Hypercholesterolemia Research Articles

Proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention.

To investigate the underlying protein molecular mechanisms of "Qi stagnation and blood stasis syndrome" (QS) and "Qi deficiency and blood stasis syndrome" (QD), as two subtypes of coronary artery disease (CAD) in Traditional Chinese Medicine (TCM), following percutaneous coronary intervention (PCI). In this study, a total of 227 CAD patients with QS and 211 CAD patients with QD were enrolled; all participants underwent PCI. Label-free quantification proteomics were employed to analyze the changes in serum in two subtypes of CAD patients before and 6 months after PCI, aiming to elucidate the intervention mechanism of PCI in treating CAD characterized by two different TCM syndromes. Biochemical analysis revealed significant changes in tumor necrosis factor-α, high density lipoprotein cholesterol, blood stasis clinical symptoms observation, and Gensini levels in both patient groups post-PCI; Proteomic analysis identified 79 and 95 differentially expressed proteins in the QS and QD patient groups, respectively, compared to their control groups. complement C8 alpha chain, complement factor H, apolipoprotein H, apolipoprotein B, plasminogen, carbonic anhydrase 2, and complement factor I were altered in both comparison groups. Furthermore, enrichment analysis demonstrated that cell adhesion and connectivity-related processes underwent changes in QS patients post-PCI, whereas lipid metabolism-related pathways, including the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix receptor interaction, underwent changes in the QD group. The protein-protein interaction network analysis further enriched 52 node proteins, including apolipoprotein B, lipoprotein (a), complement C5, apolipoprotein A4, complement C8 alpha chain, complement C8 beta chain, complement C8 gamma chain, apolipoprotein H, apolipoprotein A-Ⅱ, albumin, complement C4-B, apolipoprotein C3, among others. The functional network of these proteins is posited to contribute to the pathophysiology of CAD characterized by TCM syndromes. The current quantitative proteomic study has preliminarily identified biomarkers of CAD in different TCM subtypes treated with PCI, potentially laying the groundwork for understanding the protein profiles associated with the treatment of various TCM subtypes of CAD.

Concussion burden and later-life cardiovascular risk factors in former professional American-style football players.

Mid-life cardiovascular risk factors are associated with later cognitive decline. Whether repetitive head injury among professional athletes impacts cardiovascular risk is unknown. We investigated associations between concussion burden and postcareer hypertension, high cholesterol, and diabetes among former professional American-style football (ASF) players. In a cross-sectional study of 4080 professional ASF players conducted between January 2015 and March 2022, we used an mulitsymptom concussion symptom score (CSS) and the number of loss-of-consciousness (LOC) episodes as a single severe symptom to quantify football-related concussion exposure. Primary outcomes were hypertension, dyslipidemia, and diabetes, defined by current or recommended prescription medication use. The prevalence of hypertension, high cholesterol, and diabetes among former players (52 ± 14 years of age) was 37%, 34%, and 9%. Concussion burden was significantly associated with hypertension (lowest vs. highest CSS quartile, odds ratio (OR) = 1.99; 95%CI: 1.33-2.98; p < 0.01) and high cholesterol (lowest vs. moderate CSS, OR = 1.46, 95%CI, 1.11-1.91; p < 0.01), but not diabetes. In fully adjusted models, the prevalence of multiple CVD was associated with CSS. These results were driven by younger former players (≤ 40 year of age) in which the odds of hypertension were over three times higher in those in the highest CSS quartile (OR = 3.29, 95%CI: 1.39-7.61; p = 0.01). Results were similar for LOC analyses. Prior concussion burden is associated with postcareer atherogenic cardiovascular risk profiles among former professional American football players.

Cardiovascular and lifestyle risk factors of mild cognitive impairment in UK veterans and non-veterans.

