The benefits of improved heart health may be related to the positive impact that heart-healthy lifestyle components have on biological aging – the age of the body and its cells – according to a new study published today in the Journal of the American Heart Association, an open-access, peer-reviewed journal of the American Heart Association.
Study: Epigenetic age mediates the association between eight vital factors and cardiovascular disease and mortality. Image credit: santoelia / Shutterstock
“Our findings indicate that heart-healthy behaviors and management of heart disease risk factors are associated with younger biological age, lower risk of heart disease and stroke, and lower risk of death from heart disease, stroke, and all-cause mortality, regardless of chronological age,” said Jiantao Ma, PhD, assistant professor in the Department of Nutrition Epidemiology and Data Science at the Friedman School of Nutrition Science and Policy at Tufts University, Boston, and lead author of the study.
This study analyzed whether a chemical modification process called DNA methylation, which controls gene expression, is one of the mechanisms by which cardiovascular health factors affect cellular aging and mortality risk. DNA methylation levels are the most promising biomarkers to estimate biological age. To some extent, genetic makeup determines biological age, but lifestyle factors and stress can also affect biological age.
The researchers examined health data from 5,682 adults (mean age 56 years; 56% of participants were women) who participated in the Framingham Heart Study, a large, ongoing, multigenerational research project aimed at identifying risk factors for heart disease. Using interviews, physical exams, and laboratory tests, all participants were assessed with the American Heart Association's Life's Essential 8 tool, which combines four behavioral indicators (dietary intake, physical activity, hours of sleep per night, and smoking status) and four clinical indicators (BMI, cholesterol, blood glucose, and blood pressure) to score cardiovascular health between 0 and 100 (100 being the best). Each participant was assessed with four tools that estimate biological age based on DNA methylation and a fifth tool that assesses genetic tendencies for accelerated biological aging. Participants were followed for 11 to 14 years for new-onset cardiovascular disease, cardiovascular death, or death from any cause.
The analysis revealed the following:
For every 13-point increase in an individual's Life's Essential 8 score, there was an approximately 35% reduced risk of first-time cardiovascular disease, a 36% reduced risk of cardiovascular disease death, and a 29% reduced risk of all-cause death. For participants whose genetic risk profile was likely to lead to accelerated biological aging, the Life's Essential 8 score may have had an even greater effect on outcomes via DNA methylation: DNA methylation reduced the risk of cardiovascular disease, cardiovascular disease death, and all-cause mortality by 39%, 39%, and 78%, respectively. Overall, it was estimated that approximately 20% of the association between the Life's Essential 8 score and cardiovascular disease outcomes was due to the influence of cardiovascular health factors on DNA methylation. In contrast, for participants at high genetic risk, the association was nearly 40%.
“There are some commercially available biological age calculators based on DNA methylation, but there are no good recommendations on whether people should know their epigenetic age,” Ma said. “Our message is that everyone should be mindful of the eight health factors for heart disease and stroke: eating healthy foods, being more active, quitting smoking, getting healthy sleep, managing their weight, and maintaining healthy cholesterol, blood sugar and blood pressure levels.”
Randy Foraker, PhD, MA, FAHA, co-author of “Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health,” said the findings are consistent with previous research.
“We know that modifiable risk factors and DNA methylation are each independently associated with cardiovascular disease. What this study adds is that DNA methylation may act as a mediator between risk factors and cardiovascular disease,” said Foraker, professor of medicine in the Institute of Informatics, Data Science and Biostatistics and director of the Center for Population Health Informatics at Washington University School of Medicine in St. Louis, Mo. “This study sheds light on how cardiovascular health influences biological aging, which has important implications for healthy aging and the prevention of cardiovascular disease and potentially other health conditions.”
Study details, background and design:
The study analyzed health data from subgroups of participants examined in the Framingham Heart Study: the offspring group from 2005 to 2008 and the third generation group from 2008 to 2011. Participants were followed for an average of 14 years for the children of the first participants and 11 years for the grandchildren. Health outcomes in the analysis included incident cardiovascular disease (coronary heart disease, heart attack, stroke, or heart failure), death from any cardiovascular disease, or death from any cause. Outcomes were adjusted for sex, age, and alcohol use. All-cause mortality outcomes were adjusted for the presence of cancer (excluding nonmelanoma skin cancer) or heart disease at study enrollment. Participants who had already been diagnosed with heart disease at study enrollment were excluded from the analysis of new-onset cardiovascular disease. The four tools that measure DNA methylation-based epigenetic age scores are based on established algorithms: DunedinPACE Score, PhenoAge, DNAmTL, and GrimAge. The fifth tool, GrimAge PGS, assessed genetic propensity to accelerated biological aging.
Because this study analyzed previously collected health data, it cannot prove a causal relationship between cardiovascular health risk factors and DNA methylation. Additionally, DNA methylation measurements were taken from a single time point, limiting the validity of any mediation effects. The findings of this study are also limited because participants were primarily of European descent, and the interactions between Life's Essential 8 and genetic aging found in this study may not be generalizable to people of other races and ethnicities.
“We are now expanding our study to include people from other racial and ethnic groups to further explore the relationship between cardiovascular risk factors and DNA methylation,” Ma said.
According to the American Heart Association's 2024 Heart Disease and Stroke Statistics, more people died from heart disease and stroke in the United States in 2021 than from all types of cancer and chronic lower respiratory tract disease combined. Also, approximately 19.91 million people died from heart disease and stroke worldwide.
Co-authors, disclosures, and funding sources are listed in the manuscript.
Research published in the American Heart Association's scientific journals is peer-reviewed. The statements and conclusions of each paper are solely the views of the study authors and do not necessarily reflect the policies or positions of the Association. The Association makes no representations or warranties as to their accuracy or reliability. The Association is primarily funded by individuals, but foundations and corporations (including pharmaceutical companies, device manufacturers, and other businesses) also make donations and fund certain Association programs and events. The Association has strict policies to ensure that these relationships do not influence the scientific content. Revenues from pharmaceutical companies, biotechnology companies, device manufacturers, and health insurers, as well as the Association's overall financial information, can be found here.
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Journal References:
Epigenetic age mediates the association between essential element of life 8 and cardiovascular disease and mortality Madeleine Carbonneau BA, Yi Li MA, Brenton Prescott MS, Chunyu Liu PhD, Tianxiao Huan PhD, Roby Joehanes PhD, Joanne M. Murabito MD, Nancy L. Heard‐Costa PhD, Vanessa Xanthakis PhD, Daniel Levy MD, DOI: 10.1161/JAHA.123.032743, https://www.ahajournals.org/doi/10.1161/JAHA.123.032743
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