Hypercholesterolemia Research Articles

Causal associations of ischemic stroke, metabolic factors, and related medications with epilepsy: a Mendelian randomization study

BackgroundEarlier researches have demonstrated that ischemic stroke, metabolic factors, and associated medications may influence the risk of epilepsy. Nevertheless, the causality between these elements and epilepsy remains inconclusive. This study aims to examine whether ischemic stroke, metabolic factors, and related medications affect the overall risk of epilepsy.MethodsWe used single nucleotide polymorphisms associated with ischemic stroke, hypothyroidism, hypertension, blood glucose levels, high cholesterol, serum 25-Hydroxyvitamin D levels, testosterone, HMG CoA reductase inhibitors, and beta-blocking agents as instrumental variables in a Mendelian randomization technique to investigate causality with epilepsy. Multiple sensitivity methods were performed to evaluate pleiotropy and heterogeneity.ResultsThe IVW analysis revealed positive associations between ischemic stroke (OR = 1.29; p = 0.020), hypothyroidism (OR = 1.05; p = 0.048), high blood pressure (OR = 1.10; p = 0.028), high cholesterol (OR = 1.10; p = 0.024), HMG CoA reductase inhibitors (OR = 1.19; p = 0.003), beta-blocking agents (OR = 1.20; p = 0.006), and the risk of epilepsy. Conversely, blood glucose levels (OR = 0.79; p = 0.009), serum 25-Hydroxyvitamin D levels (OR = 0.75; p = 0.020), and testosterone (OR = 0.62; p = 0.019) exhibited negative associations with the risk of epilepsy. Sensitivity analyses confirmed the robustness of these findings (p > 0.05).ConclusionOur research suggests that ischemic stroke, hypothyroidism, high blood pressure, high cholesterol, HMG CoA reductase inhibitors, and beta-blockers may increase the risk of epilepsy, whereas serum 25-Hydroxyvitamin D levels and blood glucose levels may reduce the risk.

A review on the treatment of hyperlipidemia with Erchen Decoction

Hyperlipidemia, commonly referred to as dyslipidemia, is characterized by elevated serum cholesterol and/or triglyceride levels. This condition contributes significantly to the high mortality rates associated with cardiovascular diseases, posing a serious threat to global health. Although statins remain the predominant pharmacological treatment for hyperlipidemia, their associated side effects have led to a growing interest in alternative therapeutic approaches. Traditional Chinese Medicine (TCM) is exploring these alternatives, with the Erchen Decoction (ECD) emerging as a promising candidate. This review aims to summarize current clinical research, elucidate the mechanisms of action, and assess the compatibility of ECD in the management of hyperlipidemia. By doing so, we hope to provide valuable insights and references for clinical practice and future research.

HPB SO11 - Dropped Gallstones After Laparoscopic Cholecystectomy: An Umbrella Review

Abstract Background Gallstones (cholelithiasis) are solid formations in the gallbladder or biliary tract due to high cholesterol or bilirubin levels, affecting 10-20% of adults. Over 20% of those affected show symptoms like biliary colic. Gallstones can be cholesterol, black pigment, or brown pigment, with cholesterol stones being the most common. The persistence of gallstones following laparoscopic cholecystectomy (LC) poses a significant clinical challenge, potentially leading to morbidity and diagnostic complexities, often with delayed recognition. These complications can present as various intraabdominal conditions such as abscesses (intraabdominal or abdominal wall), fistula formation, peritonitis, bowel perforation, or ileus. Method We performed an extensive search of the academic literature spanning several databases, namely PubMed, Embase, Scopus, Web of Science, and Google Scholar. Inclusion criteria for this research encompassed systematic reviews, with or without meta-analysis, focusing on the examination of spilled gallstones in terms of signs, symptoms, diagnosis, imaging, and management. The assessment of potential bias in the final study selection was undertaken utilizing the R-AMSTAR and Risk of Bias in Systematic Reviews (ROBIS) assessment tools. Results The most prevalent sites for lost gallstones were identified as the right subhepatic, perihepatic, retroperitoneal, right flank, and pelvic regions. Multiple stones were found to be more common than single stones. Clinical presentations included the presence of abdominal masses simulating malignancy, intestinal obstruction, and pelvic pain or fistula formation. Surgical intervention emerged as the primary treatment approach. Pain localized to the right upper quadrant was reported by 24% of participants. Computed tomography (CT) was the most frequently employed diagnostic modality for stone identification (70.2%), followed by ultrasonography (US) (63.2%) and X-ray (42.9%). Conclusion Our research underscores a significant area that has received limited attention in existing literature. The occurrence of spilled gallstones presents challenges in diagnosis and carries the potential for severe post-laparoscopic cholecystectomy complications. A notable gap exists in the education of both surgeons and patients regarding this complication, emphasizing the need for heightened awareness among surgeons. Given the considerable variability observed between laparoscopic cholecystectomy procedures and the onset of associated symptoms, comprehensive studies with larger cohorts are imperative for elucidating pertinent risk factors and devising effective interventions.

