Genetic profiling for heart disease: An update

As the leading cause of premature death in this country, cardiovascular disease is to blame for more than $150 billion in lost productivity each year. Thanks to decades of research, we know a great deal about what predisposes people to coronary artery disease, the most prevalent form of heart disease and the root cause of most heart attacks. However, doctors still can't predict heart attacks very accurately. Some people who appear prone to heart attacks never have one, while others succumb to heart disease despite having no obvious risks.

Can genetic profiling help? Perhaps, according to a 2022 scientific statement from the American Heart Association that looked at the promise and challenge of such testing. Using a small sample of blood or saliva, these tests analyze millions of common variants in your DNA to create what's known as a polygenic risk score. You can have zero, one, or two copies of any gene variant, each of which may either raise or lower your risk of coronary artery disease.

Millions of variants

"Ten years ago, there were just 20 or 30 known variants that affect coronary artery disease, but today there are more than three million," says Dr. Nicholas Marston, a preventive cardiologist at Harvard-affiliated Brigham and Women's Hospital. Scientists discover variants by comparing the genetic codes of people without coronary artery disease to those of people with the disease. Many of these variants occur in genes known to affect heart disease, such as those related to cholesterol, blood pressure, and blood clotting. Others aren't well understood and may provide targets for future research, potentially fueling new drug discovery efforts, he adds.

The evidence to date

A polygenic risk score reflects the overall impact of all the variants together and is expressed as a percentile. But a high score (for instance, the 95th percentile) doesn't mean you have a 95% chance for developing the disease. Rather, it means that among 100 people, your score is higher than 95 people and the same as or lower than five.

So far, research using polygenic risk scores for coronary artery disease suggests they may offer modest improvements for predicting risk in people who are middle-aged or younger. In some cases, the score can help doctors decide whether to be more or less aggressive in prescribing cholesterol-lowering medications like statins, says Dr. Marston. For example, a 35-year-old man with a father who died of a heart attack at age 45 may wonder what he can do to escape that fate, especially if his cholesterol numbers look fine. Standard risk calculators to guide statin treatment don't apply to people under 40, so a polygenic risk score can help the doctor decide if and when the man should start a statin.

In addition to statins, more powerful cholesterol-lowering drugs like alirocumab (Praluent) and evolocumab (Repatha) are available. These drugs are expensive, and insurance doesn't always cover them. So it doesn't make sense to give them to everyone. A polygenic risk score may help identify which heart attack survivors would benefit most from these medications, says Dr. Marston.

Who offers polygenic risk scores?

Currently, people can find their scores by participating in a research study, such as the Electronic Medical Records and Genomics Network (eMERGE) study. Scientists at some hospitals at Harvard and nine other institutions around the country are investigating the genetic risk of several heart-related conditions, as well as cancer and other diseases (see www.emerge.study).

A handful of direct-to-consumer companies also provide cardiovascular-based scores for $250. Dr. Marston has recommended the test for several of his patients, who must pay out-of-pocket since insurance doesn't cover the tests. Another limitation: the scores are based mainly on people with European ancestry, which means the scores may not be reliable for people of different ethnicities. But efforts to expand the diversity of the data are under way.

For older people, polygenic risk scores for heart disease aren't as helpful. By the time you're 70, decades of lifestyle habits have shaped your risk, and genetic factors are less relevant. "Ultimately, you want the results to be actionable. We won't see a big uptake for using polygenic risk scores until they demonstrate a role in medical decision making," says Dr. Marston.

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