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Contemporary Reviews in Sleep Medicine |

Relationship Between OSA and HypertensionOSA and Hypertension FREE TO VIEW

Gerard Torres, MD; Manuel Sánchez-de-la-Torre, PhD; Ferran Barbé, MD
Author and Funding Information

From the Respiratory Department (Drs Torres, Sánchez-de-la-Torre, and Barbé), Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Catalonia; and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) (Drs Sánchez-de-la-Torre and Barbé), Madrid, Spain.

CORRESPONDENCE TO: Ferran Barbé, MD, Respiratory Department, Hospital Universitari Arnau de Vilanova, Rovira Roure, 80, 25198 Lleida, Spain; e-mail: febarbe.lleida.ics@gencat.cat


FUNDING/SUPPORT: This study was funded by Fondo de Investigación Sanitaria [PI10/02763, PI10/02745, and PI14/01266], the Spanish Respiratory Society (SEPAR), and Associació Lleidatana de Respiratori (ALLER).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(3):824-832. doi:10.1378/chest.15-0136
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There is a bidirectional association between OSA and systemic hypertension. The strengths of this relationship appear to be modulated by factors such as age, sex, and somnolence. The 24-h BP circadian pattern also appears to be influenced by OSA. Patients with this syndrome exhibit a high prevalence of nondipping or riser circadian patterns, which are related to clinical and subclinical organ damage in the heart and brain. However, the influence of OSA on nocturnal hypertension development has not yet been clarified. A special area of interest is the recognized relationship between OSA and resistant hypertension. The majority of patients with resistant hypertension suffer OSA. CPAP treatment significantly reduces BP in such patients and could play a clinical role in the management of BP in these patients. Several meta-analyses have demonstrated a concordant mild effect of CPAP on systemic hypertension. This effect is related to CPAP compliance, somnolence status, and baseline BP. The effects of oral appliances on BP in patients with OSA must be evaluated in randomized controlled trials. In the absence of additional data reported by clinical studies on other antihypertensive drug treatments, diuretics, particularly antialdosteronic diuretic agents, should be considered the first-line antihypertensive drug treatment in patients with OSA. By reducing parapharyngeal edema and secondary upper airway obstruction, these drugs appear to improve OSA severity and also to reduce BP.

Figures in this Article

OSA is a common disease that is caused by a collapse of the upper airway during sleep, which leads to transient asphyxia. Because of these events, patients experience intermittent hypoxemia, brain arousals, sleep disturbances, daytime somnolence, and poor quality of life. However, these events also lead to important metabolic and neurohormonal disturbances that may have adverse cardiovascular consequences.1 The prevalence of OSA is increasing in developed countries in parallel with the increasing prevalence of obesity. Among middle-aged adults aged 30 to 70 years, the prevalence of OSA is approximately 24% to 26% in men and 17% to 28% in women.2,3

Epidemiologic data suggest that there is a strong association between OSA and systemic hypertension, with important implications for cardiovascular outcomes. There is a high prevalence of OSA in hypertensive individuals (30%-50%).4 If we consider only patients with resistant hypertension, then a dramatic increase in prevalence, reaching 83%, is observed.5 The epidemiologic relationship between hypertension and OSA is bidirectional. Not only do patients with hypertension appear to be more likely to suffer OSA, data from community and population studies indicate that patients with OSA present a high prevalence of hypertension.6-8 The prevalence of hypertension in patients with moderate or severe OSA was reported to be 46% or 53%, respectively.8 The results of experimental studies describe pathophysiologic features that support a causal, bidirectional relationship between OSA and hypertension. On the one hand, mechanisms based on sympathetic and renin-angiotensin-aldosterone activation, as well as oxidative stress and endothelial dysfunction, implicate OSA as an independent cause of hypertension.1 On the other hand, acute increases in BP may cause an inhibition of the upper airway muscles. This phenomenon, together with volume overload and its displacement to the upper body during sleep, which can be experienced by subjects with hypertension and can lead to pharyngeal edema, may explain the link between hypertension and OSA.9-11 In addition to these observations, the purpose of this review of OSA and hypertension is to present an overview of state-of-the-art strategies that address issues that may be relevant to daily clinical practice.

Epidemiologic studies show that patients with OSA have a high prevalence of obesity.2,11 Therefore, obesity may be the nexus that explains the high prevalence of hypertension in these patients. However, the results of a large, prospective, longitudinal study, the Wisconsin Sleep Cohort Study (WSCS), suggest that moderate to severe OSA (apnea-hypopnea index [AHI] ≥ 15/h) is an independent cause of hypertension. Subjects with this degree of OSA severity showed a 3.2-fold increase in the odds of developing hypertension, compared with subjects without OSA.12 The WSCS results impacted the American guidelines for the management of hypertension (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC VII]), and OSA was recognized as the first secondary cause of hypertension.13 Similarly, Marin et al14 conducted an observational study that included 1,889 subjects without hypertension who were admitted to a sleep clinic and were followed up for a mean of 10.1 years. The authors found an increased incidence of hypertension in subjects with untreated OSA, compared with treated patients. Other studies have shown that age, somnolence, and sex could influence and modulate this independent relation. Bixler et al15 examined 741 men and 1,000 women aged 20 to 100 years and found that the strength of the association between OSA and hypertension may become attenuated with age. Haas et al16 confirmed these results and established a cutoff age of 60 years. Above this age, the strength of the association declines. Conversely, the results of a 5-year follow-up of participants in the Sleep Heart Health Study (SHHS),17 after adjusting for BMI, did not confirm the independent relationship between OSA and hypertension found in the Wisconsin cohort.

One of the most accepted explanations for these differences is the divergence between the characteristics of the two cohorts, particularly in terms of age. Subjects from the SHHS were significantly older than those from the WSCS (60 years vs 47 years old). Data reported by Kapur et al18 showed that an increase in daytime somnolence, measured with the Epworth Sleepiness Scale, correlated positively with a stronger association between OSA and the risk of hypertension. In addition, the effect of CPAP treatment on the incidence of hypertension has been evaluated in nonsleepy patients. In a randomized controlled trial (RCT) that included 725 subjects with a median follow-up of 4 years, the Spanish Sleep and Breathing Network found that CPAP did not reduce the incidences of hypertension or cardiovascular events in nonsleepy subjects.19 These data again suggest that the presence or absence of sleepiness may influence the risk of incident hypertension. Finally, in a population-based case-control study, Hedner et al20 found that the association may be more evident in men than in women.

