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Within Europe and the Asia-Pacific, the Atrial Fibrillation Better Care (ABC) pathway is the gold standard integrated care strategy for atrial fibrillation management. Atrial fibrillation diagnosis should be confirmed and characterized (CC) prior to implementation of ABC pathway components: 1) "A"- Anticoagulation/Avoid stroke; 2) "B"- Better symptom management; and 3) "C"- Cardiovascular and other comorbidity optimization. Pharmacists have the potential to expedite integrated care for atrial fibrillation across the health care continuum: hospital, community pharmacy, and general practice. This review summarizes the available evidence base for pharmacist-led implementation of the "CC to ABC" model. [ABSTRACT FROM AUTHOR]

Solid oral dosage forms (SODFs) (often called pills by patients) are the default formulation to treat medical ailments. Beneficial therapeutic outcomes rely on patients taking them as directed. Up to 40% of the population experience difficulties swallowing SODFs, resulting in reduced adherence and impaired therapeutic efficacy. Often associated with children, this also presents in adults with dysphagia, and without any organic dysphagia (non‐physiological‐related or functional dysphagia). This review aims to identify and appraise current interventions used to screen for and overcome pill aversion in adults with functional dysphagia. A comprehensive search of the literature was conducted. Articles reporting pill aversion in adults aged ≥18 years with no underlying cause, history of, or existing dysphagia were included. Study quality was determined using the STROBE tool for observational studies. A narrative synthesis of the findings was prepared. We identified 18 relevant cohort studies, which demonstrate that pill aversion is a global problem. Perceived ease of and/or SODF swallowability appears to be influenced by female gender, younger age, co‐morbidities (e.g., depression), and physical SODF properties. Patients often modify their medicines rather than raise this issue with their healthcare team. Screening for pill aversion is haphazard but controlled postural adjustments, coating SODFs and behavioural interventions appear to be successful solutions. SODF swallowing difficulties are a barrier to effective medication use. Healthcare professionals must recognise that pill aversion is a problem requiring identification through effective screening and resolution by training interventions, appropriate formulation selection or specialist referral. [ABSTRACT FROM AUTHOR]

Introduction: Pyroptosis is a regulated form of cell death, which is often a consequence of the activation of inflammatory caspases.Methods: Appropriate inflammatory responses and the induction of pyroptosis enhance the clearance of pathogens and increase innate immunity.Results: However, excessive pyroptosis contributes to a hyperinflammatory response and aggravates tissue damage, thereby causing inflammatory diseases. There have been recent reports on the modulation of pyroptosis by statins, which may explain part of the pleiotropic actions of these drugs in inflammatory diseases and cancer.Conclusions: Herein, the extant evidence for the potential value of statins in targeting pyroptosis in various diseases is reviewed. [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]

Background: Low-density lipoprotein cholesterol (LDL-C) causes atherosclerotic disease, as demonstrated in experimental and epidemiological cohorts, randomised controlled trials, and Mendelian randomisation studies.Main Text: There is considerable inconsistency between existing guidelines as to how to effectively manage patients at low overall risk of cardiovascular disease (CVD) who have persistently elevated levels of LDL-C. We propose a step-by-step practical approach for the management of cardiovascular risks in individuals with low (< 1%) 10-year risk of CVD, and elevated (> 140 mg/dL, 3.6 mmol/L) LDL-C. The strategy proposed is based on the level of adherence to lifestyle interventions (LSI), and in case of non-adherence, stepwise practical management, including lipid-lowering therapy, is recommended to achieve a target LDL-C levels (< 115 mg/dL, 3.0 mmol/L).Conclusions: Further studies are necessary to answer the questions on the long-term efficacy, safety, and cost-effectiveness of the suggested approach. This is critical, considering the ever-increasing numbers of such low-risk patients seen in clinical practice. [ABSTRACT FROM AUTHOR]

Background The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown. Objective To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents. Methods A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence. Results From 14,493 residents (median [interquartile range] age 87.0 [82.6–91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97–1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50–0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06–2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined. Conclusion An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended. [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]

