Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a systematic review and meta-analysis of six randomized controlled trials

Qiang Lei; Yunhui Lv; Kai Li; Lei Ma; Guodong Du; Yan Xiang; Xuqing Li

doi:10.1590/S1806-37562016000000190

. 2017 Sep-Oct;43(5):373–379. doi: 10.1590/S1806-37562016000000190

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Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a systematic review and meta-analysis of six randomized controlled trials

Qiang Lei ¹, Yunhui Lv ², Kai Li ¹, Lei Ma ¹, Guodong Du ¹, Yan Xiang ¹, Xuqing Li ¹

PMCID: PMC5790661 PMID: 28767770

ABSTRACT

Objective:

To evaluate systematically the effects of continuous positive airway pressure (CPAP) on blood pressure in patients with resistant hypertension and obstructive sleep apnea (OSA).

Methods:

The Cochrane Library, PubMed, ScienceDirect, and the Web of Science were searched for studies investigating the effects of CPAP on blood pressure in patients with resistant hypertension and OSA. The selected studies underwent quality assessment and meta-analysis, as well as being tested for heterogeneity.

Results:

Six randomized controlled trials were included in the meta-analysis. The pooled estimates of the changes in mean systolic blood pressure and mean diastolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring) were −5.40 mmHg (95% CI: −9.17 to −1.64; p = 0.001; I² = 74%) and −3.86 mmHg (95% CI: −6.41 to −1.30; p = 0.00001; I² = 79%), respectively.

Conclusions:

CPAP therapy can significantly reduce blood pressure in patients with resistant hypertension and OSA.

Keywords: Continuous positive airway pressure; Sleep apnea, obstructive; Hypertension; Meta-analysis

INTRODUCTION

Obstructive sleep apnea (OSA) is a chronic disease characterized by recurrent upper airway collapse during sleep leading to intermittent hypoxemia and sleep disruption.¹ It has been estimated that 24% of all males in the 30- to 60-year age bracket and 9% of all females in the same age bracket have OSA.² Several studies have shown that OSA is a risk factor for cardiovascular diseases, including hypertension, heart failure, atrial fibrillation, and coronary artery disease.³^-⁶ In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure identified OSA as an important identifiable cause of hypertension.⁷

Resistant hypertension has been defined as blood pressure that remains above goal despite concomitant use of at least three classes of antihypertensive medications. Individuals with controlled blood pressure using at least four classes of antihypertensive medications are also considered to have resistant hypertension. International guidelines now recognize OSA as one of the most common risk factors for resistant hypertension.⁸ Gonçalves et al. found that the risk of resistant hypertension is nearly five times higher in patients with OSA.⁹ Similarly, Calhoun et al. found that 63% of all patients presenting to a clinic for resistant hypertension were at high risk for OSA on the basis of their responses to the Berlin Questionnaire.¹⁰ In a prospective observational study, Lavie et al. found that the prevalence and severity of hypertension increased as the apnea-hypopnea index (AHI) increased.¹¹

Continuous positive airway pressure (CPAP) is the most widely accepted form of therapy for OSA and remains the gold standard for treatment. Although there is a significant amount of data on the effect of CPAP on hypertension, data on resistant hypertension are limited.¹² Therefore, we performed a meta-analysis to evaluate the efficacy of CPAP in patients with OSA and resistant hypertension.

METHODS

Inclusion criteria

We sought to evaluate systematically randomized clinical trials of the effects that CPAP therapy has on the blood pressure of patients with OSA and resistant hypertension. We included studies including patients over 18 years of age diagnosed with OSA and resistant hypertension, the latter having been diagnosed by ambulatory blood pressure monitoring (ABPM). Interventions included a control group receiving conventional antihypertensive therapy or placebo and a treatment group receiving CPAP therapy, treatment group patients having completed the treatment. Endpoints included mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) as assessed by 24-h ABPM.

Exclusion criteria

The exclusion criteria were as follows: studies in which the sample size was < 10; nonrandomized controlled studies; early studies (i.e., studies published before 2010); repeated trials; studies with no control group; studies in which patients were used as their own controls; studies not providing the full original data; studies whose full-text articles were unavailable; and studies whose authors we were unable to contact.

Literature retrieval

We searched the following databases: the Cochrane Library; ScienceDirect; PubMed; and the Web of Science. We used the following search terms: “continuous positive airway pressure”; “CPAP”; “obstructive sleep apnea”; “OSA”; “apnea-hypopnea index”; “AHI”; “resistant hypertension”; “RH”; “refractory hypertension”; “resistant high blood pressure”; “randomized controlled trial”; and “RCT”. The search was limited to original research articles published between January of 2010 and January of 2016. In addition, the ResearchGate social networking website was used in order to contact researchers for additional relevant studies.

Literature screening

In order to select the articles for inclusion, two researchers independently applied the inclusion and exclusion criteria to all of the studies selected by the aforementioned method. In cases of disagreement, a third member of the research team was consulted. Relevant data were extracted and cross-checked. In cases in which important data were missing from the selected studies, the authors were contacted by email or phone.

Quality assessment

The quality of the selected studies was assessed by the Jadad score, which ranges from 0 to 5. Articles with a Jadad score of more than 3 were included in our meta-analysis. Two researchers independently assessed the quality of the studies by applying the Jadad criteria. In cases of disagreement, a third member of the research team was consulted. All relevant data were subsequently extracted.