Despite all these considerations, the association between OSA and the incident risk of hypertension remains unresolved. The Vitoria Sleep Cohort (VSC)21 followed, for 7.5 years, 1,180 subjects aged 30 to 70 years who were not hypertensive. The results did not suggest an association between OSA and the incidence of hypertension after adjusting for age, sex, and BMI. These discordant results, in comparison with those of the WSCS, may be explained by two critical features: differences in population characteristics, especially in terms of BMI and sex, and differences in the diagnostic procedure used. The subject samples in the WSCS were more obese (BMI of 29 kg/m2 compared with 26 kg/m2 in the VSC) and included more men (56% compared with 48% in the VSC). However, variation in the sleep study procedures, with polysomnography applied in the WSCS and home polygraphy in the VCS, may be the most relevant difference. Polygraphy shows good concordance with polysomnography in moderate to severe OSA,22 but this effect has not been observed in normal and mild OSA. The majority of the subjects in the VSC had no or mild OSA. Among the 1,180 patients included in the study, 377 patients had OSA at baseline, and proportionately few, 149 subjects, had a respiratory disturbance index that was ≥ 14/h.

It is important to consider several potential methodologic differences in the studies that have examined BP and OSA. These differences should be considered when comparing the results from different studies. For example, the following components of the studies can vary: definition of hypertension, BP measurement methodology (patient position, time of day, technique), controlling for medications, definition of sleepiness based on multiple sleep latency tests or the Epworth Sleepiness Scale, and definition of OSA based on an AHI assessed by polysomnography or polygraphy. Moreover, several studies have suggested that the degree of hypoxemia could play an important role beyond AHI. Accounting for all of these considerations, we conclude that OSA is an independent cause of hypertension but with less significance than initially suspected.

Studies involving 24-h ambulatory BP monitoring (ABPM) have shown that subjects with hypertension with a decrease in BP of < 10% during the night (nondippers) and those who present an increase in BP at night (risers)23 exhibit greater organ damage and worse cardiovascular outcomes than do subjects with hypertension who present a decrease of > 10% during the night (dippers).24,25 Initial case-control studies using 24-h ABPM showed that patients with OSA had a high prevalence of an unfavorable circadian pattern, compared with subjects without OSA.26 One study found that 84% of patients with mild to severe OSA had a nondipper circadian pattern.27 Similarly, Ancoli-Israel et al28 studied 140 patients with hypertension and found that patients with OSA had a higher dipping ratio, defined as the ratio between the mean nighttime BP and the mean daytime BP, compared with subjects without OSA. Data from a 328-subject subsample of the WSCS, with an average of 7.2 years of follow-up, showed that there was a dose-response relationship between increased odds of developing a nondipping systolic BP (SBP) and the severity of OSA at baseline.29 These results suggest that there is a causal link between OSA and an altered circadian pattern.

The presence of a high nocturnal BP, defined as a nighttime BP ≥ 120 mm Hg (SBP) and/or 70 mm Hg (diastolic BP [DBP]), is the most important BP prognostic variable for cardiovascular outcomes,30-32 and it has shown strong correlations with subclinical brain33,34 and heart damage.35 Thus, the presence or absence of nighttime hypertension on ABPM analysis may be more important than the circadian pattern. In an initial study of 2,877 subjects, Cuspidi et al36 found a positive relationship between the nondipper pattern and left ventricular hypertrophy. However, a second study37 examined heart damage in patients with nocturnal hypertension, compared with dippers and nondippers, and no differences were detected. These results suggest that, rather than the circadian pattern, the critical factor in determining organ damage is the presence or absence of nocturnal hypertension. To date, data are lacking regarding the prevalence of a high nocturnal BP in patients with OSA.

Beat-to-beat BP monitoring studies have provided a deeper analysis of nocturnal BP in patients with OSA.38,39 These small studies (examining beat-to-beat BP and OSA) found that during apnea events in patients with severe OSA, a dramatic increase in SPB from baseline could develop. Unfortunately, the conditions in which ABPM must be performed make this tool unable to capture these BP fluctuations. Organ damage consequences related to this increase in SBP could be expected, but the magnitude of this effect in patients with hypertension has still not been elucidated. Additionally, CPAP treatment, and its protective effect against these BP increases, may be beneficial in this context.

Resistant hypertension is defined as the clinical situation in which lifestyle changes plus pharmacologic treatment with three drugs (including a diuretic) fail to lower the BP to below 140/90 mm Hg.23,40 Depending on the population studied, the prevalence of this condition ranges from 5% to 30% of subjects with hypertension.40

The reported data have shown a high prevalence of OSA in patients with resistant hypertension (71%-83%).5,41 In a study that included 125 subjects with resistant hypertension, Pedrosa et al42 found that OSA was the most frequent condition related to resistant hypertension (64%). In fact, OSA showed a much greater association with resistant hypertension than with primary hyperaldosteronism (5.6%). Demede et al43 found that patients with resistant hypertension had a 2.5-times increased risk of OSA compared with other subjects with hypertension. The high level of aldosterone in resistant hypertension and its consequences in terms of volume overload and rostral fluid shift during sleep, which lead to secondary pharyngeal edema that increases upper airway obstruction, have been hypothesized to be the mechanisms that underlie the link between hypertension and OSA.10,44

The causal relationship between OSA and resistant hypertension was recognized as relevant in the 2013 European Society of Hypertension/European Society of Cardiology guidelines23 and in the resistant hypertension consensus by the Professional Education Committee of Council for High Blood Pressure Research of the American Heart Association.40 Organ damage in resistant hypertension has been well established, but the impact of the coexistence of OSA on this damage and on the cardiovascular outcomes of patients with resistant hypertension must be clarified.

CPAP Treatment

Many studies have evaluated the effect of CPAP treatment on BP in patients with OSA (Fig 1). However, most of these studies evaluated short-term effects and had important limitations and design differences.45 These differences and limitations can be divided into two categories. One set of factors depends on the study population, such as age, sex, BMI, hypertension degree, and adequate antihypertensive treatment, as well as OSA severity. Another set of factors depends on the methodology, such as the number of subjects included, whether the study had a multicenter or a single-center design, the treatment used in the control group (sham-CPAP use or not), the hypertension definition used, how the evaluation of the effect on BP was conducted (office BP or ABPM), and the variability in follow-up time or CPAP compliance. Despite these handicaps, several meta-analyses45-52 have demonstrated a concordant mild effect of CPAP on BP, with a drop of approximately 2 mm Hg (Table 146-54). This effect is significantly inferior to those achieved by most of the commonly used antihypertensive drugs. Despite this modest decrease, this effect is not negligible and could have beneficial effects on cardiovascular outcomes.55 Moreover, similar to the effects of certain antihypertensive drugs, an increase in protective organ damage beyond that associated with the observed BP reduction cannot be excluded.

