There are 34 million people affected by FH of every sex, race, and ethnicity; 90% are undiagnosed. The participating countries are Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Egypt, France, Germany, Greece, Hungary, India, Iraq, Italy, Japan, Latvia, Malta, Mexico, the Netherlands, Norway, Oman, Philippines, Portugal, Romania, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, United Arab Emirates, United Kingdom, United States, Uruguay, and Venezuela.
eTable 1. List of National and International FH Registries
eTable 2. List of National and International FH Advocacy Organizations
Customize your JAMA Network experience by selecting one or more topics from the list below.
Representatives of the Global Familial Hypercholesterolemia Community. Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action. JAMA Cardiol. Published online January 02, 2020. doi:10.1001/jamacardio.2019.5173
Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH.
In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created.
Conclusions and Relevance
By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.
Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease (ASCVD).1,2 Carriers of a gene variant in any of the FH-related genes (ie, LDL-R, APOB, PCSK9, and LDLRAP) have a considerably greater risk of cardiovascular disease because of lifelong exposure to elevated cholesterol levels.3,4 When left untreated, FH is the most common life-threatening genetic condition and is found around the world in all races and ethnic groups, with a prevalence of about 1:200-250 and, in some cases, higher owing to founder effects.1,2 The first symptom of FH may be a myocardial infarction or sudden death at a young age.
Although the science related to FH has advanced rapidly since the 1998 World Health Organization (WHO) recommendations were published,5 public awareness and implementation of the original recommendations regarding FH care have lagged substantially. The number 1 barrier to care for the 34 million people worldwide born with FH is lack of diagnosis. Health care clinicians across high-, middle-, and low-income countries underestimate the prevalence, high level of risk for morbidity and mortality due to premature ASCVD, importance of treatment initiation within the first 2 decades of life, and the inheritance pattern necessitating family screening. Additional issues, such as variation in guidelines, understanding by affected individuals of their condition, economic ramifications of living with and affording lifelong care, and pragmatic concerns surrounding possible genetic discrimination, pose additional barriers to care in the minority of people who are able to receive an accurate diagnosis.1,2
This Global Call to Action is intended to refocus attention on FH as a global health priority. Substantial gains to global health could be achieved by optimally diagnosing and treating FH (Figure).
Familial hypercholesterolemia meets current WHO criteria for screening: there is a defined target population, it causes premature morbidity, it is common, it is diagnosable, it is treatable, evidence-based guidelines exist for care, and examples of successful implementation of screening programs exist in many different settings.1,2 In 1998, given both the need and the means available to identify and treat this population, the WHO and many members of the international FH community published the 1998 WHO Report on Familial Hypercholesterolemia5 (Box 1 and Box 2). Examples of successful implementation of FH care in the more than 20 years since that report exist globally (Table 1). Some countries have government-supported FH programs that have led to substantial improvements in recognition and treatment, with as much as a 76% reduction in premature cardiovascular disease rates for those identified.25
Governments and national institutes of health should be made aware of the existence of this health hazard.
Awareness among the general public and the medical community should be promoted. The support of education about these disorders at the public, school, paramedical and medical level is required.
Specific education about these disorders should be provided at all levels, especially in medical training. There should be skills in primary health care to counsel about the risk of the disease, the dietary modifications, and knowledge about statins so that ongoing care can be given.
<10% of patients worldwide with FH are diagnosed; clinicians have limited knowledge of FH2,6
Patients with FH require education regarding the condition.
FH care remains in specialty care, not primary care
Most countries do not have FH care programs
Popular press and media often have incorrect information about statin safety and other lipid-lowering treatments7
Models of care and funding for FH care exist in some countries (Table 2)8
Tier 1 genomic application for FH screening4
General awareness about the high cardiovascular risk entailed by high cholesterol levels is widespread, although not specifically about FH
Guidelines and scientific statements regarding FH care have been published worldwide (Table 2)
Awareness should be enhanced regarding the importance of severe hypercholesterolemia and FH as a global public health issue; awareness should be raised in a broad range with the general public, educational institutions (both public and medical), the general medical community, and health care delivery systems.
Specific attention may need to be given to the management of children with FH and careful research is called for the establishment of active patient organizations, focused on the implementation of the above-mentioned recommendations, is of utmost importance.
Very low general and medical FH awareness persists over the world.2,6
Children remain underrecognized and undertreated worldwide.2
Advocacy organizations exist in several countries (eTable 1 in the Supplement)9
Guidelines for pediatric care of FH developed (Table 2)
Establishment of country/region specific advocacy organizations, focused on the implementation of the recommendations herein, is of utmost importance. Organizations should be a partnership of patients, physicians, and other health care professionals needed for FH care.
As inherited lipid disorders are diagnosable and treatable in the primary health care context, treatment should be available on a fair basis of risk vs other chronic disorders.
FH care remains predominantly with specialists
FH screening programs do not exist in most countries around the globe; genetic testing not available in many countries
Discrimination surrounding genetic testing remains pervasive10,11
Diagnostic criteria have been developed based on genetic testing1,2,12
Consensus phenotypic criteria have been developed1
Genetic testing now exists for FH and cost is declining
Cascade and universal screening programs now exist in a few countries around the world4,13-18
Screening for FH should be performed according to country-specific conditions and guidelines. Screening, testing, and diagnosis may be based on cholesterol levels (with cutoff levels adapted to the country/target population) or positive genetic tests for an LDL cholesterol receptor function defect.
Patients must have unrestricted access to treatment and to cholesterol-lowering medication at no or low cost.
Long-term follow-up and drug adherence should be ensured.
