Association Between Electrocardiographic Age and Cardiovascular Events in Community Settings: The Framingham Heart Study

BACKGROUND:Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study). METHODS:We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (& UDelta;age) and classified individuals as having normal, accelerated, or decelerated aging, if & UDelta;age was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of & UDelta;age, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors. RESULTS:The study population included 9877 FHS participants (mean age, 55 & PLUSMN;13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9 & PLUSMN;7 years). After 17 & PLUSMN;8 years of follow-up, every 10-year increase of & UDelta;age was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12-1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17-1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05-1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30-1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14-1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74-0.95]). CONCLUSIONS:ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk.