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Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115 mg/dl, high-density lipoprotein (HDL) <40 mg/dl for males, or HDL <50 mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150 mg/dl. At the follow-up, a variation of ±40 mg/dl for LDL, ±6 mg/dl for HDL, and ±50 mg/dl for triglycerides was considered relevant. Athletes with follow-up <10 months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6 months. Mean age was 27.2 ± 4.8 years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increases in low-density lipoprotein cholesterol (LDL-C) can occur on carbohydrate restricted ketogenic diets. Lean metabolically healthy individuals with a low triglyceride-to-high-density lipoprotein cholesterol ratio appear particularly susceptible, giving rise to the novel lean mass hyper-responder (LMHR) phenotype. OBJECTIVES: The purpose of the study was to assess coronary plaque burden in LMHR and near-LMHR individuals with LDL-C ≥190 mg/dL (ketogenic diet [KETO]) compared to matched controls with lower LDL-C from the Miami Heart (MiHeart) cohort. METHODS: There were 80 KETO individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglyceride levels ≤80 mg/dL, without familial hypercholesterolemia, matched 1:1 with MiHeart subjects for age, gender, race, hyperlipidemia, hypertension, and smoking status. Coronary artery calcium and coronary computed tomography angiography (CCTA) were used to compare coronary plaque between groups and correlate LDL-C to plaque levels. RESULTS: The matched mean age was 55.5 years, with a mean LDL-C of 272 (maximum LDL-C of 591) mg/dl and a mean 4.7-year duration on a KETO. There was no significant difference in coronary plaque burden in the KETO group as compared to MiHeart controls (mean LDL 123 mg/dL): coronary artery calcium score (median 0 [IQR: 0-56]) vs (1 [IQR: 0-49]) (P = 0.520) CCTA total plaque score (0 [IQR: 0-2] vs [IQR: 0-4]) (P = 0.357). There was also no correlation between LDL-C level and CCTA coronary plaque. CONCLUSIONS: Coronary plaque in metabolically healthy individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL on KETO for a mean of 4.7 years is not greater than a matched cohort with 149 mg/dL lower average LDL-C. There is no association between LDL-C and plaque burden in either cohort. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT057333255).

Background: The physical demands of golf caddying, including walking while carrying a golf bag, may potentially affect body composition, and markers of metabolic, cardiovascular, and musculoskeletal health. Therefore, this study examined the impact of 24 weeks of caddying on physical health in middle-older aged males. Methods: Eleven full-time experienced male caddies (age: 59 [8] y; caddying experience: 14 [12] y) were recruited from a local golf course. The following were assessed at preseason and after 24 weeks of caddying (March–September 2022): body composition, heart rate, blood pressure, blood lipids, and performance tests (static and dynamic balance, strength, and submaximal fitness). Physical activity (PA) levels were assessed at preseason and at the mid-point of the caddying season. Across the caddying season, participants completed a monthly average of 24.0 (3.8) rounds. Results: Following the caddying season, improvements in static balance (Δ = 13.5 s), dynamic balance (Δ = −1.8 s), and lower back absolute strength (Δ = 112.8 N), and muscle quality (Δ = 2.0 N·kg−1) were observed (all P <.05). Additionally, blood lipids, including total cholesterol (Δ = −0.6 mmol·L−1), high-density lipoprotein cholesterol (Δ = 0.1 mmol·L−1), low-density lipoprotein cholesterol (Δ = −0.6 mmol·L−1) (all P <.05), and body composition, including body mass (Δ = −2.7 kg), fat mass (Δ = −1.9 kg), fat percentage (Δ = −1.4%), fat-to-muscle ratio (Δ = −0.03), and body mass index (Δ = −0.9 kg·m−2) (all P <.05) improved. Caddying did not offer beneficial changes to cardiovascular variables or cardiorespiratory fitness (P >.05), while coronary heart disease risk score decreased (Δ = −3.3%) (P <.05). In relation to PA, light- (Δ = 145 min) and moderate-intensity (Δ = 71 min) PA, moderate to vigorous PA (Δ = 73 min), and total PA (Δ = 218 min) between preseason and the mid-point of the caddying season increased, while sedentary time (Δ = −172 min) decreased (all P <.05). Conclusion: Golf caddying can provide several physical health benefits such as improvements in various markers of cardiometabolic health, lower back absolute strength, and static and dynamic balance. The physical health improvements that caddying offers is likely contributed to by increased PA volume and intensity through walking on the golf course. Therefore, caddying may represent a feasible model for increasing PA volume and intensity and achieve physical health–related benefits. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment is one of the non-motor symptoms in Parkinson's disease (PD) and multiple system atrophy (MSA). Few studies have previously been conducted on the correlation between serum uric acid (SUA) and lipid levels and mild cognitive impairment in PD and MSA. Methods: Participants included 149 patients with PD and 99 patients with MSA. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Evaluations were conducted on SUA and lipid levels, which included triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC). Results: Patients with PD and MSA diagnosed with mild cognitive impairment demonstrated multiple cognitive domain impairment when compared with patients with normal cognition. Attentional impairment was more pronounced in patients with MSA when compared with PD (p = 0.001). In PD, the risk of mild cognitive impairment was lower in the highest quartiles and secondary quartile of SUA than in the lowest quartiles (odds ratio [OR] = 0.281, 95% confidence intervals [CI]: 0.097-0.810, p = 0.019; and OR = 0.317, 95% CI: 0.110-0.911, p = 0.033). In MSA, the risk of mild cognitive impairment was lower in the third and highest quartile of SUA than in the lowest quartile (OR = 0.233, 95% CI: 0.063-0.868, p = 0.030; and OR = 0.218, 95% CI: 0.058-0.816, p = 0.024). In patients with PD, the MoCA scores were negatively correlated with TC levels (r = -0.226, p = 0.006) and positively correlated with SUA levels (r = 0.206, p = 0.012). In MSA, the MoCA scores were positively correlated with SUA levels (r = 0.353, p = 0.001). Conclusions: Lower SUA levels and higher TC levels are a possible risk factor for the risk and severity of mild cognitive impairment in PD. Lower SUA levels are a possible risk factor for the risk and severity of mild cognitive impairment in MSA. [ABSTRACT FROM AUTHOR]

High-intensity interval training (HIIT) is an emerging exercise strategy to improve health and fitness, but previous studies have evaluated HIIT interventions across different populations and outcomes. This review aimed to comprehensively synthesize published evidence on the effects of HIIT on key cardiometabolic health parameters in children and adolescents. We searched seven databases until February 2024. Systematic reviews were eligible if they 1) compared HIIT and active/non-active control conditions with meta-analysis, 2) examined cardiorespiratory fitness, body composition and cardiometabolic risk biomarkers, and 3) examined children and adolescents. We included 18 systematic reviews with meta-analysis, including 223 original studies and 13,900 unique participants. HIIT is effective for cardiorespiratory fitness in children and adolescents with diverse health and weight status (median standardized mean difference [SMD] = 0.75). Improvements in body composition and several cardiometabolic risk biomarkers, including systolic blood pressure (median SMD = −0.40), diastolic blood pressure (median SMD = −0.22), triglyceride (median SMD = −0.30), low-density lipoprotein cholesterol (median SMD = −0.90), and high-density lipoprotein cholesterol (median SMD = 0.34), have also been observed following HIIT, with a notably more pronounced effect in youth with overweight/obesity or metabolic disorders. Our umbrella review supports the effectiveness of HIIT in enhancing cardiometabolic health, suggesting its integration into physical activity promotion programmes in schools and communities. [ABSTRACT FROM AUTHOR]

Roux‐en‐Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic–pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed‐effect modeling approach. A parent–metabolite model with first‐order absorption, 2‐compartments for SV and 1‐compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL‐cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low‐intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post‐RYGB patients to maintain a comparable response to that of non‐operated subjects. Moderate‐intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non‐statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post‐RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non‐statin drugs to attain equivalent responses and mitigate potential adverse events. [ABSTRACT FROM AUTHOR]

