Low-density Lipoprotein Reduction Research Articles

The Effect of Crackers Enriched with Camelina Sativa Oil on Omega-3 Serum Fatty Acid Composition in Older Adults: A Randomized Placebo-Controlled Pilot Trial

BackgroundCamelina sativa oil is one of the richest dietary sources of omega-3, with polyunsaturated fatty acids amounts of over 50%, linolenic acid content of around 40–45%, and linoleic acid of about 15%. Moreover, this oil is a valuable source of antioxidants which provide oxidative stability. All those features raise interest in considering Camelina oil as an alternative and sustainable oil source providing stable omega-3-rich emulsions for functional food production.ObjectivesThe present study aimed to investigate the effects of Camelina oil-enriched crackers on serum omega-3 concentration, inflammatory markers and serum lipid profile.DesignRandomized placebo-controlled pilot trial. Setting: Research and Development Center (Complife Italia s.r.l.).ParticipantsSixty-six free-living older volunteers (aged≥65 years).InterventionOlder adults were enrolled and randomly assigned to one of two groups: the camelina group or the placebo group. Subjects consumed daily 35 g of crackers (Camelina enriched crackers or placebo ones) twice daily for 12 weeks.MeasurementsSerum polyunsaturated fatty acid profile, inflammatory status and serum lipid panel parameters were recorded pre and post-intervention.ResultsIn the camelina group, alpha-linolenic acid serum concentration was significantly higher (p<0.01) compared to the placebo group at the end of the study. Concerning inflammatory plasma markers, a significant mean pro-inflammatory interleukin-18 plasma concentration decrease in the placebo group compared to the camelina one was observed (p<0.05). No significant differences in other mean inflammatory markers concentrations post-intervention were noted in either group. Lastly, examining the change in lipid profile, it is noteworthy that a higher reduction of total cholesterol, low-density lipoprotein and triglycerides in the camelina group postintervention, despite the lack of statistical significance.ConclusionCamelina oil significantly elevated the serum alpha-linolenic acid concentration with no significant changes in inflammatory markers and lipid profile.

Coronary calcium score (CAC) appears to be independent of lipid profile in treated patients with Heterozygous Familial Hypercholesterolaemia

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary artery calcium (CAC) score has been shown to improve the risk stratification and prediction of Atherosclerotic Cardiovascular Disease (ASCVD) in cohorts of patients with Heterozygous Familial Hypercholesterolaemia (FH) [i]. Objectives We sought to examine the CAC score in patients with FH who are on treatment and correlate to the therapy, Total Cholesterol (TC), Low Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) levels. Method Retrospective Analysis of patients with established diagnosis of FH from a specialist lipid clinic who underwent CAC for risk stratification. Results The study included 64 patients, of which 33 patients (52%) were males with an average age of 57.4 years. At diagnosis, the mean elevated TC level was 7.40 ±1.60 mmol/l. 37 patients (58%) were on statin, (7 patients were on Rosuvastatin 20 mg, 20 patients were on Atorvastatin 40 mg, 8 patients were on Atorvastatin 20 mg, 2 patients were on Atorvastatin 80 mg), 8 patients (12%) were on a combination of PCSK9 and statins, 3 patients (5%) were on fibrates (fenofibrates) 160 mg, 3 patients (5%) were on Ezetimibe 10 mg, 4 patients (6%) were on Bempedoic Acid 180 mg, 9 patients (15%) were on lifestyle modifications and did not prefer to start on any lipid lowering agents. 71% of patients with TC level of 7.29 ±1.87 mmol/l had a calcium score of less than 100. CAC of &amp;gt;100 was observed in 29% of patients with a TC level of 7.44 ±1.50 mmol/l. (p value of 0.741) CAC score &amp;gt;100 appeared independent of (A) LDL level (27% with a mean LDL level of 4.81±1.81 mmol/l versus 73% with a CAC &amp;lt;100 and a mean LDL level of 4.40 ±1.38mmol/l) (p value of 0.424) and of HDL level (29% of patients with a mean HDL level of 1.45 ±0.64mmol/l versus 71% with a CAC score&amp;lt; 100 with a mean HDL level of 1.44 ±0.61mmol/l) (p value of 0.768). Despite therapy, 45 patients (27 %) had high LDL level with a mean LDL level of 4.5 ±1.50mmol/l though we found no difference in CAC score between the two groups (p value of 0.424). Conclusion In a single centre retrospective analysis of patients with Heterozygous Familial Hypercholesterolaemia on therapy, there appears to be no correlation between the CAC score of more than 100 and baseline therapy, Total Cholesterol, LDL or HDL levels achieved. We postulate that more stringent LDL reduction to ~1.4mmol/l should be adopted with further analysis of Coronary calcium score in the long term.