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. After our attempts to exclude secondary causes and to provide information about the benefits of continued statin therapy (e.g. with information that statins might prolong their life, presenting them their heart age, etc.), many patients (including those who initially described their symptoms as "intolerable") still agree to try continuing the treatment. This approach means that 95% of patients initially suffering muscle pain may be able to continue statin therapy, and only 3-5% experience complete statin intolerance [9-11]. [Extracted from the article]

Objective To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. Methods Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. Results There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8–90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised , the overall prevalence of AF was 17.4% (95% confidence interval 17.1–17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9–17.9) in 2010 to 17.0% (16.1–18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17–1.37], P  < 0.001), all-cause mortality (adjusted HR 1.14 [1.11–1.17], P  < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36–1.76], P  < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22–1.34], P  < 0.001). Conclusions Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy. [ABSTRACT FROM AUTHOR]

Abstract: Adrenaline (epinephrine) has been used for cardiopulmonary resuscitation (CPR) since 1896. The rationale behind its use is thought to be its α-adrenoceptor-mediated peripheral vasoconstriction, causing residual blood flow to be diverted to coronary and cerebral circulations. This protects these tissues from ischaemic damage and increases the likelihood of restoration of spontaneous circulation. Clinical trials have not demonstrated any benefit of adrenaline over placebo as an agent for resuscitation. Adrenaline has deleterious effects in the setting of resuscitation, predictable from its promiscuous pharmacological profile. This article discusses the relevant pharmacology of adrenaline in the context of CPR. Experimental and clinical evidences for the use of adrenaline and alternative vasopressor agents in resuscitation are given, and the properties of an ideal vasopressor are discussed. [Copyright &y& Elsevier]

Abstract: The effects of hypoxia on the vasodilator response of endothelium-denuded rat aortic rings to the calcium channel blocker, nifedipine, were examined. Under normoxic conditions, nifedipine (10−8–3×10−6 M) attenuated the contractility of noradrenaline precontracted rings in a concentration-dependent manner, although the sensitivity was less than what occurs with K+ precontracted tissues. Under hypoxic conditions there was no relaxation by nifedipine. When a concentration–response curve to noradrenaline was constructed before and in the presence of a high concentration of nifedipine (10−5 M), the response to noradrenaline was unaffected in both normoxic and hypoxic conditions. When noradrenaline was replaced by phenylephrine (10−8–10−5 M), the maximum tension was reduced in the presence of nifedipine to 59±6% of the pre-nifedipine value. Repetition of the experiment in the presence of cocaine (10−5 M) revealed the inhibitory effect of nifedipine on noradrenaline-induced contraction, the maximum contraction in the presence of nifedipine falling significantly (P <0.005) to 67±6% of the pre-nifedipine response. When propranolol (10−7 M) was present in the bath, the maximum contraction to noradrenaline was significantly (P <0.05) reduced by nifedipine to 55±4% of its previous value. The fact that nifedipine was able to inhibit phenylephrine-induced contractions and relax noradrenaline-precontracted aortic rings confirms its calcium channel blocking activity. The failure to inhibit noradrenaline when added prior to the noradrenaline-induced contractions suggests an opposing effect in addition to calcium channel blockade, which cancels out the attenuation of noradrenaline — but not phenylephrine-induced contractions. When neuronal uptake of noradrenaline was blocked with cocaine or β-adrenoceptors were blocked with propranolol, the inhibitory effect of nifedipine against noradrenaline-induced contractions was revealed. This suggests that the additional property was due to blockade of neuronal reuptake or antagonism at β-adrenoceptors. This study also showed that nifedipine is ineffective as a vasodilator in the rat aorta under hypoxic conditions. [Copyright &y& Elsevier]