A systematic literature review and meta‐analysis was performed to evaluate the effects of dapagliflozin on low‐density lipoprotein (LDL) cholesterol in type 2 diabetes mellitus. Data on changes in LDL cholesterol, adverse cardiac events (ACEs), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were pooled in a meta‐analysis. Data from dose comparison trials were separately pooled, and meta‐analysis was conducted by using RevMan (5.4.1) and R (4.1.2). Dapagliflozin increased LDL cholesterol by 2.33 mg/dL (95% CI, 1.46 to 3.19; I2 = 0%; P <.00001), increased risk of ACEs by 1.56 (95% CI, 1.02 to 2.39; I2 = 0%; P <.04), decreased HbA1c by −0.41% (95% CI, −0.44 to −0.39; I2 = 85%; P <.00001), and decreased FBG by −13.51 mg/dL (95% CI, −14.43 to −12.59; I2 = 92%; P <.00001) versus any placebo or active comparator. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 1.71 mg/dL (95% CI, −1.20 to 4.62; I2 = 53%; P =.25) versus a 5 mg dose and by 1.04 mg/dL (95% CI, −1.17 to 3.26; I2 = 62%; P =.36) versus a 2.5 mg dose. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 3.13 mg/dL (95% CI, 1.31 to 4.95; I2 = 0%; P =.0008), increased the risk of ACEs by 1.26 (95% CI, 0.56 to 2.87; I2 = 0%; P =.58), decreased HbA1c by −0.4% (95% CI, −0.45 to −0.35; I2 = 89%; P <.00001), and decreased FBG by −8.39 mg/dL (95% CI, −10 to −6.77; I2 = 96%; P <.00001) versus a placebo or active comparator. Dapagliflozin monotherapy resulted in a minimal but statistically significantly (P =.0002) increase in LDL cholesterol. However, this minor change does not increase the risk of ACEs (P =.17) when compared with placebo or active comparator. [ABSTRACT FROM AUTHOR]

Objective: Gestational diabetes mellitus (GDM) is associated with metabolic abnormalities such as an altered serum lipid profile. This study investigated the influence of polymorphisms in the lipid metabolism-related cholesteryl ester transfer protein gene (CETP) on the metabolic parameters of pregnant women with GDM. Methods: This prospective case-control study included 665 women with GDM and 1,044 women with uncomplicated pregnancies. The PCR-restriction fragment length polymorphism method was used to genotype rs708272 and rs1800775 single nucleotide polymorphisms (SNPs). Lipid and glucose metabolic parameters were assessed. Genetic associations with related traits were analyzed. Results: Genotype distributions of rs708272 and rs1800775 in patients with GDM were similar to those in normal controls. However, the two CETP SNPs were associated with altered plasma total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) concentrations in patients with GDM and in control pregnant women. Additional subgroup analysis demonstrated that the rs708272 polymorphism was associated with variations in triglyceride (TGs), TC, LDL-C, and apolipoprotein B (ApoB) levels in patients with overweight or obesity GDM, whereas both polymorphisms were associated with glucose metabolic traits (plasma insulin, glucose, or insulin) and the insulin resistance index in patients with GDM without obesity. Conclusions: In patients with GDM, the rs708272 polymorphism was associated with atherogenic lipid levels (TG, TC, LDL-C, and ApoB), whereas the rs708272 and rs1800775 polymorphisms were associated with glucose metabolism and insulin resistance parameters, which were influenced by the body mass index. These results suggest that genetic associations with atherogenic metabolic factors may increase the risk of adverse outcomes in mothers with GDM and their offspring. [ABSTRACT FROM AUTHOR]

Objective: The inconsistency in conclusions from early observational studies has sparked our interest in elucidating the relationship between lipid levels and susceptibility to hyperemesis gravidarum (HG). This study wishes to employed Mendelian randomization analysis to investigate the causal relationship between low-density lipoprotein cholesterol (LDL-C) and HG. Methods: We employed Tow-Sample MR analysis to investigate the causal associations between LDL-C and HG. Specific variables were selected from GWAS database for MR analysis, using single nucleotide polymorphisms (SNPs) as our instruments. The threshold for significant SNPs as genetic instruments has been set at 5 × 10−8. F-statistic was employed to validate the strength of exposure instruments. The causality was mainly evaluated by Inverse Variance Weighted method (IVW). To address potential bias from the selection of genetic variants with pleiotropic effects, sensitivity analysis was performed by Cochrane Q-test, MR Egger, weighted median, MR-PRESSO and Leave-one-out methods. To validate the directionality of causal relationships, we employed Steiger test to filter SNPs. At last, we conducted reverse MR to exclude the causal impact of HG on LDL-C levels. Results: Our MR results identified the effect of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG (OR:1.30; 95%CI:1.03-1.65; p = 0.028). In reverse MR analyses, no evidence was found for causal effect of HG on LDL-C levels (OR:1.00; 95%CI:1.00-1.01; p = 0.163). Sensitivity analyses were used to confirm reliability. Conclusion: This study may have provided evidence of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG. Appropriate lowering LDL-C levels may serve as a preventive and treatment measure for HG. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the likelihood of hyperglycemia postpartum in women with gestational diabetes mellitus (GDM) and to identify the predictors. Methods: The retrospective cohort study involved 1 527 GDM patients who delivered at Peking University First Hospital from 1 January 2021, to 31 December 2021. According to the blood glucose level of postpartum oral glucose tolerance test (OGTT), women were divided into a normal glucose tolerance (NGT) group and a hyperglycemia group, and their characteristics and risk factors of hyperglycemia were compared. Results: The prevalence of hyperglycemia was 33.9% (184/543) at 6–12 weeks postpartum. Compared with the NGT group, the fasting plasma glucose (FPG) of hyperglycemia group increased significantly during pregnancy and postpartum, the OGTT 1h postprandial glucose (PG) and 2hPG increased in the second trimester of pregnancy, the triglyceride (TG) increased in the first trimester of pregnancy and postpartum, the triglyceride glucose (TyG) index increased in the first trimester of pregnancy and postpartum, and the total cholesterol (TCHO) and low density lipoprotein cholesterol (LDL-C) decreased in the second trimester (p < 0.05). Fasting plasma glucose (FPG) in the first trimester [odds ratio (OR) = 3.583, p < 0.001], OGTT 2hPG in the second trimester (OR = 1.604, p < 0.001), the TyG index in the first trimester (OR = 1.863, p = 0.045) and FPG in third trimester (OR = 1.985, p = 0.024) were independent risk factors for postpartum hyperglycemia. Conclusions: Approximately one-third of women with GDM have hyperglycemia 6–12 weeks after delivery. FPG and the TyG index in the first trimester, OGTT 2hPG in the second trimester and FPG in third trimester are risk factors for postpartum hyperglycemia. [ABSTRACT FROM AUTHOR]

Aim: The aim was to examine the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), a risk factor for atherosclerotic cardiovascular disease, and its association with glycaemic control metrics in children and adolescents with type 1 diabetes (T1D). Materials and Methods: We enrolled 244 children and adolescents with T1D (115 girls, mean age: 16.2 ± 3.2 years). The diagnosis of MASLD was defined by the presence of hepatic steatosis on ultrasonography in combination with at least one of five common cardiometabolic risk factors. Metrics of short‐term and long‐term glycaemic control, blood pressure, lipids, anthropometric characteristics and three genetic variants strongly related to MASLD susceptibility (rs738409 [patatin‐like phospholipase domain‐containing 3], rs58542926 [transmembrane 6 superfamily member 2] and rs1260326 [glucokinase regulator]) were assessed. Characteristics of these subjects with and without MASLD were compared using the unpaired Student t test, Mann–Whitney test or χ2 test as appropriate. Logistic regression analyses were performed to determine the main independent predictors of MASLD. Results: The prevalence of MASLD was 27.5% in children and adolescents with T1D. Blood pressure, total cholesterol, low‐density lipoprotein (LDL) cholesterol, non‐high‐density lipoprotein cholesterol, HbA1c and time above range (TAR) were significantly higher in subjects with MASLD than in those without MASLD. Mean HbA1c values from diabetes onset (adjusted odds ratio [OR]: 1.703, 95% confidence interval [CI]: 1.040–2.787, p = 0.034), TAR (adjusted OR: 1.028, 95% CI: 1.009–1.047, p = 0.006) and plasma LDL cholesterol (adjusted OR: 1.045, 95% CI: 1.013–1.078, p = 0.004) were independently associated with the presence of MASLD. Conclusions: MASLD is a common condition in children and adolescents with T1D. The mean HbA1c values from diabetes onset, TAR and LDL cholesterol levels were the independent predictors of MASLD. [ABSTRACT FROM AUTHOR]

