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Original Research: Sleep Disorders |

Effect of CPAP on Blood Pressure in Patients With OSA/HypopneaEffect of CPAP on Blood Pressure in OSA: A Systematic Review and Meta-analysis FREE TO VIEW

Cristiano Fava, MD, PhD; Stefania Dorigoni, MD; Francesco Dalle Vedove, MD; Elisa Danese, PharmD; Martina Montagnana, MD; Gian Cesare Guidi, MD; Krzysztof Narkiewicz, MD, PhD; Pietro Minuz, MD
Author and Funding Information

From the Department of Medicine (Drs Fava, Dorigoni, Dalle Vedove, Danese, and Minuz), Division of Internal Medicine C, and Department of Life and Reproduction Sciences (Drs Danese, Montagnana, and Guidi), Clinical Biochemistry Section, University Hospital of Verona, Verona, Italy; and Department of Hypertension and Diabetology (Dr Narkiewicz), Medical University of Gdańsk, Gdańsk, Poland.

Correspondence to: Cristiano Fava, MD, PhD, Department of Medicine, Division of Internal Medicine C, Piazzale LA Scuro 10, 37134 Verona, Italy; e-mail: cristiano.fava@med.lu.se


Drs Dorigoni and Dalle Vedove contributed equally to this work.

Funding/Support: The authors have reported to CHEST that no funding was received for this study.

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


Chest. 2014;145(4):762-771. doi:10.1378/chest.13-1115
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Background:  CPAP is considered the therapy of choice for OSA, but the extent to which it can reduce BP is still under debate. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify the effect size of the reduction of BP by CPAP therapy compared with other passive (sham CPAP, tablets of placebo drug, conservative measures) or active (oral appliance, antihypertensive drugs) treatments.

Methods:  We searched four different databases (MEDLINE, EMBASE, Web of Science, and the Cochrane Library) with specific search terms and selection criteria.

Results:  From 1,599 articles, we included 31 RCTs that compared CPAP with either passive or active treatment. In a random-effects meta-analysis vs passive treatment (29 RCTs, 1,820 subjects), we observed a mean ± SEM net difference in systolic BP of 2.6 ± 0.6 mm Hg and in diastolic BP of 2.0 ± 0.4 mm Hg, favoring treatment with CPAP (P < .001). Among studies using 24-h ambulatory BP monitoring that presented data on daytime and nighttime periods, the mean difference in systolic and diastolic BP was, respectively, 2.2 ± 0.7 and 1.9 ± 0.6 mm Hg during daytime and 3.8 ± 0.8 and 1.8 ± 0.6 mm Hg during nighttime. In meta-regression analysis, a higher baseline apnea/hypopnea index was associated with a greater mean net decrease in systolic BP (β ± SE, 0.08 ± 0.04). There was no evidence of publication bias, and heterogeneity was mild (I2, 34%-36%).

Conclusions:  Therapy with CPAP significantly reduces BP in patients with OSA but with a low effect size. Patients with frequent apneic episodes may benefit the most from CPAP.

Figures in this Article

OSA is characterized by periodic reductions or cessations of respiration during sleep. When frequent apneic episodes are accompanied by symptoms of daytime somnolence or unrefreshing sleep, they suggest the OSA syndrome.1 With the increasing prevalence of obesity, the primary risk factor for OSA, this syndrome is becoming an emerging health problem and has been recognized as a risk factor for cardiovascular diseases, especially hypertension, and death.1 Hypoxia leads to hyperactivity of the sympathetic nervous system; increased oxidative stress and endothelial dysfunction; and metabolic and hormonal changes, including activation of the renin-angiotensin-aldosterone system, which accompanies the elevation of BP in these patients.2

