Lipoprotein Reduction Research Articles

The impact of tamoxifen on apolipoproteins and lipoprotein(a) levels: an updated meta-analysis of randomized controlled trials.

The existing evidence regarding the impact of tamoxifen on lipoprotein(a) and apolipoproteins remains inconsistent. Therefore, this updated meta-analysis of randomized controlled trials (RCTs) aims to enhance the quality of evidence concerning the effects of tamoxifen on these lipid parameters. Eligible RCTs published up to October 2024 were meticulously selected through a comprehensive search. A meta-analysis was then performed using a random-effects model, and results were presented as the weighted mean difference (WMD) with a 95% confidence interval (CI). Findings from the random-effects model revealed an increase in ApoA-I (WMD: 15.22 mg/dL, 95% CI: 6.43-24.01, P = 0.001), alongside decreases in ApoB (WMD: -9.33 mg/dL, 95% CI: -15.46 to -3.19, P = 0.003) and lipoprotein(a) (WMD: -3.35 mg/dL, 95% CI: -5.78 to -0.91, P = 0.007) levels following tamoxifen treatment in women. Subgroup analyses indicated a more significant reduction in lipoprotein(a) levels in RCTs with a duration of ≤24 weeks (WMD: -3.65 mg/dL) and in studies using tamoxifen doses of ≥20 mg/day (WMD: -4.53 mg/dL). This meta-analysis provides evidence that tamoxifen leads to a decrease in lipoprotein(a) levels, along with reductions in ApoB and increases in ApoA-I among women.

Hyperlipoproteinemia(a): the role of antisense­­oligonucleotides in reduction of lipoprotein(a) level. Literature review

The literature review is devoted to a relevant problem of correction of elevated level of lipoprotein(a) (LP(a)) which is a risk factor (RF) for atherosclerotic cardiovascular diseases (ACVD) and demonstrates a stability to action of existing lipid‑lowering drugs (LLD) due to genetic determination of apolipoprotein(a) (apo(a)), a structural component of LP(a) molecule. Since human lipid metabolism is regulated by many genes, the majority of them, in particular, apo(a) gene can be potential targets for innovative antisense therapy, a method of treatment based on reduction of synthesis of LP(a) involved in the development of ACVD through inhibition of apo(a) matrix ribonucleic acid (mRNA) translation due to connection with complementary short sequences called antisense oligonucleotides (ASO). Update insights into the structure and pathophysiological role of LP(a) in atherothrombosis, a necessity of hyperlipoproteinemia(a) correction caused by its proatherosclerotic and prothrombotic effects are given. A focus was made on innovative LLD with high potential in treatment of ACVD and correction of their risk factors, particularly on ASO capable of blocking a translation of apo(a) mRNA. Principal mechanisms of ASO action, the ways of their delivery to mRNA targets are presented. The data of studies on LP(a) reduction with mipomersen, pelacarsen, SLN360 agent, olpasiran and lepodisiran are presented. It is emphasized that despite the efficacy of enumerated ASO in LP(a) reduction, there are unknown long­­term consequences of its intensive reduction, particularly an influence on cardiovascular events and the functional state of organs and their systems in different diseases. The only ASO drug approved by the US Food and Drug Administration is mipomersen recommended for correction of low­­density lipoprotein cholesterol and LP(a) levels due to its ability to block apolipoprotein B­­100 synthesis. In Europe mipomersen was not registered because of its unfavorable safety profile. Thus, despite the prospects for developing new drugs based on antisense technologies, many questions remain about their efficacy and safety, especially for LLD intended for long­­term use.

Beneficial Effects of a Nutraceutical Combination on Lipid Profiles in Children with Moderate and Severe Hypercholesterolemia.

The aim of the present study was to evaluate the efficacy and safety of the long-term use of a dietary supplement containing red yeast rice (RYR), combined with other natural compounds, in children and adolescents with primary hypercholesterolemia. A nutraceutical, containing RYR, policosanols, coenzyme Q10, astaxanthin and folic acid (commercial name: Armolipid), was administered once daily in 84 children/adolescents with moderate or severe primary hypercholesterolemia. Moreover, 19 of the participants consumed 1.5-2.5 g of phytosterols daily until the initiation of dietary supplementation with Armolipid. Clinical and laboratory evaluation took place before and 6 and 16 months after treatment. Nutraceutical consumption resulted in a significant decrease in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and apolipoprotein B levels, which was maintained with long-term administration (p < 0.001). No changes were observed in high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1 and lipoprotein (a) levels. In children previously on phytosterol supplementation, Armolipid use exerted a further significant reduction in atherogenic lipoproteins. Armolipid may be an effective and safe complementary treatment for children with moderate and severe hypercholesterolemia. More prospective studies on larger cohorts are needed to establish the role of nutraceuticals containing RYR, policosanols and other natural compounds in the treatment of children with hypercholesterolemia.