Relationship of Body Fat Distribution and Anthropometric Status with Lipid Profiles in Ethnic Minang Adult Women

Background The prevalence of metabolic syndrome is increasing, and it is a risk factor for cardiovascular disease. One of the indicators of metabolic syndrome is dyslipidemia. Objective This study analyzes adult women's body fat distribution, anthropometric status, and lipid profiles. Methods This study used a cross-sectional design with simple random sampling. A total of 159 adult women aged 25-44 living in the Pesisir Selatan district participated in the study. Ethical approval was obtained, and the respondents were not taking cholesterol-lowering drugs. Body fat distribution, anthropometric status, and lipid profile data were assessed using standard procedures and compared with the categories recommended for Indonesian women. Results The average age of respondents was 36.6 years. 45.3% of the respondents suffered from dyslipidemia. Most of them were obese based on BMI and had central obesity based on WC. Additionally, 76% had an above-normal fat mass. Lipid profile data showed that some (45.3%) had high total cholesterol, 44% had high LDL, 8% had high TG, and a small proportion (15%) had low HDL levels. There was a significant relationship (p < 0.01) between body fat distribution and anthropometric status with lipid profiles, except for total cholesterol (p < 0.05). A negative correlation was found between body fat percentage, BMI, and WC with HDL, while a positive correlation existed between body fat percentage, BMI, and WC with TG and LDL levels. Conclusions Obesity is found to be higher, and dyslipidemia begins to occur in women at a younger age, increasing the risk of metabolic syndrome. Education and routine screening are necessary to prevent non-communicable diseases.

Abstract 4136889: Impact of hypercholesterolemia definitions on prevalence and prognosis of patients without standard modifiable cardiovascular risk factors and ST-segment elevation myocardial infarction.

Background: In patients with acute myocardial infarction (AMI), recent studies have intriguingly reported that up to a quarter of AMI patients have none of the 4 main standard modifiable cardiovascular (CV) risk factors (SMuRFs) (i.e. hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia (HC), and smoking) and have worse mortality. Hypothesis: We tested the hypothesis that the prevalence and prognosis of SMuRF-less patients varies with the definition of risk factors. Aim: Using a French nationwide MI cohort, we aimed to compare SMuRF-less ST-segment elevation MI (STEMI) patients according to 2 HC definitions, given the possibility of using several HC criteria. Methods: The French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing AMI cohort, collecting data from all patients hospitalized for AMI < 48 h of symptom onset in 21 French centers. STEMI patients without prior CAD admitted in 2019 to 2022 were studied. DM was defined as prior DM diagnosis, HbA1c>7% or anti-diabetic medications, ongoing or at discharge, HTN was defined as treated or previous HTN diagnosis and smoking was defined as current smoking within the past month. Restrictive HC (RHC) was defined as either a previous diagnosis of HC or statin therapy. Permissive HC (PHC) was defined as previous diagnosis of HC or lipid-lowering therapy, or LDL-C > 135 mg/dL or total Cholesterol > 213 mg/dL. Results: Among 8008 patients (mean age 61.5± 12.9y, 22.6% women), 41.4% were smokers, 17.4% had diabetes, and 38.5% HTN. According to HC definitions, the prevalence of HC almost doubled, ranging from 30.3% for RHC to 61.0% for PHC. Consequently, the prevalence of SMuRF-less was divided by ≈ two (21.1% vs 11.3%, respectively), depending on the definition of HC used. Age and sex-adjusted logistic regression analysis showed that PHC, but not RHC, was associated with lower odds of in-hospital death ( figure ). Moreover, having multiple SMuRFs was associated with higher risk of mortality than no SMuRF when using RHC, but not with PHC definition. Conclusion: The prevalence and impact on acute mortality of being SMURFless varies largely with the definition of HC. More research is needed, using HC standardized definitions to explore these patients. Frenchie: was supported in part by the RHU iVASC grant ANR-16-RHUS-00010 from the French National Research Agency (ANR) as part of the Investissements d’Avenir program. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956.

