Chen Yu-Lun, Chi Nai-Fang, Chiou Hung-Yi, Hu Chaur-Jong, Jeng Jiann-Shing, Tang Sung-Chun, Lin Huey-Juan, Hsieh Yi-Chen
School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan, ROC.
Department of Neurology, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2022 Jan 1;85(1):81-87. doi: 10.1097/JCMA.0000000000000666.
Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application.
A hospital-based cohort study was conducted including 1320 first-ever acute ischemic stroke (AIS) patients and 1210 patients who completed the follow-up at 3 months. PRSs were calculated for hyperglycemia/diabetes mellitus using results from genome-wide association studies in Asians. An unfavorable functional outcome was defined as a modified Rankin Scale score of ≥3 at 3, 6, and 12 months of follow-up. The prediction of a poor prognosis was evaluated using measures of model discrimination, calibration, and net reclassification improvement (NRI).
The second to fourth PRS quartiles (≥Q2) were significantly associated with higher risks of unfavorable outcomes at 3 months compared with the first quartile as the reference group after adjusting for age, baseline stroke severity, hypertension, diabetes, dyslipidemia, smoking, heart disease, and ischemic stroke subtype (p for trend <0.0001). The addition of the PRS to traditional risk predictors of poor outcomes after an AIS significantly improved the model fit (likelihood ratio test p < 0.0001) and enhanced measures of reclassification (NRI, 0.245; 95% confidence interval [CI], 0.195-0.596). The corrected C-index for the PRS combining traditional risk factors at 3 months after a stroke was 0.899 (95% CI, 0.878-0.980). Among hyperglycemic AIS patients, those who did not take an antidiabetic drug and whose PRS was ≥Q2 had higher risks of an unfavorable outcome at 3 months compared with patients who took the medicine.
The hyperglycemia/diabetes-derived PRS was associated with poor outcomes after an AIS, but further studies are needed to validate its use for clinical applications.
高血糖性卒中患者往往预后不良。本研究旨在构建一种源自高血糖/糖尿病的多基因风险评分（PRS），以提高对卒中后不良结局风险的预测性能，并评估其潜在的临床应用价值。
开展了一项基于医院的队列研究，纳入1320例首次发生的急性缺血性卒中（AIS）患者以及1210例在3个月时完成随访的患者。利用亚洲人群全基因组关联研究的结果计算高血糖/糖尿病的PRS。不良功能结局定义为随访3个月、6个月和12个月时改良Rankin量表评分≥3分。使用模型辨别、校准和净重新分类改善（NRI）指标评估对不良预后的预测。
在校正年龄、基线卒中严重程度、高血压、糖尿病、血脂异常、吸烟、心脏病和缺血性卒中亚型后，与作为参照组的第一四分位数相比，第二至第四PRS四分位数（≥Q2）在3个月时与不良结局风险显著相关（趋势p<0.0001）。将PRS添加到AIS后不良结局的传统风险预测因素中，显著改善了模型拟合度（似然比检验p<0.0001），并增强了重新分类指标（NRI，0.245；95%置信区间[CI]，0.195-0.596）。卒中后3个月时，结合传统风险因素的PRS校正C指数为0.899（95%CI，0.878-0.980）。在高血糖AIS患者中，与服用抗糖尿病药物的患者相比，未服用抗糖尿病药物且PRS≥Q2的患者在3个月时不良结局风险更高。
源自高血糖/糖尿病的PRS与AIS后不良结局相关，但需要进一步研究以验证其在临床应用中的价值。