Table Graphic Jump Location
TABLE 1 ]  Published Meta-analyses of the Effect of CPAP on BP in Patients With OSA

24-h DBP = 24-h ambulatory diastolic BP; 24-h SBP = 24-h ambulatory systolic BP; DBP = diastolic BP; SBP = systolic BP.

a 

Not significant.

Certain variables, such as CPAP compliance,50,51,53,56 somnolence status,51,53 and baseline BP,50,52 may modulate the strength of the effect of CPAP treatment on BP. The decrease in BP achieved by CPAP treatment is clearly related to the hours of CPAP use and likely to its use during rapid eye movement sleep.57 In relation to symptoms, a recent meta-analysis found no effect of CPAP on BP in patients without somnolence.53 Another characteristic is the influence of OSA severity on BP drop magnitude during CPAP treatment. Two meta-analyses found a relationship between OSA severity and the magnitude of the drop in BP during CPAP treatment.49,51 Conversely, Montesi et al50 showed an independent relation between OSA severity and BP reduction. A later patient-level meta-analysis, using individual patient data from the trials, confirmed these results.52

Lifestyle modifications, including weight loss, should be recommended in patients receiving hypertension treatment.23 Chirinos et al58 randomized 181 patients with obesity and moderate to severe OSA to three possible interventions for 24 weeks: CPAP treatment alone, weight-loss intervention alone, and CPAP plus weight-loss intervention. Among 136 patients who completed the study, in the per-protocol population, the reduction in SBP at 24 weeks was greater in the combined intervention group (14.1 mm Hg) than in the weight-loss group (6.8 mm Hg) or in the CPAP group (3.0 mm Hg). The reduction in mean arterial pressure was also significantly greater in the combined treatment group. Thus, the combined treatment reduced BP more than either intervention alone. These results suggest the possibility of an interaction effect between lifestyle modifications, weight-loss measures, and CPAP in the control of BP.

In patients with resistant hypertension, CPAP treatment showed a clearer drop in BP compared with other subjects with hypertension.56,59-63 A recent meta-analysis54 showed that the effects of CPAP in patients with resistant hypertension on the drop in ambulatory BP were −7.21 (95% CI, −9.04 to −5.35; P < .001; I2, 58%) and −4.99 (95% CI, −6.01 to −3.96; P > .001; I2, 31%) for SBP and DBP, respectively. Considering only the results from RCTs, the mean net changes in ambulatory BP were −6.74 mm Hg (95% CI, −9.98 to −3.49; P < .001; I2, 61%) and −5.94 mm Hg (95% CI, −9.40 to −2.47; P = .001; I2, 76%) for SBP and DBP, respectively, favoring the CPAP groups (Table 2). The study that provided the most patients for this meta-analysis was the HIPARCO (Effect of Continuous Positive Airway Pressure [CPAP] Treatment in the Control of Refractory Hypertension) RCT,56 which included 194 patients. In that study, a significant reduction in 24-h BP of 4.4 mm Hg (95% CI, 1.8-7; P = .001) was observed, and this reduction was more evident at night. This reduction was assessed according to CPAP tolerance and compliance (per-protocol analysis). The linear regression analysis showed that BP improved by 1.3 mm Hg for each additional hour of CPAP use. The HIPARCO study also showed that CPAP use led to the recovery of the normal circadian pattern, with a secondary potential cardiovascular benefit. However, there was significant variability in the BP drop among subjects, and the factors that influence the BP response to CPAP in patients with resistant hypertension have not been identified. Thus, there is a need for long-term RCTs to provide relevant information regarding the cost effectiveness of CPAP treatment in the management of resistant hypertension in these patients.

Table Graphic Jump Location
TABLE 2 ]  Randomized Controlled Trials Evaluating the Effect of CPAP on BP in Patients With OSA and Resistant Hypertension

ABPM = ambulatory BP monitoring; AHI = apnea-hypopnea index. See Table 1 for expansion of other abbreviations.

a 

> 5.8 h.

b 

> 4 h.

Oral Appliances

Oral appliances are a recommended treatment of patients with mild to moderate OSA. Currently, the studies that have evaluated the effects of this treatment on BP have included small patient sample sizes. In a meta-analysis of seven studies that included a total of 399 patients, Iftikhar et al64 found that oral appliance treatment in subjects with hypertension and OSA provided a BP reduction that was similar to that achieved with CPAP. The mean changes were −2.7 mm Hg (95% CI, −8.5 to −4.6; P = .04) for SBP, −2.7 mm Hg (95% CI, −0.9 to −4.6; P = .004) for DBP, and −2.40 mm Hg (95% CI, −4.01 to −0.80; P = .003) for BP. An important limitation of this meta-analysis is that most of the included studies were observational. Therefore, the authors recommended that these results be confirmed by performing RCTs with large patient samples.

According to the available physiopathologic knowledge of the relationship between OSA and hypertension, antihypertensive drugs that modulate sympathetic activity and the renin-angiotensin-aldosterone axis may be the best treatment options for hypertension in patients with OSA. To date, the studies that have evaluated the effects of antihypertensive drug treatment on OSA severity have included small subject samples and no comparable populations, and they have had important methodologic differences. Therefore, it is not possible to establish definitive recommendations based on the results of the available clinical studies. Previous work has evaluated β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and spironolactone. ACE inhibitors, such as enalapril and cilazapril,65,66 and β-blockers, such as atenolol,67 have been shown to control nighttime BP in patients with OSA. The classic study was conducted by Kraiczi et al,67 who evaluated the five most commonly used antihypertensive drugs (atenolol, amlodipine, enalapril, losartan, and hydrochlorothiazide) and their effects on AHI (OSA severity). They did not detect any variations in OSA severity according to the drug used, but the study was underpowered to allow for a comparison of the drugs, and it lacked a placebo control.

Data from other studies have provided controversial results. On the one hand, some studies with very limited samples executed at single centers with short-term follow-ups have shown an improvement in OSA severity in response to treatment with ACE inhibitors (cilazapril),68,69 β-blockers (metoprolol, nebivolol),69,70 and angiotensin receptor blockers (valsartan).70 On the other hand, other studies have questioned the use of ACE inhibitors in patients with hypertension and OSA because of the side effects of these antihypertensive drugs, which may cause rhinopharyngeal inflammation and increase upper airway obstruction.71 Additionally, β-blockers can favor weight gain, which may negatively impact the severity of OSA. Most of these negative side effects require a long period of time to become evident; thus, the short duration of follow-up in these studies could not rule out their impact on the severity of OSA. Additionally, Nerbass et al72 reported negative effects of calcium channel blockers that shortened sleep duration.

