PerMed FH is an innovative project, aiming to identify precision medicine tools which will help diagnose early and manage correctly familial hypercholesterolaemia (FH).
Amsterdam, the Netherlands - 2024.01.11
The Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), in Portugal, through the Cardiovascular Research Group of its Department of Health Promotion and Prevention of Non-Communicable Diseases (NCD), held a launch meeting of the European project "PerMed FH - Personalizing diagnosis and treatment for Familial Hypercholesterolemia" on 9 and 10 January at its premises in Lisbon. Coordinated by INSA researcher and FH Europe Foundation’s Advisor, Prof. Mafalda Bourbon, this project aims to develop personalised medicine tools to improve the diagnosis and management of FH.
Developed in collaboration with researchers from the University of Helsinki, the University Hospital of Rotterdam, the University of La Réunion Medical School (INSARM unit), and with the FH Europe Foundation (FHEF) patient advocates and Ambassadors, "PerMed FH" was one of the winning projects of the CaixaResearch Health Research 2023 prize, a competition organised by the "la Caixa" Foundation. As a result, this important project, fostering meaningful co-creation, will receive financial support of around 1 million Euros.
The launch meeting was attended by all the partners and its main objective was to build a strong multidisciplinary team, present the project's different Work Packages and to discuss the project's 3-year programme. On this occasion, the international partners also had the opportunity to visit the INSA laboratories where the experimental part of this work would take place, related to functional studies on genes associated with FH. In addition, these studies will also be carried out in the mRNA Metabolism and Ass ociated Diseases Group of INSA's Human Genetics Department.
The PerMed FH project aims to functionally characterise genetic variants found in the 3 genes associated with FH by determining the activity of the protein responsible for removing cholesterol from the circulation, thereby improving diagnosis and stratifying cardiovascular risk. The aim of this project is also to carry out studies to optimise the treatment of FH individuals according to the variant found in order to personalise treatment, increasing adherence to therapy and thus contributing to reducing the risk of cardiovascular events.
FH is the world’s most common monogenic disorder, affecting 1 in 300 people. This means 2.5 million Europeans, with 2 million adults and 500,000 children have FH. Yet, to date only est. 10% are diagnosed and treated causing a huge burden of CVD, which is preventable. FH is caused by variants in 3 genes, the most common being variants in the LDLR gene located by a defect on chromosome 19. The defect makes the body unable to remove a compound from the blood, low-density lipoprotein (LDL), commonly known as the ‘bad’ cholesterol. This compound accumulates in the arteries from birth and poses a very high risk of developing cardiovascular disease at an early age. In fact, compared to the general population between the ages of 20 and 40, these individuals are twenty times more likely to develop significant cardiac complications, such as angina or myocardial infarction.
It is known that FH is associated to a defect in 3 genes, leading to the existence of nearly 6.000 different variants. However, around 3.000 of these variants are of unknown significance. In other words, from the 6.000 identified, half are found in people with a clinical diagnosis of FH but the way they impact LDL receptor protein function remains unclear, so their clinical diagnosis is not confirmed. This is one particular aspect on which the project aims at filling the gap. According to Mafalda Bourbon, the project proposes the characterization of all Portuguese variants and plan to achieve a definite classification in about 70% of all variants FH worldwide. For this purpose, the research group coordinated by Dr. Simon Pfisterer from the University of Helsinki, will be of paramount importance since they established novel tools for automated quantification of intracellular lipid storage, which allows the analysis more than one variant at a time.
Concerning treatment, Mafalda Bourbon explains that: “There are several drugs available, but the condition manifests differently, according to the variant type present and the activity of the LDL receptor found, in a given patient.” This means that not all individuals with FH need the same kind of treatment. In this way, Dr. Gilles Lambert and his coworkers, from the University of La Réunion Medical School Saint Pierre, due to their experience in cell biology techniques and drug assays, will give important inputs in developing personalized therapeutic options. Consequently, “(…) treatment can be optimized in a way that each patient will receive the right treatment improving the overall outcomes - increasing its adherence and decreasing side effects.”, points out Mafalda Bourbon.
