Time to recognize continuous positive airway pressure as a blood pressure-lowering treatment in patients with obstructive sleep apnoea and resistant hypertension?

Increasing prevalence of arterial hypertension (AH), the main cause of disability and premature death worldwide, represents a major public health concern. This is especially true for the subgroup of patients with resistant hypertension, a condition associated with a two to four-fold greater risk of cardiovascular events as compared with those hypertensive patients able to achieve target blood pressure (BP) on treatment [1]. Furthermore, patients with resistant hypertension often suffer from multiple comorbidities, are frequently seen in clinics and hypertension centres and emerging evidence shows that resistant hypertension is also associated with substantially reduced quality of life [2]. Thus, patients with resistant hypertension represent a subset of hypertensive patients that deserve extra care in the management of both cardiovascular risk and patient's wellbeing. As a matter of fact, thanks to the efforts of various Scientific Societies and National Healthcare Services, prevalence of resistant hypertension in the last decade appears to have plateaued [3], due to a greater awareness, a more thorough evaluation of secondary causes of hypertension and a better treatment titration. Among the factors involved in the pathogenesis of resistant hypertension, sleep disordered breathing, and in particular obstructive sleep apnoea (OSA), plays a fundamental role being the most prevalent one (60–70%) [4]. An association between OSA and elevated BP is now well documented and mechanisms linking OSA and elevated BP entail alterations in autonomic cardiovascular regulation, hormonal and inflammatory changes, intrathoracic pressure swings with the related haemodynamic consequences and sleep structure alterations [5,6]. Furthermore, treatment of OSA by means of continuous positive airway pressure (CPAP) is associated with reductions of BP by on average 2 mmHg according to the most recent systematic review and meta-analysis published by our group [7]. Giving this strong association between OSA and hypertension, the 2018 European Society of Cardiology/European Society of Hypertension Guidelines for the management of AH recommend screening for sleep disordered breathing in particular for patients with resistant hypertension without mentioning, quite surprisingly, the role of OSA treatment in the management of patients with resistant hypertension and OSA [8]. Nevertheless, when putting together the results of the randomized controlled trials (RCTs) in patients with OSA and true resistant hypertension, CPAP treatment can achieve an overall 24-h SBP reduction of 5 mmHg (Table 1). TABLE 1 - Effect of obstructive sleep apnoea treatment on 24-h ambulatory blood pressure in patients with true resistant hypertension Reference CPAP arm Control arm ΔMean (SE) Baseline 24-h End-treatment 24-h Baseline 24-h End-treatment 24-h SBP DBP SBP DBP SBP DBP SBP DBP SBP DBP Lozano et al.[9] 130.50 76.70 129.20 74.70 129.40 75.40 131.10 76.30 –3.00 (3.54) –2.90 (1.79) Martínez-García et al.[10] 144.90 83.40 140.20 79.50 143.50 82.60 142.30 82.10 –4.20 (1.94) –3.80 (1.20) Pedrosa et al.[11] N/A N/A N/A N/A N/A N/A N/A N/A –7.80 (4.24) –5.50 (2.83) de Oliveira et al.[12] 150.00 88.00 N/A N/A 146.00 88.00 N/A N/A –9.30 (4.46) –4.40 (2.50) Lloberes et al.[13] 140.10 80.80 137.80 76.40 139.60 81.40 141.90 81.60 –4.65 (3.03) –4.65 (1.70) Joyeux-Faure et al.[14] N/A N/A N/A N/A N/A N/A N/A N/A –1.88 (3.08) –1.69 (2.28) CPAP, continuous positive airway pressure; N/A, not available; SE, standard error. However, in such studies follow-up was relatively short (<12 months) therefore, the question whether CPAP can provide a beneficial effect on BP control in such patients over the long term remains unanswered. The article by Navarro-Soriano et al.[15] on behalf the Spanish Sleep Network published in this issue of the Journal tries to fill this gap. In this study, CPAP treatment was offered to most of the patients with moderate–severe OSA and true resistant hypertension [confirmed by 24-h ambulatory BP monitoring (ABPM)] that concluded the HIPARCO RCT [10]. Patients were then followed up for a median of 59 months when a 24-h ABPM was repeated and BP data analysed by subdividing patients as a function of their adherence to CPAP treatment (using an adherence cut-off usage of ≥4 nights/week). The results showed that the positive effects of CPAP treatment on BP were maintained in the long term, with lower mean 24 h and nocturnal BP in the CPAP-adherent group compared with nonadherent patients or those left without treatment. In this extension study, the assignment to CPAP treatment was no longer randomized, being based on clinical criteria. Although the study lost the advantages of a clinical trial, it still provides a convincing piece of evidence on BP effects of CPAP with much longer follow-up duration compared with previous studies. Thus, the results strongly support the concept that CPAP therapy can still be effective on BP level reduction after 5 years in patients with good adherence to treatment. In fact, the observed 24-h BP differences between CPAP-adherent participants and controls were quite similar to those reported in the randomized study, despite lower use of antihypertensive drugs. However, the results of the study by Navarro-Soriano et al.[15] must be interpreted with caution: given the real-life nature of the study it is impossible to take a number of possible confounders into account, among which is the patients' adherence to antihypertensive medications which is usually suboptimal in patients with resistant hypertension [16]. Furthermore, authors only reported the number of antihypertensive medications taken by patients, whereas type of antihypertensive drugs and their dosage were not taken into account, thus failing to provide data on issues crucial to BP data interpretation. Nevertheless, the data by Navarro-Soriano et al. together with the previous RCTs in the field are consistent with the current literature which clearly shows that patients with resistant hypertension treated with CPAP benefit from a clinically significant BP reduction and better BP control. Thus, based on the available evidence, a crucial question is now whether the recommendation of treating patients with resistant hypertension and OSA by means of CPAP, with the aim of reducing BP, should be Class I level of evidence A, and whether it should therefore deserve to be at least mentioned by current guidelines in the management of patients with resistant hypertension. As a take home message, mounting evidence now strongly supports the treatment of OSA by means of CPAP in patients with resistant hypertension with the aim of reducing BP. Therefore, hypertension centres as well as general practitioners should consider not only screening resistant hypertension patients for sleep disordered breathing but also refer them for proper assessment and treatment with the aim of alleviating OSA-related symptoms, reducing BP and improving their cardiovascular outcome. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.