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Lipid disorders, primarily hypercholesterolemia, are the most common cardiovascular (CV) risk factor in Poland (this applies even 3/4 of people). The low-density lipoprotein cholesterol (LDL-C) serum level is the basic lipid parameter that should be measured to determine CV risk and determines the aim and target of lipid-lowering treatment (LLT). Lipid-lowering treatment improves cardiovascular prognosis and prolongs life in both primary and secondary cardiovascular prevention. Despite the availability of effective lipid-lowering drugs and solid data on their beneficial effects, the level of LDL-C control is highly insufficient. This is related, among other things, to physician inertia and patients' fear of side effects. The development of lipidology has made drugs available with a good safety profile and enabling personalisation of therapy. Pitavastatin, the third most potent lipid-lowering statin, is characterised by a lower risk of muscle complications and new cases of diabetes due to its being metabolised differently. Thus, pitavastatin is a very good therapeutic option in patients at high risk of diabetes or with existing diabetes, and in patients at cardiovascular risk. This expert opinion paper attempts at recommendation on the place and possibility of using pitavastatin in the treatment of lipid disorders. [ABSTRACT FROM AUTHOR]

This document is a summary of the year 2023 for the "Archives of Medical Science" journal, which is celebrating its 20th anniversary. The author, Maciej Banach, reflects on the journal's history and achievements. The summary includes a list of the top 10 most cited papers in 2022, as well as the papers with the highest Altmetric Scores in 2023. The topics covered in these papers range from metabolic syndrome and cardiovascular diseases to lung cancer, Alzheimer's disease, and the COVID-19 pandemic. The author acknowledges the contributions of the authors and highlights the importance of their research. [Extracted from the article]

In 2023 there are still even 75% of patients over the target of low-density lipoprotein cholesterol (LDL-C), and hypercholesterolemia is the most common and the worst monitored cardiovascular risk factor. How it is possible, considering the knowledge we have on the role of cholesterol in the process of atherosclerosis, atherosclerotic cardiovascular disease (ASCVD) and its complications, on the methods of lipid disorders diagnosis, prevention, and treatment. Nowadays, almost 4 million deaths per year are attributed to LDL-C, and even 2/3 of all CVD deaths to ASCVD, therefore hypothetically we should easily prevent few to several million of deaths with early diagnosis, and early and intensive non-pharmacological and pharmacological therapies. Moreover, lipidology is now, besides oncology, the area with the highest number of new and ongoing trials with new effective and safe medications that have already appeared and will soon be available. Therefore, we have no doubt that year 2023 should be called the year of new and prospective lipid lowering therapies (LLTs). In this State-of-the-Art paper we summarized the most important trials, studies, and recommendations on the new and prospective LLTs, with suitable graphical summaries that might be helpful for the physicians in their practice with a look to the nearest future with prospective therapies being still under investigation. Let's hope all those medications helps to render dyslipidemia a rare disease in next few years. [ABSTRACT FROM AUTHOR]

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting. [ABSTRACT FROM AUTHOR]

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies—PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib—for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review and meta-analysis focuses on PCSK9 changes in obese patients following bariatric surgery.Methods: A systematic literature search in four databases was performed. Comprehensive Meta-Analysis (CMA) V2 software used to conduct the meta-analysis. Studies were evaluated regarding heterogeneity in design, populations under investigation, and treatment duration using a random-effects model and the generic inverse variance weighting approach. A random-effect meta-regression approach was used to investigate the association with the estimated effect size.Results: The results of the meta-analysis on 4 trials including 260 individuals demonstrated a remarkable decline of PCSK9 after bariatric surgery (WMD = -57.34 ng/ml, 95% CI: -87.97, -26.71, p < 0.001; I2 = 96.25%). Consistently, a significant decrease of LDL-C after bariatric surgery (WMD = -22.57 mg/dl, 95% CI: -27.5, -17.574, p < 0.001; I2 = 86.35%) was observed.Conclusions: PCSK9 is reduced significantly after bariatric surgery. The decrease of PCSK9 might be utilized as an independent surrogate marker of improvement of atherosclerotic cardiovascular disease risk after bariatric surgery. [ABSTRACT FROM AUTHOR]