The link between poor cardiovascular health (CVH), lifestyle and mild cognitive impairment (MCI) has been well established in the general population. However, there is limited research exploring these associations in ageing UK veterans. This study explored the risk of MCI and its association with nine CVH and lifestyle risk factors (including diabetes, heart disease, high cholesterol, high blood pressure, obesity, stroke, physical inactivity, the frequency of alcohol consumption and smoking) in UK veterans and non-veterans. This prospective cohort study comprised data from the PROTECT study between 2014 and 2022. Participants comprised of UK military veterans and non-veterans aged ≥50 years at baseline. Veteran status was defined using the Military Service History Questionnaire. CVH and lifestyle risk factors were defined using a combination of self-report measures, medication history or physical measurements. MCI was defined as the presence of subjective and objective cognitive impairment. Based on a sample of 9378 veterans (n = 488) and non-veterans (n = 8890), the findings showed the risk of MCI significantly reduced in veterans with obesity, those who frequently consumed alcohol and were physically inactive compared to non-veterans. The risk of MCI significantly increased in veterans with diabetes (hazards ratio [HR] = 2.22, 95% confidence interval [CI] 1.04-4.75, P ≤ 0.05) or high cholesterol (HR = 3.11, 95% CI 1.64-5.87, P ≤ 0.05) compared to veterans without. This study identified CVH and lifestyle factors of MCI in UK veterans and non-veterans. Further work is needed to understand these associations and the underpinning mechanisms which could determine intervention strategies to reduce the risk of MCI.

A cross-sectional analysis of the relationship between the non-high density to high density lipoprotein cholesterol ratio (NHHR) and kidney stone risk in American adults

BackgroundRecent interest in the Non-High Density to High Density Lipoprotein Cholesterol ratio (NHHR) has emerged due to its potential role in metabolic disorders. However, the connection between NHHR and the development of kidney stones still lacks clarity. The primary goal of this research is to explore how NHHR correlates with kidney stone incidence.MethodsAn analysis was conducted on the data collected by the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, focusing on adults over 20 years diagnosed with kidney stones and those with available NHHR values. Employing weighted logistic regression and Restricted Cubic Spline (RCS) models, NHHR levels’ correlation with kidney stone risk was examined. Extensive subgroup analyses were conducted for enhanced reliability of the findings.ResultsThe findings indicate a heightened kidney stone risk for those at the highest NHHR levels relative to those at the lowest (reference group). A notable non-linear correlation of NHHR with kidney stone incidence has been observed, with a significant P-value (< 0.001), consistent across various subgroups.ConclusionA clear link exists between high NHHR levels and increased kidney stone risk in the American adult population. This study highlights NHHR’s significance as a potential indicator in kidney stone formation.

Changes in biomarkers of lipid in juvenile idiopathic arthritis and its association with various disease parameters: a 6-month follow-up study

Background: The objectives of our study were to determine the changes in lipid profile (total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C)) in juvenile idiopathic arthritis (JIA) and assess its association with epidemiological and clinical profile of JIA patients. Methods: This observational study was performed with 46 patients at presentation followed by 38 cases at 3 months and 18 cases at 6 months of follow up. Their demographic profile and clinical parameters including juvenile disease activity score (JADAS 27) were compared with the biomarkers of lipid profile. Results: The mean (SD) age was 105.85 (20.23) months at first visit with mean (SD) disease duration being 15 (6.4) months. Twenty-six participants had oligoarthritic (56.5%), while the rest had polyarthritis (43.4%). Most of the patients had borderline raised TG and LDL-C (cases with raised TG n=14 (30.4%), 12 (31.5%), 5 (27.7%) at 1st visit, 3 months, and 6 months respectively and LDL-C n=12 (26%), 10 (26.3%), 6 (33.3%) at 1stvisit, 3 months, and 6 months respectively). HDL-C level was low in 36 (78.2%) cases at first visit, 28 cases (73.6%) at 3 months and 12 cases (66.6%) at 6 months respectively. Lipid profile was significantly affected by gender difference, duration of disease and drug therapy (p&lt;0.05). Significant association have been found between JADAS score and TGL level with p value 0.03. Conclusions: Children with JIA definitely suffer from dyslipidemia. Among the biomarkers of lipid profile, low level of HDL-C is one of the most important highlights of our study. Further studies can help to strengthen the findings and formulate necessary interventions at an early stage.

Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements.

Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63–0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

Biobank-wide association scan identifies risk factors for late-onset Alzheimer's disease and endophenotypes.

Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer's disease (AD; n=61,212). Among 1738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits related to intelligence and education showed strong and independent associations with AD. Furthermore, we identified 41 significant associations for a variety of AD endophenotypes. While family history and high cholesterol were strongly associated with AD subgroups and pathologies, only intelligence and education-related traits predicted pre-clinical cognitive phenotypes. These results provide novel insights into the distinct biological processes underlying various risk factors for AD.

