Pereira Andreia, Mendonca Maria Isabel, Sousa Ana Célia, Borges Sofia, Freitas Sónia, Henriques Eva, Rodrigues Mariana, Freitas Ana Isabel, Guerra Graça, Ornelas Ilídio, Pereira Décio, Brehm António, Palma Dos Reis Roberto
Research Unit and Cardiology Department, Funchal Hospital Center, Avenida Luís de Camões, Funchal, Portugal.
Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugal.
Int J Clin Pract. 2017 Jun;71(6). doi: 10.1111/ijcp.12956. Epub 2017 May 15.
Several genetic risk scores (GRS) have been associated with cardiovascular disease; their role, however, in survival from proven coronary artery disease (CAD) have yielded conflicting results.
The objective of this study was to evaluate long-term cardiovascular mortality according to the genetic risk score in a Southern European population with CAD.
A cohort of 1464 CAD patients with angiographic proven CAD were followed up prospectively for up to 58.3 (interquartile range: 25.8-88.1) months. Genotyping of 32 single-nucleotide polymorphisms previously associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming codominance and categorised using the median (=26). Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan-Meier survival curves compared high vs low GRS using log-rank test. C-index was done for our population, as a measure of discrimination in survival analysis model.
During a mean follow-up of 58.3 months, 156 patients (10.7%) died, 107 (7.3%) of CV causes. High GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with Cox regression model adjusted for 8 variables showed that high GRS, dyslipidemia, diabetes and 3-vessel disease were independent risk factors for cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004; HR=2.97, P<.0001, respectively). At the end of follow-up, the estimated survival probability was 70.8% for high GRS and 80.8% for low GRS (Log-rank test 5.6; P=.018). C-Index of 0.71 was found when GRS was added to a multivariate survival model of diabetes, dyslipidemia, smoking, hypertension and 3 vessel disease, stable angina and dual antiplatelet therapy.
Besides the classical risk factors management, this work highlights the relevance of the genetic profile in survival from CAD. It is expected that new therapies will be dirsected to gene targets with proven value in cardiovascular survival.
几种遗传风险评分（GRS）已与心血管疾病相关联；然而，它们在已确诊冠心病（CAD）患者生存中的作用却产生了相互矛盾的结果。
本研究的目的是根据遗传风险评分评估南欧冠心病患者的长期心血管死亡率。
对1464例经血管造影证实患有冠心病的患者进行前瞻性随访，最长随访时间为58.3（四分位间距：25.8 - 88.1）个月。使用针对每个等位基因标记有荧光的寡核苷酸探针，对先前与冠心病相关的32个单核苷酸多态性进行基因分型。根据假设共显性的加性模型构建GRS，并使用中位数（=26）进行分类。进行Cox回归分析以确定心血管死亡率的独立多变量预测因素。使用对数秩检验比较高GRS和低GRS的Kaplan-Meier生存曲线。计算我们人群的C指数，作为生存分析模型中区分度的一种度量。
在平均58.3个月的随访期间，156例患者（10.7%）死亡，其中107例（7.3%）死于心血管原因。高GRS（≥26）与心血管生存率降低相关。对8个变量进行调整的Cox回归模型生存分析表明，高GRS、血脂异常、糖尿病和三支血管病变是心血管死亡的独立危险因素（HR分别为1.53，P = 0.037；HR = 3.64，P = 0.012；HR = 1.75，P = 0.004；HR = 2.97，P < 0.0001）。随访结束时，高GRS组的估计生存概率为70.8%，低GRS组为80.8%（对数秩检验5.6；P = 0.018）。当将GRS添加到糖尿病、血脂异常、吸烟、高血压和三支血管病变、稳定型心绞痛及双联抗血小板治疗的多变量生存模型中时，C指数为0.71。
除了经典危险因素管理外，本研究强调了基因谱在冠心病患者生存中的相关性。预计新的治疗方法将针对在心血管生存中具有已证实价值的基因靶点。