Abstract 4136294: Carbohydrate intakes and cardiovascular disease risk factors in South Asians: Results from 56,024 participants in Bangladesh, India, Pakistan, and Sri Lanka

Background: Evidence on effects of carbohydrate intake with cardiovascular disease risk factors is inconsistent and has limited generalizability to diverse populations such as South Asians, whose carbohydrate intakes are typically high. Aims: We examined the association of the quantity and types of carbohydrate intake with two risk factors for major cardiovascular events– hypertension (HT) and hypercholesterolemia (HC). Methods: We analyzed cross-sectional data from participants aged ≥18 years in the South Asia Biobank in Bangladesh, India, Pakistan, and Sri Lanka. Using dietary data assessed with interviewer-led 24h diet recalls, we calculated intakes of total and subtypes of carbohydrates and several indices of carbohydrate quality. Primary outcomes were HT and HC, defined by medication use, doctor diagnosis, blood pressure and blood lipid levels. With mixed effects Poisson regression, HT and HC was regressed on quantiles of carbohydrate intakes by country to estimate prevalence ratios (PR) and 95% confidence intervals (CI), followed by meta-analysis pooling country-specific estimates. We examined interactions by diabetes status and adiposity. Results: Of 56,024 adults, 36.6% had HT, 16.1% had HC. In pooled multivariable analyses comparing extreme quantiles, total carbohydrate intake was not associated with HT or HC prevalence. Fructose, free sugar and free sugar-to-fiber ratio were associated with higher prevalence of HT (PRs Q5vsQ1 : 1.03-1.15). Higher intakes of cereal fiber (PR Q4vsQ1 : 0.96, 95% CI: 0.95-0.98) and legume fiber (PR Q4vsQ1 : 0.98, 95% CI: 0.97-0.98) were associated with lower prevalence of HT and higher cereal fiber intake with lower HC prevalence (PR Q5vsQ1 : 0.80, 95% CI: 0.75-0.85). Diabetes and adiposity were observed as effect-modifiers (p<0.001). There were null associations in adults with diabetes but in non-diabetic adults, free sugar intake was related positively with HT (PR Q5vsQ1 : 1.07, 95% CI: 1.05-1.09) while fiber intake was inversely related (PR Q5vsQ1 : 0.98, 0.95-0.97). Starch, sugar and free sugar intake were associated positively with HT prevalence in adults with high body fat (≥20% for men; ≥30% for women) and visceral fat (≥10%) levels (PRs Q5vsQ1 : 1.03-1.20); associations were null for low body and visceral fat levels. Associations varied by country (between-country heterogeneity I 2 >60%). Conclusion: Associations of dietary carbohydrates with HT and HC depended on the quality and type of intake in South Asians.

Abstract 4130641: The Role of Oxidized Phospholipids in Triggering Trained Immunity and Accelerating Atherosclerotic Plaque Inflammation during Cholesterol Cycling

Introduction: Oxidized phospholipids (OxPL) derived from LDL play a crucial role in the development and progression of atherosclerosis by promoting chronic inflammation and formation of foam cells. The natural antibody E06, binding to OxPL, diminishes macrophage uptake of OxLDL in vitro and decreases atherosclerosis progression in vivo. In our prior work using a model of plasma cholesterol cycling (high-low-high), resulting in atherosclerotic plaque Progression (P)-Regression (PR)-re-Progression (PRP), respectively, we observed accelerated plaque inflammation in the PRP group relative to mice with non-cycling high cholesterol. Hypothesis: OxPL promotes plaque inflammation in the cholesterol cycling model via trained immunity and that the E06 antibody will mitigate this process. Methods: We utilized transgenic "E06 mice" that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter on the Ldlr−/− background. Both E06 mice and Ldlr-/- mice were subjected to high cholesterol diets (HCD) and categorized into three groups in the cholesterol cycling model: Baseline Progression (P), PR and PRP. Plaque regression was induced by ApoB-ASO injection, which significantly lowered cholesterol levels by inhibiting LDL production. Results: As before, Ldlr-/- mice in the PRP group exhibited accelerated plaque inflammation post-regression shown by CD68 staining on aortic roots. Notably, this acceleration was significantly inhibited in the E06 mice, highlighting the protective effects of E06 against plaque re-progression. Additionally, flow cytometry of peripheral blood exhibited reduced total monocytes and Ly6Chi-monocytes (thought to become inflammatory macrophages in plaques), alongside increased Ly6Clo-monocytes (thought to become inflammation resolving macrophages in plaques) among E06 mice in the PRP group compared to Ldlr-/- mice. Ex-vivo stimulation of bone marrow cells with the inflammatory stimulus LPS demonstrated higher IL-6 levels in supernatant in Ldlr-/- mice versus E06 mice in the PRP group, suggesting OXPL-induced trained immunity in bone marrow precursors of monocytes and macrophages is involved. Conclusion: The acceleration of plaque inflammation in cholesterol cycling model was significantly inhibited in the E06 mice. These results provide insight into the increased risk of cardiovascular disease in individuals with intermittent adherence to statins who undergo cholesterol cycling.