Strategic Intelligence as a Tool Against Organized Crime. A Literature Review

Objective: The objective of the study is to analyze and describe through scientific literature the application of strategic intelligence as a tool against organized crime. Theoretical Framework: The research is based on theories that link the bioactive compounds of Rubus spp. with the reduction of cholesterol, triglycerides and lipoproteins in model organisms, based on previous studies on hyperlipidemia and its treatment with natural antioxidants. Method: This study was based on a systematic literature review published between 2018 and 2024 in the Scopus and Scielo databases. We identified 38 relevant articles that included qualitative, quantitative and mixed methodologies Results and Discussion: The findings underscore that strategic intelligence, by identifying patterns and anticipating threats, strengthens the fight against criminal networks by coordinating interagency efforts and improving resource allocation.. Research Implications: It is concluded that an effective response to organized crime requires multidimensional and collaborative approaches that combine prevention, international cooperation and technological adaptation to dismantle criminal networks and mitigate their impact on society. Originality/Value: This study makes it possible to address complex problems such as corruption, the integration of crime into the economy and violence.

Sleeve gastrectomy plus single anastomosis sleeve ileal bipartition versus sleeve gastrectomy alone: The role of bipartition.

Sleeve gastrectomy (SG) with single anastomosis sleeve ileal bipartition (SASI) is a novel procedure for increasing the anti-metabolic efficacy of SG in severely people with obesity. This study aimed to compare 1-year results between SASI and SG, thereby assessing the role of bipartition. The study was conducted at the Medical University hospital. Between November 2021 and December 2022, 39 patients received an SG + SASI surgery, a total of 35 patients completed 1-year follow-up after the surgery. They were matched with a group of 70 patients with SG that were equal in age, sex, and body mass index (BMI). Operative risk, weight loss, and remission of comorbidities were evaluated after 12 months. The operation time of the SASI group was significantly longer than the SG group (140.3 ± 22.8 vs. 114.9 ± 21.6 min; p < .001). At 12 months after surgery, the SASI group had better weight loss (total weight loss: 37.0% vs. 29.7%; p = .001) and achieved a lower BMI than SG (23.4 ± 2.6 kg/m2 vs. 24.6 ± 2.9 kg/m2; p = .046). Reduction of A1C and remission of T2D was greater in the SASI group. The SASI group had a higher reduction in uric acid, low-density lipoprotein, total cholesterol, and triglyceride levels after operation than the SG group. However, the SG group is superior to the SASI group in mean corpuscular volume, calcium, and iron levels. In this study, adding an ileum bipartition to SG increases the weight loss, glycemic, and blood lipid control of SG only.

Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity.

To review the evidence and describe the biological plausibility for the benefits of inhibiting cholesteryl ester transfer protein (CETP) on multiple organ systems through modification of lipoprotein metabolism. Results from observational studies, Mendelian randomization analyses, and randomized clinical trials support the potential of CETP inhibition to reduce atherosclerotic cardiovascular disease (ASCVD) risk through a reduction of apolipoprotein B-containing lipoproteins. In contrast, raising high-density lipoprotein (HDL) particles, as previously hypothesized, did not contribute to ASCVD risk reduction. There is also an expanding body of evidence supporting the benefits of CETP inhibition for safeguarding against other conditions associated with aging, particularly new-onset type 2 diabetes mellitus and dementia, as well as age-related macular degeneration, septicemia, and possibly chronic kidney disease. The latter are likely mediated through improved functionality of the HDL particle, including its role on cholesterol efflux and antioxidative, anti-inflammatory, and antimicrobial activities. At present, there is robust clinical evidence to support the benefits of reducing CETP activity for ASCVD risk reduction, and plausibility exists for the promotion of longevity by reducing risks of several other conditions. An ongoing large clinical trial program of the latest potent CETP inhibitor, obicetrapib, is expected to provide further insight into CETP inhibition as a therapeutic target for these various conditions.

