LDL Reduction Research Articles

Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to Treat Diabetes, Alzheimer's, Cancer and Cardiovascular Disease.

Berberine is a natural product with a wide range of pharmacological effects. It has antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterollowering properties, among others. It has been used in traditional Chinese and Ayurvedic medicine for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral bioavailability, which has hindered widespread clinical use. However, recent interest has surged with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer's disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion by pancreatic β-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory cytokines such as IL-6, IL-1β, TLR4 and TNF-α. These cytokines are elevated in Alzheimer's disease, cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated with positive outcomes such as improved cognition, reduced cardiovascular events, and improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine derivatives are currently being developed that optimize LDL reduction, bioavailability, and other pharmacokinetic properties.

Viro-Immunological Efficacy and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide among Women Living with HIV: A 96-Week Post-Switch Analysis from the Real-Life SHiNe-SHiC Cohort.

Background/Objectives: Out of 39.9 million adults living with HIV in 2022, 20 million were women. Despite bearing a significant burden, women remain underrepresented in clinical trials, including those for antiretroviral treatments (ART). This study evaluates the safety and efficacy of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimen in a real-life cohort of 99 women with HIV (females with HIV, FWH) over 48 and 96 weeks. Methods: A retrospective cohort study utilized data from the Sardinian HIV Network and Sicilian HIV Cohort (SHiNe-SHiC) research group. The study included FWH, who started B/F/TAF as a treatment switch. The primary objectives were achieving and maintaining an HIV RNA level of <50 copies/mL at 48 and 96 weeks. Secondary objectives included treatment safety, durability, and reasons for discontinuation. Data on demographics, viro-immunological markers, lipid profiles, and treatment interruptions were extracted for analysis. Results: Among the 99 FWH, the median age was 51.9 years, and the median duration of HIV was 15.1 years. At baseline, 80.8% had undetectable HIV-RNA, which increased to 93.8% at 96 weeks. There was a statistically significant increase in CD4 cells/mL (48w p < 0.001, 96w p < 0.001) and CD4/CD8 ratio (48w p < 0.009, 96w p < 0.048), and reductions in total cholesterol (48w p < 0.003, 96w p < 0.006) and LDL (48w p < 0.004, 96w p < 0.009) levels at 48 and 96 weeks. Nine treatment interruptions were noted, with one due to adverse events. The regimen was well-tolerated overall. Conclusions: B/F/TAF demonstrated high efficacy and safety in this real-world cohort of FWH, highlighting the critical need for gender-focused research in HIV treatment. Ensuring equitable access to effective treatment options for women is imperative for the global health community's efforts to eliminate HIV.

Randomized study of the effects of empagliflozin and topiramate dual therapy on anthropometric and metabolic indices in non-diabetic individuals with overweight/obesity on a calorie-restricted diet

ObjectivesThe objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet.MethodsIn this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured.ResultsThe EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (− 8.92 ± 1.80 vs. − 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05).ConclusionIn non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run.Level I Randomized clinical trial.

Emerging Lipid-Lowering Therapies: A Comprehensive Review of Novel Agents Targeting Hyperlipidemia

