Hyperlipidemia Research Articles

Assessing lipid‐lowering and plasma cholesteryl ester transfer protein activity of Centranthus longiflorus and β‐Sitosterol following administration to triton WR1339‐ treated rats

AbstractThe aim of this study was to evaluate the lipid‐lowering and plasma cholesteryl ester transfer protein(CETP) activity of Centranthus longiflorus(CL) and β‐Sitosterol(βS) following intraperitoneal administration of Triton‐WR 1339 (=Tyloxapol) (TWR) to male Wistar rats. Hyperlipidemia(HL) was developed by intraperitoneal injection of TWR. The animals were divided into main eight groups of six rats each. Rats were housed in separate cages and fed a standard diet for 7 days. After 7 days, ethanol extraction of CL plant, aqueous suspension of βS and anacetrapib was given to rats by oral gavage 1 h before the triton injection. Blood samples were collected and used for the biochemical parameters analysis. Histopathological studies were also performed on liver tissue. In hyperlipidemic rats(HR), CL extract and βS reduced total cholesterol similarly. βS lowered low‐density lipoprotein(LDL‐C) more than CL extract. Both CL extract and βS approximated impaired Alanine transaminase(ALT) and Aspartate transaminase(AST) levels in HR's to the level of control. CL extract provided better protection than βS against deterioration in liver tissue samples seen in hyperlipidemic rats. Finally, CL extract and βS inhibited CETP, at which point βS was more effective. These findings showed that CL extract and βS reduce plasma lipid concentration and may have a hypolipidemic effect due to their anti‐CETP properties.

Adverse reaction of specific acute kidney injury caused by atorvastatin: an actual study based on the database of the US FDA adverse event reporting system

ABSTRACT Introduction Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin. Areas Covered Using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024), we extracted reports where atorvastatin was the primary suspect and categorized them into five populations: the general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We performed subgroup analyses by gender and age strata within these populations, assessing positive signals through disproportionality analysis using four criteria: Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EGBM). The statistical analysis evaluated differences between adverse drug reaction (ADR) occurrence and nonoccurrence, as well as between high and low induction time groups. Expert Opinion In the general population, evidence for a positive signal of AKI was insufficient. However, the sub-group analysis revealed a risk in males, with older individuals more often affected in both AMI and IS populations. In T2DM, positive signals were evident in younger age groups. For the HLD population, evidence of a positive AKI signal was insufficient across gender and age strata. Overall, atorvastatin is generally safe, but clinical vigilance for AKI is warranted in T2DM, AMI, and IS populations, particularly in older adults (65+ years).

Anti-LAN Antibodies: Clinical Implications and Case Presentation

Abstract Introduction/Objective The LAN system, originating from the 901 Series of High Incidence antigens, transitioned to a recognized System in 2012. The LAN antigen, situated on ABCB6, a multipass membrane protein associated with porphyrin transport, plays a crucial role in heme synthesis. Functionally, LAN acts as an ATP-binding cassette transporter on the red blood cell membrane. Comprising a single antigen, LAN exhibits elevated expression in various tissues including the heart, skeletal muscles, fetal liver, mitochondrial membrane, eye, and Golgi apparatus. Notably, LAN shows no specific association with any particular geographic or ethnic group. Resistant to Ficin/Papain, Trypsin, α-Chymotrypsin, and 0.2M DTT, LAN antibodies primarily consist of IgG and necessitate IAT for detection. While Anti-LAN has been implicated in Hemolytic Transfusion Reactions (HTRs), its involvement in Hemolytic Disease of the Fetus and Newborn (HDFN) remains infrequent. LAN-negative blood is exceedingly rare, often requiring Monocyte Monolayer Assay Testing (MMA) for clinical assessment. Methods/Case Report Case Presentation: An 81-year-old female with a medical history including seizure disorder, hypertension (HTN), hyperlipidemia (HLD), gastroesophageal reflux disease (GERD), small bowel obstruction, and high-grade de-differentiated metastatic retroperitoneal liposarcoma presented for preoperative evaluation. A type and screen ordered as part of outpatient preoperative assessments revealed a positive antibody screen. Further investigation traced the origin of the anti-LAN antibody to an external facility since 2017. Antibody identification indicated the reactivity of the patient’s plasma with all cells (1+ AHG in PEG), excluding the auto control. Utilizing rare frozen antisera anti-LAN, the patient was phenotyped for LAN, yielding a LAN-negative status. Subsequent testing with three rare frozen LAN-negative group O cells aimed to exclude clinically significant antibodies. Differential adsorption, employing a comprehensive baseline RBC phenotype record obtained from the external facility, ruled out anti-E, anti-K, and anti-Fyb, thereby confirming Anti-LAN specificity. Results (if a Case Study enter NA) NA Conclusion The exceptional rarity of LAN-negative blood underscores the high prevalence of reactivity to Anti-LAN antibodies, exceeding 99% in most populations. In select cases, autologous transfusion may emerge as a viable management strategy. Consequently, the patient’s surgical procedure has been deferred, with no immediate requirement for blood products.

