High-density Lipoprotein Cholesterol Levels Research Articles

Lipid disturbances induced by psychotropic drugs: clinical and genetic predictors for early worsening of lipid levels and new-onset dyslipidaemia in Swiss psychiatric samples.

Early worsening of plasma lipid levels (EWL; ≥5% change after 1 month) induced by at-risk psychotropic treatments predicts considerable exacerbation of plasma lipid levels and/or dyslipidaemia development in the longer term. We aimed to determine which clinical and genetic risk factors could predict EWL. Predictive values of baseline clinical characteristics and dyslipidaemia-associated single nucleotide polymorphisms (SNPs) on EWL were evaluated in a discovery sample (n = 177) and replicated in two samples from the same cohort (PsyMetab; n1 = 176; n2 = 86). Low baseline levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and high baseline levels of high-density lipoprotein cholesterol (HDL-C), were risk factors for early increase in total cholesterol (P = 0.002), LDL-C (P = 0.02) and triglycerides (P = 0.0006), and early decrease in HDL-C (P = 0.04). Adding genetic parameters (n = 17, 18, 19 and 16 SNPs for total cholesterol, LDL-C, HDL-C and triglycerides, respectively) improved areas under the curve for early worsening of total cholesterol (from 0.66 to 0.91), LDL-C (from 0.62 to 0.87), triglycerides (from 0.73 to 0.92) and HDL-C (from 0.69 to 0.89) (P ≤ 0.00003 in discovery sample). The additive value of genetics to predict early worsening of LDL-C levels was confirmed in two replication samples (P ≤ 0.004). In the combined sample (n ≥ 203), adding genetics improved the prediction of new-onset dyslipidaemia for total cholesterol, LDL-C and HDL-C (P ≤ 0.04). Clinical and genetic factors contributed to the prediction of EWL and new-onset dyslipidaemia in three samples of patients who started at-risk psychotropic treatments. Future larger studies should be conducted to refine SNP estimates to be integrated into clinically applicable predictive models.

Deciphering the causal landscape: genetic insights into sporadic vestibular schwannoma risk factors through Mendelian Randomization

BackgroundSporadic vestibular schwannoma, a benign tumor affecting the vestibulocochlear nerve, poses significant health challenges due to its impact on hearing, balance, and facial nerve function. Despite known associations with genetic mutations and environmental factors, the causality between potential risk factors and sporadic vestibular schwannoma remains underexplored.ObjectiveThis study aims to investigate the causal effects of various genetically predicted risk factors on sporadic vestibular schwannoma utilizing a Two-Sample Mendelian Randomization (MR) approach to enhance understanding of its etiology and inform prevention strategies.MethodsLeveraging data from genome-wide association studies (GWAS), we analyzed 29 risk factors across five categories: related diseases, lifestyle habits, nutritional status, learning ability, and laboratory indicators. The MR analysis employed instrumental variables (IVs) derived from single nucleotide polymorphisms (SNPs) to assess causal relationships, overcoming traditional observational study limitations.ResultsOur findings highlight significant associations between sporadic vestibular schwannoma and factors such as ovarian cancer, uterine fibroids and lifestyle habits including dietary intake and alcohol consumption. Notably, higher educational attainment and specific laboratory indicators like high-density lipoprotein (HDL) cholesterol levels were linked to altered disease risk. These results suggest a multifaceted etiology involving hormonal, cardiovascular, gastrointestinal, immune, and metabolic pathways.ConclusionThis comprehensive MR study provides novel insights into the diverse risk factors contributing to sporadic vestibular schwannoma, emphasizing the role of genetic predispositions, hormonal influences, and lifestyle choices in its development. The associations identified underscore the need for a multidisciplinary research approach and targeted public health strategies to mitigate sporadic vestibular schwannoma risk. Further research into the underlying mechanisms of these associations is crucial for developing effective interventions and improving patient outcomes.

Effect of PCSK9 inhibitors on major cardiac adverse events and lipoprotein-a in patients with coronary heart disease: a meta-analysis.

