IN CONTROL II

An aneurysm is a bulging or dilation of a blood vessel that usually causes no symptoms but can become life-threatening if it ruptures. It most commonly occurs in the body’s main artery (aorta) or in the brain arteries. Each year, thousands of people in the Netherlands are diagnosed with an aneurysm. The national initiative Aneurysm-NL brings together knowledge and research to improve diagnosis and treatment. By fostering collaboration between physicians, researchers, and patients, we aim to detect aneurysms earlier and treat them more safely, ultimately improving care and reducing mortality from this condition. The Research Aneurysm-NL aims to build a sustainable, nationwide infrastructure that connects medical centers, researchers, and patients to accelerate innovation in aneurysm research and care. A central focus is the development of a national data platform that integrates clinical records, imaging, biobank samples, and genetic information. This resource will allow researchers to reconstruct lifetime disease trajectories, improve risk prediction, and enable more personalized treatment. In parallel, the project develops advanced research tools, including patient-derived in vitro aneurysm models and large-scale omics-approaches to identify new therapeutic targets. By integrating clinical insights with computational modeling and real-world outcome data, Aneurysm-NL supports better decision-making and more effective interventions for both aortic and cerebral aneurysms. It also evaluates the safety and effectiveness of current endovascular and neurosurgical treatments for unruptured brain aneurysms through a large multicenter study. Aneurysm-NL also invests in building a strong and inclusive research community. The project emphasizes collaboration between researchers, clinicians, and patients, and actively works toward linking its infrastructure to national registries and existing healthcare data sources to ensure long-term sustainability and broad accessibility. By uniting expertise from across the country, Aneurysm-NL strives to generate new knowledge, enable earlier and more accurate diagnosis, and personalize treatment strategies for aneurysm patients. The Origin The Aneurysm-NL consortium was established following an exploratory initiative within the Dutch CardioVascular Alliance (DCVA), aimed at identifying opportunities for a national approach to aneurysm research. Based on this exploration, Barend Mees, Hanneke Takkenberg and Mervyn Vergouwen were appointed as coordinators to lead the formation of the consortium. Following a national call in April 2024, they brought together clinicians, researchers and patients from across the Netherlands to collaborate in this new initiative. With funding from the Dutch Heart Foundation, Aneurysm-NL now aims to grow into a nationwide network and data infrastructure, uniting clinical and scientific expertise to advance aneurysm research and care in the coming years.

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).