Changes In Lipid Parameters Research Articles

Evaluation of Malondialdehyde and Lipid Parameters in Testosterone-induced Benign Prostate Hyperplasia in Albino Rats

Benign prostate hyperplasia (BPH) refers to the enlargement of the prostate gland, a condition that is becoming prevalent in men of 40 years and older. This study investigated malondialdehyde and lipid parameters in testosterone-induced benign prostate hyperplasia in albino rats. Forty-two (42) albino rats weighing 180-240 g were acclimatized for two weeks and divided into 6 groups of 7 rats each. The BPH was induced using 4 mg/kg testosterone propionate in groups 2-6, and treatment was as follows; Group 1(Negative control), Group 2 (Positive control; induced with BPH and not treated), Group 3 (induced with BPH and treated with 1000 mg/kg of plantain root extract), group 4 (induced with BPH and treated with 0.45 mg/kg of Avodart), group 5 (induced with BPH and treated with combination of herbal extract and Avodart) and group 6 (prophylactic group; treated with herbal extract then induced with BPH). At the end of the treatment, the rats were sacrificed via cardiac puncture. Blood samples were collected into plain bottles for the assay of prostate specific antigen (PSA), malondialdehyde (MDA), and lipid profile. The results indicate that the PSA and MDA levels in the treated groups were significantly lower than the levels in the positive control group. However, there were no significant differences in the levels of the lipid parameters. The results from this study indicate that lipid abnormalities are not prevalent in the onset or progression of BPH. It is recommended that lipid parameters be assayed in the management of BPH in order to confirm or rule out changes in lipid parameters.

P1161 Effects of janus-kinase inhibitor therapy on lipid parameters in patients with IBD

Abstract Background Janus-kinase (JAK) inhibitors are an oral, small molecule therapy used in the management of a range of inflammatory conditions and are associated with lipid profile changes (1-4). We evaluated whether our centre was following recommended lipid monitoring as well as the proportion and magnitude of lipid abnormalities detected. Methods We retrospectively collected data from all 244 patients with Inflammatory Bowel Disease (IBD) who were commenced on a JAK inhibitor, from November 2018 to January 2024, in our centre. Data was collected from our centre’s pharmacy database and the hospital’s electronic patient record. We assessed whether a baseline lipid profile was measured prior to initiating therapy and whether this was re-checked within 12 weeks of initiating therapy, as per industry recommendations. Changes in lipid parameters following therapy initiation – total cholesterol (TC) and non-HDL cholesterol (non-HDL-C) – were calculated. Where applicable, changes following the transition from a higher loading drug dose to a lower maintenance dose were quantified. Rates of initiation of lipid-lowering pharmacotherapy were also calculated. Results 117, 76 and 51 patients were initiated on tofacitinib, filgotinib and upadacitinib respectively, with 55%, 100% and 100% of patients having had their baseline lipid profile checked prior to commencing therapy. 30%, 86% and 82% of patients had their lipid parameters re-checked within 3 months of starting therapy. The average change in TC (mmol/L) was -0.22, 0.24, and 0.50 for tofacitinib (n=23), filgotinib (n=65) and Upadacitinib (n=42) respectively, and the average change in non-HDL-C (mmol/L) was -0.13, 0.06 and 0.32, respectively (Fig 1). Of the patients with an abnormal lipid profile whilst receiving either tofacitinib or upadacitinib, both of which necessitate a higher induction dosing, the average subsequent decrease in TC (mmol/L) was 0.33 and 0.24 for patients receiving tofacitinib (n=12) and upadacitinib (n=11), respectively, and the average decrease in non-HDL-C was 0.40 and 0.29, respectively (median at 5 months, range 1-18 months following first abnormal lipid profile check on therapy). For filgotinib (n=27), which has stable dosing, the average decrease in TC and non-HDL-C was 0.01 and 0.05, respectively. Statin therapy was commenced in 4/117 (3%), 2/76 (3%) and 4/51 (4%) of patients commenced on tofacitinib, filgotininb and upadacitanib, respectively, with the average reduction in TC (mmol/L) being 3.14, 1.60 and 2.00, respectively. Conclusion Increases in lipid parameters following the initiation of JAK inhibitor therapy in IBD patients appear to be modest, partially reversible on switching to maintenance dosing and responsive to statin therapy.