Background: Hyperlipidemia is a major risk factor for cardiovascular diseases, often necessitating long-term pharmacological intervention to manage cholesterol and triglyceride levels. Traditional treatments, such as statins and niacin, have been effective but are often associated with adverse effects and limited efficacy in certain populations. The development of novel lipid-lowering therapies, targeting specific mechanisms of lipid metabolism, offers new potential for personalized treatment approaches. Methods: This review examines a range of emerging pharmacological therapies for hyperlipidemia, including PCSK9 inhibitors, CETP inhibitors, ACL inhibitors, MTP inhibitors, APOC3 inhibitors, ANGPTL inhibitors, and antisense oligonucleotides (ASOs). Each class of drugs was evaluated for its mechanism of action, efficacy in clinical trials, and associated side effects. Relevant clinical studies were analyzed to compare their efficacy in reducing LDL cholesterol, raising HDL cholesterol, and improving overall cardiovascular outcomes. Results and Discussion: PCSK9 inhibitors (Alirocumab and Evolocumab) demonstrated a significant 60% reduction in LDL cholesterol levels and improved cardiovascular outcomes when combined with statins. CETP inhibitors, such as Dalcetrapib, increased HDL cholesterol by 31% without affecting LDL cholesterol levels, while Bempedoic acid, an ACL inhibitor, proved effective in lowering cholesterol and glucose levels, especially in statin-intolerant patients. APOC3 inhibitors (Volanesorsen, Olezarsen) successfully reduced triglyceride levels by inhibiting lipoprotein lipase activity. ASO drugs (Mipomersen, Inclisiran) provided gene-targeted therapy for primary hypercholesterolemia, offering a novel therapeutic avenue. ANGPTL inhibitors impacted triglyceride metabolism, and icosapent ethyl significantly reduced cardiovascular risk in statin-treated individuals. These novel therapies have demonstrated significant reductions in LDL and triglyceride levels while improving HDL cholesterol and reducing cardiovascular risks.

Evaluation of probiotic efficacy of indigenous yeast strain, Saccharomyces cerevisiae Y-89 isolated from a traditional fermented beverage of West Bengal, India having protective effect against DSS-induced colitis in experimental mice.

Increasing awareness regarding health promotion and disease prevention has driven inclusion of fermented foods and beverages in the daily diet. These are the enormous sources of beneficial microbes, probiotics. This study aims to isolate yeast strains having probiotic potential and effectivity against colitis. Initially, ninety-two yeast strains were isolated from Haria, an ethnic fermented beverage of West Bengal, India. Primary screening was done by their acid (pH 4) and bile salt (0.3%) tolerance ability. Four potent isolates were selected and found effective against Entamoeba histolytica, as this human pathogen is responsible to cause colitis. They were identified as Saccharomyces cerevisiae. They showed luxurious growth even at 37 oC, tolerance up to 5% of NaCl, resistance to gastric juice and high bile salt (2.0%) and oro-gastrointestinal transit tolerance. They exhibited good auto-aggregation and co-aggregation ability and strong hydrophobicity. Finally, heat map and principal component analysis revealed that strain Y-89 was the best candidate. It was further characterised and found to have significant protective effects against DSS-induced colitis in experimental mice model. It includes improvement in colon length, body weight and organ indices; reduction in disease activity index; reduction in cholesterol, LDL, SGPT, SGOT, urea and creatinine levels; improvement in HDL, ALP, total protein and albumin levels; decrease in coliform count and restoration of tissue damage. This study demonstrates that the S. cerevisiae strain Y-89 possesses remarkable probiotic traits and can be used as a potential bio-therapeutic candidate for the prevention of colitis.

Abdominal aorta intima-media thickness in children with hypothyroidism

Hypothyroidism is associated with atherosclerosis, which is attributed mainly to an atherogenic lipid profile. Increased intima-media thickness (IMT) is the first structural change detected in atherosclerosis. This prospective cohort study investigated lipid profile and abdominal aorta IMT in patients newly-diagnosed with hypothyroidism and their change one year post-treatment. It included fifty patients divided into three groups according to their diagnosis: congenital hypothyroidism (CH), Acquired and CH stopped treatment/uncontrolled group. They were subjected to history, auxological, blood pressure, non-fasting lipid profile, and abdominal aorta IMT measurement by abdominal ultrasound. These demonstrated high basal cholesterol, triglycerides, and LDL (259.64 ± 82.06, 193.94 ± 71.54, and 144.70 ± 48.46 mg/dl, respectively) and significant reduction after treatment (216.66 ± 44.60, 165.70 ± 53.58 and 123.26 ± 29.79 mg/dl, respectively). Low basal HDL (47.92 ± 10.08 mg/dl) increased significantly (57.56 ± 7.94 mg/dl) after treatment. Abdominal aorta IMT decreased significantly after treatment and achievement of euthyroidism (1.47 ± 0.49 and 1.33 ± 0.41 mm, respectively). In conclusion, upon treatment of hypothyroidism and achievement of euthyroidism, abdominal aorta IMT, cholesterol, triglycerides, and LDL decreased significantly, and HDL increased. Abdominal aorta IMT measurement is an easy and feasible way for the early detection of atherosclerosis.