Abstract 4120312: Patient Perspectives on Barriers and Facilitators to Familial Hypercholesterolemia Cascade Testing Through the Lens of the Socio-Ecological Model

Background: Low uptake of Familial Hypercholesterolemia (FH) cascade testing, the stepwise identification of at-risk relatives, leads to missed opportunities for atherosclerotic cardiovascular disease (ASCVD) prevention. The IMPACT-FH study offered strategies (packet, chatbot, and direct contact) to support FH cascade testing. Hypothesis: We hypothesized that IMPACT-FH strategies would facilitate cascade testing uptake and overcome persistent barriers to cascade testing. Aim: We aimed to understand barriers and facilitators to FH cascade testing in the context of the socio-ecological model (SEM) which provides a framework to examine the interconnected influences of intrapersonal, interpersonal, institutional, community, and policy levels. Methods: Semi-structured interviews were conducted with IMPACT-FH study participants. The SEM informed qualitative analysis to identify barriers and facilitators to FH cascade testing. Results: A total of 15 FH probands (initial family member tested) and 12 relatives were interviewed, of whom the majority (59%) were female with an average age of 55.7 years. All relatives completed cascade testing. At the interpersonal level, probands reported that relatives’ attitudes about high cholesterol, including seriousness and treatability, were a barrier or facilitator to cascade testing. Probands explained how relatives’ beliefs were informed by interactions with their clinicians and societal beliefs about cholesterol (i.e., medication stigma). Interpersonally, probands described challenges overcoming relatives’ beliefs and a reluctance to encourage relatives to complete testing despite the availability of novel strategies. Probands and relatives reported that insurance policies and concerns about testing costs informed cascade testing decision-making. Institutional strategies to provide low-cost testing and cost transparency were described as facilitators. Variable access to clinicians with genetics expertise and licensure laws were described as barriers by out-of-state relatives. Probands and relatives agreed that strategies providing direct access genetics expertise (i.e., direct contact, chatbot) helped address these barriers. Conclusion: The IMPACT-FH study ameliorated barriers at higher levels of the SEM related to access to genetics expertise and cost. Intra- and interpersonal barriers remained challenging to overcome. To improve FH detection and ASCVD prevention, it is important to address barriers at all levels of the SEM.

Abstract 4142792: VA Lipid Optimization Reimagined Quality Improvement Project (VALOR-QI) at the Dallas VA

The Dallas VA is one of the 50 VA sites participating in a national quality improvement initiative called VALOR-QI: VA Lipid Optimization Reimagined Quality Improvement Project. VALOR-QI is a collaborative project between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting veterans’ cardiovascular (CV) health. As part of the program, VA sites work with an AHA QI Consultant to develop and deploy a local quality improvement plan to help overcome site specific barriers preventing veterans from achieving optimal cholesterol levels. We hypothesize that the QI strategies implemented will positively impact lipid levels and ultimately CV outcomes among high-risk patients. We aim to assess potential barriers to achieving LDL-C <70 mg/dL and develop efficient ways to maintain LDL-C goal. Our approach to the VALOR-QI program at Dallas VA is by enrolling patients with established ASCVD and LDL-C > 70 mg/dL from cardiology, vascular, diabetes, lipid, and independent PharmD clinics. These patients are followed by a health coach every 2- 6 months. Medical adherence is enforced by the health coach ensuring timely refills and reminders. Lifestyle modifications are encouraged via educational materials, referral to dieticians, recreation classes, and tobacco cessation. Patients are also encouraged to sign up for patient portal (my HealtheVet) to access electronic medical records and expedite communication with their healthcare team. The health coach provides individualized counseling regarding lipid lowering treatment and acts as liaison between patients and their providers. VALOR-QI was launched at Dallas VA in Jan 2023. As of May 17 th , 2024, an interim analysis showed that out of 132 veterans engaged, 49 (37.1%) achieved target LDL-C, 66 (50%) received educational material, 4 (3.03%) were referred to dieticians, 10 (7.58%) were referred to recreation programs, and 4 (17.4% of active smokers) were interested in quitting. In conclusion, our VALOR-QI strategy at Dallas VA showed encouraging results, but it is premature to make final conclusions. The support of a health coach showed improved medication adherence, health literacy, and lifestyle modification, thus achieving LDL-C target. Major barriers to achieving target LDL-C were health literacy about high cholesterol, challenges in navigating the health care system, and treatment inertia among patients and providers.

Abstract 4137713: Epsin-Mediated PCSK9-LDLR Interaction: A New Therapeutic Target for Atherosclerosis