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), " lower is better for longer", and the recent data have strongly emphasized the need of also " the earlier the better ". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta‐analysis was to evaluate the efficacy and safety of colchicine in patients with CAD. Methods: We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all‐cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short‐term effect of colchicine on inflammatory markers. Results: Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta‐analysis. At mean follow‐up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P <.001), recurrent myocardial infarction (3.41 vs. 4.41%; P =.005), stroke (0.40 vs. 0.90%; P =.002) and hospitalization due to CV events (0.90 vs. 2.87%; P =.02) compared to the control group. The 2 patient groups had similar risk for all‐cause mortality (2.08 vs. 1.88%; P =.82) and CV mortality (0.71 vs. 1.01%; P =.38). Colchicine significantly reduced high‐sensitivity C‐reactive protein (−4.25, P =.001) compared to controls but did not significantly affect interleukin (IL)‐β1 and IL‐18 levels. Conclusion: Colchicine reduced CV events and inflammatory markers, high‐sensitivity C‐reactive protein and IL‐6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all‐cause mortality requires further investigation. [ABSTRACT FROM AUTHOR]

Individuals with Familial Hypercholesterolaemia (FH) are at very high risk of cardiovascular disease, which is associated with poor outcomes from coronavirus infections. COVID-19 puts strain on healthcare systems and may impair access to routine FH services. On behalf of the International Lipid Expert Panel (ILEP) and the European FH Patient Network (FH Europe), we present brief recommendations on the management of adult patients with FH during the COVID-19 pandemic. We discuss the implications of COVID-19 infections for FH patients, the importance of continuing lipid-lowering therapy where possible, issues relating to safety monitoring and service delivery. We summarise the evidence for additional benefits of statins and other lipid-lowering drugs during viral infections. The recommendations do not override in any way the individual responsibility of physicians to make appropriate and accurate decisions taking into account the condition of a given patient and the doses, rules, and regulations applicable to drugs and devices at the time of their prescription/use. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a disease in which lipid-laden plaques are developed inside the vessel walls of arteries. The immune system is activated, resulting in inflammation and oxidative stress. Endothelial cells (ECs) are activated, arterial smooth muscle cells (SMCs) proliferate, macrophages are activated, and foam cells are developed, leading to dysfunctional ECs. Epigenetic regulatory mechanisms, including DNA methylation, histone modifications, and microRNAs are involved in the modulation of genes that play distinct roles in several aspects of cell biology and physiology, hence linking environmental stimuli to gene regulation. Recent research has investigated the involvement of DNA methylation in the etiopathogenesis of atherosclerosis, and several studies have documented the role of this mechanism in various aspects of the disease. Regulation of DNA methylation plays a critical role in the integrity of ECs, SMC proliferation and formation of atherosclerotic lesions. In this review, we seek to clarify the role of DNA methylation in the development of atherosclerosis through different mechanisms. Unlabelled Image [ABSTRACT FROM AUTHOR]

• Atherosclerotic cardiovascular disease (ASCVD) is a major cause of mortality and morbidity worldwide. • Improved visualization of early atherosclerosis and better management of residual risk can reduce ASCVD burden. • Recent research has investigated the potential of biomaterials and nanomedicines in meeting this demand. • Liposomes have a wide range of applications in both imaging and treatment of atherosclerosis. • We review the scientific and clinical evidence relating to the use of liposomes in the context of ASCVD. The consequences of atherosclerotic cardiovascular disease (ASCVD) include myocardial infarction, ischemic stroke, and angina pectoris, which are major causes of mortality and morbidity worldwide. Despite current therapeutic strategies to reduce risk, patients still experience the consequences of ASCVD. Consequently, a current goal is to enhance visualization of early atherosclerotic lesions to improve residual ASCVD risk. The uses of liposomes, in the context of ASCVD, can include as contrast agents for imaging techniques, as well as for the delivery of antiatherosclerotic drugs, genes, and cells to established sites of plaque. Additionally, liposomes have a role as vaccine adjuvants against mediators of atherosclerosis. Here. we review the scientific and clinical evidence relating to the use of liposomes in the diagnosis and management of ASCVD. This review describes the experimental and clinical evidence for the use of liposomes in the diagnosis and management of atherosclerotic cardiovascular disease. [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]

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]

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety. [Display omitted] [ABSTRACT FROM AUTHOR]