Bay Leaf Extract as a Potential Therapeutic Agent for LDL Reduction in Hypercholesterolemia: A Dose-Response Study

Bay Leaf Extract as a Potential Therapeutic Agent for LDL Reduction in Hypercholesterolemia: A Dose-Response Study

Efektivitas Penggunaan Obat Dislipidemia terhadap Kadar LDL pada Pasien Cardiovaskular Penyebab Stroke

Dyslipidemia is one of the main risk factors for cardiovascular disease, and cholesterol management therapy has significant benefits in the primary and secondary prevention of coronary heart disease and stroke. Therefore, lipid-lowering therapy, especially using HMG-CoA reductase inhibitors (statins), aims to assess the effectiveness of using statin-class dyslipidemia medications, such as simvastatin and atorvastatin, in reducing LDL levels in cardiovascular patients at X Hospital. This research method uses an observational analytic study with a retrospective research design. This study employs the purposive sampling method. The results of this study show that the majority of patients are female (75%). Based on age grouping, it was found that the highest proportion of patients were aged 56-65 years, accounting for 45%. The use of dyslipidemia drugs that achieved the target LDL reduction ≥ 50% includes Simvastatin 10 mg (33.82%), Simvastatin 20 mg (11.94%), Atorvastatin 10 mg (10.45%), and Atorvastatin 20 mg (41.79%). The most effective drug in achieving the LDL reduction target was Atorvastatin 20 mg.

Physicochemical, microbiological, and sensory properties of healthy juices containing aloe vera gel and probiotics and their antidiabetic effects on albino rats.

The consumption of fruit and vegetable juices is widely recognized as a healthy choice across all age groups. Orange, carrot, and aloe vera are renowned for their functional properties and health benefits. In this study, we investigated the potential incorporation of aloe vera gel into blended orange and carrot juices. We also evaluated the resulting mixed probiotic juices (chemical, microbiological, and sensory aspects) during a 14-day storage period at refrigerator temperature. The chemical composition and phytochemical structure of aloe vera gel were examined, followed by an assessment of the biological effects of these healthy juices on diabetic albino rats. The results indicated improvements in total soluble solids, reducing sugars, and total sugars with increasing storage duration. Furthermore, the study demonstrated that incorporating aloe vera into the natural mixed juices enhanced their phytochemical quality. The treatment supplemented with aloe vera gel gave the highest total content of phenolic and flavonoid substances, which were 310 mg of GAE/100 g and 175 mg of quercetin/100 g, respectively. Probiotic strains (Bifidobacterium animalis subsp lactis Bb12, Lactiplantibacillus plantarum 299V, and Lactobacillus acidophilus L10) exhibited good viable cell counts in orange and mixed orange and carrot probiotics juices with viable counts of 7.42-8.07 log CFU/mL. Regarding sensory attributes, the study found that increasing the ratio of orange juice improved the taste while increasing the ratio of carrot juice enhanced the color in juice mixtures. Incorporation of aloe vera into mixed natural juices also enhanced the reduction of blood glucose, triglyceride, cholesterol, LDL, creatinine, ALT, AST, and urea levels while increasing total protein and HDL levels in diabetic rats. Based on these findings, oranges, carrots, and aloe vera offer the potential to produce new, flavorful, nutritious, and appealing juices. Moreover, this study determined that a functional juice with favorable sensory properties can be created by blending 75% orange juice, 20% carrot juice, and 5% aloe vera gel. Additionally, aloe vera demonstrated greater efficacy as an antidiabetic agent in rats. Further research is suggested to explore the potential advantages of aloe vera gel and probiotic juices in mitigating diabetes and other metabolic syndromes.

