International Journal of Hypertension In a case-control study, Gonc¸alves et al. [28] demon- strated that patients with resistant hypertension are aﬀected almost 5 times more frequently by OSA—diagnosed by portable sleep monitors—compared to their well-controlled hypertensive counterparts matched for age, sex, and body mass index. Finally, in a Spanish article by Martı´nez-Garcı´a et al. [29], the severity of OSA diagnosed by polysomnography as measured by the apnea/hypopnea index was associated with the magnitude of BP levels in elderly patients with diﬃcult-to-control hypertension and OSA after adjustment for age and sex. Another study reported that, among resistant hyper- tension patients, there is a positive association between plasma aldosterone levels and severity of OSA. However, no correlation was noted between OSA and aldosterone levels in subjects without resistant hypertension with equally severe OSA [30]. These ﬁndings conﬁrm the high prevalence of OSA in resistant hypertension (85%) and are consistent with the hypothesis that hyperaldosteronism in resistant hyper- tension might exacerbate OSA—by promoting upper airway edema due to sodium and ﬂuid retention—or inversely, OSA stimulates aldosterone release, while there might even be a bidirectional relationship in that phenomenon. 3.2. Interventional Studies. Logan et al. [31] tested the therapeutic impact of CPAP therapy on ambulatory BP levels in 11 patients with drug-resistant hypertension and OSA both at a single night’s application and after a period of two months. CPAP eﬃciently applied for one night was accompanied by a signiﬁcant reduction in nocturnal BP levels. More speciﬁcally, nocturnal systolic BP exhibited a more pronounced acute reduction compared to a more limited reduction of the nocturnal diastolic component (138.3 ± 6.8 to 126.0 ± 6.3 mmHg versus 77.7 ± 4.5 to 72.9 ± 4.5 mmHg, resp.). Additionally, CPAP use for 2 months was accompanied by an 11.0 ± 4.4 mmHg decrease in 24-hour systolic BP, whereas the nocturnal diastolic BP was reduced signiﬁcantly by 7.8 ± 3.0 mmHg. In these lines, eﬃciently treating OSA in resistant hypertension might be a therapeutic “add-on” option to the underlying antihypertensive treatment to reduce BP levels within the goal. In a subsequent work on 33 elderly patients with diﬃcult- to-treat hypertension and OSA [32], Martı´nez-Garcı´a et al. highlighted, along with the beneﬁcial eﬀect of CPAP on systolic ambulatory BP levels, the fact that compliance to CPAP therapy (>4 hours at night on CPAP) is crucial for the eﬃcient reduction of BP. Indeed, those who tolerated CPAP (n = 23) showed a signiﬁcant drop in mean 24-hour systolic BP of 7.6 mmHg without signiﬁcant changes in mean 24- hour diastolic BP; however, in those who were CPAP intol- erant (n = 10), there were no signiﬁcant changes in either mean diurnal or nocturnal, either systolic or diastolic BP. Lozano et al. [33] in a randomized prospective con- trolled study evaluated the change in mean 24-hour systolic and diastolic BP at the three-month follow-up in two groups of patients with resistant hypertension and OSA: 29 patients under well-tolerated CPAP and appropriate pharmacological treatment (i.e., CPAP arm) and 35 patients 3 under appropriate pharmacological treatment alone (i.e., conventional arm). The use of CPAP for three months was accompanied by a mean reduction of almost 5 mmHg in 24- hour diastolic BP in the CPAP arm, whereas no signiﬁcant change was observed in the arm of conventional therapy. In those wearing the mask for at least 5.8 hours per day signiﬁcant changes were registered in diurnal and 24-hour diastolic BP and in 24-hour systolic BP. It is worth noting that the beneﬁcial eﬀect of CPAP on BP levels was only seen in those with resistant hypertension conﬁrmed with ambulatory BP monitoring, but not in those with resistant hypertension diagnosed only by oﬃce BP measurements. The number of patients in the CPAP arm with a nondipping pattern decreased signiﬁcantly from 51.7% at baseline to 24.1% at the three-month follow-up, whereas no changes were observed in patients of the conventional arm of the study, in line with previous ﬁndings. A ﬁnal important issue in the Lozano et al. [33] study was that, among those who accepted to wear the mask, the Epworth Sleepiness scale scoring did not diﬀer between those who used CPAP for more and less than 5.8 hours/day, suggesting that even asymptomatic patients with resistant hypertension had similar reductions in BP levels especially if CPAP was applied for more than the cut-oﬀ of 5.8 hours/day. In a retrospective chart review study [34], medical records of patients who had a polysomnography with CPAP study were reviewed and among them the researchers selected those with hypertension; OSA compliant with CPAP; oﬃce BP measurements obtained within three months of enrollment, every three months for six months and at one year after CPAP initiation. In subjects exhibiting resistant hypertension, the use of CPAP therapy was accompanied by a decrease in daytime BP at both 6 and 12 months after treatment initiation, while in almost 70% of these patients a reduction in either the dose or the number of antihypertensive drugs used at baseline was observed. On the contrary, patients with controlled hypertension and OSA demonstrated no signiﬁcant change in BP levels over the same period of time, suggesting that the eﬀect of CPAP on BP, when the latter has been already controlled with medication, is at least less pronounced or even absent in line with previous ﬁndings [35, 36]. 4. Clinical Decisions: Lost in Translation or a Simple Rationale? In patients with hypertension a thorough sleep history conﬁrmed—if applicable—by the bed partner, identiﬁcation of daytime symptoms, and a physical examination including visualization of the pharynx are all essential steps in order to separate those with a high clinical suspicion of OSA. How- ever, in patients with drug-resistant hypertension establish- ing a high or low clinical suspicion for OSA might be futile. For example, in the context of resistant hypertension, the use of clinical prediction tools, like the Epworth Sleepiness Scale could not be as helpful [33] as it may be for the general population of hypertensive patients [4]. Therefore, in clinical practice, those with true drug-resistant hypertension should be counseled to undergo polysomnography.