Background: An ideal glucose-lowering drug is expected to not only improve glycemic control, but also have positive effects on weight, blood pressure, dyslipidemia, and also cardiovascular and renal outcomes. Objective: To investigate and compare the impact of Sodium-glucose transport protein 2 (SGLT2) inhibitors on glycemic and extraglycemic laboratory parameters and the parameters which affect this impact. Methods: This retrospective study was conducted between January 2022 and December 2022. A total of 250 patients diagnosed with type 2 diabetes mellitus (T2DM) using SGLT2i were included in the study. Results: Patients had a mean age of 55.4 ± 9.6, and 53.6% (n = 134) were male. Among the patients, 19.6% (n = 49) used dapagliflozin and 80.4% (n = 201) used empagliflozin. Glucose, HbA1c, and triglyceride levels at 3 and 6 months showed significant reductions compared to baseline, while serum sodium and HDL-C levels showed significant increases (p < 0.001). Additionally, creatinine and serum potassium levels at 6 months were significantly higher than baseline, while LDL-C and urine albumin-to-creatinine ratio levels were significantly lower. Empagliflozin users exhibited significantly higher creatinine levels only at 3. months, higher serum sodium levels only at 6. months, and lower HbA1c levels only at 6. months compared to dapagliflozin users. Conclusion: While SGLT2i seem to provide positive effects on the lipid profile, as well as their well-recognized effects on glycemic parameters, there may be value in further evaluating renal safety and the long-term alterations in lipid profile. [ABSTRACT FROM AUTHOR]

Background/Purpose: The aim of the study was to assess the effect of obesity on the diagnostic accuracy of HbA1c. Methods: This retrospective cross sectional study was conducted in 108 overweight/obese and 40 normal weight Bangladeshi adults. Those satisfying the exclusion and inclusion criteria were included. Diabetes and pre-diabetes were diagnosed by oral glucose tolerance test (OGTT) and HbA1c using the 2006 World Health Organization (WHO) diagnostic criteria. HbA1c was estimated by capillary electrophoresis method. Results: 108 overweight and obese (mean body mass index (BMI) 36.33 ± 8.86 kg/m2, mean age 29.12 ± 9.28 years) and 40 normal weight (mean BMI 20.35 ± 1.68 kg/m2, mean age 28.13 ± 6.22 years) adults were included in the study. Significantly greater number of patients were diagnosed with prediabetes using HbA1c criteria than OGTT criteria (39.68% vs 19.05%, p = 0.005) in overweight and obese group. The concordance between OGTT and HbA1c for the diagnosis of prediabetes was low in overweight and obese adults [Ƙ with 95%CI = 0.031(-0.194 to 0.256), n = 52]. The specificity and discrimination of HbA1c for the diagnosis of prediabetes were low in overweight and obese compared to normal weight group (52.3% vs 93.9%; 0.64 vs 0.89, p = 0.056, 95% CI = -0.01 to 0.51, respectively). The specificity of HbA1c for the diagnosis of prediabetes in adults with BMI ≥ 23 kg/m2 increased to 90% at a cut-off of 6.15%. Conclusion: HbA1c was not accurate in the diagnosis of prediabetes in adults with BMI ≥ 23 kg/m2. A higher cut-off value for HbA1c should be used for the diagnosis of prediabetes, but not diabetes. [ABSTRACT FROM AUTHOR]

Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease. Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 μg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin–eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKβ)/AMPK signaling pathway activation. Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKβ/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice. Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKβ/AMPK signaling pathway in kidney tissue. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD. Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment. Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function. This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field. [ABSTRACT FROM AUTHOR]

The assessment of left ventricular (LV) remodeling and its association with mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate LV remodeling changes one year after kidney transplantation (KT) and identify their influencing factors. Ninety-five KTRs (68 males; ages 40.2 ± 10.8 years) were followed before and one year after KT. Traditional risk factors and bone metabolism indicators were assessed. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and left ventricular diastolic dysfunction (LVDD) were measured using two-dimensional transthoracic echocardiography. The relationship between MBD and LV remodeling and the factors influencing LV remodeling were analyzed. One year after KT, MBD was partially improved, mainly characterized by hypercalcemia, hypophosphatemia, hyperparathyroidism, 25-(OH) vitamin D deficiency, elevated bone turnover markers, and bone loss. LVMI, the prevalence of left ventricular hypertrophy (LVH), and the prevalence of LVDD decreased, while LVEF increased. LVH was positively associated with postoperative intact parathyroid hormone (iPTH) and iPTH nonnormalization. ΔLVMI was positively associated with preoperative type-I collagen N-terminal peptide and postoperative iPTH. LVEF was negatively associated with postoperative phosphorous. ΔLVEF was negatively associated with postoperative iPTH. LVDD was positively associated with postoperative lumbar spine osteoporosis. Preoperative LVMI was negatively associated with ΔLVMI and positively associated with ΔLVEF. Advanced age, increased BMI, diabetes, longer dialysis time, lower albumin level, and higher total cholesterol and low-density lipoprotein levels were associated with LV remodeling. LV remodeling partially improved after KT, showing a close relationship with MBD. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb−) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype. A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan–Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb−/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR. Among 74 IMN patients, 14 were SAb−/GAg+. Compared with SAb+/GAg + patients, SAb−/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p <.01), but similar pathological manifestations of kidney biopsy. Multivariate logistic analyses indicated that low albumin (0.79 [95%CI: 0.66–0.95], p =.01) and high cholesterol (1.81 [95%CI: 1.02–3.19], p =.04) were correlated with seropositivity of PLA2R antibody. SAb−/GAg + patients exhibited a significantly higher probability of CR (p =.03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb−/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01–18.17], p =.04). IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the association of diabetes duration with cardiovascular disease (CVD) risk and to examine the relationship between lipid levels and CVD risk over the duration. Methods Using the Korean National Health Insurance Service Cohort database, we identified 2 359 243 subjects with type 2 diabetes aged ≥ 20 years in 2015 to 2016. Baseline lipid levels and diabetes duration were evaluated and followed up until December 2020 (mean follow-up, 3.9 years). Subjects were categorized according to diabetes duration (new-onset, < 5 years, 5-9 years, or ≥ 10 years). We analyzed the new-onset diabetes group with low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL as the reference group. The hazard ratios (HRs) and 95% CIs of myocardial infarction (MI) and ischemic stroke (IS) were estimated using a Cox proportional hazards model adjusted for potential confounders. Results During follow-up, 45 883 cases of MI and 53 538 cases of IS were identified. The risk of MI or IS began to increase at LDL-C ≥ 160 mg/dL in the new-onset diabetes group, and at LDL-C ≥ 130 mg/dL in the group with diabetes duration < 5 years. Among subjects with diabetes duration of 5 to 9 years, LDL-C levels of 100-129 mg/dL, 130-159 mg/dL, and ≥ 160 mg/dL were significantly associated with the risk of MI (HR [95% CI] 1.13 [1.04-1.22], 1.28 [1.17-1.39], and 1.58 [1.42-1.76], respectively). MI risk in the diabetes duration ≥ 10 years group was increased by 16%, even in the LDL-C 70-99 mg/dL population (HR [95% CI] 1.16 [1.08-1.25]). Conclusion This population-based longitudinal study revealed that the LDL-C cutoff level for increasing the risk of CVD varied with diabetes duration and that the target LDL-C level should depend on the duration. [ABSTRACT FROM AUTHOR]

Objective: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. Methods: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. Results: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. Conclusion: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism. [ABSTRACT FROM AUTHOR]