A Clinical Study to Evaluate the Efficacy of Vyoshadi Sakthu on Elevated Lipid Profile

This single-armed open clinical study explores the efficacy of Vyoshadi Sakthu in managing hyperlipidemia, a condition marked by elevated levels of cholesterol and triglycerides, posing substantial health risks such as cardiovascular diseases and obesity. Administered orally with buttermilk, Vyoshadi Sakthu leverages its Lekhana and Medohara properties to target excess fat accumulation. The study involved 20 participants meeting diagnostic criteria, with lipid profiles assessed at baseline and after a 60th day Vyoshadi Sakthu trial. Statistical analysis, employing the paired t-test, revealed significant reductions in serum cholesterol, LDL, and VLDL levels (p &lt; 0.001) post-intervention. These findings suggest a meaningful impact on lipid metabolism attributed to Vyoshadi Sakthu's Lekhana properties. Additionally, the study highlights potential synergies between Vyoshadi Sakthu treatment and lifestyle modifications, including dietary adjustments and regular exercise. This integrated approach may enhance treatment outcomes, emphasizing holistic management strategies for hyperlipidemia and related metabolic disorders. The results contribute to the growing evidence supporting Ayurvedic interventions' therapeutic efficacy in hyperlipidemia management. However, larger controlled studies are required to validate these findings and ensure the long-term safety and efficacy of Vyoshadi Sakthu. This underscores the importance of integrating traditional knowledge systems like Ayurveda into contemporary healthcare practices to address the complexities of metabolic disorders effectively.

ALTERNATIVE THERAPIES FOR OXIDATIVE STRESS

Free radicals such as reactive oxygen species (ROS) induce oxidative stress and cause cellular damage due to lipid peroxidation. There are three important steps in lipid peroxidation, namely initiation, propagation and termination. Formation of reactive aldehydes such as MDA and 4-HNE takes place when there is a catabolism of lipid hydroperoxides. Hyperlipidemia especially LDL-cholesterol may lead to development of coronary artery disease causing morbidity or mortality due to cardiac arrhythmias. Conventional hypolipidemic drugs have unwanted effects. Herbal therapy for Hyperlipidemia is getting attention due to their less frequent side effects. In this study we have compared hypolipidemic effects of Gemfibrozil with Nigella sativa. Seventy five hyperlipidemic patients from Jinnah Hospital Lahore were enrolled for study. After getting consent all patients were divided in three groups comprising 25 patients in each group. Group 1 was on Nigella sativa, group 2 was on Gemfibrozil and third group was on placebo therapy. They were advised to take drugs for two months. After completion of study pretreatment and post treatment values of LDL cholesterol were analyzed statistically. In Nigella sativa group LDL cholesterol decreased from 191.14±3.45 to 159.40±2.98 mg/dl, means 31.7 mg/dl LDL reduction was observed when compared with placebo group. In Gemfibrozil group of patients LDL cholesterol decreased from 197.77±3.91 mg/dl to 159.62±2.20 mg/dl, means LDL reduction in mean values was 38.2 mg/dl, when compared with placebo group. These changes are highly significant with p-values of &lt;0.001. We concluded from this study that alternative therapy by herbal medication is as effective as by allopathic medication. Key words: serum lipids, oxidative stress, lethality, toxicity.

Electronic medical information and analytical system (EMIAS) as a tool for the new level of understanding and diagnosis of medication adherence in patients with myocardial infarction in primary care practice in Moscow