Counteracting apneic episodes and consequent hypoxia, CPAP is considered the gold standard therapy for OSA and has been associated, in observational studies, with a reduced mortality and morbidity in patients with moderate to severe OSA.1,2 Indeed, several studies and international guidelines have emphasized OSA as a potentially curable secondary form of hypertension.3,4 However, the magnitude of the effect of OSA on BP was modest in four meta-analyses published in 2006 and 2007.58 Another meta-analysis found similar results but did not pool studies that used 24-h ambulatory BP monitoring (ABPM) and conventional office BP measurements,9 whereas a more recent meta-analysis by Montesi et al10 referred especially to diurnal BP values from pooled estimates and subgroup analyses. Since the first meta-analyses were published, additional sound randomized controlled trials (RCTs) have been published with large sample sizes that at least double the number of subjects who can be pooled in a meta-analysis.1113 These studies attempted to respond to several unanswered issues regarding the efficacy of CPAP in subjects with metabolic syndrome or with masked or resistant forms of hypertension and to assess the efficacy of CPAP in decreasing the incidence of hypertension in normotensive people with OSA. Moreover, because of the lower number of included studies, the first meta-analyses of CPAP could not have had the power to perform a meaningful subgroup analysis to reveal which patients would most benefit from CPAP therapy. Furthermore, none of previous meta-analyses tried to grade the level of evidence by the quality of included trials.

Thus, the aim of the present study was to summarize in a systematic review and, where meaningful, in a meta-analysis old and new information about the efficacy of CPAP in decreasing BP in people with OSA with or without symptoms. In addition, we aimed to elucidate the elements linked to the severity of OSA and hypertension that could significantly influence the results.

An extended version of the Materials and Methods section is presented in e-Appendix 1. The systematic review and meta-analysis adhere to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement for reporting on systematic reviews.14 We conducted the meta-analysis in accordance with the general guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.14,15

Literature Search

We performed a systematic computerized search of MEDLINE, EMBASE, Web of Science, and the Cochrane Library (from inception to May 23, 2012) to identify all RCTs that assessed the effect of CPAP therapy on BP in patients with OSA with or without accompanying daytime somnolence or symptoms of unrefreshing sleep. The search algorithm combined the categories for “OSAS,” “CPAP therapy,” and “randomized controlled trials” by the Boolean operator AND.

Clinical Eligibility Criteria and Outcome

Studies were eligible for inclusion if they met the following criteria:

  • 1. The study populations were limited to adults aged > 18 years with a significant number of OSA episodes (> 5 apneas/hypopneas per hour of sleep).

  • 2. The diagnosis of OSA was obtained by polysomnography.

  • 3. BP measurements were available both before and after CPAP or other treatment, and treatments lasted at least 2 weeks.

  • 4. The studies were RCTs with a reasonable control group. The following comparator groups were considered:

    • a. Passive control group treatment: either sham CPAP (when CPAP is used at a lower pressure than is needed to maintain airway patency), oral tablets, or nonstructured conservative measures such as weight reduction and counseling or usual care.

    • b. Active control group treatment: (1) oral devices or (2) antihypertensive drugs.

    • When more than one passive control group was available in the same RCT, the primary analysis was conducted vs the one we considered the most appropriate control group according to this rank: (1) sham CPAP, (2) tablets, (3) conservative measures/usual care. It should be noted that in two studies, both active (oral devices) and passive (either conservative measures or oral tablets) were used vs CPAP in separate arms; thus, they were inserted in the analyses vs both passive and active treatment.16,17

  • 5. Patients with an ongoing illness other than OSA (eg, heart failure) were included. However, patients with central apnea syndromes (defined as nonobstructive apneas > 50% of total apneic episodes) were excluded.

Data Collection Process and Extracted Items

Two investigators independently retrieved and extracted data from the included studies (F. D. V., S. D.). Inconsistencies were resolved by discussion with C. F., and a final consensus was reached. For details about the extracted data, see e-Appendix 1.

Assessment of Quality

We assessed the methodological quality of the included studies with the scale by Jadad et al18 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.19 See e-Appendix 1 for more details.

Summary Effect Measures

We calculated mean net change in either systolic or diastolic BP from intervention with CPAP for each study. For both parallel and crossover trials, mean net change in BP was calculated as the difference (CPAP group − control group) of the change (baseline − follow-up) in mean values. Anticipating heterogeneity between the studies, we calculated the difference in means according to the DerSimonian and Laird20 random-effects model. The results are presented as mean ± SE. A two-sided P < .05 indicates a nominally significant overall association. For subgroup analyses, P < .01 was set for significance.

Details about methods used to assess heterogeneity21; bias across studies22,23; and how sensitivity analyses, meta-regression, and subgroup analyses were conducted are reported in e-Appendix 1. All statistical analyses were performed with Comprehensive Meta Analysis, version 2.2.064 (Biostat, Inc) software.