Previous observational studies have explored the association between serum lipids, apolipoproteins, and adverse ventricular/aortic structure and function. However, whether a causal link exists is uncertain. This study employed a two-sample Mendelian randomization (MR), colocalization, reverse, and multivariable MR (MVMR) approach to examine the causal associations among five serum lipids, two apolipoproteins, and 32 cardiac magnetic resonance (CMR) traits. Utilizing single-nucleotide polymorphisms (SNPs) linked to serum lipids and apolipoproteins as instrumental variables. CMR traits from seven independent genome-wide association studies served as preclinical endophenotypes, offering insights into aortic and cardiac structure/function. The primary analysis utilized a random-effects inverse variance method (IVW), followed by sensitivity and validation analyses. In the primary IVW MR analyses, genetically predicted low-density lipoprotein cholesterol (LDL-C) levels were positively correlated with increased descending aorta strain (DAo strain) (β = 0.098; P = 2.69E-07) and ascending aorta strain (AAo strain) (β = 0.079; P = 5.19E-05). Genetically predicted high-density lipoprotein cholesterol (HDL-C) levels were positively correlated with left ventricular radial peak diastolic strain rate (LV-PDSRll) (β = 0.176; P = 2.89E-05) and the left ventricular longitudinal peak diastolic strain rate (LV-PDSRrr) (β = 0.059; P = 2.44E-06), and negatively correlated with left ventricular regional wall thickness (LVRWT). While apolipoprotein B (ApoB) levels were positively correlated with AAo strain (β = 0.076; P = 1.16E-05), DAo strain (β = 0.065; P = 2.77E-05). A shared causal variant was identified to demonstrate the associations of ApoB with AAo strain and DAo strain using colocalization analysis. Sensitivity analyses confirmed the robustness of these associations. Targeting lipid and apolipoprotein levels through interventions may provide novel strategies for the primary prevention of CVDs. [ABSTRACT FROM AUTHOR]

Purpose of the Review: This review examines the pivotal role of monoclonal antibodies against PCSK9 in lipid-lowering therapy, emphasizing their biological and clinical impact. Recent Findings: Randomized controlled trials have validated that PCSK9 monoclonal antibodies (Mabs) effectively reduce LDL-c levels by approximately 50%, even when added to maximal statin therapy. They moreover produce a notable 15–20% relative decrease in major cardiovascular events, with a greater reduction among high-risk patients and no evidence for serious adverse effects, assuaging previous concerns. Summary: This review highlights the benefits of PCSK9 Mabs in high cardiovascular risk patients. Despite their efficacy and safety, these therapies are hindered by limited access, and require broader integration into clinical practice to optimize therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease leading to reduced (healthy) life years. The aim of this study is to quantify the societal costs associated with hypercholesterolemia. We use epidemiologic data on the distribution of cholesterol levels as well as data on relative risks regarding ischemic heart disease, stroke, and other cardiovascular diseases. The analytical approach is based on the use of population-attributable fractions applied to direct medical, direct non-medical and indirect costs using data of Austria. Within a life-cycle analysis we sum up the costs of hypercholesterolemia for the population of 2019 and, thus, consider future morbidity and mortality effects on this population. Epidemiologic data suggest that approximately half of Austria's population have low-density lipoprotein cholesterol (LDL-C) levels above the target levels (i.e., are exposed to increased risk). We estimate that 8.2% of deaths are attributable to hypercholesterolemia. Total costs amount to about 0.33% of GDP in the single-period view. In the life-cycle perspective, total costs amount to €806.06 million, €312.1 million of which are medical costs, and about €494 million arise due to production loss associated with hypercholesterolemia. The study points out that significant shares of deaths, entries into disability pension and care allowance, full-time equivalents lost to the labor market as well as monetary costs for the health system and the society could be avoided if LDL-C-levels of the population were reduced. [ABSTRACT FROM AUTHOR]

Objectives: There is a growing need to understand the potential role of soluble platelet selectin (sP-selectin) in sustained endothelial activation through increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion-1 (sVCAM-1) in people living with HIV (PLWH) on highly active antiretroviral therapy (HAART). Methodology: This was a cross-sectional study involving PLWH on HAART (n = 55), in comparison to PLWH not on treatment (HAART-naïve) (n = 29), and (iii) HIV negative controls (n = 48) from the Mankweng area in the Limpopo province, South Africa. We quantified serum levels of sP-selectin, together with sICAM-1 and sVCAM-1. Most of the HAART-exposed group were on treatment for <5 years. We further performed frequency distribution and descriptive statistics for categorical variables. Results: Soluble P-selectin was positively correlated with sVCAM-1 (r = 0.469; p<0.001) in PLWH on HAART, even after adjusting for confounding factor such as age, BMI, and total cholesterol (r = 0.467; p<0.001). Moreover, in PLWH on HAART sP-selecting was independently associated with the release of sVCAM-1 (β = 0.445; p<0.001), even after adjusting for confounders (β = 0.475; p = 0.001). Serum levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004) and total cholesterol (p<0.001) were significantly higher in PLWH on HAART as compared to the HAART-naïve group. Conclusion: There is a need for more studies to investigate the role of sP-selectin in promoting endothelial activation and CVD-risk in PLWH on HAART, especially within the sub-Saharan Africa region. [ABSTRACT FROM AUTHOR]

Background: Patients with betathalassemia have higher risk of various metabolic disturbances. The literature presents conflicting results about the patterns of abnormal lipid profile among patients with betathalassemia. This systematic review aimed to assess dyslipidemia patterns among patients with betathalassemia when compared with healthy individuals. Methods: The methods used were adherent to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Systematic searches of the literature were done across Medline/PubMed, Web of Science, Science Direct, and Regional Portal of the World Health Organization Virtual Health Library. Calculation of standardized mean difference (SMD) estimates and their associated 95% confidence intervals (CIs) were done through Jamovi software. Results: The systematic review included 21 studies meeting the criteria for the analyses. Patients with beta-thalassemia major displayed significantly elevated triglyceride levels (SMD: 0.448, 95% CI, 0.214 to 0.682; P <.001) and reduced total serum cholesterol (SMD: -2.26 (95% CI-2.834 to -1.678; P <.001), as well as decreased levels of both low-density lipoprotein cholesterol (SMD: -1.88, 95% CI, -2.614 to -1.147; P <.001) and high-density lipoprotein cholesterol (SMD: -1.32, 95% CI, -1.786 to -0.860; P <.001). Similarly, beta-thalassemia intermedia patients exhibited comparable lipid profile abnormalities to those with beta-thalassemia major. Conversely, beta-thalassemia minor patients only showed significantly lower total serum cholesterol levels (SMD: -0.66, 95% CI, -0.860 to -0.472; P <.001). Conclusion: Evidence indicates alterations in lipid profile markers among beta-thalassemia patients. The findings indicate the importance of assessing hypertriglyceridemia and hypocholesterolemia in these patients, especially those with major and intermedia forms, as these lipid profile abnormalities increase the risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Often linked with the risk of various diseases, blood low-density lipoprotein cholesterol (LDL-C) levels are typically deemed more favorable when lower. The objective of this investigation is to elucidate the link between blood LDL-C levels and the risk of prostate cancer (PCa) in middle-aged and older men without hypertension in the United States. Utilizing continuous data from the National Health and Nutrition Examination Survey (NHANES) database spanning 2003–2010, a selection of 1,223 non-hypertensive men aged ≥ 40 years was made from a pool of 41,156 participants, ensuring no missing information. Regression analyses were employed to investigate the correlation between blood LDL-C levels and the PCa risk, while identifying potential inflection points indicative of threshold effects. Additionally, we scrutinized the linkage between cholesterol-lowering prescription drug usage and PCa. In our study of 2,224 participants, we found no significant correlation between blood LDL-C levels and the PCa risk after adjusting for confounding variables (Odds Ratio = 0.99; P-value > 0.05). However, upon conducting a subgroup analysis, we discovered a meaningful correlation between lower blood LDL-C levels and an increased PCa risk in the non-hypertensive population (Odds Ratio = 0.99; P-value < 0.05). Meanwhile, we identified a threshold effect and a tipping point at an LDL-C levels of 67 mg/dl. Furthermore, a significant correlation was identified between cholesterol-lowering prescription drug usage and a heightened PCa risk in the non-hypertensive population (Odds Ratio = 18.87; P-value < 0.05; P for interaction < 0.05). Our results indicate that in non-hypertensive middle-aged and older men residing in the United States, lower blood LDL-C levels are not necessarily better and the PCa risk escalates when blood LDL-C levels drop below 67 mg/dl, which may guide early screening and prognosis of PCa in specific populations. This finding calls for further validation via larger sample sizes and a more in-depth analysis of PCa history. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite a proposed causal role for LDL-C (low-density lipoprotein cholesterol) in aortic stenosis (AS), randomized controlled trials of lipid-lowering therapy failed to prevent severe AS. We aimed to assess the impact on AS and peak velocity across the aortic valve conferred by lifelong alterations in LDL-C levels mediated by protein-disrupting variants in 3 clinically significant genes for LDL (low-density lipoprotein) metabolism (LDLR , APOB , and PCSK9). METHODS: We used sequencing data and electronic health records from UK Biobank (UKB) and All of Us and magnetic resonance imaging data from UKB. We identified predicted protein-disrupting variants with the Loss Of Function Transcript Effect Estimator (LOFTEE) and AlphaMissense algorithms and evaluated their associations with LDL-C and peak velocity across the aortic valve (UK Biobank), as well as diagnosed AS and aortic valve replacement (UK Biobank and All of Us). RESULTS: We included 421 049 unrelated participants (5621 with AS) in UKB and 195 519 unrelated participants (1087 with AS) in All of Us. Carriers of protein-disrupting variants in LDLR had higher mean LDL-C (UKB: +42.6 mg/dL; P =4.4e-237) and greater risk of AS (meta-analysis: odds ratio, 3.52 [95% CI, 2.39–5.20]; P =2.3e-10) and aortic valve replacement (meta-analysis: odds ratio, 3.78 [95% CI, 2.26–6.32]; P =4.0e-7). Carriers of protein-disrupting variants in APOB or PCSK9 had lower mean LDL-C (UKB: –32.3 mg/dL; P <5e-324) and lower risk of AS (meta-analysis: odds ratio, 0.49 [95% CI, 0.31–0.75]; P =0.001) and aortic valve replacement (meta-analysis: odds ratio, 0.54 [95% CI, 0.30–0.97]; P =0.04). Among 57 371 UKB imaging substudy participants, peak velocities across the aortic valve were greater in carriers of protein-disrupting variants in LDLR (+12.2 cm/s; P =1.6e-5) and lower in carriers of protein-disrupting variants in PCSK9 (–6.9 cm/s; P =0.022). CONCLUSIONS: Rare genetic variants that confer lifelong higher or lower LDL-C levels are associated with substantially increased and decreased risk of AS, respectively. Early and sustained lipid-lowering therapy may slow or prevent AS development. [ABSTRACT FROM AUTHOR]