A Multi-Center, Prospective, Observational Study to Evaluate the Therapeutic Effectiveness and Safety of an Olmesartan/Amlodipine Plus Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Dyslipidemia.

Introduction: This study assessed the therapeutic effectiveness of a single-pill combination (SPC) of olmesartan/amlodipine plus rosuvastatin for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in patients with hypertension and dyslipidemia. Methods: Adult patients with hypertension and dyslipidemia who were decided to be treated with the study drug were eligible. The primary endpoint was the proportion of patients who achieved BP, LDL-C and both BP and LDL-C treatment goals at weeks 24-48. Secondary endpoints were assessed at weeks 24-48 and included changes in BP and LDL-C levels from baseline; the proportion of patients who achieved treatment goals who were initially classified as uncontrolled at baseline; changes and percent changes in lipid parameters; changes in both BP and LDL-C levels among patients who reached treatment goals who were followed for more than 24 weeks; and the overall safety profile. Results: A total of 5476 patients were enrolled, and 4411 patients comprised the effectiveness evaluation set. The proportions of patients who reached the treatment goals for BP, LDL-C levels, and both BP and LDL-C levels were 67.93% [95% confidence interval (CI) 66.52-69.32], 80.19% [95% CI 78.85-81.49], and 58.07% [95% CI 56.43-59.7], respectively. Secondary endpoints showed statistically significant changes. Overall, the treatment was well tolerated. Conclusions: The treatment of patients with hypertension and dyslipidemia with the olmesartan/amlodipine plus rosuvastatin SPC was associated with significant decreases in SBP/DBP and LDL-C levels, and a high proportion of patients achieved the BP and LDL-C treatment goals. The finding of this study is worthwhile in that this study evaluated the effectiveness and safety in a broad patient population representative of those seen in everyday clinical practice.

Characterizing Lipid Changes and Use of Lipid-Lowering Medications in Patients With Alopecia Areata Treated With Baricitinib: Integrated Results From the BRAVE-AA1 and -AA2 Clinical Trials

Introduction. Elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) can occur with baricitinib treatment, consistent with a class effect of JAK inhibitors. In this analysis, we characterized changes in lipid levels and use of lipid-lowering medication among patients with severe alopecia areata (AA) treated with baricitinib through 152-weeks of treatment. Methods. Two integrated datasets from the BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) trials were analyzed: 1. Extended BARI AA includes patients treated with continuous baricitinib 2 mg (N=383) and 4 mg (N=565) from baseline and censored at dose change: 2. ALL BARI AA (N=1303) includes data for patients who received ≥1 dose of baricitinib at any time. Outcomes included abnormal changes in lipid parameters, mean change from baseline in lipids, and concomitant use of lipid-lowering medications. Results. At time of enrollment, 43% of patients had hypercholesterolemia. Incidence rates for categorical increases in total cholesterol (TC; ≥240mg/dL), LDL-C (≥130 mg/dL), and HDL-C (>60 mg/dL) were 11.8, 13.3, and 12.9 per 100 patients-years of exposure, respectively in the ALL BARI AA dataset. In the Extended BARI AA the mean maximal increase in lipids (mg/dL) for baricitinib 4 mg was 20.9 for TC, 12.4 for LDL-C, and 8.5 for HDL-C. Changes occurred early and stabilized by one year for TC and LDL-C and by 12 weeks for HDL-C. 6.1% (n=79) of patients in the ALL BARI AA dataset used lipid-lowering medication at baseline; post-baseline, 3.9% (n=51) discontinued this medication and 4.7% (n=61) initiated lipid lowering medication. No patients discontinued baricitinib treatment due to treatment-emergent adverse events related to hyperlipidemia. Conclusions. Elevations in TC, LDL-C, and HDL-C, but not triglycerides were associated with baricitinib treatment in patients with AA, consistent with a class effect of JAK inhibitors. The relatively low use of lipid-lowering medications at baseline despite the prevalence of hypercholesterolemia may reflect undermanagement of this condition in the population. Notably, the mean maximal magnitude of increase in lipid levels on baricitinib was modest. Initiation of lipid-lowering medication was infrequent, and no patients discontinued due to lipid abnormalities.

