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Background and Objectives: Lowering low-density lipoprotein (LDL-C) levels is critical for preventing atherosclerotic cardiovascular disease, yet some patients fail to reach the LDL-C targets despite available intensive lipid-lowering therapies. This study assessed the effectiveness and safety profile of alirocumab, evolocumab, and inclisiran in lipid reduction. Materials and Methods: A cohort of 51 patients (median (Q1–Q3) age: 49.0 (39.5–57.5) years) was analyzed. Eligibility included an LDL-C level > 2.5 mmol/L while on the maximum tolerated dose of statin and ezetimibe, a diagnosis of familial hypercholesterolemia, or a very high risk of cardiovascular diseases following myocardial infarction within 12 months prior to the study. Follow-ups and lab assessments were conducted at baseline (51 patients), 3 months (51 patients), and 15 months (26 patients) after the treatment initiation. Results: Median initial LDL-C levels 4.1 (2.9–5.0) mmol/L, decreasing significantly to 1.1 (0.9–1.6) mmol/L at 3 months and 1.0 (0.7–1.8) mmol/L at 15 months (p < 0.001). Total cholesterol also reduced significantly compared to baseline at both intervals (p < 0.001). No substantial differences in LDL-C or total cholesterol levels were observed between 3- and 15-month observations (p > 0.05). No statistically significant differences were noted in cholesterol reduction among the alirocumab, evolocumab, and inclisiran groups at 3 months. The safety profile was favorable, with no reported adverse cardiovascular events or significant changes in alanine transaminase, creatinine, or creatine kinase levels. Conclusions: Alirocumab, evolocumab, and inclisiran notably decreased LDL-C and total cholesterol levels without significant adverse effects, underscoring their potential as effective treatments in patients who do not achieve lipid targets with conventional therapies. [ABSTRACT FROM AUTHOR]

The clinical efficacy of adrenergic β-receptor (β-AR) blockers in significantly stabilizing atherosclerotic plaques has been extensively supported by evidencebased medical research; however, the underlying mechanism remains unclear. Recent findings have highlighted the impact of lipid-induced aberrant polarization of macrophages during normal inflammatory-repair and regenerative processes on atherosclerosis formation and progression. In this review, we explore the relationship between macrophage polarization and atherosclerosis, as well as the influence of β-AR blockers on macrophage polarization. Based on the robust evidence supporting the use of β-AR blockers for treating atherosclerosis, we propose that their main mechanism involves inhibiting monocyte-derived macrophage differentiation towards an M2-like phenotype. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with acute coronary syndrome (ACS) represent a vulnerable population. We aimed to investigate serum lipid levels of patients with ACS upon admission and during one year of the COVID-19 pandemic in a rural county hospital, and compared these findings with the data of patients with ACS in 2015 and 2017. The secondary aim of this paper was the comparison of the LDL-C values calculated with the Friedewald and Martin–Hopkins methods. Methods: A retrospective analysis of lipid-lowering data of patients treated with ACS in 2015, 2017 and in a COVID-19 year (1 April 2020–31 March 2021) was performed; the patient's numbers were 454, 513 and 531, respectively. Results: In the COVID-19 period one year after the index event, only 42% of the patients had lipid values available, while these ratios were 54% and 73% in 2017 and in 2015, respectively. Using the Friedewald formula, in the COVID-19 era the median of LDL cholesterol (LDL-F) was 1.64 (1.09–2.30) mmol/L at six months and 1.60 (1.19–2.27) mmol/L at one year, respectively. These values were 1.92 (1.33–2.27) mmol/L and 1.73 (1.36–2.43) mmol/L using the Martin–Hopkins method (LDL-MH). The LDL-F yielded significantly lower values (15% lower at six months, p = 0.044; and 8% lower at one year, p = 0.014). The LDL-F reached the previous target of 1.8 mmol/L during the COVID-19 pandemic 36% at one year vs. 48% in 2017, and 37% in 2015. The recent target LDL-C level of 1.4 mmol/L was achieved in 22% of cases in the COVID-19 pandemic, 16% in 2015 and 19% in 2017. Conclusions: A significantly lower proportion of patients with ACS had available lipid tests during the COVID-19 pandemic. Besides the lower number of available samples, the proportion of achieved 1.4 mmol/L LDL-C target lipids was stable. More rigorous outpatient care in the follow-up period may help to improve the quality of lipid lowering treatments and subsequent secondary cardiovascular prevention. If direct LDL-C determination is not available, we prefer the LDL calculation with the Martin–Hopkins method. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. While both genetic and environmental factors significantly contribute to the pathogenesis of CVDs, recent advancements in genetic technology have further emphasized the significance of genetic factors in CVDs. Growing evidence suggests genetic changes as a primary cause of CVDs and their susceptibility. The major genetic changes include chromosomal aneuploidy, abnormal chromosomal structure, and single gene mutations. Copy number variation (CNV) is a type of newly introduced structural change that influences the copy number of a genome region. CNVs could manifest with more severe phenotypes compared to single‐nucleotide polymorphism (SNP) as they affect a considerably larger segment of the genome. Additionally, for the same reason, CNVs tend to manifest earlier in life compared to SNP. Recent studies have demonstrated the fundamental role of CNVs in the development or susceptibility to cardiovascular disorders. However, it remains to be determined which CVDs should prompt CNV tests in clinical practice. In this review, we discussed the extent to which CNV could take part in CVDs and further hypothesized that testing for CNV might be most beneficial for selective patients with CVDs. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke—both standardized in their characteristic polyphenolic fractions—could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic fatty liver disease (NAFLD) in 90 healthy individuals with suboptimal cholesterol levels. Participants were randomly allocated to treatment with a pill of either active treatment or placebo. After 6 weeks, the active-treated group experienced significant improvements in levels of triglycerides (TG), apolipoprotein B-100 (Apo B-100), and apolipoprotein AI (Apo AI) versus baseline. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (Non-HDL-C), and hs-CRP also significantly decreased in the active-treated group compared to both baseline and placebo. At the 12-week follow-up, individuals allocated to the combined nutraceutical experienced a significant improvement in TC, LDL-C, Non-HDL-C, TG, Apo B-100, Apo AI, glucose, alanine transaminase (ALT), gamma-glutamyl transferase (gGT), hs-CRP, several indexes of NAFLD, and brachial pulse volume (PV) in comparison with baseline. Improvements in TC, LDL-C, Non-HDL-C, TG, fatty liver index (FLI), hs-CRP, and endothelial reactivity were also detected compared to placebo (p < 0.05 for all). Overall, these findings support the use of the tested dietary supplement containing dry extracts of bergamot and artichoke as a safe and effective approach for the prevention and management of a broad spectrum of cardiometabolic disorders. [ABSTRACT FROM AUTHOR]

This article explores the potential for personalized cardiovascular disease management in patients with acute myocardial infarction by measuring lipoprotein (a) [Lp(a)]. Lp(a) is found to be more atherogenic than low-density lipoprotein (LDL) and is associated with atherosclerotic cardiovascular disease. The article presents a case study of a high-risk patient with acute myocardial infarction and how Lp(a) measurement allowed for personalized lipid-lowering therapy. It emphasizes the need for repeated measurements due to the variability in Lp(a) concentrations. The article provides recommendations for diagnosing and managing elevated Lp(a) levels, including lifestyle changes and drug interventions. It suggests considering a combination of a lower-dose statin and ezetimibe for high-risk patients. The text also discusses the potential benefits of combination therapy and the use of PCSK9 modulators in patients with high Lp(a) levels. It concludes by mentioning ongoing research on targeted Lp(a)-lowering therapies. [Extracted from the article]