Background: Previous 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. Methods: Data 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. Results: In 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. Conclusion: Due 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. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance coexist with many metabolic disorders, whether these disorders were promotors or pathway-factors for the association of insulin resistance and cardiovascular disease (CVD) remained unclear. We aimed to investigate the pathways related to elevated the triglyceride-glucose (TyG) index and pathways through elevated TyG index to the occurrence of CVD in Chinese adults. Methods: A total of 96,506 participants were enrolled from the Kailuan study. Bayesian network model with the max-min hill climbing algorithm and maximum likelihood estimation was applied to identify factors and pathways related to the TyG index, and quantitatively infer the impact of associated factors on elevated TyG index and the occurrence of CVD by computing conditional probabilities. Results: A final Bayesian network was constructed with 14 nodes and 25 arcs, creating 28 pathways related to elevated TyG index and 8 pathways from elevated TyG index to CVD. Elevated TyG index was causally associated with CVD, the condition probability was 11.9%. Pathways to elevated TyG index were mainly through unhealthy lifestyles and the subsequent increase in lipid profiles, especially smoking and low-density lipoprotein cholesterol. The most important pathway from elevated TyG index to CVD was through overweight/obesity, hypertension, and chronic kidney disease, with a condition probability of 18.5%. The maximum relative change rate related to elevated TyG index was observed for overweight/obesity (64.3%). Conclusions: Elevated TyG index was causally associated with the risk of CVD, a combined control of lifestyles and metabolic factors may contribute to the reduction of TyG index and the prevention of CVD. [ABSTRACT FROM AUTHOR]

Background: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies. Objective: Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center. Design: Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics. Participants: We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%. Main Measures: The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR). Key Results: Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups. Conclusions: ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist. [ABSTRACT FROM AUTHOR]

Objective: Stroke risk factors often exert long-term effects, and Mendelian randomization (MR) offers significant advantages over traditional observational studies in evaluating the causal impact of these factors on stroke. This study aims to consolidate and evaluate the relationships between potential causal factors and stroke risk, drawing upon existing MR research. Methods: A comprehensive search for MR studies related to stroke was conducted up to August 2023 using databases such as PubMed, Web of Science, Embase, and Scopus. This meta-analysis examines the relationships between potential causative factors and stroke risk. Both random-effects and fixed-effects models were utilized to compile the dominance ratios of various causative elements linked to stroke. The reliability of the included studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology incorporating Mendelian Randomization (STROBE-MR) guidelines. Results: The analysis identified several risk factors for stroke, including obesity, hypertension, low-density lipoprotein cholesterol (LDL-C), chronic kidney disease (CKD), and smoking. Protective factors included high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), and educational attainment. Subgroup analysis revealed that type 2 diabetes mellitus (T2DM), diastolic blood pressure (DBP) are risk factors for ischemic stroke (IS). Conclusion: This study confirms that variables such as obesity, hypertension, elevated LDL-C levels, CKD, and smoking are significantly linked to the development of stroke. Our findings provide new insights into genetic susceptibility and potential biological pathways involved in stroke development. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO , identifier CRD42024503049. [ABSTRACT FROM AUTHOR]

In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on the cardiovascular system in RA patients remains poorly understood, especially with its long-term use. This study investigates the effect of therapy with IL-6 receptor blocker tocilizumab (TCZ) on the dynamics of cardiovascular risk (CVR), modifiable risk factors (RFs), carotid artery (CA) structural changes, and the incidence of cardiovascular complications (CVCs) in RA patients during a 265-week follow-up period. Forty-five patients with active RA (DAS28-ESR 6.2 (5.5;6.8) with ineffectiveness and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included in this study. During long-term therapy with TCZ in RA patients, no increase in CVR and no significant structural changes in CA were observed. No significant changes in the blood lipid spectrum were observed in patients without statin therapy. In the group of patients receiving statins, there was a 43% increase in high-density lipoprotein cholesterol (HDL-C), a 15% reduction in total cholesterol levels, and a 56% decrease in the atherogenicity index (p < 0.01 in all cases). Associations were found between ∆ total cholesterol and ∆ C-reactive protein (CRP) (R = 0.36, p = 0.04), ∆ low-density lipoprotein cholesterol (LDL-C), and ∆-CRP (R = 0.42, p = 0.03) in RA patients receiving statins. Initially, the thickness of the intima–media complex of carotid arteries (cIMT) positively moderately correlated with age (R = 0.7; p < 0.01), BMI (R = 0.37; p < 0.01), and systolic blood pressure (R = 0.64; p < 0.01); however, it weakly correlated with the lipid spectrum parameters: total cholesterol (R = 0.29; p < 0.01) and LDL-C (R = 0.33; p < 0.01). No new associations of cIMT by the end of the follow-up period, as well as the relationship of cIMT value with RA activity and therapy, were revealed. Patients with carotid ASPs showed an oppositely directed relationship between total cholesterol and sVCAM-1 at baseline (R = −0.25, p = 0.01) and at the end of this study (R = 0.29, p < 0.01). The incidence of cardiovascular events was 0.53 per 100 patient-years during the 265-week period of TCZ therapy. [ABSTRACT FROM AUTHOR]

