What question did this study set out to answer?

The study aims to estimate cardiovascular biological age and assess its impact on clinical outcomes independent of chronological age.

February 8, 2026

Biologically older cardiovascular system predicts adverse clinical outcome independently of chronological age

Key Points

The study aims to estimate cardiovascular biological age and assess its impact on clinical outcomes independent of chronological age.
Utilized XGBoost regression to estimate HeartAge and HeartAge-gap in UK-Biobank participants.
Conducted logistic regression to associate HeartAge-gap with cardiovascular conditions.
Employed Cox regression models to evaluate the predictive value of HeartAge-gap on cardiovascular outcomes and mortality.
Performed external validation in a separate cohort from the Multi-Ethnic Study of Atherosclerosis.
HeartAge-gap was linked to higher risks of hypertension, diabetes, and ischaemic heart disease.
Increased HeartAge-gap predicted adverse cardiovascular outcomes in both sexes after nearly 6 years of follow-up.
In females, HeartAge-gap also predicted all-cause mortality, independent of age and other risk factors.

Abstract

Abstract Background Cardiovascular ageing is the main biological driver of cardiovascular diseases, offering a unique opportunity to transform research and prevention strategies at both individual and population levels. Purpose We aimed to develop, and validate, a novel estimate of cardiovascular biological age (HeartAge) and its deviation from chronological age (HeartAge-gap) using XGBoost regression informed by readily extractable cardiovascular magnetic resonance phenotypes. Methods HeartAge and HeartAge-gap were estimated in 31,784 UK-Biobank participants (16,640 females, 64±7 years). A positive HeartAge-gap indicates an older cardiovascular system, conversely a negative HeartAge-gap indicates a younger one. Logistic regression assessed the association between HeartAge-gap and prevalent cardiovascular conditions, while Cox regression proportional hazard-ratio models evaluated its predictive value for the composite cardiovascular outcome and all-cause mortality. External validation was conducted in 897 participants (472 females, 60±10 years) from the Multi-Ethnic Study of Atherosclerosis (MESA). Results HeartAge-gap was independently associated hypertension, diabetes, and ischaemic heart disease in both sexes (P0·05 for all). Over a median follow-up of nearly 6 years, an increased HeartAge-gap predicted the composite cardiovascular outcome in females (HR:1·022, 95%CI:1·000-1·044, P=0·048) and males (HR:1·017, 95%CI:1·002-1·033, P=0·027) independently of chronological age and other major baseline confounders including, body-mass-index, ischaemic heart disease, diabetes, and hypertension. In females, an increased HeartAge-gap also predicted all-cause mortality (HR:1·061, 95%CI:1·007-1·118, P=0·027) regardless of chronological age. In MESA females, increased HeartAge-gap predicted the cardiovascular outcome (HR:1·113, 95%CI:1·025-1·210, P=0·011) independently of chronological age and other key confounders. Conclusion Our framework offers an individualised approach to estimating cardiovascular biological ageing. A biologically older cardiovascular system emerged as a robust, independent predictor of adverse cardiovascular outcomes, irrespective of chronological age and traditional risk factors. Notably, in females, advanced cardiovascular ageing also predicted all-cause mortality regardless of chronological age.Figure-1.Study outline and main outcome

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