Introduction: Atherosclerosis, a leading cause of cardiovascular diseases, causes about 17.9 million deaths annually. It is driven by high levels of LDL cholesterol (LDL-C). The liver's LDL receptor (LDLR) removes LDL-C from the bloodstream, but its degradation by PCSK9 exacerbates the condition. Epsin, an endocytic adaptor protein crucial for clathrin-mediated endocytosis, plays a significant role in atherosclerosis, particularly lipid metabolism. Hypothesis: We propose that hepatic epsins significantly contribute to atherosclerosis by facilitating the PCSK9-induced degradation of LDLR, thus impeding LDL-C clearance. Objectives: This study aims to investigate hepatic epsins' role in PCSK9-mediated LDLR degradation and its effects on LDL-C levels and atherosclerosis development. Using bioinformatics, we will analyze enriched pathways and networks to study epsins modulation, which will be validated through biochemical assays and in vivo experiments. Methods: Liver-specific double knockout (DKO) mice lacking epsin1 and epsin2 were created on an ApoE -/- background. Atherosclerosis was induced using a Western diet (WD), and blood cholesterol and triglyceride levels were monitored. We employed high-resolution single-cell RNA sequencing (scRNA-seq) to analyze cellular transitions, intercellular interactions, and Gene Ontology pathway enrichment within hepatocyte-derived data. Results: RNA velocity reveals the transition from lipogenic Alb hi Hepatocytes to glucogenic Hnf4a hi Hepatocytes in Liver-DKO mice on an ApoE -/- background on a WD. Liver-DKO mice on an ApoE -/- background on a WD exhibited significantly reduced atherogenesis and lower blood cholesterol and triglyceride levels compared with wild-type on an ApoE -/- background on a WD. Gene Ontology enrichment analysis showed elevated pathways for LDL particle clearance and enhanced LDLR-cholesterol communication scores in Liver-DKO mice, suggesting improved LDL-C clearance. Nanoparticle-encapsulated siRNAs targeting liver epsins effectively inhibited atherosclerosis. Conclusion: Epsin depletion in the liver upregulated LDLR protein levels, and PCSK9-triggered LDLR degradation was abolished, preventing atheroma progression. Targeting liver epsins presents a novel therapeutic strategy for atherosclerosis, supported by network analysis and predictive modeling for effective interventions.

Abstract 4137243: Dynamic changes of pericoronary fat attenuation index predicting changes of coronary plaque burden

Background: Percent atheroma volume (PAV) is a validated index of coronary plaque burden, linking to adverse cardiac events. Meanwhile, pericoronary fat attenuation index (FAI) on coronary computed tomography angiography (CCTA) image is a novel prognostic marker of coronary inflammation. Research Questions: It is unknown the impact of coronary inflammation (i.e., FAI) on the progression of coronary PAV in patients at an increased risk of adverse cardiac events. Methods: Patients with type 2 diabetes mellitus (T2DM) who underwent at least two clinically indicated CCTA examinations (time interval > 1 year) at our center were potentially eligible for enrollment. Eligible patients presented with more than one study plaque, defined as non-obstructive stenosis at baseline and not being intervened during serial CCTA. Longitudinal CCTA images were assessed for FAI and compositional plaque characteristics (e.g., PAV) using dedicated post-processing softwares. The relationships between changes in FAI and progression of compositional PAV were examined using the logistic and linear regression analysis. Results: A total of 204 T2DM patients (mean age, 61.2 ± 9.3 years; male, 68.1%) with 366 study plaques were enrolled. All patients were treated with statins, and their time interval between longitudinal CCTAs was 14.1 (12.9, 17.6) months. Compared with patients with improved coronary inflammation (ΔFAI ≤ 0), those with deteriorated coronary inflammation (ΔFAI > 0) had lower high density lipoprotein cholesterol and baseline FAI, whereas higher blood pressure (all p < 0.05). Meanwhile, compared to patients with ΔFAI ≤ 0, those with ΔFAI > 0 had more Δoverall and Δnon-calcified PAV (all p < 0.05). Importantly, these findings were consistent in a dedicated propensity score matching analysis. In logistic regression analysis, ΔFAI > 0 was associated with annual progression of overall PAV and non-calcified PAV, whereas ΔFAI ≤ 0 associated with annual regression of overall PAV and non-calcified PAV after adjusting for cardiac risk factors, baseline PAV and medications (all p < 0.05). Similarly, in linear regression analysis, changes of FAI were independently positively associated with annual changes of overall PAV (β=0.545, p< 0.001) and non-calcified PAV (β=0.461, p< 0.001) (Figure 1). Conclusion: In this longitudinal CCTA study, changes of coronary inflammation are closely correlated with changes of overall and non-calcified PAV among T2DM patients treated with statins.