#1172 Identification of phenyl sulfate producer phenotypes by an oral tyrosine challenge test: a microbiota-based personalized nutritional approach

Abstract Background and Aims Phenyl sulfate (PS) has been implicated in the pathogenesis of diabetic kidney disease (DKD). PS is converted from phenol, a gut microbial metabolite of dietary tyrosine, and sulfated into PS by aryl sulfotransferases in the host liver. We hypothesized that the effects of a particular diet on metabolic responses might differ from person to person. In the present study, we aimed to characterize various PS producer phenotypes using an oral tyrosine challenge test (TCT). Method We developed the TCT to determine the individual PS producing capacity. Plasma samples were collected at baseline after overnight fasting, and were then collected at 4, 8, 12, 24, 36 and 48 hours after oral administration of L-tyrosine at a dose of 100 mg/kg. PS concentrations were measured by high performance liquid chromatography. The gut microbiome was assessed by metagenomic shotgun sequencing. Results A total of 48 healthy volunteers were enrolled to undergo the TCT. The mean age of the participants was 32 ± 8 years; 50% were men, and 50% were vegetarians. The time-concentration curves of PS were similar among the participants, with the maximal increase of PS at the 24th hour (Fig. A). Participants were stratified into tertiles according to the PS levels at the 24th hour after the TCT. The 16 participants in the highest tertile were defined as high-PS producers, whereas those in the lowest tertile were defined as low-PS producers (Fig. B). We found that there was no difference in age, gender, dietary habit, BMI, eGFR, and baseline plasma PS levels between the 2 groups. However, the high-PS producers had higher levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol. In addition, distinct differences in gut microbial composition were identified. At the species level, the relative abundance of Alistipes dispar, Clostridium sp. C5-48, and Butyricimonas faecihominis was markedly increased in the high-PS producers (Fig. C). Conclusion We found high PS variability in the response to a TCT, suggesting that universal dietary recommendations may have limited utility in reducing PS levels. Further studies are warranted to investigate the potential clinical applications of the TCT in patients with DKD.

Assessing the impact of annual health screenings in identifying noncommunicable disease risk factors within Qatar’s primary health care corporation Qatari registered population

BackgroundNoncommunicable diseases (NCDs) are a significant global health burden, including in Qatar, where cardiovascular diseases cause mortality. This study examines the outcomes of the annual health checkup implemented by the Primary Health Care Corporation (PHCC) in Qatar in detecting NCDs risk factors among Qataris aged 18+ years.MethodsA cross-sectional study design was implemented to calculate the prevalence of behavioural and metabolic NCDs risk factors among Qataris who underwent annual health checkups between 2017 and 2019. Data on age, gender, tobacco consumption, height, weight, blood pressure, glycated haemoglobin (HbA1c), and cholesterol levels were extracted from electronic medical records.ResultsIn 2019, Qatar experienced an 80% rise in Annual Health checkups attendance compared to 2017. Tobacco use fluctuated between 11.79 and 12.91%, peaking at 35.67% among males in 2018. Qataris with elevated blood pressure dropped from 29.44% in 2017 to 18.52% in 2019. Obesity decreased from 48.32 to 42.29%, more prevalent in females. High HbA1c levels reduced from 13.33 to 8.52%, while pre-diabetic levels rose from 21.1 to 25.52%. High cholesterol ranged from 7.31 to 9.47%. In a regression analysis, males had 2.28 times higher odds of elevated blood pressure and 1.54 times higher odds of high HbA1c, with a 0.68 lower odds of obesity compared to females. Ages 36 and above had 2.61 times higher odds of high cholesterol compared to younger age groups.ConclusionThe annual health screening has shown promising results in detecting and addressing NCDs risk factors among Qataris. The attendance rate has increased over the three-year period, and there has been a decrease in the prevalence of elevated blood pressure, obesity, and high HbA1c levels. However, tobacco consumption and pre-diabetic levels remain significant concerns. These findings can guide the implementation of tailored preventative and curative services to improve the health and well-being of the Qatari population.