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease due to its unique apo(a) component and its association with atherosclerosis and thrombogenesis. This meta-analysis was conducted to evaluate the effects of PCSK9 inhibitors on major adverse cardiac events (MACE) and Lp(a) levels in patients with coronary heart disease. Randomized controlled trials (RCTs) were systematically searched in PubMed, the Cochrane Library, and other databases. Stata 15.1 software was used for data analysis, and a random- or fixed-effects model was selected based on inter-study heterogeneity. Egger's test was applied to detect publication bias. A total of 12 RCTs were included, involving 48 116 patients with a mean age of 62 years, comprising 65% males and diverse ethnic backgrounds. The results showed that compared with the control group, PCSK9 inhibitors significantly reduced low-density lipoprotein cholesterol (WMD = -1.24 mmol/L, 95% confidence interval (CI): -1.28 to -1.20), total cholesterol, triglycerides, and Lp(a) levels while increasing high-density lipoprotein cholesterol levels. In terms of safety, there was no increased risk of adverse reactions other than injection site reactions. For MACE, PCSK9 inhibitors significantly reduced the risk of nonfatal myocardial infarction, stroke, and coronary revascularization events (RR = 0.87, 95% CI: 0.84-0.89). PCSK9 inhibitors not only significantly improve blood lipid profiles and reduce Lp(a) levels but also reduce the risk of MACE in patients with coronary heart disease. Therefore, PCSK9 inhibitors offer an effective and safe treatment option for these patients.

Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials.

Cardiovascular disease is a leading cause of mortality, especially in individuals with type 2 diabetes mellitus and dyslipidemia. Despite adequate statin therapy, some patients fail to achieve the target low-density lipoprotein-cholesterol levels. Trials have compared doubling the statin dose with the addition of ezetimibe. A systematic literature search was performed using various databases. Forest plots were constructed for pooled analysis with statistical significance set at P < 0.05. Seven trials were included. Monotherapy showed no significant difference compared with dual therapy for low-density lipoprotein-cholesterol levels [mean difference (MD): -5.03; P = 0.37], high-density lipoprotein-cholesterol levels (MD: 0.01; P = 0.95), total cholesterol (MD: -2.38; P = 0.66), and triglycerides (MD: 5.37; P = 0.67) at follow-up compared to baseline. Monotherapy significantly reduced serious clinical adverse events (risk ratio: 0.21; P = 0.04), with no difference in treatment-related adverse effects, discontinuation due to treatment-related or overall adverse events.

Risk factors of metabolic syndrome in women of reproductive age at mining area

Lead is one of the four most dangerous heavy metal pollutants, toxic to human health, and linked to metabolic syndrome (MetS). This research aimed to analyze the relationship between respondent characteristics, blood lead level (BLL), nutrition intake, and physical activity to MetS and its components in women of reproductive age at Pemali District Mining Area, Bangka Belitung Regency. This research was conducted with a case-control approach involving 70 women of reproductive age (35 cases and 35 controls). Data was analyzed using chi-square and Mann-Witney tests for bivariate analysis and regression test logistics for multivariate analysis. Based on bivariate analysis, there is a significant relationship between body mass index (BMI) (p=0.000), salt intake (p=0.017), and seasoning intake (p=0.017) to MetS; meanwhile, BLL is not associated with MetS (p=0.473) but are associated with high-density lipoprotein cholesterol (HDLC) (p=0.019). Multivariate test results show that BMI (p=0.000; OR=7.995) and salt intake (p=0.030; OR=6.812) are significant risk factors for MetS. Women of reproductive age must maintain BMI within normal levels and reduce daily salt intake to prevent the occurrence of MetS. BLL must be controlled to prevent decreased HDLC levels in women of reproductive age.

Hovenia dulcis (Guaizao) polysaccharide ameliorates hyperglycemia through multiple signaling pathways in rats with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) poses a significant threat to human health, with its incidence and mortality rates increasing annually. This study investigated the hypoglycemic effects and underlying mechanisms of pure Hovenia dulcis (Guaizao) polysaccharide (HDPs-2A) in rats subjected to a high-fat and high-sugar diet combined with streptozotocin-induced T2DM. Oral administration of HDPs-2A resulted in significant increases in body weight and liver glycogen levels compared to untreated controls. Moreover, a reduction in fasting blood glucose levels, alleviation of hyperinsulinemia, enhanced glucose tolerance, and improved insulin resistance were observed in the HDPs-2A-treated group. HDPs-2A also effectively reversed diabetes-induced dyslipidemia, as evidenced by decreased total cholesterol and triglyceride levels, alongside increased high-density lipoprotein cholesterol levels. Histopathological analyses confirmed that HDPs-2A partially repaired liver tissue damage by mitigating oxidative stress responses in the liver. Additionally, treatment with HDPs-2A significantly elevated short-chain fatty acid levels in T2DM rats. Real-time quantitative PCR and Western blot analyses indicated that HDPs-2A significantly enhanced the expression of InsR, IRS2, PI3K, Akt, and GLUT4, suggesting that HDPs-2A regulates insulin resistance and glycometabolism through the activation of the PI3K/Akt signaling pathway. Furthermore, HDPs-2A appeared to modulate the expression of GS, GSK-3β, and FoxO1 to improve glucose metabolism and reduce insulin resistance. It also improved glucose metabolism by activating the AMPK pathway and modulating G6Pase and PEPCK expression. This study provides novel insights into the antidiabetic effects of HDPs, positioning them as promising nutritional agents for the management of T2DM.