Atherogenic low-density lipoprotein and cardiovascular risk.

Despite reductions in low-density lipoprotein (LDL) cholesterol (LDLc), residual cardiovascular risk remains due to factors beyond lipoprotein levels, such as LDL particle count, size, electronegativity and modifications. Technological advances allow detailed profiling of LDL particles, offering potential biomarkers for diagnosis, prognosis, and treatment of cardiovascular disease (CVD). The aim of this review is to provide an updated overview of the state of knowledge in the field of LDL atherosclerotic role, which is evolving rapidly due to technological advances in biomarker measurement and applications. While small dense LDL has been linked to increased CVD risk, current approaches favor a comprehensive evaluation of all lipoprotein subtypes, as this is a more feasible and standardized method. The atherogenic potential of circulating oxidized LDL (oxLDL) may be the key factor in the onset and progression of atherosclerosis. Thus, elevated oxLDL levels are recognized as a marker of increased CVD risk in both general and high-risk populations, although further research is needed to clarify some conflicting findings. The oxidized LDL receptor 1 (LOX-1) has emerged as a promising target for immunotherapy and innovative drug delivery strategies to modulate atherosclerosis. A panel of biomarkers related to LDL atherogenicity may help predict future ischemic events. An atheroprotective diet and increased physical activity could improve LDL oxidation. OxLDL has become a target for immunomodulatory antiatherosclerosis therapy and delivering LDL-based nanocarriers holds promise for both imaging and therapeutics.

Effect of Blackberry Rubus sp. in Hyperlipidemia in Rattus rattus. A Literature Review

Objective: The aim of this study was to deepen the understanding of the effects of polyphenols found in Rubus spp. on significantly reducing blood lipid levels, focusing on its potential use for treating hyperlipidemia in Rattus through a systematic review. Theoretical Framework: This research is grounded in theories linking the bioactive compounds in Rubus spp. to reductions in cholesterol, triglycerides, and lipoproteins in model organisms, based on previous studies on hyperlipidemia and its treatment with natural antioxidants. Method: This work used the literature review approach, collecting relevant articles in databases such as Scopus and Scielo. Experimental studies with Rattus were analyzed where extracts of Rubus spp. and other compounds rich in polyphenols to observe effects on lipid profiles. Results and Discussion: The reviewed studies indicate that Rubus spp., with its high levels of polyphenols and anthocyanins, significantly reduces lipid levels in rats, validating its potential in hyperlipidemia management. The study discusses the limitations and the context of these findings within cardiovascular disease management. Research Implications: The findings suggest that Rubus spp. may serve as a natural option for hyperlipidemia reduction, with potential applications in public health and preventive nutrition. Originality/Value: This study contributes to the knowledge of natural strategies for hyperlipidemia control, supporting the potential inclusion of Rubus spp. in diets for cardiovascular disease prevention.

The role of the Mediterranean Diet in preventing the development and complications of lifestyle diseases – a Review

IntroductionThe Mediterranean diet, inspired by traditional dietary habits of the Mediterranean region, exhibits anti-inflammatory and protective effects, reducing the risk of civilization diseases such as obesity, type 2 diabetes, and cardiovascular disorders. This diet is characterized by a high intake of plant-based foods, olive oil, and moderate consumption of fish and dairy products. These components provide unsaturated fatty acids, polyphenols, and antioxidants, which positively impact metabolic health and lower the risk of chronic diseases. In the face of the global obesity epidemic and an increasing number of individuals affected by lifestyle-related diseases, the Mediterranean diet offers a promising tool to support a healthy lifestyle. Aim of study This article aims to review current scientific studies evaluating the potential of the Mediterranean diet in preventing and managing civilization diseases. Particular attention is given to its effects on weight loss, improvements in glycemic markers, reductions in low density lipoproteins (LDL) cholesterol levels, and blood pressure control. The article also explores its benefits for athletes' health, as well as its potential to reduce oxidative stress and inflammatory states. Material and methods A literature review of the PubMed database was conducted, assessing relevant studies on the Mediterranean diet and its impact on lifestyle diseases.

