Genetic Risk Scores Could Identify Patients at Risk of Heart Attack

Using genetic risk scores could help identify patients at high risk of heart attack who are not presently identified using traditional clinical methods, according to a study published in the Journal of the American College of Cardiology.

Research has linked genetic variants with a higher risk of having a heart attack, enabling the calculation of polygenic risk scores (PRS) that quantify patients’ inherited susceptibility based on the number of variants they have.

A team from Massachusetts General Hospital and the Broad Institute of Massachusetts Institute of Technology and Harvard applied PRS to 47,108 individuals who were an average age of 60 and receiving care at three US health systems.

The PRS strongly associated with the presence of coronary artery disease – the cause of heart attacks. Those with scores in the top 20 percent were 1.9 times more likely to have developed disease compared with the remaining 80 percent of the population. Significantly, those with high PRS were not more likely than others to have been previously recognized as high risk by their physicians.

“We identified a subset of individuals at double the risk of heart attack on the basis of their genes. Despite this elevated risk, these individuals were neither more likely to be flagged as high risk, nor more likely to receive preventive statin therapy per our conventional clinical practices—a consistent finding across all three health systems studied,” said lead author Krishna Aragam, MD, a cardiologist at Mass General and an instructor in Medicine at Harvard Medical School.

The team determined that if coronary artery disease PRS were considered alongside current national guidelines, an additional 4.1 percent of patients who have not yet experienced a heart attack may be recommended to receive cholesterol-lowering statins.

“When coupled with clinical assessments, we estimate that genetic testing may uniquely identify a need for preventive statin therapy in approximately 1 in every 25 of such patients,” said Aragam.

Through research-based and direct-to-consumer services, assessments of polygenic risk are becoming more pervasive, the researchers noted.  

Genetic variants have helped investigators learn more about risk factors for multiple conditions, from diabetes to schizophrenia.

Recently, a team from the HudsonAlpha Institute for Biotechnology, the University of California, San Francisco (UCSF), and the University of Alabama at Birmingham (UAB) uncovered a genetic risk factor for multiple neurodegenerative conditions, including Alzheimer’s disease.

After conducting a genome analysis, the team found that rare variation in a particular gene nearly doubled an individual’s risk of developing conditions like Alzheimer’s, ALS, and frontotemporal dementia (FTD).

“Finding evidence for a risk factor that contributes to multiple neurodegenerative diseases is exciting,” said Richard M. Myers, PhD, HudsonAlpha president and science director. “We already know that these diseases share some pathologies. This work shows that the underlying causes of those pathologies may also be shared.”

The genetic risk scores used by the team at Mass General could improve upon current clinical assessments of risk, especially in cases of clinical uncertainty.

“Within our present frameworks for heart attack prevention, we speculate that genetic testing may be most immediately useful to guide clinical management for patients otherwise falling in a ‘gray area’ of intermediate risk based on standard clinical factors,” Aragam said.