Chronic hepatitis B (CHB) poses treatment challenges, with treatment response and disease outcome often determined by the immune response, particularly mononuclear phagocytes. Monocytes can differentiate into various subpopulations influenced by AHR. Statins, known for inflammation modulation, may impact monocyte function via AHR activation. This study explored rosuvastatin (RSV)'s effects on monocyte subtypes, inflammatory markers, and AHR in CHB patients. Fifteen CHB patients were randomly assigned to receive either 20 mg RSV or a placebo daily for three months. Flow cytometry assessed CD14+ CD16− (classical), CD14+ CD16+ (intermediate), and CD14dim CD16+ (patrolling) monocyte subtypes, along with AHR levels in each subset. ELISA quantified cytokines IL-6, IFN-γ, IL-12, IL-10, TNF-α, TGF-β, and IL-1β. RSV expanded CD14+ CD16− classical and reduced CD14+ CD16+ intermediate monocytes in CHB patients while increasing AHR+ cell percentages in all subsets. RSV treatment upregulated key AHR target genes (Cyp1a1, Cyp1b1, and ARNT), indicating robust AHR signaling activation. It also reduced pro-inflammatory cytokine levels (IL-6, IFNγ, IL-12, TNF-α) and elevated anti-inflammatory cytokines (IL-10, TGF-β). Thus, RSV may modulate the immune response by altering monocyte subtypes in CHB patients via AHR activation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases accompanying metabolic syndrome comprise one of the leading causes of death worldwide. The medical community undertakes attempts to improve treatment options and minimize cardiovascular diseases' numerous consequences and exacerbations. In parallel with pharmacotherapies provided by physicians, nutritionists are developing strategies for diet therapy and prevention based on lifestyle changes, with high success rates. Consumption of specified food compounds included in various products with proven protective properties can be helpful in this regard. Due to the wide possibilities of diet in metabolic health promotion, it seems necessary to systematize information about the metabolically protective and cardioprotective properties of fiber, probiotic bacteria, plant sterols, folic acid, vitamins B12, C, and E, PUFAs, lycopene, polyphenols, arginine, CoQ10, and allicin. The aim of this review was to present the food compounds with potential use in cardiometabolic prevention and diet therapy based on the latest available literature. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a significant global health burden that necessitates the exploration of effective and accessible therapeutic options. Phytotherapy has played a vital role in healthcare, with plant extracts being integral to traditional medicinal practices. The therapeutic potential of Hibiscus syriacus (Rose of Sharon), a plant with a rich ethnobotanical history, in the management of DM and its associated complications was investigated. In this study, the therapeutic potential of Hibiscus syriacus L. extract (HSE) against DM in streptozotocin (STZ)-induced diabetic rats was assessed, focusing on its effects on glucose regulation, antioxidative defense, and liver protection. The administration of the HSE extract substantially reduced hyperglycemia and increased insulin production, with concurrent improvements in body weight and hydration. The enhanced activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), suggests reduced oxidative stress, which is further supported by molecular docking results with the 3GTV superoxide dismutase enzyme, showing a binding energy of −6.3 kcal/mol. A decrease in MDA levels also indicates a reduction in oxidative stress. Notably, HSE treatment led to decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and improved lipid profiles, indicating its hepatoprotective and lipid-modifying benefits. These findings support the inclusion of HSE as an adjunctive therapy in DM management strategies. This study promotes the consideration of Hibiscus syriacus L. therapeutic properties in global health contexts. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of the present study was to determine changes of biochemical risk factors of thromboembolism especially of TFPI during the use of oral versus transdermal administration of early estrogen replacement therapy., Methods: In a 12-week prospective, randomized, cross-over trial, oestradiol was administered orally in a dose of 2 mg daily or transdermally in an equivalent dose of 0.05 mg daily. Forty-five healthy early postmenopausal women were included into the study within 12 weeks after the hysterectomy and ovariectomy (surgical castration). Forty-one women completed the study and their data were analyzed. The average age was of 49+/- 6 years., Results: After an oral therapy, the average value of TFPI decreased significantly (p < 0.0001) from 87.5 +/- 38.5 ng/ml to 68 +/- 37 ng/ml but remained stable in transdermal group (81.9 +/- 36.8 ng/ml). No significant changes occurred in D-dimers. In both groups AT-III and fibrinogen decreased without exceeding their physiological ranges., Conclusions: The oral therapy reduced significantly TFPI levels compared to transdermal route of administration. The results confirm more pronounced impact of oral estrogen on hemostasis variables.

