JACC. AsiaAug 16, 2025

Faster Biological Aging, Genetic Risk, and New Cases of Heart Valve Disease

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

During a median follow-up of 13.58 years, 8,146 cases of valvular heart disease (VHD) were documented among 341,460 participants.

Older biological age, as measured by the Klemera-Doubal method, is associated with a 35% increased risk of VHD for each 1-standard deviation increase in biological age acceleration.
An association is observed between PhenoAge acceleration and VHD, resulting in a 29% increased risk for each 1-standard deviation increase.
Individuals in the highest quartile of KDM-BA acceleration have an 86% higher risk of developing VHD compared to those in the lowest quartile.
There is an additive interaction between KDM-BA acceleration and polygenic risk scores, suggesting a combined effect on VHD risk.
Similar associations are found between PhenoAge acceleration and the risk of VHD.

Simplified

BACKGROUND: The association between biological aging and valvular heart disease (VHD) has not yet been evaluated.

OBJECTIVES: This study aimed to evaluate the associations between 2 biological age indicators, Klemera-Doubal method biological age (KDM-BA) acceleration and PhenoAge acceleration, and the risk of VHD, as well as explore the potential gene-environment interplay.

METHODS: The study included 341,460 UK Biobank participants without VHD at enrollment. Biological age was assessed using KDM-BA and PhenoAge methods. Genetic risk was measured by genome-wide-association study-based polygenic risk scores (PRS). Cox models were used to assess the individual and joint effects of biological age and PRS on incident VHD. Both multiplicative and additive interactions between the 2 factors were also estimated.

RESULTS: During a median follow-up of 13.58 years (Q1-Q3: 12.83-14.25 years), 8,146 VHD cases were documented. The results showed a significant association between older biological age and an increased risk of VHD, with a HR of 1.35 (95% CI: 1.32-1.38) for each 1-SD increase in KDM-BA acceleration, and 1.29 (95% CI: 1.26-1.32) for PhenoAge acceleration. Compared with individuals in the first quartile group (Q1) for KDM-BA acceleration, those in Q4 showed the highest risk of VHD, with an 86% higher risk (HR: 1.86; 95% CI: 1.74-1.99). There was an additive interaction between KDM-BA acceleration and PRS for VHD. Similar results were found for the association between PhenoAge acceleration and VHD.

CONCLUSIONS: Advanced biological aging was significantly associated with an increased risk of VHD and could serve as a potential target for clinical prediction and intervention.

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Competing interests

Funding Support and Author Disclosures This work was supported by the Open Research Fund of the National Health Commission Key Laboratory of Birth Defects Prevention and the Henan Key Laboratory of Population Defects Prevention (ZD202303), the 2022 International Postdoctoral Exchange Fellowship Program [Talent-Introduction Program] (No. YJ20220181), Henan Medical Science and Technology Research Program (No.232102310069). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

PubMed

Faster Biological Aging, Genetic Risk, and New Cases of Heart Valve Disease

Abstract

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