EGEA_30years

Asthma and cardiovascular (CV) diseases are two common conditions with important public health and economic burden. Despite growing evidence that asthma is associated with increased risk of major CV events, the mechanisms by which asthma may affect the risk for CV events remain poorly understood. In particular, whether asthma and CV diseases share common etiological processes (such as anthropometric, lifestyle, social, environmental and/or genetic factors), or whether CV diseases are a consequence of some asthma characteristics (such as asthma treatments or systemic inflammation) remains unknown. The limited knowledge on this mechanism hampers preventive intervention. We aim to disentangle the complex association between asthma and early markers of CV risk, in order to provide new directions in clinical management of patients with asthma and in preventive intervention to prevent CV comorbidities in asthma. To reach this objective, specific aims are: (1) WP1: To collect new data, the 4th follow-up at 30 years of the EGEA (Epidemiological study on the Genetics and Environment of Asthma) cohort to accurately assess: - anthropometric, lifestyle, social and environmental factors through questionnaire, smartphone application, validated 24-h dietary records, passive sampler for individual NO2 assessment, geographical information system-based models; - treatments, hospitalizations, causes of death and long-term illnesses through data linkage with health administrative databases (SNDS); - phenotypic information through detailed questionnaires and clinical examination of the participants including anthropometric measures, lung function, 6-minute walk test, blood pressure and markers of cardiovascular risk (aortic pulse wave velocity [aPWV], Coronary Calcium Score (CAC) assessed by computed tomographic scanner, and biomarkers providing prognostic information on CV risk that will be measured longitudinally (hypersensitive CRP, IL6, hypersensitive Troponine (I), NT-proBNP, and soluble ST2)); (2) WP2: To characterize the longitudinal association of asthma and asthma specific phenotypes with markers of CV risk (aPWV, CAC and biomarkers of CV risk); (3) WP3: To clarify the causal association between asthma and markers of CV risk. Two alternative explanations will be investigated: 1) how much the co-occurrence of asthma and markers of CV risk might be explained by the presence of shared anthropometric, lifestyle, social environmental and genetic common causes; and 2) the role of asthma on markers of CV risk through causal direct and indirect effects (e.g. mediated by asthma treatments or inflammatory pathways). One major asset of the EGEA_30years program is the new follow-up at 30 years of a unique existing cohort including a group of asthma cases recruited in chest clinics, their first-degree relatives and a group of controls (total n=2120), particularly well characterized across the different follow-ups (clinical examination, biomarkers, lifestyle, social, environment, genetic (GWAS), epigenetic (methylome) and metabolomic data) and underpinned by a rich biobank. Given the high follow-up rates achieved in previous EGEA follow-ups, the family and multicentric design of the study, we anticipate that ~1300 individuals will complete the 30-year follow-up questionnaire including ~1000 participants with a clinical examination. Further strengths relate to the expertise of the consortium in setting-up and coordinating cohorts, in asthma and CV research, in analysing large scale omic and exposome data and in applying advanced statistical techniques including cluster and mediation analyses. Our multidisciplinary program will provide tools for identifying and prioritizing determinants of CV risk in asthma and feed into risk prediction, new directions in clinical management as well as development of preventive interventions in asthma. EGEA_30years may unravel actionable levers of life-threatening CV comorbidities in asthma.