Abstract 4137414: Uncovering MLKL as a Novel Regulator of Endothelial Cells in the Splenic Niche to Repress Hematopoiesis During Atherosclerosis

Background: Atherosclerosis occurs as lipid and immune cell rich plaques deposit within the arterial wall of the heart. These immune cells are produced from hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) and spleen, a process known as hematopoiesis that is dictated by their microenvironment, including endothelial cells (ECs). Objective: While others have shown adverse remodeling of BM ECs during atherogenesis, whether splenic ECs show a similar dysfunction leading to exacerbated hematopoiesis has not been described. Methods: We analyzed RNA sequencing data from chow fed C57Bl/6 mice and high cholesterol diet (HCD) fed Apoe -/- mouse BM and splenic ECs obtained from published studies, as well as our own. In vivo studies were performed in mice on an atherogenic background ( Apoe -/-& Ldlr -/-) fed a HCD for 4 to 16 weeks. Knockdown of the mixed lineage kinase domain-like protein ( Mlkl KD) was achieved by weekly administration of antisense oligonucleotides (ASOs) or scrambled control (50mg/kg sc.). In vitro studies were performed in primary mouse splenic ECs transfected with siRNA. Results: Pathway analysis revealed remarkable tissue-specific responses to an atherogenic milieu, including dysregulation of Lipid Metabolism, Endocytosis and Cell Death pathways in splenic ECs. Interestingly, we previously showed that the mixed lineage kinase domain-like protein (MLKL) regulates the endocytic trafficking of lipids and cell death in macrophages. Indeed using Mlkl KD Apoe -/- mice, transplantation of Mlkl -/- BM into Ldlr -/- mice or EC-specific Mlkl -/- Apoe -/- mice, we show that loss of MLKL drives myelopoiesis and plaque development through regulation of splenic ECs. Both in vivo and in vitro , silencing Mlkl in splenic but not BM ECs potently increased lipid content and disrupted endocytosis by an accumulation of the multivesicular body marker CHMP4B, which mirror the dysregulated pathways we identified above. Furthermore, co-culture with Mlkl KD splenic ECs increased HSPC activation (pStat5) and myeloid colony formation, an effect that was lost when ECs were pre-treated with the upstream endocytosis inhibitor Dynasore. Conclusions: In conclusion, we establish a novel role for MLKL in regulating the balance of HSPCs, specifically through preservation of splenic, but not BM, ECs that repress hematopoiesis, highlighting the importance of splenic lipid metabolism and endocytosis and its impact on atherogenesis.

EPCO-06. DIFFUSE MIDLINE GLIOMAS: FROM CELL CYCLE TO THERAPEUTIC OPPORTUNITIES

Abstract The fatal Diffuse Midline Gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3. K27M impairs normal development by stalling of differentiation. As replication timing influences gene expression, cell fate, and cellular response to therapeutics, we undertook a multi-omics approach (Repli-seq, cell cycle RNA-seq, single cell RNA-seq) in DMG cells (H3.1K27M and H3.3K27M subgroups) and tumors in comparison to normal brain to gain an appreciation for targetable pathways in DMG. DMG cells presented differential replication timing in each subgroup, which, in turn, correlated with significant differential gene expression including the cholesterol biosynthesis pathway. Consistent with these findings, DMG tumors presented high replication stress and cholesterol biosynthesis pathway signatures. Moreover, DMG cells were specifically vulnerable to an inhibitor of the cholesterol pathway and to a replication stress therapy, singly and in combination. In conclusion, this combinatorial genomics approach revealed insights into therapeutic opportunities for this incurable disease.

The Integration of Machine Learning in information technologies: Future Trends and predictions

Hypertension and high cholesterol can cause heart attack and heart failure. Therefore, preventative measures to effectively anticipate, diagnose, and control high hypertension and cholesterol levels are needed to reduce myocardial infarction risk and offer more effective treatment alternatives. The study used new machine learning models (SVM, LR, RF, and NB) to predict cardiac illnesses, which were not used in a prior study. The study utilized four new machine learning models (SVM, LR, RF, and NB) to predict cardiac diseases, which had not been previously studied. The study used a 1970–2023 dataset of UK males with cardiac issues. Results showed that machine learning methods have gained popularity and can predict cholesterol and hypertension. The study shows that machine learning algorithms lower hypertension and cholesterol. Machine learning techniques must be improved and tested on larger datasets.

Lactobacillus johnsonii CCFM1376 improves hypercholesterolemia in mice by regulating the composition of bile acids

Aim: Strains with high bile salt hydrolase (BSH) activity have the potential to regulate cholesterol metabolism. This study aimed to assess the alleviating effect of Lactobacillus johnsonii (L. johnsonii ) CCFM1376, a strain with high BSH activity, on mice with hypercholesterolemia and explore the mechanism of its effect through the modulation of bile acid metabolism. Methods: The BSH activity was measured using the ninhydrin method. C57BL/6J mice were given a high-cholesterol diet to induce hypercholesterolemia with simultaneous gavage of L. johnsonii CCFM1376 for 8 weeks. The biochemical parameters in the serum and liver of hypercholesterolemic mice were measured to assess the alleviating effect of L. johnsonii CCFM1376 on hypercholesterolemia. Bile acid content in the mouse liver, serum, distal ileum contents, and feces was determined using liquid chromatograph mass spectrometer (LC-MS). RNA was extracted from mouse ileum and liver, and the expression levels of relative genes implicated in bile acid metabolism were measured by quantitative real-time PCR (qPCR). Results: Compared to the model group, the group treated with L. johnsonii CCFM1376 exhibited significantly reduced levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), along with a significant increase in high density lipoproteins cholesterol (HDL-C) level. Moreover, hepatic levels of TC and LDL-C in the CCFM1376 group also decreased significantly. Furthermore, the content and amount of unconjugated bile acids in the hepatic-enteric circulation of the L. johnsonii CCFM1376 group significantly increased, and the total bile acid content in the feces also significantly increased. In the L. johnsonii CCFM1376 group, the relative expression levels of ileal farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were downregulated, while the relative expression level of CYP7A1 was upregulated. Conclusion: These results indicated L. johnsonii CCFM1376 improves hypercholesterolemia in mice by regulating the composition of bile acids. This provides a reference for probiotic strategy to regulate cholesterol metabolism.

