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This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. FH, a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide., (© 2023. Springer Nature Limited.)

Familial hypercholesterolaemia (FH) is under-recognized and under-treated in Europe leading to significantly higher risk for premature heart disease in those affected. As treatment beginning early in life is highly effective in preventing heart disease and cost-effective in these patients, screening for FH is crucial. It has therefore now been recognized by the European Commission Public Health Best Practice Portal as an effective strategy. Model programmes exist in Europe to identify young individuals with FH, which are based on cascade screening of first-degree relatives of affected individuals, universal screening for high cholesterol, opportunistic screening of high-risk individuals, or a combination of the above approaches. Recommendations presented herein to improve identification of FH emphasize that every country should have an FH screening programme. These programmes should be adapted from existing strategies to best fit the individual country's healthcare system, governments should provide financial support for these programmes and related care, and further research to optimize care and implementations should be conducted., Competing Interests: Conflict of interest: S.S.G. is a consultant at Esperion Therapeutics. A.W. reports research support for pharmaceutical trials of lipid-modifying agents from Amgen, Regeneron, Novartis, and Silence Therapeutics. T.F. was supported by the Ministry of Health of the Czech Republic [grant NU20-02-00261], by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) - Funded by the European Union – Next Generation EU, and received honoraria from Sanofi, Amgen, and Novartis, outside the submitted work. M.D. is a Chief Executive of FH Europe. N.B. is a senior advisor with FH Europe. K.K.R. reports grants and personal fees from Amgen, Sanofi/Regeneron, Pfizer, AstraZeneca, Medicines Company, Kowa, Novartis, Lilly, Algorithm, Boehringer Ingelheim, MSD, Abbvie, Silence Therapeutics, Bayer, Daiichi Sankyo, Esperion, Abbott, New Amsterdam, Resverlogix, outside the submitted work. R.D.S. has received honoraria related to consulting, research, and/or speaker activities from: Abbott, Amgen, Aché, Astra Zeneca, Esperion, EMS, GETZ Pharma, Kowa, Libbs, Merck, MSD, Novo-Nordisk, Novartis, PTC Therapeutics, Pfizer, Roche, and Sanofi. L.T. has received honoraria from Abbott, Actelion, Amgen, Bayer, Daiichi Sankyo, MSD, Mylan, Novartis, Novo Nordisk, Sanofi, Servier, Pfizer, and Recorda. K.I.D. reports grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daichii Sankyo, and Regeneron, and personal fees from Bayer, outside the submitted work. N.P. reports grants from AMGEN, SHIRE, ALEXION, Nutricia, NHC, Biocodex, and NHS. U.G., J.S., M.H., I.G.-I., F.J.P., and M.G. have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Atherosclerotic cardiovascular diseases (ASCVD) including myocardial infarction, stroke and peripheral arterial disease continue to be major causes of premature death, disability and healthcare expenditure globally. Preventing the accumulation of cholesterol-containing atherogenic lipoproteins in the vessel wall is central to any healthcare strategy to prevent ASCVD. Advances in current concepts about reducing cumulative exposure to apolipoprotein B (apo B) cholesterol-containing lipoproteins and the emergence of novel therapies provide new opportunities to better prevent ASCVD. The present update of the World Heart Federation Cholesterol Roadmap provides a conceptual framework for the development of national policies and health systems approaches, so that potential roadblocks to cholesterol management and thus ASCVD prevention can be overcome., Methods: Through a review of published guidelines and research papers since 2017, and consultation with a committee composed of experts in clinical management of dyslipidaemias and health systems research in low-and-middle income countries (LMICs), this Roadmap identifies (1) key principles to effective ASCVD prevention (2) gaps in implementation of these interventions (knowledge-practice gaps); (3) health system roadblocks to treatment of elevated cholesterol in LMICs; and (4) potential strategies for overcoming