#1071 The effect and mechanism of SGLT2 inhibitor on improving inflammatory injury of glomerular endothelial cells in diabetes

Abstract Background and Aims ATP-binding cassette transporter A1 (ABCA1), which reduces intracellular cholesterol accumulation, is highly expressed in the kidney. Studies have shown that sodium-glucose co-transporter 2 inhibitors (SGLT2) inhibitors promote ABCA1 expression in multiple tissues and organs. However, the effect of SGLT2 inhibitors on ABCA1 expression in diabetic kidney disease (DKD) is unclear. In this study, the effect of empagliflozin, an SGLT2 inhibitor, on ABCA1 in glomerular endothelial cells(GECs) of DKD and the possible mechanisms linking ABCA1 to GECs inflammatory injury were investigated. Method Kidney tissues were obtained from renal biopsies of patients with early and advanced DKD. db/db mice were used as animal models of type 2 diabetes and the effects of SGLT2 inhibitors on ABCA1 were analyzed by treatment with empagliflozin. The effects of ABCA1 overexpression on glomerular lipid deposition and kidney injury were examined in a type 2 diabetic mouse model with ABCA1 overexpression (db/db + ABCA1 mice), and human renal glomerular endothelial cells (HRGECs) cultured in high glucose and high cholesterol conditions, which simulated type 2 diabetes in vitro. Results The expression of ABCA1 in the glomeruli of DKD patients and db/db mice was significantly decreased. Enhancing ABCA1 expression in the kidney tissue of diabetic mice by adenovirus transduction improved renal cholesterol deposition, inhibited the overactivation of C3a/C5a, and improved renal inflammatory injury. In addition, in cultured HRGECs under high glucose and high cholesterol conditions, ABCA1 deficiency increased the deposit of cellular cholesterol, contributed to overactivation of C3a/C5a, and induced inflammatory injury. Overexpression of ABCA1 enhancing cholesterol efflux or inhibition of C3a/C5a activation in vitro significantly protected against glomerular endothelial injury stimulated by high glucose and high cholesterol. Moreover, SGLT2 inhibitor empagliflozin up-regulated the expression of ABCA1 and down-regulated the levels of cholesterol, C3a/C5a and inflammatory cytokines in diabetic mice and HRGECs. Conclusion SGLT2 inhibitor (empagliflozin) might play a renal protective role by up-regulating ABCA1-mediated cholesterol outflow, inhibiting the activation of C3a/C5a, and then ameliorating the inflammatory injury of GECs.

#1439 Risk factors and significance of a reduction of serum albumin after start of PD

Abstract Background and Aims A reduction in the serum level of albumin following the initiation of peritoneal dialysis (PD) has been reported to associate with impaired survival. Our aim was to identify pre-PD risk factors of drop of serum albumin, and to estimate how a decrease in albumin level affects PD patients’ survival prognosis. Method We included all adult patients who had been on PD for at least half a year in the Helsinki area in Finland during the years 2004 to 2019. Patients who had a dialysis history longer than 1 year before transferal to PD were excluded. We analysed the serum albumin level at start of PD and the last available albumin level before 6 months after start of PD. A 20% reduction of serum albumin was considered significant. Logistic regression was used to assess the association between risk factors (age, sex, primary kidney disease, comorbidities, laboratory variables) and a 20% drop of serum albumin. Cox regression was employed to study the effect of albumin drop on survival with adjustment for confounders. Results Of 379 patients, 80 (21%) showed a reduction of serum albumin of at least 20% after start of PD. High age, high albumin level at start of PD, high level of HDL cholesterol and low level of ionized calcium all associated independently with the risk of an albumin drop in the logistic regression analysis. The albumin level at start (hazard ratio 0.94 per one g/l increment, 95% CI 0.89-0.98) and a 20% or larger drop of albumin level (HR 2.3, 95% CI 1.4-3.9) were connected to impaired survival irrespective of each other. Other independent predictors of worse survival were high age, peripheral vascular disease, a history of stroke, and diabetes. Conclusion A drop of serum albumin after start of PD is frequent and associates with impaired survival. Drop of albumin is more common among elderly patients and those with high values HDL cholesterol or low levels of ionized calcium.