Study Selection

From a total of 1,599 reports in the initial search, we identified 31 studies1113,16,17,2449 that met the inclusion criteria and included these in the systematic review, with 29 being included in the main meta-analysis (n = 1,820) (Fig 1).12,13,16,17,2440,4249 The κ statistic indicated a strong agreement between the extracting investigators (0.89 ± 0.04). Characteristics of the individual studies are summarized in Table 1, and a detailed description is presented in e-Appendix 2. Only one study evaluated the effect of CPAP vs usual care on the incidence of hypertension (e-Appendix 2).11 Two RCTs examined CPAP vs an oral device,16,17 and one RCT compared CPAP to an antihypertensive agent.41 These last three studies, because of their distinctive features, were not included in the main analysis (CPAP vs passive treatment) but were analyzed separately (CPAP vs active treatment).

Figure Jump LinkFigure 1. Flow diagram illustrating the number of citations identified, retrieved, extracted, and included in the final analysis. RCT = randomized controlled trial.Grahic Jump Location
Table Graphic Jump Location
Table 1 —Characteristics of the Included RCTs on the Effect of CPAP Therapy vs Passive and Active Treatment on BP

ABPM = ambulatory BP monitoring; AHI = apnea/hypopnea index; co = crossover; ESS = Epworth Sleepiness Scale; GRADE = Grading of Recommendations Assessment, Development and Evaluation; HT = hypertension; incid = incidence; ns = not specified; OA = oral appliance; p = parallel; RCT = randomized controlled trial.

a 

Jadad quality scores range from 0 (very poor) to 5 (rigorous) points.

b 

GRADE scale scores range from ≤ 1 (very-low quality) to 4 (high quality).

c 

According to inclusion criteria.

d 

Median.

e 

Obtained by Norman et al.50

f 

Study not included in the main meta-analysis.

Impact of CPAP vs Passive Treatment in Mean Net BP Change

As illustrated in the forest plots (Figs 2, 3), the mean net decrease in systolic and diastolic BP was highly significant compared with a low to moderate effect size (systolic BP, 2.6 ± 0.6 mm Hg; diastolic BP, 2.0 ± 0.4 mm Hg), favoring treatment with CPAP (P < .001 for both). Among studies using ABPM and in which a separate analysis of daytime and nighttime values was available (n = 14), the mean difference in systolic and diastolic BP was, respectively, 2.2 ± 0.7 and 1.9 ± 0.6 mm Hg during daytime and 3.8 ± 0.8 and 1.8 ± 0.6 mm Hg during nighttime (P < .001) (e-Figs 1, 2); Q was 2.31 (1 degree of freedom, P = .13) for the difference between daytime and nighttime systolic BP and 0.019 (1 degree of freedom, P not significant) for the difference between daytime and nighttime diastolic BP. A single study evaluated the impact of CPAP in a population of normotensive subjects on future incidence of hypertension and observed a nonsignificant association with respect to usual care (not pooled in the main meta-analysis).11

Figure Jump LinkFigure 2. Effect of CPAP with respect to passive treatment on mean net change in systolic BP in 29 randomized controlled trials.Grahic Jump Location
Figure Jump LinkFigure 3. Effect of CPAP with respect to passive treatment on mean net change in diastolic BP in 29 randomized controlled trials.Grahic Jump Location
Impact of CPAP vs Active Treatment in Mean Net BP Change

When directly compared with an antihypertensive treatment (in a single study of valsartan 160 mg per day) in subjects with an apnea/hypopnea index (AHI) > 15/h and hypertension but naive of any treatment, CPAP was inferior to the drug in decreasing BP values (−7.00 mm Hg; 95% CI, 10.9-3.1 mm Hg; P > .001 between the groups in mean arterial pressure).41 In two trials, CPAP was also tested against an oral appliance and a passive control group arm with conflicting results (e-Appendix 2).16,17

Sensitivity Analysis

In a cumulative meta-analysis according to the time of publication (e-Fig 3), statistical significance was reached and maintained after nine to 10 studies were published with a slightly increasing effect size over time. In the cumulative meta-analysis according to sample size, no clear trend was apparent (e-Fig 4).

Meta-analysis in Subgroups and According to Quality Score

Results from meta-analyses in subgroups and according to the quality score are shown in Tables 2 and 3. In Table 3, only studies graded 3 to 4 on the basis of the GRADE system (ie, intermediate- to high-quality studies as indicated in Table 1) were analyzed. e-Appendix 1 provides a complete description on which elements of the single RCTs were evaluated for the grading. The main finding is that in studies of subjects with an average AHI < 30/h and an average Epworth Sleepiness Scale score < 10, the difference in both systolic and diastolic BP was not statistically significant.