Role of Obeticholic Acid, a Farnesoid X Receptor Agonist, in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Background. Obeticholic acid (OCA) has emerged as a promising drug in the management of nonalcoholic fatty liver disease (NAFLD). This meta-analysis aimed to analyse the therapeutic effect of OCA on NAFLD. Methods. Randomized controlled trials (RCTs) involving patients with NAFLD receiving OCA in the intervention arm and placebo in the control arm were searched throughout the electronic databases. The primary outcomes were changes in non-invasive markers of hepatic fibrosis and liver histology. The secondary outcomes included changes in liver enzymes, metabolic parameters from baseline and adverse events (AEs). Results. Four RCTs involving 1,278 subjects met the inclusion criteria. Over 6 weeks to 18 months of clinical use, OCA outperformed placebo in resolving definite nonalcoholic steatohepatitis (odds ratio [OR] 1.60, 95% confidence interval [CI] [1.04-2.48], p=0.03) and improving fibrosis (OR 2.23, 95% CI [1.56-3.20], p<0.0001), hepatocellular ballooning (OR 1.83, 95% CI [1.35-2.47], p<0.0001) and lobular inflammation (OR 1.62, 95% CI [1.13-2.32], p=0.009). OCA did not improve the enhanced liver fibrosis score and steatosis better than placebo, and demonstrated superior efficacy compared with the placebo in reducing serum alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase levels. Although a favourable effect of OCA over placebo was seen in body-weight reduction, the OCA use was associated with adverse changes in lipid parameters. Except for the greater risk of pruritus and constipation, the AE profile was comparable between the OCA and placebo groups. Conclusions. OCA has a favourable efficacy in improving liver histology and liver enzymes. However, the worsening of lipid parameters and other AEs with the OCA use warrants further investigation.

Assessing clinical and metabolic responses related to hyperlipidemia, MASLD and type 2 diabetes: sleeve versus RYGB

ObjectiveBoth Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are effective at inducing weight loss, but more information is needed on their comparative effectiveness at improving clinical/biochemical outcomes related to the presence of hyperlipidemia, metabolic dysfunction–associated steatotic liver disease (MASLD), or type 2 diabetes (T2D) at baseline. Here we aimed to assess this in real-world practice. MethodsThis is a prospective cross-sectional and cohort study of 142 patients who underwent RYGB or LSG as per clinical practice. Clinical/biochemical data were collected at baseline, prior to surgery and 12 months post–bariatric surgery. Liver biopsy was performed during surgery to diagnose MASLD. The main outcome was 12-month changes in lipid parameters, mainly total cholesterol, between types of surgery. Results: A total of107 participants underwent RYGB and 35 underwent LSG. Both groups were similar at baseline except for a higher proportion of males and waist circumference in the LSG group. At 12 months postsurgery, RYGB versus LSG resulted in a significantly lower body mass index, triglycerides, total cholesterol, and low-density lipoprotein. However, alanine aminotransferase was significantly lower in those who underwent LSG. In subgroup analyses RYGB was superior at improving lipid-related parameters in those with hyperlipidemia, whereas LSG was superior at reducing alanine aminotransferase in those with MASLD. ConclusionsRYGB versus LSG leads to greater reductions in body mass index and lipid parameters, especially in those with hyperlipidemia, whereas LSG showed greater improvements in liver enzymes in those with MASLD.

Efficacy and outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia: an updated systematic review and meta-analysis of randomized controlled trials.

Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies by Nissen et al., which boast the largest sample size. Literature search was done on Medline, EMBASE, and Cochrane Library. The primary endpoint was a change in low-density lipoprotein-cholesterol (LDL-C) levels, while secondary endpoints encompassed changes in lipid parameters, clinical endpoints, and safety endpoints. The least-square mean (LSM) percent change was utilized for lipid changes, with statistical significance set at P < 0.05. This analysis included 12 randomized control trials with 22,249 participants. BA exhibited a substantial reduction in LDL-C levels [LSM % change, -24.34; 95% confidence interval (CI), -27.80 to -20.88; P < 0.0001], total cholesterol levels (LSM % change, -16.62; 95% CI, -21.70 to -11.54; P < 0.00001) and high-density lipoprotein-cholesterol (HDL-C) levels (LSM % change, -4.22; 95% CI, -5.51 to -2.92; P < 0.00001) compared to the placebo. BA significantly lowers LDL-C, total cholesterol, HDL-C, non-HDL-C, high sensitivity C reactive protein, and apolipoprotein levels.