Prevalence and predictors of coronary heart disease among individuals with and without obesity in North Dakota.

Coronary heart disease (CHD) is the most common cardiovascular disease in the United States and heart disease is the leading cause of death in North Dakota. Although obesity is a major risk factor for CHD, some studies have reported an inverse relationship between body mass index (BMI) and CHD outcomes. Understanding the epidemiology of CHD among individuals with and without obesity is essential to guide health planning. Therefore, the objectives of this study were to estimate the prevalence and identify predictors of CHD among North Dakota adults with and without obesity. Behavioral Risk Factor Surveillance System data from 2017 to 2021 were provided by the North Dakota Department of Health and Human Services. Weighted prevalence estimates and 95% confidence intervals (CIs) were computed for CHD and potential risk factors among respondents with and without obesity (BMI ≥30 kg/m2). Multivariable logistic regression was used to identify significant predictors of CHD in both groups. A total of 17,092 respondents were included in the study. Respondents with obesity had a higher prevalence of CHD (4.7%, 95% CI: 4.2-5.4) than those without obesity (3.0%, 95% CI: 2.7-3.4). Predictors of CHD among both groups included age, sex, self-reported general health, high blood pressure, high cholesterol, chronic obstructive pulmonary disease, and diabetes. Having a personal doctor (Odds Ratio [OR] = 1.91, 95% CI: 1.13-3.23) and arthritis (OR = 1.72, 95% CI: 1.34-2.22) were significant predictors of CHD among respondents without obesity, but not among those without obesity. While the prevalence of CHD was significantly higher among adults with obesity compared to those without obesity, the findings of the stratified analysis indicated that predictors of the condition tended to be similar for the two groups. This study provides useful information to guide health planning and control programs that aim to reduce the burden of CHD in North Dakota.

Correlation of Lipid Profile and BMI with Fasting Blood Glucose

The prevalence in Libya of overweight people has more than tripled from 19.5% in 1984 to 63.5% in 2009, while the rate of obesity has more than doubled over the past three decades leading to a much higher incidence of Type 2 diabetes T2DM. This makes investigation of links between BMI and lipid profiles in Libyan T2DM patients of vital importance. This study was conducted to determine the cor-relation between body mass index (BMI) and lipid profiles in patients with T2DM attending outpatient clinics in the Diabetes and Endocrinology Centre (Ibn Al-Nafees Hospital) Tripoli, Libya. The second objective was to compare BMI, FBS and lipid profiles between T2DM patients and a control group. The study was carried out during the period of June and July 2024 included 122 T2DM patients and 55 healthy subjects. The subject’s serum was analysed for total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The possible correlation of BMI with lipid values were analysed. The Pearson’s co-efficient between the BMI and the lipid parameters did not show any significant correlation in T2DM patients. Comparisons of various parameters between T2DM patients and the control group showed that the mean values of fasting glucose levels, weight, BMI, TG, HDL-C and LDL-C were significantly higher in the T2DM group than the control group. There was no correlation found between BMI and lipid profiles in T2DM patients. Type 2 diabetic patients have significantly higher mean weight, BMI, FBS, TG, HDL-C and LDL-C compared with healthy controls

Minor ailment interventions and the pivotal role of the community pharmacist in greece