Integrated network pharmacology, metabolomics and molecular docking analysis to reveal the mechanisms of quercetin in the treatment of hyperlipidemia

Hyperlipidemia (HLP) is a significant contributor to cardiovascular diseases. Quercetin (QUE), a naturally occurring flavonoid with diverse bioactivities, has garnered attention due to its potential therapeutic effects. However, the precise mechanisms underlying the effects of QUE on HLP remain unclear. In this study, an ultra-high-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive-MS) metabolomics strategy was employed to obtain metabolite profiles, and potential biomarkers were identified following data analysis. Network pharmacology and Drug Affinity Responsive Target Stability (DARTS) assays were utilized to explore the potential targets of QUE for HLP treatment. The results of metabolomics and network pharmacology were then integrated to identify the key targets and metabolic pathways involved in the therapeutic action of the QUE against HLP. Molecular docking and experimental validation were performed to confirm these key targets. A comprehensive database search identified 138 QUE-HLP-related targets. A protein-protein interaction (PPI) network was constructed using STRING, and the shared targets were filtered with Cytoscape. Among these, AKT1, TNF, VEGFA, mTOR, SREBP1, and SCD emerged as potential therapeutic targets. These findings were validated using in vitro cell experiments. Additionally, the mechanism of action of QUE against HLP was evaluated by integrating network pharmacology with metabolomics, identifying two metabolomic pathways crucial to HLP treatment. DARTS experiments confirmed the stable binding of QUE to FASN, p-mTOR, SREBP1, and p-AKT. In HepG2 cells treated with palmitic acid (PA), QUE significantly reduced the mRNA expression of ACLY, ACACA, FASN, and SCD (p < 0.05). Western blot analysis revealed that PA significantly increased protein expression of p-mTOR, SREBP1, FASN, and p-AKT (p < 0.05). In summary, our study provides novel insights into the protective mechanisms of QUE against HLP and offers valuable information regarding its potential benefits in clinical treatment.

Analysis of the Association between Eosinophilic Esophagitis and MASLD: Retrospective, Observational, Cohort Analysis of the National Inpatient Sample 2016-2020.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory condition. Associated pathologies for EoE are similar to those with metabolic-dysfunction-associated steatotic liver disease (MASLD). This study assesses whether an association exists between MASLD and EoE. We used National Inpatient Sample (NIS) 2020 data to identify adult patients. ICD-10 codes were used to identify patients with MASLD and EoE. The relationship between MASLD and EoE was assessed by multivariate analysis after adjusting for confounding factors, such as patient demographics, hospital characteristics, Charlson comorbidity index, obesity, obstructive sleep apnea (OSA), diabetes, hypertension (HTN), hyperlipidemia (HLD), inflammatory bowel disease (IBD), celiac disease (CD), gastroesophageal reflux disease (GERD), smoking, alcohol use, and irritable bowel syndrome (IBS). Out of 26 million patients, 4,820 had a diagnosis of EoE. The majority of the patients were between 18 and 44 years of age (47.82%), male (54.05%), had private insurance (50.1%), and were in the highest income quartile (29.25%). A higher incidence of MASLD was noted in the EoE group than those without (6.1% vs.2.9%, p<0.001). After adjusting for confounding factors, MASLD had 2.38 times higher odds of having EoE (95% CI-1.82-3.11, p<0.001). Other factors noted to be associated with higher odds of EoE included younger age, Caucasian race, IBS, GERD, IBD, and CD. Our study reports a novel finding that MASLD and EoE are associated. Future prospective studies are needed to confirm and understand the clinical significance of this relationship and how one disease affects the other.