Relationships Between Changes in Serum Ketone Body Levels and Metabolic Effects in Patients with Severe Obesity Who Underwent Laparoscopic Sleeve Gastrectomy

BackgroundSerum ketone bodies increase due to dynamic changes in the lipid metabolisms of patients undergoing bariatric surgery. However, there have been few studies on the role of ketone bodies after bariatric surgery. We aimed to clarify the role of and relationship between the changes in serum ketone bodies and weight loss, as well as between those changes and the metabolic effects after laparoscopic sleeve gastrectomy (LSG).MethodsWe recruited 52 patients with severe obesity who underwent LSG. We measured acetoacetic acid (AcAc) and β-hydroxybutyric acid (β-OHB) at the baseline, 1 month, and 6 months after LSG. Subsequently, we compared the changes in the serum ketone bodies with weight-loss effects and various metabolic parameters.ResultsAt 1 month after LSG, β-OHB significantly increased (p = 0.009), then significantly decreased 6 months after LSG (p = 0.002). In addition, β-OHB in patients without Type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH) was notably higher than in patients with T2D at 1 month after LSG (p < 0.001).In the early phase, both AcAc and β-OHB mainly had strong positive correlations with changes in T2D- and MASH-related parameters. In the middle term after LSG, changes in both AcAc and β-OHB were positively correlated with changes in lipid parameters and chronic kidney disease-related parameters.ConclusionWe demonstrated that the postoperative surge of ketone bodies plays a crucial function in controlling metabolic effects after LSG. These findings suggest the cause- and consequence-related roles of ketone bodies in the metabolic benefits of bariatric surgery.Graphical

A46 METABOLIC OUTCOMES 12-MONTHS POST-BARIATRIC SURGERY: SLEEVE VERSUS ROUX-EN-Y GASTRIC BYPASS

Abstract Background Obesity and its related comorbidities, such as type 2 diabetes (T2D), hyperlipidemia, cardiovascular disease (CVD), and non-alcoholic fatty liver disease (NAFLD) are on the rise. When lifestyle modifications, such as diet and exercise, are ineffective at producing sustained weight loss and improvements in obesity-related comorbidities, other interventions may be recommended. Bariatric surgery is considered in those who have a body mass index (BMI) over 40 kg/m2 or with comorbid conditions and a BMI between 35-40 kg/m2. Two commonly used procedures within this category of surgery are Roux-en-Y gastric bypass (RYGB), the gold standard for weight loss; and laparoscopic sleeve gastrectomy (LSG). Though both surgeries are effective at inducing weight loss, more information is needed on their comparative effectiveness in improving clinical and biochemical outcomes in patients with T2D, hyperlipidemia, and NAFLD in real-world practice. Aims Therefore, our objective was to determine the overall effectiveness of RYGB versus LSG at 12-months post-surgery and specifically assess their responses in those with hyperlipidemia, T2D and NAFLD. We chose to analyze both glucose and lipid parameters along with anthropometric measures as they not only provide insight into improvements in comorbid outcomes of obesity but also little-to-no prospective studies compare all of these outcomes in one study using the same cohort. Methods This is a prospective cross-sectional and cohort study of 142 patients who underwent bariatric surgery. Clinical and biochemical data were collected at baseline, prior to surgery and 12-months post-bariatric surgery. A liver biopsy was collected during surgery to diagnose NAFLD. The main outcome was 12-month changes in lipid parameters, mainly total cholesterol, between types of surgery. Results 107 individuals underwent RYGB (75.4%) and 35 underwent LSG (24.6%). Both groups were similar at baseline except for the higher waist circumference and proportion of males undergoing LSG. At 12-months post-surgery, RYGB versus LSG resulted in a significantly lower BMI (pampersand:003C0.0001), triglycerides (pampersand:003C0.05), total and LDL cholesterol (pampersand:003C0.005). Interestingly, ALT was significantly lower in those who underwent LSG (pampersand:003C0.005). In subgroup analysis for determining the effect of the type of surgery in those with comorbidities of obesity, RYGB was superior at improving lipid-related parameters in those with hyperlipidemia with a significant decrease in total cholesterol -0.48 (-0.84, 0.34) (pampersand:003C0.05) whereas LSG was superior at reducing ALT in those with NAFLD with significant decreases in total cholesterol and LDL. Conclusions RYGB leads to greater reductions in BMI and lipid parameters, especially in those with hyperlipidemia, whereas LSG showed greater improvements in liver enzymes in those with NAFLD. Funding Agencies CIHR

Comparison of metabolic parameters between oral and total parenteral nutrition in children with severe eating disorders.