Newer medications are not available everywhere in the world (PCSK9 inhibitors, lomitapide)6
Limited studies on statin adherence for FH
Highly effective generic medications now exist (statins, ezetimibe)1
FH care is cost-effective with statins and ezetimibe16-18
Scientific rationale for early intervention established19
Integration of health care clinicians other than physicians and social media present new opportunities for organizing care
Abbreviations: FH, familial hypercholesterolemia; LDL, low-density lipoprotein; PCSK9, proprotein convertase subtilisin kexin type 9; WHO, World Health Organization.
a The order of the 11 WHO recommendations has been modified to align with 2019 recommendations and many of the 1998 recommendations overlap with more than 1 of the new recommendations.
b See article body for full recommendations; text in the Box has been shortened for space considerations.
Constraints for treating risk. If plasmapheresis is not available, statins with proven efficacy in homozygous FH should be considered.
Patients with homozygous FH remain difficult to treat and have reduced life expectancy20
High risk for atherosclerotic heart disease exists for those with very high LDL cholesterol regardless of heterozygous FH or homozygous FH status, presence of additional risk factors including lipoprotein(a) add risk1,3,12,20,21
New therapies for homozygous FH are available and more are in development; liver transplant used in children20
Life expectancy for those with homozygous FH has increased20
Create, as a special case, separate guidelines for severe and homozygous FH, defined as either the presence of LDL cholesterol level ≥400 mg/dL or a pathogenic gene variant in any of the FH-related genes on 2 different alleles.
A focus should be made on the family and the effect that bereavement could have on children. The plight of children with homozygous FH may need special consideration within budgetary.
Integrated care across the lifespan remains underdeveloped worldwide
Protection against genetic discrimination needed
Improved understanding of the importance of family-based care for FH demonstrated8,19
Develop a family-based care plan with opportunities for patient involvement and shared decision-making over the continuum of the life span.
Registries require sustained funding
FH registries exist worldwide and are providing important data on the state of FH care around the globe (eTable 1 in the Supplement).22-24
Fund national and international FH registries for research to quantify current practices and identify the gaps between guidelines and health care delivery, to publish outcome metrics for monitoring and standardizing care, identify areas for future resource deployment, dissemination and defining best practices, as well as facilitating FH awareness and screening.
Research into the genetic and environmental factors influencing the expression of inherited lipid disorders, the development of atherosclerosis, and the pharmacologic characteristics and efficacy of lipid-lowering drugs should be stimulated. An indication is needed for ongoing research into the factors influencing heart disease, and how to intervene in the pathogenesis of the atherosclerotic process.
FH research underfunded internationally vs other conditions with similar or lower morbidity and mortality
A research agenda for FH, identifying gaps, has been published and gained international acceptance1
Existing scientific statements, reviews, and guidelines continuously update FH research and progress (Table 2)
Improved understanding of the genetic causes of FH, including mutations in LDL-R, APOB, PCSK9, LDLRAP1, and LPA
Conduct basic science, genetic, epidemiologic, clinical, and implementation science research to improve FH care.
WHO should issue guidelines for identification, diagnosis, and medical management of inherited lipid disorders.
Cost of therapies for new medications remains high
Cost-effectiveness and value analyses of FH care exist and are being updated4,13-18
An international guideline has been developed; European scientific statements have been published. Many country-specific guidelines exist (Table 2)2,12
Understand value in FH care, both for the family and for society, including gained years of life expectancy, gained years of life without disability, and lost productivity.
Abbreviations: ASCVD, atherosclerotic cardiovascular disease; FH, familial hypercholesterolemia; LDL, low-density lipoprotein; PCSK9, proprotein convertase subtilisin kexin type 9; WHO, World Health Organization.
SI conversion factor: To convert LDL cholesterol to millimoles per liter, multiply by 0.0259.
For most of the world’s countries, few of the 11 WHO recommendations have been widely implemented, and today 9 of 10 people born with FH remain undiagnosed and therefore are not properly treated.2,6 This lack of care leaves them and their families at high risk for ASCVD. The WHO report suggests the need for an interdisciplinary FH model of care that integrates primary and specialty therapy and includes lifelong care, emotional support (dealing with a genetic diagnosis, stress related to ASCVD, and lifelong need for medication), genetic counseling, and medication adherence strategies.5,8 Advances in the understanding of FH, including basic science, epidemiologic factors, genetics, and drug development, have improved the prognosis for FH since the 1998 report. However, failure to implement the original recommendations has led to a lack of achievement of ASCVD prevention for most of the worldwide FH population, despite the presence of low-cost generic medications to lower cholesterol levels and guidelines for direct care (Box 1 and Box 2).12,26,27
The lack of awareness regarding FH among the general population, health care professionals, health care systems, and the public health community has created many health disparities. These disparities range from age- and sex-based differences for ASCVD prevention to the lack of access to preventive care and medications. Homozygous FH, as an especially severe form of FH affecting younger persons, requires additional resources with care guaranteed by government programs. Concerns about genetic discrimination have created barriers to FH recognition and early treatment. A need to provide new public policy recommendations following the WHO framework was perceived by the global FH community.
In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation partnered to convene the international FH community of individuals with FH, advocacy leaders, scientific experts, and policy makers. The Call to Action was initiated at the FH Foundation Global Summit in Marina Del Rey, California, at a meeting held on October 3, 2018. Representatives from 23 countries agreed to attend and participated in the meeting, including members of advocacy groups and international societies dedicated to improving care for individuals with FH, to revise the original WHO 1998 recommendations and work as an international community to drive global policy change regarding FH. On October 3, 2018, a revised set of recommendations was developed. With goals of increasing inclusion from the international community and further revising and updating the 1998 WHO recommendations, a second meeting was held during the World Congress of Cardiology and Cardiovascular Health in Dubai on December 6, 2018. The international coalition now represents 40 countries and added new advocacy organizations (Figure). Overall attendance included authors of the original 1998 WHO report on FH, patient advocacy organizations from around the world, and international scientific, medical, and public health experts.