Introduction. The global community is increasingly using patients' prescription claims data as a dominant method for assessing medication adherence, which encouraged us to conduct this study.Aim. To adapt the existing international experience of using digital technologies to measure medication adherence to the routine practice of domestic health care at the outpatient level.Methods. We conducted a retrospective study of adherence to statin therapy in patients with myocardial infarction (MI) at a large primary care clinic in Moscow, which included 2 stages: 1st stage — compilation of international experience on medication adherence studies using pharmacy dispensing records; 2nd stage — testing the method of electronic prescription refill record to measure adherence. We calculated the proportion of days covered (PDC) by statin therapy over a 12‑month period following MI. Data on demography, anamnesis, lipid profile, and statin prescriptions were obtained from the electronic medical records of patients with acute MI from January 1 — December 31, 2022. A total of 109 patients were included according to the prespecified selection criteria.Results. An analysis of international experience demonstrated that the pharmacy dispensing record method has become widespread in recent decades in foreign countries and has established itself as an objective, noninvasive, and inexpensive method for measuring medication adherence. The study of adherence to statin therapy in post-MI patients using the electronic prescription refill record method revealed a mean PDC = 63.0±29.7 %. Optimal adherence (PDC≥80 %) throughout the 12‑month follow-up period was noted in 38 % of patients. When PDC was calculated separately for the 1st and 2nd half year, it was found that the proportion of patients with optimal adherence decreased by 17.6 % (p=0.04). Adherence correlated with the efficacy of statin therapy — a more pronounced reduction of LDL–C was observed in patients with PDC≥80 % compared with those who were insufficiently adherent (–1.47±1.09 vs –0.96±1.16 mmol/L; p=0.043).Conclusion. This study demonstrated the efficiency and information value of an electronic prescription refill record system for domestic primary care. After operational tuning, the proposed method can be integrated into EMIAS for routine medication adherence assessment.

Reduction of postweaning stress by fasting regimen and probiotics supplementation and study its effects on cecal microbiota and physiological parameters of growing rabbits.

The aim of this work was to reduce the postweaning stress of growing rabbits by using fasting regimen and probiotic supplementation. Twenty-four weaned males new Zealand rabbits (5 weeks of age) were randomly divided into four equal groups including (1) rabbits fed ad labium diet served as control, (2) rabbits fasted for 12 h (two days/week) for 8 weeks, (3) rabbits fed ad labium diet with 2.0 cm3 probiotic/litter for 8 weeks, (4) rabbits fasted for 12 h (2 days/week) and take 2.0 cm3 probiotic/litter for 8 weeks. The probiotic inclusion corresponded to Bacillus subtilis and Bacillus licheniformis were supplemented to water in the probiotic groups. Results showed that food consumption was significantly higher (p < 0.01) in growing rabbits of ad libitum group (control group) compared to other in restricted rabbits, but body weight (BW) of growing rabbit in probiotic group at 6 and 12 week of age increased by12 and 19%, respectively, than other in control group and also improved daily weight gain (DWG) during all experimental periods. Compared with control, significant reductions (p < .01) in Plasma cholesterol, triglycerides, HDL, LDL, ALT, AST and urea were found in oral probiotic groups with or without fasting programme. Oral administration of probiotic without fasting regimen significantly improved all carcass characteristics compared to other groups. Total bacteria, fungi, coliforms and cellulolytic bacteria counts were significantly improved in the fasting group with or without adding probiotics compared to control group. Conclusively, using probiotics with or without fasting regimen for 8 weeks postweaning improved growth performance during fattening and enhancement cecum activity of growing rabbits.

Role of Arthrospira Platensis in Preventing and Treating High-Fat Diet-Induced Hypercholesterolemia in Adult Rats.

Hyperlipidaemia is a recognised risk factor for cardiovascular disease. In this study, the antihyperlipidaemic properties of spirulina (Arthrospira platensis, strain S2 from Serbia) were tested in adult Wistar rats before and after induction of hypercholesterolaemia by a high-fat diet (HFD) to compare the preventive with the curative effect. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured in the blood samples. The chemical composition (lipids, proteins and cholesterol) and the content of bile acids in the faeces of the animals were also analysed. Feeding rats with an atherogenic diet for 10 weeks led to the successful development of hyperlipidaemia, as serum TC and LDL-C levels as well as lipids, cholesterol and bile acids in the animals' faeces were significantly increased. Pre- and post-treatment with spirulina led to a reduction in serum LDL, TC and ALT levels. Administration of spirulina resulted in both a significant increase in primary bile acids excretion and a decrease in bile acids metabolism, with pre-treatment being more effective than post-treatment in some cases. These results suggest that increased excretion of bile acids as well as an effect on the gut microbiota may be the mechanism responsible for the anti-hyperlipidaemic activity of the tested spirulina strain.