Clinical Efficacy of Ezetimibe Combined with Rosuvastatin in the Treatment of Patients with Primary Hypercholesterolemia Inadequately Controlled by Statin Therapy

Aims/Background Primary hypercholesterolemia (PHC) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Although the fact that statins effectively lower low-density lipoprotein cholesterol (LDL-C) levels, some patients fail to achieve target LDL-C levels and continue to have a high risk of cardiovascular disease. This study aims to evaluate the clinical efficacy and safety of ezetimibe combined with rosuvastatin in patients with PHC. Methods This study retrospectively examined 101 patients with PHC who received statins at the cardiology department of Jilin Province FAW General Hospital, between 2021 and 2024. Patients were divided into the observation (ezetimibe combined with rosuvastatin, n = 45) and control (rosuvastatin, n = 66) groups in accordance with their treatment regimens. Data were sourced from the hospital's electronic health records system, and statistical analysis was performed by using SPSS 25.0 software (IBM Corporation, Armonk, NY, USA). Results Baseline characteristics were similar between the two groups. After 12 weeks of treatment, the reduction in LDL-C levels in the observation group (–0.373 [–0.427, –0.348]) was greater than that in the control group (–0.240 [–0.318, –0.222], p &lt; 0.001). The percentage changes in total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels were significantly better in the observation group (TC: –0.230 [–0.302, –0.144], TG: –0.292 [–0.333, –0.237], and HDL-C: 0.081 [0.067, 0.111]) than in the control group (TC: –0.127 [–0.158, –0.119], TG: –0.082 [–0.101, –0.067], and HDL-C: 0.000 [–0.163, 0.133] with p &lt; 0.001, p &lt; 0.001, and p = 0.011, respectively). Regarding drug safety, the incidence of adverse events was comparable between the two groups (11.10% vs. 12.10%, p = 0.871). Conclusion The combination of ezetimibe and rosuvastatin demonstrates superior lipid-lowering efficacy and good safety in patients with PHC inadequately controlled by statin therapy, providing an effective alternative treatment option. Further large-scale, multicenter randomized controlled trials are warranted to confirm its long-term efficacy and safety.

Effect of Pemafibrate on Cerebrovascular Atherosclerosis in Patients with Stroke and Hypertriglyceridemia.

The Pemafibrate for Prevention of Atherosclerotic Diseases in Stroke (PPAR Stroke) study aimed to assess the effects of pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, on the progression of cerebrovascular atherosclerosis in patients with stroke and hypertriglyceridemia. Ninety-nine patients (mean age, 65.6 years; male, 74.7%) with hypertriglyceridemia and a history of stroke or transient ischemic attack of non-cardioembolic origin were included in this prospective single-arm study. Hypertriglyceridemia was defined as a fasting serum triglyceride (TG) level ≥ 150 mg/dL. All patients were treated with pemafibrate (0.2 mg or 0.1 mg/day) for 2 years. The primary outcome was change in carotid intima-media thickness (IMT) from baseline at 2 years, as assessed using carotid ultrasonography. The secondary outcomes were changes in blood biomarker levels and progression of intracranial artery stenosis on magnetic resonance angiography. The mean TG level significantly decreased from 269 mg/dL at baseline to 139 mg/dL at 2 years (P＜0.001) and high-density lipoprotein cholesterol level increased from 49 to 54 mg/dL (P＜0.001), whereas low-density lipoprotein cholesterol level remained unchanged. Significant reductions in high-sensitivity C-reactive protein and interleukin-6 levels were also observed (P=0.003 and P=0.002, respectively). With regard to mean IMT in the internal carotid arteries, the difference was significant for the left side (1.59 mm at baseline vs. 1.52 mm at 2 years; P=0.009) and borderline significant for the right side (1.32 mm at baseline vs. 1.28 mm at 2 years; P=0.053). Among the 48 stenotic lesions in the intracranial arteries, regression and progression was observed in 9 (18.8%) and 4 (8.3%) cases, respectively. Pemafibrate was observed to have TG-lowering and anti-inflammatory effects and could attenuate atherosclerosis progression in the intra- and extracranial arteries of patients with stroke and hypertriglyceridemia.