Hibernation serves as an energy-conserving strategy that enables animals to withstand harsh environments by reducing their metabolic rate significantly. However, the mechanisms underlying energy adaptation in hibernating ectotherms, such as Pelodiscus sinensis, remain contentious. This paper first reports the decrease in lipid levels and the expression of metabolism-related genes in P. sinensis during hibernation. The results of physiological and biochemical analysis showed that adipocyte cell size was reduced and liver lipid droplet (LD) contents were decreased during hibernation in P. sinensis. Concurrently, serum levels of triglycerides (TGs), total cholesterol (TC), non-esterified fatty acids (NEFAs), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were diminished (n = 8, p < 0.01), while an increase in serum glucose (Glu) (n = 8, p < 0.01) was noted among hibernating P. sinensis. These observations suggest a shift in energy metabolism during hibernation. To gain insights into the molecular mechanisms, we performed integrated transcriptomic and lipidomic analyses of adipose tissue and livers from summer-active versus overwintering P. sinensis, which revealed downregulation of free fatty acids (FFAs), triglycerides (TGs), diglycerides (DGs), and ceramides (Cers) during hibernation. The results of GSEA analysis showed that metabolic pathways associated with lipid metabolism, including glycerolipid metabolism and regulation of lipolysis in adipocytes, were suppressed significantly. Notably, acute cold exposure induced significant downregulation of genes related to lipolysis such as PNPLA2, ABHD5, LPL, CPT1A, and PPARα. The results indicate that lipolysis is suppressed during hibernation in P. sinensis. Collectively, these findings deepen our understanding of survival mechanisms and elucidate the unique energy adaptation strategies employed by hibernating ectotherms. Future research should explore the implications of these findings for the conservation of ectotherms and the applications for artificially inducing hibernation. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia is an autosomal hereditary disease defined by an increased level of low-density lipoprotein cholesterol (LDL-C), which predisposes significant risks for premature cardiovascular disorders. We present a family trio study: proband, a 13-year-old Kazakh girl with homozygous familial hypercholesterolemia (HoFH) and her parents. HoFH is much more rare and severe than a heterozygous form of the disorder. HoFH patients generally present with LDL-C levels exceeding 13 mmol/L, resulting in early and life-threatening cardiovascular events within the first decades of life. In cases of neglected treatment, young patients have a risk of death from coronary diseases before the age of 30. The aim of this research was to identify genetic mutations in the affected patient and her parents. Genetic testing was necessary due to highly elevated LDL-C levels and the presence of multiple xanthomas. Targeted next-generation sequencing (NGS) was performed in this study using the Illumina TruSight cardio panel, which targets 174 genes related to cardiac disorders. The girl was diagnosed with HoFH based on the results of genetic testing. A biallelic mutation was observed in exon 3 of the low-density lipoprotein receptor (LDLR): c. 295 G>A (p.Glu99Lys). Sanger sequencing confirmed that the mutant gene was inherited from both parents. After confirming the genetic diagnosis of HoFH, the patient was treated with LDL apheresis and statins. This case report is the first study of HoFH in a pediatric patient from the Central Asian region. Globally, it emphasizes the need for increased clinical awareness among healthcare providers, as early detection and intervention are important for improving outcomes, particularly in pediatric patients with this rare genetic disorder. [ABSTRACT FROM AUTHOR]

Meta-analysis of genome-wide association studies (GWAS) across diverse populations offers power gains to identify loci associated with complex traits and diseases. Often heterogeneity in effect sizes across populations will be correlated with genetic ancestry and environmental exposures (e.g. lifestyle factors). We present an environment-adjusted meta-regression model (env-MR-MEGA) to detect genetic associations by adjusting for and quantifying environmental and ancestral heterogeneity between populations. In simulations, env-MR-MEGA has similar or greater association power than MR-MEGA, with notable gains when the environmental factor has a greater correlation with the trait than ancestry. In our analysis of low-density lipoprotein cholesterol in ~19,000 individuals across twelve sex-stratified GWAS from Africa, adjusting for sex, BMI, and urban status, we identify additional heterogeneity beyond ancestral effects for seven variants. Env-MR-MEGA provides an approach to account for environmental effects using summary-level data, making it a useful tool for meta-analyses without the need to share individual-level data. Adjusting for and quantifying environmental heterogeneity in the meta-analysis of genomewide association studies of diverse populations identifies additional heterogeneity beyond ancestral effects. [ABSTRACT FROM AUTHOR]

Background: Statins are the gold standard in the treatment of dyslipidemia, significantly reducing the risk of cardiovascular disease. Objective: To systematically review the efficacy and safety of Moderate-intensity Rosuvastatin Plus Ezetimibe compared with High-intensity Rosuvastatin in treating Composite Cardiovascular Events. Methods: PubMed, Embase, Cochrane Library, CINAHL, Web of Science, China Knowledge Network, China Biological Literature Database, Wan Fang Database, and Weipu Database were searched to retrieve randomized controlled trials assessing the safety and efficacy of the two therapies from the time of construction to December 2023. The Jadad scale assessment tool was used to evaluate the quality of the included literature, and Review Manager 5.4 software was used for meta-analysis. The heterogeneity of outcomes was estimated by the I2 test, where we applied risk ratios (RR) and 95% confidence intervals (CI) to assess dichotomous outcomes and mean difference (MD) and 95% CI to present continuous outcomes. We used funnel plots to assess study publication bias and sensitivity analysis was used to address significant clinical heterogeneity. Results: The meta-analysis described 21 RCTs involving 24592 participants. The findings indicated that moderate-intensity statin combination therapy improved low-density lipoprotein cholesterol (LDL-C) (MD -8.06, 95% CI [-9.48, -6.64] p < 0.05), total cholesterol (TG) (MD -5.66, 95% CI [-8.51, -2.82] p < 0.05), and non-high-density lipoprotein cholesterol (non-HDL-C) (MD -17.04, 95% CI [-29.55, -4.54] p < 0.05) to a greater extent and superior in achieving LDL-C <70 (RR1.26, 95% CI [1.22, 1.29] p < 0.05) and LDL-C <55 (RR1.66, 95% CI [1.56, 1.77] p < 0.05) ratios and in the incidence of adverse events than the high-intensity Rosuvastatin monotherapy group. However, there was no statistical difference between the two in improving HDL-C, total cholesterol (TC), and preventing long-term composite adverse cardiovascular events (ACE). Funnel plots indicated publication bias. Sensitivity analysis suggested instability in long-term composite cardiovascular events, HDL-C, and TC results. Conclusions: Moderate-intensity statin plus ezetimibe with combination therapy had better efficacy and safety than high-intensity statins. Future validation is needed with more long-term high-quality large samples. [ABSTRACT FROM AUTHOR]

Background: The extent to which type 2 diabetes (T2D) reduces life expectancy depends on the risk of complications. We aimed to characterise the relationship between risk factors for diabetes complications and life expectancy, in individuals with T2D, free from major chronic disease, in a regional database linked with national New Zealand health databases. Methods: A prospective cohort study design was employed, analysing data from individuals with T2D drawn from the comprehensive Diabetes Care Support Service database (1994–2018). Participants with known values for all five within-target risk factors (WTRF +) including blood pressure, glycaemia, and LDL cholesterol, alongside being non-smoking with normal renal function at baseline, were included. Life expectancy free from cardiovascular disease (CVD), cancer, and dementia at age 50 years was estimated using multistate life tables, adjusting for demographics and clinical metrics. Results: Women and men with no WTRF + at enrolment had a life expectancy free from CVD, cancer, or dementia of 13.1 (95% confidence interval: 9.1–19.0) and 11.2 (6.7–18.6) years, respectively. For the most socioeconomically deprived groups or Māori with no WTRF + at baseline, life expectancies were markedly lower. Life expectancies were 23.7 (18.9–29.7) years for women and 23.2 years (17.2–31.4) years for men with four or five WTRF + at baseline, respectively. While an increasing number of WTRF + at baseline was significantly associated with improved outcomes in men and certain subgroups (e.g. Other ethnicity group), this trend was not statistically significant for women overall or in most subgroups. Conclusions: Having multiple WTRF + at baseline is associated with a considerable increase in life expectancy free from major chronic disease among individuals with T2D. This highlights the importance of lifestyle and clinical interventions in the management of T2D and in the prevention and management of associated chronic conditions. [ABSTRACT FROM AUTHOR]