Lipid nanoparticle delivery of TALEN mRNA targeting LPA causes gene disruption and plasma lipoprotein(a) reduction in transgenic mice

Lipoprotein(a), or Lp(a), is encoded by the LPA gene and is a causal genetic risk factor for cardiovascular disease. Individuals with high Lp(a) are at risk for cardiovascular morbidity and are refractory to standard lipid-lowering agents. Lp(a)-lowering therapies currently in clinical development require repetitive dosing, while a gene editing approach presents an opportunity for a single-dose treatment. In this study, mRNAs encoding Transcription Activator-Like Effector Nucleases (TALENs) were designed to target human LPA for gene disruption and permanent Lp(a) reduction. TALEN mRNAs were screened in vitro and found to cause on-target gene editing and target protein reduction with minimal off-target editing. TALEN mRNAs were then encapsulated with LUNAR®, a proprietary lipid nanoparticle (LNP), and administered to transgenic mice that expressed a human LPA transgene. A single dose of TALEN mRNA-LNPs reduced plasma Lp(a) levels in mice by over 80%, which was sustained for at least 5 weeks. Moreover, both standard and long-read next generation sequencing confirmed the presence of gene-inactivating deletions at LPA transgene loci. Overall, this study serves as a proof-of-concept for using TALEN-mediated gene editing to disrupt LPA in vivo, paving the way for the development of a feasible gene editing therapy for patients with high Lp(a).

Reduction of triglyceride-rich lipoproteins with retatrutide in type 2 diabetes may be explained by concurrent reduction in ANGPTL3/8 levels

Abstract Background/Introduction In the recent phase 2 study (NCT04867785) in patients with type 2 diabetes (T2D), retatrutide, an agonist of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon receptors, reduced triglycerides (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) up to 35.0% and 20.7%, respectively. The angiopoietin-like 3/8 complex (ANGPTL3/8) is the most potent circulating inhibitor of lipoprotein lipase (LPL), and its serum levels have been shown to be directly correlated with TG and low-density lipoprotein cholesterol (LDL-C). Purpose In the aforementioned phase 2 study, we examined the effects of retatrutide on circulating ANGPTL3/8 complex concentrations to help understand the mechanism by which retatrutide reduced TG and non-HDL-C. Methods Patients with T2D were randomly assigned to receive once-weekly injections of placebo, 1.5 mg dulaglutide, or retatrutide doses of 0.5 mg, 4 mg, 8 mg, or 12 mg. Fasting serum samples were collected at baseline, week 2, week 4, week 8, week 12, week 16, and week 24, and ANGPTL3/8 levels were measured at all time points using a sensitive and selective immunoassay. Plasma PCSK9 levels were also measured at baseline and 24 weeks. Data were analyzed using a mixed model for repeated measures with log-transformation. Results Baseline ANGPTL3/8 levels (mean 26.3 ng/mL, IQR 17.4-33.0 ng/mL) were not different among all study groups. Mean percent changes of ANGPTL3/8 from baseline at week 24 were -1.3%, -12.0%, -48.7% and -51.0% in 0.5 mg, 4 mg, 8 mg and 12 mg retatrutide groups, respectively (Figure). Percent changes of ANGPTL3/8 in 8 mg and 12 mg retatrutide groups were significantly different from placebo group (p &amp;lt; 0.0001). Mean percent changes of PCSK9 levels from baseline to 24 weeks were not different from placebo for any treatment arm (+6.2%, -3.9%, -3.8% and -9.6% for retatrutide 0.5 mg, 4 mg, 8 mg and 12 mg groups, respectively, and -1.5% for dulaglutide and -6.5% for placebo). Conclusions In patients with T2D, retatrutide dose-dependently decreased serum concentrations of ANGPTL3/8, the most potent circulating LPL inhibitor. These data suggest that retatrutide may reduce TG-rich lipoproteins by decreasing ANGPTL3/8 levels.

Reversal of Atherosclerotic Plaque Growth and Vulnerability: Effects of Lipid-Modifying and Anti-Inflammatory Therapeutic Agents.