EVALUATING THE ASSOCIATION BETWEEN APOLIPOPROTEIN A5 SINGLE NUCLEOTIDE POLYMORPHISMS (APOA5 SNPS) AND HYPERTRIGLYCERIDEMIA

The retrospective study was conducted at the Faisalabad Institute of Cardiology from January 2022 to January 2023 to evaluate the association between apolipoprotein A5 single nucleotide polymorphisms (APOA5 SNPS) and hypertriglyceridemia in the Pakistani population and assess the efficacy of fibrate therapy in hypertriglyceridemic patients. Blood samples of patients were collected for DNA extraction by the standard inorganic method. Extracted DNA was analyzed biochemically and genetically following the selection and genotyping of the APOA5 gene to know SNP variants with risk alleles. We analyzed lipid profiles, including TG (triglyceride), HDL (high-density lipoprotein), and LDL (low-density lipoprotein) levels of hypertriglyceridemic patients, then compared them to normal and fibrate-treated individuals. We compared APOA5 (rs662799) SNP (single nucleotide polymorphism) among 50 hypertriglyceridemic, 50 healthy controls, and among the same 50 hypertriglyceridemic patients who were given fibrate. Results showed that fibrate decreased TG level and LDL by about 30-45% and 20-25%, respectively; increased high-density lipoprotein by 10-15% and total cholesterol decreased by 6-8% in Pakistani. Hypertriglyceridemia risk was significantly increased by a minor allele of APOA5 rs662799 polymorphism. Minor allele carriers of rs662799 had an odd ratio of (95% CI) 1.5 (1.03-2.18) (P = 0.032). Risk allele frequency differed among hypertriglyceridemic patients, healthy controls, and fibrate-treated hypertriglyceridemic individuals. We analyzed that 87.5% of healthy controls exhibited no risk allele, while 78% did not show this risk allele among hypertriglyceridemic patients. It was concluded that APOA5 rs662799 polymorphism is a genetic determinant of hypertriglyceridemia. Fibrate caused a reduction in TG and LDL and caused an elevation of HDL-C among hypertriglyceridemic patients.

The Feasibility and Effects of Smartphone-Based Application on Cardiac Rehabilitation for Patients After Percutaneous Coronary Intervention: A Randomized Controlled Trial.

Cardiac rehabilitation (CR) referral and participation are generally found to be underused worldwide. The data in Asian regions suggest significant underutilization compared with western countries. To promote the continuity and effects of CR, this study aimed at supporting self-care and improving CR effects in phase II CR with mobile health application for Macao patients who have undergone percutaneous coronary intervention. The study was a randomized controlled trial conducted between January 2018 and June 2020 in a nongovernmental Hospital. Social cognitive theory was applied in the intervention for an experimental group. Measurements including anxiety and depression level, medication adherence, exercise capacity, physical activity level, cardiovascular risk modification, self-efficacy, quality of life, use of healthcare resources, mHealth CR utility, and satisfaction were analyzed. One hundred forty eligible patients were recruited, and 110 patients completed the study. Significant interventional effects of the experimental group were found on the reduction of total cholesterol, low-density lipoprotein, sitting time, anxiety level, and total anxiety and depression level ( P < .05). In addition, significant improvement on the 6-minute walk test, regular exercise performance, self-efficacy of cardiac exercise and diet, and quality of life were found as interventional effects in the experimental group ( P < .05). The feasibility of intervention was achieved in a satisfactory level. This theoretically grounded mobile health CR study was a unique program tailor-made to meet the care needs of patients post percutaneous coronary intervention. It was feasible and effective to support CR effects and adherence and would inform further design of clinical practice and public policies.

