People whose bodies age faster may benefit most from good heart health

Maintaining good cardiovascular health may affect a key process in how cells age, allowing people who are genetically predisposed to faster aging to reduce their risk for cardiovascular disease and death, new research suggests.

The study, published Wednesday in the Journal of the American Heart Association, confirmed the benefits of following heart-healthy behaviors for all people but showed an even larger benefit in reducing the risk for heart disease and stroke, cardiovascular-related death and death from all causes for adults whose bodies showed signs of accelerated aging.

"Our study showed that people with high genetic risks for aging faster can modify the risk they were born with," said the study's senior author Dr. Jiantao Ma, an assistant professor at the Friedman School of Nutrition Science and Policy at Tufts University in Boston.

The study investigated the link between a chemical process known as DNA methylation, which regulates how genes perform their designated role, biological aging and cardiovascular health and mortality risks.

Cardiovascular health was determined using the American Heart Association's Life's Essential 8, or LE8, a collection of metrics centered on diet, physical activity, nicotine exposure, sleep duration, body mass index, and blood glucose, cholesterol and blood pressure levels. Prior research has shown maintaining optimal levels of these factors lowers cardiovascular disease and mortality risk as well as the risk for other chronic illnesses, even in people at high genetic risk for heart disease.

Previous studies also have shown both genetics and lifestyle can affect DNA methylation, a critical component of biological, or epigenetic, aging – a measure of cell, tissue and organ health as people grow older that may not always align with their chronological age.

DNA methylation can accelerate or decelerate the aging process by turning genes on or off, explained Dr. Donald Lloyd-Jones, chair of the department of preventive medicine at Northwestern University Feinberg School of Medicine in Chicago and a past president of the AHA.

"The gene code you inherit is fixed for life," he said. "However, you can modify the expression of those genes, and that's where epigenetics comes in."

DNA methylation alterations have been linked to cardiovascular risk factors such as obesity, high blood glucose, high cholesterol and high blood pressure, suggesting they play a role in the development of cardiovascular disease.

In the new study, researchers analyzed the role DNA methylation-based epigenetic age scores play in the relationship between LE8 and cardiovascular disease, cardiovascular mortality and all-cause mortality.

Ma and his colleagues used interviews, physical exams and lab tests to calculate cardiovascular health and epigenetic age for 3,693 people in a subgroup of the Framingham Heart Study, a large multigenerational study exploring common factors and family patterns contributing to cardiovascular disease. Participants were 56 years old, on average.

After an average follow-up of 11 to 14 years, people with higher LE8 scores on a 100-point scale had younger epigenetic age scores regardless of chronological age. As LE8 scores went up, the risk of developing or dying from cardiovascular disease – defined as heart attack, stroke, coronary heart disease or heart failure – or dying from any cause went down. For every 13-point increase in LE8 score, there was a 35% lower risk of cardiovascular disease, a 36% decrease in cardiovascular-related death and a 29% lower risk for death from all causes.

Overall, BMI, blood glucose, cholesterol and blood pressure levels were more strongly associated with cardiovascular disease and related deaths, while smoking, physical activity, diet and sleep were more strongly associated with the risk of death from all causes.

In participants whose bodies were genetically predisposed to aging faster, 39% of the association between LE8 scores and cardiovascular disease or death was due to the effects of cardiovascular health factors on DNA methylation. By comparison, it was 21% in participants with any epigenetic age.

Similarly, DNA methylation determined 78% of the connection between LE8 scores and death from any cause in people with an older epigenetic age, compared to 65% in those with any epigenetic age.

"Having a good LE8 score, which shows you are maintaining good cardiovascular health, is always important," Ma said. "But for people with higher genetic risks, our findings show doing so is especially important because there is more room for improvement."

Researchers have long known that heart-healthy behaviors such as not smoking and eating a healthy diet reduce the risk for cardiovascular disease and death. But they couldn't show how those behaviors were changing a person's body at the molecular level, said Lloyd-Jones, whose research also involves epigenetics, though he was not part of the new study.

"Until the last couple years, we did not realize just how powerful epigenetics might be in this process," he said. "We did not understand the pathways by which this was happening."

This study shows that, as a result of lifestyle behaviors, "people have molecular changes at the cellular level that are much more favorable or less favorable over the life course," Lloyd-Jones said. "There are actual molecular changes happening for people who don't smoke, who eat a healthy diet and get good sleep."

While most people have no way of knowing their epigenetic age score, Lloyd-Jones emphasized that everyone could benefit from adhering to the eight metrics for good heart health and that it is never too late to begin. Even small changes help.

"Change matters at every stage of life," he said. "You don't need to do all eight things at once. That can feel overwhelming. Pick one component of the eight and improve that. If you need to do more, do more. The sooner you do it, the better. But it is never, ever too late."