This study investigated changes of lipid parameters in children with severe eating disorders during refeeding in order to explore the optimal timing for lipid preparation administration. We prospectively assessed the physical conditions of patients with eating disorders after the start of nutrition therapy. The assessments were performed at admission and at 2 and 4 weeks. Lipid metabolism was assessed based on triglyceride (TG), total cholesterol (TC), and free carnitine (FC) levels, as well as acylcarnitine/free carnitine (AC/FC) ratio. A total of 18 patients were included. Of these, 12 and 6 received an oral diet (OD group) and total parenteral nutrition (TPN group), respectively. The mean body mass indexes at hospital admission were 12.8 kg/m2 in the OD group and 12.7 kg/m2 in the TPN group. At 2 weeks after the start of refeeding, TC, TG, and AC/FC levels were significantly lower in the TPN group than in the OD group. Other blood test results did not show any significant differences between the two groups. Fat-free glucose-based nutrition promoted lipid metabolism over a 2-week period after the start of refeeding, suggesting that balanced energy and lipid intake are essential, even in TPN.

Comparison of metabolic parameters between oral and total parenteral nutrition in children with severe eating disorders

This study investigated changes of lipid parameters in children with severe eating disorders during refeeding in order to explore the optimal timing for lipid preparation administration. We prospectively assessed the physical conditions of patients with eating disorders after the start of nutrition therapy. The assessments were performed at admission and at 2 and 4 weeks. Lipid metabolism was assessed based on triglyceride (TG), total cholesterol (TC), and free carnitine (FC) levels, as well as acylcarnitine/free carnitine (AC/FC) ratio. A total of 18 patients were included. Of these, 12 and 6 received an oral diet (OD group) and total parenteral nutrition (TPN group), respectively. The mean body mass indexes at hospital admission were 12.8 kg/m2 in the OD group and 12.7 kg/m2 in the TPN group. At 2 weeks after the start of refeeding, TC, TG, and AC/FC levels were significantly lower in the TPN group than in the OD group. Other blood test results did not show any significant differences between the two groups. Fat-free glucose-based nutrition promoted lipid metabolism over a 2-week period after the start of refeeding, suggesting that balanced energy and lipid intake are essential, even in TPN.

Epigenetic Aspects of a New Probiotic Concept-A Pilot Study.

Several studies report the important role of an altered gut microbiota in the development of obesity, highlighting the potential use of probiotics in the treatment of obesity. The aim of this study is to investigate the effect of a novel probiotic approach on the expression of specific miRNAs and mRNAs associated with obesity in combination with the hypocholesterolemic octacosanol. Twenty overweight/obese women participated in a randomized, placebo-controlled, double-blind study and were randomly divided into two groups: the intervention group (daily one capsule containing Lactobacillus plantarum 299v (DSM9843), Saccharomyces cerevisiae var. boulardii, and 40 mg octacosanol; N = 12) and the placebo group (N = 8). Changes in lipid parameters and expression of miRNAs and mRNAs were assessed before (T0) and after the 12-week intervention (T1). After the intervention, the expression of miR-155-5p (9.38 ± 0.85 vs. 8.38 ± 1.06, p = 0.05) and miR-24-3p (3.42 ± 0.38 vs. 2.71 ± 0.97, p = 0.031) showed significant decreases in the intervention group when compared to the control group. At T1, the expression of miR-155-5p (8.69 ± 1.31 vs. 9.3 ± 0.85, p = 0.04), miR-125b-5p (5.41 ± 1.18 vs. 5.99 ± 1.36, p = 0.049), and TNF-α (10.24 ± 1.66 vs. 11.36 ± 1.12, p = 0.009) were significantly decreased in the intervention group. No changes in lipids and anthropometric parameters were observed. The novel probiotic approach had a positive effect on regulating the expression of certain miRNAs and mRNAs important for regulating inflammation and adipogenesis, which are essential for obesity onset and control.

