PREDICT 2

Promoting a healthy lifestyle and maintaining it for a long time is crucial for the prevention of cardiovascular diseases. Lifestyle change areonly sustainable and impactful if it takes into account the context in which it occurs. The research Therefore, this netwerk will disseminate this insight widely to policymakers, researchers and everyone who contributes to promoting healthy behaviors. In this way, we can collectively achieve greater health gains when implementing potentially successful interventions. The ultimate goal is to achieve sustainable and impactful lifestyle change in the population. In the projects LIKE, BENEFIT and SUPREME NUDGE, unique expertise has been gained in the field of (1) embedding lifestyle interventions in complex systems, and (2) changing systems underlying lifestyle behavior. Within this national network, we want to disseminate and embed this expertise among researchers, practice professionals and policy makers. We will combine this expertise in the form of two toolboxes; a toolbox for practice professionals and policy makers and a toolbox for researchers. To this end, existing tools will be adapted, where necessary, to make them more widely usable. We aim to embed the toolboxes in (existing) structures and will make the toolboxes findable and disseminated through this netwerk. This network will serve as a structure for connections between stakeholders and contribute to the realization of a sustainable knowledge infrastructure. With this project we identify and create important conditions for successful further development and upscaling of innovative and sustainable ways to sustain healthy living for longer. With this we go further than many existing networks and knowledge infrastructures that focus only on 'effective interventions' but not on the structural embedding in systems or addressing the systems themselves. The origin From 2017, the Dutch Heart Foundation, together with ZonMw, invested in research by three healthy living consortia (LIKE, BENEFIT and SUPREME NUDGE). The common goal was to find new ways to achieve sustainable and impactful lifestyle change in the population. Heart Foundation and ZonMw asked the three healthy living consortia Supreme Nudge, LIKE and Benefit to join forces within this theme by using the knowledge they have gained over the past few years. Although the three consortia each had a different approach, the research leaders agreed on what is needed for lifestyle change to be truly successful: a shift in thinking about lifestyle change. Subsequently, the Dutch Heart Foundation and ZonMw provided follow-up funding to join forces and acquired knowledge in a new knowledge infrastructure.

The IN-CONTROL II consortium builds upon the success of IN-CONTROL I, which highlighted the pivotal role of the microbiome in low-grade inflammation associated with atherosclerotic cardiovascular diseases (CVD) and related risk factors such as lipid levels and microbiome-derived metabolites. These insights are crucial for addressing the rising rates of CVD-related mortality, particularly in aging and overweight populations. The Focus The objectives of IN-CONTROL II are to: Investigate the mechanisms underlying trained immunity in CVD patients, considering factors like senescence, age, sex, and obesity. Elucidate the interactions between microbiome-derived signals (aromatic amino acids, metabolites, bile acids) and immune senescence in obesity-related cardio-metabolic diseases. Identify novel therapeutic targets and develop pharmacological and microbiome-based therapies to counteract inappropriate induction of trained immunity and inflammation in cardiovascular disease. The Research The consortium aims to shift from association to causality, from population-based cohorts to patient groups with atherosclerotic cardiovascular disease (CVD) and from observation to intervention. In this transition, it will also take advantage of recent developments in the network of the consortium, delineating cellular senescence as a druggable target for the broad spectrum of age-related chronic diseases, including cardiovascular diseases, and identification of components of the bile acid-signaling system for this purpose. Another recent development of the recognition of innate immune memory (‘trained immunity’) as pathophysiological mechanism in atherosclerotic CVD. The consortium will conduct proof-of-principle trials in specific patient cohorts, employing advanced experimental techniques such as systems biology, single cell sequencing, innovative animal models, and metabolic flux quantification (fluxomics). A talent program will facilitate knowledge transfer and skill development for young researchers within the consortium, emphasizing rapid translation of research findings into clinical applications. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.