Gastric cancer is the fourth most common cause of cancer-linked deaths in the world. Gastric tumor cells have biological characteristics such as rapid proliferation, high invasiveness, and drug resistance, which result in recurrence and poor survival. Helicobacter pylori (H. pylori) has been proposed as a first‐class carcinogen for gastric cancer according to the 1994 world health organization (WHO) classification. One of the important mechanisms by which H. pylori affects the gastric environment and promotes carcinogenesis is triggering inflammation. H. pylori induces an inflammatory response and a plethora of different signal transduction processes, leading to gastric mucosal disturbance, chronic gastritis, and a multi-step complex pathway that initiates carcinogenesis. It seems undeniable that the interaction between various cell types, including immune cells, gastric epithelium, glands, and stem cells, is vital for the progression and development of carcinogenesis concerning H. pylori. The interactions of H. pylori with surrounding cells play a key role in cancer progression. In this review, we discuss the interplay between H. pylori and tumor-supportive cells, including mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid derived-suppressor cells (MDSCs) in gastric cancer. It is hoped that clarifying the specific mechanisms for 'cross-talk' between H. pylori and these cells will provide promising strategies for developing new treatments. [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]

Aims: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a key risk factor for ischaemic stroke. Following AF detection, treatment with oral anticoagulation can significantly lower mortality and morbidity rates associated with this risk. The availability of several hand-held devices which can detect AF may enable trained health professionals to adopt AF screening approaches which do not interfere with people's daily routines. This study aims to investigate the effectiveness of a hand-held device (the MyDiagnostick single-lead Electrocardiogram (ECG) sensor) in screening for AF when embedded into the handles of supermarket trolleys. Methods: A mixed methods two-phase approach will be taken. The quantitative first phase will involve the recruitment of 2000 participants from a convenience sample at four large supermarkets with pharmacies. Prospective participants will be asked to conduct their shopping using a trolley embedded with a MyDiagnostick sensor. If the device identifies a participant with AF, the in-store pharmacist will be dispatched to take a manual pulse measurement and a static control sensor reading and offer a cardiologist consultation referral. When the sensor does not detect AF, a researcher will confirm the reading with a manual pulse measurement. ECGs will be compiled, and the sensitivity, specificity and positive and negative predictive values will be determined. A qualitative second phase will consist of semi-structured interviews carried out with those pharmacists and store managers in-store during the running of the trial period. These will explore the perceptions of staff regarding the merits of embedding sensors in the handles of supermarket trolleys to detect AF. Conclusion: This feasibility study will inform a larger future definitive trial. [ABSTRACT FROM AUTHOR]

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold. [ABSTRACT FROM AUTHOR]

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. [ABSTRACT FROM AUTHOR]

Risk-factor identification and risk stratification are prerequisites to the effective primary and secondary prevention of cardiovascular disease (CVD). Patients at the highest risk benefit the most from the intensive risk-factor reduction. However, the high-risk patients' group is heterogeneous, and it is increasingly recognised that there is an 'extreme-risk' category of patients who may require particularly close attention and intensive therapeutic approach. The aim of this study was to identify subgroups of patients at the highest risk of death following myocardial infarction (MI) that might be considered as those at extremely high CVD risk. We used data from 19,582 participants of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry (NCT03065543) of patients with ischaemic heart disease in Poland from 2006 to present. Characteristics of 13,052 patients with chronic coronary syndromes (CCS) were compared with those of 4295 patients with myocardial infarction (STEMI and NSTEMI). Multivariable logistic regression with stepwise backward elimination was used to identify risk factors associated with mortality in the 12–36 months following the index hospitalisation. The mortality rates were significantly higher in patients after MI than in patients with CCS. In the multivariable analysis, the risk factors most strongly associated with 12-month mortality in patients after MI were left ventricular ejection fraction (LVEF) lower than 35% (hazard ratio [HR] 3.83, 95% confidence interval [CI] 3.14–4.67), age >75 years (HR 1.91, 95%CI 1.55–2.35), multivessel coronary artery disease (HR 1.61, 95%CI 1.30–1.99), atrial fibrillation (HR 1.53, 95%CI 1.21–1.94) diabetes mellitus (HR 1.35, 95%CI 1.11–1.64) and increased LDL-C (HR per 1 mmol/l 1.09, 95%CI 1.01–1.19) or creatinine levels (HR per 10 μmol/L 1.04, 95% CI 1.04–1.05). The risk factors that influenced mortality after 24–36 months were consistent with those after 12 months, with additional low haemoglobin (20–25% risk increase per 1 mmol reduction) and chronic obstructive pulmonary disease (65% risk increase after 36 months). In our large, single-center real-world analysis, we identified the patients with the highest risk of death who could probably benefit the most from the most intensive therapy, and hence should be considered to be an 'extreme risk' population. [Display omitted] • There is still a large discussion on the most suitable definition of extremely high-risk CVD patients. • To the best of our knowledge, it is the first analysis that validates the available definitions of the extremely high risk patients. • LVEF<35%, age>75 years, AF, MVCAD, DM, increased LDL-C or Cr and decreased Hb levels were the RFs associated with higher mortality in MI patients. • The patients with these risk factors constitute the population with the highest risk of death that should be considered the 'extreme risk' population. • These patients are expected to derive the most benefit from intensive lipid-lowering combination therapy. [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]