Effects of propolis consumption on blood pressure, lipid profile and glycemic parameters in adults: a GRADE-assessed systematic review and dose-response meta-analysis.

Propolis, as a by-product of honey production, has shown several beneficial effects on cardiovascular risks in past randomised controlled trials, although the findings are not conclusive. In this review, we intend to evaluate the effects of propolis consumption on cardiovascular risk factors by conducting a meta-analysis. The Web of Science, Medline and Scopus databases were comprehensively searched until September 2023. Eligible studies were identified by screening, and their data were extracted. Weighted mean differences with a 95 % CI for each outcome were estimated using the random-effects model. This meta-analysis revealed that propolis consumption led to a significant decrease in the levels of TAG (weighted mean differences (WMD): -10·44 mg/dl 95 % CI: -16·58, -4·31; P = 0·001), LDL-cholesterol (WMD: -9·31 mg/dl; 95 % CI: -13·50, -5·12 mg; P < 0·001), fasting blood glucose (WMD: -7·30 mg/dl; 95 % CI: -11·58, -3·02; P = 0·001), HbA1c (WMD: -0·32 %; 95 % CI: -0·60, -0·05; P = 0·01), insulin (WMD: -1·36 μU/ml; 95 % CI: -2·36, -0·36; P = 0·007), homeostatic model assessment for insulin resistance (WMD: -0·39; 95 % CI: -0·74, -0·03; P = 0·020) and systolic blood pressure (WMD: -2·24 mmHg 95 % CI: -4·08, -0·39; P = 0·010), compared with the control groups. Furthermore, propolis consumption had a significant increasing effect on HDL-cholesterol levels (WMD: 2·03 mg/dl; 95 % CI: 0·24, 3·83; P = 0·020). In contrast, the consumption of propolis had no significant effect on total cholesterol and diastolic blood pressure levels. This systematic review and dose-response meta-analysis suggested that propolis intake may be effective in cardiometabolic improvement in adults. Further, well-designed studies are required to confirm and elucidate all aspects of these findings.

The effect of breakfast skipping and sleep disorders on glycemic control, cardiovascular risk, and weight loss in type 2 diabetes

Background & AimsMeal timing is an emerging branch of science that investigates the influence of eating patterns on the circadian rhythm and overall health. There are still discrepancies in the literature as to whether late distribution of food intake and sleep disorders could impact biochemical, anthropometric, and cardiovascular markers. The objectives of this study were firstly observe skipping breakfast and sleep disorders over 12 months. Secondarily, analyze the individual influence of these findings on changes biochemical, anthropometric, and cardiovascular markers during the same period. MethodsThis descriptive study is part of a tertiary analysis in a recently published study. This research recruited 84 participants with Type 2 Diabetes (T2D) who were divided: Control-40 participants received only medical care; Intervention-44 participants received the same medical care along with nutritional assessment. Consultations occurred quarterly over 12th months, and a follow-up was conducted after 3 months. For influence analysis, non-normal variables were compared using Mann-Whitney, while normal variables were compared using unpaired t-tests. In all instances, α = 0.05 and P < 0.05 were adopted. ResultsAnalysis revealed a high percentage of patients in both groups who skipped breakfast, slept less than 6 hours, and experienced nighttime awakenings during the 1st visit. By the 12th month, there was deterioration in all data in the control group and significant improvement in the intervention group. Those with sleep disturbances also had lower HDL-cholesterol (HDL-C) values (p=0.0054). For the other analyzes no significant differences were found. ConclusionParticipants who skipped breakfast and had more nocturnal awakenings possibly had worse glycemic and weight control, but this difference was not statistically significant and only trends were observed. Sleep disorders could affect HDL-C levels. However, the influence analysis does not establish a causal relationship and more clinical trials are needed to analyze this topic on T2D.