The pharmacokinetics of dabigatran in a rat model of hyperlipidaemia induced by poloxamer 407

Various pharmacokinetic changes have been reported in experimental hyperlipidemic (HL) animal models. To evaluate whether P-glycoprotein (P-gp) activity was affected in HL rats, we assessed the pharmacokinetics of dabigatran after oral administration of dabigatran etexilate (DABE); this is a dabigatran prodrug and a well-known P-gp substrate. HL and control rats exhibited similar area under the plasma concentration-time curve (AUC), total body clearance (CL), and steady state volume of distribution (Vss) values following intravenous administration of dabigatran (1 mg/kg). This suggested that the distribution and elimination of dabigatran were similar in control and HL rats. The hepatic and intestinal P-gp protein levels did not differ significantly between control and HL rats. The dabigatran AUC and extent of absolute oral bioavailability (F) values were similar in control and HL rats following oral administration of DABE (10 mg/kg as dabigatran). Therefore, there was no apparent change in intestinal P-gp activity in HL rats compared to control rats. This study revealed no significant change in P-gp expression or activity in the intestine or liver of HL rats, and similar pharmacokinetics of dabigatran. Hyperlipidaemia may not directly affect the oral absorption of P-gp substrate drugs.

Immunobiological efficacy of a new sodium polyprenyl phosphate based medicine for the treatment and prevention of experimenrtal metabolic syndrome

The aim of the research was to study the population composition of the splenic lymphoid cells, to assess the functional activity of lymphocytes as well as the state of the gastrointestinal tract microbiota in experimental modeling of metabolic syndrome (MS).The studies were conducted using two experimental models of MS and hyperlipidemia (HL), based on prolonged drinking of animals with 20% aqueous fructose solution with added cholesterol and intraperitoneal administration of Poloxamer 407 to mice, respectively.The results of the experiments indicate a change in the population composition of splenocytes (decrease in CD4+ and CD8+T cells, activation of CD4+CD25+FoxP3+Thed cells), accompanied by a decrease in T cell activity and increased proliferation of B lymphocytes, impaired production of IL-15 and IL-22, as well as lipid and carbohydrate metabolism (adiponectin, leptin, insulin), which serves as a prerequisite for the development of chronic inflammation, which is a pathogenetic sign of MS.We found changes in the intestinal microbiota of mice characteristic of the manifestation of metabolic dysbiosis – an increase in the representation of Firmicutes bacteria (staphylococci, streptococci, enterococci) in the biomaterial, changes in the content of facultative (E. coli) and transient (Enterobacter) microflora.In order to develop a new kind of medicine for therapy and prevention of HL and MS, we used a combination of sodium polyprenyl phosphate (PP) and beta-sitosterol (BSS), polyisoprenoid derivatives of plant origin.More pronounced changes were found in the splenocyte population composition and activation parameters of Treg cells in HL modeling compared with the MS model. The introduction of PP and BSS has an immunocorrective effect during treatment.The therapeutic effect of this drug, as well as the prevention of the MS symptoms, is accompanied by normalization of the microbiota state.The data obtained indicate the prospects of using PP and BSS for the prevention and treatment of HL and MS in order to influence the leading links in the pathogenesis of metabolic disease.

