Care Of Familial Hypercholesterolaemia Research Articles

International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia.

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.

Integrated Guidance for Enhancing the Care of Familial Hypercholesterolaemia in Australia

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits all Australian families with or at risk of FH.

Gaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry

Familial hypercholesterolaemia (FH) is under-diagnosed and under-treated worldwide, including Australia. National registries play a key role in identifying patients with FH, understanding gaps in care and advancing the science of FH to improve care for these patients. The FH Australasia Network has established a national web-based registry to raise awareness of the condition, facilitate service planning and inform best practice and care services in Australia. We conducted a cross-sectional analysis of 1,528 FH adults enrolled in the registry from 28 lipid clinics. The mean age at enrolment was 53.4±15.1 years, 50.5% were male and 54.3% had undergone FH genetic testing, of which 61.8% had a pathogenic FH-causing gene variant. Only 14.0% of the cohort were family members identified through cascade testing. Coronary artery disease (CAD) was reported in 28.0% of patients (age of onset 49.0±10.5 years) and 64.9% had at least one modifiable cardiovascular risk factor. The mean untreated LDL-cholesterol was 7.4±2.5 mmol/L. 80.8% of patients were on lipid-lowering therapy with a mean treated LDL-cholesterol of 3.3±1.7 mmol/L. Among patients receiving lipid-lowering therapies, 25.6% achieved an LDL-cholesterol target of <2.5 mmol/L without CAD or <1.8 mmol/L with CAD. Patients in the national FH registry are detected later in life, have a high burden of CAD and risk factors, and do not achieve guideline-recommended LDL-cholesterol targets. Genetic and cascade testing are under-utilised. These deficiencies in care need to be addressed as a public health priority.

Results of the National Program for Detection and Care of Familial Hypercholesterolemia In Uruguay

Results of the National Program for Detection and Care of Familial Hypercholesterolemia In Uruguay

An enquiry based on a standardised questionnaire into knowledge, awareness and preferences concerning the care of familial hypercholesterolaemia among primary care physicians in the Asia-Pacific region: the “Ten Countries Study”

ObjectiveTo determine physicians’ knowledge, awareness and preferences regarding the care of familial hypercholesterolaemia (FH) in the Asia-Pacific region.SettingA formal questionnaire was anonymously completed by physicians from different countries/regions in the...

Knowledge and Practice Gaps in the Care of Familial Hypercholesterolaemia in Australia Compared with China

Knowledge and Practice Gaps in the Care of Familial Hypercholesterolaemia in Australia Compared with China

Progress in the care of familial hypercholesterolaemia: 2016.

Familial hypercholesterolaemia (FH) is the most common autosomal dominant condition, with a prevalence of between one in 200 and one in 350 people in the general population. Untreated FH is associated with premature atherosclerotic cardiovascular disease (CVD). The prevalence of homozygous or compound heterozygous FH is now considered to be about one in 300 000 people. Treating children with FH reduces progression of atherosclerotic CVD and future CVD events. Most individuals with FH are undiagnosed, which together with the recent frequency data in the population and in individuals with premature coronary disease creates a public health challenge and mandates a key role for primary care. Childhood is the optimal period for detecting FH, since low-density lipoprotein cholesterol (LDL-c) concentrations better differentiate affected from unaffected individuals. In an Australian community setting, over 70% of adults with an LDL-c level ≥ 6.5 mmol/L have clinical FH; of these, 30% have a detectable mutation. The community laboratory has an important role in identifying FH, with interpretive comments leading to additional reductions in LDL-c concentrations, and a phone call from the pathologist to the general practitioner improving detection of cases. Cascade screening using DNA testing is cost-effective and acceptable to screenees. Next generation genetic sequencing may differentiate people with polygenic hypercholesterolaemia alone from those with FH. Smoking, hypertension, elevated lipoprotein(a) levels, chronic kidney disease and diabetes are additional atherosclerotic CVD risk factors in FH. Equations for assessing absolute risk of CVD in primary prevention underestimate risk in FH. The adult LDL-c goal is a greater than 50% reduction in LDL-c levels, followed by a target of <2.5 mmol/L, or <1.8 mmol/L for individuals with CVD or other CVD risk factors. Proprotein convertase subtilisin/kexin type 9 inhibitors significantly reduce LDL-c and lipoprotein(a) levels in people with FH. Registries are essential for improving the care of people with FH.

International comparison of services and facilities for the care of familial hypercholesterolaemia (FH)

International comparison of services and facilities for the care of familial hypercholesterolaemia (FH)

International Developments in the Care of Familial Hypercholesterolemia: Where Now and Where to Next?

Several international guidelines and consensus statements have recently been published on the care of familial hypercholesterolemia (FH)(1-3)). They agree on approaches to case detection and cascade testing, protocols in children, lifestyle and drug treatment strategies, and indications for lipoprotein apheresis. However, most countries in the world still do not have integrated, systematic FH screening programs to adequately detect and treat cases in the community. This study provides a comprehensive overview of recent and future international initiatives for closing the gaps in the care of FH.

Recent advances in the understanding and care of familial hypercholesterolaemia: significance of the biology and therapeutic regulation of proprotein convertase subtilisin/kexin type9.

Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder that markedly raises plasma low-density lipoprotein-cholesterol (LDL-C) concentration, causing premature atherosclerotic coronary artery disease (CAD). FH has recently come under intense focus and, although there is general consensus in recent international guidelines regarding diagnosis and treatment, there is debate about the value of genetic studies. Genetic testing can be cost-effective as part of cascade screening in dedicated centres, but the full mutation spectrum responsible for FH has not been established in many populations, and its use in primary care is not at present logistically feasible. Whether using genetic testing or not, cholesterol screening of family members of index patients with an abnormally raised LDL-C must be used to determine the need for early treatment to prevent the development of CAD. The metabolic defects in FH extend beyond LDL, and may affect triacylglycerol-rich and high-density lipoproteins, lipoprotein(a) and oxidative stress. Achievement of the recommended targets for LDL-C with current treatments is difficult, but this may be resolved by new drug therapies. Lipoprotein apheresis remains an effective treatment for severe FH and, although expensive, it costs less than the two recently introduced orphan drugs (lomitapide and mipomersen) for homozygous FH. Recent advances in understanding of the biology of proprotein convertase subtilisin/kexin type 9 (PCSK9) have further elucidated the regulation of lipoprotein metabolism and led to new drugs for effectively treating hypercholesterolaemia in FH and related conditions, as well as for treating many patients with statin intolerance. The mechanisms of action of PCSK9 inhibitors on lipoprotein metabolism and atherosclerosis, as well as their impact on cardiovascular outcomes and cost-effectiveness, remain to be established.

A framework for bridging the gap in the care of familial hypercholesterolaemia in the community: pragmatic and economic perspectives.

To analyze various business models for improving the diagnosis and treatment of familial hypercholesterolaemia. Five different strategies were analyzed and data were collected through documentary analysis and structured interviews. Interviewees included professionals from universities, Western Australia Department of Health, private medical practitioners and not-for-profit organizations. Two business models are recommended: alliance with general practitioners and primary health care organizations and a joint venture model between private cardiology clinics and lipid disorder clinics in the public sector. Primary care providers are in a good position to co-ordinate across the multi-disciplinary health services required to treat familial hypercholesterolaemia within the population. Devolution of knowledge on treatment of familial hypercholesterolaemia from centralized specialist hospital clinics to primary care services is required to improve the rate of detection of this condition in the community. An International Classification of Disease (ICD)-10 and/or a Diagnosis-Related Group (DRG) code is required to codify, catalogue and document new cases and treatment, as well as to facilitate research and re-imbursement strategies. Primary Health Care Organizations can usefully facilitate the transfer of knowledge on best standard of care to general practice, but the best model of care will require close integration of care with specialist and academic centres.

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation.

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected and current treatment is often suboptimal.To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of non-cholesterol risk factors and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed.This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.

Familial hypercholesterolemia in China: Prevalence and evidence of underdetection and undertreatment in a community population

Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism that causes premature coronary and heart disease [ [1] Watts G.F. Gidding S. Wierzbicki A.S. et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol. 2014; 171: 309-325 Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar ]. FH is often undetected and undertreated [ [1] Watts G.F. Gidding S. Wierzbicki A.S. et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol. 2014; 171: 309-325 Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar ]. The prevalence of FH is at least one in 500 in the general population, depending on diagnostic criteria [ [2] Benn M. Watts G.F. Tybjaerg-Hansen A. Nordestgaard B.G. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012; 97: 3956-3964 Crossref PubMed Scopus (468) Google Scholar ]. Currently there is no consensus on the diagnosis of FH although the Dutch Lipid Clinic Network (DLCN) criteria have been widely used [ [1] Watts G.F. Gidding S. Wierzbicki A.S. et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol. 2014; 171: 309-325 Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar ]. In Asia, diagnostic criteria has been proposed by Harada-Shiba et al. [ [3] Harada-Shiba M. Arai H. Oikawa S. et al. Guidelines for the management of familial hypercholesterolemia. J Atheroscler Thromb. 2012; 19: 1043-1060 Crossref PubMed Scopus (144) Google Scholar ], but as with the Simon-Broome criteria from the UK [ [4] Scientific Steering Committee Simon Broome Register Group Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ. 1991; 303: 893-896 Crossref PubMed Google Scholar ], may have low sensitivity for detecting FH, since it does not use a numerical score and relies on the detection of tendon xanthomata, an infrequent sign in young subjects.

Integrated guidance on the care of familial hypercholesterolemia from the International FH Foundation

Familial hypercholesterolemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected, and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment, and management of FH in adults and children and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of noncholesterol risk factors, and the safe and effective use of low-density lipoprotein-lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be used to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.

Impact of the Integrated Guidance on the Care of Familial Hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus- based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of noncholesterol risk factors and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.

Detection and care of familial hypercholesterolaemia in the community: is there a role for the pharmacist?

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that causes marked elevation in plasma cholesterol and premature coronary heart disease. It is estimated that there are at 40 million people with FH worldwide, but most remain unrecognised and inadequately treated. To bridge this gap in coronary prevention several guidelines on detecting and managing FH have been published. We briefly review these and comment on the potential role of pharmacists in case detection, point-of-care testing and pharmacotherapy.