Introduction: The impact of low-density lipoprotein cholesterol (LDL-C) on the risk of different types of strokes is unclear. Therefore, we systematically evaluated the impact of LDL-C levels (cohort studies) and lipid-lowering agents (LLAs) (randomized controlled trials) on the different types of stroke.Material and methods: PubMed, SCOPUS, Web of Science and Google Scholar were searched up to 1st September 2019. The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. The leave-one-out method was performed as sensitivity analysis. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 35% reduction in outcomes after administration of LLAs.Results: Participants in the highest category of LDL-C had a lower risk of hemorrhagic stroke (RR = 0.91, 95% CI: 0.85-0.98, I2 = 0%) compared with the lowest category of LDL-C. Subjects with the highest category of LDL-C had a higher risk of ischemic stroke (RR = 1.11, 95% CI: 1.07-1.14, I2 = 0%) compared to the lowest LDL-C category. LLAs decreased the risk of all types of strokes for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.88, 95% CI: 0.80-0.96, absolute risk reduction (ARR): 0.7%, number needed to treat (NNT): 143, I2 = 53%, n = 13). Statin therapy decreased the risk of all strokes (RR = 0.88, 95% CI: 0.80-0.97, ARR = 0.6%, NNT = 167, I2 = 56%). With regard to ischemic stroke only, LLAs decreased the risk of ischemic stroke for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.75, 95% CI: 0.67-0.83, ARR = 1.3%, NNT = 77, I2 = 0%); the same was observed for statins (RR = 0.76, 95% CI: 0.69-0.84, ARR = 1.3%, NNT = 77, I2 = 32%). TSA indicated that both benefit boundaries and optimal sample size were reached. There was no significant effect of LLAs regardless of the achieved level of LDL-C on the risk of hemorrhagic stroke; however, TSA indicated that further studies are needed to settle the question and most of the effects were subject to high levels of heterogeneity.Conclusions: Our study sheds light on the debatable association between low LDL-C and different type of strokes. This information can help determine the optimal LDL-C range for stroke prevention, and help plan future LLA studies. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of bempedoic acid on glycaemic and lipid variables in patients with hypercholesterolaemia. Methods: A patient‐level pooled analysis of four phase 3, randomized, double‐blind, placebo‐controlled trials evaluated changes in glycaemia, change from baseline in LDL‐C, and adverse events. Patients (N = 3621) on maximally tolerated statins were randomized 2:1 to oral bempedoic acid 180 mg or placebo once daily for 12 to 52 weeks with the results analysed by baseline glycaemic status (diabetes, prediabetes, or normoglycaemia). Results: The annual rate of new‐onset diabetes for bempedoic acid versus placebo in patients with normoglycaemia at baseline (n = 618) was 0.3% versus 0.8%, and for patients with prediabetes at baseline (n = 1868) it was 4.7% versus 5.9%. In patients with diabetes or prediabetes, bempedoic acid significantly (P <.0001) reduced HbA1c by −0.12% and −0.06%, respectively, and did not worsen fasting glucose versus placebo. Bempedoic acid significantly and consistently lowered LDL‐C levels versus placebo, regardless of baseline glycaemic status (placebo‐corrected difference range, −17.2% to −29.6%; P <.001 for each stratum). The safety of bempedoic acid was comparable with placebo and similar across glycaemic strata. Conclusions: Bempedoic acid significantly lowered LDL‐C across glycaemic strata and did not worsen glycaemic variables or increase the incidence of new‐onset diabetes versus placebo over a median follow‐up of 1 year. [ABSTRACT FROM AUTHOR]

Introduction: The phase IIIb open-label ODYSSEY APPRISE study prospectively assessed the safety and efficacy of alirocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in a real-life setting in high cardiovascular risk patients with heterozygous familial hypercholesterolemia or low-density lipoprotein cholesterol (LDL-C) not at goal despite maximally tolerated dose statins ± other lipid-lowering therapies (NCT02476006). This post-hoc analysis assessed patient adherence to statins and alirocumab, plus alirocumab efficacy and safety, according to concomitant statin intensity and prior ezetimibe usage.Material and methods: Patients received alirocumab 75 or 150 mg (dose adjustment based on physician's judgment) every 2 weeks (for ≥ 3 to ≤ 30 months).Results: Of 994 enrolled and treated patients, 58.4% received concomitant high-intensity statins, 18.2% received moderate/low-intensity statins, and 23.4% received no statin; 55.9% received prior ezetimibe. Mean alirocumab adherence (percent adherence defined as injections received/theoretical injections × 100) was 96.6% over 72.4 weeks' mean treatment duration. Mean LDL-C reduction from baseline at Week 12 was similar between statin intensity subgroups (53.6-55.7%). More patients achieved LDL-C < 1.8 mmol/l and/or ≥ 50% reduction from baseline in the ≥ 100% versus < 100% adherent to alirocumab subgroup; high-intensity and low/moderate-intensity subgroups versus no statin subgroup; and prior ezetimibe versus no prior ezetimibe subgroup. Treatment-emergent adverse events occurred in 65.2-75.1% and 68.0-76.3% of patients across statin and ezetimibe subgroups, respectively.Conclusions: In a real-life setting, patient adherence to alirocumab was high. Alirocumab provided clinically significant reductions in LDL-C, with most patients achieving LDL-C treatment targets across background statin therapy and prior ezetimibe therapy subgroups. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a cardiometabolic comorbidity that may predispose COVID‐19 patients to worse clinical outcomes. This study sought to determine the prevalence of diabetes in hospitalized COVID‐19 patients and investigate the association of diabetes severe COVID‐19, rate of acute respiratory distress syndrome (ARDS), mortality, and need for mechanical ventilation by performing a systematic review and meta‐analysis. Methods: Individual studies were selected using a defined search strategy, including results up until July 2021 from PubMed, Embase, and Cochrane Central Register of Controlled Trials. A random‐effects meta‐analysis was performed to estimate the proportions and level of association of diabetes with clinical outcomes in hospitalized COVID‐19 patients. Forest plots were generated to retrieve the odds ratios (OR), and the quality and risk assessment was performed for all studies included in the meta‐analysis. Results: The total number of patients included in this study was 10 648, of whom 3112 had diabetes (29.23%). The overall pooled estimate of prevalence of diabetes in the meta‐analysis cohort was 31% (95% CI, 0.25‐0.38; z = 16.09, P <.0001). Diabetes significantly increased the odds of severe COVID‐19 (OR 3.39; 95% CI, 2.14‐5.37; P <.0001), ARDS (OR 2.55; 95% CI, 1.74‐3.75; P = <.0001), in‐hospital mortality (OR 2.44; 95% CI, 1.93‐3.09; P <.0001), and mechanical ventilation (OR 3.03; 95% CI, 2.17‐4.22; P <.0001). Conclusions: Our meta‐analysis demonstrates that diabetes is significantly associated with increased odds of severe COVID‐19, increased ARDS rate, mortality, and need for mechanical ventilation in hospitalized patients. We also estimated an overall pooled prevalence of diabetes of 31% in hospitalized COVID‐19 patients. [ABSTRACT FROM AUTHOR]

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]