Atherosclerotic plaque development constitutes the primary substrate of coronary artery disease (CAD) and is the outcome of an intricate process involving endothelial damage, inflammation, and lipid retention. The clinical efficacy of many lipid-lowering therapies in patients with CAD has been well established. Over the past few decades, a substantial and significant advance regarding the use of invasive and non-invasive imaging modalities has been observed. Numerous studies have been conducted using these imaging techniques and have investigated the changes in morphology (e.g., atheroma volume) and composition (e.g., lipid burden, fibrous cap thickness, macrophage accumulation) at the plaque level that explain the improved clinical outcomes by various pharmacological interventions. Lipid-lowering agents, such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, demonstrate direct effects on plaque volume and composition that enhance plaque stabilization and/or regression beyond the reduction of low-density lipoproteins. An increasing amount of clinical research is also focused on the role of inflammation in plaque vulnerability and future adverse cardiac events. Consequently, there is a pressing need to explore therapeutic strategies that are capable of disrupting the inflammatory response as well as reducing atheroma burden and modifying high-risk plaque characteristics. This review provides a comprehensive analysis of the current evidence regarding the effects of traditional and novel therapeutic strategies targeting modification of the lipid profile and inflammatory processes on reversing plaque growth and attenuating vulnerable features, thereby promoting plaque stabilization and passivation.

Role of Lipoprotein(a) Reduction in Cardiovascular Disease.

Recent studies have shown that lipoprotein(a) (Lp(a)) is an important risk factor for a plethora of different cardiovascular diseases. It has been proven that Lp(a) levels are genetically determined and correlate with risk of cardiovascular disease, independent of lifestyle factors. As of yet, treatment options to reduce Lp(a) levels are limited, but new research into Lp(a) reduction yields promising results. This review delves into Lp(a)'s biochemistry and mechanism of effect, the association between Lp(a) and cardiovascular diseases, and possible therapies to minimise cardiovascular disease.

Dynamics of Blood Lipids Before, During, and After Diurnal Fasting in Inactive Men: Quasi-Experimental Study.

There is a lack of investigation into the dynamics of blood lipids before, during, and after diurnal fasting, especially in inactive men. This study determined dynamic changes in blood lipids in inactive men before, during, and after they underwent diurnal fasting. A total of 44 young men aged a mean 27.6 (SD 5.8) years were recruited to evaluate their habitual physical activity and diet using a questionnaire developed for this study. Body composition was evaluated using a bioelectrical impedance analysis machine (Tanita BC-980). An 8-ml blood sample was collected to evaluate blood lipids and glucose. All measurements were taken 2-3 days before Ramadan, during Ramadan (at week 2 and week 3), and 1 month after Ramadan. A 1-way repeated measures ANOVA was used to compare the measured variables before, during, and after the month of Ramadan. When a significant difference was found, post hoc testing was used. Differences were considered significant at P<.05. There was a significant reduction in low-density lipoprotein during Ramadan compared to before and after Ramadan (83.49 mg/dl at week 3 vs 93.11 mg/dl before Ramadan [P=.02] and 101.59 mg/dl after Ramadan [P=.007]). There were significant elevations in fasting blood glucose (74.60 mmol/L before Ramadan vs 81.52 mmol/L at week 3 [P=.03] and 86.51 mmol/L after Ramadan [P=.01]) and blood pressure (109 mm Hg before Ramadan vs 114 mm Hg after Ramadan; P=.02) reported during and even after the month of Ramadan, although both fasting blood glucose and blood pressure were within normal levels. Ramadan fasting could be an independent factor in reducing low-density lipoprotein. Further investigations are encouraged to clarify the impact of diurnal fasting on blood lipids in people with special conditions.

Effects of metformin and curcumin in women with polycystic ovary syndrome: A factorial clinical trial

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder in women, associated with dyslipidemia, insulin resistance, and hormonal imbalances. Metformin and curcumin have shown promise in improving these metabolic and hormonal parameters individually, but their combined effects in PCOS remain unclear. MethodsWe conducted a randomized, double-blind, placebo-controlled, 12-week factorial trial involving 200 women with PCOS. Participants were randomly assigned in a 1:1:1:1 ratio to receive metformin (500-mg/8 h) + placebo, nanocurcumin soft gel capsule (80-mg/8 h) + placebo, metformin (500-mg/8 h) + nanocurcumin (80-mg/8 h), or double placebo. Lipid profiles, glucose metabolism markers, hormonal parameters, body weight, and body mass index (BMI) were assessed at baseline and week 12. ResultsThe combination of metformin and curcumin demonstrated significant improvements in lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI compared to individual agents or placebo. Greater reductions in low-density lipoproteins (LDL) cholesterol, total cholesterol (TC), and triglyceride (TG) levels were observed with the combination therapy, along with increased high-density lipoproteins (HDL) cholesterol. Additionally, the combination therapy significantly improved markers of glucose metabolism and showed synergistic effects in reducing body weight and BMI. Reductions in testosterone and improvements in Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) levels were also observed with combination therapy. ConclusionThe combination of metformin and curcumin demonstrates superior efficacy in improving lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI in women with PCOS compared to individual agents or placebo. This highlights the potential synergistic effects of combining these agents for the management of PCOS.