PCSK9 Inhibition in Patients After Heart Transplantation: a Retrospective Review and Literature Analysis.

Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective.

Oridonin supplementation in rabbits may help to improve the outcome of induced atherosclerosis via autophagy induction.

Inflammation plays a crucial role in the development of atherosclerotic plague. Oridonin is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens. It is a natural terpenoids that is known as a strong anti-inflammatory supplement by acting as a potent inhibitor of the TXNIP/NLRP3 pathway. Hence, it can reduce the severity of inflammation and improve the outcome of atherosclerotic changes. This study aims to evaluate the anti-inflammatory effects of oridonin in the progression of atherosclerotic plague in rabbits. Sixty-three male rabbits were included. The rabbits were randomly assigned to one of the three study groups (21 rabbits in each group), normal control diet (NC) fed normal diet for 8 weeks, atherogenic control (AC) fed atherogenic diet (2% cholesterol-enriched diet) for 8 weeks, and oridonin treated group (OT) fed atherogenic diet (2% cholesterol-enriched diet) with oridonin (purity 94%, Sigma-Aldrich, USA) at 20 mg/kg orally daily for 8 weeks. After the end of the study, blood and tissue samples were collected for analysis of various markers of inflammation and atherosclerotic plaque progression. Serum lipids showed a statistically significant improvement in terms of reduction in total cholesterol and low-density lipoprotein (LDL) in the OT group compared to the AC group. This was associated with a significant reduction in serum F2-isoprostane (marker of inflammation) and LC3B (marker of tissue autophagy) between the OT group compared to the AC group. There was also a significant reduction in NLRP3 inflammasome RNA expression in OT group, P<0.001. In animal model, with atherogenic diet, oridonin supplementation can significantly improve the outcome of atherosclerosis by its strong anti-inflammatory action.

Acute coronary syndromes: hospital management of dyslipidaemia with proprotein convertase subtilisin/kexin 9 inhibitors: time to act.

Atherosclerotic cardiovascular disease (ASCVD) in its countless clinical presentations is, in industrialized countries, the most frequent cause of death and, in recent years, a leading role in the prevention of ASCVD has been attributed to the treatment of dyslipidaemias. If statins and ezetimibe remain the cornerstone of pharmacological treatment, an increasingly relevant role is attributed to the inhibitors of the proprotein convertase subtilisin/kexin 9 (PCSK9i), as a result of the excellent results obtained in their respective trials, not only on the reduction of low-density lipoprotein (LDL) or LDL cholesterol (LDL-C) but also on plaque stabilization and regression. The addition of PCSK9 inhibitors leads to a further reduction in LDL levels and a consequent improvement in prognosis and it is recommended in 'fast-track' administration (intrahospital/discharge) in patients with acute coronary syndromes (ACSs) or multiple cardiovascular events already on statin therapy and LDL >70 mg/dL and in statin-naïve ACS patients and LDL >140 mg/dL. By applying guidelines and fast-track, ∼25% of patients with ACS should receive PCSK9i at discharge but unfortunately patients are currently undertreated.

Evinacumab-dgnb (Evkeeza-REGN1500), A Novel Lipid-Lowering Therapy for Homozygous Familial Hypercholesterolemia.

Chronically elevated low-density lipoprotein (LDL) has harmful effects on the vasculature including increased vasoconstriction and the formation of plaques which may rupture, causing coronary heart disease and stroke. In patients with familial hypercholesterolemia, adequate reduction of LDL is especially challenging. Although HMG-CoA reductase inhibitors (statins) are the mainstays for LDL lowering, other treatments such as proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, incliseran, lomitapide, and apheresis have been employed in an effort to achieve adequate LDL reduction in these patients. Despite these available therapies, many patients with familial hypercholesterolemia do not meet the LDL targets suggested in current guidelines. Evinacumab is a novel lipid-lowering therapy that exerts its LDL-lowering effect through inhibition of angiopoietin-like protein 3 (ANGPTL3). ANGPTL3 inhibits the breakdown of triglyceride-rich lipoproteins, such as very low-density lipoprotein and chylomicrons. By inhibiting ANGPTL3, evinacumab allows these lipoproteins to be degraded, ultimately leading to reductions in LDL, high-density lipoprotein, and triglycerides. Clinical trials have demonstrated evinacumab to be safe and effective in reducing LDL. However, data are lacking regarding its potential to reduce risk of atherosclerotic cardiovascular disease. Evinacumab is generally well tolerated with the primary adverse effects comprising infusion reactions, nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. While evinacumab is an interesting therapy, until it is proven to reduce cardiovascular events, its high cost leaves its anticipated role in therapy somewhat ambiguous. In the meantime, it may be a useful therapy for those with homozygous familial hypercholesterolemia.