The global coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 coronavirus started in March 2020. The conclusions from numerous studies indicate that people with comorbidities, such as arterial hypertension, diabetes, obesity, underlying cardiovascular disease, are particularly vulnerable to the severe course of COVID-19. The available data also suggest that patients with dyslipidemia, the most common risk factor of cardiovascular diseases, are also at greater risk of severe course of COVID-19. On the other hand, it has been shown that COVID-19 infection has an influence on lipid profile leading to dyslipidemia, which might require appropriate treatment. Owing to antiviral, anti-inflammatory, immunomodulatory, and cardioprotective activity, statin therapy has been considered as valuable tool to improve COVID-19 outcomes. Numerous observational studies have shown potential beneficial effects of lipid-lowering treatment on the course of COVID-19 with significant improved prognosis and reduced mortality. [ABSTRACT FROM AUTHOR]

An inverse correlation between high-density lipoprotein cholesterol (HDL-C) and cancer risk has been shown by several epidemiological studies. Some studies have even suggested that HDL-C can be used as a prognostic marker in patients with certain types of cancer. However, whether reduced HDL-C level is a consequential or causal factor in the development and progression of cancer remains a controversial issue. In this review, we update and summarize recent advances that highlight the role of HDL and some of its components in prognosis, diagnosis and treatment of cancer. [ABSTRACT FROM AUTHOR]

Cancer is one of the most frequent causes of worldwide death and morbidity and is a major public health problem. Although, there are several widely used treatment methods including chemo-, immune- and radiotherapies, these mostly lack sufficient efficiency and induce toxicities in normal surrounding tissues. Thus, finding new approaches to mitigate side effects and potentially accelerate treatment is paramount. In line with this, increasing preclinical evidence indicates that caloric restriction (CR) and fasting might have anticancer effects by reducing tumor progression, enhancing death of cancer cells, and elevating the effectiveness and tolerability of chemo- and radiotherapies. Nonetheless, clinical studies assessing the potential of CR and fasting in cancer are scarce and inconsistent, and more investigations are still required to clarify their effect in different aspects of cancer treatment. In this review, we have summarized the findings of preclinical and clinical studies of CR and fasting with respect to efficacy and on the adverse effects of standard cancer treatments. [ABSTRACT FROM AUTHOR]

Introduction: In the absence of a European standardized postmarketing food supplement surveillance system (nutrivigilance), some member states and companies have developed their own approaches to monitoring potential adverse reactions to secure a high level of product safety. This paper describes the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected adverse reactions associated with food supplements containing red yeast rice (RYR).Material and Methods: We report the data from a widely used product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1st October 2004 to 31st December 2019, this system captured cases of suspected adverse reactions spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality.Results: The total number of case reports received mentioning the RYR food supplement product line was 542, in which 855 adverse events (AEs) were reported. The total reporting rate of AEs was estimated to be 0.037% of 2,287,449 exposed consumers. Of the 542 cases, 21 (0.0009% of exposed consumers) included suspected serious adverse events (SAEs). After careful investigation, 6 cases (0.0003% of consumers exposed) and 6 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical.Conclusions: This nutrivigilance-derived data analysis clearly demonstrates a low prevalence of suspected adverse events associated with the red yeast rice product line. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement's labeling. [ABSTRACT FROM AUTHOR]

This European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients. Evidence-based review. Statin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus. This guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment. • This EAS Task Force gives practical guidance for combination lipid lowering therapy in high- and very-high-risk patients. • In patients unlikely to reach the LDL-C goal with a statin alone combination with ezetimibe is suggested as first choice. • A PCSK9 inhibitor may be added if LDL-C levels remain high. • For type 2 diabetes with high triglycerides on statin, fenofibrate may be considered for macro- and microvascular benefits. • •High-dose icosapent ethyl may be also considered for high triglycerides on statin treatment, weighing benefit vs. risk. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Comorbidities in primary care do not occur in isolation but tend to cluster together causing various clinically complex phenotypes. This study aimed to distinguish phenotype clusters and identify the risks of all‐cause mortality in primary care.The baseline cohort of the LIPIDOGEN2015 sub‐study involved 1779 patients recruited by 438 primary care physicians. To identify different phenotype clusters, we used hierarchical clustering and investigated differences between clinical characteristics and mortality between clusters. We then performed causal analyses using causal mediation analysis to explore potential mediators between different clusters and all‐cause mortality.A total of 1756 patients were included (mean age 51.2, SD 13.0; 60.3% female), with a median follow‐up of 5.7 years. Three clusters were identified: Cluster 1 (n = 543) was characterised by overweight/obesity (body mass index ≥ 25 kg/m2), older (age ≥ 65 years), more comorbidities; Cluster 2 (n = 459) was characterised by non‐overweight/obesity, younger, fewer comorbidities; Cluster 3 (n = 754) was characterised by overweight/obesity, younger, fewer comorbidities. Adjusted Cox regression showed that compared with Cluster 2, Cluster 1 had a significantly higher risk of all‐cause mortality (HR 3.87, 95% CI: 1.24–15.91), whereas this was insignificantly different for Cluster 3. Causal mediation analyses showed that decreased protein thiol groups mediated the hazard effect of all‐cause mortality in Cluster 1 compared with Cluster 2, but not between Clusters 1 and 3.Overweight/obesity older patients with more comorbidities had the highest risk of long‐term all‐cause mortality, and in the young group population overweight/obesity insignificantly increased the risk in the long‐term follow‐up, providing a basis for stratified phenotypic risk management. [ABSTRACT FROM AUTHOR]