The Importance of Dermatological Detection of Xanthomas and Xanthelsemas in Pediatric Patients: A Summary of Case Reports

Diseases such as sitosterolemias, familial hyperlipidemias, and familial hypercholesterolemias are characterized by unique dermatological manifestations, including eruptive xanthomas and xanthelasmas. Although these conditions are relatively rare in dermatology, they hold significant implications for cardiovascular health, potentially leading to fatal outcomes such as atherosclerotic disease, acute coronary syndrome or hypertensive encephalopathy if untreated. These diseases are particularly notable in pediatric populations and effective preventative treatment can be administered if these lipid-related disorders are detected early. This case series summary highlights various case reports to underscore the critical qualitative dermatological findings associated with these lipid disorders in children. By identifying these signs early through comprehensive dermatological examinations, it is possible to initiate preventative treatments that mitigate the risk of severe cardiovascular disease and other systemic diseases later in adulthood. The aim of this case series is to highlight these dermatological indicators clearly, providing dermatologists with a reliable reference for early diagnosis and intervention, thus highlighting the importance of dermatological assessment in preventing serious health outcomes associated with pediatric lipid disorders.

Evaluation of plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects

BackgroundPatients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging. MethodsHere we retrospectively recruited seven families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned four groups. ResultsAs expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these two groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis. ConclusionOur study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.

Cardioprotective Effects of Phlorizin on Hyperlipidemia-induced Myocardial Injury: Involvement of Suppression in Pyroptosis via Regulating HK1/NLRP3/Caspase-1 Signaling Pathway.

Hyperlipidemia (HLP) is a prevalent and intricate condition that plays a pivotal role in impairing heart function. The primary objective of this study was to assess the lipid-lowering and cardioprotective properties of phlorizin (PHZ) and to investigate its potential molecular mechanisms in rats. In this investigation, Sprague-Dawley rats were subjected to a high-fat diet for a period of 28days to induce an HLP model. Subsequently, the rats received oral doses of PHZ or metformin from day 14 to day 28. We assessed various parameters using commercially available kits, including serum lipid deposition, myocardial injury biomarkers, oxidative stress markers, and inflammatory cytokine levels. We also employed electron microscopy to examine myocardial ultrastructural changes and conducted Western blot analyses to assess apoptosis factors and pyroptosis markers. Comparing the PHZ group with the model group, we observed significant improvements in blood lipid deposition and heart injury biomarkers. Furthermore, PHZ demonstrated a clear reduction in myocardial tissue oxidative stress and inflammatory factors, as well as a suppression of cell apoptosis. Subsequent investigations indicated that PHZ treatment led to a decreased inflammatory response and lowered levels of hexokinase 1 (HK1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1. In summary, PHZ proved to be an effective remedy for alleviating HLP-induced cardiac damage by reducing blood lipid levels, mitigating oxidative stress, curbing inflammation, and suppressing pyroptosis. The inhibition of pyroptosis by PHZ appears to be linked to the regulation of the HK1/NLRP3/Caspase-1 signaling pathway.

Spectrum of APOE variants and their association with autosomal dominant familial dysbetalipoproteinemia

Spectrum of APOE variants and their association with autosomal dominant familial dysbetalipoproteinemia

Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification

BackgroundLipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification. MethodsHuman intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated β-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways. ResultsOur study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model.ConclusionsSo our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.

Association between organophosphate esters individual and mixed exposure with the risk of hyperlipidemia and serum lipid levels among adults in Wuhan, China.