The anti-dyslipidemia property of saffron petal hydroalcoholicextract in cardiovascular patients: A double-blinded randomized clinical trial

Dyslipidemia is one of the most important risk factors of cardiovascular diseases (CVDs). Despite developments in pharmacological treatments for dyslipidemia there are several challenges. Recently some herbs highly considered to control dyslipidemia due to their low toxicity and high potency. In this study we investigated the effects of saffron petals on the lipid profile of dyslipidemia patients as well as several other biochemical blood factors. In this double blind, placebo controlled, clinical trial, we used systematic random sampling to divide 40 patients with at least two abnormalities in the following factors: (high-density lipoproteins (HDL) ≤40, low-density lipoproteins (LDL) ≥130, triglycerides (TG) ≥200, total cholesterol (Cho) ≥200), into 2 groups of 21 ones. At the end of the intervention period, serum lipid factors, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, creatinin (CR) and fasting blood sugar (FBS) were measured and statistically compared with their values just before the intervention. We found that the saffron petal pills markedly (P<0.001) decreased the serum lipid levels of patients (TG, Cho and LDL) in the intervention group (113.81±12.93, 56.52±4.68 and 48.28±3.70) as compared to the placebo group (18.42±15.79, 4.57±4.40 and 7.38±3.54). Also, comparing the mean value of differences in two groups before and after the intervention showed significant reduction in TG (113.81±26), Cho (56.53±0.30) and LDL (48.28±4.30) levels (P<0.001). The saffron petal pills considerably reduced blood serum lipid profile and as well as urea and CR of dyslipidemia patients. So, this plant may be used as a potent phytomedicine for treatment and prevention of dyslipidemia and cardiovascular disorders. However, the results indicated that no statistical change was observed in the level of other biochemical blood factors such as ALT, AST, ALP and FBS.

Real-World Outcomes of Proprotein Convertase Subtilisin Kexin-9 Inhibitor Use.

Although the proprotein convertase subtilisin kexin-9 inhibitors (PCSK9i) were shown to significantly lower low-density lipoprotein and reduce atherosclerotic cardiovascular disease events in clinical trials, there is a dearth of use data on these agents in real-world settings. This study compares PCSK9i use in a population of real-world patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia. This was a matched cohort study of adult patients who were dispensed a PCSK9i along with adult patients who did not receive a PCSK9i. PCSK9i patients were matched on a propensity to have received a PCSK9i score up to 1:10 to non-PCSK9i patients. The primary outcomes were changes in cholesterol levels. Secondary outcomes included a composite outcome of all-cause mortality, major cardiovascular events, and ischemic strokes along with health care utilization during follow-up. Adjusted conditional, multivariate Cox proportional hazards, and negative binomial modeling were performed. Ninety-one PCSK9i patients were matched to 840 non-PCSK9i patients. Seventy-one percent of PCSK9i patients either discontinued or switched PCSK9i therapy. PCSK9i patients had greater median reductions in low-density lipoprotein (-73.0 mg/dL vs. -30.0 mg/dL) and total (-77.0 vs. -31.0) cholesterol (both P < 0.001). No adjusted between-group differences in the composite outcome or individual components of the composite outcome were identified (all P > 0.05). PCSK9i patients had a lower rate of medical office visits during follow-up (adjusted incidence rate ratio = 0.61, P = 0.019). These findings support the effectiveness of PCSK9i therapy in real-world settings but suggest that use may be limited by PCSK9i adverse reactions and patient cost barriers.

