Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.
Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.
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DOI：
10.1001/jamacardio.2022.4466
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发表时间：
2022-12
期刊：
影响因子：
24
通讯作者：
N. Marston;J. Pirruccello;G. Melloni;S. Koyama;Frederick K. Kamanu;L. Weng;C. Roselli;Y. Kamatani;I. Komuro;K. Aragam;A. Butterworth;K. Ito;S. Lubitz;P. Ellinor;M. Sabatine;C. Ruff
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作者：
N. Marston;J. Pirruccello;G. Melloni;S. Koyama;Frederick K. Kamanu;L. Weng;C. Roselli;Y. Kamatani;I. Komuro;K. Aragam;A. Butterworth;K. Ito;S. Lubitz;P. Ellinor;M. Sabatine;C. Ruff
冠状动脉疾病（CAD）的多基因风险评分（PRS）的临床效用尚未建立。目的探讨在考虑年龄和临床风险后，CAD PRS在一级预防中指导他汀类药物启动的能力。设计、设置和参与者这是一项纵向队列研究，从2006年1月1日开始招募，到2010年12月31日结束，数据更新到2021年中期，使用的数据来自英国生物银行，一项针对英国公民的长期人口研究。在日本生物样本库中进行了重复分析。该分析包括所有无CAD病史且未接受降脂治疗的患者。数据分析时间为2022年1月1日至6月30日。使用包括241个全基因组显著单核苷酸变异（SNV）的CAD PRS，将CAD的多基因风险定义为低（底部20%）、中等和高（顶部20%）。合并的队列方程用于估计10年动脉粥样硬化性心血管疾病（ASCVD）的风险，并将个体归类为低风险（60岁：HR，1.42; 95%CI，1.37-1.48;相互作用P <0.001）。在50岁以下的患者中，与低PRS类别的患者相比，高PRS类别的患者的MI相关风险增加3至4倍。在日本生物样本库中复制了CAD PRS与年龄之间的显著相互作用。当CAD PRS测试被添加到年龄小于50岁的个体的临床ASCVD风险评分中时，4373例具有临界风险的患者中的591例（20%）被风险分层为中等风险，从而阻止开始他汀类药物治疗，7477例具有临界或中等风险的患者中的3198例（20%）被分层为低风险，从而不阻止治疗。结论和相关性本队列研究的结果表明，CAD PRS的预测能力在年轻个体中更高，可用于更好地识别具有临界和中等临床风险的患者，这些患者应开始他汀类药物治疗。
Importance The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established. Objective To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk. Design, Setting, and Participants This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022. Exposures Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy. Conclusions and Relevance Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.