SFRN Centers Prevention

Center Director: Philip Greenland, M.D.

At Northwestern University in Chicago, researchers studied environmental factors that affect cardiovascular health throughout the lifespan. “No one before had ever looked at harmonizing the data collected from studies of three different age groups to create a picture of risk factor change across the lifespan,” said Center Director Philip Greenland, M.D.

The clinical project enrolled college students in a research study exploring the impact of different types of health education programs on environmental risk factors for cardiovascular disease, such as stress, diet and exercise. The basic science researchers used blood samples from students in their freshman and senior years for epigenetic analyses. Epigenetics refers to changes in gene functions caused by environmental factors. The scientists will compare the changes in students who maintained or adopted a healthy lifestyle with those who developed risk factors for cardiovascular disease.

The basic science team also analyzed blood samples stored from Northwestern’s ongoing Coronary Artery Risk Development in Young Adults study. Their studies showed that people who had more risk factors had more adverse effects on their epigenomes. The study also showed an association between metabolic syndrome — a cluster of conditions that increases risk for cardiovascular disease and stroke — and epigenetic changes associated with accelerated aging. This novel finding was published in Clinical Epigenetics.

The population science researchers analyzed data from previous studies that looked at distinct age groups to investigate changes in cardiovascular risk factors from childhood through middle age.

The center’s work launched additional basic, clinical and population studies investigating why hearthealth measures decline from childhood to middle age, and how to help people maintain ideal heart health or reverse declines. The center’s work also led to multiple publications and grant awards, including two additional SFRNs.

Center Director: Valentin Fuster, M.D., Ph.D.

The Icahn School of Medicine at Mount Sinai in New York City studied the benefits of a community-based heart-health education program in preschools in Harlem. One of the best approaches to preventing disease is to work with children, according to Center Director Valentin Fuster, M.D., Ph.D.

“Children at this age absorb and store in their brains what you tell them,” Fuster said. “We are taking advantage of how centers of the brain connect when we teach children this information when they are in preschool.”

The population scientists tested a 60-hour heart health education program, FAMILIA, that was developed for preschool-age children. This work complemented the clinical science research, which investigated whether peer coaching or individual lifestyle coaching could get parents and caregivers to integrate healthier behaviors into family life. The basic scientists studied genetic and genomic data collected from the children and their parents or caregivers to seek clues to cardiovascular disease prevention.

Findings were presented at the American Heart Association’s Scientific Sessions in Philadelphia in November 2019. The center’s research advanced previous work by Fuster and his colleagues on cardiovascular health promotion and disease prevention in children in Colombia and Spain.

“The American Heart Association allowed us to bring this study to the U.S.,” Fuster said.

After learning about the research, the children’s television show “Sesame Street” created a Muppet named Dr. Ruster who, like Dr. Fuster, teaches children how to make heart-healthy lifestyle choices.

Fuster has received additional funding to follow the 50,000 children taking part in his research worldwide until they’re 20. He also has applied for a grant from the National Institutes of Health to extend the work to all five boroughs of New York City.

Center Director: Joseph Hill, M.D., Ph.D

At UT Southwestern Medical Center in Dallas, researchers made significant advances that could lead to new treatments for patients with heart failure with preserved ejection fraction (HFpEF), which is increasing in prevalence worldwide and has no effective treatment.

“Our observations completely turned the field upside down, providing an explanation for why previous clinical trials have failed and opening up new ideas on how to move forward with new treatments,” said Center Director Joseph Hill, M.D., Ph.D.

Heart failure is a chronic condition in which the heart can’t pump the blood and oxygen cells need. People with HFpEF have a heart that can pump normally but is too stiff to fill properly. Diabetes, high blood pressure, kidney disease and obesity all increase the risk for HFpEF.

Hill was conducting basic science research on HFpEF when he learned about the Prevention SFRN.

“I thought we were uniquely positioned to bring basic, clinical and population science together because of the programs we already had in place,” he said. “So we looped in the clinical and population science groups and put together a truly cohesive multidisciplinary program.”

The clinical science project studied middle-age patients at high risk for developing HFpEF. It demonstrated that a one-year aerobic exercise program could reverse stiffening in the heart muscle.

This research tied into the population scientists’ study on the relationship between physical activity level and heart failure. This study enrolled African American women and men, who have higher rates of heart disease than white women and men. It found that people who already had heart damage and an enlarged left ventricle — the heart’s main pumping chamber — had nearly a 40% risk of being diagnosed with heart failure over the next 10 years. This study was also the first to show that people who engage in higher levels of physical activity are less likely to develop HFpEF.

The basic science project developed a new preclinical mouse model of HFpEF. In addition to having HFpEF, these mice had the health issues most often seen in these patients: obesity, diabetes and high blood pressure. Their studies showed that prior mouse models did not accurately represent HFpEF in humans. This work was published in April 2019, in Nature.

“Our success came out of our three teams asking the same questions but using different strategies to approach them,” Hill said. “Honestly, this is the most important research I have ever done.”

Center Director: David Harrison, M.D.

At Vanderbilt University, scientists united to investigate how salt damages heart tissue and to identify new approaches to prevent and treat high blood pressure, a leading cause of cardiovascular disease.

The basic science project showed that sodium enters cells that are important in activating the immune system. This, in turn, causes an inflammatory response which activates other immune cells that can damage the heart, blood vessels and kidneys. The basic science researchers also discovered that sodium can activate centers in the brain that get the central nervous system to activate inflammatory processes.

“With the American Heart Association funding we discovered ways that sodium enters cells — in particular, immune cells, which no one suspected are affected by sodium — and the intercellular signals that occur in response,” said Center Director David Harrison, M.D.

“Identifying these targets is the first step to developing medications that can intervene in these processes to reduce inflammation and, in turn, bring blood pressure back to normal levels,” Harrison said.

The clinical science research, done in collaboration with the center’s basic scientists, used sodium magnetic resonance imaging to measure tissue concentrations of salt. These studies showed that people with high tissue concentrations of sodium had inflamed immune cells, pinpointing a new mechanism for identifying high-risk patients.

The population research tied together the basic and clinical science studies, investigating how a polypill that contains low doses of three drugs used to treat high blood pressure and one drug used to lower cholesterol affects risk for cardiovascular disease in underserved populations.

The study, published in the New England Journal of Medicine in September 2019, showed that the single pill reduced the estimated risk of cardiovascular disease by 25%, a finding that attracted widespread media attention. Currently polypills aren’t sold in the U.S., but they’re available in other countries.

“Without this funding, we wouldn’t have been able to do any of these studies,” Harrison said.