Objectives: Emerging publications indicate that diabetes predisposes patients with COVID-19 to more severe complications, which is partly attributed to inflammatory condition. In the current review, we reviewed recent published literature to provide evidence on the role of insulin resistance (IR) in diabetes, the association between diabetes and COVID-19 severity and mortality, the impact of COVID-19 infection on incident new-onset diabetes, mechanisms responsible for IR in COVID-19 patients, and the predictive value of different surrogates of IR in COVID-19. Method: The literature search performs to find out studies that have assessed the association between IR surrogates and morbidity and mortality in patients with COVID-19. Results: We showed that there is a bulk of evidence in support of the fact that diabetes is a potent risk factor for enhanced morbidity and mortality in COVID-19 patients. COVID-19 patients with diabetes are more prone to remarkable dysglycemia compared to those without diabetes, which is associated with an unfavourable prognosis. Furthermore, SARS-COV2 can make patients predispose to IR and diabetes via activating ISR, affecting RAAS signaling pathway, provoking inflammation, and changing the expression of PPARɣ and SREBP-1. Additionally, higher IR is associated with increased morbidity and mortality in COVID-19 patients and different surrogates of IR can be utilized as a prognostic biomarker for COVID-19 patients. Conclusion: Different surrogates of IR can be utilized as predictors of COVID-19 complications and death. [ABSTRACT FROM AUTHOR]

With the global expansion of coronavirus disease 2019 (COVID-19) and the declaration of its outbreak as a Public Health Emergency of International Concern by the World Health Organization, there is an urgent need for vaccines and medicines to prevent and treat COVID-19. The responsible pathogen for the disease is the newly severe acute respiratory syndrome coronavirus (SARS-CoV) 2 belonging to the same family of viruses SARS-CoV and Middle East respiratory syndrome coronavirus that originally are zoonotic and have been associated with severe illness during the outbreaks in 2003 and 2012, respectively. The virulence of coronavirus strains is mainly associated with variations in surface proteins mediating cellular entry of the virus, which can help in finding effective therapeutic targets. In this review, we seek evidence showing the role of coronavirus spike protein (S-protein) and its potential cellular receptor, angiotensin-converting enzyme 2 (ACE2), during infection of coronaviruses, including the newly SARS-CoV-2 and its similar strain SARS-CoV. This review also discusses the therapeutic effect of inhibiting the renin–angiotensin system cascade, a target of ACE2, in patients having coronavirus with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid. Patients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) "on statins" and 2) "low-dose or no statin". Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non–HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex. Overall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acid vs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p ≤ 0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (−21.2% vs. −17.4%; p = 0.044), non–HDL-C (−17.3% vs. −12.1%; p = 0.003), TC (−13.8% vs. −10.5%; p = 0.012), and Apo B (− 16.0% vs. −11.3%; p = 0.004) in the ASCVD and/or HeFH on statins pool. Women had similar reductions to men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes. In this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid. [Display omitted] • Bempedoic acid lowered lipid parameters vs. placebo in both sexes. • Greater reductions in some lipids, including LDL-C, were seen in women than men. • Bempedoic acid safety was comparable between men and women. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a chronic progressive inflammatory condition characterized by the formation of lipid-laden lesions in arterial walls, is associated with substantial morbidity (including ischaemic stroke and myocardial infarction) and mortality. Risk factors for atherosclerosis are well understood and can be ameliorated by evidence-based and guideline-directed pharmaceutical agents (e.g. the reduction of circulating concentrations of low-density lipoprotein cholesterol by statins). Additionally, many natural products (usually food derivatives) and 'nutraceuticals' (pharmaceutical formulations prepared from components of foods) have been shown to have favourable effects on risk factors for atherosclerotic cardiovascular disease. This literature review summarises the evidence for anti-atherogenic natural compounds. The article focuses on agents which are discussed in international guidelines and are supported by extensive high-quality randomized-controlled trial (RCT) data. We focus on micronutrients (compounds present in food in small quantities) and nutraceuticals, in particular, phytosterols, polyunsaturated ω-3 fatty acids and red-yeast rice. We conclude that the 'nutraceutical approach' (identify the active ingredients in natural products; produce high-quality products according to Good Manufacturing Practice guidelines; evaluate them in long-term outcomes trials) is the mechanism by which the domains of natural product research and evidence-based medicine can move closer together. Image 1 • A variety of nutraceuticals have favourable effects on risk factors for atherosclerotic disease, however long-term outcomes trials are rare. • Phytosterols reduce blood cholesterol levels and are well tolerated, however, the effects on cardiovascular disease risk are conflicting. • In long-term clinical trials, high-dose, pure eicosapentaenoic acid reduced cardiovascular events. • Red-yeast rice contains monacolin K, which is identical to lovastatin, and reduces cardiovascular events in long-term trials. • Nutraceuticals are generally safe, but some preparations may contain contaminants, and long-term data are often lacking. [ABSTRACT FROM AUTHOR]

Introduction: In women, an increase in blood pressure is observed after the menopause. However, the confounding effect of aging and comorbidities should be taken into account. Current guidelines don't recommend any specific treatment of post-menopausal hypertension. This study aimed to assess the influence of gender on the outcome of hypertension treatment in patients above 40 years old. Material and methods: Data for this retrospective, single-center study were collected from the disease cards of hypertensive pharmacologically treated patients hospitalized on the cardiological ward. 268 patients, aged over 40, were divided into two groups: women and men. Additional data regarding compliance and efficacy of treatment after hospitalization were obtained in phone interview. Statistical analysis was performed using the IBM SPSS Statistics25 package. Results: We analyzed the data in term of comorbidities and medical history of cardiological interventions. The significant differences between studied groups were noted only in the frequency of hyperlipidemia and coronary artery bypass graft, both were more often in men. Significantly more men have been using combined products (24 men - 32.4%) vs. 40 women (20.6%) (p = 0.03). Regarding the drug classes in treatment of hypertension, the only significant difference was observed in the frequency of alfa-blocker use (more often in men). We did not observe any significant difference in the willingness to participate in follow-up between women and men (146, 75.3% vs. 57, 77%, respectively, p = 0.45). There were no significant differences in the follow-up results. Conclusions: In the studied group of patients, gender did not affect the outcome of hypertension treatment. [ABSTRACT FROM AUTHOR]