Association of Lipid-Lowering Drugs With Risk of Psoriasis

Lipid pathways have been implicated in the pathogenesis of psoriasis, and some lipid-lowering drugs, such as statins, are hypothesized to have disease-modifying properties. However, large population-level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding. To investigate the causal association between genetically proxied lipid-lowering drugs and psoriasis risk. This 2-sample mendelian randomization study was performed from August to October 2022 and included population-level genome-wide association studies of psoriasis in the UK Biobank and FinnGen studies and low-density lipoprotein (LDL) by the Global Lipids Genetics Consortium. The inverse variance-weighted method was used with pleiotropy robust methods and colocalization as sensitivity analyses. Genetically proxied inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR, targeted by statins), Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by, eg, alirocumab), using LDL as the biomarker. Risk of psoriasis. Data from 12 116 patients with psoriasis and approximately 1.3 million individuals with LDL measurement were analyzed. Genetically proxied PCSK9 inhibition was associated with reduced risk of psoriasis (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003), which was replicated in FinnGen (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002). Sensitivity analyses did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for HMGCR or NPC1L1 inhibition. This mendelian randomization study suggests that PCSK9 is implicated in psoriasis pathogenesis, and its inhibition is associated with reduced psoriasis risk. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of psoriasis.

The Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Clinical Populations: A Systematic Review and Meta-Analysis.

Over the last two decades, a plethora of disease models and human studies have confirmed the beneficial effects of molecular hydrogen (H2), a simple biotherapeutic gas. Recent small-scale studies evaluating the effects of hydrogen-rich water (HRW) on various metabolic conditions pointed to advantageous effects of HRW in regulating blood lipid profiles. However, to the best of the authors' knowledge, no systematic review and/or meta-analysis (SRMA) were published considering HRW consumption and lipid/lipoprotein status. Therefore, the aim of this SRMA was to assess the effects of HRW consumption on blood lipid panel in clinical populations. The search strategy was designed using PRISMA guidelines, and the databases PubMed/Medline, Web of Science, and Scopus were explored from inception until 4 October 2022. A total of seven studies satisfied all the eligibility criteria and were included in SRMA. The results for the pooled meta-analysis showed a significant reduction in total cholesterol, low-density lipoprotein, and triglycerides after HRW intake (p = 0.01), with small to moderate effects (pooled SMD = -0.23 (from -0.40 to 0.05); pooled SMD = -0.22 (from -0.39 to 0.04); pooled SMD = -0.38 (from -0.59 to 0.18), respectively). Our findings indicate that drinking HRW can significantly improve lipid status in the clinical populations. Additional studies are warranted to further validate this connection.

PS-BPC12-6: ASSESSMENT OF LDL CONTROL IN POST-ACUTE CORONARY SYNDROME PATIENTS: STATINS ARE NOT ENOUGH

Objective: Cardiovascular disease (CVD) is one of the leading causes of death worldwide, with nearly 18 million people dying from CVD in 2019. In the UK, CVD was responsible for the premature deaths of nearly 170,000 people with around 65,000 being attributed to acute coronary syndrome (ACS). High levels of low-density lipoprotein (LDL) is one of the main risk factors associated with ACS. A recent European guideline has set out a target for secondary prevention in ACS patients of a LDL &lt; 1.4 mmol/l and 50% or more reduction from baseline. This study seeks to identify the proportion of patients meeting the LDL reduction target for secondary prevention and also to assess whether there are other alternative treatments that are more effective in achieving satisfactory lipid control. Design and Methods: The Myocardial Ischaemia National Audit Project (MINAP) database was used to identify patients admitted into the University Hospitals of Leicester NHS Trust (UHL) between May 2017 and May 2018. The MINAP database records information on how patients admitted into hospital with ACS are cared for. 694 patients were identified. Hospital records were reviewed at 6 months post discharge to determine medications prescribed on discharge and LDL levels. The study was part of a quality improvement project to optimise lipids in patients with ACS (UHL internal audit number 9397). Results: This study found that 97.5% of patients were prescribed a statin upon discharge, which is marginally higher than the national average of 96.4%. 83.4% of patients were discharged with a high-intensity statin as recommended by national guidelines. However only 37.6% of patients reached a LDL level of below 1.4 mmol/l at follow-up. Furthermore of those patients with a baseline LDL prior to or during the myocardial infarction related admission, only 25.1% of patients also achieved a LDL reduction of 50% or more. Patients that were prescribed Ezetimibe showed a slightly better reduction in LDL with 57.1% of patients achieving a LDL level of below 1.4 mmol/l at follow-up and 28.6% of them also achieving a LDL reduction of 50% or more. Conclusions: This study suggests that patients are not achieving a reduction in their LDL levels to &lt; 1.4 mmol/l and 50% or more reduction from baseline despite the majority of patients being prescribed a high-intensity statin as recommended by national guidelines. Therefore there may be a need for the most high risk of patients being offered Ezetimibe in addition to ensure LDL reduction targets are reached.

