Association between plasma proteomic profiles and subclinical variations in left atrial strain in adults without overt cardiovascular disease: the role of cardiometabolic factors

INTRODUCTION: Associations between plasma proteomic profiles and left atrial (LA) strain may provide insight into biological processes underlying variation in atrial function in adults without overt cardiovascular disease. OBJECTIVES: To assess the associations between circulating proteins and phasic LA strain and to explore the potential influence of cardiometabolic factors on these relationships. PATIENTS AND METHODS: Participants were drawn from the population cohort of the Bialystok Polish Longitudinal University Study (Bialystok PLUS, 2018 to 2024), including adults aged 35-70 years who had complete echocardiographic data and available plasma samples for proteomic profiling. Individuals with overt cardiovascular, inflammatory, neoplastic, or neurodegenerative disease were excluded. LA reservoir (LASr), conduit (LAScd), and contraction (LASct) strain were assessed using speckle-tracking echocardiography. Plasma proteomic profiling was performed using the Olink® Reveal platform (Olink Proteomics AB, Uppsala, Sweden). Associations between 1034 proteins and LA strain parameters were analyzed using age-adjusted linear models with false discovery rate (FDR) correction (q ≤ 0.10). Additional analyses evaluated the influence of cardiometabolic risk factors and overlap with conventional echocardiographic parameters. RESULTS: The study included 414 adults (median age, 51 years; 47.3% men). After age adjustment, significant associations were observed exclusively for LAScd, with 30 proteins meeting the FDR threshold, whereas no proteins were related to LASr or LASct. The proteins linked to LAScd were mainly involved in metabolic regulation, inflammation, cellular stress responses, and tissue remodeling. The proteomic signature of LAScd showed only partial overlap with conventional echocardiographic phenotypes. After further adjustment for cardiometabolic risk factors, no associations remained significant after FDR correction. CONCLUSIONS: In adults without overt cardiovascular disease, LAScd was the only component of LA strain associated with a distinct age-adjusted plasma proteomic profile. The observed associations were substantially influenced by cardiometabolic risk factors, suggesting that the identified proteomic patterns primarily reflect underlying cardiometabolic processes. Further longitudinal studies are needed to determine the clinical significance of these findings.