However, statin therapy may be not sufficient to reduce significantly the CV risk in high and very-high CV, and especially ultra/extremely high risk patients [[7]], and consequentially there may be an indication to use a statin in combination with other non-statin lipid-lowering drugs, such as ezetimibe, acting through a different mechanism of action. For most (even 95%) of those who experienced statin-associated muscle symptoms (SAMS) it is still possible to use statins by modifying the dose and type of statin, apply alternate-day statin therapy, or alternatively a non-statin dug or specific nutraceuticals with lipid-lowering properties can be considered [[38]]. Our recommendation is that only subjects with low CV risk, without overt characteristics of eligibility for statin therapy, or having conditions/risk factors that may predispose to an increased risk of statin-associated SAMS, may be advised to use RYR, and physicians should discuss with the patients the possible benefit as well as adverse events associated with RYR use. • In case of reluctance of your patient to take classical statins, clarify the exact reason: (1) adverse effect (intolerant patient), (2) specific worries about the chemical nature of a drug (the patients prefer natural medicine) or (3) worries about the statin administration in general. [Extracted from the article]

In the last several years there has been a large debate whether patients with type 2 diabetes (T2DM) should be treated as those with high or very high cardiovascular risk, and whether T2DM should be considered as equivalent to coronary heart disease (CHD). It all started in the 2001 in National Cholesterol Education Program - Adult Treatment Panel III recommendations, and the knowledge has changed on this issue at least several times. But the main problem is that due to these inconsistencies and different approaches to the cardiovascular risk of T2DM patients, we have more and more patients with T2DM not effectively treated, and diabetologists mostly focus on glucose (glucocentric approach), often forgetting about the overall cardiovascular risk of those patients. In this review we discuss the above-mentioned topic, try to give some practical suggestions, and raise the issue of whether we should start a discussion on treating all patients with T2DM as those at very high cardiovascular risk, or to at least to try to unify the definition and find such variables/risk factors which are easy to measure to help physicians to treat those patients optimally. We have obviously discussed these issues in the context of new European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) Guidelines 2019. [ABSTRACT FROM AUTHOR]

The study aimed to identify biomarkers predictive of cryptogenic stroke in patients aged <65. We investigated 520 patients with ischemic stroke. Out of them we assigned 65 patients to the cryptogenic stroke group (age 54 (47–58), 42% male) and 36 without stroke to the control group (age 53 (47–58), 61% male). In all patients we assessed carotid intima-media thickness (cIMT) and the levels of biomarkers which might be involved in the underlying biological mechanism of ischemic stroke. There were no differences between stroke and control groups in the levels of syndecan 4, resistin, leptin, low-density lipoprotein cholesterol, triglycerides, prothrombin time, or activated partial thromboplastin time. There was no statistically significant difference in cIMT between groups. The level of high-density lipoprotein cholesterol was statistically significantly lower in the cryptogenic stroke group than in the controls (1.1 mmol/L (0.95–1.46) vs 1.37 (1.19–1.6) p = 0.02). Patients in the stroke group had higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) (391 pg/ml (107–1249) vs 109 (46–236); p = 0.003), interleukin 6 (2.6 pg/ml (0.8–8.1) vs 0.7 (0.4–1.2) p = 0.002) and asymmetric dimethylarginine (ADMA) (0.44 μmol/L (0.39-0.55) vs 0.36 (0.32-0.4); p = 0.0002) than the control group. In the multivariate analysis Il-6 was the only biomarker statistically significant associated with the occurrence of cryptogenic stroke (odds ratio 1.918, 95% confidence interval 1.029–3.575; p = 0.04). Endothelial dysfunction assessed by increased level of ADMA affects the inflammatory state in patients with cryptogenic stroke. Increase in the inflammatory cytokine IL-6 by 1 pg/ml almost doubles the risk of stroke. [ABSTRACT FROM AUTHOR]

Similarly in the case of statin intolerance, it may be preferable to start treatment immediately with available non-statin agents, rather than waiting months until the maximally tolerated dose of statin can be titrated, increasing the risk of LDL-C visit-to-visit variability and increased CVD event risk [5]. Keywords: Bempedoic acid; Combination therapy; Lipid-lowering therapy; Statins EN Bempedoic acid Combination therapy Lipid-lowering therapy Statins 86 88 3 03/03/21 20210301 NES 210301 Exposure to low-density lipoprotein cholesterol (LDL-C) causes atherosclerotic cardiovascular disease (ASCVD) [1], and the importance of the mantra "lower is better for longer"[2],[3] cannot be understated. However, muscle symptoms are often misattributed to statins [11] and with careful management, including switching between statins and dose reduction, applying alternate-day statin therapy or combination therapy [12], approximately 95% of seemingly intolerant patients can manage some degree of statin therapy [13]. Statins, the mainstay of lipid-lowering therapy since the 1990s, reduce hepatic production of cholesterol, and are effective at reducing ASCVD events, and are generally well-tolerated [9], but might be associated with adverse effects such as muscle symptoms - which in extreme cases (usually less than 5%) can lead to complete statin intolerance and in the consequence statin discontinuation [10]. [Extracted from the article]

Graphical abstract Abstract Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1–5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects. [ABSTRACT FROM AUTHOR]

