Article Impact Level: HIGH Data Quality: STRONG Summary of Journal of the American Heart Association, e032743. https://doi.org/10.1161/JAHA.123.032743 Dr. Madeleine Carbonneau et al.
Points
- The study involved 5682 participants from the Framingham Heart Study to investigate the relationship between Life’s Essential 8 (LE8) score, DNA methylation‐based epigenetic age biomarkers, and cardiovascular health.
- A 1 standard deviation increase in the LE8 score was associated with a 35% lower risk of incident cardiovascular disease (CVD), a 36% lower risk of CVD-specific mortality, and a 29% lower risk of all-cause mortality.
- The associations between LE8 score and cardiovascular health outcomes were partially mediated by epigenetic age biomarkers, particularly the GrimAge and the DunedinPACE scores.
- Participants with a higher genetic predisposition for older epigenetic age exhibited more profound mediation effects by epigenetic age biomarkers than those with lower genetic risk.
- DNA methylation‐based epigenetic age scores, such as GrimAge and DunedinPACE, play a mediating role in the associations between the LE8 score and incident CVD, CVD-specific mortality, and all-cause mortality, especially in individuals with a higher genetic predisposition for older epigenetic age.
Summary
In a study involving 5682 participants from the Framingham Heart Study, the relationship between Life’s Essential 8 (LE8) score, DNA methylation‐based epigenetic age biomarkers, and cardiovascular health was investigated. The LE8 score, an enhanced cardiovascular health metric, was associated with a lower risk of incident cardiovascular disease (CVD), CVD-specific mortality, and all-cause mortality. Specifically, a 1 standard deviation increase in the LE8 score was linked to a 35% lower risk of incident CVD, a 36% lower risk of CVD-specific mortality, and a 29% lower risk of all-cause mortality.
These associations were partially mediated by epigenetic age biomarkers, particularly the GrimAge and the DunedinPACE scores. Notably, the mediation effects by epigenetic age biomarkers were more pronounced in participants with a higher genetic predisposition for older epigenetic age compared to those with lower genetic risk.
The study revealed that DNA methylation‐based epigenetic age scores, such as GrimAge and DunedinPACE, mediate the associations between the LE8 score and incident CVD, CVD-specific mortality, and all-cause mortality. This mediation was particularly evident in individuals with a higher genetic predisposition for older epigenetic age. For instance, participants with higher GrimAge polygenic scores exhibited a substantial proportion of mediation for the association of the LE8 score with incident CVD, CVD-specific mortality, and all-cause mortality. Conversely, no significant mediation was observed in participants with lower GrimAge polygenic scores.
In conclusion, this study’s findings suggest that DNA methylation‐based epigenetic age biomarkers mediate the relationship between the LE8 score and cardiovascular health outcomes, especially in individuals with a higher genetic predisposition for older epigenetic age. These results provide valuable insights into the interplay between cardiovascular health, biological aging, and genetic factors, highlighting the potential utility of epigenetic age biomarkers in assessing disease risks and mortality.
Link to the article: https://www.ahajournals.org/doi/10.1161/JAHA.123.032743
References Carbonneau, M., Li, Y., Prescott, B., Liu, C., Huan, T., Joehanes, R., Murabito, J. M., Heard‐Costa, N. L., Xanthakis, V., Levy, D., & Ma, J. (2024). Epigenetic Age Mediates the Association of Life’s Essential 8 With Cardiovascular Disease and Mortality. Journal of the American Heart Association, e032743. https://doi.org/10.1161/JAHA.123.032743