Background: The importance of an apolipoprotein AV (apoAV) gene for plasma triglyceride (TG) level determination has been shown on transgenic and knockout mice. The influence of apoAV polymorphisms (T-1131/C and Ser19/Trp) on plasma TG levels was evaluated in a representative sample of 1191 men and 1368 women, in 435 patients with myocardial infarction (MI) and in 83 individuals with extreme TG levels (20.4+/-12.8 mmol/L)., Methods: ApoAV variants were analyzed using polymerase chain reaction and restriction analysis., Results: T-1131/C variation in the apoAV gene affects plasma TG levels, showing a higher level in C-1131 carriers than in T/T-1131 homozygotes. This association has been observed both in men (P<0.05) and in women (P<0.01). TG levels were also influenced by the Ser19/Trp apoAV genotypes. In both males and females, the Trp19 carriers have higher plasma TGs (P<0.01) than do Ser19 homozygotes. In hypertriglyceridemic patients, the frequency of carriers of the T/C-1131 and C/C-1131 genotypes (32.5% versus 15.4%, P<0.0001) and Ser/Trp19 and Trp/Trp19 genotypes (30.1% versus 14.1%, P<0.0001) was much higher than in the population sample. In a group of MI patients (n=435), the frequency of the disadvantageous homozygous genotypes, with their effect of increasing the TG concentration (C/C-1131 and/or Trp/Trp19), was significantly higher than in the population sample (7.4% versus 2.0%, P<0.00001)., Conclusion: Variation(s) in the apoAV gene play an important role in the genetic determination of plasma TG levels and influence the risk of MI.

We should also always remember about the nocebo effect or more correctly called the drucebo effect (as it is directly linked to statin therapy) - the psychological attitude that adverse effects after statins will certainly appear [[14], [16]]. Introducing the "Drucebo" effect in statin therapy: A systematic review of studies comparing reported rates of statin-associated muscle symptoms, under blinded and open-label conditions. Lipid disorders are the most common risk factors of cardiovascular disease (CVD) [[1]] and, more importantly, the worst monitored and controlled, with only a third of patients being on the low-density lipoprotein cholesterol (LDL-C) target in Europe [[2]], and only 24% in the Central and Eastern European (CEE) countries [[3]]. One of the reasons of this ineffectiveness is therapy non-adherence, and the most important reason for non-adherence is statin-associated side effects, mainly including statin-associated muscle symptoms (SAMS) that is generally called statin intolerance (SI) [[7]]. [Extracted from the article]

LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 in cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation of LY86 mRNA in atherosclerosis; nevertheless, the regulatory mechanism by which LY86 is involved in this disease remains unclear. In this study, we aimed to investigate whether LY86 affects ox-LDL-induced lipid accumulation in macrophages. Firstly, we confirmed that LY86 is indeed involved in the process of atherosclerosis and found high expression levels of LY86 in human atherosclerotic plaque tissue. Furthermore, our findings suggest that LY86 may mediate intracellular lipid accumulation induced by ox-LDL through the SREBP2/HMGCR pathway. This mechanism could be associated with increased cholesterol synthesis resulting from enhanced endoplasmic reticulum stress response. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to identify the relationship between coenzyme Q 10 (CoQ10)-related gene polymorphisms and statin-related myotoxicity (SRM). Methods: We retrospectively analyzed prospectively collected samples from February to May 2021. To investigate the association between CoQ10-related genetic factors and SRM, we selected 37 single nucleotide polymorphisms from five genes (COQ2, COQ3, COQ5, COQ6, and COQ7). The odds ratio (OR) and adjusted OR with 95% confidence intervals (CI) were calculated for univariate and multivariable logistic regression analyses, respectively. Results: A total of 688 stroke patients were included in the analysis, including 56 SRM cases. In the multivariable analysis, two models were constructed using demographic factors only in model I, and demographic and genetic factors in model II. Compared to other statins, atorvastatin decreased the SRM risk whereas ezetimibe use increased the SRM risk in model I and model II. Patients with COQ2 rs4693075 G allele, COQ3 rs11548336 TT genotype, and COQ5 rs10849757 A allele had a 2.9-fold (95% CI: 1.6--5.3), 1.9-fold (95% CI: 1.1--3.5), and 3.3-fold (95% CI: 1.5--8.3) higher risk of SRM, respectively. Conclusion: This study could be utilized to develop a personalized medicine strategy in patients treated with statins. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) stands as the leading cause of mortality worldwide. At its core lies a progressive process of atherosclerosis, influenced by multiple factors. Among them, lifestyle-related factors are highlighted, with inadequate diet being one of the foremost, alongside factors such as cigarette smoking, low physical activity, and sleep deprivation. Another substantial group of risk factors comprises comorbidities. Amongst others, conditions such as hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), or familial hypercholesterolemia (FH) are included here. Extremely significant in the context of halting progression is counteracting the mentioned risk factors, including through treatment of the underlying disease. What is more, in recent years, there has been increasing attention paid to perceiving atherosclerosis as an inflammation-related disease. Consequently, efforts are directed towards exploring new anti-inflammatory medications to limit ASCVD progression. Simultaneously, research is underway to identify biomarkers capable of providing insights into the ongoing process of atherosclerotic plaque formation. The aim of this study is to provide a broader perspective on ASCVD, particularly focusing on its characteristics, traditional and novel treatment methods, and biomarkers that can facilitate its early detection. [ABSTRACT FROM AUTHOR]

Long-term exposure to even slightly elevated plasma cholesterol levels significantly increases the risk of developing cardiovascular disease. The latest evidence recommends an improvement in plasma lipid levels, even in children who are not affected by severe hypercholesterolemia. The risk–benefit profile of pharmacological treatments in pediatric patients with moderate dyslipidemia is uncertain, and several cholesterol-lowering nutraceuticals have been recently tested. In this context, the available randomized clinical trials are small, short-term and mainly tested different types of fibers, plant sterols/stanols, standardized extracts of red yeast rice, polyunsaturated fatty acids, soy derivatives, and some probiotics. In children with dyslipidemia, nutraceuticals can improve lipid profile in the context of an adequate, well-balanced diet combined with regular physical activity. Of course, they should not be considered an alternative to conventional lipid-lowering drugs when necessary. [ABSTRACT FROM AUTHOR]

Cell stiffness is regulated by dynamic interaction between ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1) proteins, besides other biochemical and molecular regulators. In this study, we investigated how the Placental Growth Factor (PlGF) changes endometrial mechanics by modifying the actin cytoskeleton at the maternal interface. We explored the global effects of PlGF in endometrial stromal cells (EnSCs) using the concerted approach of proteomics, atomic force microscopy (AFM), and electrical impedance spectroscopy (EIS). Proteomic analysis shows PlGF upregulated RhoGTPases activating proteins and extracellular matrix organization-associated proteins in EnSCs. Rac1 and PAK1 transcript levels, activity, and actin polymerization were significantly increased with PlGF treatment. AFM further revealed an increase in cell stiffness with PlGF treatment. The additive effect of PlGF on actin polymerization was suppressed with siRNA-mediated inhibition of Rac1, PAK1, and WAVE2. Interestingly, the increase in cell stiffness by PlGF treatment was pharmacologically reversed with pravastatin, resulting in improved trophoblast cell invasion. Taken together, aberrant PlGF levels in the endometrium can contribute to an altered pre-pregnancy maternal microenvironment and offer a unifying explanation for the pathological changes observed in conditions such as pre-eclampsia (PE). High levels of placental growth factor can result in a stiffer microenvironment milieu impeding trophoblast invasion of endometrial cells prior to pregnancy, providing insight into the pathogenesis of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Over several decades, the approach to treating dyslipidaemias during pregnancy remains essentially unchanged. The lack of advancement in this field is mostly related to the fact that we lack clinical trials of pregnant patients both with available as well as new therapies. While there are numerous novel therapies developed for non-pregnant patients, there are still many limitations in dyslipidaemia treatment during