No association between changes in lipid parameters and total PCSK9 in coronary artery disease patients treated with PCSK9 inhibitors

No association between changes in lipid parameters and total PCSK9 in coronary artery disease patients treated with PCSK9 inhibitors

Impaired brain equanimity and neurogenesis in the diet-induced overweight mouse: a preventive role by syringic acid treatment

ABSTRACT Objectives In this study mice were fed a high-fat diet for 12 weeks to establish diet-induced obesity and syringic acid (SA) was assessed for anti-obese, neuroprotective, and neurogenesis. Method Animals were given HFD for 12 weeks to measure metabolic characteristics and then put through the Barns-maze and T-maze tests to measure memory. Additionally, the physiology of the blood–brain barrier, oxidative stress parameters, the expression of inflammatory genes, neurogenesis, and histopathology was evaluated in the brain. Result DIO raised body weight, BMI, and other metabolic parameters after 12 weeks of overfeeding. A reduced spontaneous alternation in behavior (working memory, reference memory, and total time to complete a task), decreased enzymatic and non-enzymatic antioxidants, oxidative biomarkers, increased neurogenesis, and impaired blood–brain barrier were all seen in DIO mice. SA (50 mg/kg) treatment of DIO mice (4 weeks after 8 weeks of HFD feeding) reduced diet-induced changes in lipid parameters associated with obesity, hepatological parameters, memory, blood–brain barrier, oxidative stress, neuroinflammation, and neurogenesis. SA also reduced the impact of malondialdehyde and enhanced the effects of antioxidants such as glutathione, superoxide dismutase (SOD), and total thiol (MDA). Syringic acid improved neurogenesis, cognition, and the blood–brain barrier while reducing neurodegeneration in the hippocampal area. Discussion According to the results of the study, syringic acid therapy prevented neurodegeneration, oxidative stress, DIO, and memory loss. Syringic acid administration may be a useful treatment for obesity, memory loss, and neurogenesis, but more research and clinical testing is needed.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: evaluation of lipid parameters in the phase 3 POETYK PSO-1 and PSO-2 trials

Introduction: Tyrosine kinase 2 (TYK2), an intracellular kinase, mediates signaling of cytokines (IL-23 and Type I interferons) involved in psoriasis pathogenesis. Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in the phase 3 POETYK PSO-1 and PSO-2 trials. We evaluated changes in lipid parameters in these trials.&#x0D; Methods: PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were 52-week, double-blind trials conducted globally. Patients with moderate to severe plaque psoriasis (PASI ≥12, sPGA ≥3, BSA involvement ≥10%) were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. This analysis evaluated serum lipids in patients taking placebo, deucravacitinib, or apremilast during Weeks 0-16 and those taking deucravacitinib continuously during Weeks 0-52 in PSO-1 and PSO-2. Mean changes in total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels are reported, as are shifts from baseline in CTCAE v5 severity grade of hypercholesterolemia and hypertriglyceridemia.&#x0D; Results: 666 and 1020 patients were randomized in PSO-1 and PSO-2, respectively. Mean baseline levels of total cholesterol, HDL cholesterol, and LDL cholesterol were comparable between treatment groups. Mean changes from baseline to Week 16 were small; none was clinically meaningful. Worsening of hypercholesterolemia grade from baseline was observed with similar frequencies among patients receiving placebo, deucravacitinib, and apremilast (10.6%, 11.7%, and 8.4%, respectively); nearly all shifts were 1 grade, and there was no grade ≥3 event. Baseline triglyceride levels were near the upper limit of normal (150 mg/dL) across treatment groups. A 10.3 mg/dL increase in mean triglycerides from baseline to Week 16 was observed with deucravacitinib, but worsening in hypertriglyceridemia &gt;1 grade from baseline was rare (1.2%) and comparable to placebo (1.4%). Most deucravacitinib-treated patients maintained the same or shifted to a lower grade of hypertriglyceridemia from baseline to Week 16. Among patients treated with deucravacitinib continuously for 52 weeks, mean changes in total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were small. Shifts in &gt;1 grade from baseline for hypercholesterolemia and hypertriglyceridemia were uncommon (0.2% and 1.9%, respectively). No patient discontinued deucravacitinib due to a lipid-related adverse event.&#x0D; Conclusion: There were no meaningful changes in total cholesterol, HDL cholesterol, and LDL cholesterol levels with deucravacitinib treatment. Minimal increases in mean triglyceride levels from baseline to Weeks 16 and 52 were accompanied by very few worsening shifts &gt;1 grade.

