Per Svensson

Background: Improved understanding on how family history (FH) of disease and social determinants of health interacts and cause cardiovascular disease (CVD) during the life course can inform new treatments and reduce health inequity. Objective: To identify key proteins, metabolic and mechanistic pathways for how FH of different diseases and trajectories of socioeconomic status (SES) during the life course cause CVD to find new drug target and important lifestyle habits in order to improve health equity. To study whether uptake of preventive treatment are mediators for a worse prognosis in lower SES in important clinical settings. Work plan: The population-based SCAPIS, EpiHealth and TwinGene-studies will be used with linkage to national registers. We will explore new pathways for how 1) FH of disease and 2) trajectories of SES during the life course relate to coronary atherosclerosis and incident CVD using proteomic, genetic and metabolomic biomarker platforms with a multi-omics approach. For significant proteins and metabolites, causal associations will be studied using two-sample mendelian randomization, their role in mediating atherosclerosis will be studied using structural equation modelling, independence of traditional risk factors and life-style factors will be studied. We will perform pathway enrichment analyses for identified genes and search druggability databases. The project will also use SWEDEHEART and Svenskt Akutvårdsregister with linkage to national registers. Causal mediation analysis will be used to study whether treatments in the acute setting or during secondary prevention after a first MI mediate the deleterious effect of SES on incident CVD. Linkage to national registers have been performed for TwinGene, SCAPIS and other data is delivered. Similar linkage is planned for EpiHealth with data delivery expected during 2026. A post-doc and PhD-student will be recruited 2026 and work with the project in a multidisciplinary research environment. Significance: The project will answer important questions on how genes and environment cause CVD and will identify new and more precise targets for treatment to reduce CVD and reduce health inequity in CVD.