The most promising class of antihypertensive drug treatment, based on their effects on OSA severity and BP, are diuretics,73,74 especially spironolactone.74 By reducing parapharyngeal edema and secondary upper airway obstruction, these drugs appear to improve OSA severity74 and to greatly reduce BP. In conclusion, there is a need for well-designed, multicenter, large-sample studies with long follow-up periods to improve our knowledge and allow solid recommendations to be established.

There is an epidemiologic relationship between OSA and hypertension that is especially important in subjects with resistant hypertension. Despite this, the causal relationship between OSA and hypertension is probably not as important as initially thought. Certain population characteristics, such as age, sleepiness associated with OSA, and sex, may be important in determining the role of OSA as a cause of hypertension. OSA may also lead to the development of an unfavorable circadian pattern of BP, with worse cardiovascular outcomes. In addition, some characteristics that are specifically linked to the nocturnal BP effect of sleep apnea remain to be clarified.

Meta-analyses and RCTs have reported a modest effect of CPAP on the decrease in BP of approximately 2 mm Hg in patients with OSA. The effect of CPAP is more evident in patients with resistant hypertension (a decrease of approximately 6 mm Hg). Long-term RCTs are needed to clarify the role of CPAP treatment in the clinical management of resistant hypertension. Compliance with CPAP is the key issue for the achievement of BP reduction. However, other features, such as somnolence status and BP level prior to treatment, could be relevant. The interaction between CPAP treatment, lifestyle modifications, and antihypertensive drugs and their effects on decreases in BP must be explored.

The effects on BP of oral appliances used for OSA may be similar to those of CPAP, but only a limited number of studies have investigated this topic. Finally, diuretics, particularly antialdosteronic diuretic agents, in the absence of additional data reported by clinical studies on other antihypertensive drug treatments, should be considered the first-line antihypertensive drug treatment in patients with OSA.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Barbé received research grants from ResMed, Australia, a company that develops products related to sleep apnea; the Health Research Fund, Spanish Ministry of Health; the Spanish Respiratory Society (SEPAR); the Catalonian Cardiology Society, Esteve-Teijin (Spain); Oxigen Salud (Spain); and ALLER to develop the ISAACC clinical trial (NCT01335087). Drs Torres and Sánchez-de-la-Torre have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

ABPM

ambulatory BP monitoring

ACE

angiotensin-converting enzyme

AHI

apnea-hypopnea index

DBP

diastolic BP

RCT

randomized controlled trial

SBP

systolic BP

VSC

Vitoria Sleep Cohort

WSCS

Wisconsin Sleep Cohort Study

Sánchez-de-la-Torre M, Campos-Rodriguez F, Barbé F. Obstructive sleep apnoea and cardiovascular disease. Lancet Respir Med. 2013;1(1):61-72. [CrossRef] [PubMed]
 
Durán J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea-hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med. 2001;163(3 pt 1):685-689. [CrossRef] [PubMed]
 
Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006-1014. [CrossRef] [PubMed]
 
Silverberg DS, Oksenberg A. Are sleep-related breathing disorders important contributing factors to the production of essential hypertension? Curr Hypertens Rep. 2001;3(3):209-215. [CrossRef] [PubMed]
 
Logan AG, Perlikowski SM, Mente A, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19(12):2271-2277. [CrossRef] [PubMed]
 
Young T, Peppard P, Palta M, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med. 1997;157(15):1746-1752. [CrossRef] [PubMed]
 
Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;283(14):1829-1836. [CrossRef] [PubMed]
 
Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ. 2000;320(7233):479-482. [CrossRef] [PubMed]
 
Jhamb M, Unruh M. Bidirectional relationship of hypertension with obstructive sleep apnea. Curr Opin Pulm Med. 2014;20(6):558-564. [CrossRef] [PubMed]
 
Friedman O, Bradley TD, Chan CT, Parkes R, Logan AG. Relationship between overnight rostral fluid shift and obstructive sleep apnea in drug-resistant hypertension. Hypertension. 2010;56(6):1077-1082. [CrossRef] [PubMed]
 
Wolk R, Somers VK. Obesity-related cardiovascular disease: implications of obstructive sleep apnea. Diabetes Obes Metab. 2006;8(3):250-260. [CrossRef] [PubMed]
 
Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378-1384. [CrossRef] [PubMed]
 
Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee; National Hight Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure. Hypertension. 2003;42(6):1206-1252. [CrossRef] [PubMed]
 
Marin JM, Agusti A, Villar I, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307(20):2169-2176. [CrossRef] [PubMed]
 
Bixler EO, Vgontzas AN, Lin HM, et al. Association of hypertension and sleep-disordered breathing. Arch Intern Med. 2000;160(15):2289-2295. [CrossRef] [PubMed]
 
Haas DC, Foster GL, Nieto FJ, et al. Age-dependent associations between sleep-disordered breathing and hypertension: importance of discriminating between systolic/diastolic hypertension and isolated systolic hypertension in the Sleep Heart Health Study. Circulation. 2005;111(5):614-621. [CrossRef] [PubMed]
 
O’Connor GT, Caffo N, Newman AB, et al. Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2009;179(12):1159-1164. [CrossRef] [PubMed]
 
Kapur VK, Resnick HE, Gottlieb DJ; Sleep Heart Health Study Group. Sleep disordered breathing and hypertension: does self-reported sleepiness modify the association? Sleep. 2008;31(8):1127-1132. [PubMed]
 
Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, et al; Spanish Sleep And Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled tria. JAMA. 2012;307(20):2161-2168. [CrossRef] [PubMed]
 
Hedner J, Bengtsson-Boström K, Peker Y, Grote L, Råstam L, Lindblad U. Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study. Eur Respir J. 2006;27(3):564-570. [CrossRef] [PubMed]
 
Cano-Pumarega I, Durán-Cantolla J, Aizpuru F, et al. Obstructive sleep apnea and systemic hypertension: longitudinal study in the general population: the Vitoria Sleep Cohort. Am J Respir Crit Care Med. 2011;184(11):1299-1304. [CrossRef] [PubMed]
 
Masa JF, Corral J, Sanchez de Cos J, et al; Collaborating group. Effectiveness of three sleep apnea management alternatives. Sleep. 2013;36(12):1799-1807. [PubMed]
 
ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2013;31(10):1925-1938. [CrossRef] [PubMed]
 