pregnancy. Besides pharmacotherapy and careful clinical assessment, the initiation of behavioural modifications as well as pre-conception management is very important. Among the various lipid-lowering medications, bile acid sequestrants are the only ones officially approved for treating dyslipidaemia in pregnancy. Ezetimibe and fenofibrate can be considered if their benefits outweigh potential risks. Statins are still considered contraindicated, primarily due to animal studies and human case reports. However, recent systematic reviews and meta-analyses as well as data on familial hypercholesterolaemia (FH) in pregnant patients have indicated that their use may not be harmful and could even be beneficial in certain selected cases. This is especially relevant for pregnant patients at very high cardiovascular risk, such as those who have already experienced an acute cardiovascular event or have homozygous or severe forms of heterozygous FH. In these cases, the decision to continue therapy during pregnancy should weigh the potential risks of discontinuation. Bempedoic acid, olezarsen, evinacumab, evolocumab and alirocumab, and inclisiran are options to consider just before and after pregnancy is completed. In conclusion, decisions regarding lipid-lowering therapy for pregnant patients should be personalized. Despite the challenges in designing and conducting studies in pregnant women, there is a strong need to establish the safety and efficacy of dyslipidaemia treatment during pregnancy. [ABSTRACT FROM AUTHOR]

Familial Hypercholesterolemia (FH) is a hereditary disorder characterised by elevated blood cholesterol levels, predominantly Low-density Lipoprotein Cholesterol (LDL-C). This condition poses a significant risk for early-onset atherosclerotic cardiovascular diseases. A critical step toward effective clinical management is the precise identification of pathogenic variants responsible for FH. The present study aimed to unravel the genetic cause of FH through comprehensive variant effect prediction and comparison with clinical manifestations in a nine-year-old girl with hyperlipidemia. Whole Exome Sequencing (WES) was performed on the proband, and a set of three key genes associated with hyperlipidemia {Apolipoprotein E (APOE), Low -density Lipoprotein Receptors (LDLR), Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9)} were evaluated for the presence of pathogenic mutations. The data were meticulously analysed based on the American College of Medical Genetics (ACMG) guidelines for variant classification. The analysis revealed two pathogenic variations in the LDLR gene: c.1A>C (p.Met1Leu) in exon 1 and a splice site variant c.1187-10G>A in intron 8. Sanger sequencing of family members confirmed the presence of one mutation each in the father and mother, while a younger sibling also carried both pathogenic variants. Genetic testing confirmed Heterozygous FH (HeFH) in the parents and Homozygous FH (HoFH) in both siblings. Proper classification of genetic variants is crucial for informed clinical decision-making and patient management. The study provides valuable insights into the molecular basis of FH in an Indian patient and contributes to the growing knowledge of the LDLR gene mutation spectrum. [ABSTRACT FROM AUTHOR]

Refractory hypercholesterolemia (RH) is characterized by the failure of patients to achieve therapeutic targets for low-density lipoprotein-cholesterol (LDL-C) despite receiving maximal tolerable doses of standard lipid-lowering treatments. It predominantly impacts individuals with familial hypercholesterolemia (FH), thereby elevating the risk of cardiovascular complications. The prevalence of RH is now recognized to be substantially greater than previously thought. This review provides a comprehensive insight into current and emerging therapies for RH patients, including groundbreaking genetic-based therapeutic approaches. The review places emphasis on the dependency of therapies on low-density lipoprotein receptors (LDLRs) and highlights the critical role of considering LDLR activity in RH patients for individualization of the treatment. Refractory hypercholesterolemia (RH) is a condition where patients are unable to get below target levels of 'bad' cholesterol despite receiving maximum doses of standard treatments. It is commonly present in those with a genetic disorder, called familial hypercholesterolemia (FH), known to increase the risk of heart complications. RH's prevalence is now understood to be higher than previously believed and this review offers insights into current and emerging therapies for RH, including genetic-based