Immuno-Informatics Insight into the Relationship Between Cholesterol and Cytokines in Cutaneous Leishmaniasis: From clinics to computation.

The role of serum cholesterol and its interactions with cytokines in human cutaneous leishmaniasis (CL) pathophysiology is unknown. This study aimed to evaluate the correlation among serum total cholesterol (TC), very-low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and cytokines (including interleukin [IL] 10), IL-12 and tumour necrosis factor-alpha [TNF-α]) in CL. The cholesterol-cytokine network was analysed to illuminate the pathogenesis of CL. This case-control study was conducted from December 2022 to March 2023 in hospitals within Baghdad and Wasit provinces, Iraq, and included CL and CL-free subjects ranging between 20-30 years of age. The serum samples were analysed via commercial kits to detect TC, IL-10, IL-12, TNF-α, VLDL-C, LDL-C, HDL-C and TG levels. Computational efforts to dissect cholesterol-protein interaction networks were employed using STITCH. A total of 50 CL and 25 control subjects were included. The TC, HDL-C and LDL-C levels in CL patients were markedly lower (P = 0.0001) than in control subjects, whereas the IL-10, IL-12, TNF-α, VLDL-C and TG levels were higher in CL patients. Serum cholesterol showed no correlation with cytokines; however, a significant correlation (r = 0.57; P = 0.026) was observed between IL-12 and TNF-α. Within the cholesterol-protein network, cholesterol potentially interacted with IL-10, connecting cholesterol to modules with immunological significance, including TRAF1, TRAF2 and TNF receptor superfamily member 1B, as well as IL-10, IL-10RA and IL-12RB1. This study showed the alteration of lipid and lipoprotein in CL and introduced 2 immunological modules in CL, highlighting the importance of the altered cholesterol-cytokine interaction network in CL.

Identification and optimization of relevant factors for chronic kidney disease in abdominal obesity patients by machine learning methods: insights from NHANES 2005–2018

BackgroundThe intake of dietary antioxidants and glycolipid metabolism are closely related to chronic kidney disease (CKD), particularly among individuals with abdominal obesity. Nevertheless, the cumulative effect of multiple comorbid risk factors on the progression and complications of CKD remains inadequately characterized.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey (NHANES) dat abase (2005–2018), to examine potential factors related to CKD, including glycolipid metabolism, dietary antioxidant intake, and pertinent medical history. To explore the associations between these variables and CKD, the present study used a multivariable-adjusted least absolute shrinkage and selection operator (LASSO) regression model, along with a restricted cubic spline (RCS) model. Furthermore, an optimal predictive model was developed for CKD using ten machine learning algorithms and enhanced model interpretability with the Shapley Additive Explanations (SHAP) method.ResultsA cohort comprising 8,764 eligible individuals (52% male, including 1,839 CKD patients) with abdominal obesity aged 20–85 years were included. The findings revealed significant positive correlations in patients with abdominal obesity between the presence of CKD and age, a history of heart failure, hypertension, diabetes, elevated lipid accumulation product (LAP) and triglyceride glucose-waist circumference (TyG-WC) levels. Conversely, negative correlations were identified between CKD and variables such as sex, high-density lipoprotein cholesterol (HDL-C) levels, and the composite dietary antioxidant index (CDAI). In parallel, RCS regression analysis revealed significant nonlinear associations between the CDAI, HDL-C, TyG-WC, and CKD among patients with abdominal obesity aged 60–80 years. The development of predictive models demonstrated that the CatBoost model surpassed other models, achieving an accuracy of 86.74% on the validation set. The model’s area under the receiver operator curve (AUC) and F1 score were 0.938 and 0.889, respectively. The SHAP values revealed that age was the most significant predictor, followed by diabetes history, hypertension, HDL-C levels, CDAI index, TyG-WC, and LAP.ConclusionCatBoost models, along with glycolipid metabolism indexes and dietary antioxidant intake, are effective for early CKD detection in patients with abdominal obesity.

Metabolic syndrome and related factors in Cameroonian women under contraceptive use.