Hoshide S, Kario K, Hoshide Y, et al. Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives. Am J Hypertens. 2003;16(6):434-438. [CrossRef] [PubMed]
 
Boggia J, Li Y, Thijs L, et al; International Database of Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO) investigators. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet. 2007;370(9594):1219-1229. [CrossRef] [PubMed]
 
Pankow W, Nabe B, Lies A, et al. Influence of sleep apnea on 24-hour blood pressure. Chest. 1997;112(5):1253-1258. [CrossRef] [PubMed]
 
Loredo JS, Ancoli-Israel S, Dimsdale JE. Sleep quality and blood pressure dipping in obstructive sleep apnea. Am J Hypertens. 2001;14(9 pt 1):887-892. [CrossRef] [PubMed]
 
Ancoli-Israel S, Stepnowsky C, Dimsdale J, Marler M, Cohen-Zion M, Johnson S. The effect of race and sleep-disordered breathing on nocturnal BP “dipping”: analysis in an older population. Chest. 2002;122(4):1148-1155. [CrossRef] [PubMed]
 
Hla KM, Young T, Finn L, Peppard PE, Szklo-Coxe M, Stubbs M. Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin Sleep Cohort Study. Sleep. 2008;31(6):795-800. [PubMed]
 
Ohkubo T, Hozawa A, Yamaguchi J, et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens. 2002;20(11):2183-2189. [CrossRef] [PubMed]
 
Dolan E, Stanton A, Thijs L, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46(1):156-161. [CrossRef] [PubMed]
 
Hansen TW, Li Y, Boggia J, Thijs L, Richart T, Staessen JA. Predictive role of the nighttime blood pressure. Hypertension. 2011;57(1):3-10. [CrossRef] [PubMed]
 
Kario K, Pickering TG, Umeda Y, et al. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation. 2003;107(10):1401-1406. [CrossRef] [PubMed]
 
Henskens LH, Kroon AA, van Oostenbrugge RJ, et al. Associations of ambulatory blood pressure levels with white matter hyperintensity volumes in hypertensive patients. J Hypertens. 2009;27(7):1446-1452. [CrossRef] [PubMed]
 
Perez-Lloret S, Tobilli JE, Cardinali DP, Malateste JC, Milei J. Nocturnal hypertension defined by fixed cut-off limits is a better predictor of left ventricular hypertrophy than non-dipping. Int J Cardiol. 2008;127(3):387-389. [CrossRef] [PubMed]
 
Cuspidi C, Giudici V, Negri F, Sala C. Nocturnal nondipping and left ventricular hypertrophy in hypertension: an updated review. Expert Rev Cardiovasc Ther. 2010;8(6):781-792. [CrossRef] [PubMed]
 
Cuspidi C, Sala C, Valerio C, Negri F, Mancia G. Nocturnal hypertension and organ damage in dippers and nondippers. Am J Hypertens. 2012;25(8):869-875. [CrossRef] [PubMed]
 
Imadojemu VA, Gleeson K, Gray KS, Sinoway LI, Leuenberger UA. Obstructive apnea during sleep is associated with peripheral vasoconstriction. Am J Respir Crit Care Med. 2002;165(1):61-66. [CrossRef] [PubMed]
 
Jelic S, Bartels MN, Mateika JH, Ngai P, DeMeersman RE, Basner RC. Arterial stiffness increases during obstructive sleep apneas. Sleep. 2002;25(8):850-855. [PubMed]
 
Calhoun DA, Jones D, Textor S, et al; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117(25):e510-e526. [CrossRef] [PubMed]
 
Gonçalves SC, Martinez D, Gus M, et al. Obstructive sleep apnea and resistant hypertension: a case-control study. Chest. 2007;132(6):1858-1862. [CrossRef] [PubMed]
 
Pedrosa RP, Drager LF, Gonzaga CC, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58(5):811-817. [CrossRef] [PubMed]
 
Demede M, Pandey A, Zizi F, et al. Resistant hypertension and obstructive sleep apnea in the primary-care setting. Int J Hypertens. 2011;2011:340929. [PubMed]
 
Dudenbostel T, Calhoun DA. Resistant hypertension, obstructive sleep apnoea and aldosterone. J Hum Hypertens. 2012;26(5):281-287. [CrossRef] [PubMed]
 
Durán-Cantolla J, Aizpuru F, Martínez-Null C, Barbé-Illa F. Obstructive sleep apnea/hypopnea and systemic hypertension. Sleep Med Rev. 2009;13(5):323-331. [CrossRef] [PubMed]
 
Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension. 2007;50(2):417-423. [CrossRef] [PubMed]
 
Alajmi M, Mulgrew AT, Fox J, et al. Impact of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea hypopnea: a meta-analysis of randomized controlled trials. Lung. 2007;185(2):67-72. [CrossRef] [PubMed]
 
Mo L, He QY. Effect of long-term continuous positive airway pressure ventilation on blood pressure in patients with obstructive sleep apnea hypopnea syndrome: a meta-analysis of clinical trials [in Chinese]. Zhonghua Yi Xue Za Zhi. 2007;87(17):1177-1180. [PubMed]
 
Haentjens P, Van Meerhaeghe A, Moscariello A, et al. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med. 2007;167(8):757-764. [CrossRef] [PubMed]
 
Montesi SB, Edwards BA, Malhotra A, Bakker JP. The effect of continuous positive airway pressure treatment on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med. 2012;8(5):587-596. [PubMed]
 
Fava C, Dorigoni S, Dalle Vedove F, et al. Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic review and meta-analysis. Chest. 2014;145(4):762-771. [CrossRef] [PubMed]
 
Bakker JP, Edwards BA, Gautam SP, et al. Blood pressure improvement with continuous positive airway pressure is independent of obstructive sleep apnea severity [published correction appears inJ Clin Sleep Med. 2014;10(6):711]. J Clin Sleep Med. 2014;10(4):365-369. [PubMed]
 
Bratton DJ, Stradling JR, Barbé F, Kohler M. Effect of CPAP on blood pressure in patients with minimally symptomatic obstructive sleep apnoea: a meta-analysis using individual patient data from four randomised controlled trials. Thorax. 2014;69(12):1128-1135. [CrossRef] [PubMed]
 
Iftikhar IH, Valentine CW, Bittencourt LR, et al. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis. J Hypertens. 2014;32(12):2341-2350. [CrossRef] [PubMed]
 
Turnbull F; Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362(9395):1527-1535. [CrossRef] [PubMed]
 