Table Graphic Jump Location
Table 2 —WMD in Systolic and Diastolic BP in Subjects Treated With CPAP vs Passive Therapy in Specific Subgroups

AHT = antihypertensive; na = not applicable; ns = not significant; UC = usual care; WMD = weighted mean difference. See Table 1 legend for expansion of other abbreviations.

a 

Having a diagnosis of HT was a necessary criterion to be included in the trial.

b 

Either systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg or use of AHT drug.

c 

P < .01 for the comparison between studies with low to moderate vs severe OSA.

Table Graphic Jump Location
Table 3 —WMD in Systolic and Diastolic BP in Subjects Treated With CPAP vs Passive Therapy When Only RCTs With Intermediate and High Quality (GRADE) Are Included

See Table 1 and 2 legends for expansion of abbreviations.

a 

Having a diagnosis of HT was a necessary criterion to be included in the trial.

b 

Either systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg or use of AHT drug.

c 

P < .01 for the comparison between studies with average age ≥ 50 y vs studies with average age < 50 y.

Metaregression

In a metaregression, studies showed that a greater AHI is associated with a greater mean net decrease in systolic BP (β ± SE, 0.08 ± 0.04, P < .01) (e-Fig 5). This suggests that for each increase in AHI of 10/h from baseline, a systolic BP decrease of approximately 1 mm Hg could be expected in subjects treated by CPAP compared with passive treatment.

Publication Bias

A funnel plot of the studies included in the main meta-analysis is shown in e-Figure 6, with no significant asymmetry detectable. See e-Appendix 2 for details.

The results of the present meta-analysis indicate that CPAP is associated with a significant reduction in both systolic and diastolic BP with respect to passive treatment with a low to moderate effect size. Because most of the included primary studies showed either a low or very-low quality, these results should be regarded with caution. However, when analyzing only the intermediate- to high-quality studies, the results are strengthened, and there is a tendency toward a more marked BP lowering effect of CPAP.

In any case, the effect size of CPAP on BP is at least one-half the magnitude of most of the commonly used antihypertensive drugs when examined by meta-analytic methods.51 Thus, even the less-than-overwhelming difference of 2.6/2.0 mm Hg for systolic/diastolic BP could be clinically meaningful, as was also demonstrated by observational data on stroke and mortality in subjects treated with CPAP.1,2 However, most of the CPAP trials included in the present review lasted only a few weeks, and the results about the maintenance of BP in the long run are difficult to extrapolate.1,2

The effect size appears to be greater at night than during the day when measured by ABPM. Moreover, this result was always significant when subjects with hypertension were not excluded from the primary studies, especially when they were not receiving antihypertensive therapy.

The present meta-regression and subgroup analyses reveal that the decrease in BP is significant in trials where OSA episodes are more frequent and somnolence more marked, suggesting that the severity of the OSA syndrome per se is associated with a better BP response to CPAP. Additionally, the effect of adherence to CPAP could be important (not confirmed when only intermediate- to high-quality studies where analyzed).

International guidelines emphasize the role of the OSA syndrome as a secondary and potentially curable form of hypertension3,4; however, according to the present data, the treatment of OSA by CPAP can rarely normalize BP by itself. A single study that specifically evaluated the effect of CPAP in subjects with resistant hypertension found that the CPAP in combination with existing antihypertensive therapy was superior to conventional treatment only in subjects with ABPM-confirmed resistant hypertension and not in the entire cohort.36 Moreover, the only head-to-head study comparing CPAP with an antihypertensive agent (valsartan) revealed a marked difference in BP decrease, favoring the drug.42 Thus, more studies are needed to understand which kind of patient with hypertension may benefit more from CPAP therapy in addition or as an alternative to common antihypertensive medications.52