Statistical analysis

Meta-analysis

Meta-analysis was performed with the Review Manager (RevMan) software, version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark). The I² statistics was used in order to assess heterogeneity (clinical heterogeneity and statistical heterogeneity), the level of significance being set at p < 0.1. For studies showing clinical homogeneity and statistical homogeneity (i.e., p > 0.1 and I² ≤ 50%), a fixed effect model was used; for those showing clinical homogeneity and statistical heterogeneity (i.e., p < 0.1 and I² > 50%), a random effects model was used. In the presence of significant clinical heterogeneity, only descriptive statistics were used. Continuous variables included weighted mean difference and standardized mean difference, the effects being expressed as 95% CIs. The level of significance was set at p < 0.05. Funnel plots were used in order to determine whether there was significant publication bias.

Heterogeneity test

Heterogeneity was analyzed by the method of subgroup analysis, which consists of dividing the data into smaller units and comparing the subgroups. On the basis of the AHI, body mass index (BMI), SBP, DBP, total duration of CPAP treatment, mean daily duration of CPAP treatment, Epworth Sleepiness Scale (ESS) score, and geographic location of the institutions, we divided the study sample into eight subgroups in order to analyze potential factors leading to heterogeneity.

Sensitivity analysis

Sensitivity analysis was performed by excluding studies that might affect the analysis and by using different correlation coefficients to observe the stability of the results.

RESULTS

A total of 423 articles were initially retrieved, and a total of 308 remained after duplicate entries were removed. Of the remaining articles, 6¹³^-¹⁸ were included in our meta-analysis (Figure 1). The 6 included articles were randomized controlled trials (RCTs) and comprised a total of 479 patients. Of those, 245 had been control group patients and 234 had been treatment group patients. The basic characteristics of the 6 RCTs included in the meta-analysis are shown in Table 1. Table 2 shows the baseline AHI, ESS score, BMI, SBP (as assessed by 24-h ABPM), and DBP (as assessed by 24-h ABPM) in the 6 RCTs included in our meta-analysis.

Table 1. Basic characteristics of the six studies included in the meta-analysis.

Author	Year	Number of patients	Male gender, %	Mean age ± SD, years	CPAP compliance, h	Type of study	Treatment duration	Method of BP measurement	Country	Jadad score
Muxfeldt et al.⁽¹⁷⁾	2015	46 (CPAP)	37.9	60.8 ± 8.0	4.8	RCT	6 months	ABPM	Brazil	3
		60 (Control)
de Oliveira et al.⁽¹³⁾	2014	24 (CPAP)	58	59.5 ± 7.3	≥ 4	RCT	8 weeks	ABPM	Brazil	4
		23 (Control)
Lloberes et al.⁽¹⁴⁾	2014	27 (CPAP)	72.4	58.7 ± 9.5	5.7 ± 1.5	RCT	3 months	ABPM	Spain	3
		29 (Control)
Pedrosa et al.⁽¹⁸⁾	2013	19 (CPAP)	74	57 ± 2^a	6.01 ± 0.20	RCT	6 months	ABPM	Brazil	3
		16 (Control)
Martínez-García et al.⁽¹⁶⁾	2013	98 (CPAP)	72.4	56.0 ± 9.5	5 ± 1.9	RCT	3 months	ABPM	Spain	3
		96 (Control)
Lozano et al.⁽¹⁵⁾	2010	20 (CPAP)	75.9	59.2 ± 8.7	5.6 ± 1.5	RCT	3 months	ABPM	Spain	3
		21 (Control)

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CPAP: continuous positive airway pressure; BP: blood pressure; RCT: randomized controlled trial; and ABPM: ambulatory blood pressure monitoring. ^aData expressed as mean ± SE.

Table 2. Baseline apnea-hypopnea index, Epworth Sleepiness Scale score, body mass index, systolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring), and diastolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring).^a.

Study	AHI	ESS score	BMI	SBP	DBP
Muxfeldt et al.⁽¹⁷⁾	41 (21)	11 (6)	33.4 (5.3)	129 (16)	75 (12)
de Oliveira et al.⁽¹³⁾	20 (18-31)^b	10 (6-15)^b	29.8 ± 4.4^c	148 ± 17	88 ± 13
Lloberes et al.⁽¹⁴⁾	50.1 ± 20.6	6.76 ± 3.7	31.4 (4.9)	139.2 ± 11.5	80.8 ± 10.8
Pedrosa et al.⁽¹⁸⁾	29 (24-48)^b	10 ± 1c	32 (28-39)^b	162 ± 4	97 ± 2
Martínez-García et al.⁽¹⁶⁾	40.4 (18.9)	9.1 (3.7)	34.1 (5.4)	144.2 (12.5)	83.0 (10.5)
Lozano et al.⁽¹⁵⁾	52.67 ± 21.5	6.14 ± 3.30	30.8 ± 5.0	129 (16)	75 (12)

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AHI: apnea-hypopnea index; ESS: Epworth Sleepiness Scale; BMI: body mass index; SBP: systolic blood pressure; and DBP: diastolic blood pressure. ^aValues expressed as n (%) or mean ± SD, except where otherwise indicated. ^bData expressed as median (range). ^cData expressed as mean ± SE.

All 6 RCTs examined the effects of CPAP treatment on mean SBP (as assessed by 24-h ABPM) in patients with OSA and resistant hypertension. The pooled estimate of the change in mean SBP was −5.40 mmHg (95% CI: −9.17 to −1.64; p = 0.005; I² = 74%). Five of the 6 RCTs examined the effects of CPAP treatment on mean DBP (as assessed by 24-h ABPM) in patients with OSA and resistant hypertension. The pooled estimate of the change in mean DBP was −3.86 mmHg (95% CI: −6.41 to −1.30; p = 0.003; I² = 82%). There was significant heterogeneity among the studies, and a random effects model was therefore used in order to analyze the results (Figures 2 and 3).

Five studies examined the effects of CPAP treatment on mean daytime and nocturnal SBP in patients with OSA and resistant hypertension. The pooled estimates of the changes in mean daytime SBP and mean nocturnal SBP were −4.11 mmHg (95% CI: −9.06 to −0.84; p = 0.10; I² = 85%) and −3.17 mmHg (95% CI: −6.25 to −0.09; p = 0.04; I² = 90%), respectively (Table 3). The pooled estimates of the changes in mean daytime DBP and mean nocturnal DBP were −2.11 mmHg (95% CI: −4.16 to −0.05; p = 0.04; I² = 0%) and −1.55 mmHg (95% CI: −2.81 to −0.29; p = 0.02; I² = 0%), respectively (Table 4). Because there was significant heterogeneity among the studies regarding mean daytime SBP/DBP, a random effects model was used in order to analyze the results. Because there was no significant heterogeneity among the studies regarding mean nocturnal SBP/DBP, a fixed effect model was used in order to analyze the results.

Table 3. Subgroup analysis of mean changes in systolic blood pressure as assessed by 24-h ambulatory blood pressure monitoring.

Subgroup		SBP (as assessed by 24-h ABPM)
Subgroup		No. of studies	Mean net change	95% CI	p; I² (%)
AHI	≥ 30	4	−3.07	−5.50 to −0.65	p = 0.01; I² = 22%
	> 30	2	−9.58	−11.70 to −7.46	p < 0.00001; I² = 0%
Baseline SBP/DBP, mmHg	> 145/85	2	−9.58	−11.70 to −7.46	p < 0.00001; I² = 0%
	< 145/85	4	−3.07	−5.50 to −0.65	p = 0.01; I² = 22%
BMI, kg/m²	≥ 32	3	−6.81	−8.55 to −5.08	p < 0.00001; I² = 89%
	< 32	3	−6.47	−10.53 to −2.42	p = 0.002; I² = 0%
CPAP compliance, h	> 5	4	−7.47	−9.18 to −5.76	p < 0.00001; I² = 70%
	≤ 5	1	1.20	−4.12 to 6.52	p = 0.66; I² = 0%
Treatment duration, months	> 3	2	−8.03	−10.06 to −6.00	p < 0.00001; I² = 93%
	≤ 3	4	−4.71	−7.29 to −2.12	p = 0.0004; I² = 0%
ESS score	≥ 10	3	−5.89	−13.33 to 1.55	p = 0.12; I² = 85%
	< 10	3	−4.19	−6.92 to −1.47	p = 0.003; I² = 0%
Location	Europe	3	−4.19	-6.92 to −1.47	p = 0.003; I² = 0%
	South America	3	−8.10	−10.07 to −6.13	p < 0.00001; I² = 85%
Study sample size	≥ 25	3	−0.20	−0.41 to −0.01	p = 0.06; I² = 36%
	< 25	3	−0.96	−1.36 to −0.57	p < 0.00001; I² = 88%

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SBP: systolic blood pressure; DBP: diastolic blood pressure; ABPM: ambulatory blood pressure monitoring; AHI: apnea-hypopnea index; BMI: body mass index; CPAP: continuous positive airway pressure; and ESS: Epworth Sleepiness Scale.

Table 4. Subgroup analysis of mean changes in diastolic blood pressure as assessed by 24-h ambulatory blood pressure monitoring.

Subgroup		DBP (as assessed by 24-h ABPM)
Subgroup		No. of studies	Mean net change	95% CI	p; I² (%)
AHI	≥ 30	4	−2.76	−4.06 to −1.46	p < 0.0001; I² = 64%
	< 30	1	−6.60	−8.17 to −5.03	p < 0.00001; I² = 0%
Baseline SBP/DBP, mmHg	> 145/85	1	−6.60	−8.17 to −5.03	p < 0.00001; I² = 0%
	< 145/85	4	−2.76	−4.06 to −1.46	p < 0.0001; I² = 64%
BMI, kg/m²	≥ 32	3	−4.24	−5.32 to −3.15	p < 0.00001; I² = 91%
	< 32	2	−4.79	−7.39 to −2.18	p = 0.0003; I² = 0%
CPAP compliance, h	> 5	4	−5.18	−6.28 to −4.09	p < 0.00001; I² = 55%
	≤ 5	1	0.30	−2.23 to 2.83	p = 0.82; I² = 0%
Treatment duration, months	> 3	2	−4.67	−6.00 to −3.33	p < 0.00001; I² = 95%
	≤ 3	3	−3.87	−5.39 to −3.35	p < 0.00001; I² = 0%
ESS score	≥ 10	2	−4.67	−6.00 to −3.33	p < 0.00001; I² = 95%
	< 10	3	−3.87	−5.39 to −2.35	p < 0.00001; I² = 0%
Location	Europe	3	−3.87	−5.39 to −2.35.	p < 0.00001; I² = 0%
	South America	2	−4.67	−6.00 to −3.33	p < 0.00001; I² = 95%
Study sample size	≥ 25	3	−2.53	−3.89 to −1.16	p = 0.0003; I² = 72%
	< 25	2	−6.40	−7.88 to −4.93	p < 0.00001; I² = 0%

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DBP: diastolic blood pressure; SBP: systolic blood pressure; ABPM: ambulatory blood pressure monitoring; AHI: apnea-hypopnea index; BMI: body mass index; CPAP: continuous positive airway pressure; and ESS: Epworth Sleepiness Scale.

