The 12-lead electrocardiogram as a biomarker of biological age

Background We have demonstrated that a neural network is able to predict a person’s age from the electrocardiogram (ECG) [artificial intelligence (AI) ECG age]. However, some discrepancies were observed between ECG-derived and chronological ages. We assessed whether the difference between AI ECG and chronological age (Age-Gap) represents biological ageing and predicts long-term outcomes. Methods and results We previously developed a convolutional neural network to predict chronological age from ECGs. In this study, we used the network to analyse standard digital 12-lead ECGs in a cohort of 25 144 subjects ≥30 years who had primary care outpatient visits from 1997 to 2003. Subjects with coronary artery disease, stroke, and atrial fibrillation were excluded. We tested whether Age-Gap was correlated with total and cardiovascular mortality. Of 25 144 subjects tested (54% females, 95% Caucasian) followed for 12.4 ± 5.3 years, the mean chronological age was 53.7 ± 11.6 years and ECG-derived age was 54.6 ± 11 years (R2 = 0.79, P < 0.0001). The mean Age-Gap was small at 0.88 ± 7.4 years. Compared to those whose ECG-derived age was within 1 standard deviation (SD) of their chronological age, patients with Age-Gap ≥1 SD had higher all-cause and cardiovascular disease (CVD) mortality. Conversely, subjects whose Age-Gap was ≤1 SD had lower all-cause and CVD mortality. Results were unchanged after adjusting for CVD risk factors and other survival influencing factors. Conclusion The difference between AI ECG and chronological age is an independent predictor of all-cause and cardiovascular mortality. Discrepancies between these possibly reflect disease independent biological ageing.