To our knowledge, six meta-analyses (four published between 2006 and 2007 and two more recently)59 analyzed the BP response to CPAP; the present results go in the same direction as suggested by the cumulative analysis according to time. We included additional articles in the present study that at least double the number of subjects who could be pooled in the meta-analysis and were careful to exclude studies where an overlap of subjects existed, as confirmed by the corresponding authors.50,5355 Another strength of the present meta-analysis is the in-depth sensitivity analysis, including subgroup analyses and metaregressions. In contrast with other meta-analyses, we decided to exclude studies with a follow-up time of < 2 weeks8,56 because, in our opinion, this length is the minimum amount of time required to achieve a stable effect in BP by CPAP. We also decided not to include trials where BP information could not be retrieved from the published studies (ie, provided directly from the authors but not included in the published material) or where not the initiation of the CPAP but its suspension was tested. In particular, at variance with Montesi et al,10 we chose to take 24-h BP when available and not just the daytime BP in the analysis. This choice was motivated by the fact that CPAP effects on BP could be relevant mostly during the night when OSA occurs and CPAP is used, and 24-h BP is more reproducible with respect to partitioned daytime and nighttime measures57; moreover, different definitions of the daytime and nighttime periods were used in different studies included in the meta-analysis, potentially increasing heterogeneity. All these differences could explain some discrepancies in the subgroup analyses. Furthermore, a specific distinctive trait of the present meta-analysis is its attention to the quality of the analyzed studies.

The present results appear robust, and no single study seems to be primarily responsible for the observed differences between the treatment arms. It is important to note that 23 of the 29 studies indicated a positive trend (either systolic or diastolic) in BP response to CPAP, and for nine studies, the effect was statistically significant when analyzed as the δ difference with respect to baseline. The funnel plot is fairly symmetrical, and no publication or small study bias seems plausible. Sensitivity analyses found no significant changes and reversal results; thus, we consider the results of the present meta-analysis to be stable and reliable.

Only two studies evaluated the effect of oral devices compared with CPAP. No firm conclusion can be drawn from these data.

This systematic review and meta-analysis have several limitations. First, although we applied a highly sensitive search strategy for the retrieval of potentially eligible studies, we cannot rule out that some studies might have been overlooked. Second, we excluded results from RCTs existing only as abstracts. Only 14 of the total 29 studies used sham CPAP as a placebo, which we consider the ideal comparator in these types of studies. The Jadad and GRADE scores indicate that most of the included trials are not considered high quality, thus influencing the overall quality of the results. However, the subgroup analyses performed specifically in the intermediate- and high-quality studies are substantially similar in effect size and significance to the main meta-analysis.

In conclusion, this meta-analysis confirms that CPAP can significantly lower BP in patients with OSA but with a low effect size. CPAP has proven to be efficacious in treating symptoms, such as daytime somnolence, especially in patients with frequent apneic episodes. Observational studies have suggested that CPAP might also decrease cardiovascular outcomes in patients with OSA.1,2 Because of its beneficial effect on BP, even if low, CPAP might be prescribed as an adjunct to antihypertensive drugs to all patients with hypertension and OSA, especially when apneic/hypopneic episodes are frequent and somnolence severe, with the aim also of improving BP. The small effect size, inferior to that of a common antihypertensive drug, should alert physicians to the fact that in most patients, CPAP is not the only treatment that should be prescribed to normalize BP. Furthermore, even if no important side effects are associated with the use of CPAP, compliance with the device is problematic.58 Additional high-quality studies are needed to assess the capacity of CPAP to prevent hypertension incidence or its worsening over time, to normalize BP in patients with resistant or refractory forms of hypertension, and to quantify its effect compared with oral devices or antihypertensive drugs.

Note added in proof: An earlier Online First version of this article cited and used data from “Sharma SK, Agrawal S, Damodaran D, et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med. 2011;365(24):2277-2286.” Because that article was retracted October 31, 2013 (“Retraction: CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med. 2011;365:2277-2286. N Engl J Med. 2013;369:1770”), the authors reworked their analysis of the data in this version of the article, eliminating material from the retracted article. Because the results and conclusions did not change after elimination of the Sharma article, the revised manuscript was accepted for publication.

Author contributions: Dr Fava had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Fava: contributed to the study design, literature search, data extraction, statistical analysis, and drafting of the manuscript.

Dr Dorigoni: contributed to the study design, retrieval of studies, data extraction from the original articles, statistical analysis, and drafting of the manuscript.

Dr Dalle Vedove: contributed to the study design, retrieval of studies, data extraction from the original articles, statistical analysis, and drafting of the manuscript.

Dr Danese: contributed to the study coordination and drafting of the manuscript.

