Transcriptomic signature of frailty in elderly patients with cardiovascular disease

Frailty in elderly cardiovascular disease (CVD) patients is linked to declining functional capacity and procedural complications. This study investigated the transcriptomic signature of frailty in patients =70 years undergoing cardiac surgery or TAVI. Frailty was assessed using mobility, gait speed, and handgrip strength. Muscle samples were collected during surgery for RNA sequencing, and gene expression was analyzed. Transcriptomic analysis identified 10 frailty-associated genes, with S100A1 showing the strongest association. Functional studies confirmed S100A1's role in muscle function, and higher blood S100A1 levels correlated with handgrip strength in a second cohort. S100A1 is a potential target for addressing frailty in elderly CVD patients and offers insights into genetic factors contributing to frailty. Overall design: Patients aged =70 undergoing elective cardiac surgery or TAVI were recruited. Frailty was assessed using impaired mobility (Timed Up-and-Go =10 or =20 sec), low gait speed (5-meter Walk Test =6 sec), or reduced handgrip strength (male =27, female =16 kg). Muscle specimens (quadriceps femoris) collected during surgery were used for RNA sequencing. Differential gene expression and regression analyses explored associations between frailty and gene expression levels.