Dietary Modulations in Preventing Cardiometabolic Risk in Individuals with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a complex health issue include obesity, high cholesterol, high blood pressure, and chronic inflammation that increase the risk of cardiovascular diseases (CVDs). CVDs are of great concern in the disease progression and prognosis of T2DM. This review is a comprehensive examination of the literature on the relationship between T2DM and cardiovascular risk, nutrition-related cardiometabolic risk (CMR) factors, and impact of dietary modulations on CMR. In recent years the researches has been focus on the importance of a comprehensive treatment approach like dietary modulations to address multiple cardiovascular risk reductions, including hypertension and dyslipidemia. Modulation of dietary patterns are the most promising interventions to prevent CMR factors and T2DM via affecting the body weight, glucose control, and microbial diversity of individuals. Current evidence suggests that high-quality dietary patterns such as the Dietary Approaches to Stop Hypertension (DASH) eating plan and the Mediterranean diet is important in the metabolic control processes of T2DM with anti-inflammatory and antioxidant compounds, glucagon-like peptide agonist compounds, and intestinal microbiota changes. Nutrition plays a critical role in preventing and improving CVD outcomes in patients with T2DM. Dietary modulations should be planned considering individual differences in responses to dietary composition and nutritional changes, personal preferences, eating behaviors and gut microbiota differences.

Exploring associations of financial well-being with health behaviours and physical and mental health: a cross-sectional study among US adults

BackgroundHealth disparities exist across socioeconomic status levels, yet empirical evidence between financial well-being (FWB) and health are limited.MethodsThis cross-sectional study combined data from 25 370 adults aged ≥18 years in...

A Case for Regularly Obtaining Nutrition History

This Teachable Moment discusses providing patients with an opportunity to initiate dietary change before prescribing statin therapy for even severely high low-density lipoprotein cholesterol levels.

The Influence of Emodin Succinyl Ethyl Ester on Non-alcoholic Steatohepatitis Induced by a Diet High in Fructose, Cholesterol, and Fat in Mice.

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/d. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.

Effects of gut microbiome on type 1 diabetes susceptibility and complications: A large-scale bidirectional Mendelian randomization and external validation study.

To assess and verify the effect of the gut microbiome on the susceptibility and complications of type 1 diabetes (T1D). To achieve this aim, a two-sample and reverse Mendelian randomization (MR) analysis was conducted. In addition, an external validation study was performed using individual microbiome data of patients with T1D from the gutMEGA datasets and the National Clinical Research Center for Metabolic Diseases. The circulating metabolites facilitated two-sample MR analysis, mediation and multivariable MR analysis to evaluate the direct relationship between the gut microbiome and T1D complications. The MR analysis results from the discovery and validation phases confirmed that Veillonellaceae can potentially reduce the susceptibility of T1D. In the gutMEGA dataset, the average relative abundance of Veillonellaceae in patients with T1D was 0.66%, compared with 1.09% in the controls. Furthermore, the external validation, which included 60 patients with T1D and 30 matched healthy controls, found that the median relative abundance of Veillonellaceae was also lower than controls at 1.10% (95% CI 0.50%-1.80%). Specifically, the Eubacterium coprostanoligenes group, known for its ability to regulate cholesterol, was significantly associated with a lower risk of developing renal, neurological and ophthalmic complications in T1D. Moreover, high cholesterol in small high-density lipoprotein and cholesteryl esters in high-density lipoprotein were associated with a reduced risk of T1D renal and ophthalmic complications. The mediation and multivariable MR analysis combining cholesterol indicated that the E. coprostanoligenes group is the most dominant factor influencing T1D complications. Our findings supported the potential causal effect of gut microbiota on the susceptibility and complications of T1D.

Sex difference in the associations among risk factors with gastroesophageal reflux disease in a large Taiwanese population study

BackgroundGastroesophageal reflux disease (GERD) is a common global health issue. Previous studies have revealed a higher prevalence of GERD in females than in males, however few studies have investigated sex differences in the risk factors associated with GERD. Therefore, the aim of this population-based study was to examine sex differences in the risk factors for GERD in a large cohort of over 120,000 Taiwanese participants.MethodsWe enrolled 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) from the Taiwan Biobank. The presence of GERD was ascertained using self-reported questionnaires. Sex differences in the risk factors associated with GERD were examined using multivariable logistic regression analysis.ResultsThe overall prevalence of GERD was 13.7%, including 13.0% in the male participants and 14.1% in the female participants (p < 0.001). Multivariable analysis showed that older age, hypertension, smoking history, alcohol history, low fasting glucose, and low uric acid were significantly associated with GERD in the male participants. In the female participants, older age, diabetes, hypertension, smoking history, alcohol history, low systolic blood pressure, low fasting glucose, high hemoglobin, high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), low low-density lipoprotein cholesterol, and low uric acid were significantly associated with GERD. Significant interactions were found between sex and age (p < 0.001), diabetes (p < 0.001), smoking history (p < 0.001), fasting glucose (p = 0.002), triglycerides (p = 0.001), HDL-C (p = 0.001), and estimated glomerular filtration rate (p = 0.002) on GERD.ConclusionsOur results showed a higher prevalence of GERD among females compared to males. Furthermore, sex differences were identified in the risk factors associated with GERD, and older age, diabetes, smoking history, and low HDL-C were more closely related to GERD in females than in males.