Toxicologic studies reported that organophosphate esters (OPEs) may disrupt lipid metabolism, thus affecting serum lipid levels. However, epidemiological evidence regarding the association between OPEs and the risk of hyperlipidemia (HPL) as well as serum lipid levels is scarce. In the present study, our aim was to investigate the impact of individual and mixed OPE exposure on HPL. A total of 1981 Chinese adults were involved based on a cross-sectional design. Overall, we found a positive association between bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and the risk of HPL. Bis(1-chloro-2-propyl) phosphate (BCIPHIPP) showed a positive association with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). BDCIPP, diphenyl phosphate (DPHP), di-ocresyl phosphate and di-p-cresyl phosphate (Docp&Dpcp), and 4-hydroxyphenyl-diphenyl phosphate (4-OH-DPHP) exhibited a negative association with high-density lipoprotein cholesterol (HDL-C). In stratified analyses, BDCIPP and BCIPHIPP were significantly correlated with the increased risk of HPL in the age ≤ 45 group. Bis(2-butoxyethyl) phosphate (BBOEP) was in relationship with an elevated risk of HPL in the subgroup of BMI < 24kg/m2. BDCIPP was also positively associated with HPL in men. Quantile-based g computation (qgcomp) and generalized weighted quantile sum regression (gWQS) models demonstrated a negative association between OPEs mixed exposure and HDL-c in the total population, as well as a positive effect of them on HPL in the subgroup of age ≤ 45years, which is consistent with the individual analyses. Furthermore, joint effect analyses revealed that participants with detected BDCIPP urinary levels and unhealthy lifestyles had the highest risk of HPL. Our findings offer evidence supporting the correlation between exposure to OPE and the risk of HPL, necessitating further prospective studies for validation.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Epidemiological topology data analysis links severe COVID-19 to RAAS and hyperlipidemia associated metabolic syndrome conditions.

The emergence of COVID-19 (C19) created incredible worldwide challenges but offers unique opportunities to understand the physiology of its risk factors and their interactions with complex disease conditions, such as metabolic syndrome. To address the challenges of discovering clinically relevant interactions, we employed a unique approach for epidemiological analysis powered by redescription-based topological data analysis (RTDA). Here, RTDA was applied to Explorys data to discover associations among severe C19 and metabolic syndrome. This approach was able to further explore the probative value of drug prescriptions to capture the involvement of RAAS and hypertension with C19, as well as modification of risk factor impact by hyperlipidemia (HL) on severe C19. RTDA found higher-order relationships between RAAS pathway and severe C19 along with demographic variables of age, gender, and comorbidities such as obesity, statin prescriptions, HL, chronic kidney failure, and disproportionately affecting Black individuals. RTDA combined with CuNA (cumulant-based network analysis) yielded a higher-order interaction network derived from cumulants that furthered supported the central role that RAAS plays. TDA techniques can provide a novel outlook beyond typical logistic regressions in epidemiology. From an observational cohort of electronic medical records, it can find out how RAAS drugs interact with comorbidities, such as hypertension and HL, of patients with severe bouts of C19. Where single variable association tests with outcome can struggle, TDA's higher-order interaction network between different variables enables the discovery of the comorbidities of a disease such as C19 work in concert. Code for performing TDA/RTDA is available in https://github.com/IBM/Matilda and code for CuNA can be found in https://github.com/BiomedSciAI/Geno4SD/. Supplementary data are available at Bioinformatics online.

Evaluation of mandibular trabecular and cortical structure by fractal analysis in hyperlipidemia and hypertension patients

IntroductionThis study aimed to evaluate the mandibular trabecular and cortical changes in patients with hyperlipidemia (HL) and/or hypertension (HT) using fractal dimension (FD) analysis, mandibular cortical width (MCW), panoramic mandibular index (PMI) and mandibular cortical index (MCI). Materials and methodsPanoramic radiographs of 100 patients were evaluated. FD measurement of three region of interest (ROI) including the angulus, corpus and interdental bone area were made. MCW, PMI and MCI were also measured and noted. ResultsAngulus, corpus and interdental FD values were significantly lower in three disease groups than the control group. Angulus, corpus, and interdental FD values were significantly lower in the HL+HT group than in the HL group and HT group. MCW value was significantly lower in the HL group, HT group, and HL+HT group than the control group. The cortical index C1 was more common in the control group while C2 was more common in the HT, HL and HL+HT group. ConclusionThe fact that FD was significantly lower in the HL+HT group compared to the HL and HT groups indicates the positive effect of their association on bone loss and quality. FD measurements on images obtained using a direct digital panoramic system can be used for treatment planning and follow-up of patients with HL and/or HT.

