Primary prevention of coronary artery disease based on genetic prediction

Prevention of coronary artery disease (CAD) following a cardiac event has been successful by modifying known conventional risk factors, such as cholesterol. These risk factors are age-dependent and less effective for primary prevention. To halt the pandemic spread of CAD, the number one killer in the world requires primary prevention of cardiac events. 50 percent of all Americans will experience a cardiac event; the challenge is identifying those asymptomatic individuals at risk. Genetics account for 40-60 percent of predisposition for CAD. Since the discovery of the first genetic risk variant, 9p21, in 2007, hundreds of genetic risk variants had been discovered. The genetic burden for CAD can be expressed in a single number, referred to as the Genetic Risk Score (GRS). Retrospective genotyping of clinical trials performed to assess the effect of statin therapy confirmed that GRS improves risk stratification of CAD and detects those benefitting most from statin therapy. In a prospective study of 55,685 individuals, the group with the high GRS had a 91 percent higher risk for cardiac events. Individuals with a healthy lifestyle, and a high GRS, had a 46 percent lower risk for cardiac events in comparison to those with an unfavorable lifestyle. In another trial, risk stratification by GRS showed those at highest genetic risk and performed the most physical activity, had a 50 percent reduction in cardiac events. Genetic risk stratification for CAD has been shown to be superior to conventional risk factors, and the risk is markedly attenuated by lifestyle changes and drug therapy. Genetic risk for CAD can be determined at any time; from birth on since one's DNA does not change in one's lifetime. Utilizing the GRS to risk stratify young, asymptomatic individuals could provide a paradigm shift in the primary prevention of CAD and significantly halt its pandemic spread.