Genetic risk score may reshape primary prevention

Robert Roberts

MUNICH — The time has come for the genetic risk score, which is simple to calculate and inexpensive to acquire, to play a larger role in primary prevention of CAD, an expert said at the European Society of Cardiology Congress.

“Utilizing the genetic risk score … is truly a paradigm shift in terms of how we want to approach what is now a pandemic disease and the No. 1 killer in the world,” Robert Roberts, MD, FRCPC, MACC, FAHA, FESC, LLD, cardiologist at Banner – University Medicine Heart Institute in Phoenix, professor of medicine at the University of Arizona College of Medicine – Phoenix, International Society for Cardiovascular Translational Research (ISCTR) chair and a member of the Cardiology Today Editorial Board, said during a presentation.

At this point, more than 160 genetic risk variants predisposing to CAD have been identified, and “genetic risk for CAD is proportional to the number of variants inherited, rather than a specific risk variant,” Roberts said.

It has been well-documented that CAD is preventable and “a genetic risk score to risk-stratify and prevent CAD can significantly alter the spread of this disease,” he said.

An individual’s genetic risk score can be calculated by summing the product of genetic risk variants inherited by that individual for each generic risk variant, weighted by the natural log of the OR, he noted.

Authors of a study published in The Lancet in 2015 risk-stratified participants based on 27 genetic risk variants and determined that the number needed to treat to prevent one cardiac event in those at high genetic risk was 25, compared with 42 for those at intermediate risk and 66 for those at low genetic risk.

In addition, Roberts said, when more than 10,000 participants from the WOSCOPS study of primary prevention of statin therapy were genotyped with 57 genetic risk variants, researchers found that statin therapy conferred a 44% risk reduction (number needed to treat to prevent one cardiac event, 13) in people at high genetic risk vs. a 24% risk reduction (number needed to treat to prevent one cardiac event, 38) in the rest of the population.

As Cardiology Today previously reported, a study published in 2016 in The New England Journal of Medicine showed that “lifestyle can modify genetic risk and eliminates the myth that whatever is in your genes is fixed and cannot be modified,” opening up the possibility of using genetic risk scores to enhance primary prevention, he said.

“The genetic risk score predicts cardiac events relatively independent of clinical risk factors used in the Framingham Risk Score, the Pooled Cohort Equations, etc, and is significantly more discriminating,” Roberts said. “It does not vary over time. It does not vary with meals. It does not vary with drugs. It does not vary with gender. And it can be determined by a single test: One saliva sample per lifetime, since one’s DNA does not change over one’s lifetime.”

The genetic risk score may be most useful in asymptomatic premenopausal women and asymptomatic young men, neither of whom are likely to get CT scans or angiograms barring symptoms, he said.

“We know that for people born in the Western world today who live a normal life span, 49% will have a cardiac event before they die,” he said. “Based on the data that have been published, using the genetic risk score, rather than treating all men between ages 45 and 74 and all women between ages 55 and 74 with statins as has been proposed, we could treat about half of them depending on where you want to make the cutoff, and that would save costs and minimize side effects.

“We should in our daily practice start to use the genetic risk score,” Roberts concluded. “It has consistently shown to be very effective and very accurate. It’s available to people with low, medium and high incomes and is cheaper than most blood tests. And whether you do it with lifestyle or statin therapy, you can modify genetic risk in the same way that we’re used to modifying conventional risk factors.” – by Erik Swain

References:

Roberts R. Big data, precision care: Where are we now and where will we be in the future? Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.

Khera AV, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1605086.

Mega JL, et al. Lancet. 2015;doi:10.1016/S0140-6736(14)61730-X.

Natarajan P, et al. Circulation. 2017;doi:10.1161/CIRCULATIONAHA.116.024436.

Roberts R. Circulation. 2018;doi:10.1161/CIRCULATIONAHA.118.034732.

Disclosure: Roberts reports he serves on the scientific advisory committee for Cumberland Pharmaceuticals.