Echocardiographic heart ageing patterns predict cardiovascular and non-cardiovascular events and reflect biological age: the SardiNIA study

Aims: Age is a crucial risk factor for cardiovascular (CV) and non-CV diseases. As people age at different rates, the concept of biological age has been introduced as a personalized measure of functional deterioration. Associations of age with echocardiographic quantitative traits were analysed to assess different heart ageing rates and their ability to predict outcomes and reflect biological age. Methods: Associations of age with left ventricular mass, geometry, diastolic function, left atrial volume, and aortic root size were measured in 2614 healthy subjects. Based on the 95% two-sided tolerance intervals of each correlation, three discrete ageing trajectories were identified and categorized as "slow", "normal", and "accelerated" hearts ageing patterns. The primary endpoint included fatal and non-fatal CV events, and the secondary endpoint was a composite of CV and non-CV events and all-cause death. The heart phenotypic age (HeartPhAge) was estimated as a proxy of biological age. Results: The slow ageing pattern was found in 8.7% of healthy participants, the normal pattern in 76.8%, and the accelerated pattern in 14.3%. Kaplan-Meier curves of the heart ageing patterns diverged significantly (P=0.0001) for both primary and secondary endpoints, with the event rate being lowest in the slow, intermediate in the normal, and highest in the accelerated pattern. In Cox proportional-hazards model, heart aging patterns predicted both primary (P=0.01) and secondary (P=0.03 to <0.0001) endpoints, independent of chronological age and risk factors. Compared to chronological age, HeartPhAge was 9 years younger in slow, 4 years older in accelerated (both P<0.0001), and overlapping in normal ageing patterns. Conclusion: Standard Doppler-echocardiography detects slow, normal, and accelerated heart ageing patterns. They predict CV and non-CV events, reflect biological age, and provide a new tool to calibrate prevention timing and intensity.