New Test For Early Heart Disease Risk Based on Multiple Genetic Differences

Caption: A new test is able to better predict the risk for heart disease.

A new test could provide a better prediction of an individual’s risk for early-onset heart disease.

The new system calculates a risk score based on multiple genetic differences, or polygenic risk scores, to predict significantly more cases of early-onset heart disease than standard tests for single genetic disorders.

“Our results provide convincing evidence that the polygenic risk score could be added to the genetic investigation of patients with very early coronary artery disease,” Dr. Sébastien Thériault, an assistant professor at Laval University in Quebec City and researcher at the Quebec Heart and Lung Institute, said in a statement.

Heart disease is the leading cause of death worldwide. Coronary artery disease—which occurs when the blood vessels to the heart narrow or harden—is the most common form of heart disease.

The majority of people can decrease their risk of this disease by refraining from smoking, being physically active, maintain a healthy diet and body weight, and controlling cholesterol, blood pressure and blood sugar.

However, there are rare occurrences where high blood levels of LDL cholesterol result from a genetic defect called familial hypercholesterolemia (FH). Patients who have this defect have an increased risk for early-onset heart disease.

The polygenic risk score is based on 182 genetic differences related to coronary artery disease. In the study, researchers compared polygenic risk scores between study participants with and without early-onset heart disease.

“These results suggest a significant polygenic contribution in individuals presenting with EOCAD [early onset coronary artery disease], which could be more prevalent than familial hypercholesterolemia,” the study states. “Determination of the polygenic risk component could be included in the diagnostic workup of patients with EOCAD.”

The researchers examined the relationship between a risk score based on multiple genetic differences and early-onset heart disease and found that the polygenic risk score predicted a high risk for early-onset disease in one in 53 people at the same level as FH does. The prevalence of FH is 1 in 256 individuals for the single genetic test for FH.

“The increase in genetic risk was independent of other known risk factors, suggesting that testing for multiple genetic differences is clinically useful to evaluate risk and guide management,” senior author Dr. Guillaume Paré, an associate professor of medicine at McMaster University and Hamilton Health Sciences in Hamilton, Canada, and the director of the Genetic and Molecular Epidemiology Laboratory, said in a statement.

“Combining polygenic screening with current testing for familial hypercholesterolemia could potentially increase five-fold the number of cases for which a genetic explanation can be found,” he added.

The study included 30 patients with early-onset heart disease seen in the researchers’ clinic between 2014 and 2016. None of the study participants had the single, rare genetic defect for FH.

The study also included 96 patients with early-onset heart disease that enrolled in the UK Biobank study between 2006 and 2010. As controls, the study also included 111,283 UK Biobank participants without early-onset heart disease.

All study participants were of European descent, so the results may not apply to other populations. Another limitation is its inclusion of patients with severe early-onset heart disease, which is more likely to have genetic causes than milder disease.

The study was published in Circulation: Cardiovascular Genetics.