This Global Call to Action aims to reinvigorate the WHO’s interest in recognizing FH within their cardiovascular disease prevention strategies as well as advance national efforts to elevate FH as a public health priority. Final recommendations should be considered by countries around the world for implementation as new public policy initiatives regarding FH. The work herein reflects the discussion generated by these 2 meetings, which was reviewed, edited, and signed by all contributors.
The prevalence of FH, originally thought to be about 1:500, has now been demonstrated to be approximately 1:250 worldwide, making it the most common genetic condition causing premature morbidity and mortality associated with ASCVD.4 Improvements in FH knowledge have occurred in the past 20 years. These advances are highlighted in Boxes 1 and 2 and summarized in the FH-specific guidelines, medical reviews, and scientific statements presented in Table 2. International and country-specific, evidence-based lipid guidelines often embed sections regarding FH care. An FH code was introduced in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, in 2016.1
Successful screening programs, using cascade testing of first-degree relatives of identified adults and cascade testing of first-degree relatives of affected infants, have been reported.13-15 These programs identify large numbers of previously unrecognized and untreated individuals with FH and are cost-effective.16-18 Scoring systems to identify probands have been used successfully in many programs, including MEDPED, Simon Broome Registry, and Dutch Lipid clinics.51 Probands identified are often younger than the index cases, have not experienced any ASCVD event, and are untreated.4 An approach to genetic testing, including a definition of index cases for whom genetic testing should be considered, has been published.4
Beyond underdiagnosis, important barriers to FH care exist.10,11 Cost of care, knowledge levels of health care clinicians and patients, guideline variation, competing health issues, understanding of risk, perceptions regarding personal control over health outcomes, and family influence all affect decision-making for this condition, because it is lifelong and puts different demands on families at different times of life. There appears to be clear value to families in establishing a diagnosis of FH that explains high cholesterol levels independent of lifestyle; however, in many countries, there is a personal cost to having this information, such as difficulty in obtaining life insurance or other forms of genetic discrimination.
Research on risk stratification, including the influence of lipoprotein(a), conventional cardiovascular risk factors, subclinical atherosclerosis imaging, and genetics is ongoing.22 Effective lipid-lowering therapies, including statins and ezetimibe, are now available as generic medications for children and adults. In addition, there have been major advances in drug development for the treatment of FH.12,26,27 Potent lipid-lowering therapies, such as inhibitors of proprotein convertase subtilisin kexin type 9 (PCSK9), have been shown to be safe and effective in large clinical trials and are available for patients who do not meet recommended lipid goals during statin and ezetimibe treatment. New therapies, such as lomitapide, are available in some jurisdictions for patients with homozygous FH, and a variety of other investigational agents are currently in development or being evaluated in clinical trials.1,20
Future research must address current gaps in knowledge. While observational data suggest that FH outcomes improve significantly with treatment earlier in life and carrying an FH gene triples the risk for ASCVD at any given level of low-density lipoprotein (LDL) cholesterol, therapeutic inertia exists.10,11 Consensus has not been achieved on the exact timing of treatment initiation, FH-specific LDL cholesterol level goals related to early treatment, and the value of universal screening to identify FH.2,19 Implementation research strategies to increase physician knowledge about FH and improve treatment adherence are needed and should be specific to individual countries.
National and international registries for FH were called for in the 1998 report and have been developed in many countries. Cystic fibrosis registries provide an example for how registries can facilitate improved care and outcomes.52 A list of FH registries is presented in eTable 1 in the Supplement. The registries have provided information regarding the natural history of FH, documenting the harm of late recognition of FH, including the failure to prevent premature ASCVD, and care disparities for women and the underserved population. Registries also document the success of family-based FH screening in identifying previously untreated and unrecognized cases.6,22-25,53 Registries have the potential to serve as resources of information spanning medical, scientific, and social aspects of care; repositories of data showing regional/geographic differences in care; a platform for patients enabling them to be participants in clinical trials; and vehicles for quality improvement and implementation of FH care, including transition of care from childhood to adulthood. International experience demonstrates that registries require governmental funding and support for sustainability. Components of a successful registry have been published.23,24,53
Recognized in the 1998 report as key factors in better individual outcomes, patient advocacy organizations for FH have been established by individuals with FH in many countries.9 A list of these organizations and components is presented in eTable 2 in the Supplement. Components of a successful advocacy organization have been published.9 Advocacy organizations maintain registries, cultivate community support, connect stakeholders with disparate backgrounds, lead in enhancing patient-centered care, and provide a bridge between science and policy.
Advocacy organizations create an FH community that provides peer support. Such organizations help navigate long-term care and facilitate family screening, especially for homozygous FH, the most severe form. The organizations identify high-quality lipid treatment programs in individual countries and often facilitate the referral of patients from generalists to lipid specialists for advanced care, as well as provide education for patients and health care professionals, advocacy for government programs, funding and initiation of research, and awareness-raising campaigns.
Screening and care for FH have been demonstrated to be cost-effective as has use of traditional cholesterol management guidelines on treating people with lower risk than those with FH.16-18,54,55 Care for individuals with FH results in potential freedom from myocardial infarction, increased life expectancy, increased productivity, and absence of the strain placed on families owing to the occurrence of premature ASCVD or sudden death in a young mother or father.