Hyperlipidemia, Obesity, and Diabetes, and Risk of Ossification of the Posterior Longitudinal Ligament

Several risk factors of ossification of the posterior longitudinal ligament (OPLL) have been established, including diabetes and obesity. However, the relationship between hyperlipidemia (HLD) and OPLL is incompletely understood. PearlDiver was queried to identify adults with (+) and without (-) HLD, diabetes, and obesity. Comparative analyses were performed on demographics, comorbidities, and OPLL rates before and after matching for age, sex, and comorbidities. Stepwise logistic regression modeling assessing the relationship between HLD and OPLL with the addition of predictor variables was also performed. In total, 31,677 cervical OPLL patients, as well as 170,467 HLD+ and 118,665 HLD-, 168,985 Diabetes+ and 137,966 Diabetes-, and 150,363 Obesity+ and 142,553 Obesity- patients, were examined. Mean age ranged 43.44-59.46years, 54.94-63.12% were females, and mean Charlson Comorbidity Index ranged from 0.06 from 1.53, all higher in those with the comorbidity. Before matching, OPLL rates were higher in those with HLD (HLD+=0.05% vs. HLD-=0.03%, P= 0.005), diabetes (Diabetes+=0.06% vs. Diabetes-=0.02%, P < 0.001), and obesity (Obesity+=0.05% vs. Obesity-=0.02%, P= 0.001). However, after matching by age, sex, and Charlson Comorbidity Index, the associations between the studied comorbidities and OPLL were attenuated (all P > 0.05). Stepwise regression modeling revealed an association between HLD and cervical OPLL that was most impacted by the addition of age (OR=1.95, R2= 0.029 to OR=1.38, R2= 0.075) and obesity (OR=1.21, R2= 0.086 to OR=1.07, R2= 0.111) into the model. Cervical OPLL rates were higher in patients with HLD even after accounting for demographics and comorbidities. HLD may be an independent risk factor for OPLL development.

Association of baseline hypertension and hyperlipidemia with the clinical characteristics and outcomes in patients with colorectal cancer: A single institution experience.