#1294 The impact of plant-based diet on renal function and metabolic profile in kidney transplant recipients

Abstract Background and Aims Controlling and reducing protein intake is the most used approach to preserve renal function in CKD patients. Compared to protein restriction alone, plant-based diets have received particular attention. However, data on the potential risks and benefits of a plant-based diet in kidney transplant patients remains sparse, and evidence in this population is indirect. The primary purpose of this study was to evaluate if a plant-based diet affects proteinuria and eGFR in renal transplant patients. Establishing whether it influences acid load, glycolipid profile, nutritional status, and performance status were secondary objectives. Method 26 renal transplant recipients with eGFR &amp;gt;20 ml/min/1.73 m², urinary protein excretion &amp;gt;0.5 g/day, and transplant age &amp;gt;1 year were considered eligible for the study. Enrolled subjects underwent dietary assessment and biochemical tests at baseline, three and six months after starting the plant-based diet. All subjects underwent performance tests: sit-to-stand and handgrip tests. Results Only 18 patients were included in the statistical analysis. After six months, no significant changes in levels of proteinuria, urinary anion gap, triglycerides, and grip strength were detected. However, there was a statistically significant reduction in total cholesterol (p=0.03), LDL (p=0.04), and fasting blood sugar levels (p=0.001). A statistically significant reduction in eGFR (p=0.033) was observed, likely the regression of the previous hyperfiltration caused by the animal protein diet. A significant improvement was found in sit-to-stand test performance (p=0.037). Finally, a direct relationship between azoturia and urinary anion gap was observed. Conclusions The work carried out has highlighted how some of the potential benefits of the plant-based diet may also be relevant among kidney transplant patients. The plant-based diet is also associated with improved performance tests.

NON–RESPONSE TO INCLISIRAN THERAPY IN THREE PATIENTS WITH STATIN INTOLERANCE: A CASE SERIES

Abstract Background Inclisiran is the first silencing–RNA therapy used to reduce LDL–C. It is also recommended in patients with statin intolerance. We describe a case series of three no–responder patients to inclisiran. Case Series 64–year–old man with medical history of type II diabetes mellitus, obesity, hypertension, chronic kidney disease (eGFR 38 ml/min/1.73 m^2), dyslipidemia and statin intolerance. In 2022 the coronary angiography showed diffuse atherosclerosis without significant stenosis. His LDL–c was 115 mg/dl. Rosuvatatin 10 mg was prescribed however it was withdrawn due myalgia. Inclisiran and ezetimibe were prescribed, however one, three and four months later his LDL–C was 96 mg/dl, 114 mg/dl, and 115 mg/dl respectively (Fig 1). Due to the lack of effect, lovastatin 20 mg was added after the third dose of inclisiran, reaching LDL–C levels of 100 mg/dl one month after the initiation of lovastatin. Inclisiran was withdraw (as well as statin due to myalgia) and evolocumab 140 mg was administrated three months later the last dose of inclisiran. Ten days after evolocumab, LDL value was 66 mg/dl. 60–year–old man with hypertension, obesity, and dyslipidemia (LDL 152 mg/dl) with a moderate cardiovascular risk (target LDL–C &amp;lt;70 mg/dl). Patient refused statin therapy because he was scared about myalgia. In October 2021 (first Italian patient out of clinical trial) inclisiran was administrated. However, LDL–C did not change one month after the first and the second dose (147 mg/dl and 134 mg/dl respectively, Fig1). Due to the inefficacy, inclisiran was withdraw and the combination rosuvastatin and ezetimibe 10/10 mg was started with a reduction in LDL–cholesterol levels (51 mg/dl) four months later. However, this treatment was withdrawn due to myalgia in favor of bempedoic acid. One month later LDL–C level was 79 mg/dl. 79–year–old woman with history of coronary revascularization. She was statin and ezetimibe–intolerant, so she was treated with alirocumab 150 mg (LDL–C 89 mg/dl). Since the treatment was ineffective to reach the LDL target values, alirocumab was stopped in favor to inclisiran. However, LDL values increased over the time reaching 103 mg/dl one month after the first dose and 120 mg/dl two months later the second dose (Fig1). Conclusion some patients may be no–responder to inclisiran. A polymorphism of the asialoglycoprotein receptors might be a possible reason. Statin intolerance may also affect inclisiran efficacy.

