AtheroNeth

2025

Atherosclerotic cardiovascular disease (ASCVD) is the main cause of mortality in Europe. During the last decades, successful strategies have been developed to treat ASCVD targeting traditional and novel risk factors leading to an unprecedented arsenal to reduce the cardiovascular disease burden. Unfortunately, current strategies are all aimed at adding novel therapeutic agents on top of the standard therapeutic moieties, adopting the one-size-fits-all dogma. This strategy has major limitations including unaddressed heterogeneity of patients, ignoring patients’ side-effects, lack of response to therapy and decreased compliance. With ATHERONETH, we aim to bring forward stratification tools that help to improve the prediction of the actual cardiovascular risk of individual patients, and in particular the pathophysiological mechanisms the contribute to this risk in the individual patient. This will allow clinicians to better tailor their therapeutic regimens.

The Research

Our main objective is to identify biological parameters that can be utilized to better stratify patients with atherosclerotic cardiovascular disease for improved and personalized prevention and treatment. Utilization can be reached by finding circulating biomarkers or imaging characteristics that reflect plaque phenotypes, underlying pathophysiology, and ASCVD incidence.

By combining frontline knowledge, clinical data resources and multimodal technologies, the consortium members will execute the following workplan.

1 - In ATHERONETH we will fine-tune the local phenotypic diversity of human plaques on a multi-omics level and define plaque types that associate with biology and clinical events. These plaque types will be associated with systemic read-outs (biomarkers).

2 - We will define systemic inflammatory and lipid metabolism related determinants of heterogeneity in plaque phenotype and ASCVD.

3 - We will utilise existing data from (large) cohorts to determine (epi)genetic, lipidomic/proteomic, and microbiome-related biomarkers of ASCVD and build algorithms that define subgroups of patients.

4 -We will study imaging parameters of plaque characteristics and inflammation that point to differential disease progression and potential treatment benefit.

The Origin

AtheroNeth leverages scientific power that was generated over the past decade by (inter)national research consortia. This consortium resulted from the DCVA exploration on atherosclerosis. Our vision for the future is to achieve a reduction in ASCVD-associated morbidity and mortality, an improvement in the quality of life for patients, and a reduction of the associated healthcare burden and costs.

Our program has a strong match with the challenges as reported in the “Nationale Hart en Vaat agenda” (National Cardiovascular Agenda) of the Dutch Heart Foundation. It is evident that the current proposal addresses the challenges “Oog voor verschillen” (Eye for differences) and “Behandel op maat” (Tailored treatment).

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Collaborators

Funded

Contact person:

Netherlands Heart Institute

Principal investigators

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COVID@Heart

2020
About 10% of the COVID-19 affected patients develop critical illness with a high mortality rate. This critical illness appears to be strongly linked with cardiovascular disease, as the prevalence of cardiovascular comorbidities and risk factors (such as diabetes and obesity) are often found among hospitalized COVID-19 patients. The consortium COVID@Heart believes that mitigating this cardiovascular burden of Covid-19 should start early, while patients are (still) outside the hospital. The Research COVID@Heart has three core activities: Develop a tool to identify high-risk cardiovascular patients with COVID-19 in a home environment, before the critical illness emerges. This tool will allow general practitioners to better notify high-risk patients, monitor them more closely (e.g. by using home saturation measurements), prescribe preventive cardiovascular medication earlier ('moon shot') and refer them to a hospital promptly when needed. Create a diagnostic tool to improve early differentiation between COVID-19 and a myocardial infarction, addressing the challenge of overlapping symptoms faced by general practitioners. Design a questionnaire supplemented by select biomarkers and blood tests to enhance the detection of cardiovascular disease in COVID-19 survivors experiencing prolonged symptoms of fatigue and shortness of breath, as these symptoms are potentially linked to accelerated subclinical cardiovascular disease. Origin Accurate information on how cardiovascular patients fared while still at home is lacking. This information is crucial to prevent hospital admissions. Therefore, COVID@HEART focuses on people who are not hospitalized but are at home and treated by their general practitioners. The Dutch Heart Foundation supports and funds this research into the best treatment for cardiovascular patients with a coronavirus infection.  
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EMBRACE

2023
Atrial fibrillation (AF) is not benign. It commonly progresses from paroxysmal AF (PAF) to permanent AF. AF progression is associated with major adverse cardiovascular/cerebral events (MACCE). Cardiovascular risk factors and comorbidities (CVR) are present long before the first AF episode, causing a progressive atrial cardiomyopathy (ACM). The mechanisms of ACM vary between patients hindering effective AF management. The EmbRACE network now aims to unravel the diversity of mechanisms underlying ACM, identify simple diagnostic tools to identify them, and develop a therapeutic approach to prevent ACM progression. The Research Early rhythm-control therapy is one promising intervention to potentially interfere with ACM progression next to CVR management. For a sustained impact we aim to develop care pathways to prevent ACM and AF progression and MACCE. Therefore, we will identify and validate relevant cellular and molecular determinants of ACM and AF and their clinical surrogate parameters; develop an in-silico platform to simulate identified mechanisms of ACM and AF and their effects on AF progression and, based on these data, make suggestions for future refinement of ACM therapy; explore the variety of temporal patterns of PAF as markers of ACM subtypes, demonstrate their prognostic relevance and identify surrogate markers available in clinical practice, based on AI and machine learning; test in a randomized trial stratified for sex the hypothesis that early AF ablation and optimal CVR management in AF patients with ACM delays ACM progression and reduces MACCE; explore whether lifestyle management reduces ACM progression, whereas with only rate control ACM progresses; validate the RACE V AF progression score in real life cohorts and translate this and other knowledge into novel care pathways for AF. The origin Atrial fibrillation is the most common cardiac arrhythmia and can lead to a variety of complications, such as stroke. Currently, there are limited treatment options for this cardiac arrhythmia. Moreover, the disease is often noticed late, which makes proper treatment even more difficult. Therefore, the Dutch Heart Foundation funded the RACE V consortium. Afterwards, the Dutch Heart Foundation guided an exploration to form a national consortium as a follow-up around this theme. This led to the EmbRACE consortium, which is a national network of six university medical centers, UMC Groningen, Maastricht UMC+, UMC Utrecht, Amsterdam UMC and LUMC and Erasmus MC, and hospitals in Arnhem and Eindhoven. The Dutch Heart Foundation funds the research.
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