All successful FH care programs around the world have benefited from government support to a multifactorial approach, including medical, nursing, pharmacologic, genetic counseling, nutrition, and psychology resources. Government support helps mandate and optimize medical care in parallel with the work of advocacy organizations’ efforts to improve FH care, but a country-specific approach is needed. Although treatment strategies are clear, best practices to deliver guideline-based care in diverse settings need to be evaluated. Because resources and social structure vary by region and country, health care must be scalable for high-, middle-, and low-income countries.6,56 How governments have created successful programs, raised awareness, educated health care professionals, addressed disparities, and monitored population outcomes is presented in Table 1. The final recommendations of this report should be considered for adoption as health policy around the world, as government support is necessary to guarantee care for the patients with FH who are the most severely affected and prevent genetic discrimination.
Awareness should be enhanced regarding the importance of severe hypercholesterolemia and FH as a global public health issue. Without general awareness of the need for detection and treatment beginning early in life, risk of ASCVD cannot be reduced in the estimated 34 million individuals affected worldwide. Awareness should be raised in a broad range of constituencies, including the general public, educational institutions (both public and medical), the general medical community (including primary and specialty care), and health care delivery systems. The annual worldwide FH Awareness Day is September 24.
Establishment of country/region-specific advocacy organizations, focused on the implementation of the recommendations presented herein, is important. Organizations should be a partnership of patients, physicians, and other health care professionals needed for FH care. Organizations should provide education and patient support for obtaining medical care. A country-specific toolkit should be developed to facilitate a basic understanding of how to create an advocacy organization, such as understanding the determinants of government health care policy, the health technology assessment process, regulations for lobbying governments, advocacy (including against genetic discrimination), communications, dissemination of information, and other basic fundamentals, regardless of income levels.
Screening for FH should be performed according to country-specific conditions and guidelines. Screening may be based on cholesterol levels (with cutoff levels adapted to the country/target population) or positive genetic tests for an LDL receptor function defect. A combination of universal child-parent screening and cascade testing of first- and second-degree relatives of index cases is more useful. Because many individuals with FH meet phenotypic criteria, these criteria could be used as a first step for wide screening programs and to identify those who may benefit the most from undergoing genetic testing where resources are limited. Resources for screening and diagnosis throughout the life course and risk stratification beginning in childhood should be available on a fair basis, respecting the best interests of the child, similar to other genetic conditions.
Treatment for FH to prevent premature ASCVD should be person centered, available, and affordable. Ideally, treatment should begin in childhood and continue over the life course.
As a special case, separate guidelines should be created for severe and homozygous FH, defined as either the presence of LDL cholesterol levels 400 mg/dL or greater (to convert to millimoles per liter, multiply by 0.0259) or a pathogenic gene variant in any of the FH-related genes on 2 different alleles. Guidelines should include strategies for FH identification, genetic diagnosis, differential diagnosis, and medical management of both secondary ASCVD and aortic valve disease. Specialized centers for diagnosis and management for these individuals are a requirement for optimal care. Care of individuals with severe and homozygous FH should be guaranteed by government.
A family-based care plan should be developed with opportunities for patient involvement and shared decision-making over the continuum of the life span. The model of care is best served via integration of primary and specialty care, screening of family members, genetic counseling, social support, community health workers, and developmentally specific resources (eg, childhood, pregnancy, adulthood, management of morbidities, grief counseling).
National and international FH registries for research should be funded to quantify current practices and identify the gaps between guidelines and health care delivery, publish outcome metrics for monitoring and standardizing care, identify areas for future resource deployment, disseminate and define best practices, and facilitate FH awareness and screening. If feasible, patient-centered approaches should be considered, such as a patient platform for data entry and education. Privacy and confidentiality should be ensured by health care professionals, patient advocacy organizations, data processors, and data handlers.
Funding should be provided for research on the genetic and environmental factors influencing the expression of inherited lipid disorders, their natural history, the development of atherosclerosis, interventions to halt the progression of atherosclerosis, risk stratification, and the pharmacologic characteristics, safety, and efficacy of new and existing lipid-lowering drugs. Implementation science should be funded to determine optimal, affordable, and acceptable integrated health care delivery systems applicable to the regional structure. Implementation science has to address health care delivery using existing evidence-based guidelines at multiple levels: government, society as a whole, health care infrastructure, and health care encounters.
Understanding the value of FH care, both for the family and society, including gained years of life expectancy, gained years of life without disability, and lost productivity, is necessary. If FH-specific health economic models (health technology assessment tool) to assess the value of intervention are considered, they must be flexible enough to allow each country to use them according to local circumstances. Ideally, models would be used to calculate value in quality-adjusted life-years or other acceptable metrics. The models should accommodate changes in characteristics (eg, cost of medication and testing) over time. Model components should include prevalence; screening approach (type of testing); cost of treatments, including events; and payers. The models should allow delineation of cost savings from preventive care and identification of previously untreated individuals from cascade testing if applicable.
Historically, FH has served as a paradigm for the cholesterol hypothesis with regard to ASCVD and translational medicine (discovery of the LDL receptor and PCSK9). Given the recent technological advances in both computing and genomics, in the future, FH may serve as a paradigm for bringing together the strengths of both public health and precision medicine approaches to care. The policies advocated herein may help to achieve long-term prevention goals for millions of people in a cost-effective manner.