Martínez-García MA, Capote F, Campos-Rodríguez F, et al; Spanish Sleep Network. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA. 2013;310(22):2407-2415. [CrossRef] [PubMed]
 
Mokhlesi B, Finn LA, Hagen EW, Young T, Hla KM, Van Cauter E, Peppard PE. Obstructive sleep apnea during REM sleep and hypertension. Results of the Wisconsin Sleep Cohort. Am J Respir Crit Care Med. 2014;190(10):1158-1167. [CrossRef] [PubMed]
 
Chirinos JA, Gurubhagavatula I, Teff K, et al. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med. 2014;370(24):2265-2275. [CrossRef] [PubMed]
 
Martínez-García MA, Gómez-Aldaraví R, Soler-Cataluña JJ, Martínez TG, Bernácer-Alpera B, Román-Sánchez P. Positive effect of CPAP treatment on the control of difficult-to-treat hypertension. Eur Respir J. 2007;29(5):951-957. [CrossRef] [PubMed]
 
Logan AG, Tkacova R, Perlikowski SM, et al. Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Eur Respir J. 2003;21(2):241-247. [CrossRef] [PubMed]
 
Lozano L, Tovar JL, Sampol G, et al. Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: a randomized, controlled trial. J Hypertens. 2010;28(10):2161-2168. [CrossRef] [PubMed]
 
Litvin AY, Sukmarova ZN, Elfimova EM, et al. Effects of CPAP on “vascular” risk factors in patients with obstructive sleep apnea and arterial hypertension. Vasc Health Risk Manag. 2013;9:229-235. [CrossRef] [PubMed]
 
Pedrosa RP, Draguer LF, de Paula LK, Amaro AC, Bortolotto LA, Lorenzi-Filho G. Effects of OSA treatment on BP in patients with resistant hypertension: a randomized trial. Chest. 2013;144(5):1487-1494. [CrossRef] [PubMed]
 
Iftikhar IH, Hays ER, Iverson MA, Magalang UJ, Maas AK. Effect of oral appliances on blood pressure in obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med. 2013;9(2):165-174. [PubMed]
 
Zou D, Grote L, Eder DN, Radlinski J, Hedner J. A double-blind crossover study of Doxazosin and Enalapril on peripherical vascular tone and nocturnal blood pressure in sleep apnea patients. Sleep Med. 2010;11(3):325-328. [CrossRef] [PubMed]
 
Grote L, Wutkewicz K, Knaack L, Ploch T, Hedner J, Peter JH. Association between blood pressure reduction with antihypertensive treatment and sleep apnea activity. Am J Hypertens. 2000;13(12):1280-1287. [CrossRef] [PubMed]
 
Kraiczi H, Hedner J, Peker Y, Grote L. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161(5):1423-1428. [CrossRef] [PubMed]
 
Peter JH, Gassel W, Mayer J, et al. Effects of cilazapril on hypertension, sleep, and apnea. Am J Med. 1989;87(6B):72S-78S. [CrossRef] [PubMed]
 
Weichler U, Herres-Mayer B, Mayer J, Weber K, Hoffmann R, Peter JH. Influence of antihypertensive drug therapy on sleep pattern and sleep apnea activity. Cardiology. 1991;78(2):124-130. [CrossRef] [PubMed]
 
Heitmann J, Greulich T, Reinke C, et al. Comparison of the effects of nebivolol and valsartan on BP reduction and sleep apnoea activity in patients with essential hypertension and OSA. Curr Med Res Opin. 2010;26(8):1925-1932. [CrossRef] [PubMed]
 
Cicolin A, Mangiardi L, Mutani R, Bucca C. Angiotensin-converting enzyme inhibitors and obstructive sleep apnea. Mayo Clin Proc. 2006;81(1):53-55. [CrossRef] [PubMed]
 
Nerbass FB, Pedrosa RP, Genta PR, Drager LF, Lorenzi-Filho G. Calcium channel blockers are independently associated with short sleep duration in hypertensive patients with obstructive sleep apnea. J Hypertens. 2011;29(6):1236-1241. [CrossRef] [PubMed]
 
Bucca CB, Brussino L, Battisti A, et al. Diuretics in obstructive sleep apnea with diastolic heart failure. Chest. 2007;132(2):440-446. [CrossRef] [PubMed]
 
Gaddam K, Pimenta E, Thomas SJ, et al. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J Hum Hypertens. 2010;24(8):532-537. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
TABLE 1 ]  Published Meta-analyses of the Effect of CPAP on BP in Patients With OSA

24-h DBP = 24-h ambulatory diastolic BP; 24-h SBP = 24-h ambulatory systolic BP; DBP = diastolic BP; SBP = systolic BP.

a 

Not significant.

Table Graphic Jump Location
TABLE 2 ]  Randomized Controlled Trials Evaluating the Effect of CPAP on BP in Patients With OSA and Resistant Hypertension

ABPM = ambulatory BP monitoring; AHI = apnea-hypopnea index. See Table 1 for expansion of other abbreviations.

a 

> 5.8 h.

b 

> 4 h.

References

Sánchez-de-la-Torre M, Campos-Rodriguez F, Barbé F. Obstructive sleep apnoea and cardiovascular disease. Lancet Respir Med. 2013;1(1):61-72. [CrossRef] [PubMed]
 
Durán J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea-hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med. 2001;163(3 pt 1):685-689. [CrossRef] [PubMed]
 
Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006-1014. [CrossRef] [PubMed]
 
Silverberg DS, Oksenberg A. Are sleep-related breathing disorders important contributing factors to the production of essential hypertension? Curr Hypertens Rep. 2001;3(3):209-215. [CrossRef] [PubMed]
 
Logan AG, Perlikowski SM, Mente A, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19(12):2271-2277. [CrossRef] [PubMed]
 
Young T, Peppard P, Palta M, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med. 1997;157(15):1746-1752. [CrossRef] [PubMed]
 
Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;283(14):1829-1836. [CrossRef] [PubMed]
 
Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ. 2000;320(7233):479-482. [CrossRef] [PubMed]
 
Jhamb M, Unruh M. Bidirectional relationship of hypertension with obstructive sleep apnea. Curr Opin Pulm Med. 2014;20(6):558-564. [CrossRef] [PubMed]
 
Friedman O, Bradley TD, Chan CT, Parkes R, Logan AG. Relationship between overnight rostral fluid shift and obstructive sleep apnea in drug-resistant hypertension. Hypertension. 2010;56(6):1077-1082. [CrossRef] [PubMed]
 