Dr Montagnana: contributed to the study coordination and drafting of the manuscript.

Dr Guidi: contributed to the study coordination and drafting of the manuscript.

Dr Narkiewicz: contributed to the study coordination and drafting of the manuscript.

Dr Minuz: contributed to the study coordination and drafting of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The authors thank all the authors of the primary studies who promptly answered questions.

Additional information: The e-Appendixes and e-Figures can be found in the “Supplemental Materials” area of the online article.

ABPM

ambulatory BP monitoring

AHI

apnea/hypopnea index

GRADE

Grading of Recommendations Assessment, Development and Evaluation

RCT

randomized controlled trial

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Campos-Rodriguez F, Grilo-Reina A, Perez-Ronchel J, et al. Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: a placebo-controlled trial. Chest. 2006;129(6):1459-1467. [CrossRef]
 
Egea CJ, Aizpuru F, Pinto JA, et al; Spanish Group of Sleep Breathing Disorders. Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study. Sleep Med. 2008;9(6):660-666. [CrossRef]
 
Hui DS, To KW, Ko FW, et al. Nasal CPAP reduces systemic blood pressure in patients with obstructive sleep apnoea and mild sleepiness. Thorax. 2006;61(12):1083-1090. [CrossRef]
 
Ip MS, Tse HF, Lam B, Tsang KW, Lam WK. Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med. 2004;169(3):348-353. [CrossRef]
 
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]
 
Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med. 2004;169(3):361-366. [CrossRef]
 
Mills PJ, Kennedy BP, Loredo JS, Dimsdale JE, Ziegler MG. Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea. J Appl Physiol. 2006;100(1):343-348. [CrossRef]
 
Monasterio C, Vidal S, Duran J, et al. Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med. 2001;164(6):939-943. [CrossRef]
 
Nguyen PK, Katikireddy CK, McConnell MV, Kushida C, Yang PC. Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea. J Cardiovasc Magn Reson. 2010;12:50. [CrossRef]
 
Noda A, Nakata S, Koike Y, et al. Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome. Hypertens Res. 2007;30(8):669-676. [CrossRef]
 
Pépin JL, Tamisier R, Barone-Rochette G, Launois SH, Lévy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010;182(7):954-960. [CrossRef]
 
Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002;359(9302):204-210. [CrossRef]
 
Barnes M, Houston D, Worsnop CJ, et al. A randomized controlled trial of continuous positive airway pressure in mild obstructive sleep apnea. Am J Respir Crit Care Med. 2002;165(6):773-780. [CrossRef]
 
Comondore VR, Cheema R, Fox J, et al. The impact of CPAP on cardiovascular biomarkers in minimally symptomatic patients with obstructive sleep apnea: a pilot feasibility randomized crossover trial. Lung. 2009;187(1):17-22. [CrossRef]
 
Coughlin SR, Mawdsley L, Mugarza JA, Wilding JP, Calverley PM. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J. 2007;29(4):720-727. [CrossRef]
 
Cross MD, Mills NL, Al-Abri M, et al. Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial. Thorax. 2008;63(7):578-583. [CrossRef]
 
Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med. 2001;163(2):344-348. [CrossRef]
 
Robinson GV, Smith DM, Langford BA, Davies RJ, Stradling JR. Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients. Eur Respir J. 2006;27(6):1229-1235. [CrossRef]
 
Engleman HM, Gough K, Martin SE, Kingshott RN, Padfield PL, Douglas NJ. Ambulatory blood pressure on and off continuous positive airway pressure therapy for the sleep apnea/hypopnea syndrome: effects in “non-dippers”. Sleep. 1996;19(5):378-381.
 
Norman D, Loredo JS, Nelesen RA, et al. Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension. 2006;47(5):840-845. [CrossRef]
 
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]
 
Zanchetti A. What should be learnt about the management of obstructive sleep apnea in hypertension? J Hypertens. 2012;30(4):669-670. [CrossRef]
 
Arias MA, García-Río F, Alonso-Fernández A, Martínez I, Villamor J. Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study. Eur Heart J. 2006;27(9):1106-1113. [CrossRef]
 
Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med. 2003;348(13):1233-1241. [CrossRef]
 
Usui K, Bradley TD, Spaak J, et al. Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure. J Am Coll Cardiol. 2005;45(12):2008-2011. [CrossRef]
 