By developing health systems to manage FH, the perfect model case to evaluate both the strengths and limitations of family-centered lifelong prevention will be created. Evaluating the implementation of programs that initiate simple population screening at young ages and then evolve in complexity to identify individuals who may benefit from new low-cost screening, genetic screening, and then more precise evaluation of family members through targeted cascading of first-degree relatives is both prudent and encompassing. Public awareness of efficient screening paired with providing generic medications for all individuals and improving access to more advanced therapies to those at high risk will serve as a model for how we evaluate the full spectrum of risk for atherosclerotic disease. Tailoring specific and life-saving therapies to those who can benefit most from them is the ultimate goal.
Accepted for Publication: September 27, 2019.
Corresponding Author: Samuel S. Gidding, MD, Familial Hypercholesterolemia Foundation, 959 E Walnut St, Ste 220, Pasadena, CA 91106 (firstname.lastname@example.org).
Published Online: January 2, 2020. doi:10.1001/jamacardio.2019.5173
The Global Familial Hypercholesterolemia Community Authors: The following investigators take authorship responsibility for the study results: Katherine A. Wilemon; Jasmine Patel, MPH; Carlos Aguilar-Salinas, MD; Catherine D. Ahmed, MBA; Mutaz Alkhnifsawi, MD; Wael Almahmeed, MD; Rodrigo Alonso, MD; Khalid Al-Rasadi, MD; Lina Badimon, PhD; Luz M. Bernal, PhD, MSc; Martin P. Bogsrud, MD, PhD; Lynne T. Braun, PhD, CNP; Liam Brunham, MD, PhD; Alberico L. Catapano, MD, PhD; Kristyna Čillíková; Pablo Corral, MD; Regina Cuevas; Joep C. Defesche, PhD; Olivier S. Descamps, MD, PhD; Sarah de Ferranti, MD, MPH; Jean-Luc Eiselé, PhD, MSc; Gerardo Elikir, MD; Emanuela Folco, PhD; Tomas Freiberger, MD, PhD; Francesco Fuggetta, BA; Isabel M. Gaspar, MD; Ákos G. Gesztes, PharmD; Urh Grošelj, MD, PhD; Ian Hamilton-Craig, MBBS, PhD; Gabriele Hanauer-Mader; Mariko Harada-Shiba, MD, PhD; Gloria Hastings; G. Kees Hovingh, MD, PhD; Maria C. Izar, MD, PhD; Allison Jamison, MBA; Gunnar N. Karlsson; Meral Kayikçioğlu, MD; Sue Koob, MPA; Masahiro Koseki, MD, PhD; Stacey Lane, JD; Marcos M. Lima-Martinez, MD; Greizy López, PhD; Tania L. Martinez; David Marais, MD; Letrillart Marion; Pedro Mata, MD; Inese Maurina; Diana Maxwell; Roopa Mehta, MD; George A. Mensah, MD; André R. Miserez, MD; Dermot Neely, MD; Stephen J. Nicholls, MBBS, PhD; Atsushi Nohara, MD, PhD; Børge G. Nordestgaard, MD, DMSc; Leiv Ose, MD, PhD; Athanasios Pallidis; Jing Pang, PhD; Jules Payne; Amy L. Peterson, MD; Monica P. Popescu; Raman Puri, MD; Kausik K. Ray, MD; Ashraf Reda, MD; Tiziana Sampietro, MD, PhD; Raul D. Santos, MD; Inge Schalkers, PhD; Laura Schreier, PhD; Michael D. Shapiro, DO; Eric Sijbrands, MD, PhD; Daniel Soffer, MD; Claudia Stefanutti, MD, PhD; Mario Stoll, MD; Rody G. Sy, MD; Martha L. Tamayo, MD, MSc; Myra K. Tilney, MD, MBA; Lale Tokgözoğlu, MD; Brian Tomlinson, MD, BSc; Antonio J. Vallejo-Vaz, MD, PhD; Alejandra Vazquez-Cárdenas, MD, PhD; Patrícia Vieira de Luca, MSc; David S. Wald, MD; Gerald F. Watts, DSc, PhD; Nanette K. Wenger, MD; Michaela Wolf; David Wood, MD; Aram Zegerius; Thomas A. Gaziano, MD, MSc; Samuel S. Gidding, MD.
