DOUBLE DOSE

2021

Cardiomyopathies, caused by genetic mutations affecting cardiac muscle components, pose significant economic and societal burdens due to their hereditary nature and early onset. Despite known genetic defects, predicting disease progression remains challenging due to extreme clinical variability. Recent research indicates that cardiomyopathy mutations induce metabolic stress, exacerbated by factors like obesity, which can accelerate disease progression. The Double Dose hypothesis suggests that targeting metabolic stress may offer preventive or curative strategies for these conditions.

The Focus
The Double Dose Consortium aims to understand how cardiomyopathy-causing mutations lead to structural changes in cardiomyocytes. This interdisciplinary effort combines experts in preclinical research, clinical genetics, health technology assessment, and clinical care focused on cardiomyopathy in both children and adults.

The Research
The consortium combines experts in preclinical research, clinical genetics, health technology assessment and clinical researchers with a strong clinical focus on cardiomyopathy in children and adults. These experts investigate how obesity and muscle adiposity contribute to vascular and cardiac muscle dysfunction in mutation carriers through the analysis of clinical data, patient samples, and experimental models. They will also study the mechanisms underlying ultrastructural changes in cardiomyocytes caused by these mutations, leading to impaired metabolism, contraction, relaxation defects, and disrupted cellular communication within the heart.

Utilizing extensive patient cohorts and ongoing studies, the consortium aims to optimize care for cardiomyopathy patients by assessing the cost-effectiveness of diagnostics and clinical interventions. They plan to translate findings on metabolic alterations into clinical trials targeting treatments that reduce metabolic stress. The Double Dose program will establish biobanks containing serum, tissue, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to provide mechanistic insights into cardiomyopathy pathophysiology and improve diagnosis and care.

Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation, together with Stichting Hartedroom. The consortium is a continuation of the Dosis consortium, in which the interaction between mutation and external factors was investigated. They found that cardiomyopathy-mutations induce metabolic stress and that secondary metabolic stress, such as obesity accelerates disease progression.

 

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Collaborators

Contact person:

Dr. J. van der Velden (Jolanda)

Principal investigators

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Supreme Nudge

2017
A healthy lifestyle - a healthy diet and adequate exercise - contribute significantly to chronic disease prevention. People with a lower socioeconomic position (SEP) often have an unhealthier lifestyle than people with a higher SEP. However, interventions aimed at promoting a healthy lifestyle reach precisely this lower SEP target group poorly and may increase social inequality. A possible explanation is that interventions traditionally tend to focus on individual determinants of behavior such as knowledge, attitudes and intentions. Moreover, these interventions are often not effective, partly because they do not take into account the - social, physical and political - context in which lifestyle choices are made: unhealthy behavior can be seen as an automatic reaction to the 'obesogenic' environment. Changes in and of the environment in which people live can go a long way in promoting healthy lifestyles and reaching all target groups. Changes in the environment should ensure that the healthy choice becomes the easy choice, the obvious choice or even the only choice, especially also for the hard to reach and change target groups such as people with lower education. However, whether environmental interventions are also effective in improving cardiovascular disease risk factors in the longer term is not known and needs to be investigated. The Research Supermarkets form one of the most important point-of-choice settings with the potential to directly influence purchasing behaviors. ‘Nudges’ (small environmental encouragements) target the quick, automatic choices and do not require conscious decision making, and pricing strategies can seduce consumers to buy healthier alternatives. Such environmental cues can make it easier to initiate and maintain a healthy lifestyle, and as such, to improve cardiometabolic health. In addition, the use of theory-based mobile applications is an effective way to provide tailored and context-specific feedback on physical activity behaviors through the stimulation of ‘goal setting’ and ‘self-management’. Being incorporated in structures and systems, environmental interventions can make the healthy choice an easy choice for everyone. As such, these types of interventions are especially effective in reaching otherwise difficult-to-reach groups such as people with a lower socioeconomic position (SEP). In particular, a combination of ‘nudging’ (targeting automatic behaviors), ‘pricing’ (responding to the price-sensitivity of low income consumers) and tailored physical activity feedback and support (which works better than general education), seems promising for lowering cardiometabolic risk in individuals with low SEP. Yet, the existing evidence is mostly restricted to short-term effects on (proxies of) health behaviors, and little is known about long-term impact of such integrated interventions on cardiometabolic risk factors. With SUPREME NUDGE we expand a previous successful Dutch supermarket pricing strategy intervention, and incorporate promising elements such as nudging and ICT applications to provide real-time and context-specific physical activity feedback. We will investigate the effects of this approach on dietary behaviors, physical activity and established cardiometabolic risk factors in adults with a lower SEP. Using principles from Participatory Action Research and systems thinking, we will consult with the relevant stakeholders to explore options for upscaling and further implementation in society. Outcomes will provide policy- and practice relevant evidence with clear, stepwise and realistic leverage points for helping individuals to maintain healthy behaviors and improve their cardiometabolic health by making the healthy choice the easy choice. SUPREME NUDGE is coordinated by the Amsterdam UMC, location VU University, and includes partners from the VU University, University of Amsterdam, Utrecht University Medical Center, Utrecht University, the Dutch Nutrition Center, Te Velde Research, Nynke van der Laan (ICT developer), Duwtje (creative designers) and supermarket chain Coop. The origin The Heart Foundation aims for more people to make healthy choices, so that they feel vital and run less risk of developing (again) cardiovascular diseases, which was one of the themes of the reserach agenda. With its prevention programs, ZonMw contributes to the improvement of prevention practice, to health gains and to reducing socioeconomic health disparities. Results from research show that healthy behavior cannot be taken for granted, and is strongly influenced by people's social and physical environment and socioeconomic status. Proven effective, innovative and accessible methods to enable people to maintain a healthy lifestyle for a long time are lacking. Therefore, the Dutch Heart Foundation and ZonMw have collaborated to form the program "Gezond leven: goed voor het Hart!". SUPREME NUDGE is one of the projects funded from this program.
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DEFENCE

2021
Currently, it is largely unknown to what extent the heart is involved in COVID-19. The aim of this project is to assess the incidence and consequences of cardiac damage in patients who have experienced COVID-19. How often does COVID-19 lead to myocardial damage? What are the short- and long-term consequences of this damage and what can we do to prevent it from occurring? These are the central questions that will be answered within the DEFENCE consortium. The Research The DEFENCE consortium integrates several national studies initiated at the onset of the COVID-19 pandemic, encompassing diverse patient groups as part of the COPP study, ranging from elite athletes (COMMIT study) and individuals recovering at home (COVID@Heart study) to hospitalized patients (CAPACITY-COVID registry and CAPACITY 2 study) and children with post-infection inflammatory syndromes affecting the heart (MIS-C). By harmonizing these initiatives, a unique cohort spanning the entire spectrum of COVID-19 severity has been established. The ongoing studies are extended at multiple levels within the DEFENCE project. This includes: Standardized Healthcare Pathway Implementation: Implementing and evaluating a standardized healthcare pathway to assess cardiac damage occurrence within 6 months post-hospitalization for COVID-19. Serial Cardiac Magnetic Resonance (CMR) Imaging: Performing serial CMR imaging to determine the prevalence and reversibility of myocardial damage, with all scans assessed in a core lab. Evaluation of Cardiovascular Symptoms: Assessing the incidence of cardiovascular symptoms such as chest pain and palpitations in the post-acute phase through patient questionnaires. Linking Data to National Datasets: Linking study data to national datasets at Statistics Netherlands to analyze long-term cardiovascular morbidity and mortality. To evaluate whether cardiovascular disease is a characteristic feature of COVID-19, a comparison with other respiratory tract infections, including seasonal influenza will be made. Origin This research has is funded by ZonMw, but has been set up through the efforts of WCN, NLHI, NHR, the Dutch Heart Foundation, NVVC, NVIC, Harteraad, and the EuroQol Research Foundation, who collaborate within the Dutch CardioVascular Alliance.
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