Trajectories of lipids around the menopause transition in Chinese women: results of the Kailuan cohort study

To investigate changes in lipid parameters around the final menstrual period (FMP) in Chinese women. A prospective community-based cohort study. Three thousand seven hundred fifty six Chinese women from the Kailuan cohort study who participated in the first examination and reached their FMP by the end of the seventh examination. Health examinations were performed every 2 years. Multivariable piece-wise linear mixed-effect models were used for repeated measures of lipids as a function of time around FMP. Number of years before or after FMP at each examination. Lipids at each examination, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Total cholesterol, LDL-C, and TGs began to increase in early transition, regardless of baseline age. Moreover, TC and LDL-C had a maximum annual increase from 1 year before to 2 years after FMP; TGs had a maximum annual increase from early transition to the fourth-year after menopause. The trajectories in other postmenopause segments differed across subgroups of different baseline ages. Furthermore, HDL-C remained stable around FMP if baseline age was <45 years, whereas if baseline age was ≥45 years, HDL-C would first decline and then rise during postmenopause. Women with a higher body mass index (BMI) underwent less adverse changes in TC and TGs during postmenopause and had decline in HDL-C before menopause. A later FMP age was associated with less adverse changes in TC, LDL-C, and TGs and greater increase in HDL-C during postmenopause; it was associated with a greater increase in LDL-C during early transition. This repeated measurement cohort study of indigenous Chinese women demonstrated that, regardless of baseline age, the adverse effect of menopause on lipids was since early transition, and the most adverse change time was from 1 year before to 2 years after FMP; HDL-C decreased first and then increased during postmenopause in older women; BMI and FMP age affected lipid trajectory mainly during postmenopause. We highlighted positive lipid management during menopause to reduce the burden of postmenopausal dyslipidemia. For lipid stratification management in postmenopausal women, BMI and FMP age are important factors.

PS-C05-4: EFFECT OF EVOLOCUMAB ON CAROTID MAXIMUM INTIMA-MEDIA THICKNESS IN PATIENTS UNDERGOING STATIN THERAPY

Background: This study investigated the effect of evolocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, on carotid maximum intima media thickness (IMT), an established surrogate marker of atherosclerosis, in patients taking statins with and without renal impairment (estimated glomerular filtration rate (eGFR) &lt; 60 ml/min/1.73 m2). Methods: The annual change in carotid maximum IMT before and after administration of evolocumab was retrospectively analyzed in 229 statin treated patients (148 men and 81 women; mean age: 72.6 ± 8.6 years). The annual change in carotid maximum IMT was compared between patients with and without renal impairment (n = 73; mean eGFR 48.8 ± 8.3 ml/min/1.73 m2 vs. n = 156; mean eGFR 77.1 ± 11.9 ml/min/1.73 m2). The changes in lipid parameters were also evaluated. Results: Evolocumab significantly reduced the progression rate of carotid maximum IMT in whole patients (0.17 ± 0.38 mm/year to 0.08 ± 0.47 mm/year, p &lt; 0.005). Evolocumab significantly reduced the progression rate of carotid maximum IMT in patients without renal impairment (0.18 ± 0.39 mm/year to 0.08 ± 0.46 mm/year, p &lt; 0.05) but did not in patients with renal impairment (0.15 ± 0.36 mm/year to 0.06 ± 0.50 mm/year, p = 0.12). However, it significantly reduced total cholesterol, low density lipoprotein cholesterol, triglyceride, and lipoprotein (a), and increased high density lipoprotein cholesterol in both patients with and without renal impairment. Conclusion: Evolocumab attenuated the progression of carotid maximum IMT in patients undergoing statin therapy without renal impairment but not in patients with renal impairment. However, it improved lipid parameters in both patients with and without renal impairment. These results suggest that evolocumab protects against carotid atherosclerosis in only patients undergoing statin therapy without renal impairment.

Management of Familial Hypercholesterolemia with Special Emphasis on Evinacumab.

