Plasma Proteomic Signatures of Left Atrial Dysfunction and Cerebral Small Vessel Disease

Reduced left atrial (LA) strain is associated with cerebral small vessel disease (CSVD). In memory clinic patients without atrial fibrillation, LA reservoir strain and LA conduit strain were significantly associated with white matter hyperintensity volume and cerebral microinfarcts. From plasma proteomic profiling of 1,441 proteins, we identified 23 proteins significantly associated with LA reservoir strain, 425 with LA conduit strain, 199 with white matter hyperintensity volume, and 247 with cerebral microinfarcts. Among them, 13 proteins were commonly associated with both LA strain and CSVD, with 8 proteins showing evidence of significant mediation effects for the association between LA strain and CSVD. The mediators included tumor necrosis factor receptor superfamily member (TNFRSF)-11A, TNFRSF1B, TNFRSF10B, cystatin-C, nectin-4, insulin-like growth factor–binding protein, CD27, and brorin. Partial correlation network analysis also supported TNFRSF11A and insulin-like growth factor–binding protein as highly interconnected proteins in this study population. These plasma proteins may offer pathobiological clues linking LA dysfunction to CSVD.