Magnitude of low-density lipoprotein reduction and impact on major cardiovascular outcomes.

Magnitude of low-density lipoprotein reduction and impact on major cardiovascular outcomes.

Effect of Rosuvastatin and Glibenclamide in Alone or in Combination on Glucose Homeostasis in Diabetic Male Albino Wistar Rats: An Observer-blinded Experimental Interventional Study

Introduction: Metabolic Syndrome (MetS) is a complex of metabolic disorders which include obesity, insulin resistance, hyperglycaemia, hypertension along with dyslipidemia. It is not clear whether rosuvastatin is having role in new onset diabetes. Aim: To assess the effect of rosuvastatin in comparison to glibenclamide on blood sugar levels and insulin resistance in diabetic rats. Materials and Methods: This experimental study was carried out at Sri Manakula Vinayagar Medical College and Hospital, Kalitheerthalkuppam, Puducherry on 42 adult male Wistar rats, for 8 weeks. Diabetes was created by feeding rats with High Fat and High Sugar (HFHS) diet over a period of 8 weeks. In total, 42 rats were allocated to in 7 groups, consisting of 6 animals per group. Group I -vehicle treated animals (control), group II - HFHS diet animals (Diabetic Control- DC), group III- glibenclimide (G) (5 mg/kg) + HFHS, group IV-rosuvastatin (R) (5 mg/kg) + HFHS, group V-R (10 mg/kg) + HFHS, group VI-G (5 mg/kg) + R (5 mg/kg) + HFHS diet, group VII-G (5 mg/kg) + R (10 mg/kg) + HFHS diet continued for 4 weeks. Rosuvastatin and glibenclamide were dissolved in distilled water and 95% ethanol respectively, and were given orally daily for 4 weeks after induction of diabetes. Data were subjected to one-way ANOVA using Statistical Package for the Social Sciences (SPSS) version 24.0 followed by non parametric test with significance level set for p-value&lt;0.05. Results: By end of 8th week, on comparison of control group with HFHS diet and glibenclamide treated group, there was significant rise in body weight, serum Low Density Lipoprotein (LDL), in addition to Very Low Density Lipoprotein (VLDL) and Triglycerides (TG) levels. Glibenclamide treated (group III) animals on comparison with groups IV, V, VI, VII revealed reduction in body weight, serum LDL, VLDL and TG levels (p &lt;0.001). Glibenclamide treated (group III) on comparing with groups IV, V, VI, VII, there was significant high serum HDL level (p&lt;0.001). By 8th week, significant decrease in serum insulin and HOMA-IR level was observed when glibenclamide group III was compared with groups IV to VII treated animals (p &lt;0.001). Conclusion: The study results indicate that the combination therapy of rosuvastatin and glibenclamide demonstrate beneficial effects on weight reduction, lipid profile and insulin resistant.