Wolk R, Somers VK. Obesity-related cardiovascular disease: implications of obstructive sleep apnea. Diabetes Obes Metab. 2006;8(3):250-260. [CrossRef] [PubMed]
 
Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378-1384. [CrossRef] [PubMed]
 
Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee; National Hight Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure. Hypertension. 2003;42(6):1206-1252. [CrossRef] [PubMed]
 
Marin JM, Agusti A, Villar I, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307(20):2169-2176. [CrossRef] [PubMed]
 
Bixler EO, Vgontzas AN, Lin HM, et al. Association of hypertension and sleep-disordered breathing. Arch Intern Med. 2000;160(15):2289-2295. [CrossRef] [PubMed]
 
Haas DC, Foster GL, Nieto FJ, et al. Age-dependent associations between sleep-disordered breathing and hypertension: importance of discriminating between systolic/diastolic hypertension and isolated systolic hypertension in the Sleep Heart Health Study. Circulation. 2005;111(5):614-621. [CrossRef] [PubMed]
 
O’Connor GT, Caffo N, Newman AB, et al. Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2009;179(12):1159-1164. [CrossRef] [PubMed]
 
Kapur VK, Resnick HE, Gottlieb DJ; Sleep Heart Health Study Group. Sleep disordered breathing and hypertension: does self-reported sleepiness modify the association? Sleep. 2008;31(8):1127-1132. [PubMed]
 
Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, et al; Spanish Sleep And Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled tria. JAMA. 2012;307(20):2161-2168. [CrossRef] [PubMed]
 
Hedner J, Bengtsson-Boström K, Peker Y, Grote L, Råstam L, Lindblad U. Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study. Eur Respir J. 2006;27(3):564-570. [CrossRef] [PubMed]
 
Cano-Pumarega I, Durán-Cantolla J, Aizpuru F, et al. Obstructive sleep apnea and systemic hypertension: longitudinal study in the general population: the Vitoria Sleep Cohort. Am J Respir Crit Care Med. 2011;184(11):1299-1304. [CrossRef] [PubMed]
 
Masa JF, Corral J, Sanchez de Cos J, et al; Collaborating group. Effectiveness of three sleep apnea management alternatives. Sleep. 2013;36(12):1799-1807. [PubMed]
 
ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2013;31(10):1925-1938. [CrossRef] [PubMed]
 
Hoshide S, Kario K, Hoshide Y, et al. Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives. Am J Hypertens. 2003;16(6):434-438. [CrossRef] [PubMed]
 
Boggia J, Li Y, Thijs L, et al; International Database of Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO) investigators. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet. 2007;370(9594):1219-1229. [CrossRef] [PubMed]
 
Pankow W, Nabe B, Lies A, et al. Influence of sleep apnea on 24-hour blood pressure. Chest. 1997;112(5):1253-1258. [CrossRef] [PubMed]
 
Loredo JS, Ancoli-Israel S, Dimsdale JE. Sleep quality and blood pressure dipping in obstructive sleep apnea. Am J Hypertens. 2001;14(9 pt 1):887-892. [CrossRef] [PubMed]
 
Ancoli-Israel S, Stepnowsky C, Dimsdale J, Marler M, Cohen-Zion M, Johnson S. The effect of race and sleep-disordered breathing on nocturnal BP “dipping”: analysis in an older population. Chest. 2002;122(4):1148-1155. [CrossRef] [PubMed]
 
Hla KM, Young T, Finn L, Peppard PE, Szklo-Coxe M, Stubbs M. Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin Sleep Cohort Study. Sleep. 2008;31(6):795-800. [PubMed]
 
Ohkubo T, Hozawa A, Yamaguchi J, et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens. 2002;20(11):2183-2189. [CrossRef] [PubMed]
 
Dolan E, Stanton A, Thijs L, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46(1):156-161. [CrossRef] [PubMed]
 
Hansen TW, Li Y, Boggia J, Thijs L, Richart T, Staessen JA. Predictive role of the nighttime blood pressure. Hypertension. 2011;57(1):3-10. [CrossRef] [PubMed]
 
Kario K, Pickering TG, Umeda Y, et al. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation. 2003;107(10):1401-1406. [CrossRef] [PubMed]
 
Henskens LH, Kroon AA, van Oostenbrugge RJ, et al. Associations of ambulatory blood pressure levels with white matter hyperintensity volumes in hypertensive patients. J Hypertens. 2009;27(7):1446-1452. [CrossRef] [PubMed]
 
Perez-Lloret S, Tobilli JE, Cardinali DP, Malateste JC, Milei J. Nocturnal hypertension defined by fixed cut-off limits is a better predictor of left ventricular hypertrophy than non-dipping. Int J Cardiol. 2008;127(3):387-389. [CrossRef] [PubMed]
 
Cuspidi C, Giudici V, Negri F, Sala C. Nocturnal nondipping and left ventricular hypertrophy in hypertension: an updated review. Expert Rev Cardiovasc Ther. 2010;8(6):781-792. [CrossRef] [PubMed]
 
Cuspidi C, Sala C, Valerio C, Negri F, Mancia G. Nocturnal hypertension and organ damage in dippers and nondippers. Am J Hypertens. 2012;25(8):869-875. [CrossRef] [PubMed]
 
Imadojemu VA, Gleeson K, Gray KS, Sinoway LI, Leuenberger UA. Obstructive apnea during sleep is associated with peripheral vasoconstriction. Am J Respir Crit Care Med. 2002;165(1):61-66. [CrossRef] [PubMed]
 
Jelic S, Bartels MN, Mateika JH, Ngai P, DeMeersman RE, Basner RC. Arterial stiffness increases during obstructive sleep apneas. Sleep. 2002;25(8):850-855. [PubMed]
 
Calhoun DA, Jones D, Textor S, et al; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117(25):e510-e526. [CrossRef] [PubMed]
 
Gonçalves SC, Martinez D, Gus M, et al. Obstructive sleep apnea and resistant hypertension: a case-control study. Chest. 2007;132(6):1858-1862. [CrossRef] [PubMed]
 
Pedrosa RP, Drager LF, Gonzaga CC, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58(5):811-817. [CrossRef] [PubMed]
 
Demede M, Pandey A, Zizi F, et al. Resistant hypertension and obstructive sleep apnea in the primary-care setting. Int J Hypertens. 2011;2011:340929. [PubMed]
 
Dudenbostel T, Calhoun DA. Resistant hypertension, obstructive sleep apnoea and aldosterone. J Hum Hypertens. 2012;26(5):281-287. [CrossRef] [PubMed]
 
