使用遗传、社会和生活方式-心理因素构建冠心病发病综合预测模型并进行评估：英国生物银行前瞻性分析
Development and Evaluation of a Comprehensive Prediction Model for Incident Coronary Heart Disease Using Genetic, Social, and Lifestyle-Psychological Factors: A Prospective Analysis of the UK Biobank.
作者信息
Naderian Mohammadreza, Norland Kristjan, Schaid Daniel J, Kullo Iftikhar J
机构信息
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota (M.N., K.N.).
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota (D.J.S.).
出版信息
Ann Intern Med. 2025 Jan;178(1):1-10. doi: 10.7326/ANNALS-24-00716. Epub 2024 Dec 10.
BACKGROUND
Clinical risk calculators for coronary heart disease (CHD) do not include genetic, social, and lifestyle-psychological risk factors.
OBJECTIVE
To improve CHD risk prediction by developing and evaluating a prediction model that incorporated a polygenic risk score (PRS) and a polysocial score (PSS), the latter including social determinants of health and lifestyle-psychological factors.
DESIGN
Cohort study.
SETTING
United Kingdom.
PARTICIPANTS
UK Biobank participants recruited between 2006 and 2010.
MEASUREMENTS
Incident CHD (myocardial infarction and/or coronary revascularization); 10-year clinical risk based on pooled cohort equations (PCE), Predicting Risk of cardiovascular disease EVENTs (PREVENT), and QRISK3; PRS (Polygenic Score Catalog identification: PGS000018) for CHD (PRS); and PSS from 100 related covariates. Machine-learning and time-to-event analyses and model performance indices.
RESULTS
In 388 224 participants (age, 55.5 [SD, 8.1] years; 42.5% men; 94.9% White), the hazard ratio for 1 SD increase in PSS for incident CHD was 1.43 (95% CI, 1.38 to 1.49; <0.001) and for 1 SD increase in PRS was 1.59 (CI, 1.53 to 1.66, < 0.001). Non-White persons had higher PSS than White persons. The effects of PSS and PRS on CHD were independent and additive. At a 10-year CHD risk threshold of 7.5%, adding PSS and PRS to PCE reclassified 12% of participants, with 1.86 times higher CHD risk in the up- versus down-reclassified persons and showed superior performance compared with PCE as reflected by improved net benefit while maintaining good calibration relative to the clinical risk calculators. Similar results were seen when incorporating PSS and PRS into PREVENT and QRISK3.
LIMITATION
A predominantly White cohort; possible healthy participant effect and ecological fallacy.
CONCLUSION
A PSS was associated with incident CHD and its joint modeling with PRS improved the performance of clinical risk calculators.
PRIMARY FUNDING SOURCE
National Human Genome Research Institute.
背景
冠心病（CHD）的临床风险计算器未纳入遗传、社会和生活方式心理风险因素。
目的
通过开发和评估一个包含多基因风险评分（PRS）和多社会评分（PSS）的预测模型来改善CHD风险预测，后者包括健康的社会决定因素和生活方式心理因素。
设计
队列研究。
地点
英国。
参与者
2006年至2010年招募的英国生物银行参与者。
测量指标
新发CHD（心肌梗死和/或冠状动脉血运重建）；基于合并队列方程（PCE）、预测心血管疾病事件风险（PREVENT）和QRISK3的10年临床风险；CHD的PRS（多基因评分目录标识：PGS000018）；以及来自100个相关协变量的PSS。机器学习和事件发生时间分析以及模型性能指标。
结果
在388224名参与者中（年龄55.5[标准差8.1]岁；42.5%为男性；94.9%为白人），PSS每增加1个标准差，新发CHD的风险比为1.43（95%CI，1.38至1.49；P<0.001），PRS每增加1个标准差，风险比为1.59（CI，1.53至1.66，P<0.001）。非白人的PSS高于白人。PSS和PRS对CHD的影响是独立且相加的。在10年CHD风险阈值为7.5%时，将PSS和PRS添加到PCE中对12%的参与者进行了重新分类，重新分类后风险增加的参与者患CHD的风险是风险降低参与者的1.86倍，并且与PCE相比表现更优，表现为净效益提高，同时相对于临床风险计算器保持良好的校准。将PSS和PRS纳入PREVENT和QRISK3时也观察到类似结果。
局限性
主要为白人队列；可能存在健康参与者效应和生态学谬误。
结论
PSS与新发CHD相关，其与PRS的联合建模改善了临床风险计算器的性能。
主要资金来源
国家人类基因组研究所。
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