Key result
A high genetic risk score for coronary artery disease was associated with a 91% higher risk for cardiac events, while a favorable lifestyle reduced these events by 46% in high-risk individuals.
Why the study?
Primary CAD prevention is limited by the lack of biomarkers to detect asymptomatic young individuals at risk, as traditional risk factors are age-dependent and often absent until the sixth or seventh decade.
Does genetic risk score assessment improve risk stratification for primary prevention of CAD compared to traditional risk factors?
Does genetic risk score assessment improve risk stratification for primary prevention of CAD compared to traditional risk factors?
Genetic risk scores offer a potentially superior and independent biomarker compared to traditional risk factors for identifying young, asymptomatic individuals at high risk for CAD who may benefit from early intervention.
Coronary artery disease (CAD) is a pandemic disease and the number one cause of death in the world. Predisposition to CAD is about 50% acquired and 50% genetic. CAD prevention has been proven in randomized clinical trials with statin therapy. However, primary prevention is limited by the lack of biomarkers to detect asymptomatic young individuals at risk. Traditional risk factors (TRFs) such as hypertension or Type 2 Diabetes are age-dependent and often not present until the sixth or seventh decade. In contrast, genetic risk determined at conception is potentially a biomarker to detect young individuals at risk for CAD. The first genetic risk variant for CAD (9p21) was discovered in 2007, and subsequently, over 200 risk variants for CAD were discovered. A genetic risk score (GRS) based on the genetic risk variants for CAD was evaluated in over one million individuals. Retrospective analysis of clinical trials assessing the effect of statin therapy showed that individuals with the highest GRS had the highest risk for cardiac events and also the most benefit from lowering cholesterol. In a recent study of 55,685 individuals, those with the highest GRS (20%) had a 91% higher risk for cardiac events. Furthermore, those with high genetic risk on a favorable lifestyle had 46% fewer cardiac events than those with an unfavorable lifestyle. The GRS is superior and independent of TRFs. Incorporation into clinical practice will be a paradigm shift in preventing this pandemic.
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Roberts et al. (2022) conducted a review in Coronary artery disease. Genetic risk score (GRS) was evaluated. A high genetic risk score for coronary artery disease was associated with a 91% higher risk for cardiac events, while a favorable lifestyle reduced these events by 46% in high-risk individuals.
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