The plasma protein profile of left ventricular diastolic function

We aimed to characterize associations between plasma proteins and indices of left ventricular (LV) diastolic function in two population-based studies. Eighty-six cardiovascular-related plasma proteins measured by proximity extension assay (PEA) and echocardiography were assessed in the population-based studies PIVUS ( n  = 1,016; all aged 70) and POEM ( n  = 502; all aged 50). PIVUS served as the discovery cohort, and the Benjamini-Hochberg procedure was applied to control the false-discovery rate (FDR) < 0.05. POEM was used as the replication cohort. The protein panel was related to diastolic echocardiographic parameters. A larger protein panel of 1,322 proteins was examined only in POEM. Seven of 86 proteins showed replicated associations to the E/A ratio: CD40 ligand (CD40LG), proto-oncogene tyrosine-protein kinase Src (SRC), heat shock protein beta-1 (HSPB1), epidermal growth factor (EGF), TNF superfamily member 14 (TNFSF14), vascular endothelial growth factor D (VEGFD), and endothelial cell-specific molecule 1 (ESM1). Using the larger protein panel in POEM, 81 proteins showed significant associations with the E/A ratio, and five showed significant associations with LA diameter. Pathways linked to LV diastolic filling pattern were signal transduction, metabolic, disease and immune system pathways, enhancing the understanding of LV diastolic function and offering potential for future drug development.