PCSK9 inhibitors as safer therapeutics for atherosclerotic cardiovascular disease (ASCVD): Pharmacophore design and molecular dynamics analysis.

Cardiovascular disorders are still challenging and are among the deadly diseases. As a major risk factor for atherosclerotic cardiovascular disease, dyslipidemia, and high low-density lipoprotein cholesterol in particular, can be prevented primary and secondary by lipid-lowering medications. Therefore, insights are still needed into designing new drugs with minimal side effects. Proprotein convertase subtilisin/kexin 9 (PCSK9) enzyme catalyses protein-protein interactions with low-density lipoprotein, making it a critical target for designing promising inhibitors compared to statins. Therefore, we screened for potential compounds using a redesigned PCSK9 conformational behaviour to search for a significantly extensive chemical library and investigated the inhibitory mechanisms of the final compounds using integrated computational methods, from ligand essential functional group screening to all-atoms MD simulations and MMGBSA-based binding free energy. The inhibitory mechanisms of the screened compounds compared with the standard inhibitor. K31 and K34 molecules showed stronger interactions for PCSK9, having binding energy (kcal/mol) of -33.39 and -63.51, respectively, against -27.97 of control. The final molecules showed suitable drug-likeness, non-mutagenesis, permeability, and high solubility values. The C-α atoms root mean square deviation and root mean square fluctuation of the bound-PCSK9 complexes showed stable and lower fluctuations compared to apo PCSK9. The findings present a model that unravels the mechanism by which the final molecules proposedly inhibit the PCSK9 function and could further improve the design of novel drugs against cardiovascular diseases.

Longitudinal analysis of vitamin D levels considering sunshine duration and suggestion for a standardised approach for vitamin D supplementation in children and adolescents with obesity

BackgroundChildren with obesity have low 25 hydroxy-vitamin D (25-OH-D3) levels compared to lean children. Recommendations on when to start vitamin D supplementation differ largely between countries. Longitudinal data on 25-OH-D3 levels to guide treatment decisions are scarce since they are largely influenced by solar radiation and are difficult to compare.MethodsWe carried out a retrospective analysis of multiple 25-OH-D3 and parathyroid hormone (PTH) measurements in a cohort of 543 patients without vitamin D supplementation. All measurements were taken at the local paediatric obesity clinic as documented in the German-Austrian-Swiss APV (Prospective Documentation of Overweight Children and Adolescents) registry from 2009 to 2019. Serial 25-OH-D3 and PTH levels were adjusted for sunshine duration over the last 30 days to account for seasonal variation, as well as for sex and body mass index (BMI). We further performed an exploratory analysis of the association of sunshine duration, sex, BMI SDS (standard deviation score), abnormal lipid levels or dysglycemia with the 25-OH-D3 trend.Results229 obese patients (mean BMI SDS: 2,58 (± 0,56), 53% females, mean age: 12 (± 3) years, range: 2–21 years) with two, 115 with three and 96 with four repeated 25-OH-D3 measurements were identified. Mean adjusted 25-OH-D3 (48.2 nmol/l) and PTH (34.9 ng/l) levels remained stable over 120 weeks. 5% of the patients had an elevated PTH > 65 ng/l. High total cholesterol ≥ 200 mg/dl and high triglycerides ≥ 130 mg/dl were associated with higher 25-OH-D3 levels.ConclusionWe propose a simple method to include sunshine duration in the analysis of 25-OH-D3 levels to minimise the bias of seasonal variation. Based on our data we established the pragmatic strategy of limiting vitamin D supplementation to patients with biochemical signs of mineralisation disorders such as elevated PTH and alkaline phosphatase (AP). In children with normal PTH and AP we recommend adjustment of calcium intake and increase of outdoor activity instead.