these., Results: Reducing the future burden of ASCVD will require diverse approaches throughout the life-course. These include: a greater focus on primordial prevention; availability of affordable cholesterol testing; availability of universal cholesterol screening for inherited dyslipidaemias; risk stratification moving beyond 10-year risk to look at lifetime risk with adequate risk estimators; wider availability of affordable cholesterol-lowering therapies which should include statins as essential medications globally; use of adequate doses of potent statin regimens; and combination therapies with ezetimibe or other therapies in order to attain and maintain robust reductions in LDL-C in those at highest risk. Continuing efforts are needed on health literacy for both the public and healthcare providers, utilising multi-disciplinary teams in healthcare and applications that quantify both ASCVD risk and benefits of treatment as well as increased adherence to therapies., Conclusions: The adverse effects of LDL-cholesterol and apo B containing lipoprotein exposure are cumulative and result in ASCVD. These are preventable by implementation of different strategies, aimed at efficiently tackling atherosclerosis at different stages throughout the human life-course. Preventive strategies should therefore be updated to implement health policy, lifestyle changes and when needed pharmacotherapies earlier with investment in, and a shift in focus towards, early preventive strategies that preserve cardiovascular health rather than treat the consequences of ASCVD., Competing Interests: Kausik K. Ray has received honoraria for consulting, lectures from Kowa, Amgen, Regeneron Pharmaceuticals, Sanofi, Daiichi Sankyo, Pfizer, Viatris, AstraZeneca, Eli Lilly, Esperion, New Amsterdam Pharma, Novartis, Silence Therapeutics, Bayer, Boehringer Ingelheim, Novo Nordisk, SCRIBE, CRISPR, Cargene, Vaxxinity, Abbott, Resverlogix. In addition, he has received research grant support to his institution from Sanofi, Daiichi Sankyo, Amgen, Pfizer and MSD and support from the NIHR Imperial Biomedical Research Centre. Brian A. Ference has received research grants from Novartis, Amgen, Pfizer, Merck, and Esperion Therapeutics. In addition, the author has received personal fees for consulting, advisory board participation and lectures from Novartis, Amgen, Regeneron, Sanofi, Merck, Pfizer, Eli Lilly, Novo Nordisk, AstraZeneca, Viatris, The Medicines Co, Mylan, Daiichi Sankyo, dalCOR, CiVi Pharma, KrKa Phamaceuticals, the American College of Cardiology, the European Society of Cardiology, and the European Atherosclerosis Society. Dirk J. Blom has received research grants from Amgen, Amryt, AstraZeneca, IONIS, LIB Therapeutics, Novartis, Regeneron, Sanofi; Lecture fees and personal fees from Amgen, Novartis, Organon, Sandoz, Sanofi and has participated in advisory board for Amgen, Amryt (Chair of the LOWER study steering committee), and Sanofi. Stephen J. Nicolls has benefitted from research support from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience and consulting and honoraria fees from AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Sequirus. Rodrigo Alonso has received honorary fees and participation in pharma symposia or advisory boards in the last five years from Amgen, Tecnofarma, SAVAL, ABBOTT, NovoNordisk, Boehringer-Ingelheim and Teva. Piotr Jankowski has received Honoraria and travel grants from Amgen, Sanofi, Servier. Roopa Mehta has been part of the speakers’ bureau for Amgen. Nathan D. Wong has received Research support through his institution from Novartis and Novo Nordisk and has been a consultant to Novartis. As Co-Principal Investigator of INTERASPIRE, David A. Wood’s Institute is in receipt of Independent Investigator Initiated grants from Abbott, Novartis, Pfizer, Sanofi, Viatris. Samuel S. Gidding has been a consultant on paediatric clinical trials of bempedoic acid for Esperion. Fausto J. Pinto has participated in Advisory Board, Speaker’s bureau, and clinical trials with Astra-Zeneca, Daichii Sankyo, Amgen, Sanofi. Raul D. Santos has received honoraria related to speaker activities, consulting or research from: Abbott, Ache, Abbott, Amgen, Astra Zeneca, Biolab, EMS, Hypera, Libbs, Esperion, Kowa, Getz pharma, Novo-Nordisk, Novartis, Merck, PTC therapeutics, Pfizer, and Sanofi., (Copyright: © 2022 The Author(s).)