Contraceptive is a device or drug that prevents a woman from becoming pregnant. Some types of contraceptive can cause a myriad of secondary effects such as overweight, increase of blood pressure triglycerides, and glucose intolerance. The combination of these secondary effects could, in the long term, develop metabolic syndrome in these women. The purpose of this study was to determine the prevalence of metabolic syndrome and related factors in Cameroonians women on contraceptives. This was a cross-sectional study that included 231 Cameroonians fasting women from 18 to 49 years of age, on contraceptives. Sociodemographic, lifestyle, anthropometric and biochemical characteristics were collected. Metabolic syndrome was diagnosed using the criteria of the National Cholesterol Education Program- Adult Treatment Panel III. After validation of the data, statistical analysis was performed using Epi-Info software version 7.2.2.16 and the statistical level of significance was set at 5.0%. 231 were using a modern contraceptive method, 28 were not using a contraceptive method, and 12 were non-consenting. The contraceptive method use rate was 89.19% and the most commonly used method was injectable contraception (49.35%). According to National Cholesterol Education Program criteria, almost 38.96% of these women were overweight and 50.65% had a serum high density lipoproteins cholesterol level of less than 0.50 g/L. Among women on contraceptives, the prevalence of metabolic syndrome was 22.08%. However, there was no significant association between contraceptive use and the occurrence of metabolic syndrome (p = 0.63). Contraceptive use was certain in all the participants, it's reported that, according to the NCEP-ATPIII a prevalence of 22.08% of metabolic syndrome among women using modern contraceptive methods in Douala, Republic of Cameroon. The high-risk groups were women using injectable method. Therefore, lipid profiles should be assessed in those women in order to manage them better.

Impact of Oxidative Stress on Sperm Quality in Oligozoospermia and Normozoospermia Males Without Obvious Causes of Infertility

Background: Male factors contribute to approximately 50% of infertile couples. However, obvious causes remain unknown in many cases. This observational study aimed to investigate the associations of clinical and lifestyle parameters with sperm parameters. Methods: This study enrolled 41 men in infertile couples without obvious causes for male infertility from July 2023 to April 2024. Semen samples were evaluated for sperm number, motility, DNA fragmentation, and oxidative stress (OS) marker oxidation–reduction potential (ORP). Blood samples were analyzed for biochemical parameters, including advanced glycation end products (AGEs), and systemic OS marker diacron-reactive oxygen metabolites (d-ROMs). Skin-accumulated AGE levels were identified with an autofluorescence method. Lifestyle factors were assessed with a lifestyle questionnaire. Results: Most of the participants were under 40 years old and non-obese with normal clinical parameters. Multiple regression analyses revealed that body mass index, serum d-ROMs, and semen ORP levels were independently associated with decreased sperm number. Additionally, serum zinc and semen ORP levels were associated with sperm motility. Furthermore, serum zinc and high-density lipoprotein cholesterol levels were associated with sperm progressive motility and DNA fragmentation, respectively. The rest of the clinical and lifestyle factors, including skin-accumulated and serum AGE levels, were not correlated with any sperm parameters. Furthermore, serum d-ROM and semen ORP levels were not correlated with each other or any of the clinical and lifestyle factors. Conclusions: Our present study indicates that both systemic and local OS may be independently involved in sperm abnormality in healthy men without obvious causes for male infertility.

Association between metabolic syndrome and chronic obstructive pulmonary disease development in young individuals: a nationwide cohort study

BackgroundThe association between metabolic syndrome (MetS) and chronic obstructive pulmonary disease (COPD) has not been studied well, particularly in young individuals. We investigated the risk of COPD development in young individuals based on MetS and its components.MethodsWe used the Korean National Health Information Database to identify 6,891,400 individuals aged 20–39 years who participated in the national health check-up service between 2009 and 2012. Then, we identified individuals with MetS and investigated COPD development based on health insurance claims. Cox proportional hazard regression models were used to calculate the adjusted hazard ratio (aHR) for the risk of COPD development.ResultsDuring a mean follow-up period of 8.35 years, 13,784 individuals were newly diagnosed with COPD. MetS was associated with an increased risk of COPD (aHR, 1.18; 95% confidence interval [CI], 1.11–1.24). Among the MetS components, except for hyperglycemia, abdominal obesity (aHR, 1.27; 95% CI, 1.19–1.34), hypertension (aHR, 1.05; 95% CI, 1.01–1.10), hypertriglyceridemia (aHR, 1.11; 95% CI, 1.07–1.16), and low high-density lipoprotein cholesterol levels (aHR, 1.16; 95% CI, 1.11–1.22) were significantly associated with COPD development. A higher number of MetS components correlated with an increased risk of COPD development, with the highest risk observed when all five MetS components were present (aHR, 1.55; 95% CI, 1.28–1.87).ConclusionMetS was associated with COPD development in young individuals. The risk of COPD development increased along with the increasing number of MetS components. These findings suggest that careful monitoring for COPD development is necessary in young individuals with MetS, especially those with multiple components of MetS.