EFFECT OF ANTI–PCSK9 ANTIBODIES ON ARTERY STRUCTURE AND FUNCTION: THE NIGUARDA HOSPITAL COHORT

Abstract Background PCSK9 inhibitors antibodies (PCSK9–i) are a valid option to reduce LDL cholesterol in patients who failed to reach therapeutic target with maximized lipid–lowering therapies or in patient with statins intolerances. These antibodies reduce the frequency of new cardiovascular events, however if this effect is due only to LDL reduction or also to an improvement in arterial function and structure is yet to be proved. Our study aim was to evaluate aortic stiffness (Pulse Wave Velocity – PWV), carotid’s Intima–Media Thickness (IMT) and endothelial function (brachial Flow Mediated Dilatation – FMD) in patients treated with Alirocumab and Evolocumab. Methods This is a monocentric prospective longitudinal study on patients who received PCSK9–i administrations at the Niguarda Hospital’s cardiovascular rehabilitation and prevention unit. They underwent 3 evaluations of PWV, FMD and IMT (T0 the same day of the first injection, T1 after 6 months and T2 after 12 months of therapy). Results 39 patients concluded the 12 months period. The group average age is 66.8 ± 7.6 years, most of them were male (64.1%). LDL cholesterol average levels were significantly reduced by the therapy (128.3 ± 27.7 vs 44.7 ± 29.3 mg/dL, p&amp;lt;0.001), however, there were no significant changes in PWV (10.2 ± 3.0 vs 10.6 ± 2.5 m/s, p=0.404), FMD (8.6 ± 7.0 vs 8.9 ± 7.4 %, p=0.560) and IMT (768.7 ± 175.4 vs 733.5 ± 147.2 µm, p=0.270) values. Conclusions It was not possible to prove a significant effect of PCSK9–i on vascular properties, however, the stability of these indexes may suggest a deceleration of the atherosclerotic disease which it could have worsen in this population, especially considering the risk factors of our patients.

The Impact of Metabolic and Bariatric Surgery on Apo B100 Levels in Individuals with high BMI: A Multi-Centric Prospective Cohort Study.

Metabolic and Bariatric surgery (MBS) leads to significant weight loss and improvements in obesity-related comorbidities. However, the impact of MBS on Apolipoprotein B100 (Apo-B100) regulation is unclear. Apo-B100 is essential for the assembly and secretion of serum lipoprotein particles. Elevated levels of these factors can accelerate the development of atherosclerotic plaques in blood vessels. This study aimed to evaluate changes in Apo-B100 levels following MBS. 121 participants from the Iranian National Obesity and Metabolic Surgery Database (INOSD) underwent Laparoscopic Sleeve Gastrectomy (LSG) (n = 43), One-Anastomosis Gastric Bypass (OAGB) (n = 70) or Roux-en-Y Gastric Bypass (RYGB) (n = 8). Serum Apo-B100, lipid profiles, liver enzymes, and fasting glucose were measured preoperatively and six months postoperatively. Apo-B100 levels significantly decreased from 94.63 ± 14.35 mg/dL preoperatively to 62.97 ± 19.97 mg/dL after six months (p < 0.01), alongside reductions in total cholesterol, triglycerides, LDL, VLDL, AST, and ALT (p < 0.05). Greater Apo-B100 reductions occurred in non-diabetics versus people with diabetes (p = 0.012) and strongly correlated with baseline Apo-B100 (r = 0.455, p < 0.01) and LDL levels (r = 0.413, p < 0.01). However, surgery type did not impact Apo-B100 changes in multivariate analysis (p > 0.05). Bariatric surgery leads to a significant reduction in Apo-B100 levels and improvements in lipid profiles and liver enzymes, indicating a positive impact on dyslipidemia and cardiovascular risk in individuals with high BMI.