Familial hypercholesterolemia (FH) is an underdiagnosed disease that contributes to a significant number of cardiovascular incidents through high serum Low-Density Lipoprotein Cholesterol (LDL-C) values. Its treatment primarily requires healthy lifestyle and therapy based on statins, ezetimibe and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); however, there are also new treatment options that can be used in patients who do not respond to therapy, among which we highlight evinacumab. Elevated LDL-C values, together with clinical manifestations associated with cholesterol deposition (e.g., tendon xanthomas, xanthelasma and arcus cornealis) and family history are the main elements in the diagnosis of FH. Pathognomonic signs of FH include extensor tendon xanthomas; however, their absence does not exclude the diagnosis. Elevated LDL-C levels lead to premature Atherosclerotic Cardiovascular Disease (ASCVD), which is why early diagnosis and treatment of FH is essential. Evinacumab, a novelty in pharmacological practice, having a complex mechanism of action, causes desirable changes in lipid parameters in patients with homozygous form of familial hypercholesterolemia (HoFH). This review collects and summarizes the most important aspects of the new drug, especially being a discovery in the treatment of HoFH, giving these patients hope for a longer and more comfortable life.

Olanzapine-induced lipid disturbances: A potential mechanism through the gut microbiota-brain axis.

Objective: Long-term use of olanzapine can induce various side effects such as lipid metabolic disorders, but the mechanism remains to be elucidated. The gut microbiota-brain axis plays an important role in lipid metabolism, and may be related to the metabolic side effects of olanzapine. Therefore, we explored the mechanism by which olanzapine-induced lipid disturbances through the gut microbiota-brain axis. Methods: Sprague Dawley rats were randomly divided into two groups, which underwent subphrenic vagotomy and sham surgery. Then the two groups were further randomly divided into two subgroups, one was administered olanzapine (10 mg/kg/day) by intragastric administration, and the other was administered normal saline by intragastric administration (4 ml/kg/day) for 2 weeks. The final changes in lipid parameters, gut microbes and their metabolites, and orexin-related neuropeptides in the hypothalamus were investigated among the different groups. Results: Olanzapine induced lipid disturbances as indicated by increased weight gain, elevated ratio of white adipose tissue to brown adipose tissue, as well as increased triglyceride and total cholesterol. Olanzapine also increased the Firmicutes/Bacteroides (F/B) ratio in the gut, which was even aggravated by subphrenic vagotomy. In addition, olanzapine reduced the abundance of short-chain fatty acids (SCFAs) metabolism related microbiome and 5-hydroxytryptamine (5-HT) levels in the rat cecum, and increased the gene and protein expression of the appetite-related neuropeptide Y/agouti-related peptide (NPY/AgRP) in the hypothalamus. Conclusion: The abnormal lipid metabolism caused by olanzapine may be closely related to the vagus nerve-mediated gut microbiota-brain axis.

Decreased low-density lipoprotein and the presence of pulmonary arterial hypertension among newly diagnosed drug-naïve patients with systemic lupus erythematosus: D-dimer as a mediator.

Pulmonary arterial hypertension (PAH) is commonly associated with systemic lupus erythematosus (SLE). The present study investigated the relationship between coagulation and changes in lipid parameters in newly-diagnosed patients with SLE in the presence of PAH and whether the coagulation parameters were mediators between lipids and PAH presence. A total of 301 subjects scheduled for new-onset drug-naïve SLE were consecutively enrolled. Baseline data for patients without PAH and with PAH were gathered and compared. Coagulation and lipid parameters were compared across patients without lipid regulating and anticoagulation medications. Multivariable logistic regression model was applied to examine potential predictors of PAH in SLE. The relationships between them were examined using Spearman's correlation analysis. The relationship between coagulation index and lipids with SLE-PAH was evaluated using mediation analysis. Female patients accounted for 88.0% of the 301 subjects, and the average age was 32 years (range, 25-45 years). A total of 40 patients (13.3%) had PAH, and the average pulmonary artery systolic pressure (sPAP) was 55.825±26.67 mmHg. Patients with PAH were older and had higher levels of fibrin/fibrinogen degradation products (FDP), D-dimer, C-reactive protein, lower levels of complement 3, complement 4 and 25-hydroxy vitamin D3 compared with the non-PAH group. Multivariable logistic regression analysis showed that age and D-dimer were independent predictor factors for PAH. Among patients without lipid regulating and anticoagulation medications, patients in the PAH group had higher levels of D-dimer and FDP, and lower low-density lipoprotein (LDL) levels compared with patients without PAH. There was also a positive relationship between sPAP and D-dimer and FDP, and a negative relationship between sPAP and total cholesterol and LDL. Mediation analysis indicated that 25.61% of the effect of low LDL on PAH presence in systemic lupus erythematosus was mediated by D-dimer. Overall, the effect of low LDL on SLE-PAH appeared to be mediated by D-dimer, which mediated 25.61% of this effect.