Dimsdale JE, Loredo JS, Profant J. Effect of continuous positive airway pressure on blood pressure: a placebo trial. Hypertension. 2000;35(1):144-147. [CrossRef]
 
Palatini P, Mormino P, Canali C, et al. Factors affecting ambulatory blood pressure reproducibility. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study. Hypertension. 1994;23(2):211-216. [CrossRef]
 
Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev. 2011;15(6):343-356. [CrossRef]
 

Figures

Figure Jump LinkFigure 1. Flow diagram illustrating the number of citations identified, retrieved, extracted, and included in the final analysis. RCT = randomized controlled trial.Grahic Jump Location
Figure Jump LinkFigure 2. Effect of CPAP with respect to passive treatment on mean net change in systolic BP in 29 randomized controlled trials.Grahic Jump Location
Figure Jump LinkFigure 3. Effect of CPAP with respect to passive treatment on mean net change in diastolic BP in 29 randomized controlled trials.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Characteristics of the Included RCTs on the Effect of CPAP Therapy vs Passive and Active Treatment on BP

ABPM = ambulatory BP monitoring; AHI = apnea/hypopnea index; co = crossover; ESS = Epworth Sleepiness Scale; GRADE = Grading of Recommendations Assessment, Development and Evaluation; HT = hypertension; incid = incidence; ns = not specified; OA = oral appliance; p = parallel; RCT = randomized controlled trial.

a 

Jadad quality scores range from 0 (very poor) to 5 (rigorous) points.

b 

GRADE scale scores range from ≤ 1 (very-low quality) to 4 (high quality).

c 

According to inclusion criteria.

d 

Median.

e 

Obtained by Norman et al.50

f 

Study not included in the main meta-analysis.

Table Graphic Jump Location
Table 2 —WMD in Systolic and Diastolic BP in Subjects Treated With CPAP vs Passive Therapy in Specific Subgroups

AHT = antihypertensive; na = not applicable; ns = not significant; UC = usual care; WMD = weighted mean difference. See Table 1 legend for expansion of other abbreviations.

a 

Having a diagnosis of HT was a necessary criterion to be included in the trial.

b 

Either systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg or use of AHT drug.

c 

P < .01 for the comparison between studies with low to moderate vs severe OSA.

Table Graphic Jump Location
Table 3 —WMD in Systolic and Diastolic BP in Subjects Treated With CPAP vs Passive Therapy When Only RCTs With Intermediate and High Quality (GRADE) Are Included

See Table 1 and 2 legends for expansion of abbreviations.

a 

Having a diagnosis of HT was a necessary criterion to be included in the trial.

b 

Either systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg or use of AHT drug.

c 

P < .01 for the comparison between studies with average age ≥ 50 y vs studies with average age < 50 y.

References

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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 trial. JAMA. 2012;307(20):2161-2168. [CrossRef]
 
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Barnes M, McEvoy RD, Banks S, et al. Efficacy of positive airway pressure and oral appliance in mild to moderate obstructive sleep apnea. Am J Respir Crit Care Med. 2004;170(6):656-664. [CrossRef]
 
Lam B, Sam K, Mok WY, et al. Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea. Thorax. 2007;62(4):354-359. [CrossRef]
 
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DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188. [CrossRef]
 
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-1558. [CrossRef]
 
Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol. 2001;54(10):1046-1055. [CrossRef]
 
Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455-463. [CrossRef]
 
Barbé F, Mayoralas LR, Duran J, et al. Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness. A randomized, controlled trial. Ann Intern Med. 2001;134(11):1015-1023. [CrossRef]
 
Takaesu Y, Inoue Y, Komada Y, Kagimura T, Iimori M. Effects of nasal continuous positive airway pressure on panic disorder comorbid with obstructive sleep apnea syndrome. Sleep Med. 2012;13(2):156-160. [CrossRef]
 
Ruttanaumpawan P, Gilman MP, Usui K, Floras JS, Bradley TD. Sustained effect of continuous positive airway pressure on baroreflex sensitivity in congestive heart failure patients with obstructive sleep apnea. J Hypertens. 2008;26(6):1163-1168. [CrossRef]
 
Arias MA, García-Río F, Alonso-Fernández A, Mediano O, Martínez I, Villamor J. Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men. Circulation. 2005;112(3):375-383. [CrossRef]
 
Barbé F, Durán-Cantolla J, Capote F, et al; Spanish Sleep and Breathing Group. Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010;181(7):718-726. [CrossRef]
 
