Association of biological age acceleration with cardiovascular disease and premature mortality: a population-based
Yingying Yang1, Shaohua Yin2, Dan Li3,4
1Clinical Research Unit, Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, School of Medicine, Tongji University, Shanghai, China.
Insights
Accelerated biological ageing increases cardiovascular disease (CVD) and premature mortality risk. This risk is higher in males, suggesting a need for sex-specific health strategies.
Area of Science:
- Gerontology
- Cardiovascular Medicine
- Epidemiology
Background:
- Accelerated biological ageing is linked to age-related diseases.
- Sex differences in biological age acceleration's impact on cardiovascular disease (CVD) and premature mortality are not well understood.
Purpose of the Study:
- To assess the association between biological age (BA) acceleration and CVD risk.
- To evaluate the association between BA acceleration and premature mortality.
- To examine potential sex differences in these associations.
Main Methods:
- A population-based prospective cohort study using UK Biobank data (N=122,133).
- Biological age (BA) calculated using Klemera-Doubal method (KDM-BA) and PhenoAge algorithms.
- BA acceleration defined as residuals from regression of BA on chronological age.
- Cox proportional hazards models used to analyze incident CVD and premature mortality risks.
Main Results:
- Higher BA acceleration correlated with increased risks of incident CVD and premature mortality.
- The highest quartile of KDM-BA acceleration showed HRs of 1.32 for CVD and 1.10 for premature mortality.
- PhenoAge acceleration showed corresponding HRs of 1.23 for CVD and 1.21 for premature mortality.
- These associations were significantly more pronounced in males.
Conclusions:
- Increased biological age acceleration is a significant risk factor for CVD and premature mortality.
- The association between BA acceleration and adverse health outcomes is stronger in men.
- Findings highlight the importance of considering BA acceleration as a modifiable risk factor and developing sex-specific health interventions.
Introduction:
Accelerated biological ageing is associated with age-related diseases, but sex differences in its association with cardiovascular disease (CVD) and premature mortality remain largely unknown. We aimed to assess the associations between biological age (BA) acceleration and CVD, premature mortality, and examine potential sex differences.
Methods:
This population-based prospective cohort study included participants aged 39 to 71 years from UK Biobank study, recruited between 2006 and 2010, and followed up until Dec 20, 2022. BA, derived from clinical biomarkers, was calculated using the Klemera-Doubal method (KDM-BA) and PhenoAge algorithms. BA acceleration was defined as the residual from regressing BA based on chronological age. Incident CVD and premature mortality (defined as death before age 70) were identified using ICD-9 and ICD-10 codes. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) across BA acceleration quartiles.
Results:
Among 122,133 participants who were free of CVD at baseline (mean [SD] age, 56.0 [8.1] years; 65,442 [53.6%] women), 24,281 incident CVD cases and 3,614 premature deaths were reported. Restricted cubic splines showed progressively increasing risks of incident CVD and premature mortality associated with higher BA acceleration. Compared with the lowest quartile of KDM-BA acceleration, the largest adjusted HRs for incident CVD and premature mortality were 1.32 (95% CI 1.27-1.37) and 1.10 (95% CI 1.05-1.21) for quartile 4, respectively. For PhenoAge acceleration, the corresponding HRs were 1.23 (95% CI 1.19-1.28) and 1.21 (95% CI 1.10-1.33), respectively. These associations were more pronounced among male participants (P-interaction<0.05).
Discussion:
In this cohort study, higher BA acceleration was associated with increased risks of incident CVD and premature mortality, with more pronounced association observed in males. These findings suggest the need to exploring BA acceleration as a modifiable risk factor to optimize risk assessment, and to implement sex-specific strategies to improve health outcome.
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