Ethanolic Extract Clove-loaded Chitosan Nanoparticles Reduce Dyslipidemia, Enhance Liver and Kidney Functions, and Improve the Antioxidant System in Obese Rats

Background: Obesity, a chronic low-grade inflammatory disease characterized by multiple metabolic dysfunctions, poses a considerable worldwide health risk to adults and children. Clove has also shown that it possesses anti-inflammatory, anti-fungal, antibacterial, antioxidant, antiglycation, and anti-aging properties. Aim: The current study aimed to investigate the antiobesity effect of clove-loaded chitosan nanoparticles in obese rats. objective: The current study investigated the antiobesity effect of clove-loaded chitosan nanoparticles in obese rats. Method: Obesity is induced in rats by the administration of a High-Fat Diet (HFD) for 4 weeks. 24 rats were divided into 4 groups; Control group, in which rats were fed normal; HDF group, in which rats were HFD along with distilled water; HFD + empty nanoparticles (ENPs), in which rats were HFD along with ENPs (45 mg/kg); and HFD + clove nanoparticles (CNPs), in which rats were HFD along with CNPs (45 mg/kg) for four weeks. Results: Administration of ENPs and CNPs led to a notable reduction in glucose, aminotransferases, alkaline phosphatase, cholesterol, triglycerides, low-density lipoproteins, malondialdehyde, nitric oxide, caspase-3, PCNA, leptin, and DNA fragmentation. Additionally, it promoted an increase in total proteins, albumin, high-density lipoprotein, glutathione, catalase, and adiponectin. Also, the histopathological investigation of the liver and kidney showed the protective effect of ENPs and CNPs on the tissues of obese rats. Conclusion: The present investigation elucidated the preventive effects of chitosan nanoparticles loaded with clove on dyslipidemia in obese rats. Clove nanoparticles exhibited hypolipidemia, antioxidant, hypoglycemia, and hepatoprotective activities.

Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder characterized by excessive hepatic fat accumulation without alcohol intake. It can progress to non-alcoholic steatohepatitis, increasing the risk of cirrhosis and liver failure. This study aims to evaluate the efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in treating NAFLD. A systematic review and meta-analysis was conducted including studies published from January 2018 to June 2023. Databases searched included PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Inclusion criteria comprised randomized controlled trials and cohort studies involving human subjects or animal models with NAFLD. Data were extracted and analyzed to assess the impact of omega-3 PUFAs on liver fat, hepatic enzymes, and serum lipid profiles using RevMan 5.4. A total of 15 studies met the inclusion criteria. Omega-3 supplementation significantly decreased alanine aminotransferase (ALT) (mean difference = -2.12, 95% confidence interval (CI) = -3.36, -0.87) and aspartate aminotransferase (AST) (mean difference = -1.50, 95% CI = -2.59, -0.42). Gamma-glutamyl transferase levels showed a trend toward reduction (mean difference = -0.82, 95% CI = -1.66, 0.02). Serum lipid profiles improved significantly with reductions in triglycerides, low-density lipoprotein, and total cholesterol along with significant reductions in AST, ALT, and alkaline phosphatase in animal models. Omega-3 PUFAs appear to offer beneficial effects on liver enzymes, serum lipid profiles, and anthropometric indices in NAFLD patients. While their impact on liver fat content remains uncertain, omega-3 supplementation could serve as a valuable adjunct treatment for enhancing metabolic profiles and liver function in NAFLD patients.

