Christiansen Morten Krogh, Nyegaard Mette, Larsen Sanne Bøjet, Grove Erik Lerkevang, Würtz Morten, Neergaard-Petersen Søs, Hvas Anne-Mette, Jensen Henrik Kjærulf, Kristensen Steen Dalby
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Int J Cardiol. 2017 Aug 15;241:411-416. doi: 10.1016/j.ijcard.2017.04.045. Epub 2017 Apr 19.
Genetic risk scores (GRSs) may predict cardiovascular risk in community-based populations. However, studies investigating the association with recurrent cardiovascular events in patients with established coronary artery disease (CAD) are conflicting.
We genotyped 879 patients with high-risk stable CAD and created a GRS based on 45 single nucleotide polymorphisms previously reported to be associated with CAD in genome-wide association studies. Patients were categorised into high or low GRS according to the median GRS and followed for recurrent cardiovascular events using national Danish registries. The primary endpoint was a composite of myocardial infarction, coronary revascularisation, and cardiovascular death.
Median (interquartile range) follow-up time was 2.8 (2.4-3.8)years. The cumulative incidence proportions of the primary endpoint at 1 and 3years were 6.4% and 11.5% in high-GRS patients vs. 2.5% and 7.3% in low-GRS patients. The corresponding relative risks were 2.56 (95% confidence interval (CI) 1.29-5.07), and 1.57 (95% CI 1.02-2.44). The adjusted hazard ratio (HR) of the primary endpoint was 1.50 (95% CI 1.00-2.25). The most pronounced effect of a high GRS was observed on coronary revascularisations (adjusted HR 2.10 [95% CI 1.08-4.07]). Risks of cardiovascular death (adjusted HR 1.07 [95% CI 0.46-2.48]) and all-cause death (adjusted HR 1.15 [95% CI 0.65-2.03]) were unaffected.
A GRS predicts recurrent cardiovascular events in high-risk stable CAD patients. The observed effect was mainly driven by coronary revascularisations.
遗传风险评分（GRSs）可能预测社区人群的心血管风险。然而，关于其与已确诊冠心病（CAD）患者心血管事件复发之间关联的研究结果相互矛盾。
我们对879例高危稳定型CAD患者进行基因分型，并基于此前在全基因组关联研究中报道的与CAD相关的45个单核苷酸多态性创建了一个GRS。根据GRS中位数将患者分为高GRS组或低GRS组，并利用丹麦国家登记系统对心血管事件复发情况进行随访。主要终点是心肌梗死、冠状动脉血运重建和心血管死亡的复合终点。
中位（四分位间距）随访时间为2.8（2.4 - 3.8）年。高GRS组患者1年和3年时主要终点的累积发生率分别为6.4%和11.5%，而低GRS组患者分别为2.5%和7.3%。相应的相对风险分别为2.56（95%置信区间[CI] 1.29 - 5.07）和1.57（95% CI 1.02 - 2.44）。主要终点的校正风险比（HR）为1.50（95% CI 1.00 - 2.25）。高GRS对冠状动脉血运重建的影响最为显著（校正HR 2.10 [95% CI 1.08 - 4.07]）。心血管死亡风险（校正HR 1.07 [95% CI 0.46 - 2.48]）和全因死亡风险（校正HR 1.15 [95% CI 0.65 - 2.03]）未受影响。
GRS可预测高危稳定型CAD患者的心血管事件复发。观察到的效应主要由冠状动脉血运重建驱动。