e15522 Background: Hypertension (HTN) and hyperlipidemia (HLD) are widely prevalent diseases, but their effect on colorectal cancer (CRC) outcomes is limited. We aimed to study the effects of baseline HTN and HLD on CRC survival. Methods: We identified patients with stage 1-4 colorectal cancer diagnosed between 2011 and 2017 from tumor registry of a large safety-net hospital and NCI-designated Comprehensive Cancer Center. Patients with a diagnosis of HTN (ICD-9/10: I10, 401.9) and HLD (ICD 9/10: E78.0-E78.5, 272.0-272.4) at CRC diagnosis were compared with patients who did not have these comorbidities. Chi-square tests were used to compare categorical differences between groups. Multivariable logistic regression was used to identify factors associated with HTN and HLD. Overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazards model with an index date of tumor diagnosis until death. Patients who did not meet endpoint of interest were censored at the date of last clinical contact. Results: We identified 1,921 patients - 627 (33%) had HTN, 403 (21%) had HLD and 309 (16%) had HTN and HLD. The median age of diagnosis of CRC was 61 (IQR: 54-68) for HTN patients and 61 (IQR: 53-69) for HLD patients. Compared to patients without HTN or HLD, patients with HTN or HLD were more likely to be non-Hispanic Blacks (HTN: 39% vs 19%; HLD: 30% vs 24%), uninsured (HTN: 33% vs 17%; HLD: 36% vs 18%) and treated at safety-net hospital (HTN: 53% vs 24%; HLD: 55% vs 27%). These patients had a higher prevalence of other comorbidities including diabetes mellitus (HTN: 39% vs 7%; HLD: 50% vs 9%), anxiety (HTN:12% vs 3%; HLD: 14% vs 4%), and tobacco use (HTN: 16% vs 5%; HLD: 14% vs 7%). On multivariable analysis, HTN and HLD patients were older (HTN-OR: 1.05, 95CI: 1.04-1.06; HLD-OR: 1.03, 95CI: 1.02-1.05), had concurrent diabetes mellitus (HTN-OR: 4.2, 95CI: 2.9-6.3; HLD-OR: 4.5, 95CI: 3.2 - 6.4), depression (HTN-OR: 2.0, 95CI: 1.3-3.2; HLD-OR: 1.9, 95CI: 1.2-3.0), and cirrhosis (HTN-OR: 2.6, 95CI: 1.3-5.2; HLD-OR: 2.1, 95CI: 1.1-3.9) and treated at safety-net hospital (HTN-OR: 2.7, 95CI: 1.7-4.3; HLD-OR: 1.4, 95CI: 0.9-2.2). Compared to patients without HTN or HLD, OS was improved for HLD alone patients (HR: 0.58; 95CI: 0.38-0.89; P: 0.01), while it was not different for patients with HTN without HLD (HR: 0.99; 95CI: 0.81-1.2; P: 0.55) or HTN and HLD (HR: 0.92; 95CI: 0.75-1.13; P: 0.34). The 5-year yr OS for these groups were 65%, 77%, 66%, and 69% respectively. Conclusions: In this single institution cohort that includes a safety-net hospital, the prevalence of HTN or HLD at CRC diagnosis was higher among older and non-Hispanic Black CRC patients and associated with coexisting diabetes mellitus, anxiety, and tobacco use. CRC patients with HLD alone had a significantly better 5-yr OS compared to those without HTN or HLD, with HTN alone, and with HTN and HLD.

Metabolic factors affecting response to adjuvant anti-PD1 therapy for melanoma.

9589 Background: Given the intersection between metabolism and the immune system, and with the increasing use of immune checkpoint inhibitors (ICIs) in the treatment of solid tumors, it is important to determine whether metabolic factors are associated with outcomes for patients treated with ICIs. Obesity is often associated with improved response to immunotherapy for patients with melanoma. However, the impact of other metabolic disorders, such as type 2 diabetes (T2DM), hypertension (HTN), and hyperlipidemia (HLD), on immunotherapy response is not as well understood. The purpose of this study is to determine the impact of these metabolic disorders on immunotherapy treatment. Methods: Patients with stage II or III melanoma who were treated with adjuvant anti-PD-1 therapy and consented to the University of Pittsburgh Melanoma Center repository were included in this study. A retrospective chart review was conducted of the eligible 281 patients. Results: HTN, T2DM, HLD, and body mass index (BMI) &gt; 35 were analyzed together in two multivariate Cox proportional hazard models, one considering overall survival (OS) and the other recurrence free survival (RFS). T2DM (n=49) was significantly associated with both a decreased OS (HR=2.51, 95% CI 1.14-5.52; p=0.0219) and RFS (HR=1.92, 95% CI 1.16-3.164; p=0.011). No significant differences were observed for patients with HTN (n=156) in OS (HR=1.45, 95% CI 0.73-2.87; p=0.29) or RFS (HR=1.22, 95% CI 0.80-1.86; p=0.35), HLD (n=140) in OS (HR=0.62, 95% CI 0.30-1.29; p=0.20) or RFS (HR=0.69, 95% CI 0.44-1.07; p=0.098), or BMI &gt; 35 in OS (HR=1.01, 95% CI 0.48-2.13; p=0.99) or RFS (HR=0.78, 95% CI 0.47-1.29; p=0.34). After adjusting for common pre-treatment comorbidities (coronary artery disease, chronic kidney disease, and smoking), age, and sex, T2DM was no longer significantly associated with reduced OS (HR=1.78, 95% CI 0.83-3.8; p=0.14), but the association with RFS remained significant (HR=1.69, 95% CI 1.04-2.76; p=0.034). In patients with T2DM alone, metformin use (n=24) during immunotherapy treatment was associated with improved OS in univariate (HR=0.28, 95% CI 0.08-0.9; p=0.0385) and multivariate (HR=0.18, 95% CI 0.05-0.7; p=0.0098) analyses controlling for age, sex, and the comorbidities listed above. It was also near significant for increased RFS in a univariate (HR=0.46, 95% CI 0.20-1.06; p=0.067) and multivariate (HR=0.42, 95% CI 0.17-1.06; p=0.065) model. Baseline A1C (n=15) values were not significantly associated with OS (HR=0.18, 95% CI 0.001-24.7; p=0.49) or RFS (HR=0.60, 95% CI 0.21-1.76; p=0.35) in univariate models. Conclusions: T2DM is associated with decreased RFS for patients with melanoma treated with adjuvant anti-PD-1 therapy. Within the T2DM cohort, metformin use was associated with significantly improved RFS and OS. A1C did not correlate with either OS or RFS, suggesting that the effects of both T2DM and metformin may be independent of glycemic control.