treatments. It stresses the importance of the mechanistic pathways behind cholesterol clearance, particularly low-density lipoprotein receptor (LDLR) activity, in RH treatment customization. Article highlights Refractory hypercholesterolemia – definition, epidemiological data. Therapeutic targets for the treatment of refractory hypercholesterolemiaLow-density lipoprotein receptor (LDLR)-dependent therapies targeting cholesterol production and upregulating LDLR The efficacy of lipid-lowering treatments that depend on low-density lipoprotein receptor (LDLR) activity may be limited in patients with importantly reduced LDLR function, particularly among homozygous familial hypercholesterolemia (HoFH) patients with very low or no residual LDLR activity. 3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) inhibitors (statins) Statins as first-line lipid-lowering drugs, mechanism, efficacy, side effects. Adenosine triphosphate (ATP)-citrate lyase inhibitor Bempedoic acid is a good therapeutic option for statin-intolerant patients. Mechanism of action, efficacy, side effects. PCSK9 inhibitors Review of therapeutic options aimed at PCSK9 inhibition including monoclonal antibodies, siRNA, and therapeutic genome editing. LDLR gene replacement therapy and gene editing strategies Clinical trial of LDLR gene replacement therapy in HoFH, potential of clustered regularly interspaced short palindromic repeats (CRISPR)-based methods. LDLR-independent therapiesAngiopoietin-like 3 inhibition Angiopoietin-like 3 (ANGPTL3) inhibition as a therapeutic target which is LDLR independent. Efficacy of monoclonal antibodies, siRNA, and therapeutic genome editing. MTP inhibition Mechanism of action, efficacy, and side effects of lomitapide. CETP inhibition Drug development history, efficacy, and limitations of use. Inhibition of apolipoprotein B (apoB) formation Mechanism of action, efficacy, and side effects leading to Mipomersen cessation. Cholesterol absorption inhibition: ezetimibe Mechanism of action, efficacy, and side effects of ezetimibe. Agents targeting Lipoprotein (a) (Lp[a]) Atherogenic mechanisms of Lipoprotein (a) (Lp[a]). Lp(a) lowering the potential of currently available drugs. Novel therapies aimed at Lp(a) reduction are available within clinical trials. Combination of therapies Summary of lipid-lowering potential of drug combinations. LDL and Lp(a) apheresis Types of aphereses, indications, limitations of use. High-density lipoprotein (HDL) autotransfusion The efficacy of plasma delipidation system (PDS-2TM) in patients with atherosclerosis, who do not respond adequately to available pharmacological options. Refractory hypercholesterolemia beyond LDL-cholesterol: residual cardiovascular risk associated with remnant cholesterol The role of remnant cholesterol in triglyceride-rich lipoproteins in residual cardiovascular risk and potential therapeutic role of anti-apolipoprotein C-III (APOC3) therapy. Refractory hypercholesterolemia in the pediatric population Summary of available therapeutic options for pediatric population with severe hypercholesterolemia. Conclusion Refractory hypercholesterolemia appears to be a more prevalent condition than might be initially perceived. In terms of its management, it is of particular importance to custom-tailor the appropriate treatment regimen depending on the underlying etiology. The principal determinant for therapy selection should be based on LDL receptor activity. [ABSTRACT FROM AUTHOR]

Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

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Background and aim: Metabolic syndrome is one of the major public-health challenges, affecting one-quarter of the world population. Fatty acid quality indices are novel determinants of this disease and their interactions with genetic factors may have an impact on metabolic syndrome risk. Therefore, we aimed to investigate the interaction between genetic risk score (GRS) and fatty acid quality indices with metabolic syndrome (MetS) among overweight and obese women. Methods: In the present cross-sectional study, 279 overweight and obese women (18–48 years old) were included. Several anthropometric measurements such as weight, height, body mass index (BMI), waist circumference (WC), and body fat percent (BF%) were measured. Also, systolic and diastolic blood pressure (SBP and DBP) were measured. Biochemical determination was performed for fasting blood glucose (FBS), triglyceride (TG), and high-density lipoprotein (HDL). MetS was determined according to National Cholesterol Education Program (NCEP ATP III) criteria. Dietary