Depression is a common and serious comorbidity of cardiovascular disease (CVD) affecting one in three patients, among which women earlier and more frequently. Depression increases the risk for CVD development, acute events and mortality by >2 fold, independently of traditional risk factors, and constitutes an enormous socioeconomic burden in terms of morbidity, mortality and healthcare costs. Still, the patients at risk, disease trajectories and causative mechanisms involved remain unknown. TO_AITION addresses the hypothesis that immune-metabolic dysregulation, occurring as a result of genetic, lifestyle and environmental risk factors ‘training’ innate immunity, drives low grade systemic inflammation leading to the development of CVD-depression comorbidity. It integrates basic (cell models, immune-metabolic mechanisms, myeloid cell reprogramming), preclinical (animal models, CRISPR genome editing) and clinical (longitudinal cohorts with comprehensive existing data) research, in order to characterise immune-metabolic mechanisms driving CVD-depression comorbidity. Both hypothesis and data-driven strategies will be employed to address causality, focusing on genetic, epigenetic, transcriptional, metabolic and other disturbances leading to the development of comorbidity. Drug-drug interactions and their effects on causative mechanisms and disease trajectories will also be determined. Pathways identified will be evaluated in cell-based and animal models to prove their causal role and obtain mechanistic insight. Finally, new risk models will be developed, and relevant regulatory, cost-effectiveness and feasibility issues addressed. Effective patient-oriented awareness actions, dissemination, exploitation and management activities are also provisioned. TO_AITION will therefore rationally change our current understanding of the causative mechanisms driving CVD-depression comorbidity, unravelling patients’ complexity and improving their diagnosis, monitoring and management.

Immune-mediated diseases (IMDs) are increasing rapidly in the developed countries constituting a huge medical, economic and societal challenge. The reasons to this epidemic are not known, but exposome needs to play an important role since genetic factors cannot explain such a rapid change. In the HEDIMED project altogether 20 academic and industrial partners will join their multidisciplinary and supplementary forces to identify exposomic determinants which are driving this epidemic. The project is based on a combination of data and biological samples from large clinical cohorts constituting the largest clinical resource in this field including 350.000 pregnant women, 28.000 children prospectively followed from birth and 6.600 children from cross-sectional studies. HEDIMED focuses on common chronic IMDs that cause a significant disease burden, including type 1 diabetes, celiac disease, allergies and asthma. Exposomic disease determinants and the underlying biological pathways will be identified by exploratory approach using advanced omics and multiplex technologies combined with cutting–edge datamining technologies. Particular emphasis is paid on early fetal and childhood exposome since the disease process is known to start early. Inclusion of several IMDs makes it possible to identify determinants that are common for many IMDs facilitating the development of widely operating treatments. HEDIMED includes also data and samples from clinical trials that have used exposomice interventions and cell and organ culture models to help the identification of causal associations. HEDIMED will generate an open-access toolbox that offers various kind of data, new technologies, interactions forums, latest information and functional tools for several stakeholders to facilitate the efforts to find ways to control the IMD epidemic. HEDIMED will generate several innovations which can become exploited widely in diagnostic, therapeutic, preventive and health-economical applications. HEDIMED will work together with the other projects (EXPANSE, HEAP, ATHLETE, EQUAL-LIFE, LONGITOOLS, EPHOR, REMEDIA and EXIMIOUS) funded within the Human Exposome programme call H2020 SC1-BHC-2018-2020, in order to achieve collaboration and synergy

In the EU more than 6 million new cardiovascular disease (CVD) cases are reported yearly, along with 1.8 million related deaths, posing a substantial burden on the national healthcare systems and society in general. Development of effective preventive interventions, adopted for each individual and population, will not only reduce the overall cost of patient management, but will also justify the assertion that CVDs could be ultimately prevented and controlled. The exploration of existing clinical, genetic and real-world data sources can contribute to this direction, however several challenges related to the data availability, management and processing remain open. The 48-month project CVDLINK aims to tackle these challenges by implementing a privacy-by-design European-wide federated platform-as-a-service (PaaS) for the delivery of effective data-driven human-centric interventions and the advancement of research and management in the CVD domain. CVDLINK is based on two major offerings: (1) the seamless and legally compliant linking and integration, secure sharing and automated curation of existing data; and (2) a set of AI and data-enabled precision medicine tools and pipelines, for better diagnosis, risk stratification and treatment. In the context of the project, 7 different cardiovascular conditions will be examined, making use of different retrospective datasets, cohort studies and biobanks from 7 counties, aiming to set a paradigm of the how heterogeneous data sources, can be effectively exploited for building comprehensive AI-driven tools, in order to bring substantial benefits for health systems, patients, industry and EU citizens. The developed tools will be prospectively validated in 5 countries, demonstrating the impact of CVDLINK. Additionally, a set of best practices will be generated, which along with a cost-effectiveness analysis, and systematic raising awareness campaigns will promote its wide adoption in the mid-term.