Associations between metabolic syndrome-related diseases and colorectal cancer risk: A propensity score-matched analysis using the NIH All of Us research program.

10515 Background: The risk of colorectal cancer (CRC) is known to increase in patients with metabolic disorders such as hypertension (HTN), hyperlipidemia (HLD), type 2 diabetes (T2DM), and metabolic associated fatty liver disease (MASLD). Both metabolic disorders and CRC share similar demographic, socioeconomic, geographic, and environmental risk factors. This study aims to examine the associations between metabolic syndrome-related diseases and CRC incidence, controlling for confounding risk factors. Methods: This was a propensity score matched case-control study using NIH All of UsResearch Program, Registered Tier version 7. CRC diagnoses was defined as having two or more diagnosis codes in EHR. We matched CRC patients to participants without CRC diagnosis with 1:2 ratio, aligning age, gender, race/ethnicity, income, education, region, and cigarette exposure. Income level per year ( &lt; $25K, $25-100K, &gt; $100K), education level (grade 12 or less, some college, college graduate), cigarettes exposure ( &gt; 100 cigs per lifetime), region (Northeast, Midwest, South, West) were assessed using the survey. Height and weight measurement collected at the time of enrollment was used to calculate BMI and define obese (BMI ≥ 30 kg/m2 ) and underweight (BMI &lt; 18.5 kg/m2) status. We compared the average BMI between two groups, and calculated the odds ratios for obesity, underweight status, HTN, HLD, T2DM, and MASLD to assess the likelihood of these conditions being associated with colon cancer. Results: Between the control (n = 3,528) and CRC groups (n = 1,764), there was no significant differences in matched factors. The CRC group had a similar obesity prevalence and a lower mean BMI (28.8, SD 6.9) compared to the control group (29.3, SD 6.9, p = 0.017). Underweight status was linked to a 76% increase in CRC odds (OR 1.76, CI 1.21-2.56, p = 0.003), T2DM to a 26% increase (OR 1.26, CI 1.06-1.49, p = 0.008), HTN to a 58% increase (OR 1.58, CI 1.41-1.78, p &lt; 0.001), HLD to a 32% increase (OR 1.32, CI 1.18-1.49, p &lt; 0.001), and MASLD to over a two-fold increase (OR 2.16, CI 1.78-2.61 p &lt; 0.001). Conclusions: Our study reinforces the significant link between metabolic dysregulation and CRC risk. The higher prevalence of metabolic disorders in the CRC group, despite a lower obesity prevalence and average BMI, suggests that other factors, potentially treatment effects, might contribute to these findings. Further research is warranted to elucidate the causal pathways linking metabolic disorders to the pathogenesis of CRC. [Table: see text]