肥胖相关的心力衰竭预后遗传决定因素。

Obesity-Related Genetic Determinants of Heart Failure Prognosis.

机构信息

Laboratorio no. 6. Edif. Consultas externas (planta -2), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Servicio de Cardiología y Unidad de Hemodinámica, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Travesía da Choupana s/n, Santiago de Compostela, 15706, A Coruña, Spain.

CIBERCV, Madrid, Spain.

出版信息

Cardiovasc Drugs Ther. 2019 Aug;33(4):415-424. doi: 10.1007/s10557-019-06888-8.

DOI:10.1007/s10557-019-06888-8

PMID:31209632

Abstract

PURPOSE

Recent advances in genomics offer a smart option for predicting future risk of disease and prognosis. The objective of this study was to examine the prognostic value in heart failure (HF) patients, of a series of single nucleotide polymorphisms (SNPs).

METHODS

A selection of 192 SNPs found to be related with obesity, body mass index, circulating lipids or cardiovascular diseases were genotyped in 191 patients with HF. Anthropometrical and clinical variables were collected for each patient, and death and readmission by HF were registered as the primary endpoint.

RESULTS

A total of 53 events were registered during a follow-up period of 438 (263-1077) days (median (IQR)). Eight SNPs strongly related to obesity and HF prognosis were selected as possible prognostic variables. From these, rs10189761 and rs737337 variants were independently associated with HF prognosis (HR 2.295 (1.287-4.089, 95% CI); p = 0.005), whereas rs10423928, rs1800437, rs737337 and rs9351814 were related with bad prognosis only in obese patients (HR 2.142 (1.438-3.192, 95% CI); p = 0.00018). Combined scores of the genomic variants were highly predictive of poor prognosis.

CONCLUSIONS

SNPs rs10189761 and rs737337 were identified, for the first time, as independent predictors of major clinical outcomes in patients with HF. The data suggests an additive predictive value of these SNPs for a HF prognosis. In particular for obese patients, SNPs rs10423928, rs1800437, rs737337 and rs9351814 were related with a bad prognosis. Combined scores weighting the risk of each genomic variant could effect interesting new tools to stratify the prognostic risk of HF patients.

摘要

目的

基因组学的最新进展为预测疾病未来风险和预后提供了一种明智的选择。本研究的目的是探讨一系列单核苷酸多态性（SNP）在心力衰竭（HF）患者中的预后价值。

方法

在 191 例 HF 患者中，对与肥胖、体重指数、循环脂质或心血管疾病相关的 192 个 SNP 进行了基因分型。为每位患者收集了人体测量学和临床变量，并将死亡和 HF 再入院作为主要终点进行登记。

结果

在 438（263-1077）天的随访期间共登记了 53 例事件（中位数（IQR））。选择了与肥胖和 HF 预后密切相关的 8 个 SNP 作为可能的预后变量。其中，rs10189761 和 rs737337 变异与 HF 预后独立相关（HR 2.295（1.287-4.089，95%CI）；p=0.005），而 rs10423928、rs1800437、rs737337 和 rs9351814 仅在肥胖患者中与不良预后相关（HR 2.142（1.438-3.192，95%CI）；p=0.00018）。基因组变异的综合评分对不良预后具有高度预测性。

结论

首次发现 SNP rs10189761 和 rs737337 是 HF 患者主要临床结局的独立预测因子。数据表明，这些 SNP 对 HF 预后具有附加预测价值。特别是对于肥胖患者，rs10423928、rs1800437、rs737337 和 rs9351814 与不良预后相关。加权每个基因组变异风险的综合评分可能为 HF 患者的预后风险分层提供有趣的新工具。