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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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest No professional writer was involved in the preparation of this review., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Acute and chronic physical exercises may enhance the development of statin-related myopathy. In this context, the recent (2019) guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend that, although individuals with dyslipidemia should be advised to engage in regular moderate physical exercise (for at least 30 min daily), physicians should be alerted with regard to myopathy and creatine kinase (CK) elevation in statin-treated sport athletes. However it is worth emphasizing that abovementioned guidelines, previous and recent ESC/EAS consensus papers on adverse effects of statin therapy as well as other previous attempts on this issue, including the ones from the International Lipid Expert Panel (ILEP), give only general recommendations on how to manage patients requiring statin therapy on regular exercises. Therefore, these guidelines in the form of the Position Paper are the first such an attempt to summary existing, often scarce knowledge, and to present this important issue in the form of step-by-step practical recommendations. It is critically important as we might observe more and more individuals on regular exercises/athletes requiring statin therapy due to their cardiovascular risk., Competing Interests: Declaration of Competing Interest NK has given talks, attended conferences and participated in trials sponsored by Amgen, Astra Zeneca, Bausch Health, Boehringer Ingelheim, Elpen, MSD, Mylan, Novo Nordisk, Sanofi and Servier; GB has given talks and attended conferences sponsored by KRKA, Trepharm, Bosnalijek, Akaloid and Novartis; AC has received honoraria as scientific consultant from Meda-Mylan, Menarini International and Sharper; EB - consulting/presentation: Amgen, Genfit, MSD, Sanofi-Regeneron, Aegerion, Chiesi, Rottapharm, Lilly, Ionis pharmaceuticals, Servier, Mylan and Akcea; FA has given talks, attended conferences and participated in trials sponsored by Amgen, AMRYT Pharma and Sanofi; MB - speakers bureau: Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Polpharma, Sanofi-Aventis, Servier and Valeant; consultant to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Freia Pharmaceuticals, Esperion, Lilly, MSD, Polfarmex, Resverlogix, Sanofi-Aventis; Grants from Sanofi and Valeant; All other authors have nothing to declare. #International Lipid Expert Panel (ILEP) Experts (alphabetically): Fahad Alnouri (Cardiovascular Prevention Unit, Adult Cardiology Department. Prince Sultan Cardiac Centre Riyadh, Saudi Arabia), Fahma Amar (Unit of Diabetes &Metabolism, Alexandria University, Alexandria, Egypt), Atanas G. Atanasov (Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland; Department of Pharmacognosy, University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria; Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria), Gani Bajraktari (Institute of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; Clinic of Cardiology, University Clinical Centre of Kosovo, Prishtina, Kosovo; Medical Faculty, University of Prishtina, Prishtina, Kosovo), Maciej Banach (Department of Hypertension, Medical University of Lodz, Poland; Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland, Cardiovascular Research Centre, University of Zielona-Gora, Zielona-Gora, Poland), Marcin A. Bartlomiejczyk (Department of Hypertension, Medical University of Lodz, Poland; Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland), Bojko Bjelakovic (Clinic of Pediatrics, Clinical Center, Nis, Faculty of Medicine, University of Nis, Serbia), Eric Bruckert (Pitié-Salpetrière Hospital and Sorbonne University, Cardio metabolic Institute, Paris, France), Agata Bielecka-Dabrowa (Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland), Alberto Cafferata (Facultad de Medicina, Instituto Universitario de Ciencias de la Salud, Fundación H.A. Barceló, Argentina), Richard Ceska (Third Department of Medicine - Department of Endocrinology and Metabolism of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic), Arrigo F.G. Cicero (Atherosclerosis and Hypertension Research Group, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy), Xavier Collet (Institute of Metabolic and Cardiovascular Diseases, Inserm, Toulouse, France), Olivier Descamps (Department of Internal Medicine, Centres Hospitaliers Jolimont, Haine Saint-Paul, Belgium; Department of Cardiology, Cliniques Universitaires Saint-Luc, Bruxells, Belgium), Nair Devaki (Department of Clinical Biochemistry, the Royal Free London NHS Foundation Trust, Pond Street, London, UK), Dragan Djuric (Institute of Medical Physiology "Richard Burian" Faculty of Medicine, University of Belgrade, Belgrade, Serbia), Ronen Durst (Cardiology Department, Hadassah Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel), Marat V. Ezhov (National Cardiology Research Center, Moscow, Russia), Zlatko Fras (Preventive Cardiology Unit, Department of Vascular Medicine, Division of Medicine, University Medical Centre Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia), Dan Gaita (Institutul de Boli Cardiovasculare, Universitatea de Medicina si Farmacie Victor Babes din Timisoara, Romania), Stephan von Haehling (Department of Cardiology and Pneumology, Heart Center Göttingen, University of Göttingen Medical Center, Georg-August-University, Göttingen, Germany), Adrian V. Hernandez (Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, CT, USA; Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL), Lima, Peru), Steven R. Jones (the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA), Jacek Jozwiak (Department of Family Medicine and Public Health Faculty of Medicine University of Opole, Opole, Poland), Nona Kakauridze (Department of Internal Medicine, Faculty of Medicine, Tbilisi State Medical University, Tbilisi, Georgia), Niki Katsiki (Second Department of Propaedeutic Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece), Amit Khera (Division of Cardiology, UT Southwestern, Dallas, TX, USA), Karam Kostner (Mater Hospital, University of Queensland, St Lucia, QLD, Australia), Raimondas Kubilius (Department of Rehabilitation, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania), Gustavs Latkovskis (Institute of Cardiology and Regenerative Medicine, Faculty of Medicine, University of Latvia, Riga, Latvia; Pauls Stradins Clinical University Hospital, Riga, Latvia), G.B. John Mancini (Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada), A. David Marais (Chemical Pathology Division of the Department of Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa), Seth S. Martin (Ciccarone Center for Prevention of Heart Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA), Julio Acosta Martinez (Medico Cardiologo de la Policlinica Metropolitana, Carcass, Venezuela), Mohsen Mazidi (Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Strand, London, UK), Dimitri P. Mikhailidis (Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK), Erkin Mirrakhimov (Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan), Andre R. Miserez (diagene Research Institute, Reinach, Switzerland; President of Swiss Society of Familial Forms of Hypercholesterolemia (SSFH), Breitenbach, Switzerland; University of Basel, Basel, Switzerland), Olena Mitchenko (Dyslipidaemia Department, Institute of Cardiology AMS of Ukraine, Ukraine; Ukrainian Atherosclerosis Society), Patrick Moriarty (Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA), Seyed Mohammad Nabavi (Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran), Demosthenes B. Panagiotakos (School of Health Science and Education, Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece), György Paragh (University of Debrecen Faculty of Medicine, Department of Internal Medicine, Debrecen, Hungary), Daniel Pella (1 st Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University, Košice, Slovakia), Peter E. Penson (School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK), Zaneta Petrulioniene (Vilnius University Faculty of Medicine, Vilnius, Lithuania; Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania), Matteo Pirro (Department of Medicine, University of Perugia, Perugia, Italy), Arman Postadzhiyan (Bulgarian Society of Cardiology, Medical University of Sofia, Sofia, Bulgaria), Raman Puri (I P Apollo Hospital, New Delhi, India), Ashraf Reda (Menoufia University, President of EAVA), Željko Reiner (University Hospital Center Zagreb, Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia), Jemaa Riadh (Laboratory of Biochemistry, Faculty of Medicine of Tunis, Rabta Hospital, University of Tunis El Manar, Tunis, Tunisia), Dimitri Richter (Cardiac Department, Euroclinic, Athens, Greece), Manfredi Rizzo (Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy), Massimiliano Ruscica (Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy), Amirhossein Sahebkar (Biotechnology Research Center, Pharmaceutical Technology Institute, Neurogenic Inflammation Research Center, and School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran), Naveed Sattar (Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK), Maria-Corina Serban (Department of Functional Sciences, Discipline of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania), Abdulla M.A Shehab (Medical Education Department, United Arab Emirates University, Al Ain, United Arab Emirates), Aleksandr B. Shek (Department of Ischemic Heart Disease and Atherosclerosis, Republican Specialised Center of Cardiology, Tashkent, Uzbekistan), Cesare R. Sirtori (Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano Centro Dislipidemie, Grande Ospedale Metropolitano, Niguarda Ca'Granda President, Fondazione Carlo Sirtori), Claudia Stefanutti (Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy), Tomasz Tomasik (Department of Family Medicine, Chair of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland), Peter P. Toth (The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA), Margus Viigimaa (Tallinn University of Technology, North Estonia Medical Centre, Tallinn, Estonia), Dragos Vinereanu (Cardiology Department, University and Emergency Hospital, Bucharest, Romania, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania), Branislav Vohnout (Institute of Nutrition, Faculty of Nursing and Health Professional Studies and Coordination Centre for Familial Hyperlipoproteinemias, Slovak Medical University in Bratislava, Bratislava, Slovakia; Institute of Epidemiology, School of Medicine, Comenius University, Bratislava, Slovakia), Michal Vrablik (1 st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic), Nathan D. Wong (Department of Medicine, School of Medicine University of California, Irvine, CA, USA; Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, California, USA), Hung-I Yeh (Department of Medicine, Mackay Medical College, Taipei, Taiwan; Cardiovascular Division, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan), Jiang Zhisheng (Institute of Cardiovascular Disease, University of South China, Hengyang, Hunan, China), Andreas Zirlik (University Heart Centre Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany). With the official endorsement of: Association of Cardiologists of the Republic of Uzbekistan, Baltic Society of Atherosclerosis, Chinese Atherosclerosis Society, College of Family Physicians in Poland, Croatian Atherosclerosis Society, Czech Society for Atherosclerosis, Egyptian Association for Endocrinology, Diabetes and Atherosclerosis (EAEDA), French Atherosclerosis Society, Hellenic Atherosclerosis Society, Hellenic Lipidology Society, Hungarian Atherosclerosis Society, International Natural Product Sciences Taskforce (INPST), Israeli Society for Treatment and Prevention of Atherosclerosis, Italian Nutraceuticals Society (SINut), Italian Society for Cardiovascular Prevention (SIPREC), Kosovo Society of Cardiology, Kyrgyz Atherosclerosis Society, Latvian Society of Cardiology, Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group, Lithuanian Heart Association, Mighty Medic, Polish Lipid Association (PoLA), Romanian National Forum for Prevention, Romanian Society of Cardiology, Russian National Atherosclerosis Society, Saudi Group for Cardiovascular Prevention and Rehabilitation of the Saudi Heart Association, Serbian Association for Arteriosclerosis, Thrombosis and Vascular Biology Research (SAATVBR), Slovak Association of Atherosclerosis, Slovenian Society of Cardiology, Society of Endocrine and Metabolic Disease of South Africa, Society on Sarcopenia, Cachexia and Wasting Disorders, South African Heart Association, Swiss Society for Familial forms of Hypercholesterolemia (SSFH), Tunisian Association of Study and Research on Atherosclerosis, Ukrainian Atherosclerosis Society, Very Large Database of Lipids (VLDL)., (Copyright © 2020. Published by Elsevier Ltd.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Familial hypercholesterolemia (FH) is a genetic autosomal dominant disorder caused by an impaired receptor-mediated low-density lipoprotein (LDL) removal from the circulation, mainly due to disruptive autosomal co-dominant mutations in the LDL receptor (LDLr) gene, but also less frequently in the apolipoprotein B100 (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. A rare form of autosomal recessive FH has been also described due to LDLr adaptor protein 1 (LDLRAP1) gene mutations. FH is characterized by very high levels of plasma LDL cholesterol associated with the high incidence of premature atherosclerotic cardiovascular disease (CVD). Despite heterozygous FH (HeFH) patients are still poorly recognized and treated, there is today a large availability of drugs (i.e., statins, ezetimibe and PCSK9 inhibitors) allowing theoretically the normalization of plasma LDL cholesterol levels in this population. Homozygous FH patients (HoFH) have a more severe form of FH, characterized by low responsiveness to the conventional lipid-lowering treatment and often associated with unfavorable prognosis in the young age. Inspired by promising outcomes obtained by orthotopic liver transplantation (OLT), scientists are investigating the possibility of correcting the defective LDLr in these patients by using gene therapy approaches to achieve a novel therapeutic solution with high efficiency. In this article, we tried to review the in vitro, ex vivo, and in vivo attempts conducted to correct FH-causing LDLr gene mutations by using different methods of gene delivery, gene editing, and stem cell manipulation. We also discussed some clinical trials performed in this context., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Orlistat, an inhibitor of intestinal lipase, promotes body weight reduction. The lipid-lowering efficacy of orlistat is controversial and the effect of orlistat-induced body weight reduction on lipid changes has not been explored in meta-regression analyses. A systematic literature search was conducted to identify randomized controlled trials investigating the efficacy of orlistat on plasma total, low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides and lipoprotein(a) levels. Thirty-three studies were included in the meta-analysis (5522 and 4210 participants in the orlistat therapy and control groups, respectively). Orlistat reduced body weight (weighted mean difference: -2.12, p <0.001), total-cholesterol (weighted mean difference: -0.30mmol/L, p <0.001), low-density lipoprotein cholesterol (weighted mean difference: -0.27mmol/L, p <0.001), high-density lipoprotein cholesterol (weighted mean difference: -0.034mmol/L, p <0.001) and triglyceride (weighted mean difference: -0.09mmol/L, p <0.001) concentrations, while no effect on lipoprotein(a) was observed. Total- and low-density lipoprotein cholesterol-lowering were associated negatively with duration of orlistat treatment and positively with body weight changes. In conclusion, Orlistat treatment slightly reduces cholesterol and triglyceride levels, but not lipoprotein(a) levels. Total- and low-density lipoprotein cholesterol levels reductions are more consistent in patients with greater body weight reduction and shorter duration of orlistat treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)