Predictive value of direct bilirubin and total bile acid in lung adenocarcinoma patients treated with EGFR-TKIs

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma.

Healthier Lipid Profiles of Japanese Adults, Especially in Women with Elevated High-Density Lipoprotein Cholesterol (HDL-C), Are Associated with Low HDL-C Peroxide Content

Japanese adults typically have healthier lipid profiles than American and European adults and a lower prevalence and later onset of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between HDL-C level and HDL-C peroxide content, a bioindicator of unhealthy lipid metabolism in Japanese adults. Blood samples were collected from 463 participants, 31–84 years of age, who lived in Tokyo. A second blood sample was collected 5 years later from 241 of the participants, allowing us to evaluate the temporal stability of the inverse correlation between HDL-C level and HDL-C peroxide content. Glucoregulation and inflammatory activity were assessed because both can be associated with dyslipidemia and HDL-C dysfunction. Obesity and central adiposity were also considered. Overall, women had healthier HDL-C profiles than men. Elevated HDL-C (&gt;90 mg/dL) was common (16.6%) and found more often in women. Higher HDL-C peroxide content was associated with older age and central adiposity and incremented further when HA1c and CRP were higher. When assessed 5 years later, lower HDL-C peroxide content continued to be evident in adults with higher HDL-C. While similar associations have been described for other populations, most Japanese adults typically had healthier levels of HDL-C with lower HDL-C peroxide content than previously reported for American adults.

Circulating levels of blood biomarkers and risk of benign prostatic hyperplasia: Results from two large cohorts in Europe and East Asia.

As one of the most prevalent chronic non-communicable diseases affecting aging males, the burden of benign prostatic hyperplasia is growing over the world. Our study aims at investigating the potential relationships between various blood biomarkers and benign prostatic hyperplasia (BPH) in middle-aged and older men in European and East Asian population cohorts. We included 229 022 male adults from the UK Biobank (UKB) and 20 284 male adults from the China Health and Retirement Longitudinal Study (CHARLS) in this study. Forty-four blood biomarkers in UKB cohort and 16 blood biomarkers in the CHARLS cohort were analysed to examine their association with benign prostatic hyperplasia. Cox, logistic analyses and restricted cubic spline models were used to investigate linear and nonlinear longitudinal associations. In our research, elevated high-density lipoprotein cholesterol showed significant associations with a decreased risk of benign prostatic hyperplasia, and these associations remained significant after accounting for potential covariates both in UKB cohort (hazard ratio (HR) = 0.83; 95% CI = 0.79-0.88, P < 0.001) and CHARLS cohort (odds ratio (OR) = 0.992; 95% CI = 0.985-0.999, P = 0.033). Apolipoprotein A was also found to be inversely associated with BPH (HR = 0.76; 95% CI = 0.70-0.81, P < 0.001). L-shaped relationships were discovered between level of high-density lipoprotein cholesterol and apolipoprotein A with incidence of benign prostatic hyperplasia. This large prospective biomarker-based study highlights that high-density lipoprotein (HDL) cholesterol and apolipoprotein A are significant protective factors against the development of BPH, with L-shaped associations suggesting an optimal protective range. In contrast, biomarkers related to glucose metabolism, inflammation, and hormone levels were not found to significantly influence BPH progression. Our findings support the potential involvement of lipid biomarkers in the early stages of BPH development, suggesting that future strategies should prioritise lipid-related pathways in the prevention and management of BPH.