The other aspect of innovation in PerMed FH is the engagement of patients alongside other researchers, clinicians and relevant stakeholders as experts and contributors in relevant surveys and focus groups, using the Delphi method, which will be led by Prof Eric Sijbrands, University Hospital Rotterdam, Rotterdam.
The role of FH Europe Foundation and its Patient Ambassadors is to identify patient experts, co-create appropriate communication and a dissemination plan, to collect patient stories, where FH was misdiagnosed, or incorrect use of treatment was applied in the absence of correct genetic diagnosis. The project aims to develop user-friendly communication strategies to increase health literacy among patients, their caregivers (often family members, parents and or spouses) and prospective patients, to educate about FH, the role of genetics and gene variants, precision medicine, and to empower them to better advocate for themselves, have more informed discussions with their practitioners to enable a shared decision process regarding FH management for better outcomes.
“We hear very often, from people with FH, that they are not included on finding the solutions for a better clinical management and care of their condition”, confesses Mafalda Bourbon. Taking this into account, the project includes an innovation way of building up the model of care to be further on applied in the clinical practice. It foresees a focus group with clinicians, scientists and, most importantly, people affected with FH and HoFH, where they will be able to co-create the model of care to better respond to their needs and expectations.
“The project offers a scientific breakthrough to address key unmet clinical needs for more than 30 million individuals affected around the globe. It will reduce not only the disease burden but also the emotional, economic, and societal burden – for the individuals, families, society and health care systems. It will enable earlier and correct diagnosis of the individuals including their relatives, which will inform more optimal disease management, preventing (further) cardiovascular disease and improving quality of life. For us this project means that we will be part of this change and that our work will save lives.” – concludes Magdalena Daccord.
Early diagnosis of FH, and differentiation between heterozygous FH or its rare form, the homozygous FH, enables appropriate management to be applied from childhood and is crucial to reduce the likelihood of suffering a heart attack and other cardiovascular health issues. In this regard, researchers and FH patients will collaborate to develop tools to better classify those affected with FH based on their gene defect and protein function, stratifying their cardiovascular risk and allowing for selection of the best treatment for each individual. These personalised medicine tools can be integrated into clinical protocols to provide early diagnoses and the implementation of effective management measures to prevent premature cardiovascular diseases and death, thereby promoting cardiovascular health and improving the quality of life and life expectancy of the affected individuals.
The major expected outcome – will be accomplished within the duration of the project (3 years) by means of the development of three main tasks. Researchers will make efforts to improve the diagnosis and the treatment and, finally, building up the model of care itself, being the latter one informed by the conclusions found in the two first ones.
Note: The project comes at the time when a great emphasis is put on cardiovascular disease prevention and cardiovascular health promotion with efforts like the one of the European Alliance for Cardiovascular Heath, of which FHEF is a Partner. The project compliments other efforts of the wider community related to early screening an FH diagnosis for CVD prevention, like the PERFECTO project, coordinated by FHEF.
Personalizing diagnosis and treatment for Familial Hypercholesterolaemia patients
999,912.00 €
*Project awarded in collaboration with the Fundação para a Ciência e a Tecnología
3 years
Season's Greetings and Tips for a Healthy Holiday Season
Welcome to the festive season, a time of joy, togetherness, and celebration! FH Europe Foundation extends heartfelt wishes for a wonderful holiday season and a prosperous New Year ahead.
As we enter this time of the year, we know it can be challenging to strike a balance between enjoying the festivities and maintaining a healthy lifestyle and we are here to help you.
We would like you to embrace the importance of prioritising health and well-being, especially keeping in mind the impact it may have on those living with inherited lipid conditions and the importance of looking after yourself and each other.
With the help of our community and experts, we are delighted to share some tips and helpful resources that will help us all to celebrate joyfully and mindfully, with a focus on our overall health and happiness, especially looking after our hearts.