Durán-Cantolla J, Aizpuru F, Martínez-Null C, Barbé-Illa F. Obstructive sleep apnea/hypopnea and systemic hypertension. Sleep Med Rev. 2009;13(5):323-331. [CrossRef] [PubMed]
 
Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension. 2007;50(2):417-423. [CrossRef] [PubMed]
 
Alajmi M, Mulgrew AT, Fox J, et al. Impact of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea hypopnea: a meta-analysis of randomized controlled trials. Lung. 2007;185(2):67-72. [CrossRef] [PubMed]
 
Mo L, He QY. Effect of long-term continuous positive airway pressure ventilation on blood pressure in patients with obstructive sleep apnea hypopnea syndrome: a meta-analysis of clinical trials [in Chinese]. Zhonghua Yi Xue Za Zhi. 2007;87(17):1177-1180. [PubMed]
 
Haentjens P, Van Meerhaeghe A, Moscariello A, et al. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med. 2007;167(8):757-764. [CrossRef] [PubMed]
 
Montesi SB, Edwards BA, Malhotra A, Bakker JP. The effect of continuous positive airway pressure treatment on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med. 2012;8(5):587-596. [PubMed]
 
Fava C, Dorigoni S, Dalle Vedove F, et al. Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic review and meta-analysis. Chest. 2014;145(4):762-771. [CrossRef] [PubMed]
 
Bakker JP, Edwards BA, Gautam SP, et al. Blood pressure improvement with continuous positive airway pressure is independent of obstructive sleep apnea severity [published correction appears inJ Clin Sleep Med. 2014;10(6):711]. J Clin Sleep Med. 2014;10(4):365-369. [PubMed]
 
Bratton DJ, Stradling JR, Barbé F, Kohler M. Effect of CPAP on blood pressure in patients with minimally symptomatic obstructive sleep apnoea: a meta-analysis using individual patient data from four randomised controlled trials. Thorax. 2014;69(12):1128-1135. [CrossRef] [PubMed]
 
Iftikhar IH, Valentine CW, Bittencourt LR, et al. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis. J Hypertens. 2014;32(12):2341-2350. [CrossRef] [PubMed]
 
Turnbull F; Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362(9395):1527-1535. [CrossRef] [PubMed]
 
Martínez-García MA, Capote F, Campos-Rodríguez F, et al; Spanish Sleep Network. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA. 2013;310(22):2407-2415. [CrossRef] [PubMed]
 
Mokhlesi B, Finn LA, Hagen EW, Young T, Hla KM, Van Cauter E, Peppard PE. Obstructive sleep apnea during REM sleep and hypertension. Results of the Wisconsin Sleep Cohort. Am J Respir Crit Care Med. 2014;190(10):1158-1167. [CrossRef] [PubMed]
 
Chirinos JA, Gurubhagavatula I, Teff K, et al. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med. 2014;370(24):2265-2275. [CrossRef] [PubMed]
 
Martínez-García MA, Gómez-Aldaraví R, Soler-Cataluña JJ, Martínez TG, Bernácer-Alpera B, Román-Sánchez P. Positive effect of CPAP treatment on the control of difficult-to-treat hypertension. Eur Respir J. 2007;29(5):951-957. [CrossRef] [PubMed]
 
Logan AG, Tkacova R, Perlikowski SM, et al. Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Eur Respir J. 2003;21(2):241-247. [CrossRef] [PubMed]
 
Lozano L, Tovar JL, Sampol G, et al. Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: a randomized, controlled trial. J Hypertens. 2010;28(10):2161-2168. [CrossRef] [PubMed]
 
Litvin AY, Sukmarova ZN, Elfimova EM, et al. Effects of CPAP on “vascular” risk factors in patients with obstructive sleep apnea and arterial hypertension. Vasc Health Risk Manag. 2013;9:229-235. [CrossRef] [PubMed]
 
Pedrosa RP, Draguer LF, de Paula LK, Amaro AC, Bortolotto LA, Lorenzi-Filho G. Effects of OSA treatment on BP in patients with resistant hypertension: a randomized trial. Chest. 2013;144(5):1487-1494. [CrossRef] [PubMed]
 
Iftikhar IH, Hays ER, Iverson MA, Magalang UJ, Maas AK. Effect of oral appliances on blood pressure in obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med. 2013;9(2):165-174. [PubMed]
 
Zou D, Grote L, Eder DN, Radlinski J, Hedner J. A double-blind crossover study of Doxazosin and Enalapril on peripherical vascular tone and nocturnal blood pressure in sleep apnea patients. Sleep Med. 2010;11(3):325-328. [CrossRef] [PubMed]
 
Grote L, Wutkewicz K, Knaack L, Ploch T, Hedner J, Peter JH. Association between blood pressure reduction with antihypertensive treatment and sleep apnea activity. Am J Hypertens. 2000;13(12):1280-1287. [CrossRef] [PubMed]
 
Kraiczi H, Hedner J, Peker Y, Grote L. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161(5):1423-1428. [CrossRef] [PubMed]
 
Peter JH, Gassel W, Mayer J, et al. Effects of cilazapril on hypertension, sleep, and apnea. Am J Med. 1989;87(6B):72S-78S. [CrossRef] [PubMed]
 
Weichler U, Herres-Mayer B, Mayer J, Weber K, Hoffmann R, Peter JH. Influence of antihypertensive drug therapy on sleep pattern and sleep apnea activity. Cardiology. 1991;78(2):124-130. [CrossRef] [PubMed]
 
Heitmann J, Greulich T, Reinke C, et al. Comparison of the effects of nebivolol and valsartan on BP reduction and sleep apnoea activity in patients with essential hypertension and OSA. Curr Med Res Opin. 2010;26(8):1925-1932. [CrossRef] [PubMed]
 
Cicolin A, Mangiardi L, Mutani R, Bucca C. Angiotensin-converting enzyme inhibitors and obstructive sleep apnea. Mayo Clin Proc. 2006;81(1):53-55. [CrossRef] [PubMed]
 
Nerbass FB, Pedrosa RP, Genta PR, Drager LF, Lorenzi-Filho G. Calcium channel blockers are independently associated with short sleep duration in hypertensive patients with obstructive sleep apnea. J Hypertens. 2011;29(6):1236-1241. [CrossRef] [PubMed]
 
Bucca CB, Brussino L, Battisti A, et al. Diuretics in obstructive sleep apnea with diastolic heart failure. Chest. 2007;132(2):440-446. [CrossRef] [PubMed]
 
Gaddam K, Pimenta E, Thomas SJ, et al. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J Hum Hypertens. 2010;24(8):532-537. [CrossRef] [PubMed]
 
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