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The influence of accelerated aging-related cardiac remodeling on cardiovascular outcomes: an observational study

Zhi Lv1, Kexin Li1, Chang Liu1

  • 1Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|April 29, 2026
PubMed

Insights

Accelerated biological aging, measured by phenotypic age acceleration (PhenoAgeAccel), is linked to higher risks of cardiovascular disease (CVD) and mortality. Improving cardiac structure and metabolic health may reduce these risks.

Area of Science:

  • Cardiology
  • Gerontology
  • Biomarkers

Background:

  • Phenotypic age acceleration (PhenoAgeAccel) is a measure of biological aging.
  • Cardiovascular disease (CVD) remains a leading cause of mortality worldwide.
  • Understanding factors contributing to CVD risk is crucial for public health.

Purpose of the Study:

  • To investigate the association between PhenoAgeAccel and CVD outcomes and mortality.
  • To examine the relationship between PhenoAgeAccel and cardiac structure/function using cardiac magnetic resonance imaging (CMR).
  • To explore potential mediating pathways, including cardiac remodeling and cardiometabolic diseases.

Main Methods:

  • PhenoAgeAccel was calculated as the residual of PhenoAge (derived from nine biomarkers) regressed on chronological age.
  • 31,722 UK Biobank participants with complete biomarker and CMR data were analyzed.
  • Cox proportional hazards models and multivariable linear regression were used to assess associations and mediating roles.

Main Results:

  • Higher PhenoAgeAccel was independently associated with increased risks of CVD, ischemic heart disease, heart failure, and mortality.
  • Each SD increase in PhenoAgeAccel correlated with significant increases in CVD and mortality risks, particularly in women.
  • PhenoAgeAccel was linked to adverse cardiac remodeling, with partial mediation by cardiac remodeling and cardiometabolic diseases.

Conclusions:

  • Accelerated biological aging is associated with adverse cardiac phenotypes and increased CVD risk.
  • Cardiac remodeling and cardiometabolic health play a mediating role in the relationship between accelerated aging and CVD outcomes.
  • Interventions targeting cardiac remodeling and metabolic health may mitigate CVD risk associated with biological aging.
Abstract

Keywords:
Cardiac magnetic resonance imagingCardiometabolic diseasesCardiovascular diseaseMediation analysisPhenotypic age acceleration

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