Subgroup analysis was used in order to explore potential factors leading to heterogeneity. With regard to changes in mean SBP (as assessed by 24-h ABPM) before and after CPAP therapy, no heterogeneity was found among the eight subgroups for an AHI ≥ 30; an AHI < 30; a baseline SBP/DBP > 145/85 mmHg; a baseline SBP/DBP < 145/85 mmHg; a BMI < 32 kg/m²; a CPAP treatment duration ≤ 3 months; a European location; or a study sample size ≥ 25 (Table 3). With regard to changes in mean DBP (as assessed by 24-h ABPM) before and after CPAP therapy, it was unlikely that an AHI ≥ 30, a BMI < 32 kg/m², a CPAP treatment duration ≤ 3 months, an ESS score of < 10, a European location, or a study sample size of < 25 were the factors leading to heterogeneity (Table 4).

Meta-regression analysis showed that the ESS score, BMI, AHI, and age were not the factors leading to heterogeneity in mean SBP as assessed by 24-h ABPM. In contrast, there was a significant correlation between age and heterogeneity in mean DBP as assessed by 24-h ABPM (Table 5).

Table 5. Meta-regression of 24-h ambulatory blood pressure monitoring data.

Explanatory variable	SBP		DBP
Explanatory variable	No. of studies	p	No. of studies	p
ESS score	6	0.74	5	0.44
BMI	6	0.14	5	0.25
AHI	6	0.22	5	0.70
Age	6	0.47	5	< 0.0001

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SBP: systolic blood pressure; DBP: diastolic blood pressure; ESS: Epworth Sleepiness Scale; BMI: body mass index; and AHI: apnea-hypopnea index.

A sensitivity analysis was performed by removing one study at a time from the combined effects model in order to observe mean changes in effects and determine whether there were any differences between the combined effects model and the original model regarding heterogeneity and CIs. One study was found to have led to heterogeneity. Different standard deviations and correlation coefficients were used, but the results were not significantly different. Funnel plots showed no significant publication bias (Begg’s test, p = 0.707; Egger’s test, p = 0.347).

DISCUSSION

OSA has been acknowledged as an independent risk factor for hypertension,¹¹^,¹⁹^,²⁰ being an adverse clinical factor that makes it impossible to control hypertension; in addition, OSA is the most common factor leading to resistant hypertension.²¹ Given that CPAP performs extraordinarily well in maintaining continuous positive pressure in the respiratory tract and that it can effectively reduce the AHI, cardiovascular morbidity, and cardiovascular mortality,²²^,²³ it is currently one of the most effective ways to treat mild, moderate, and severe OSA. However, there is still controversy as to whether CPAP can effectively control blood pressure.

The present meta-analysis showed that, in patients with OSA and resistant hypertension undergoing CPAP treatment, mean SBP and DBP (as assessed by 24-h ABPM) decreased by 5.40 mmHg and 3.86 mmHg, respectively. In addition, mean nocturnal SBP and DBP decreased value after CPAP treatment (2.11 mmHg and 1.55 mmHg, respectively). Although mean daytime SBP and DBP decreased by 4.11 mmHg and 3.17 mmHg, respectively, after CPAP treatment, the combined effects of CPAP on SBP were statistically significant.

We found two observational studies showing the effects of CPAP treatment on blood pressure in patients with OSA and resistant hypertension. Dernaika et al.²⁴ found that mean arterial pressure decreased by 5.6 mmHg after CPAP therapy (95% CI: 2.0-8.7; p = 0.03). Frenţ et al.²⁵ suggested that long-term CPAP treatment can significantly control blood pressure in patients with OSA and resistant hypertension. The findings of the two aforementioned studies are consistent with those of the present study.

Durán-Cantolla et al.²⁶ found that mean SBP and DBP (as assessed by 24-h ABPM) decreased by 2.1 mmHg (95% CI: 0.4-3.7; p = 0.01) and 1.3 mmHg (95% CI: 0.2-2.3; p = 0.02), respectively. Barbé et al.²⁷ found that, after CPAP treatment, mean SBP and DBP decreased by 1.89 mmHg (95% CI: −0.11 to 3.9; p = 0.0654) and 2.19 mmHg (95% CI: 0.93-3.46; p = 0.0008), respectively. Therefore, it can be inferred that CPAP treatment has significant effects on the blood pressure of patients with OSA and resistant hypertension. Iftikhar et al.²⁸ performed a meta-analysis of the effects of CPAP on blood pressure in patients with resistant hypertension and OSA and reported that the risk of target organ damage and cardiovascular complications is higher in patients with resistant hypertension than in those with nonresistant hypertension, having found that CPAP treatment resulted in a favorable reduction in blood pressure in the former.

In the present study, we performed a combined effects analysis of mean daytime SBP/DBP, and the results of the heterogeneity test revealed a fairly large heterogeneity in daytime SBP/DBP across the studies. A sensitivity analysis revealed that the heterogeneity was mainly due to a study conducted by Pedrosa et al.,¹⁸ who concluded that CPAP treatment cannot significantly improve mean nocturnal SBP/DBP but can significantly improve mean daytime SBP/DBP. This finding is similar to those of the present meta-analysis.

We found two studies in which patients received CPAP treatment, conventional antihypertensive therapy, or a combination of the two. Lozano et al.¹⁵ found that the combined use of CPAP treatment and conventional antihypertensive therapy resulted in a more significant reduction in mean DBP (as assessed by 24-h ABPM) than did the use of conventional antihypertensive therapy alone. The results obtained by Litvin et al.²⁹ are consistent with those obtained by Lozano et al.,¹⁵ the former group of authors having found that the combined use of CPAP and conventional antihypertensive therapy resulted in a more significant reduction in blood pressure. Therefore, patients with resistant hypertension should receive a combination of antihypertensive therapy and CPAP treatment, the effects of which are more significant than are those of antihypertensive therapy alone.