intake was evaluated by a validated and reliable 147-item semi-quantitative food frequency questionnaire. Cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (ω-6/ω-3) essential fatty acids were considered as fat quality indices. The salting-out method was used to extract the total DNA. The unweighted GRS was calculated using the risk alleles of the three single nucleotide polymorphisms. The total average GRS value was 2 and the sum of the risk alleles of the 3 polymorphisms was 6. Result: The results of our analysis showed that after controlling for age, energy intake, BMI, and physical activity, there was a positive interaction between T2 of GRS and T2 of N6/N3 ratio on WC (β = 7.95, 95%CI = 0.83,15.08, P = 0.029), T3 of GRS and T2 of N6/N3 ratio on DBP (β = 5.93, 95%CI= -0.76,12.63, P = 0.083), and FBS (β = 6.47, 95%CI = 0.59,13.53, P = 0.073), T3 of GRS and T3 of N6/N3 ratio on TG (β = 54.42, 95%CI = 1.76,107.08, P = 0.043), and T3 of GRS and T3 of CSI on BF% (β = 3.55, 95%CI= -0.35,7.45, P = 0.075). Also T2 of GRS in the interaction with T3 of CSI leads to an decrease − 8.35 mg/dl in HDL level after adjustment in (β= -8.35, 95%CI= -17.34,0.62, P = 0.068). Conclusion: It seems the interaction of GRS and fatty acid quality indices is positively associated with several components of metabolic syndrome such as WC, TG and BF%. Our findings are of importance to public health, considering the high consumption of foods that are high on fatty acids. Conflicting evidence of many previous studies regarding the effect of fat intake and obesity and cardiovascular diseases could be because of the gene-diet interactions and genetic heterogeneity across various ethnic groups. Hence, the synergism effect of genetic and dietay intakes should be considered in future studies. [ABSTRACT FROM AUTHOR]

Background: Individuals diagnosed with type 2 diabetes mellitus (T2DM) are more prone to experiencing severe cardiovascular (CV) events, often occurring at a younger age, due to a complex interplay of risk factors. T2DM diagnosis inherently classifies patients as belonging to a higher CV risk group. In light of the increased susceptibility to severe CV outcomes, our study aims to assess the distribution of CV risk categories and the attainment of therapeutic targets among Romanian patients diagnosed with T2DM. Methods: A cross-sectional analysis was performed, including 885 patients diagnosed with T2DM who were consecutively admitted to a secondary care hospital unit between January and July 2019. Data collection included demographics, lipid profile, glycated hemoglobin (HbA1c), blood pressure (BP), estimated glomerular filtration rate (eGFR), and medication specifics for T2DM and associated conditions. Patients were stratified into CV risk categories based on the ESC/EAS guidelines, encompassing moderate, high, and very high risk categories. The rationale for selecting these guidelines for CV risk categories was that they were current and provided best practice recommendations for T2DM patients during the cross-sectional evaluation. We assessed therapeutic target achievement rates for LDL-C, HbA1C, and BP for each CV risk category. Additionally, we examined utilization rates of statins and novel cardio- and reno-protective, non-insulin antidiabetic medications. Results: The group's average age was 62.9 ± 7.7 years and comprised 53.7% females. An average HbA1c level of 7.1 ± 1.3% was observed in the group. Within the cohort, 83% had hypertension, with a mean systolic BP of 132 ± 16.2 mm Hg and mean diastolic BP of 80 ± 9.6 mm Hg. Additionally, 64.6% of patients were obese, with a mean body mass index of 32.3 ± 5.3 kg/m2. Mean LDL-C levels varied across the different CV risk categories: 106.6 ± 35.6 mg/dL in the very high risk category, 113 ± 39.3 mg/dL in the high risk category, and 124.3 ± 38.3 mg/dL in the moderate risk category. Most treatment schemes included metformin (87.0%) and statins (67.0%), with variable use rates for other glucose-lowering and CV risk-modifying therapies. The percentage of patients using GLP-1 RAs was 8.1%, while 3.9% used SGLT2 inhibitors. Conclusions: Most Romanian patients with T2DM are at very high or high CV risk. Despite reaching glycemic control targets, most patients are not achieving the composite target, which includes, besides glycemic control, BP values and lipid profile. Many patients with T2DM are not benefiting from DM therapies with additional cardiorenal benefits or statins. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Endocrinología, Metabolismo y Nutrición is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)