Genetic risk stratification enables primary prevention of CAD

Abstract

Coronary artery disease accounts for one-third of all deaths in the world and it is estimated that 50% of the American population will have a cardiac event in a normal lifespan. Prevention of CAD has been successful, particularly for secondary prevention. Determining who is at risk for primary prevention based on traditional risk factors (TRFs) is inadequate because the TRFs are often not present until the 6 th or 7 th decade. Sensitivity based on TRFs is further compromised by the recent observation that early primary prevention, based on results of Mendelian Randomization Studies, is threefold more effective. Genetic risk stratification has been assessed in multiple studies involving over one million participants and found to be superior and complementary to methods based on TRS. The upper 20% of the genetic risk score exhibits one to threefold increased risk of CAD. Stratification based on the 10-year risk, as determined by the Pooled Cohort Equation in the current guidelines, would recommend only about 45% of these individuals to receive statin therapy. Results of randomized clinical trials show genetic risk is markedly reduced by statin therapy, lifestyle changes, and physical activity. Genetic risk score has a major advantage over risk stratification based on TRFs, since it is independent of age and provides the same risk at birth as anytime later in life since one’s DNA does not change in one’s lifetime. The test, performed on blood, saliva, or tissue, is inexpensive and is available throughout the world. Statin (those off-patent), the number one drug for prevention, is inexpensive and available worldwide. Genetic risk stratification will enable the implementation of primary prevention of CAD early in life throughout the world. risk score calculated from the genotyping, one can categorize the risk into high, intermediate, and low risk. Multiple studies indicate that the top 20% of genetic risk carries The at risk may vary with both