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高血压的遗传风险评分与胸主动脉瘤风险相关。

A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm.

作者信息

Tagetti A, Bonafini S, Ohlsson T, Engström G, Almgren P, Minuz P, Smith G, Melander O, Fava C

机构信息

Department of Medicine, University of Verona, Section of General Medicine and Hypertension, Verona, Italy.

Department of Clinical Sciences, Lund University, University Hospital of Malmö, Verona, Sweden.

出版信息

J Hum Hypertens. 2019 Sep;33(9):658-663. doi: 10.1038/s41371-018-0159-6. Epub 2019 Jan 18.

Abstract

A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdominal (AAA) aortic aneurysm. More than 25,000 people from the Swedish Malmo Diet and Cancer Study had information on at least 24 SNPs and were followed up for a median ≥ 18 years. The number of BP elevating alleles of each SNPs, weighted by their effect size in the discovery studies, was summed into a BP-GRS. In Cox regression models, adjusted for traditional cardiovascular risk factors including hypertension, we found significant associations of the BP-GRS, prospectively, with incident TAA (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.081-2.475 comparing the third vs. the first tertile; p = 0.020) but not with either AAA or aortic dissection. Calibration, discrimination and reclassification analyses show modest improvement in prediction using the BP-GRS in addition to the model which used only traditional risk factors. A GRS for hypertension associates with TAA suggesting a link between genetic determinants of BP and aortic disease. The effect size is small but the addition of more SNPs to the GRS might improve its discriminatory capability.

摘要

基于29个与高血压(BP)相关的单核苷酸多态性(SNP)构建的遗传风险评分(GRS),与高血压、中风和心血管事件的发生呈前瞻性关联。本研究的目的是评估该GRS对主动脉疾病发生率的影响,包括主动脉夹层(AD)、胸主动脉瘤(TAA)或腹主动脉瘤(AAA)破裂或手术。来自瑞典马尔默饮食与癌症研究的25000多人至少有24个SNP的信息,并进行了中位数≥18年的随访。将每个SNP的血压升高等位基因数量,按照其在发现研究中的效应大小进行加权,汇总成一个血压GRS。在Cox回归模型中,对包括高血压在内的传统心血管危险因素进行校正后,我们发现血压GRS与TAA的发生存在显著的前瞻性关联(风险比(HR)为1.64,第三分位数与第一分位数比较,95%置信区间(CI)为1.081 - 2.475;p = 0.020),但与AAA或主动脉夹层无关。校准、区分和重新分类分析表明,除了仅使用传统危险因素的模型外,使用血压GRS可使预测有适度改善。高血压的GRS与TAA相关,提示血压的遗传决定因素与主动脉疾病之间存在联系。效应大小较小,但在GRS中添加更多SNP可能会提高其区分能力。

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