Abstract Introduction Community pharmacists (CPs) play a vital role in providing advice and treatment for minor ailments, offering accessible and convenient healthcare services to the public1. The selection of appropriate management strategies is crucial for promoting self-care and empowering individuals to take an active role in addressing their health issues2. Aim This study aimed to measure the level of knowledge and perceptions of pharmacists regarding primary pharmaceutical care practices and the management of minor ailments. Methods This quantitative, cross-sectional study used a survey-based questionnaire developed after extensive literature review. It consisted of both closed-ended questions (multiple-choice questions) and Likert-type questions scale ranged from 1 to 5 (Strongly Agree to Strongly Disagree) to rate their level of agreement or disagreement. Ethical approval was obtained from the Pharmaceutical Association of Attica (PAA). This study employed purposive sampling to select participants, ensuring their participation was both anonymous and voluntary. The study commenced in December 2023, and data collection (both face-to-face and electronically via the university’s Moodle platform) was completed by March 2024. Data were analysed using Microsoft Excel®. Results The PAA informed 68 CPs from the Southern sector of Athens, and 60 CPs responded, resulting in a response rate of approximately 88.24%. The survey results show that the majority of respondents were women, N=33 (55%). The main age groups were 31-40 and 41-50 years, each with N=13 (21.7%), and most were pharmacy owners, N=34 (38.6%). Most participants were pharmacy graduates, N=52 (86.7%), with only N=8 (13.3%) holding postgraduate degrees. The majority of CPs were able to accurately identify and distinguish minor ailments. Only a small percentage mistakenly included conditions typically classified as chronic, with 8.3% (N=5) listing high cholesterol and 1.7% (N=1) listing hypertension.The survey-results indicate that a significant portion of the respondents perceive the role of the CP as central to the healthcare system, with 78.3% (N=47) affirming its importance. All participants felt confident in detecting and recommending treatment for minor ailments; 83.3% (N=50) considered their university training adequate. The main obstacles for CPs were a lack of time (90%, N=54) and the absence of compensation for extended services (50%, N=30). Additionally, 98.3% (N=59) supported lifelong learning, with continuous professional development in primary care being the top choice (46.7%, N=28), followed by advanced clinical training (36.7%, N=22). Participants hope to play a more active role in disease management within five years (35%, N=21) and seek autonomy in prescribing (30%, N=18). They expect support through collaboration (48.3%, N=29), policy reforms (28.3%, N=17), and compensated services (20%, N=12). Additionally, 96.7% (N=58) feel prepared to offer extensive pharmacy services, viewing it as an opportunity to demonstrate their clinical skills. Discussion/Conclusion This seems to be the first study of its kind in Greece.The study faced limitations such as potential response bias, restriction to a specific pharmacist population, and a limited time frame, which may affect generalisability. Despite these, the findings offer valuable insights into pharmaceutical care practices in Athens' southern sector, providing a foundation for future research and targeted interventions to enhance care in Greece.

Hypothyroidism in a Psychiatric Outpatient Population of People With Intellectual Disabilities.

Hypothyroidism is a chronic health condition which causes physical, cognitive and psychiatric symptoms. The prevalence of hypothyroidism in adults with intellectual disabilities is under researched. Hypothyroidism was examined among 463 patients within an outpatient intellectual disability psychiatric team. Clinic records were utilised for this study, including sociodemographic, psychiatric and physical health diagnoses. Among the 463 patients, 43 (9%) had hypothyroidism. Compared to those without hypothyroidism, the hypothyroid group were significantly older, more likely to be female, and had increased rates of high cholesterol, diabetes, Down's Syndrome and dementia. Rates of hypothyroidism within this cohort of patients with intellectual disabilities were high (9%). The results suggest hypothyroidism in intellectual disability should be the focus of prospective research, in larger, more representative samples. This study indicates a need for increased awareness of, and resources for hypothyroidism in health services.

Advances in ECG and PCG-based cardiovascular disease classification: a review of deep learning and machine learning methods

Cardiovascular diseases (CVD) have been found to be prevalent in society, frequently ending in death. According to the findings of a recent survey, the mortality rate is increasing due to the prevalence of adult cigarette consumption, elevated blood pressure, high cholesterol levels, and obesity. The previously mentioned causes are exacerbating the severity of the condition. A pressing necessity exists for a study on the variability of these factors and their impact on cardiovascular disease (CVD). This involves the use of advanced tools to detect the disease early on and aid in the reduction of fatality rates. With their extensive methodologies that would help in the early CVD prediction and recognition of behavioral patterns in large amounts of data, artificial intelligence, and data mining disciplines offer a broad study potential. The results of these predictions will help physicians make decisions and early diagnoses, decreasing the risk of patient death. This work compares and reports the classification, machine learning, and deep learning algorithms that predict cardiovascular illnesses. For this study, articles from 2012 to 2023 were considered; after filtering, 82 articles were chosen for primary research. Future researchers will benefit from this review on cardiovascular disorders by better understanding the Deep Learning and Machine Learning models now in the healthcare sector. The review encompasses commonly employed methodologies such as support vector machine, decision tree, random forest, and convolutional neural networks (CNNs). Additionally, this survey aggregates and presents information on the performance metrics used to report accuracy. It also goes over the most popular datasets used by various diagnostic models (ECG and PCG signals datasets). In addition, it emphasizes prominent publishers, journals, and conferences that serve as platforms for the evaluation of scholarly works. Additionally, it will facilitate their understanding of the unresolved challenges or hurdles experienced by past researchers. A lack of more extensive and consistent datasets was the most common issue, followed by the need to improve existing models.