Scientists have discovered more than 100 new epigenetic biomarkers that may help predict cardiovascular disease risk and inform preventive care measures to improve long-term outcomes, according to a recent study published in Circulation.
The study builds on previous work led by Yinan Zheng, ’17 PhD, assistant professor of Preventive Medicine in the Division of Cancer Epidemiology and Prevention, which found that long-term cardiovascular health from young adulthood through midlife leaves detectable epigenetic changes in patient blood samples that, when measured, can help predict cardiovascular disease risk and mortality.
“This study raised several important follow-up questions that we tried to answer in this new study: do these cardiovascular health-associated methylation markers replicate in diverse populations across age, sex and race/ethnicity, and do these methylation patterns serve as early biomarkers that can predict incident cardiovascular disease and mortality beyond traditional risk factors?” said Zheng, who was a co-author of the current study and is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
To better understand the association of overall cardiovascular health with changes in DNA methylation, the investigators conducted an epigenome-wide association study across five patient cohorts totaling over 10,000 participants, which included the Coronary Artery Risk Development in Young Adults (CARDIA) Study, the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA) study.
The scientists also integrated into the analysis the American Heart Association (AHA) Life’s Essential 8 score, which measures cardiovascular health based on blood pressure, cholesterol, glucose, BMI and health behaviors including diet, sleep, exercise, and smoking.
Next, the scientists analyzed more than 440,000 DNA methylation markers — chemical “tags” on DNA that can turn genes on or off — in patient blood samples and then applied advanced bioinformatics tools to identify methylation markers associated with cardiovascular health, or the AHA Life’s Essential 8 score.
“We investigated the biological pathways involved, and tested whether these markers can predict cardiovascular disease, mortality and other health outcomes,” Zheng said.
The analysis revealed a total of 609 methylation markers significantly associated with cardiovascular health. Of these markers, 141 were potentially causal for cardiovascular disease including stroke, heart failure and gestational hypertension.
Surprisingly, the investigators also discovered these epigenetic markers were highly predictive of future cardiovascular events and mortality independent of traditional risk factors, and that these results were consistent across diverse patient populations.
“For example, people with more favorable methylation profiles had up to 32 percent lower risk of incident cardiovascular disease, 40 percent lower cardiovascular mortality and 45 percent lower all-cause mortality,” Zheng said.
The findings support the use of using routine blood draws as a tool to provide a more comprehensive picture of a patient’s health history and inform preventive health measures that can improve long-term health outcomes, Zheng said.
“These findings deepen our understanding of how health behaviors ‘get under the skin’,” Zheng said. “Our lifestyles can indeed leave lasting marks on our biology, which is detectable through changes like DNA methylation.”
Zheng said his team is interested in further studying how these epigenetic biomarkers can be used alongside existing screening tools to improve early detection of cardiovascular disease and how these markers respond to lifestyle changes or treatment to identify patients who may benefit more from early treatment.
“Our next steps are centered on translating these findings into clinical practice,” Zheng said. “We also hope to collaborate with biotech and diagnostics companies to develop affordable, minimally invasive blood test kits that could be used in primary care or preventive cardiology clinics.”
Additional co-authors include Jun Wang, PhD, research associate professor of Preventive Medicine in the Division of Cancer Epidemiology and Prevention; Hongyan Ning, MD, MS,
Research assistant professor of Preventive Medicine in the Division of Biostatistics and Informatics; and Lifang Hou, MD, PhD, chief of Cancer Epidemiology and Prevention in the Department of Preventive Medicine.
This Framingham Heart Study (FHS) was supported by NIH contracts N01-HC-25195, HHSN268201500001I and 75N92019D00031. Support for the Multi-Ethnic Study of Atherosclerosis (MESA) projects are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (75N92023D00002 & 75N92023D00005), Northwestern University (75N92023D00004), University of Minnesota (75N92023D00006), and Kaiser Foundation Research Institute (75N92023D00003). The DNA methylation laboratory work and data processing were funded by the American Heart Association (17SFRN33700278 and 14SFRN20790000) and NHLBI TOPMed.
