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抗高血压合并阻塞性睡眠呼吸暂停患者的精准医学:持续气道正压通气治疗的血压反应。

Precision Medicine in Patients With Resistant Hypertension and Obstructive Sleep Apnea: Blood Pressure Response to Continuous Positive Airway Pressure Treatment.

机构信息

Respiratory Department, Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.

Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Pritzker School of Medicine, University of Chicago, Chicago, Illinois; Department of Pediatrics, University of Chicago, Chicago, Illinois.

出版信息

J Am Coll Cardiol. 2015 Sep 1;66(9):1023-32. doi: 10.1016/j.jacc.2015.06.1315.

DOI:10.1016/j.jacc.2015.06.1315
PMID:26314530
Abstract

BACKGROUND

In patients with resistant hypertension (RH) and obstructive sleep apnea (OSA), the blood pressure response to continuous positive airway pressure (CPAP) treatment is highly variable and could be associated with differential micro-ribonucleic acid (miRNA) profiles. Currently, no available methods exist to identify patients who will respond favorably to CPAP treatment.

OBJECTIVES

The aim of this study was to identify plasma miRNA profiles that predict blood pressure responses to CPAP treatment.

METHODS

Cardiovascular system-focused circulating miRNA expression was evaluated in plasma samples using an 84-miRNA array among patients with RH and OSA at baseline and after 3 months of adherent CPAP use. Pathway analysis and miRNA target gene enrichment were performed in silico. Plasma levels of peptides and hormones related to cardiovascular function were also measured.

RESULTS

The OSA responder group exhibited blood pressure decreases exceeding the observed median (>4.5 mm Hg) after CPAP, which were not present in the nonresponder group (≤4.5 mm Hg) (p < 0.01). Three miRNAs provided a discriminatory predictive model for such a favorable blood pressure response to CPAP (area under the curve: 0.92; p = 0.01). Additionally, CPAP treatment significantly altered a total of 47 plasma miRNAs and decreased aldosterone-to-renin ratios in the responder group (p = 0.016) but not in the nonresponder group.

CONCLUSIONS

A singular pre-CPAP treatment cluster of 3 plasma miRNAs predicts blood pressure responses to CPAP treatment in patients with RH and OSA. CPAP treatment is accompanied by changes in cardiovascular system-related miRNAs that may potentially influence the risk for cardiovascular disease among patients with OSA and RH. (Effect of Continuous Positive Airway Pressure [CPAP] Treatment in the Control of Refractory Hypertension; NCT00616265).

摘要

背景

在难治性高血压(RH)和阻塞性睡眠呼吸暂停(OSA)患者中,持续气道正压通气(CPAP)治疗的血压反应差异很大,可能与差异微小核糖核酸(miRNA)谱有关。目前,尚无可用的方法来识别对 CPAP 治疗反应良好的患者。

目的

本研究旨在确定预测 CPAP 治疗血压反应的血浆 miRNA 谱。

方法

在基线和接受 3 个月 CPAP 治疗后,使用 84 个 miRNA 阵列评估 RH 和 OSA 患者的心血管系统靶向循环 miRNA 表达。进行了通路分析和 miRNA 靶基因富集的计算机分析。还测量了与心血管功能相关的肽和激素的血浆水平。

结果

CPAP 治疗后,OSA 反应组的血压下降超过观察中位数(>4.5mmHg),而非反应组(≤4.5mmHg)则没有(p<0.01)。三个 miRNA 为 CPAP 治疗这种有利的血压反应提供了一个有区别的预测模型(曲线下面积:0.92;p=0.01)。此外,CPAP 治疗在反应组中显著改变了总共 47 个血浆 miRNA,降低了醛固酮与肾素的比值(p=0.016),但在非反应组中没有。

结论

单一的 CPAP 治疗前治疗簇 3 个血浆 miRNA 可预测 RH 和 OSA 患者对 CPAP 治疗的血压反应。CPAP 治疗伴随着与心血管系统相关的 miRNA 的变化,这些变化可能会影响 OSA 和 RH 患者的心血管疾病风险。(持续气道正压通气 [CPAP] 治疗对难治性高血压控制的影响;NCT00616265)。

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