UNASSIGNED: We recruited a cohort of 1,776 Chinese CAD patients and performed medical follow-up for up to 11 years. A pruning and thresholding method was used to calculate PRS of CAD and its 14 risk factors. Their correlations with all-cause death were computed via Cox regression.
UNASSIGNED: We found that the PRS for CAD and its seven risk factors, namely myocardial infarction, ischemic stroke, angina, heart failure, low-density lipoprotein cholesterol, total cholesterol and C-reaction protein, were significantly associated with death (P ≤ 0.05), whereas the PRS of body mass index displayed moderate association (P < 0.1). Elastic-net Cox regression with 5-fold cross-validation was used to integrate these nine PRS models into a meta score, metaPRS, which performed well in stratifying patients at different risks for death (P < 0.0001). Combining metaPRS with clinical risk factors further increased the discerning power and a 4% increase in sensitivity. The metaPRS generated from the genetic susceptibility to CAD and its risk factors can well stratify CAD patients by their risks of death. Integrating metaPRS and clinical risk factors may contribute to identifying patients at higher risk of poor prognosis.
■我们招募了1,776名中国CAD患者,并进行了长达11年的医学随访。使用修剪和阈值法计算CAD的PRS及其14个危险因素。通过Cox回归计算它们与全因死亡的相关性。
■我们发现CAD的PRS及其七个危险因素,即心肌梗塞,缺血性卒中,心绞痛,心力衰竭,低密度脂蛋白胆固醇,总胆固醇和C反应蛋白,与死亡显著相关(P≤0.05),而体重指数的PRS表现出中等相关性(P<0.1)。使用5倍交叉验证的Elastic-netCox回归将这9个PRS模型整合到一个meta评分中,metaPRS,在对不同死亡风险的患者进行分层方面表现良好(P<0.0001)。将metaPRS与临床危险因素相结合,进一步增加了辨别能力和4%的敏感性。由对CAD的遗传易感性及其危险因素产生的metaPRS可以很好地根据CAD患者的死亡风险对其进行分层。整合metaPRS和临床危险因素可能有助于确定预后不良风险较高的患者。