Abstract Objectives Atrial fibrillation (AF) is common in older adults and associated with increased risk of cardiovascular events including thromboembolism. However, less is known about its association with noncardiovascular events, especially geriatric syndromes and conditions such as dementia, depression, impaired physical function, polypharmacy, falls, and poor quality of life. This review aims to help healthcare professionals integrate the special needs of older adults into their management of AF. Design Nonsystematic review. A literature search on published articles on AF and geriatric syndromes and conditions was performed using the electronic databases MEDLINE, EMBASE and SCOPUS, and DARE until December 2017. Non-English articles were excluded. Settings and participants Older adults with and without AF from different settings. Measures Various cognitive, mood, and functional measurements were used in these studies. In studies regarding polypharmacy, the Beers or PRISCUS criteria were used to identify inappropriate medications. In quality of life measurements studies, instruments like Medical Outcomes Study Short Form 36 and Atrial Fibrillation Quality of Life questionnaire were used. Results This literature review finds that AF has a substantial association with geriatric syndromes and conditions and that AF is a risk factor for the development of geriatric syndromes and conditions. Evidence is limited regarding the potential benefit of long-term treatment of AF in lowering the risk of developing geriatric syndromes and conditions. Conclusions/Implications Considering the impact of AF on cardiovascular outcomes and geriatric syndromes and conditions in older adults, healthcare professionals need to consider these complex dynamics while managing AF in older adults. An individual approach to AF management is needed in older adults with multiple comorbidity and polypharmacy that may help lower the risk of disease-disease, disease-drug, and drug-drug interactions. Special consideration needs to be given to patients' cognitive and functional impairment and ability to adhere to therapy. [ABSTRACT FROM AUTHOR]

The discovery of statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) is a consequence of the highly targeted, arduous search for naturally occurring compounds that inhibit cholesterol biosynthesis. An enormous amount of basic scientific, genetic, and clinical research substantiated the role of lipoprotein-derived cholesterol in atherogenesis. Quantifying the impact of lipid lowering on cardiovascular event rates became an issue of utmost urgency. Although a variety of nonstatin drugs had been tested in clinical trials, they found limited utility in the clinical setting due to lack of mortality reduction or tolerability issues. As multiple prospective randomized statin trials began publishing their results, it became clear that reducing atherogenic lipoprotein burden with these drugs was highly efficacious, safe, and generally well tolerated. Statins have been shown to reduce risk for nonfatal MI, ischemic stroke, need for revascularization, and cardiovascular and all-cause mortality. They have also been shown to stabilize and even regress established atherosclerotic plaque. For the first 2 decades of their use, statin dosing was largely determined by risk-stratified low-density lipoprotein cholesterol (LDL-C) goals. More recently, there has been a transition away from LDL-C goal attainment with a focus more on cardiovascular risk and percent LDL-C reduction. Unfortunately, long-term adherence rates with statin therapy remain low and, even when used, they tend to be underdosed. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a major cause of death globally. Addressing cardiovascular risk factors, particularly dyslipidemia, represents the most robust clinical strategy towards reducing the CVD burden. Statins inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and represent the main therapeutic approach for lowering cholesterol and reducing plaque formation/rupture. The protective effects of statins extend beyond lowering cholesterol. MicroRNAs (miRNAs or miRs), small noncoding regulatory RNAs, likely mediate the positive pleiotropic effects of statins via modulation of lipid metabolism, enhancement of endothelial function, inhibition of inflammation, improvement of plaque stability, and immune regulation. miRNAs are implicated in statin-related interindividual variations in therapeutic response, directly via HMG-CoA reductase, or indirectly through targeting cytochrome P450 3A (CYP3A) functionality and proprotein convertase subtilisin/kexin type9 (PCSK9) biology. Highlights miRs have been suggested to mediate pleiotropic effects of statins, including improvement of endothelial function as well as anti-inflammatory and immunomodulatory activities. miRs have been suggested to be implicated in the variations in the statin response. This role might be, at least in part, mediated via interaction of miRs with cytochrome P450 isoenzymes that are involved in statin metabolism. Upregulation of selected miRs by statins might enhance plaque stability by modulating multiple pathways, namely, repression of angiogenesis, atherosclerosis-related cell proliferation, monocyte migration, platelet adhesion, and the coagulation cascade. [ABSTRACT FROM AUTHOR]

Introduction: We conducted a systematic review and meta-analysis to estimate the prevalence of overweight and obesity in children (aged 5-12 years) and adolescents (aged 12-19 years) in Asian countries. Study design: Systematic review and meta-analysis.Material and Methods: We comprehensively searched specialised databases for relevant studies conducted in Asian countries between January 1, 1999, and May 30, 2017. Random effects models (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis. Sensitivity analysis was conducted using the 'leave-one-out' method. Heterogeneity was quantitatively assessed using the I2 index. Systematic review registration: CRD42016033061.Results: Among 22,286 identified citations, 41 studies met the inclusion criteria with n = 71,998 and n = 353,513 for children and adolescents. The pooled prevalence (overall, boys and girls) was 5.8% (n = 4175), 7.0% (n = 2631) and 4.8% (n = 1651) for obesity in children aged 5-11 years; 8.6% (n = 30,402), 10.1% (n = 17,990) and 6.2% (n = 10,874) for obesity in adolescents age 12-19 years. For overweight in children the values for overall, boys and girls were 11.2% (n = 7900), 11.7% (n = 4280) and 10.9% (n = 3698) respectively; and for overweight in adolescents, 14.6% (n = 46,886), 15.9% (27,183), and 13.7% (20,574). These findings were robust in sensitivity analyses. In children and adolescents a higher percentage of boys than girls are obese (children = 7.0 vs. 4.8%, adolescents = 10.1 vs. 6.2%, p < 0.001, respectively). Furthermore, in children and adolescents a higher percentage of boys than girls are overweight (children = 11.7 vs. 10.9%, adolescents = 15.9 vs. 13.7%, p < 0.001, respectively).Conclusions: In view of the number of children who are overweight or obese, the associated detrimental effects on health, and the cost to health-care systems, implementation of programmes to monitor and prevent unhealthy weight gain in children and adolescents is needed throughout Asian countries. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Patients with hyperlipidemia who are unable to tolerate optimal statin therapy are at increased cardiovascular risk due to ongoing elevations in low-density lipoprotein cholesterol (LDL-C). The objective of CLEAR Tranquility (NCT03001076) was to evaluate the efficacy and safety of bempedoic acid when added to background lipid-modifying therapy in patients with a history of statin intolerance who require additional LDL-C lowering. Methods This phase 3, multicenter, randomized, double-blind, placebo-controlled study enrolled patients with a history of statin intolerance and an LDL-C ≥100 mg/dL while on stable lipid-modifying therapy. After a 4-week ezetimibe 10 mg/day run-in period, patients were randomized 2:1 to treatment with bempedoic acid 180 mg or placebo once daily added to ezetimibe 10 mg/day for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C. Results The study population comprised 269 patients (181 bempedoic acid, 88 placebo). Bempedoic acid added to background lipid-modifying therapy that included ezetimibe reduced LDL-C by 28.5% more than placebo (p < 0.001; −23.5% bempedoic acid, +5.0% placebo). Significant reductions in secondary endpoints, including non-high-density lipoprotein cholesterol (−23.6%), total cholesterol (−18.0%), apolipoprotein B (−19.3%), and high-sensitivity C-reactive protein (−31.0%), were observed with bempedoic acid vs. placebo (p < 0.001). Bempedoic acid was well tolerated; rates of treatment-emergent adverse events, muscle-related adverse events, and discontinuations were similar in the bempedoic acid and placebo treatment groups. Conclusions Bempedoic acid may provide an oral therapeutic option complementary to ezetimibe in statin intolerant patients who require additional LDL-C lowering. Highlights • Bempedoic acid provides additional LDL-C lowering when added to ezetimibe. • Bempedoic acid lowers atherogenic lipids and hsCRP in statin intolerant patients. • Bempedoic acid is well tolerated including a low muscle-related adverse event rate. [ABSTRACT FROM AUTHOR]