EXPLORING the prophylactic potential of Azadirachta indica leaf extract against dyslipidemia

Ethnopharmacological relevanceSeveral studies revealed that different parts of Azadirachta indica A. Juss, has therapeutic potential against inflammatory issues and dyslipidemia which is a major contributing cause to cardiovascular diseases, oxidative stress and serum glucose levels, etc. Aim of studyPresent study was conducted to evaluate anti-dyslipidemic capacity of Azadirachta indica leaf extract in dyslipidemic rabbits. Materials and methodsEthanolic extract of Azadirachta indica leaves was obtained by using Soxhlet apparatus. This extract was used for efficacy study on rabbits. In this context, 25 healthy rabbits were selected for study, Efficacy trial involved five groups of rabbits, 5 rabbits in each group; NC (Negative Control); healthy rabbits received normal diet. In remaining 20 rabbits, dyslipidemia was induced by using high fat diet for 28 days followed by administration of Azadirachta indica leaf ethanolic extract for 60 days in a dose-dependent manner. PC (Positive Control) include dyslipidemic rabbits received normal diet while G1, G2, G3 groups included dyslipidemic rabbits receiving different concentrations of Azadirachta indica leaf extract (i.e. 300, 500 and 700 mg/kg of body weight, respectively). Blood samples were analyzed for serum lipid profile after every 15 days to determine the effect of treatments. ResultsSignificant reduction in total cholesterol (60 ± 3.4 mg/dL), triglycerides (40.31 ± 2.5 mg/dL) and low-density lipoprotein (28.87 ± 2.1 mg/dL) was observed in G2 (P ≤ 0.05)while a significant increase was observed in high-density lipoprotein (60.47 ± 1.7 mg/dL) of G2 (P ≤ 0.05) as compared to other groups. ConclusionResults revealed that ethanolic extract of Azadirachta indica leaves in G2 group (@ 500 mg/kg of body weight) normalized lipid profile in dyslipidemic rabbits after 60 days of extract administration which significantly lowered TC, TG, LDL levels (P ≤ 0.05) and improved HDL level.

Targeting PCSK9 With Antibodies and Gene Silencing to Reduce LDL Cholesterol.

The discovery of PCSK9 and its role in regulating the low-density lipoprotein (LDL) receptor, and the effect of loss-of-function mutations of its gene, identified it as a therapeutic target in 2006. Fully humanized monoclonal antibodies to PCSK9 (alirocumab and evolocumab) proved effective for lowering LDL cholesterol and subsequently for reducing atherosclerotic events in large outcome trials. Suppressing PCSK9 synthesis via gene silencing using inclisiran, a small interfering RNA, is another approach that effectively reduces LDL cholesterol, and a cardiovascular outcome trial is in progress. These treatments are given subcutaneously on a background of maximally tolerated statin treatment and are long-lasting: dosing is once or twice a month, self-administered, for alirocumab and evolocumab, and every 6 months for inclisiran, in the clinic, with an extra dose at 3 months in the initial year of therapy. These 3 agents produce mean LDL reductions of about 55% with no important adverse effects detectable to date. They are indicated in patients with atherosclerotic vascular disease or familial hypercholesterolemia who cannot achieve LDL cholesterol targets with maximally tolerated statin treatment. Such therapy can produce very low plasma LDL cholesterol and PCSK9, but there is no evidence this is harmful. Introduction into clinical practice has been impeded by economic considerations. The barrier to their use has not been scientific or medical, but rather the impact on healthcare resources. Prices have been reduced, but whether they are now cost-effective varies from country to country.

Effectiveness in the short-term of a novel nutraceutical for the management of hypercholesterolemia: an observational multicenter primary care experience

Purpose: Increasing evidence reinforces the benefits of reduction of low-density lipoprotein (LDL-C) levels on cardiovascular outcomes. Different targets are suggested based on cardiovascular risk (CVR). According to the current European guidelines, a goal of LDL-C≤ 115mg/dL is desirable for patients with low-moderate CVR. However, a high percentage of these patients are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. In this retrospective analysis, we evaluate the effects of dietary supplementation with a novel monacolin/berberine/bergamot nutraceutical formulation on plasma lipid levels of subjects with low-moderate hypercholesterolemia who are not treated with conventional drug or other dietary supplements. Patients and Methods:526 adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners according to prespecified criteria. All selected patients had a baseline and 30-day value of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, and transaminases and have started a dietary supplementation with this novel nutraceutical. Similarly, 104 subjects with comparable clinical features but not treated with any supplements were also selected. Results:At 30-day, the administration of nutraceuticals was associated with a significant reduction of LDL-C (124 ± 14 vs. 100 ± 13 mg/dL, Δ 24.5mg, p-value &lt;0.0001) and TC levels (210 ± 56 vs. 187 ± 60, p-value &lt; 0.0001), in the absence of a significant change of transaminase levels. No side effects were reported in the database during the observation period. Conclusion: This novel nutraceutical is an effective dietary supplement to achieve a significant and early LDL-C reduction in patients with hypercholesterolemia at low-moderate CVR.Keywords:Cardiovascular Risk; Hypercholesterolemia; Nutraceuticals