Our subgroup analysis revealed that the AHI, BMI, and ESS score were in the subgroup at risk of developing OSA and might be factors leading to heterogeneity. This is possibly due to the fact that the severity of OSA has an impact on the treatment of hypertension.

The present meta-analysis has some advantages over two earlier meta-analyses.²⁸^,³⁰ First, all 6 studies included in our meta-analysis are RCTs. Second, we compiled a more comprehensive literature set, our results therefore being more convincing. Finally, in order to explore as many factors leading to heterogeneity as possible and provide a better explanation for the observed results, we adopted a variety of approaches to testing heterogeneity.

The present study has limitations. First, because of the limitations of our method of literature retrieval, it is possible that relevant studies were left out. Second, the number of RCTs included in our meta-analysis was rather small. Third, we did not control for confounding factors such as mean patient age, type of antihypertensive medication, degree of obesity, and genetic factors. Finally, the control groups were not homogeneous across studies. Despite these limitations, the results of the present study can be used in order to inform future studies.

In conclusion, CPAP treatment has an effect on patients with OSA and resistant hypertension. When treating patients with hypertension, physicians can prescribe CPAP treatment or CPAP treatment in combination with conventional antihypertensive therapy for those with concomitant OSA.

Study carried out in the Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming, China.

Financial support: None

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J Bras Pneumol. 2017 Sep-Oct;43(5):373–379. [Article in Portuguese]

Efeitos da pressão positiva contínua nas vias aéreas na pressão arterial em pacientes com hipertensão resistente e apneia obstrutiva do sono: revisão sistemática e meta-análise de seis ensaios clínicos controlados aleatórios

Qiang Lei ¹, Yunhui Lv ², Kai Li ¹, Lei Ma ¹, Guodong Du ¹, Yan Xiang ¹, Xuqing Li ¹

RESUMO

Objetivo:

Avaliar sistematicamente os efeitos da continuous positive airway pressure (CPAP, pressão positiva contínua nas vias aéreas) na pressão arterial em pacientes com hipertensão resistente e apneia obstrutiva do sono (AOS).

Métodos:

Estudos que investigassem os efeitos da CPAP na pressão arterial em pacientes com hipertensão resistente e AOS foram buscados nos seguintes bancos de dados eletrônicos: Cochrane Library; PubMed; ScienceDirect e Web of Science. Os estudos selecionados foram submetidos a avaliação de qualidade, meta-análise e teste de heterogeneidade.

Resultados:

Foram incluídos na meta-análise seis ensaios clínicos controlados aleatórios. As estimativas combinadas das alterações das médias de pressão arterial sistólica e pressão arterial diastólica (medidas por meio de monitoração ambulatorial da pressão arterial durante 24 h) foram de −5,40 mmHg (IC95%: −9,17 a −1,64; p = 0,001; I² = 74%) e −3,86 mmHg (IC95%: −6,41 a −1,30; p = 0,00001; I² = 79%), respectivamente.

Conclusões:

O tratamento com CPAP é capaz de reduzir significativamente a pressão arterial em pacientes com hipertensão resistente e AOS.

Descritores: Pressão positiva contínua nas vias aéreas, Apneia do sono tipo obstrutiva, Hipertensão, Metanálise

INTRODUÇÃO

A apneia obstrutiva do sono (AOS) é uma doença crônica caracterizada por colapso recorrente das vias aéreas superiores durante o sono que resulta em hipoxemia intermitente e interrupção do sono.¹ Estima-se que 24% dos homens na faixa etária de 30 a 60 anos e 9% das mulheres na mesma faixa etária tenham AOS.² Diversos estudos mostraram que a AOS é um fator de risco de doenças cardiovasculares, incluindo hipertensão, insuficiência cardíaca, fibrilação atrial e doença arterial coronariana.³^-⁶ Em 2003, o Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (Sétimo Relatório do Comitê Nacional Conjunto de Prevenção, Detecção, Avaliação e Tratamento da Hipertensão Arterial) identificou a AOS como sendo uma importante causa identificável de hipertensão.⁷

A hipertensão resistente é a pressão arterial que permanece acima da meta não obstante o uso concomitante de pelo menos três classes de anti-hipertensivos. Considera-se que indivíduos com pressão arterial controlada que usem pelo menos quatro classes de anti-hipertensivos também têm hipertensão resistente. As diretrizes internacionais agora reconhecem a AOS como um dos mais comuns fatores de risco de hipertensão resistente.⁸ Gonçalves et al. constataram que o risco de hipertensão resistente é quase cinco vezes maior em pacientes com AOS.⁹ Da mesma forma, Calhoun et al. constataram que 63% dos pacientes que procuraram uma clínica de hipertensão resistente apresentavam alto risco de AOS com base em suas respostas ao Questionário de Berlim.¹⁰ Em um estudo observacional prospectivo, Lavie et al. constataram que a prevalência e a gravidade da hipertensão aumentaram à medida que o índice de apneia-hipopneia (IAH) aumentou.¹¹

A continuous positive airway pressure (CPAP, pressão positiva contínua nas vias aéreas) é a forma mais aceita de terapia para AOS e continua a ser o padrão ouro para o tratamento. Embora haja uma quantidade significativa de dados sobre o efeito da CPAP na hipertensão, os dados a respeito da hipertensão resistente são limitados.¹² Portanto, realizamos uma meta-análise para avaliar a eficácia da CPAP em pacientes com AOS e hipertensão resistente.

