Rader-new Daniel J. Rader, MD

Mr. H is a 45-year-old non-smoker with healthy cholesterol levels, borderline high blood pressure, no signs of diabetes or hypertension, and some family history of coronary artery disease. He exhibits no active heart disease. Yet his physician is about to prescribe a cholesterol-managing statin drug for him. Why? Because Daniel J. Rader, MD, sees heart disease in Mr. H's genes. 

“By current guidelines, you wouldn’t dream of putting this patient on a statin,” said Rader, who is director of Penn’s Preventive Cardiovascular Medicine and Lipid Clinic. “But when you have additional information from a genetic test suggesting his risk is substantially elevated, you may very well prescribe a statin despite the fact that the cholesterol level itself is not elevated.”

New methods to identify heart disease and other disorders have emerged from the sequencing of the human genome. At Penn, cardiology is one of the first specialties to use genetic risk to assess and treat patients, zeroing in on DNA variants that are clearly associated with heart disease. Based on the genetic profile of Mr. H, Rader has the potential to treat his patient’s inherited risk before it manifests as heart disease.

“The first heart attack is hard to predict; it is suddenly lethal .. and it’s preventable,” Rader said. However, only 60 percent of heart attacks are attributable to traditional risk factors for cardiovascular disease, including family history, smoking, obesity, high cholesterol and high blood pressure.

Only 60 percent of heart attacks are attributable to traditional risk factors for heart disease. Genetics might help identify the other 40% at risk before they have a heart attack.

Rader and his colleagues have been actively involved in cutting edge resaerch leading to the identification of new genes that predispose a person to the risk of heart attack. Based on these results, the Preventive Cardiovascular Medicine program has begun testing eight common variants within the human genome that have been conclusively linked to heart attacks to assess risk for cardiovascular disease.

Mr. H’s genetic profile allows Rader to take his patient’s health care recommendations to a new, personalized level. “We are at a point in time when we can take genetic variants that we know are associated with risk of a serious disease and apply them clinically to attempt to prevent the disease,” said Rader.  “The era of personalized preventive medicine is at hand.”

A Truly Personalized Approach

Personalized medicine offers patients genetic information about their risk for such common diseases as cancer and diabetes to share with their health-care providers, who then can prescribe, recommend, and treat with greater precision.

A genetic profile allows physicians and patients to take preventive medicine to a deeper level.

In addition to taking a statin as a preventive measure, Mr. H may take his genetic profile as motivation to exercise and lose weight, further lowering his risk for heart disease. Rader said that learning of genetic risk seems to be a greater incentive for people to change their behaviors than even family history. Rader may also recommend further blood pressure testing for Mr. H to assess his slightly elevated blood pressure readings. “Fish oil and aspirin are other considerations for prevention of heart attack in a setting of high genetic risk.”

Genetic markers for various diseases are common, emphasized Rader, and they do not automatically indicate that an individual will develop a particular disease. Rather, a genetic profile allows physicians and patients to take preventive medicine to a deeper level. Health-care providers also can learn of a genetic predisposition for adverse reactions to certain drugs, helping doctors and nurse practitioners prescribe more accurately for an individual patient.

Gaining Insight

The use of genetic profiles in health is a nascent concept. “We have a lot to work through as a society and as a medical community to figure out what the appropriate tests are, in what situations we should be doing them, and how much information should be given to patients, ” Rader said.

An ongoing collaborative study at Penn and the Coriell Institute is probing the motivations of people who seek out this tailored information. The study is part of the Coriell Personalized Medicine Collaborative, longterm research examining the impact of personalized medicine on health management and clinical decision-making. Study participants receive personalized results on their risks for common diseases like cancer, heart disease and diabetes, as well as their ability to metabolize certain medications. They then complete follow-up questionnaires to inform the medical and scientific communities about using genetic information in medical care.

The Penn-Coriell study assesses the attitudes and experiences of early users of personalized medicine. Barbara A. Bernhardt, MS, CGC, who serves as co-director of the Penn Center for the Integration of Genetic Healthcare Technologies, is study investigator,

Whether to share genetic information with health-care providers is a significant issue in personalized medicine.

How do people feel about using genetic profiles as part of their health care portfolios? The study showed that 95 percent of people involved wanted to learn about the diseases for which they are at risk, ways to improve their health, and more about their genes, and to help others through research. Other motivations included interest in their ancestry or because they were adopted.

Whether to share genetic information with health-care providers is a significant issue in personalized medicine. In the Penn-Coriell study, one-third of interviewees had already shared results with their doctors, mainly because they believed their doctors would be interested in having the results and so their doctors could provide recommendations for screening and risk reduction. Physician responses varied from ““What am I supposed to do with these?” to “. . . she knew about my family history so she was glad to know the results.”

One participant clearly benefited: “I was a little surprised that I had the melanoma gene [so] I went to a dermatologist after that for a full body check. . . . I had a mole removed from my back that turned out to be melanoma. Now I’m here with no melanoma because [the mole] was stage zero. I’m really grateful for having taken this test because it caught it at that stage.”

Bridges Still to Cross

The promise of personalized medicine, still in its earliest phases, is not without possible pitfalls, said Arthur Caplan, PhD, director of the Penn Center for Bioethics. As participants in the Penn-Coriell study found, the results might prove difficult to interpret for doctors who aren’t steeped in genetics. “Competent personalized medicine,” said Caplan, “will require focused training for health care providers, genetic counselors, and pharmacists.”

“I think it’s self-evident that we should not have testing without counseling -- end of story, no exception.” - Art Caplan, PhD

At the same time, he said that patients will need well-considered counseling to understand their risks based on their genetic profiles and how to manage them, raising key ethical points. “We don’t have agreement on who should set the standards yet about when a test is ready for prime-time,” he said, noting the availability of home genetic testing kits and Internet services claiming to offer genetic profiles. “And I think it’s self-evident that we should not have testing without counseling -- end of story, no exception.”

On the insurance front, health insurance falls under the protection of the Genetic Information Nondiscrimination Act of 2008, but life insurance does not. Caplan foresees a “failure to pay” among insurance companies who can fault a “pre-existing condition” derived from a genetic profile.

With personalized medicine and health-care reform on the horizon, Caplan envisions these areas converging because both involve primary care access and will require a larger pool of primary care providers. “One bit of good news is that [the issue of genetic profiles] is not separated from health reform, so you have more people enfranchised to seek and get primary care,” he said. “The bad news is that no one has created more primary care providers. . . . We will need to extend and train that labor pool.” 

-- by Jennifer Baldino Bonett