Affiliations of The Global Familial Hypercholesterolemia Community Authors: Familial Hypercholesterolemia Foundation, Pasadena, California (Wilemon, Patel, Ahmed, Jamison, Lane, Shapiro, Gidding); Familial Hypercholesterolemia IberoAmericana Network, Madrid, Spain (Aguilar-Salinas, Alonso, Corral, Elikir, Lima-Martinez, Mata, Santos, Schreier, Stoll, Vazquez-Cárdenas); Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México (Aguilar-Salinas, Mehta); Departamaento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México (Aguilar-Salinas, Mehta); Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México (Aguilar-Salinas); International Atherosclerosis Society, Milan, Italy (Alkhnifsawi, Alonso, Al-Rasadi, Folco, Santos); Faculty of Medicine, University of Al-Qadisiyah, Al Diwaniyah, Iraq (Alkhnifsawi); Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates (Almahmeed); Fundación Hipercolesterolemia Familiar, Madrid, Spain (Alonso, Mata); Nutrition Department, Clínica las Condes, Santiago de Chile, Chile (Alonso); Medical Research Center, Sultan Qaboos University Hospital, Muscat, Oman (Al-Rasadi); Cardiovascular Program-ICCC, IR-Hospital de la Santa Creu I Sant Pau, CiberCV, Barcelona, Spain (Badimon); European Society of Cardiology, Biot, France (Badimon); Escuela de Ciencias de la Salud, Universidad Nacional Abierta y a Distancia, Bogotá, Colombia (Bernal); Unit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Oslo University Hospital, Oslo, Norway (Bogsrud); Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity, and Preventive Medicine, Oslo University Hospital, Oslo, Norway (Bogsrud); Department of Adult Health and Gerontological Nursing, Rush University, Chicago, Illinois (Braun); Centre for Heart Lung Innovation, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada (Brunham); Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Institute for Research, Hospitalization, and Health Care, Milano, Italy (Catapano); European Atherosclerosis Society, Göteborg, Sweden (Catapano, Ray, Tokgözoğlu); Diagnóza FH, Czech Republic (Čillíková); FH Europe, Europe (Čillíková, Descamps, Fuggetta, Gesztes, Hanauer-Mader, Hastings, Karlsson, Kayikçioğlu, Marion, Mata, Maurina, Maxwell, Pallidis, Payne, Popescu, Schalkers); FASTA University School of Medicine, Mar del Plata, Argentina (Corral, Wolf); Pacientes de Corazón, Mexico City, Mexico (Cuevas); Department of Clinical Genetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands (Defesche); Centres Hospitaliers Jolimont, Haine Saint-Paul, Belgium (Descamps); Belchol, Belgium (Descamps); Department of Pediatrics, Harvard Medical School, Boston, Massachusetts (de Ferranti); Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts (de Ferranti); World Heart Federation, Geneva, Switzerland (Eiselé, Wood); Sociedad Argentina de Lípidos, Cordoba, Argentina (Elikir, Gaziano); Italian Heart Foundation-Fondazione Italiana Per il Cuore, Milan, Italy (Folco); Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic (Freiberger); Central European Institute of Technology and Medical Faculty, Masaryk University, Brno, Czech Republic (Freiberger); Associazione Nazionale Ipercolesterolemia Familiare, Rome, Italy (Fuggetta); Lisbon Medical School, Centro Hospitalar de Lisboa Ocidental and Genetics Laboratory, Medical Genetics Department, University of Lisbon, Lisbon, Portugal (Gaspar); Szivesen Segitünk Neked, FH Hungary Patient Organisation, Budapest, Hungary (Gesztes); University Medical Centre Ljubljana, University Children’s Hospital, Ljubljana, Slovenia (Grošelj); Flinders University School of Medicine, Adelaide, South Australia, Australia (Hamilton-Craig); FHchol Austria, Vienna, Austria (Hanauer-Mader); National Cerebral and Cardiovascular Centre Research Institute, Suita, Osaka, Japan (Harada-Shiba); Gruppo Italiano Pazienti-Familial Hypercholesterolemia, Milano, Italy (Hastings); Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands (Hovingh); Federal University of São Paulo, São Paulo, São Paulo, Brazil (Izar); FH Sverige, Uppsala, Sweden (Karlsson); Department of Cardiology, Medical Faculty, Ege University, Izmir, Turkey (Kayikçioğlu); Ailevi Hiperkolesterolemi Derneği (Association of Familial Hypercholesterolemia), Bayraklı/İzmir, Turkey (Kayikçioğlu); Preventive Cardiovascular Nurses Association, Madison, Wisconsin (Koob); Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan (Koseki); Department of Physiological Sciences, Universidad de Oriente, Ciudad Bolivar, Venezuela (Lima-Martinez); Endocrinology, Diabetes, Metabolism, and Nutrition Unit, Ciudad Bolivar, Venezuela (Lima-Martinez); Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia (López, Tamayo); São Paulo Heart Institute, São Paulo, Brazil (Martinez); Division of Chemical Pathology, Health Science Faculty, University of Cape Town, Cape Town, South Africa (Marais); Association Nationale des Hypercholestérolémies Familiales, Reims, France (Marion); ParSirdi.lv Patient Society, Riga, Latvia (Maurina); Center for Translation Research and Implementation Science, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (Mensah); Diagene Research Institute, Swiss FH Center, Reinach, Switzerland (Miserez); Faculty of Medicine, University of Basel, Basel, Switzerland (Miserez); Department of Blood Sciences, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom (Neely); HEART UK, Berkshire, United Kingdom (Neely, Payne); Monash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, Australia (Nicholls); Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan (Nohara); Copenhagen General Population Study, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark (Nordestgaard); Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (Nordestgaard); Lipid Clinic, Department of Endocrinology, Morbid Obesity, and Preventive Medicine, Oslo University Hospital, Oslo, Norway (Ose); Institute of Basic Medical Sciences, Department of Nutrition, University of Oslo, Oslo, Norway (Ose); Association of Familial Hypercholesterolemia, LDL Greece, Greece (Pallidis); Faculty of Health and Medical Sciences, University of Western Australia School of Medicine, Perth, Western