Efficacy and safety of Resmetirom, a selective thyroid hormone receptor-β agonist, in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD): a systematic review and meta-analysis

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health problem owing to its high prevalence and associated morbidity and mortality secondary to progressive liver disease and cardiovascular events. Resmetirom, a selective thyroid hormone receptor-β agonist has been developed as a therapeutic modality for MASLD. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of resmetirom compared to a placebo in the treatment of MASLD. Eligible studies were systematically identified by screening PubMed, Scopus, Web of Science, Cochrane library, Embase, and ClinicalTrials.gov from 2014 to 2024. Only randomized controlled trials comparing the efficacy and safety of resmetirom in the treatment of MASLD against placebo were included in the analysis. Meta-analysis was performed using RevMan 5.4 software. Four studies with low risk of bias and involving a total of 2359 participants were identified. The metanalysis included only three clinical trials with 2234 participants. A significant reduction in MRI-proton density fat fraction (MRI-PDFF) with 80 mg Resmetirom compared to that with placebo [SMD − 27.74 (95% CI − 32.05 to − 32.42), p < 0.00001] at 36–52 weeks as well as at 12–16 weeks [SMD − 30.92 (95% CI − 36.44 to − 25.40), p < 0.00001]. With Resmetirom 100 mg dose at 36–52 weeks [SMD − 36.05 (95% CI − 40.67 to − 31.43), p < 0.00001] and 12–16 weeks [SMD − 36.89 (95% CI − 40.73 to − 33.05), p < 0.00001] were observed. Resmetirom treatment was associated with a significant reduction in LDL-c triglyceride, lipoproteins. and liver enzymes. There was significant reduction FT4 and increase in SHBG and sex steroids with Resmetirom compared to placebo. There was no major difference in the overall treatment emergent adverse events at 80 mg [OR 1.55 (95% CI 0.84 to 2.87), and 100 mg [OR 1.13 (95% CI 0.78 to 1.63), doses of Resmetirom compared to placebo. However, gastrointestinal adverse events diarrhoea and nausea occurred in ≥ 10% in the Resmetirom group compared to placebo at < 12 week. Resmetirom treatment showed modest efficacy in treating MASLD with reduction in MRI-PDFF, LDL-c, triglyceride, lipoproteins, liver enzymes and NASH biomarkers without significant safety concerns. Larger and long-term RCTs may further confirm this promising outcomes of Resmetirom use in MASLD.

RNA interference therapy in cardiology: will new targets improve therapeutic goals?

The discovery of RNA interference in 1998 opened avenues for the manipulation of gene expression, leading to the development of small interfering RNA (siRNA) drugs. Patisiran, the first FDA-approved siRNA medication, targets hereditary transthyretin amyloidosis with polyneuropathy. Givosiran, lumasiran and nedosiran further expand siRNA applications in treating rare genetic diseases, demonstrating positive outcomes. In cardiology, inclisiran, approved for hypercholesterolaemia, showcases sustained reductions in LDL cholesterol levels. However, ongoing research aims to establish its impact on cardiovascular outcomes. Lipoprotein(a), an independent risk factor for atherosclerotic cardiovascular disease, has become a focus of siRNA therapies, precipitating the development of specific siRNA drugs like olpasiran, zerlasiran and lepodisiran, with promising reductions in lipoprotein(a) levels. Research to assess the effectiveness of these medications in reducing events is currently under way. Zodasiran and plozasiran address potential risk factors for cardiovascular diseases, targeting triglyceride-rich lipoproteins. Zilebesiran, which targets hepatic angiotensinogen mRNA, has demonstrated a dose-related reduction in serum angiotensinogen levels, thereby lowering blood pressure in patients with systemic arterial hypertension. The evolving siRNA methodology presents a promising future in cardiology, with ongoing studies assessing its effectiveness in various conditions. In the future, larger studies will provide insights into improvements in cardiovascular outcomes, long-term safety and broader applications in the general population. This review highlights the historical timeline of the development of siRNA-based drugs, their clinical indications, potential side-effects and future perspectives.

Zodasiran silences hepatic ANGPTL3 leading to deep and durable reductions in atherogenic lipids and lipoproteins in mixed dyslipidemia patients: Final results from arches-2, double-blind period

Zodasiran silences hepatic ANGPTL3 leading to deep and durable reductions in atherogenic lipids and lipoproteins in mixed dyslipidemia patients: Final results from arches-2, double-blind period