Currently available antiproprotein convertase subtilisin/kexin type 9 monoclonal antibodies can effectively decrease low-density lipoprotein cholesterol (LDL-C) levels, but require frequent dosing. Recaticimab is a novel humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9. In a phase 1b/2 trial, recaticimab as add-on to stable statins showed robust LDL-C reduction with a dosing interval up to every 12 weeks (Q12W) in patients with hypercholesterolemia. REMAIN-2 (REcaticiMab Add-on therapy In patients with Nonfamilial hypercholesterolemia) aimed to assess the efficacy and safety of 48-week treatment with recaticimab as add-on therapy to statins in nonfamilial hypercholesterolemia. REMAIN-2 was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. During the run-in period, patients received stable moderate or high-intensity statin, with or without cholesterol absorption inhibitors (ezetimibe) or fenofibrate, for ≥4 weeks. Patients with an LDL-C of ≥1.8 mmol/L (if with atherosclerotic cardiovascular disease [ASCVD]) or ≥2.6 mmol/L (if without ASCVD) were then randomized (2:2:2:1:1:1) to receive recaticimab 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg Q12W, or matching placebo injections (Q4W, Q8W, or Q12W) for 48 weeks. The primary efficacy endpoint was percentage change from baseline to week 24 in LDL-C level. A total of 689 randomly assigned patients received treatment (mean age, 55.8 years; male, 64.4%; ASCVD history, 69.5%; concomitant ezetimibe, 11.2%; mean baseline LDL-C, 2.8 mmol/L). Percentage change in LDL-C from baseline to week 24 was significantly more pronounced with recaticimab vs placebo (P < 0.0001), with least-squares mean differences of −62.2% (95% CI: −67.0% to −57.4%), −59.7% (95% CI: −65.0% to −54.4%), and −53.4% (95% CI: −58.7% to −48.2%) for the 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W regimens, respectively. The decreases in LDL-C with recaticimab were maintained through week 48. Secondary lipid variables, including non–high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) also favored the recaticimab groups. During the treatment period, the incidence of treatment-related adverse events (28.5% vs 26.6%) and serious treatment-related adverse events (0.4% vs 0.4%) was similarly low in both the recaticimab and placebo groups. Recaticimab as add-on to stable statin therapy significantly decreased LDL-C levels at week 24 and sustained the decreases through week 48, providing a novel therapeutic alternative with a dosing interval of up to every 12 weeks in patients with nonfamilial hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have been used to reduce the level of low-density lipoprotein cholesterol (LDL-C), but require either biweekly or monthly dosing frequency. Recaticimab is a new humanized monoclonal antibody selectively targeting PCSK9, with long-acting characteristic. The purpose of this study was to assess the efficacy and safety of recaticimab monotherapy in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk, and to explore different dosing strategies to provide patients with flexible administration options. This was a randomized, double-blind, placebo-controlled, phase 3 study conducted at 59 sites in China. Patients with fasting LDL-C ≥2.6 to <4.9 mmol/L, fasting triglyceride ≤5.6 mmol/L, and 10-year ASCVD risk score <10% were randomly assigned (2:2:2:1:1:1) to receive subcutaneous injections of recaticimab at 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg every 12 weeks (Q12W), or matching placebo, on background lipid-lowering diet. Primary endpoint was percentage change in LDL-C from baseline to week 12 for 150 mg Q4W and 450 mg Q12W and to week 16 for 300 mg Q8W. A total of 703 patients underwent randomization and received recaticimab (n = 157, 156, and 155 for 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W, respectively) or placebo (n = 78, 79, and 78, respectively). Compared with placebo, recaticimab further reduced LDL-C by 49.6% (95% CI: 44.2%-54.9%) at 150 mg Q4W, 52.8% (95% CI: 48.3%-57.2%) at 300 mg Q8W, and 45.0% (95% CI: 41.0%-49.0%) at 450 mg Q12W (P < 0.0001 for all comparisons). Safety with recaticimab was comparable to placebo. After 12 or 16 weeks of treatment, patients who received recaticimab continued treatment until week 24, whereas those allocated to placebo were switched to recaticimab treatment with the same dosing strategy. Both 24-week recaticimab and 12- or 8-week recaticimab switched from placebo were effective. With 24 weeks of recaticimab treatment, the most common treatment-related adverse event was injection site reaction (n = 23 [4.9%]). Recaticimab monotherapy yielded significant LDL-C reductions and showed comparable safety vs placebo in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate ASCVD risk, even with an infrequent dosing interval up to Q12W. [ABSTRACT FROM AUTHOR]

Background: Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk. Methods: We used data from a nested case–control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects). Results: The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00–5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13–4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93–4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05–1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75–1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol. Conclusion: Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify novel prognostic factors for Morbihan disease (MD) treatment outcomes and evaluate the efficacy of combination therapy in an Asian population, addressing the gaps in current understanding of this rare condition. Methods: We conducted a retrospective analysis of MD patients diagnosed and treated at a tertiary hospital between 2017 and 2023. Patients received combinations of oral medications (tetracycline, isotretinoin, corticosteroids), topical treatments (tacrolimus, ivermectin), and intralesional steroid injections. Treatment response (TR) was defined as complete symptom remission, while partial remission or recurrence was considered a poor response (PR). Clinical, histological, and biochemical parameters were analyzed to identify prognostic factors. Results: The study included 24 patients (18 men; mean age 61.3 years). Ten patients (41.7%) achieved TR, while 14 (58.3%) showed PR. Significant prognostic factors for TR included shorter symptom duration (≤ 3 months, p = 0.016), lower LDL cholesterol levels (≤ 89 mg/dL, p = 0.046), combination treatment with oral and topical medications (p = 0.033 at 6 months), and partial response at 1 month (p = 0.017). GLMM analysis identified the number of visits (p < 0.001), symptom duration (p = 0.020), and dyslipidemia (p = 0.006) as significant prognostic factors. Histologically, perivascular and perifollicular lymphocytic infiltration were the most common findings (83.3%). Notably, 50% of patients were ANA-positive, challenging previous diagnostic criteria. Conclusion: This study identifies novel prognostic factors for favorable outcomes in MD, including early intervention and lipid management. Combination therapy, particularly with tacrolimus ointment, shows promise in improving treatment responses. These findings suggest a potential link between lipid metabolism and MD pathophysiology, opening new avenues for targeted therapies. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate risk factors for new-onset atrial fibrillation (NOAF) post-percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI), aiming to develop a predictive nomogram for NOAF risk. Methods: A retrospective cohort study involving 397 AMI patients who underwent PCI at a tertiary hospital in Anhui, China, from January 2021 to July 2022 was performed. Patients were divided into NOAF (n = 63) and non-NOAF (n = 334) groups based on post-PCI outcomes. Clinical data were extracted from the hospital information system (HIS) and analyzed using univariate and multivariate logistic regression to identify independent risk factors. A nomogram was generated utilizing R software (version 3.6.1), with its performance evaluated through receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and Bootstrap resampling. Results: Independent risk factors for NOAF included age, left atrial diameter (LAD), Gensini score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), alanine transaminase (ALT), low-density lipoprotein cholesterol (LDL-C), left ventricular end-systolic diameter (LVESD), and ventricular rate (P < 0.05). The nomogram's ROC curve demonstrated an area under the curve (AUC) of 0.925 (95% CI: 0.887–0.963), supported by a Bootstrap-verified AUC of 0.924 (95% CI: 0.883–0.954), reflecting strong discriminative capability. The calibration curve indicated a mean absolute error (MAE) of 0.031 and 0.017 prior to and following Bootstrap verification, respectively, signifying robust calibration. The DCA curve illustrated that the nomogram offered optimal clinical net benefit for patients with a threshold probability of NOAF ranging from 0.01 to 0.99. Conclusion: The nomogram developed from independent risk factors for NOAF exhibits significant predictive accuracy and clinical relevance for evaluating the risk of NOAF in AMI patients following PCI, thereby enabling the identification of high-risk individuals for targeted interventions. [ABSTRACT FROM AUTHOR]

Background: The impact of baseline triglyceride-glucose (TyG) index and abnormal low or high-density lipoprotein cholesterol (LDL-C or HDL-C) levels on all-cause and cardiovascular disease (CVD) mortality remains unclear. This study aimed to investigate the relationship between TyG index and LDL-C or HDL-C and all-cause and CVD mortality. Methods: This retrospective cohort study analyzed data from health examinations of 69,068 older adults aged ≥60 in Xinzheng City, Henan Province, China, between January 2013 and January 2023. Cox proportional risk regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the TyG index and LDL-C or HDL-C about all-cause and CVD mortality. Restricted cubic spline was used to assess the dose-response relationship. Results: During 400,094 person-years of follow-up (median follow-up 5.8 years [interquartile range 3.0-9.12]), 13,664 deaths were recorded, of which 7,045 were due to CVD. Compared with participants in the second quartile of the TyG index, participants in the fourth quartile had a 16% increased risk of all-cause mortality (HR: 1.16, 95% CI: 1.12,1.22), and an 8% increased risk of CVD mortality (HR: 1.08, 95% CI: 1.01,1.16). Similar results were observed in LDL-C and HDL-C, with all-cause and CVD mortality risks for participants in the fourth quartile compared with participants in the third quartile for LDL-C of (HR: 1.07, 95% CI: 1.02,1.12) and (HR: 1.09, 95% CI: 1.01,1.17), respectively. The risk of all-cause and CVD mortality in participants in the fourth quartile group compared with those in the second HDL-C quartile group was (HR: 1.10, 95% CI: 1.05,1.16) and (HR: 1.11, 95% CI: 1.04,1.18), respectively. We found that the TyG index was nonlinearly associated with all-cause and CVD mortality (P non-linear <0.05), and LDL-C was nonlinearly associated with all-cause mortality (P non-linear <0.05) but linearly associated with CVD mortality (P non-linear >0.05). HDL-C, on the other hand, was in contrast to LDL-C, which showed a non-linear association with CVD mortality. We did not observe a significant interaction between TyG index and LDL-C or HDL-C (P >0.05). Conclusion: TyG index and LDL-C or HDL-C increased the risk of all-cause and CVD mortality, especially a high TyG index combined with abnormal LDL-C. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). Methods: We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients' blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. Results: The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. Conclusion: TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation. [ABSTRACT FROM AUTHOR]

