PDF(Pubmed)
Abstract：
BACKGROUND: A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores.
RESULTS: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals.
CONCLUSIONS: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.
RESULTS: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals.
CONCLUSIONS: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.
摘要：
背景：一项研究旨在调查冠状动脉疾病多基因风险评分（CAD-PRS）是否可以指导降脂治疗的开始以及在一级预防中的推迟超过既定的临床风险评分。
结果：参与者是来自英国生物银行的311799名没有动脉粥样硬化性心血管疾病的个体，糖尿病,慢性肾病,和基线时的降脂治疗。参与者被归类为他汀类药物，他汀类药物适应症不明确，或未按照欧洲和美国的他汀类药物使用指南所定义的他汀类药物。中位数为11.9(11.2-12.6)年，发生8196例主要冠状动脉事件。将CAD-PRS添加到欧洲系统冠状动脉风险评估2（European-SCORE2）和美国集合队列方程（US-PCE）中，确定了18％和12％的他汀类药物适应症不明确个体的主要冠状动脉事件风险与他汀类药物指示个体的平均风险相同或高于他汀类药物指示个体的平均风险，16％和12％的他汀类药物指示个体的主要冠状动脉事件风险与他汀不明确个体对于主要的冠状动脉和动脉粥样硬化性心血管疾病事件，在他汀类药物适应症或他汀类药物适应症不明确的个体中，CAD-PRS改善的C统计学比没有他汀类药物适应症的个体更大。对于动脉粥样硬化性心血管疾病事件，将CAD-PRS添加到欧洲评估和美国方程式中，他汀类药物的净重新分类改善了13.6％（95％CI，11.8-15.5）和14.7％（95％CI，13.1-16.3）。10.8%（95%CI，9.6-12.0）和15.3%（95%CI，13.2-17.5）的他汀类药物适应症不明确，在未应用他汀类药物的个体中，分别为0.9%（95%CI，0.6-1.3）和3.6%（95%CI，3.0-4.2）。
结论：CAD-PRS可以指导欧洲和美国指南定义的他汀类药物适应症不明确或他汀类药物适应症个体的开始和推迟。CAD-PRS在他汀类药物未指示的个体中几乎没有临床效用。
结果：参与者是来自英国生物银行的311799名没有动脉粥样硬化性心血管疾病的个体，糖尿病,慢性肾病,和基线时的降脂治疗。参与者被归类为他汀类药物，他汀类药物适应症不明确，或未按照欧洲和美国的他汀类药物使用指南所定义的他汀类药物。中位数为11.9(11.2-12.6)年，发生8196例主要冠状动脉事件。将CAD-PRS添加到欧洲系统冠状动脉风险评估2（European-SCORE2）和美国集合队列方程（US-PCE）中，确定了18％和12％的他汀类药物适应症不明确个体的主要冠状动脉事件风险与他汀类药物指示个体的平均风险相同或高于他汀类药物指示个体的平均风险，16％和12％的他汀类药物指示个体的主要冠状动脉事件风险与他汀不明确个体对于主要的冠状动脉和动脉粥样硬化性心血管疾病事件，在他汀类药物适应症或他汀类药物适应症不明确的个体中，CAD-PRS改善的C统计学比没有他汀类药物适应症的个体更大。对于动脉粥样硬化性心血管疾病事件，将CAD-PRS添加到欧洲评估和美国方程式中，他汀类药物的净重新分类改善了13.6％（95％CI，11.8-15.5）和14.7％（95％CI，13.1-16.3）。10.8%（95%CI，9.6-12.0）和15.3%（95%CI，13.2-17.5）的他汀类药物适应症不明确，在未应用他汀类药物的个体中，分别为0.9%（95%CI，0.6-1.3）和3.6%（95%CI，3.0-4.2）。
结论：CAD-PRS可以指导欧洲和美国指南定义的他汀类药物适应症不明确或他汀类药物适应症个体的开始和推迟。CAD-PRS在他汀类药物未指示的个体中几乎没有临床效用。