Australia, Australia (Pang, Watts); Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (Peterson); Fundația pentru Ocrotirea Bolnavilor cu Afectuni Cardiovasculare, Bucharest, Romania (Popescu); Department of Cardiology, Apollo Hospital, New Delhi, India (Puri); Lipid Association of India, New Delhi, India (Puri); Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College of London School of Public Health, London, United Kingdom (Ray, Vallejo-Vaz); Cardiology Department, Menofia University, Shibin Al Kawm, Al Minufiyah, Egypt (Reda); Egyptian Association of Vascular Biology and Atherosclerosis, Cairo, Egypt (Reda); Lipoapheresis Unit, Reference Center for Inherited Dyslipidemias, Fondazione CRN-Toscana Gabriele Monasterio, Pisa, Italy (Sampietro); Italian Association of Inherited Dyslipidemias, Cascina Pisa, Italy (Sampietro); Lipid Clinic Heart Institute, Hospital Israelita Albert Einstein, University of São Paulo Medical School Hospital, São Paulo, Brazil (Santos); Harteraad, the Hague, the Netherlands (Schalkers); Laboratorio de Lípidos y Aterosclerosis, Departamento de Bioquímica Clínica, IndianaFIBIOC-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina (Schreier); Section of Cardiovascular Medicine, Center for Preventive Cardiology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina (Shapiro); Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (Sijbrands); University of Pennsylvania Health System, Philadelphia, Pennsylvania (Soffer); Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy (Stefanutti); Extracorporeal Therapeutic Techniques Unit, Lipid Clinic, Regional Centre for Rare Metabolic Diseases, Umberto I Hospital, Rome, Italy (Stefanutti); Honorary Commission for Cardiovascular Health, Montevideo, Uruguay (Stoll); Department of Medicine, University of the Philippines–Philippine General Hospital, Manila, Philippines (Sy); Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Msida, Malta (Tilney); Lipid Clinic, Mater Dei Hospital, Msida, Malta (Tilney); Department of Cardiology of Cardiology, Hacettepe Univeristy, Ankara, Turkey (Tokgözoğlu); Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR (Tomlinson); Facultad de Medicina, Universidad Autónoma de Guadalajara, Zapopan, Jalisco, México (Vazquez-Cárdenas); Associación Mexícana de Hipercolesterolemia Familiar, México (Vazquez-Cárdenas); Associação Brasileira de Hipercolesterolemia Familiar, Brazil (de Luca); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Wald); Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia (Watts); Emory Women’s Heart Center, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia (Wenger); Patients’ Organization for Patients with Familial Hypercholesterolaemia or Related Genetic Lipid Disorders, Frankfurt, Germany (Wolf); Individuals With Familial Hypercholesterolemia, the Hague, the Netherlands (Zegerius); Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts (Gaziano); Department of Health Policy and Management, Harvard T. H. Chan School of Public Health, Boston, Massachusetts (Gaziano).
Conflict of Interest Disclosures: Ms Wilemon and Drs Patel and Ahmed reported being salaried employees of the Familial Hypercholesterolemia (FH) Foundation. Dr Alonso reported receiving personal fees from Amgen, Aegerion, Novo Nordisk, and Sanofi; personal fees from Tecnofarma; and nonfinancial support from the FH Foundation and Familial Hypercholesterolaemia Studies Collaboration European Atherosclerosis Society outside the submitted work. Dr Al-Rasadi reported receiving grants from Sanofi, Abbott, and Pfizer. Dr Badimon reported serving on the advisory board of Sanofi. Dr Brunham reported serving on the advisory boards of Amgen and Sanofi. Dr Catapano reported receiving grants from Pfizer, Merck, Sanofi, Regeneron, Mediolanum, and Amgen; nonfinancial support from SigmaTau, Menarini, Kowa, Recordati, and Eli Lilly; and personal fees from Merck, Sanofi, Regeneron, Pfizer, AstraZeneca, Amgen, Sigma Tau, Recordati, Aegerion, Kowa, Menarini, Eli Lilly, Amryt, Medco, and Genzyme outside the submitted work. Dr Corral reported receiving grants and personal fees from Amagen and Sanofi and personal fees from Boehringer Ingelheim outside the submitted work. Dr Descamps reported receiving grants and personal fees from Sanofi, Amgen, and Merck outside the submitted work. Dr Eiselé reported receiving grants from Amgen and Sanofi during the conduct of the study, and grants from Novartis, Pfizer, Bristol-Myers Squibb, Astra Zeneca, Boehringer Ingelheim, Manulife, Philips, Access Accelerated, Medtronics, and Edwards outside the submitted work. Dr Elikir reported receiving nonfinancial support from the FH Foundation and Sanofi during the conduct of the study; personal fees from Aegerion Pharmaceuticals and Eurofarma; and nonfinancial support from Teva Pharmaceutical Industries Ltd and Sanofi outside the submitted work. Dr Freiberger reported receiving grants from the Ministry of Health, Czech Republic, and personal fees from Sanofi and from Amgen outside the submitted work. Dr Gesztes reported receiving grants from Amgen and Sanofi outside the submitted work. Dr Harada-Shiba reported receiving grants and personal fees from Amgen Astellas Biopharma and Sanofi; grants from Takeda, Kaneka Medics, Aegerion, and Recordati; personal fees from Kowa and Daiichi Sankyo during the conduct of the study; and serving as an unpaid board member for Liid Pharm outside the submitted work. Dr Hovingh has served as consultant and speaker for biotech and pharmaceutical companies that develop molecules that influence lipoprotein metabolism, including Regeneron, Pfizer, MSD, Sanofi, and Amgen, and serving as principal investigator for clinical trials conducted with Amgen, Sanofi, Eli Lilly, Novartis, Kowa, Genzyme, Pfizer, Decima, and Astra Zeneca. The Amsterdam University Medical Center Department of Vascular Medicine receives honoraria and investigator fees for sponsor-driven studies/lectures. Since April 2019, Dr Hovingh has been employed part-time by Novo Nordisk and Amsterdam University Medical Center. Dr Izar reported receiving personal fees and nonfinancial support from Amgen and