Becker HF, Jerrentrup A, Ploch T, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation. 2003;107(1):68-73. [CrossRef]
 
Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2007;176(7):706-712. [CrossRef]
 
Campos-Rodriguez F, Grilo-Reina A, Perez-Ronchel J, et al. Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: a placebo-controlled trial. Chest. 2006;129(6):1459-1467. [CrossRef]
 
Egea CJ, Aizpuru F, Pinto JA, et al; Spanish Group of Sleep Breathing Disorders. Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study. Sleep Med. 2008;9(6):660-666. [CrossRef]
 
Hui DS, To KW, Ko FW, et al. Nasal CPAP reduces systemic blood pressure in patients with obstructive sleep apnoea and mild sleepiness. Thorax. 2006;61(12):1083-1090. [CrossRef]
 
Ip MS, Tse HF, Lam B, Tsang KW, Lam WK. Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med. 2004;169(3):348-353. [CrossRef]
 
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]
 
Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med. 2004;169(3):361-366. [CrossRef]
 
Mills PJ, Kennedy BP, Loredo JS, Dimsdale JE, Ziegler MG. Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea. J Appl Physiol. 2006;100(1):343-348. [CrossRef]
 
Monasterio C, Vidal S, Duran J, et al. Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med. 2001;164(6):939-943. [CrossRef]
 
Nguyen PK, Katikireddy CK, McConnell MV, Kushida C, Yang PC. Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea. J Cardiovasc Magn Reson. 2010;12:50. [CrossRef]
 
Noda A, Nakata S, Koike Y, et al. Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome. Hypertens Res. 2007;30(8):669-676. [CrossRef]
 
Pépin JL, Tamisier R, Barone-Rochette G, Launois SH, Lévy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010;182(7):954-960. [CrossRef]
 
Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002;359(9302):204-210. [CrossRef]
 
Barnes M, Houston D, Worsnop CJ, et al. A randomized controlled trial of continuous positive airway pressure in mild obstructive sleep apnea. Am J Respir Crit Care Med. 2002;165(6):773-780. [CrossRef]
 
Comondore VR, Cheema R, Fox J, et al. The impact of CPAP on cardiovascular biomarkers in minimally symptomatic patients with obstructive sleep apnea: a pilot feasibility randomized crossover trial. Lung. 2009;187(1):17-22. [CrossRef]
 
Coughlin SR, Mawdsley L, Mugarza JA, Wilding JP, Calverley PM. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J. 2007;29(4):720-727. [CrossRef]
 
Cross MD, Mills NL, Al-Abri M, et al. Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial. Thorax. 2008;63(7):578-583. [CrossRef]
 
Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med. 2001;163(2):344-348. [CrossRef]
 
Robinson GV, Smith DM, Langford BA, Davies RJ, Stradling JR. Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients. Eur Respir J. 2006;27(6):1229-1235. [CrossRef]
 
Engleman HM, Gough K, Martin SE, Kingshott RN, Padfield PL, Douglas NJ. Ambulatory blood pressure on and off continuous positive airway pressure therapy for the sleep apnea/hypopnea syndrome: effects in “non-dippers”. Sleep. 1996;19(5):378-381.
 
Norman D, Loredo JS, Nelesen RA, et al. Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension. 2006;47(5):840-845. [CrossRef]
 
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]
 
Zanchetti A. What should be learnt about the management of obstructive sleep apnea in hypertension? J Hypertens. 2012;30(4):669-670. [CrossRef]
 
Arias MA, García-Río F, Alonso-Fernández A, Martínez I, Villamor J. Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study. Eur Heart J. 2006;27(9):1106-1113. [CrossRef]
 
Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med. 2003;348(13):1233-1241. [CrossRef]
 
Usui K, Bradley TD, Spaak J, et al. Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure. J Am Coll Cardiol. 2005;45(12):2008-2011. [CrossRef]
 
Dimsdale JE, Loredo JS, Profant J. Effect of continuous positive airway pressure on blood pressure: a placebo trial. Hypertension. 2000;35(1):144-147. [CrossRef]
 
Palatini P, Mormino P, Canali C, et al. Factors affecting ambulatory blood pressure reproducibility. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study. Hypertension. 1994;23(2):211-216. [CrossRef]
 
Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev. 2011;15(6):343-356. [CrossRef]
 
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