Atherosclerosis is a progressive, inflammatory cardiovascular disorder characterized by the development of lipid-filled plaques within arteries. Endothelial cell dysfunction in the walls of blood vessels results in an increase in vascular permeability, alteration of the components of the extracellular matrix, and retention of LDL in the sub-endothelial space, thereby accelerating plaque formation. Epigenetic modification by SUMOylation can influence the surface interactions of target proteins and affect cellular functionality, thereby regulating multiple cellular processes. Small ubiquitin-like modifier (SUMO) can modulate NFκB and other proteins such as p53, KLF, and ERK5, which have critical roles in atherogenesis. Furthermore, SUMO regulates leukocyte recruitment and cytokine release and the expression of adherence molecules. In this review, we discuss the regulation by SUMO and SUMOylation modifications of proteins and pathways involved in atherosclerosis. [ABSTRACT FROM AUTHOR]

The risk of atherosclerotic cardiovascular disease (ASCVD) is strongly related to lifetime exposure to low-density lipoprotein (LDL)-cholesterol in longitudinal studies. Lipid-lowering therapy (using statins, ezetimibe and PCSK9 inhibitors) substantially ameliorates the risk and is associated with long-term reduction in cardiovascular (CV) events. The robust evidence supporting these therapies supports their continued (and expanding) role in risk reduction. In addition to these 'conventional' therapeutics, while waiting for other innovative therapies, growing evidence supports the use of a range of 'nutraceuticals' (constituents of food prepared as pharmaceutical formulations) including preparations of red yeast rice (RYR), the product of yeast (Monascus purpureus) grown on rice, which is a constituent of food and is used in traditional Chinese medicine. The major active ingredient, monacolin K, is chemically identical to lovastatin. RYR preparations have been demonstrated to be safe and effective in reducing LDL-C, and CV events. However, surprisingly, RYR has received relatively little attention in international guidelines – and conventional drugs with the strongest evidence for event reduction should always be preferred in clinical practice. Nevertheless, the absence of recommendations relating to RYR may preclude the use of a product which may have clinical utility in particular groups of patients (who may anyway self-prescribe this product), what in the consequence might help to reduce population CV risk. This Position Paper of the International Lipid Expert Panel (ILEP) will use the best available evidence to give advice on the use of red-yeast rice in clinical practice. [Display omitted] [ABSTRACT FROM AUTHOR]