MÉTODOS

Critérios de inclusão

Buscamos avaliar de forma sistemática ensaios clínicos aleatórios que investigassem os efeitos do tratamento com CPAP na pressão arterial de pacientes com AOS e hipertensão resistente. Foram incluídos estudos com pacientes com idade superior a 18 anos e diagnóstico de AOS e hipertensão resistente, o diagnóstico desta tendo sido feito por meio de monitoração ambulatorial da pressão arterial (MAPA). As intervenções consistiram em um grupo controle que tivesse recebido terapia anti-hipertensiva convencional ou placebo e um grupo de tratamento que tivesse recebido CPAP (e completado o tratamento). Os desfechos foram as médias de pressão arterial sistólica (PAS) e pressão arterial diastólica (PAD) medidas por meio de MAPA durante 24 h.

Critérios de exclusão

Os critérios de exclusão foram os seguintes: estudos cuja amostra foi < 10; estudos controlados não randomizados; estudos antigos (isto é, estudos publicados antes de 2010); ensaios repetidos; estudos sem grupo controle; estudos nos quais os pacientes foram usados como seus próprios controles; estudos sem os dados originais completos; estudos cujos artigos completos não estavam disponíveis e estudos cujos autores não conseguimos contatar.

Busca de estudos

Foram realizadas buscas nos seguintes bancos de dados eletrônicos: Cochrane Library; ScienceDirect; PubMed e Web of Science. Nas buscas, foram usados os seguintes termos: “continuous positive airway pressure”; “CPAP”; “obstructive sleep apnea”; “OSA”; “apnea-hypopnea index”; “AHI”; “resistant hypertension”; “RH”; “refractory hypertension”; “resistant high blood pressure”; “randomized controlled trial” e “RCT”. A busca limitou-se a artigos originais de pesquisa publicados entre janeiro de 2010 e janeiro de 2016. Além disso, a rede social ResearchGate foi usada para contatar pesquisadores com o intuito de obter mais estudos relevantes.

Seleção de estudos

A fim de selecionar os artigos para inclusão na meta-análise, dois pesquisadores aplicaram de forma independente os critérios de inclusão e exclusão a todos os estudos recuperados pelo método supracitado. Em casos de discordância, um terceiro membro da equipe de pesquisa foi consultado. Os dados relevantes foram extraídos e cruzados. Nos casos em que faltavam dados importantes nos estudos selecionados, os autores foram contatados por e-mail ou telefone.

Avaliação da qualidade

A qualidade dos estudos selecionados foi avaliada pela pontuação na escala de Jadad, que varia de 0 a 5. Artigos cuja pontuação na escala de Jadad foi > 3 foram incluídos em nossa meta-análise. Dois pesquisadores avaliaram de forma independente a qualidade dos estudos por meio da aplicação dos critérios de Jadad. Em casos de discordância, um terceiro membro da equipe de pesquisa foi consultado. Todos os dados relevantes foram em seguida extraídos.

Análise estatística

Meta-análise

A meta-análise foi realizada por meio do programa Review Manager (RevMan), versão 5.3 (The Nordic Cochrane Centre, Copenhague, Dinamarca). O coeficiente I² foi usado para avaliar a heterogeneidade (clínica e estatística); o nível de significância adotado foi de p < 0,1. Para os estudos que apresentaram homogeneidade clínica e estatística (isto é, p > 0,1 e I² ≤ 50%), foi usado um modelo de efeito fixo; para os que apresentaram homogeneidade clínica e heterogeneidade estatística (isto é, p < 0,1 e I² > 50%), foi usado um modelo de efeitos aleatórios. Na presença de heterogeneidade clínica significativa, foi realizada apenas a análise estatística descritiva. As variáveis contínuas foram a diferença de média ponderada e a diferença de média padronizada; os efeitos foram expressos em forma de IC95%. O nível de significância adotado foi de p < 0,05. Gráficos de funil (funnel plots) foram usados para determinar se houve viés de publicação significativo.

Teste de heterogeneidade

A heterogeneidade foi analisada pelo método de análise de subgrupos, que consiste em dividir os dados em unidades menores e comparar os subgrupos. Com base no IAH, índice de massa corporal (IMC), PAS, PAD, tempo total de tratamento com CPAP, média de duração diária do tratamento com CPAP, pontuação na Escala de Sonolência de Epworth (ESE) e localização geográfica das instituições, a amostra foi dividida em oito subgrupos, a fim de analisar fatores que pudessem resultar em heterogeneidade.

Análise de sensibilidade

A análise de sensibilidade foi realizada por meio da exclusão de estudos que pudessem afetar a análise e do uso de diferentes coeficientes de correlação para observar a estabilidade dos resultados.

RESULTADOS

Foram inicialmente recuperados 423 artigos, e 308 permaneceram após a exclusão das duplicatas. Dos artigos restantes, 6¹³^-¹⁸ foram incluídos em nossa meta-análise (Figura 1). Os 6 artigos incluídos foram ensaios clínicos controlados aleatórios (ECCA) e compreenderam um total de 479 pacientes. Destes, 245 haviam feito parte do grupo controle e 234 haviam feito parte do grupo de tratamento. As características básicas dos 6 ECCA incluídos na meta-análise são apresentadas na Tabela 1. A Tabela 2 apresenta o IAH, pontuação na ESE, IMC, PAS (medida por meio de MAPA durante 24 h) e PAD (medida por meio de MAPA durante 24 h) basal nos 6 ECCA incluídos em nossa meta-análise.

Tabela 1. Características básicas dos seis estudos incluídos na meta-análise.

