 2019 and December 2020. Age, Body Mass Index, diabetes duration, glycaemic control (HbA1c and random glucose), blood pressure, estimated renal function, lipid profile, diabetes complications and current medication were documented at presentation and during subsequent visits. For all patients with type 1 diabetes and type 2 diabetes, age at presentation was 17.7 and 48.1 years, BMI 19.6 kg/m2 and 28.9 kg/m2 and HbA1c 9.6% and 8.7%, respectively (all medians). One-third (29%) of patients with type 2 diabetes presented either with interrupted or with no previous pharmacological treatment. Insulin was administered to only 21% of refugees with poorly controlled type 2 diabetes. Only half of the patients (48%) with hypertension were taking antihypertensive medication and one-sixth (17%) were taking lipid-lowering medication. Forty-two per cent (42%) of patients were lost to follow-up. Our results showed that a significant portion of refugees with diabetes have either no treatment at all or have had their treatment discontinued, that insulin is still underutilised and that a significant portion of patients are lost to follow-up. It is essential to enhance our ability to identify refugees who may be at risk of developing diabetes or experiencing complications related to the disease. Additionally, it is important to expand access to crucial treatment and monitoring services. By improving our policies for managing non-communicable diseases, we can better support the health and well-being of these vulnerable populations. Furthermore, it is vital to recognize that Greece cannot bear the burden of the refugee crisis alone; international support and collaboration are necessary to address these challenges effectively.