Balancing Traditional Feasts with Healthier Options
Did you know that each 100g portion of Christmas pudding contains a very high number of sugars (32,6g), a medium amount of fat (9,7g) and salt (0,5g), as well as 296 calories? Or that by eating two classic chocolate bonbons, you consume 9g of sugar and 5g of fat (and it´s hard to eat only two, right?).
Traditional Christmas dinners can be health-friendly.
Mindful Eating Practices
Mindful eating is about being aware of what we are doing and actively participating in making those choices.
Studies show that being mindful of what we eat helps us avoid overeating since it takes time for our brain to register that our stomach is full and enjoy the flavours and experiences of the food we eat.
The top tips for incorporating mindful eating into your daily life include:
Smart Dining Strategies when not eating at home
Other smart tips:
No idea what or how to cook healthily?
Check out the following websites with healthy recipes:
You can also download:
Whether you have a specific diet or not, we encourage you to read the food labels and get to know more about your food intake (sugar/salt/fat/etc):
Mindful drinking
Alcohol raises cholesterol and blood pressure and causes weight gain. For your health, limit your Christmas consumption.
Here are some tips how to be more drink-aware during December:
Here are some links to help you understand alcohol and your heart health:
Amidst the joyous celebrations, it's crucial to recognize and manage the potential increase in stress levels. We understand the link between the holiday season and heightened stress, and we're here to lend a helping hand. Managing stress becomes pivotal during this time, and we have some effective tips to share. Alongside this, we strongly advocate for self-care activities as a means of alleviating stress. Whether it's taking intentional breaks or indulging in hobbies that bring you joy, prioritize these activities to nurture your well-being.
Here are some tips:
In essence, prioritize self-care during this holiday season. Sing your heart out, practice meditation, and cherish moments with loved ones. These self-care activities significantly contribute to your well-being, fostering joy and resilience. Remember, you're not alone in managing holiday stress. We're here to support you every step of the way, offering guidance and encouragement.
As the holiday season unfolds, maintaining physical activity becomes pivotal, and we're here to aid you in infusing activity into your celebrations with some tips:
Remember, incorporating physical activity into your holiday routine not only enhances your physical health but also elevates your spirits and contributes to your overall well-being. Share our tips for staying active and embracing healthier choices during this festive period, and feel free to exchange your methods for sustaining a healthy and joyful holiday season!
Other useful Resources:
The latest findings from the European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC), the global FH registry, were published in The Lancet on Tuesday, December 12. The evidence clearly supports the efforts of FH Europe Foundation and its Network of Patient Organisations and the wider community advocating for early universal for cholesterol screening, known as the FH paediatric screening.
This landmark publication comes on the same day as the multidisciplinary advocacy community under the umbrella of European Alliance for Cardiovascular Health (EACH) comes together in Strasbourg at the European Parliament to call upon the European Union to prioritize cardiovascular health and asks for a robust policy response in a form of a Cardiovascular Health Plan for Europe, where prevention and early screening for inherited CVD risk factors like FH are clearly named in the effort to promote cardiovascular health across Europe.
FH Europe Foundation and the patients community are proud to partner with EAS FHSC and jointly advocate for a change in how FH is screened for, detected and managed to prevent atherosclerotic CDV.
Continue reading the press release below [adapted from the official press release here].
Finding children with familial hypercholesterolaemia (FH), the most common inherited lipid disorder, relies on family cascade screening, usually after a parent or relative has a heart attack, as physical signs of FH in children are uncommon, meaning that detection is delayed in most. These were the key findings from the European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry, including nearly 12,000 children with FH from 48 countries, which were published in The Lancet on 12th December .[1] As early detection and treatment of FH are essential to prevent heart attacks associated with high cholesterol in later life, these data make the case for a paradigm shift to universal screening in children to avoid delays in detection.