Abstract 11354: Role of PCSK9 Inhibitors in Acute Coronary Syndromes - A Pilot Study

Introduction: The proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have been guideline-approved for intolerant patients to statin therapy or unable to achieve target LDL levels with maximally tolerated therapies. The study aimed to determine whether early initiation of PCSK9 inhibitor with statin therapy in acute coronary syndromes (ACS) patients is beneficial in relation to low-density lipoprotein (LDL) reduction and short-term cardiovascular outcomes. Methods This pilot study included eighty ACS patients randomized to receive either PCSK9 inhibitor (Evolocumab) with statin therapy (n=40) or statin monotherapy (n=40). Patients were followed up for 6 months to assess for LDL levels, left ventricular ejection fraction (LVEF), and major adverse cardiovascular events (MACE) (a composite of myocardial infarction, heart failure, and cardiovascular death). Results Eighty patients with ACS (mean age 59±11 years, 66.3% male) had LDL and LVEF measured at baseline, 3 months, and 6 months. There was no difference between baseline LDL levels (153.1±39.5 vs 146.1±32, p=0.39). LDL levels in PCSK9 inhibitor/statin group were significantly lower at 3 months and 6 months compared to statin monotherapy (76.2±27.7 vs 118.6±31, p&lt;0.0001 and 78.2±22.1 vs 103.7±22.5, p&lt;0.0001, respectively). There was no significant difference between incidences of cardiovascular death (1 vs 3, p=0.31) and MACCE (4 vs 6, p=0.5) between both groups at 6-month follow-up. Conclusion The early initiation of PCSK9 inhibitors/statin combination therapy in ACS patients was associated with a significant reduction of LDL levels at 3 and 6 months yet there was no significant difference in relation to short-term cardiovascular outcomes at a 6-month follow-up. Further research is required to determine whether early initiation of PCSK9 inhibitors in combination with statins or as monotherapy in ACS patients can be associated with improved short or long-term cardiovascular outcomes.

Comparing Simvastatin Monotherapy V/S Simvastatin-Ezetimibe Combination Therapy for the Treatment of Hyperlipidemia: A Meta-Analysis and Review.

Longstanding hyperlipidemia canincrease the risk of cardiovascular disease. Statins are currently the mainstay of treatment in hyperlipidemia. Combination therapy of statin with ezetimibe is only indicated for severe hypercholesterolemia and very high-risk atherosclerotic cardiovascular disease (ASCVD) population. There is a paucity of studies comparing statin monotherapy vs combination therapy with ezetimibe. This study aims to perform a meta-analysis of the existing literature and compare the effectiveness of statin monotherapy with statin-ezetimibe combination therapy in the management of hyperlipidemia. A systematic electronic search of the scientific literature was performed in PubMed, EMBASE, and Scopus. Only randomized controlled trials comparing simvastatin monotherapy vs simvastatin-ezetimibe combination therapy between the years 2000 and 2021 and published in English language were included. Fifteen studies were included in the final analysis. The main outcomes that were compared were a reduction in low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Our study showed that combination therapy led to a higher reduction of LDL-C (Mean difference: -20.22(-26.38, -14.07); P<0.0001) compared to monotherapy with a statin alone. There was no significant difference in the reduction of HDL-C values (Mean difference: -0.07(-0.45,0.32); P-0.04)between the two groups. Our study indicates that the combination therapy of simvastatin and ezetimibe is more effective in reduction of LDL-Clevels compared to simvastatin monotherapy alone. Currently, guidelines recommend combination therapy only for severe hypercholesterolemia and high-risk ASCVD patients, more studies are needed to study the effectiveness of simvastatin-ezetimibe combination therapy in low-risk ASCVD population.