Autor	Ano	Número de pacientes	Sexo masculino, %	Média de idade ± dp, anos	Adesão à CPAP, h	Tipo de estudo	Tempo de tratamento	Método de medição da PA	País	Pontuação na escala de Jadad
Muxfeldt et al.⁽¹⁷⁾	2015	46 (CPAP)	37,9	60,8 ± 8,0	4,8	ECCA	6 meses	MAPA	Brasil	3
		60 (Controle)
de Oliveira et al.⁽¹³⁾	2014	24 (CPAP)	58	59,5 ± 7,3	≥ 4	ECCA	8 semanas	MAPA	Brasil	4
		23 (Controle)
Lloberes et al.⁽¹⁴⁾	2014	27 (CPAP)	72,4	58,7 ± 9,5	5,7 ± 1,5	ECCA	3 meses	MAPA	Espanha	3
		29 (Controle)
Pedrosa et al.⁽¹⁸⁾	2013	19 (CPAP)	74	57 ± 2^a	6,01 ± 0,20	ECCA	6 meses	MAPA	Brasil	3
		16 (Controle)
Martínez-García et al.⁽¹⁶⁾	2013	98 (CPAP)	72,4	56,0 ± 9,5	5 ± 1,9	ECCA	3 meses	MAPA	Espanha	3
		96 (Controle)
Lozano et al.⁽¹⁵⁾	2010	20 (CPAP)	75,9	59,2 ± 8,7	5,6 ± 1,5	ECCA	3 meses	MAPA	Espanha	3
		21 (Controle)

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CPAP: continuous positive airway pressure (pressão positiva contínua nas vias aéreas); PA: pressão arterial; ECCA: ensaio clínico controlado aleatório; e MAPA: monitoração ambulatorial da pressão arterial. ^aDados expressos em forma de média ± ep.

Tabela 2. Índice de apneia-hipopneia, pontuação na Escala de Sonolência de Epworth, índice de massa corporal, pressão arterial sistólica (medida por meio de monitoração ambulatorial da pressão arterial durante 24 h) e pressão arterial diastólica (medida por meio de monitoração ambulatorial da pressão arterial durante 24 h) basal.^a.

Estudo	IAH	Pontuação na ESE	IMC	PAS	PAD
Muxfeldt et al.⁽¹⁷⁾	41 (21)	11 (6)	33,4 (5,3)	129 (16)	75 (12)
de Oliveira et al.⁽¹³⁾	20 (18-31)^b	10 (6-15)^b	29,8 ± 4,4^c	148 ± 17	88 ± 13
Lloberes et al.⁽¹⁴⁾	50,1 ± 20,6	6,76 ± 3,7	31,4 (4,9)	139,2 ± 11,5	80,8 ± 10,8
Pedrosa et al.⁽¹⁸⁾	29 (24-48)^b	10 ± 1^c	32 (28-39)^b	162 ± 4	97 ± 2
Martínez-García et al.⁽¹⁶⁾	40,4 (18,9)	9,1 (3,7)	34,1 (5,4)	144,2 (12,5)	83,0 (10,5)
Lozano et al.⁽¹⁵⁾	52,67 ± 21,5	6,14 ± 3,30	30,8 ± 5,0	129 (16)	75 (12)

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IAH: índice de apneia-hipopneia; ESE: Escala de Sonolência de Epworth; IMC: índice de massa corporal; PAS: pressão arterial sistólica; e PAD: pressão arterial diastólica. ^aValores expressos em forma de n (%) ou média ± dp, exceto onde indicado. ^bDados expressos em forma de mediana (variação). ^cDados expressos em forma de média ± ep.

Todos os 6 ECCA examinaram os efeitos do tratamento com CPAP na média de PAS (medida por meio de MAPA durante 24 h) em pacientes com AOS e hipertensão resistente. A estimativa combinada da alteração da média de PAS foi de −5,40 mmHg (IC95%: −9,17 a −1,64; p = 0,005; I² = 74%). Cinco dos 6 ECCA examinaram os efeitos do tratamento com CPAP na média de PAD (medida por meio de MAPA durante 24 h) em pacientes com AOS e hipertensão resistente. A estimativa combinada da alteração da média de PAD foi de −3,86 mmHg (IC95%: −6,41 a −1,30; p = 0,003; I² = 82%). Como houve heterogeneidade significativa entre os estudos, um modelo de efeitos aleatórios foi usado para analisar os resultados (Figuras 2 e 3).

Cinco estudos examinaram os efeitos do tratamento com CPAP na média de PAS diurna e noturna em pacientes com AOS e hipertensão resistente. As estimativas combinadas das alterações das médias de PAS diurna e noturna foram de −4,11 mmHg (IC95%: −9,06 a −0,84; p = 0,10; I² = 85%) e −3,17 mmHg (IC95%: −6,25 a −0,09; p = 0,04; I² = 90%), respectivamente (Tabela 3). As estimativas combinadas das alterações das médias de PAD diurna e noturna foram de −2,11 mmHg (IC95%: −4,16 a −0,05; p = 0,04; I² = 0%) e −1,55 mmHg (IC95%: −2,81 a −0,29; p = 0,02; I² = 0%), respectivamente (Tabela 4). Como houve heterogeneidade significativa entre os estudos no que tange à média de PAS/PAD diurna, um modelo de efeitos aleatórios foi usado para analisar os resultados. Como não houve heterogeneidade significativa entre os estudos no que tange à média de PAS/PAD noturna, um modelo de efeito fixo foi usado para analisar os resultados.

Tabela 3. Análise de subgrupos da média de alteração da pressão arterial sistólica medida por meio de monitoração ambulatorial da pressão arterial durante 24 h.

