Accelerated biological aging and incident degenerative valvular heart disease: Findings from 408,783 UK Biobank participants

Dec 1, 2025International journal of cardiology. Heart & vasculature

Faster biological aging linked to new cases of heart valve disease in over 400,000 UK Biobank participants

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Abstract

Over a median follow-up of 13.9 years, 10,364 incident degenerative valvular disease events (2.5%) were documented.

Elevated biological age accelerations (BAA) are significantly associated with increased risk of aortic stenosis (AS).
For the PhenoAge metric, the adjusted AS incidence rates per 10,000 person-years increased from 3.73 in the lowest quartile to 7.79 in the highest quartile.
The adjusted hazard ratio for aortic stenosis in the highest quartile of PhenoAge is 2.15 compared to the lowest quartile.
Similar associations were observed with the Klemera-Doubal method Biological Age, showing an adjusted hazard ratio of 1.98 for the highest quartile.
Increased risks were also noted for aortic regurgitation and related events, while no significant association was found for mitral regurgitation-related events.

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BACKGROUND: Although prior studies have linked frailty and accelerated biological aging to aortic stenosis, comprehensive evidence across the spectrum of degenerative valvular diseases (VHD) and related clinical events remains unclear in middle-aged adults.

METHODS: We analyzed 408,783 UK Biobank participants free of baseline valvular disease. Biological age accelerations (BAA) measures were derived from clinical traits using Phenotypic Age (PhenoAge) algorithm and the Klemera-Doubal method Biological Age (KDM-BA). Outcomes included incident aortic stenosis (AS), aortic regurgitation (AR), mitral regurgitation (MR), and related interventions or mortality.

RESULTS: Over a median follow-up of 13.9 years, 10,364 incident degenerative VHD events (2.5 %) were documented, comprising 4602 AS, 1678 AS-related events, 1639 AR, and 4903 MR cases. Elevated BAA was significantly associated with higher AS risk. For PhenoAge, adjusted AS incidence rates (per 10,000 person-years; 95 % confidence interval) across quartiles (Q1-Q4) were 3.73 (3.37-4.12), 4.44 (4.05-4.88), 5.11 (4.67-5.59), and 7.79 (7.18-8.46), yielding an adjusted hazard ratio (HR) of 2.15 (1.96-2.35) for Q4. Comparable trends were observed for KDM-BA, with an adjusted HR of 1.98 (1.83-2.15) for Q4 vs Q1. AS-related events followed a similar pattern, with HRs of 1.80 (1.55-2.09) for PhenoAge Q4 and 2.22 (1.94-2.54) for KDM-BA Q4. Significant associations were also found for AR, AR-related events, and MR, but not for MR-related events.

CONCLUSIONS: Among middle-aged adults, both BAA metrics were associated with increased risks of degenerative VHD and related adverse events, except for MR-related events. These findings highlight BAA as a potential tool for early risk stratification and targeted prevention.

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Accelerated biological aging and incident degenerative valvular heart disease: Findings from 408,783 UK Biobank participants

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