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

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.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.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.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.Age is the main risk factor for cardiovascular disease. Since people age and develop diseases at very different rates, biological age has been proposed as a more accurate measure of the body's functional decline. This study aimed to investigate the ageing rates of the heart and to assess their impact on cardiovascular events. The phenotypic age of the heart was also estimated as a proxy for biological age. Associations of age with Doppler echocardiographic parameters were analysed in a subgroup of 2614 clinically healthy subjects, part of a larger cohort of 3817 adults of both sexes. Three patterns of slow, normal, and accelerated ageing rates of the heart were detected. They predicted both cardiovascular and non-cardiovascular events, with different and progressively increasing event rates from the slow to the accelerated pattern. Compared to chronological age, the phenotypic (biological) age of the heart was 9 years younger in the slow pattern, 4 years older in the accelerated pattern, and comparable in the normal pattern. A standard Doppler echocardiogram is therefore able to detect three distinct heart ageing patterns, which reflect different biological susceptibilities to age-dependent diseases and provide a new tool for personalising timeliness and intensity of prevention.