Report
Teaser, summary, work performed and final results
Periodic Reporting for period 2 - MMAF (Novel multimodal approach to atrial fibrillation risk assessment and identification of targets for prevention by interdisciplinary exploitation of omics, advanced electrocardiography, and imaging)
Teaser
Atrial fibrillation is an increasingly common disease in aging populations. Despite its public health impact, risk prediction is in its infancy. The main objective of the project is to enhance and validate our initial risk prediction algorithm for atrial fibrillation developed...
Summary
Atrial fibrillation is an increasingly common disease in aging populations. Despite its public health impact, risk prediction is in its infancy. The main objective of the project is to enhance and validate our initial risk prediction algorithm for atrial fibrillation developed in international cohorts. Through the exploration of a multimodal approach, including electrocardiographic (ECG), imaging, and biomarkers/omics in blood and tissue we aim to achieve novel pathophysiological insights into the genesis of atrial fibrillation and novel information for risk prediction in clinic and the general population.
Work performed
Broad rhythm monitoring and ECG collection in patients at high risk for atrial fibrillation (clinical cohorts) and community-based individuals (Hamburg City Health Study, http://hchs.hamburg/) is well established and the measurement is ongoing. Cardiac magnetic resonance projects on cardiac morphology and function are ongoing.
Our genome-wide association study data on electrocardiographic phenotypes related to atrial fibrillation entered large-scale consortial analyses in the CHARGE-AF (https://www.cardia.dopm.uab.edu/) consortium. An early repolarization genome-wide association study is ongoing, first results will be available in autumn.
In European cohorts (https://thl.fi/morgam/, http://www.biomarcare.eu/) we have identified a possible association of a specific metabolite that undergoes functional work-up in engineered heart tissue by our colleagues in experimental cardiology. At the population level we are working on a genetic risk score.
We systematically addressed gender/sex differences in atrial fibrillation epidemiology, risk, treatment and outcome in review articles and in European community cohorts as well as European patient samples.
Well-received and broadly discussed in the media and expert panels was our publication on gender differences in atrial fibrillation risk factors in more than 100,000 community-based individuals with more than 20 years of follow-up where we could demonstrate differences in risk factor burden, incidence, risk factor associations, in particular body mass index, and population attributable risks. Work on heart failure as a common comorbidity is ongoing.
All further project activities will carefully assess gender differences to account for our striking findings.
We have already generated an abundance of information in diverse data sets with atrial fibrillation information. In a multiple biomarkers approach we are examining circulating biomarkers in relation to atrial fibrillation in European cohorts and will have the results soon. In the population-based Gutenberg Health Study we correlated asymmetric dimethylarginine, homoarginine and other arginine derivatives representative of oxidative stress and vascular function in relation to atrial fibrillation. Whereas we found weak to moderate associations with intermediate phenotypes derived by imaging (echocardiographic atrial size and function) and electrocardiography, the association with atrial fibrillation was weak after adjustment for confounders indicating the importance of classical cardiovascular risk factors in the pathophysiological process.
We generate countless statistically significant associations through omics interrogation. However the clinical value for risk prediction as additional biomarkers often remains unclear. We have taken data integration at the epidemiological level a step further, using efficient data integration, reliable candidate selection and network analysis towards a systems medicine approach.
Final results
In community-based and clinical cohorts we are collecting comprehensive biological and epidemiologic information on atrial fibrillation in more than 100,000 individuals. Deep-phenotyping including tissue and blood biomarkers will provide insights that have not been possible before. Sex/gender differences have undergone thorough epidemiological work-up with clear differences and disparities that need to be addressed in prevention and treatment of the disease. Our findings, brought to a broad audience, will hopefully change the management of atrial fibrillation in practice.
Exploitation of omics has provided novel pathophysiological pathways that will be addressed in detailed work-up. Overall, we will be able to improve risk prediction of atrial fibrillation using a multimodal approach with the aim to help prevention of disease, thus reduce morbidity and improve wellbeing in aging societies.