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

https://doi.org/10.1016/j.jacc.2015.06.1315Get rights and content
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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)

Key Words

cardiovascular disease
miRNA
personalized medicine
sleep apnea

Abbreviations and Acronyms

AUC
area under the curve
BP
blood pressure
CI
confidence interval
CPAP
continuous positive airway pressure
CVD
cardiovascular disease
miRNA
micro–ribonucleic acid
OSA
obstructive sleep apnea
qRT-PCR
quantitative real-time reverse transcription polymerase chain reaction
RH
resistant hypertension

Cited by (0)

This study was supported by Philips-Respironics, Sociedad Española de Neumología, Instituto de Salud Carlos III (PI14/01266), Sociedad Valenciana de Neumología, Fundació Catalana de Neumología, Agència de Gestió d’Ajuts Universitaris i de Recerca, and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.