Coronary artery disease (CAD) risk increases in proportion to the magnitude and duration of exposure to plasma low-density lipoprotein cholesterol (LDL-C), doubling every additional decade of exposure. Early primary prevention is three times more effective than initiated later. Several clinical trials show plasma LDL-C of 15–40 mg/dL is more effective and equally safe as the Current Cardiovascular Clinical Practice Guidelines (CCCPG) recommended target of 70mg/dL. The cholesterol in the blood is the excess synthesized by the cells and secreted into the blood for disposal in the liver. The CCCPG is inadequate since traditional risk factors (TRF) are not detectable until the sixth and seventh decade. The genetic risk score (GRS) evaluated in 1 million individuals as a risk stratifier for CAD is superior to TRF. Genetic risk for CAD was reduced by 30–50% by statin therapy, PCSK9 inhibitors, and lifestyle changes. The GRS does not change during one’s lifetime and is inexpensive. Incorporating genetic risk stratification into CCCPG would induce a paradigm shift in the primary prevention of CAD.

冠状动脉疾病 (CAD) 风险与暴露于血浆低密度脂蛋白胆固醇 (LDL-C) 的量级和持续时间成正比，每增加 10 年暴露一倍。早期一级预防的效果是后期开始的三倍。几项临床试验表明，与当前心血管临床实践指南 (CCCPG) 推荐的 70mg/dL 目标相比，15–40 mg/dL 的血浆 LDL-C 更有效且同样安全。血液中的胆固醇是由细胞合成并分泌到血液中以供肝脏处理的过量胆固醇。CCPGG 是不够的，因为传统的风险因素 (TRF) 直到第六和第七个十年才被发现。在 100 万个人中评估的作为 CAD 风险分层的遗传风险评分 (GRS) 优于 TRF。通过他汀类药物治疗、PCSK9 抑制剂和生活方式的改变，CAD 的遗传风险降低了 30-50%。GRS 在一个人的一生中不会改变，而且价格低廉。将遗传风险分层纳入 CCCPG 将导致 CAD 一级预防的范式转变。