Associations of per- and polyfluoroalkyl substances and heavy metals with blood lipid profiles in a representative sample of Korean adolescents

BackgroundPrevious studies on the associations of per- and polyfluoroalkyl substances (PFASs) and heavy metals with lipid profiles among adolescents have been scarce. We sought to investigate the associations of PFASs and heavy metals with blood lipid levels in a representative sample of Korean adolescents.MethodsData from the Korean National Environmental Health Survey (2018–2020) were used. Concentrations of PFASs [perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid, perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDeA)], lead, and mercury were measured in serum, whole blood, and urine samples, respectively. Linear regression, Bayesian kernel machine regression (BKMR), and k-means clustering analyses were employed to evaluate the associations between pollutants and lipid levels.ResultsIn the linear regression analyses, PFOA levels were associated with higher low-density lipoprotein cholesterol (LDL-C) levels; PFOS with higher total cholesterol (TC) levels; PFNA with higher TC, LDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C) levels; PFDeA with higher TC, LDL-C, non-HDL-C, and high-density lipoprotein cholesterol levels; and mercury with higher TC and non-HDL-C levels. The BKMR analysis revealed that the PFAS and heavy metal mixture was associated with higher LDL-C levels (1.8% increase in LDL-C at the 75th percentile of all PFAS and heavy metal concentrations compared to their median values, 95% credible interval: 0.5, 3.1), primarily driven by the effect of PFDeA. Compared to individuals in the low pollutant exposure cluster (geometric mean levels of PFOA, PFOS, PFHxS, PFNA, PFDeA, lead, and mercury were 2.7 μg/L, 6.2 μg/L, 1.6 μg/L, 0.7 μg/L, 0.4 μg/L, 0.8 μg/dL, and 0.3 μg/L, respectively), those in the high pollutant exposure cluster (5.1 μg/L, 10.7 μg/L, 3.7 μg/L, 1.3 μg/L, 0.6 μg/L, 0.9 μg/dL, and 0.4 μg/L, respectively) demonstrated higher TC levels (2.5% increase in TC, 95% confidence interval: 0.1, 5.0) in the k-means clustering analysis.ConclusionDue to the limitations of this study, such as its cross-sectional design, these results should be interpreted cautiously and confirmed in future studies before drawing implications for public health strategies aimed at promoting health during adolescence and later in life.

HDL Cholesterol-Associated Shifts in the Expression of Preselected Genes Reveal both Pro-Atherogenic and Atheroprotective Effects of HDL in Coronary Artery Disease.

The associations of high-density lipoprotein (HDL) level and functionality with lipid metabolism, inflammation, and innate immunity in coronary artery disease (CAD) remain controversial. The differential expression of a set of genes related to HDL metabolism (24 genes) and atherogenesis (41 genes) in peripheral blood mononuclear cells (PBMC) from CAD and control patients with varied HDL cholesterol (HDL-C) levels was compared. 76 male patients 40-60 years old with CAD diagnosed by angiography and 63 control patients were divided into three groups with low, normal (1.0-1.4 mM), and increased HDL-C levels. Transcript levels were measured by real-time PCR. The differentially expressed genes (DEGs) and associated metabolic pathways were analyzed for three groups, with prevalent CAD as an outcome. The common feature was the increased odds ratio values for liver X receptor (LXR) gene expression for three patient groups. CAD patients with low HDL-C possessed 24 DEGs with lower expression of genes involved in cholesterol efflux, and down-regulated SREBF1 and ABCG1 are suggested as gene signatures. CAD patients with normal HDL-C possessed nine DEGs with down-regulated ITGAM and ALB as gene signatures. CAD patients with increased HDL-C possessed 19 DEGs with down-regulated APOA1 and HMGCR as gene signatures. With gene expression signatures, one standard deviation higher average gene expressions were associated with 5.1-, 48.8-, and 38.9-fold fewer CAD cases for three patient groups. As HDL-C increased in CAD patients, the expression of ABCG1, CUBN, and HDLBP genes increased, while the expression of HMGCR and NPC2 genes, involved in cholesterol synthesis and trafficking, decreased. The expression of CD14, CD36, S100A8, S100A9, S100A12, TLR5, TLR8, and VEGFA genes, involved in angiogenesis and inflammation mainly via nuclear factor-κB (NF-κB), decreased. The increased accumulation of cholesteryl ester in PBMC from patients with low HDL-C was suggested. This assumption contrasts with the suggested accumulation of free cholesterol in PBMC from patients with increased HDL-C, concomitant with suppression of cholesterol synthesis and traffic to the plasma membrane, and with an inflammatory state controlled by depressed CD36-mediated and upregulated apoE-mediated immunometabolic signaling. Gene signatures may be used for the diagnosis, prognosis, and treatment of CAD in dependence on HDL-C levels.