Cystatins, a family of proteins known for their inhibitory role against cysteine proteases, have garnered significant attention in the field of neurodegeneration. Numerous genetic, experimental, and clinical studies concerning cystatin C suggest it plays an important role in the course of neurodegenerative diseases. Its beneficial effects are associated with cysteine protease inhibition, impact on β-amyloid aggregation, as well as regulation of cell proliferation, autophagy, and apoptosis. Cystatin isolated from chicken egg white, called ovocystatin, has been widely used in medical and pharmaceutical research due to its structural and biological similarities to human cystatin C. This article focuses on the potential use of cystatins, with special emphasis on easily obtained ovocystatin, in the treatment of neurodegenerative diseases, such as dementia. The current evidence on cystatin use has shed light on its mechanisms of action and therapeutic implications for neuroprotection and maintenance of cognitive functions. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to identify factors that may cause the presence of long COVID and to assess factors that affect chronic limited exercise tolerance in spiroergometry after one-year follow-up in patients who had recovered from COVID-19. Methods: Of 146 patients hospitalised in the Cardiology Department, 82 completed a one-year follow-up (at least 15 months post-COVID-19 recovery). We compared their conditions at initial screening and follow-up to analyse the course of long COVID and exercise intolerance mechanisms. Clinical examinations, laboratory tests, echocardiography, cardiopulmonary exercise testing, and body composition analysis were performed. Results: The patients, after one-year follow-up, had significantly higher levels of high-sensitivity cardiac troponin T (hs-cTnT) (p = 0.03), left atrium diameter (LA) (p = 0.03), respiratory exchange ratio (RER) (p = 0.008), and total body water content percentage (TBW%) (p < 0.0001) compared to the 3-month assessment. They also had lower forced vital capacity in litres (FVC) (p = 0.02) and percentage (FVC%) (p = 0.001). The factors independently associated with a decline in maximum oxygen uptake (VO2max) after one-year follow-up included the percentage of fat (OR 2.16, 95% CI: 0.51–0.77; p = 0.03), end-diastolic volume (EDV) (OR 2.38, 95% CI 0.53–0.78; p = 0.02), and end-systolic volume (ESV) (OR 2.3, 95% CI: 0.52–0.78; p = 0.02). Conclusions: Higher left ventricular volumes and fat content (%) were associated with a reduced peak VO2max when assessed 15 months after COVID-19 recovery. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Asymptomatic severe aortic stenosis (AS) during pregnancy remains challenging; however, the postponement of surgery with the possibility of valvuloplasty as a bridge therapy seems reasonable. Our case showed that despite physiological changes during pregnancy, the aortic valve defect did not worsen, which allowed us to avoid dilemmas related to anticoagulation on artificial valve. A 31‐year‐old woman, with a bicuspid aortic aorta, post‐aortic valvulotomy, was listed for cardiac surgery because of severe aortic stenosis. However, the operation was postponed due to procreation plans. During the pregnancy and delivery, we did not observe neither deterioration of symptoms nor changes of echocardiographic parameters. Subsequent monthly echocardiographic studies did not reveal a significant increase of peak and mean aortic gradient. Presented case reports showed that despite physiological changes associated with pregnancy, the aortic valve defect did not worsen, which allowed to avoid dilemmas related to anticoagulation on artificial valves. [ABSTRACT FROM AUTHOR]

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction. [ABSTRACT FROM AUTHOR]