Objective: Small dense low-density lipoprotein cholesterol (sdLDL-C), as an emerging atherogenic factor of cardiovascular diseases, requires additional tests. We aimed to establish a sdLDL-C equation using standard lipid profile and evaluate its capacity of identifying the residual cardiovascular risk beyond LDL-C and apolipoprotein B (ApoB). Methods: This cross-sectional study included 25 435 participants from Health Management Cohort and 11 628 participants from China Health and Retirement Longitudinal Study (CHARLS) to construct and evaluate the sdLDL-C equation by least-squares regression model. The equation for sdLDL-C depended on low-density lipoprotein cholesterol (LDL-C) and an interaction term between LDL-C and the natural log of triglycerides (TG). Results: The modified equation (sdLDL-C = 0.14*ln(TG)*LDL-C − 0.45*LDL-C + 10.88) was more accurate than the original equation in validation set (slope = 0.783 vs. 0.776, MAD = 5.228 vs. 5.396). Using the 80th percentile (50 mg/dL) as a risk-enhancer rule for sdLDL-C, accuracy of the modified equation was higher than the original equation in validation set (90.47% vs. 89.73%). The estimated sdLDL-C identified an additional proportion of high-risk individuals in BHMC (4.93%) and CHARLS (1.84%). Conclusion: The newly developed equation in our study provided an accurate tool for estimating sdLDL-C level among the Chinese population as a potential cardiovascular risk-enhancer. [ABSTRACT FROM AUTHOR]

Background: Vegan and vegetarian dietary patterns are known to beneficially modulate risk factors for cardiovascular disease; however, the current literature does not differentiate between various plant-based diets. This study aimed to examine the association between various plant-based diets and plasma lipids and glycaemic indices compared to a regular meat-eating diet. Methods: A cross-sectional study of Australian adults (n = 230) aged 30-75yrs habitually consuming the following were recruited: vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian, or regular meat-eater. Multivariable regression analysis was used to adjust for covariates. Results: Compared to regular meat-eaters, vegans had significantly lower total cholesterol (-0.77mmol/L,95% CI -1.15, -0.39, P < 0.001), low-density lipoprotein cholesterol (LDL-C, -0.71mmol/L, 95% CI -1.05, -0.38, P < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C, -0.75mmol/L, 95% CI -1.11, -0.39, P < 0.001), total cholesterol/HDL-C-ratio (-0.49mmol/L, 95% CI -0.87, -0.11, P = 0.012), fasting blood glucose (FBG, -0.29mmol/L, 95% CI -0.53, -0.06, P = 0.014), haemoglobin A1C (-1.85mmol/mol, 95% CI -3.00, -0.71, P = 0.002) and insulin (-1.76mU/L, 95% CI -3.26, -0.26, P = 0.021) concentrations. Semi-vegetarians had significantly lower LDL-C (-0.41mmol/L, 95% CI -0.74, -0.08, P = 0.041) and non-HDL-C (-0.40mmol/L, 95% CI -0.76, -0.05, P = 0.026) and lacto-ovo vegetarians had significantly lower FBG (-0.34mmol/L, 95% CI -0.56, -0.11, P = 0.003) compared to regular meat-eaters. There were no differences in HDL-C and triglycerides between plant-based and regular-meat diets. Conclusions: Plasma lipaemic and glycaemic measures as a collective were more favourable among vegans, whereas among lacto-ovo vegetarians and semi-vegetarians, only some measures were favourable. Trial registration: ACTRN12621000743864. Date 6/11/2021. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression. Methods: This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms. Results: The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically. Conclusions: The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion This study aimed to elucidate the effects of repetitive transcranial magnetic stimulation (rTMS) on weight, body mass index (BMI), and lipid metabolism in patients with treatment‐resistant depression (TRD).This retrospective observational study included patients with TRD who received rTMS treatment at the Jikei University Hospital from September 2018 to August 2021. The patients were diagnosed based on the DSM‐5 and ICD‐10 criteria and treated using the NeuroStar TMS System. For 3–6 weeks, 10‐Hz rTMS was administered to the left dorsolateral prefrontal cortex at 120% motor threshold. The primary outcomes were changes in weight and BMI, whereas the secondary outcomes included changes in total, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL) cholesterol levels, thyroid function indicators, as well as HAMD‐17, HAMD‐24, and Montgomery–Åsberg Depression Rating Scale (MADRS) scores. Statistical analysis was conducted using paired t‐tests and repeated measures ANOVA.Among the 34 patients (20 men and 14 women) included, no significant changes were observed in weight or BMI after rTMS treatment (average weight reduction: −0.50 kg, 95% CI: −0.14 to 0.56, p = 0.24; average BMI reduction: −0.21, 95% CI: −0.10 to 0.61, p = 0.15). However, significant reductions in total, HDL, and LDL cholesterol levels and FT4 were observed. Furthermore, the HAMD‐17, HAMD‐24, and MADRS scores significantly increased post‐treatment.rTMS treatment did not affect weight or BMI in patients with TRD but is believed to improve lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between coal dust exposure and the occurrence of dyslipidemia in coal mine workers, and identify relevant risk factors. Methods: We selected a population who underwent occupational health examinations at Huainan Yangguang Xinkang Hospital from March 2020 to July 2022. Participants were divided into two groups based on the presence or absence of dyslipidemia, and their baseline information was collected, including records of coal dust exposure. We employed single-factor analysis to identify risk factors for dyslipidemia and adjusted for confounding factors in the adjusted models. Additionally, we explored the effects in different populations using stratified analysis, smooth curve fitting, and propensity score matching. Finally, we confirmed the causal relationship between coal dust exposure and dyslipidemia by examining tissue sections and lipid-related indicators in a mouse model of coal dust exposure. Results A total of 5,657 workers were included in the study, among whom 924 individuals had dyslipidemia and 4,743 individuals did not have dyslipidemia. The results of the single-factor analysis revealed that dust exposure, age, BMI, blood pressure, and smoking were statistically significant risk factors for dyslipidemia (p < 0.05). Additionally, the three multivariate models, adjusted for different confounders, consistently showed a significant increase in the risk of dyslipidemia associated with coal dust exposure (Model 1: OR, 1.869; Model 2: OR, 1.863; Model 3: OR, 2.033). After conducting stratified analysis, this positive correlation remained significant. Furthermore, propensity score matching analysis revealed that with increasing years of work, the risk of dyslipidemia gradually increased, reaching 50% at 11 years. In the mouse model of coal dust exposure, significant coal dust deposition was observed in the lungs and livers of the mice, accompanied by elevated levels of total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and low-density lipoprotein cholesterol (LDL-C). Conclusion Exposure to coal dust significantly increases the risk of developing dyslipidemia, and this positive correlation exists in different populations, particularly with increasing years of work, resulting in a higher risk. Keywords: Dust, occupational health, dyslipidemia, risk factors, cross-sectional study. [ABSTRACT FROM AUTHOR]

Background: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians. Objective: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians. Methods: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes. Results: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P < 0.05) and elevated the TB level (P < 0.001). Atorvastatin plasma levels were greater in CYP3A4*1B (T/T) (P < 0.05) and CYP3A5*3 (C/C) (P < 0.001) genotype carriers. Both SNPs significantly affected the pharmacokinetics of atorvastatin compared with those of Egyptian volunteers and various ethnic populations. Conclusions: The CYP3A4*1B and CYP3A5*3 variants were prevalent in the study participants and could impact the effectiveness and safety of atorvastatin therapy. The mutant genotype of the CYP3A4*1B SNP and the CYP3A5*3 SNP led to high atorvastatin levels. Both variants had a notable effect on the pharmacokinetics of atorvastatin among Egyptians compared with healthy Egyptians and volunteers from other ethnic populations. Overall, clinicians can learn more about the impact of both variants in response to atorvastatin. [ABSTRACT FROM AUTHOR]