Sanofi; nonfinancial support from AstraZeneca, and personal fees from Abbott outside the submitted work. Dr Kayikçioğlu reported receiving grants from Amryrt Pharma, Abbott, Recordati, and Regenerone during the conduct of the study; and grants from Pfizer Novo Nordisk outside the submitted work. Dr Koseki reported receiving grants and personal fees from Kowa; grants from Rohto; and personal fees from Merck Sharp & Dohme, Sanofi, and Amgen Astellas BioPharma outside the submitted work. Dr Marais reported receiving grants from the FH Foundation during the conduct of the study, serving as an investigator in pharmaceutical trials undertaken at the university, providing paid consultation for pharmaceutical companies more than 2 years ago. Dr Mata reported receiving research grants from Amgen and Sanofi and personal fees from Amgen outside the submitted work. Dr Neely reported receiving personal fees from Amgen, Sanofi Regeneron, Novartis, and Akcea outside the submitted work. Dr Nicholls reported receiving grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi Regeneron, and LipoScience, and personal fees from AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim during the conduct of the study. Dr Nohara reported receiving personal fees from Sanofi KK, Amgen Astellas Biopharma, and Aegerion Pharmaceuticals outside the submitted work. Dr Pallidis reported grants and non-financial support from Sanofi and grants and non-financial support from Amgen outside the submitted work. Dr Payne reported receiving grants from Amgen, Sanofi, Amryt, Akcea Therapeutics, Fresenius Medical Care, Novo Nordisk, BHR Pharmaceuticals, Eurofins Biomnis, Linc Medical, Merck-Sharp & Dohme, Bayer, and Alexion Pharma during the conduct of the study; and grants from Amgen, Sanofi, Amryt, Akcea Therapeutics, Fresenius Medical Care, Novo Nordisk, BHR Pharmaceuticals, Eurofins Biomnis, Linc Medical, Merck Sharp & Dohme, Bayer, and Alexion Pharma outside the submitted work. Dr Ray reported receiving grants and personal fees from Amgen, Sanofi, Regeneron, Pfizer, and Merck Sharp & Dohme; personal fees from AbbVie, The Medicines Company, Esperion, Kowa, Cerenis, Bayer, Daiichi Sankyo, Silence Therapeutics, Akcea, Zuelling Pharma, Cipla, Dr Reddys, Novo Nordisk, Astra Zeneca, Boehringer Ingelheim, and Takeda outside the submitted work. Dr Santos reported receiving personal fees from Amgen, Astra Zeneca, Akcea, Kowa, Merck, Novo Nordisk, Esperion, Merck Sharp & Dohme, Sanofi/Regeneron, and Biolab outside the submitted work. Dr Schreier reported receiving grants from Amgen and personal fees and nonfinancial support from Sanofi during the conduct of the study. Dr Shapiro reported receiving grants from the National Institutes of Health outside the submitted work, serving as an unpaid member of the scientific advisory board of Esperion and consultant for Amarin, and has received support from the FH Foundation as an investigator in the FH CASCADE Registry. Dr Sijbrands reported receiving grants from Amgen, Netherlands Heart Foundation, Dutch Health Care Authority, and Pfizer during the conduct of the study. Dr Soffer reported receiving compensation for serving on advisory boards for Medicure, Amgen Inc, and Regeneron; speaking fees from Amgen Inc, Akcea Therapeutics, and Sanofi; and participating in clinical trials (paid to the institution) from Novartis, Regenx Bio, Astra Zeneca, Regeneron, Amgen Inc, and Akcea Therapeutics during the conduct of the study; and providing paid continuing medical education (CME) presentations for the National Lipid Association, Horizon CME, and Catalyst CME. Dr Sy reported receiving grants and personal fees from MSD Philippines and Sanofi, personal fees from Amgen outside the submitted work; OEP for lecture honorarium; payment for serving on the advisory board for Boehringer Ingelheim; and lecture honorarium from Servier Philippines. Dr Tilney reported receiving personal fees from Sanofi outside the submitted work. Dr Tokgözoğlu reported receiving personal fees from Amgen, Abbott, Bayer, Merck Sharp & Dohme, Mylan, Pfizer, Recordati, Sanofi, Servier, and Actelion outside the submitted work. Dr Tomlinson reported receiving personal fees from Amgen Inc, Dr Reddy's Laboratories Ltd, Kowa, and Merck Sharp & Dohme, and grants from Pfizer Inc and Roche outside the submitted work. Dr Vallejo-Vaz reported receiving honoraria for lectures from Amgen, Mylan, and Akcea; nonfinancial support from Regeneron Pharmaceuticals, Inc; and participation in research grants from Amgen, Sanofi, Merck Sharp & Dohme, and Pfizer to the Imperial College London/European Atherosclerosis Society outside the submitted work. Ms Vieira de Luca reported receiving grants from Amgen, Sanofi, AstraZeneca, and Merck; and nonfinancial support from MedLevensohn, MexGlobal, and Roche Diagnostics outside the submitted work. Dr Watts reported receiving grants and personal fees from Amgen and Sanofi Regeneron; grants from Novartis; and personal fees from Gemphire and Kowa outside the submitted work. Dr Wolf reported receiving grants from Lipid Liga eV, Sanofi GmbH, Diamed GmbH, Amgen GmbH, Fresenius Medical GmbH, and AstraZeneca GmbH during the conduct of the study. Dr Gidding reported receiving grants from Amgen and Sanofi Regeneron during the conduct of the study. No other disclosures were reported.
Funding/Support: Funding to support the 2 international meetings to achieve consensus was provided by Amgen and Sanofi Regeneron Pharmaceuticals.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Information: The manuscript for this article was assembled as described in the section Developing the Global Call to Action. Four authors (Ms Wilemon, Ms Patel, Dr Gaziano, and Dr Gidding) examined the original 1998 Recommendations and assessed the gaps within, presented them for discussion at the international meetings for feedback, and revised the text after each meeting based on group discussions. Drafts were circulated to all coauthors 3 times: for review and comment after each of the 2 international meetings and for final comments and approval in early March 2019.
Create a personal account or sign in to: