Genetic tests mean new options for treating and preventing heart disease


The number of genes known to be associated with heart disease keeps rising. Common genetic variants have been identified that are associated with coronary artery disease, cholesterol levels, hypertension, diabetes, and other risk factors.

Yet, to date, cardiovascular genetics has had little impact on clinical practice. This situation is likely to change in the near future as point-of-care genetic screening becomes available, guiding treatment and stratifying risk.

A major milestone was reached when the University of Ottawa Heart Institute developed the world’s first bedside genetic test in order to tailor drug therapy for cardiac stent patients. The RAPID GENE trial, published recently in The Lancet, demonstrated that the test successfully protected all patients with a particular genetic variant from subsequent adverse events, while 30 per cent of patients treated with standard therapy did not receive adequate protection.

Until now, turnaround times have been a significant barrier to the use of genetic screening in clinical settings. With results taking days to come back, point-of-care testing has been impractical or impossible. The RAPID GENE test, developed in partnership with Spartan Bioscience, uses a simple cheek swab to identify patients with the CYP2C19*2 genetic variant within an hour. Cardiac stent patients with this variant are at risk of reacting poorly to standard anti-platelet therapy with Plavix® (clopidogrel).

“For the first time in medicine, nurses were able to perform DNA testing at the patient’s bedside,” says Dr. Derek So, Heart Institute interventional cardiologist and RAPID GENE principal investigator. “This is a significant step towards the vision of personalized medicine.”

Also important was the limited technical knowledge needed to conduct the screening. “All genetic testing in the trial was done by clinical nurses who required only a half-hour training session on how to use the machine. With that minimal training, we could identify at-risk variants very quickly and alter therapy,” adds Dr. So.

His team is now conducting a follow-up trial to look at whether screening for two additional variants can better guide anti-platelet therapy.

Another group of Heart Institute researchers is busy developing a blood test to identify people at heightened genetic risk for heart disease. Such a test could reveal increased risk before symptoms emerge, offering a high-impact opportunity for prevention.

The most significant known genetic risk factor is the 9p21 genetic variant. It increases the risk of coronary artery disease by 15 to 20 per cent in individuals with one copy and 30 to 40 per cent in individuals with two copies. Half of the Caucasian population falls into the first category while another quarter falls into the second.

Alexandre Stewart, principal investigator in the Ruddy Canadian Cardiovascular Genetics Centre, was part of the team that discovered 9p21, and he now leads the effort to develop a blood test to screen for it. His group has discovered that a protein called interferon alpha-21 (INFα-21) is a biomarker for 9p21. INFα-21 is found in the blood of people who carry two copies of the variant at concentrations up to 30 times higher than in people with no copies.

Findings from the Heart Institute and others suggest that a blood test for IFNα-21 would be reliable in detecting CAD in about a fifth of the world’s population, without having to do an angiogram. The benefits of avoiding a costly and invasive procedure would be substantial for both patients and the health care system. “These people could immediately be targeted for aggressive therapy,” says Stewart. The team is now looking at whether an existing test approved for laboratory research purposes can be adapted for clinical use.

Other research has shown that having a high genetic risk profile for heart disease does not mean a person’s future health is written in stone. A study of carriers of 9p21 indicated that those individuals can still reduce their risk of heart disease substantially through a healthy diet high in fruits and vegetables. This means that having the genetic information at their fingertips can give individuals the impetus to make important and effective lifestyle changes.

“We have to always think in terms of these risk variants interacting with the environment,” says Dr. Robert Roberts, president and CEO of the Heart Institute. “If you modify your environment, you affect your risk. Our genes only mean something when they interact with the environment.”

As tests such as those being developed at the University of Ottawa Heart Institute become available, practical and timely access to relevant genetic information is becoming a reality. With this information in hand, physicians will be able to guide treatment more precisely and patients will have a better basis for making decisions about their own care and personal health choices. While the clinical value of personal genome sequencing remains a prospect for the future, these targeted approaches have the potential to make an impact in the near-term.