The sirtuins, silent mating-type information regulation 2 (SIRTs), are a family of nicotinamide adenine dinucleotide (NAD + )-dependent histone deacetylases with important roles in regulating energy metabolism and senescence. Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants, prompting investigation of the roles of these proteins in atherogenesis. Although clinical data are currently limited, the availability and safety of SIRT activators such as metformin and resveratrol provide an excellent opportunity to conduct research to better understand the role of SIRTs in human atherosclerosis. Encouraging observations from preclinical studies necessitate rigorous large, prospective, randomized clinical trials to determine the roles of SIRT activators on the progression of atherosclerosis and ultimately on cardiac outcomes, such as myocardial infarction and mortality. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel cholesterol-lowering treatment for decreasing the risk of atherosclerosis. We have previously shown that active immunization using the antiPCSK9 vaccine could decrease hypercholesterolemia and impede the development of atherosclerotic lesions in the experimental model of atherosclerosis. Here, we evaluated the toxicity of the vaccine in healthy mice. Forty male and female albino mice were divided into 4 experimental groups, including vaccine female (10 mice) and male (10 mice) groups receiving the antiPCSK9 vaccine as well as the corresponding control female (10 mice) and male (10 mice) groups receiving the phosphate buffer. Vaccination was planned based on 4 subcutaneous injections of the vaccine formulation (10 µg/mouse) in bi-weekly intervals. The toxicity study was performed by the subacute protocol, 28 days after the last vaccine injection. To this end, the plasma levels of lipid indexes, urea, creatinine, AST, ALT, ALP, and fasting plasma glucose (FPG), as well as the CBC test were measured. To evaluate histopathological alterations, various tissues including the heart, liver, kidney, spleen, and brain were studied using hematoxylin & eosin (H&E) staining by an expert pathologist. The severity of damage to the tissue was considered based on the standard classification; grade 1 as light damage, grade 2 as moderate damage, grade 3 as near intense damage, and grade 4 as intense damage. The results showed non-significant changes of total cholesterol, LDL-C, triglyceride, HDL-C, FBS, creatinine, urea, AST, ALP, ALT, and PAB in the vaccinated mice when compared with control mice. The CBS test indicated that there were no significant changes in the levels of WBC, RBC, HGB, HCT, MCH, MCHC, PLT, LYM, NEUT, MCV, RDW-S, PDW, and MPV in the vaccinated mice when compared with control mice. Evaluating histopathological alterations in various tissues indicated no significant adverse effects in vaccinated mice when compared to control mice. The findings of the present study indicate that antiPCSK9 is safe and exerts no adverse effects on the function of different organs and blood levels of cellular and biochemical biomarkers in healthy mice. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as "neo-antigens" and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner. [ABSTRACT FROM AUTHOR]

PCSK9 (proprotein convertase subtilisin kexin type 9) is a liver secretory enzyme that regulates plasma low-density lipoprotein (LDL) cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR) density on the surface of hepatocytes. Inhibition of PCSK9 using monoclonal antibodies can efficiently lower plasma LDL-C, non-high-density lipoprotein cholesterol and lipoprotein (a). PCSK9 inhibition is also an effective adjunct to statin therapy; however, the cost-effectiveness of currently available PCSK9 inhibitors is under question. Nutraceuticals offer a safe and cost-effective option for PCSK9 inhibition. Several nutraceuticals have been reported to modulate PCSK9 levels and exert LDL-lowering activity. Mechanistically, those nutraceuticals that inhibit PCSK9 through a SREBP (sterol-responsive element binding protein)-independent pathway can be more effective in lowering plasma LDL-C levels compared with those inhibiting PCSK9 through the SREBP pathway. The present review aims to collect available data on the nutraceuticals with PCSK9-inhibitory effect and the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as effective low-density lipoprotein cholesterol-lowering compounds. Although the results of available epidemiological, preclinical, and clinical studies suggest a positive association of plasma PCSK9 levels with glycemic parameters and risk of type 2 DM (T2DM), genetic findings have shown contradictory results. Overall, the impact of PCSK9 inhibitors on glycemic control parameters in patients with DM remains unclear. Here, we assess the available evidence for the association of PCSK9 status with the incidence and control of DM in preclinical and clinical studies, and identify molecular mechanisms regulating PCSK9 expression in the diabetic state. [ABSTRACT FROM AUTHOR]

Cardiovascular disease associated with myocardial infarction (MI) is among the leading causes of mortality worldwide, in part, due to the limited regenerative capacity of tissues. Although various approaches have been employed to generate bioartificial myocardial tissues, including surgical reconstruction and the use of biosynthetic or biological cell-free grafts, many challenges still remain. Natural biomaterials based on decellularization have made significant inroads into the development of favorable biomatrices for myocardial tissue regeneration. This process occurs with the concept of removing whole cellular contents, while preserving the extracellular matrix components and all the necessary features of native tissues. Furthermore, acellular-derived matrices serve to stimulate proliferation and recruitment of endothelial cells by providing proliferation signals to cells. This review highlights a novel approach to generate natural three dimensional myocardial scaffolds for clinical applications. [ABSTRACT FROM AUTHOR]

The key lipid-lowering target is to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new treatment strategies for lipid-lowering therapy include using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to reduce residual risk of cardiovascular diseases (CVD). However, concerns about possible adverse effects, including neurocognitive disorders, were issued by the Food and Drug Administration (FDA). The current disputable evidence does not allow definite conclusions as to whether statins contribute to, or cause, clinically meaningful cognitive impairment. Some evidence indicates a high rate of memory loss, while other evidence suggests a benefit in dementia prevention. This debate should not discourage appropriate statin and other lipid-lowering drug administration. However, prescribers should be aware of such potential drug-related side effects. Prospective controlled studies comparing the short- and long-term effects of different statins on cognitive function are warranted. The effects of intensive LDL-C lowering on neurocognition might be attributed to an off-target effect. It is also possible that pre-existing pathology and vascular risk may already be present outweighing any effect related to lipids. Gender, genetic, LDL-C-related genotypes and aging-related changes should also be considered. Some data indicate that carriers of apolipoprotein E (apoE) ε-4 allele, with low levels of apoA1 and high-density lipoprotein cholesterol have a distinct plasma lipid profile and may be more susceptible to neurocognitive dysfunction. Future research on lipid-lowering drugs and cognition is needed; careful study design and analysis will be critical. [ABSTRACT FROM AUTHOR]