A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the years 2015 and 2016. A total of 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. The prevalence of hypertension, diabetes mellitus, dyslipidaemia, and CVD were similar in urban and rural areas (49.5 vs. 49.4%; 13.7 vs. 13.1%; 84.2 vs. 85.2%; 14.4 vs. 14.2%, respectively). The prevalence of obesity (32.3 vs. 37.5%, p < 0.01) and excessive waist circumference (77.5 vs. 80.7%, p < 0.01), as well as abdominal obesity (43.2 vs. 46.4%, p < 0.01), were higher in rural areas in both genders. Mean levels of LDL-C (128 vs. 130 mg/dL, p = 0.04) and non-HDL-C (147 vs. 148 mg/dL, p = 0.03) were slightly higher in rural populations. Altogether, 14.3% of patients with CVD from urban areas and 11.3% from rural areas reached LDL <70 mg/dL (p = 0.04). There were no important differences in the prevalence of hypertension, diabetes, dyslipidaemia, and CVD, or in mean levels of blood pressure, cholesterol fractions, glucose, and HbA1c between Polish urban and rural primary care patient populations. A high proportion of patients in cities and an even-higher proportion in rural areas did not reach the recommended targets for blood pressure, LDL-C, and HbA1c, indicating the need for novel CVD-prevention programs. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia (FH) is a genetic autosomal co-dominant metabolic disorder leading to elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Early development of atherosclerotic cardiovascular disease (ASCVD) is common in affected patients. We aimed to evaluate the characteristics and differences in the diagnosis and therapy of FH children and adults. Methods: All consecutive patients who were diagnosed with FH, both phenotypically and with genetic tests, were included in this analysis. All patients are a part of the European Atherosclerosis Society FH-Study Collaboration (FHSC) regional center for rare diseases at the Polish Mother's Memorial Hospital Research Institute (PMMHRI) in Lodz, Poland. Results: Of 103 patients with FH, there were 16 children (15.5%) at mean age of 9 ± 3 years and 87 adults aged 41 ± 16; 59% were female. Children presented higher mean levels of total cholesterol, LDL-C, and high-density lipoprotein cholesterol (HDL-C) measured at the baseline visit (TC 313 vs. 259 mg/dL (8.0 vs. 6.6 mmol/L), p = 0.04; LDL 247 vs. 192 mg/dL (6.3 vs. 4.9 mmol/L), p = 0.02, HDL 53 vs. 48 mg/dL (1.3 vs. 1.2 mmol/L), p = 0.009). Overall, 70% of adult patients and 56% of children were prescribed statins (rosuvastatin or atorvastatin) on admission. Combination therapy (dual or triple) was administered for 24% of adult patients. Furthermore, 13.6% of adult patients and 19% of children reported side effects of statin therapy; most of them complained of muscle pain. Only 50% of adult patients on combination therapy achieved their treatment goals. None of children achieved the treatment goal. Conclusions: Despite a younger age of FH diagnosis, children presented with higher mean levels of LDL-C than adults. There are still urgent unmet needs concerning effective lipid-lowering therapy in FH patients, especially the need for greater use of combination therapy, which may allow LDL-C targets to be met in most of the patients. [ABSTRACT FROM AUTHOR]

In addition to their cholesterol-lowering effects, statins are associated with pleiotropic effects including improvements in heart failure (HF), reduced blood pressure, prevention of the rupture of atherosclerotic plaques and improved angiogenesis. In addition to these cardiovascular benefits, statins have been implicated in the treatment of neurological injuries, cancer, sepsis, and cirrhosis. These cholesterol-independent beneficial effects of statins are predominantly mediated through signaling pathways leading to increased production and bioavailability of nitric oxide (NO). In this review, the mechanistic pathways and therapeutic effects of statin-mediated elevations of NO are described and discussed. [ABSTRACT FROM AUTHOR]

Statins beside their main effect on reducing the progression of cardiovascular disease through pharmacological inhibition of the endogenous cholesterol synthesis, have additional pleiotropic effects including antiinflammatory effects mediated through the induction of suppressor regulatory T cells (Tregs). Statin-induced expansion of Tregs reduces chronic inflammation and may have beneficial effects in autoimmune diseases. However, statins could represent a double-edged sword in immunomodulation. Drugs that act by increasing the concentration of Tregs could enhance the risk of cancers, particularly in the elderly and may have adverse effects in neurodegenerative disorders and infectious diseases. In the present paper, we review the experimental studies that evaluate the effects of statins on Treg cells in autoimmune and inflammatory diseases and we discuss potential therapeutic applications of statins in this setting. [ABSTRACT FROM AUTHOR]