Department of Primary Care & Public Health, Imperial College London, UK), who leads the FHSC registry: ‘Twenty-five years ago, the World Health Organization (WHO) recognised FH as a public health priority, recommending early identification and treatment to prevent cardiovascular complications in later life.[2] These recommendations have been echoed recently by patient advocacy groups, the European Commission, and scientific societies as part of the Prague Declaration[3] to move towards universal screening for FH.[4,5] Early childhood is the ideal opportunity to detect FH and improve long term outcome. However, as shown by these latest data from the FHSC, the current realities of FH care show that children are not the primary focus of detection strategies. For a condition in which early intervention prevents heart attacks in later life, we should be shifting to universal cholesterol screening in early life, to identify and treat children with FH across the world so that they can live long and healthy lives.’
FH affects about one in 300 people,[6] meaning that worldwide in 2023, there are more than 6 million children and adolescents with FH. With nearly half a million born with FH annually,[7] low current identification rates (<10%) will translate to a further 7.3 million affected children by 2040, unless urgent action is taken.
The FHSC registry was established in 2015 with the mission of empowering the global clinical community to seek change in how FH is detected and managed. First data from over 42,000 adults with FH published in 2021 showed that only about 2% are diagnosed as children,[8] meaning that delayed diagnosis may account for one in 10 heart attacks under the age of 50 years.[9]
The work of the EAS FHSC, the global registry, and the initial findings published in the Lancet on the children with FH, have been recently shared with the FH Europe Foundation patients and advocates community at the FH Europe Foundation Annual Network Meeting in Amsterdam, which you can watch below.
This latest report from the FHSC is the largest global analysis of children and adolescents with FH, providing a snapshot of current practices for finding FH in this population. The registry includes 11,848 children with FH, about half of whom were girls, with a median age of 9.6 years at entry.1 The median low-density lipoprotein (LDL) cholesterol level for untreated children was 5.0 mmol/L (about 195 mg/dL), higher in those under 9 years and in girls.
Over two-thirds of children with FH are found with family cascade screening after a parent or relative has a heart attack or other cardiovascular event, or suspected cardiovascular disease, rather than identified directly. Importantly, clinical criteria used for detecting FH in adults have limited relevance for detecting FH in children. For example, irrespective of world region, physical signs of FH such as xanthomas or bumps in the skin containing cholesterol, are uncommon, seen in less than 2% of children with FH in high-income countries and less than 15% of those in less affluent regions. Therefore, relying on clinical criteria is likely to miss most children with FH, especially among those with a milder phenotype.
In adults, LDL cholesterol cut-offs are integral to the diagnosis of clinical FH, especially in lower-income regions with limited access to genetic testing, the gold standard for diagnosis. Even when these LDL cholesterol cut-offs are adapted for children, their use would miss between a quarter and over one-half of children with FH, when compared with genetic testing. Instead, the FHSC registry showed that novel age-specific LDL cholesterol distributions may have potential as a screening tool to improve early diagnosis, as these were able to differentiate children with and without FH from the first year of life.[1]
‘These latest findings from the FHSC show that we urgently need to implement universal cholesterol screening from an early age into public health policy and clinical care. The clock is ticking; already there are more than 6 million children with FH globally, with the vast majority undetected. We need to act now to reduce the widening gap between new cases and detection, and identify and treat children with FH early to avoid costly preventable heart disease in later life,’ said Professor Ray.
Chief Executive of FH Europe Foundation, Magdalena Daccord added: ‘These results from the FHSC on the detection and diagnosis of FH in children are alarming. However, there is now an important shift to promoting cardiovascular disease prevention and cardiovascular health. With the Prague Declaration, evidence from this global registry, and the cost effectiveness of screening on the one hand, and multidisciplinary collaborations that influence national and regional health policies together with increased awareness, education, and patient-citizen engagement on the other, we have a new opportunity to bend the curve. The right to health is a fundamental human right and with early FH detection through universal cholesterol screening we can deliver on the right for cardiovascular health for those children in the future and cardiovascular disease prevention for their parents today.’