Familial hypercholesterolaemia (FH) is the most common inherited metabolic disorder characterized by high cholesterol and if left untreated leads to premature cardiovascular disease, such as heart attacks. Treatment that begins early in life, particularly in childhood, is highly efficacious in preventing cardiovascular disease and cost-effective, thus early detection of FH is crucial. However, in Europe, less than 10% of people living with FH are diagnosed and even less receive life-saving treatment. The Prague Declaration is a call to action for national and European Union policymakers and decision-makers and a result of the Czech EU Presidency meeting on FH Paediatric Screening (early detection of inherited high cholesterol) at the Czech Senate in Prague on 6th September 2022. It builds on a considerable body of evidence which was discussed at the Technical Meeting under the auspices of the Slovenian EU Presidency in October 2021. The Prague meeting addressed the outstanding barriers to the systematic implementation of FH paediatric screening across Europe. In this article, we present the key points from the Prague meeting and concrete actions needed to move forward., Competing Interests: NB is a senior advisor to FH Europe. HB receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799, PI21/01572), Sociedad Española de Cardiología, AstraZeneca, PhaseBio and Novartis; has received consulting/speaking fees from Astra-Zeneca, Novartis, Novo Nordisk and Organon: and is a scientific advisor for MEDSCAPE-the heart.og. KID reports grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron, during the conduct of the study; and personal fees from Bayer, outside the submitted work. BAF received grants from Novartis, Amgen, Merck, Esperion Therapeutics, Pfizer; and personal fees for lectures, advisory boards, and/or consulting from Novartis, Amgen, Regeneron, Sanofi, Merck, AstraZeneca, Pfizer, Eli Lilly, Novo Nordisk, The Medicines Co, Mylan, Daiichi Sankyo, Viatris, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, KrKa Phamaceuticals, American College of Cardiology, European Atherosclerosis Society, European Society of Cardiology. TF is supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) – Funded by the European Union – Next Generation EU. TF received honoraria from Sanofi, Amgen and Novartis in the last 3 years, outside the submitted work. SSG is a consultant at Esperion Therapeutics. UG and part of preparatory work for the Declaration were supported by the Slovenian Research Agency (grants No. J3-2536 and P3-0343). FJP reports grants and modest personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Novartis, Pfizer, Philips, Sanofi/Regeneron, Servier, Vifor, outside the submitted work. KKR has received honoraria for consulting, lectures from Kowa, Amgen, Regeneron Pharmaceuticals, Sanofi, Daiichi Sankyo, Pfizer, Viatris, AstraZeneca, Eli Lilly, Esperion, New Amsterdam Pharma, Novartis, Silence Therapeutics, Bayer, Boehringer Ingelheim, Novo Nordisk, SCRIBE, CRISPR, Cargene, Vaxxinity, Abbott, Resverlogix. In addition, he has received research grant support to his institution from Sanofi, Daiichi Sankyo, Amgen, Pfizer and MSD ŽR has received honoraria from Novartis. RDS honoraria related to consulting, research and/or speaker activities from: Abbott, Ache, Amgen, Amryt, Astra Zeneca, Biolab, Esperion, Eli-Lilly, Getz Pharma, Hypera Farma, Kowa, Libbs, Novo-Nordisk, Novartis, Merck, Pfizer, PTC Therapeutics and Sanofi. HS received honoraria and grants from MSD SHARP & DOHME, AMGEN, Bayer Vital GmbH, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Servier, Brahms, Bristol-Myers Squibb, Medtronic, Sanofi Aventis, Synlab, Astra-Zeneca, Pfizer and Vifor. LT received honoraria from the following companies: Abbott, Amgen, Bayer, Daiichi Sankyo, Janssen, Novartis, Novo Nordisk, Sanofi, Pfizer, Recordati. AW reports research support for pharmaceutical trials of lipid-modifying agents from Amgen, Regeneron, Novartis and Silence Therapeutics. Authors declaring no conflicts of interest: MA, BB, MB, RC, ZC, KC, MD, CdB, MG, MH, NJ, TN, OM, AP, NP, BR, JR, JŠ, MS, MV, IGI., (Copyright © 2022 Bedlington et al.)

Background and Aims: Elevated concentrations of Lipoprotein (a) [Lp(a)] is an inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). This study aims to investigate the clinical utility for patients, and the economic benefit to healthcare systems and society of measuring Lp(a) concentrations more widely today., Methods: We conducted a structured literature review to identify the economic and health benefits and costs of measuring the Lp(a) concentration, potential barriers hindering the uptake of the measure, and potential solutions to address them. These findings were then discussed in an advisory board attended by experts and patient organisations., Results: It was found that if Lp(a) concentration is measured more widely today, patients, healthcare system and society would experience clinical and economic benefits even before specific Lp(a) lowering pharmacological treatments become available. Furthermore, a wider uptake of the Lp(a) measurement would support the development of epidemiological data., Conclusions: For Lp(a) measurement to be more widely used, key barriers which are hindering its uptake need to be addressed. These include i) the perception that the measure may have limited clinical value, ii) lack of awareness on Lp(a), iii) lack of data on the CV benefit of reducing Lp(a), iv) technical and clinical guidelines barriers, and v) healthcare system barriers. Scientific communities and industry should collaborate to address technical challenges and deficiencies in clinical guidelines. However, policy intervention will be crucial for national ASCVD plans to acknowledge the importance of Lp(a)., (Copyright © 2022 Elsevier B.V. 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.)