Landmark study Reveals Biological Links Between Cardiovascular Disease and Depression
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A groundbreaking European Union-funded project has uncovered critical biological connections between cardiovascular disease (CVD) and depression, paving the way for earlier diagnosis, more accurate risk prediction, and personalized treatment strategies for these often-co-occurring conditions.
The TO_AITION project, completed in December 2025, investigated the underlying causes of inflamm
“Cardiovascular disease and mental health have been underestimated and underexplored,” explained a senior researcher involved in the project. “Patients with CVD and depression are among the moast vulnerable, yet their multimorbidity remains poorly understood. We are changing that.”
The Scale of the Problem
CVD remains the leading cause of death globally, with 10.2 million Europeans falling ill with the disease annually. Within Europe, CVD accounts for over 3 million deaths each year, including over 1.6 million among women and 1.5 million among men. Concurrently, depression affects over 300 million people worldwide, increasing CVD risk and mortality by a factor of two to three. Alarmingly,one in three CVD patients experiences depression,and half will develop it following a major cardiac event.
Unraveling the Biological Connection
TO_AITION researchers hypothesized that immune-metabolic dysregulation, driven by genetic predispositions, lifestyle factors, and environmental influences, fuels low-grade systemic inflammation, ultimately leading to the advancement of CVD-depression comorbidity.The project aimed to fundamentally transform our understanding of the causative mechanisms behind this complex interplay,improving diagnosis,monitoring,and management of both conditions.
the consortium, comprised of 14 partner organizations across Europe – including the European Society of Cardiology (ESC) – harmonized and analyzed large-scale human cohorts, incorporating proteomic, epigenetic, and microbiome data. These analyses revealed overlapping inflammatory and metabolic mechanisms, identified potential “driver nodes” of multimorbidity, and pinpointed candidate biomarkers for both diagnosis and prognosis.
Further laboratory and preclinical studies significantly advanced understanding of the CVD-depression connection, identifying proteins, fats, messenger RNAs, and epigenetic signatures associated with the comorbid disease state.Researchers also developed early prototypes of a lab-on-chip assay and a multiscale risk-prediction platform.
A New Platform for Risk Stratification
A key achievement of the project was the demonstration of the TO_AITION cloud risk stratification platform at the ESC Congress 2025 in Madrid. Presented by Dr. Antonis Sakellarios of the University of Ioannina, Greece, this web-accessible platform is designed to support diagnosis, prognosis, and treatment decisions for caregivers, cardiologists, psychiatrists, mental health physicians, and industry partners.
The project has also yielded notable scientific output, including published research in peer-reviewed journals, such as a study exploring the shared genetic basis of major depression and atherosclerotic disease.This research, currently submitted to MedRxiv for peer review, demonstrates that these conditions share genetic risk factors that may contribute to depression’s development through gene expression in blood, brain, and heart tissues.
Inflammation: A Common Thread
“the TO_AITION project concludes that systemic low-grade inflammation, possibly maintained by trained innate immunity, is a likely causal contributor to the development of CVD-depression multimorbidity,” stated dr. Evangelos Andreakos, Director of the Center for Clinical research at the Biomedical Research Foundation of the Academy of Athens, and the project’s coordinator. “TO_AITION has generated an integrated mechanistic framework, identified actionable biomarkers, and produced early prototypes of diagnostic and risk-stratification tools that can improve patient monitoring and management.”
the knowledge generated by TO_AITION promises to enable earlier diagnosis of comorbidity, better prediction of high-risk patients, and more effective, personalized treatment strategies. By clarifying the intricate relationship between these diseases, researchers hope to design interventions that disrupt the cycle of comorbidity, rather than simply managing its consequences. Raising awareness of the strong links between cardiovascular and mental health is essential, empowering clinicians, patients, and policymakers to act sooner and more effectively.
