The Next Frontier in Heart Care; Research Aims to Personalize Treatment With Genetics

The Next Frontier in Heart Care

Research Aims to Personalize Treatment With Genetics

RON WINSLOW

Nov. 25, 2013 7:18 p.m. ET

Two influential heart studies are joining forces to bring the power of genetics and other 21st century tools to battle against heart disease and stroke. Ron Winslow and study co-director Dr. Vasan Ramachandran explain. Photo: Shubhangi Ganeshrao Kene/Corbis.

Scientists from two landmark heart-disease studies are joining forces to wield the power of genetics in battling the leading cause of death in the U.S. Cardiologists have struggled in recent years to score major advances against heart disease and stroke. Although death rates have been dropping steadily since the 1960s, progress combating the twin diseases has plateaued by other measures.Genetics has had a profound impact on cancer treatment in recent years. Now, heart-disease specialists hope genetics will reveal fresh insight into the interaction between a person’s biology, living habits and medications that can better predict who is at risk of a heart attack or stroke.

“There’s a promise of new treatments with this research,” said Daniel Jones, chancellor of the University of Mississippi and former principal investigator of the 15-year-old Jackson Heart Study, a co-collaborator in the new genetics initiative.

Prevention efforts also could improve with the help of genetics research, Dr. Jones said. For example, an estimated 75 million Americans currently have high blood pressure, or hypertension, but only about half of those are able to control it with medication. It can take months of trial-and-error for a doctor to get the right dose or combination of pills for a patient. Researchers hope genetic and other information might enable doctors to identify subgroups of hypertension that respond to specific treatments and target patients with an appropriate therapy.

Also collaborating on the genetics project is the 65-year-old Framingham Heart Study. Its breakthrough findings decades ago linked heart disease to such factors as smoking, high blood pressure and high cholesterol. Framingham findings have been a foundation of cardiovascular disease prevention policy for a half-century.

More than 15,000 people have participated in the Framingham study. The Jackson study, with more than 5,000 participants, was launched in 1998 to better understand risk factors in African-Americans, who were underrepresented in Framingham and who bear a higher burden of cardiovascular disease than the rest of the population. Both studies are funded by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

Exactly how the collaboration, announced last week, will proceed hasn’t been determined. One promising area is the “biobank,” the collection of more than one million blood and other biological samples gathered during biennial checkups of Framingham study participants going back more than a half century.

The samples are stored in freezers in an underground earthquake-proof facility in Massachusetts, said Vasan Ramachandran, a Boston University scientist who takes over at the beginning of next year as principal investigator of the Framingham Heart Study. Another 40,000 samples from the Jackson study are kept in freezers in Vermont. By subjecting samples to DNA sequencing and other tests, researchers say they may be able to identify variations linked to progression of cardiovascular disease—or protection from it.

Each study is likely to enroll new participants as part of the collaboration to allow tracking of risk factors and diet and exercise habits, for instance, in real time instead of only during infrequent checkups.

Heart disease is linked to about 800,000 deaths a year in the U.S. In 2010, some 200,000 of those deaths could have been avoided, including more than 112,300 deaths among people younger than 65, according to a recent analysis by the Centers for Disease Control and Prevention. But those avoidable deaths reflected a 3.8% per year decline in mortality rates during the previous 10 years.

Now, widespread prevalence of obesity and diabetes threatens to undermine such gains. And a large gap remains between how white patients and minorities—especially African-Americans—benefit from effective strategies.

There have been few new transformative cardiovascular treatments since the mid-1980s to early 1990s, when a stream of large-scale trials of new agents ranging from clot-busters to treat heart attacks to the mega class of statins electrified the cardiology field with evidence of significant improvements in survival from the disease. One reason: Some of those remedies have proven tough to beat with new treatments.

What’s more, use of the current menu of medicines for reducing heart risk remains an imprecise art. Besides blood pressure drugs, cholesterol-lowering statins also are widely prescribed. Drug-trial statistics show that to prevent a single first heart attack in otherwise healthy patients can require prescribing a statin to scores of patients, but no one knows for sure who actually benefits and who doesn’t.

“It would be great if we could make some more paradigm-shifting discoveries,” said Michael Lauer, director of cardiovascular sciences at the NHLBI, which is a part of the National Institutes of Health.

Finding new treatments isn’t the only aim of the new project. “You could use existing therapies smarter,” said Joseph Loscalzo, chairman of medicine at Brigham and Women’s Hospital in Boston.

The American Heart Association launched the initiative and has committed $30 million to it over the next five years. The AHA sees the project as critical to its goal to achieve a 20% improvement in cardiovascular health in the U.S. while also reducing deaths from heart disease and stroke by 20% for the decade ending in 2020, said Nancy Brown, the nonprofit organization’s chief executive.

The Jackson study has already identified characteristics of cardiovascular risk among African-American patients “that may have promise for new insights” in a collaborative effort, said Adolfo Correa, professor of medicine and pediatrics at University of Mississippi Medical Center and interim director of the Jackson study.

For instance, there is a higher prevalence of obesity among Jackson participants than seen in the Framingham cohorts. Obesity is associated with high blood pressure, diabetes and cardiovascular risk. Diabetes is also more prevalent among blacks than whites.

But African-Americans of normal weight appear to have higher rates of hypertension and diabetes than whites of normal weight. “The question is, should [measures] for defining diabetes be different or the same for the [different] populations and are they associated with the same risk of cardiovascular disease?” said Dr. Correa. The collaboration, he said, may provide better comparisons.

Researchers, who plan to use tools other than genetics, think more might be learned about blood pressure and heart and stroke risk by monitoring patients in real time using mobile devices rather than taking readings only in periodic office visits. For example, high blood pressure during sleep or spikes during exercise could indicate risks that don’t show up in a routine measurement in the doctors’ office.

A big challenge is making sense of the huge amounts of data involved in sequencing DNA and linking it to medical records, diet and exercise habits and other variables that influence risk.

“The analytical methods for sorting out these complex relationships are still in evolution,” said Dr. Loscalzo, of Brigham and Women’s Hospital. “The cost of sequencing is getting cheaper and cheaper. The hard part is analyzing the data.”