Inspiratory Muscle Strength Training to Improve Cardiometabolic Health in Patients with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a complex, chronic metabolic disease that is associated with a high prevalence of comorbid conditions. Traditional lifestyle interventions (e.g., diet and exercise) can counter some adverse effects of T2DM; however, participation in these activities is low. High-resistance inspiratory muscle strength training (IMST) is a time-effcient and simple breathing exercise that significantly reduces blood pressure (BP) and improves vascular endothelial function in several nondiabetic populations. Herein, we performed a blinded, randomized, sham-controlled trial to investigate the effects of a 6-week IMST regimen (30 breaths/day, 6 days/week) on glycemic control and insulin sensitivity in adults with T2DM. Currently, we have eight participants (aged 35-71 years, 5 females and 3 males) who have completed either low-resistance sham training (15% maximal inspiratory mouth pressure, n=5) or high-resistance IMST (75% maximal inspiratory mouth pressure, n=3). Our data suggests that fasting plasma glucose and fasting serum insulin did not significantly change by IMST or sham training. Utilizing a homeostatic model assessment of insulin sensitivity to evaluate insulin action, our results indicate no change by either IMST or sham training. IMST revealed a trend towards a reduction in systolic BP (pre: 133.0 ± 4.8 vs. post: 128.8 ± 4.9) and diastolic BP (pre: 84.8 ± 2.7 vs. post: 81.7 ± 3.6). These findings align with prior research indicating improved resting BP, further corroborating previous studies. We performed an exploratory analysis to examine the potential impact of IMST on lipid levels. Interestingly, IMST resulted in a trend towards a reduction in cholesterol (pre: 259.3 ± 29.4 vs. post: 230.3 ± 3.7) and LDL (pre: 153.3 ± 19.7 vs. post: 127.7 ± 8.7). Analysis of the endothelial function data is forthcoming until we have enough individuals to complete those analyses. In conclusion, our results to date are preliminary; however, we expect to see continued improvements in resting BP and cholesterol/LDL with IMST. Moreover, with a higher number of individuals in the study (our goal is to have 12 in each group), we anticipate seeing changes in glycemia or insulin action. Lastly, IMST stands out as a distinctive and time-effective exercise method, addressing adherence challenges while demonstrating enhancements in cardiometabolic health. This could be particularly advantageous for T2DM patients with an increased cardiovascular disease risk. University of Arizona College of Medicine SPARK Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy of Drumstick Tree (Moringa oleifera) Leaves Powder on Lipid Profile and Hematological Indices in Chickens on a High Fat Diet

Moringa oleifera belongs to the Moringaceae family and genus Moringa. Moringa oleifera has many beneficial pharmaceutical and nutritional properties. The present study aimed to investigate the effects of dietary supplements of Moringa oleifera leaves powder after consumption of a high-fat diet on cholesterol TG, HDL, LDL, VLDL and hematological parameters such as Hb, MCV, MCH, MCHC, PCV, RBCs, WBCs, PLT neutrophil, heterophil and lymphocytes count in chicks. Golden Misri Chickens were divided into 4 groups: Group 1 (the Control group) was given Feed-13. Group 2 (Experimental Group) was given Feed-13 and mustard oil (high-fat diet) Group 3 (experimental Group) was given Feed-13 + mustard oil and 1.5% Moringa oleifera leaves powder. Group 4 (experimental Group) was given Feed-13 and 1.5% of Moringa oleifera leaves powder for four weeks. The results of the current study showed a significant (p &lt; 0.05) increase in body weight in Experimental Group 3. Experimental group 3 showed a significant increase in levels of HDL, TG, RBCs, and Hb, while significantly decreased (p &gt; 0.05) in LDL, TLC, WBCs, MCHC, MCV, MCH, TC, TP, Monocytes count, neutrophil count, and platelet counts. Moringa oleifera supplementation showed a significant reduction in cholesterol, LDL, and TC levels. The findings of this study demonstrated that powdered Moringa oleifera is a beneficial and effective dietary supplement that increases HDL, TG, Hb, and RBCs, and decreases cholesterol levels.