Subgrupo		PAS (medida por meio de MAPA durante 24 h)
Subgrupo		N. de estudos	Média de alteração líquida	IC95%	p; I² (%)
IAH	≥ 30	4	−3,07	−5,50 a −0,65	p = 0,01; I² = 22%
	> 30	2	−9,58	−11,70 a −7,46	p < 0,00001; I² = 0%
PAS/PAD basal, mmHg	> 145/85	2	−9,58	−11,70 a −7,46	p < 0,00001; I² = 0%
	< 145/85	4	−3,07	−5,50 a −0,65	p = 0,01; I² = 22%
IMC, kg/m²	≥ 32	3	−6,81	−8,55 a −5,08	p < 0,00001; I² = 89%
	< 32	3	−6,47	−10,53 a −2,42	p = 0,002; I² = 0%
Adesão à CPAP, h	> 5	4	−7,47	−9,18 a −5,76	p < 0,00001; I² = 70%
	≤ 5	1	1,20	−4,12 a 6,52	p = 0,66; I² = 0%
Tempo de tratamento, meses	> 3	2	−8,03	−10,06 a −6,00	p < 0,00001; I² = 93%
	≤ 3	4	−4,71	−7,29 a −2,12	p = 0,0004; I² = 0%
Pontuação na ESE	≥ 10	3	−5,89	−13,33 a 1,55	p = 0,12; I² = 85%
	< 10	3	−4,19	−6,92 a −1,47	p = 0,003; I² = 0%
Local	Europa	3	−4,19	-6,92 a −1,47	p = 0,003; I² = 0%
	América do Sul	3	−8,10	−10,07 a −6,13	p < 0,00001; I² = 85%
Tamanho da amostra	≥ 25	3	−0,20	−0,41 a −0,01	p = 0,06; I² = 36%
	< 25	3	−0,96	−1,36 a −0,57	p < 0,00001; I² = 88%

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PAS: pressão arterial sistólica; PAD: pressão arterial diastólica; MAPA: monitoração ambulatorial da pressão arterial; IAH: índice de apneia-hipopneia; IMC: índice de massa corporal; CPAP: continuous positive airway pressure (pressão positiva contínua nas vias aéreas); e ESE: Escala de Sonolência de Epworth.

Tabela 4. Análise de subgrupos da média de alteração da pressão arterial diastólica medida por meio de monitoração ambulatorial da pressão arterial durante 24 h.

Subgrupo		PAD (medida por meio de MAPA durante 24 h)
Subgrupo		N. de estudos	Média de alteração líquida	IC95%	p; I² (%)
IAH	≥ 30	4	−2,76	−4,06 a −1,46	p < 0,0001; I² = 64%
	< 30	1	−6,60	−8,17 a −5,03	p < 0,00001; I² = 0%
PAS/PAD basal, mmHg	> 145/85	1	−6,60	−8,17 a −5,03	p < 0,00001; I² = 0%
	< 145/85	4	−2,76	−4,06 a −1,46	p < 0,0001; I² = 64%
IMC, kg/m²	≥ 32	3	−4,24	−5,32 a −3,15	p < 0,00001; I² = 91%
	< 32	2	−4,79	−7,39 a −2,18	p = 0,0003; I² = 0%
Adesão à CPAP, h	> 5	4	−5,18	−6,28 a −4,09	p < 0,00001; I² = 55%
	≤ 5	1	0,30	−2,23 a 2,83	p = 0,82; I² = 0%
Tempo de tratamento, meses	> 3	2	−4,67	−6,00 a −3,33	p < 0,00001; I² = 95%
	≤ 3	3	−3,87	−5,39 a −3,35	p < 0,00001; I² = 0%
Pontuação na ESE	≥ 10	2	−4,67	−6,00 a −3,33	p < 0,00001; I² = 95%
	< 10	3	−3,87	−5,39 a −2,35	p < 0,00001; I² = 0%
Local	Europa	3	−3,87	−5,39 a −2,35,	p < 0,00001; I² = 0%
	América do Sul	2	−4,67	−6,00 a −3,33	p < 0,00001; I² = 95%
Tamanho da amostra	≥ 25	3	−2,53	−3,89 a −1,16	p = 0,0003; I² = 72%
	< 25	2	−6,40	−7,88 a −4,93	p < 0,00001; I² = 0%

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PAD: pressão arterial diastólica; PAS: pressão arterial sistólica; MAPA: monitoração ambulatorial da pressão arterial; IAH: índice de apneia-hipopneia; IMC: índice de massa corporal; CPAP: continuous positive airway pressure (pressão positiva contínua nas vias aéreas); e ESE: Escala de Sonolência de Epworth.

A análise de subgrupos foi usada para explorar fatores que pudessem resultar em heterogeneidade. No tocante a alterações da média de PAS (medida por meio de MAPA durante 24 h) antes e depois do tratamento com CPAP, não houve heterogeneidade entre os oito subgrupos para IAH ≥ 30; IAH < 30; PAS/PAD basal > 145/85 mmHg; PAS/PAD basal < 145/85 mmHg; IMC < 32 kg/m²; tempo de tratamento com CPAP ≤ 3 meses; localização europeia ou amostra ≥ 25 (Tabela 3). No tocante a alterações da média de PAD (medida por meio de MAPA durante 24 h) antes e depois do tratamento com CPAP, é provável que IAH ≥ 30, IMC < 32 kg/m², tempo de tratamento com CPAP ≤ 3 meses, pontuação na ESE < 10, localização europeia e amostra < 25 não tenham sido os fatores que resultaram em heterogeneidade (Tabela 4).

A análise de metarregressão mostrou que a pontuação na ESE, o IMC, o IAH e a idade não foram os fatores que resultaram em heterogeneidade na média de PAS medida por meio de MAPA durante 24 h. Por outro lado, houve uma correlação significativa entre a idade e a heterogeneidade na média de PAD medida por meio de MAPA durante 24 h (Tabela 5).

Tabela 5. Metarregressão dos dados obtidos por meio de monitoração ambulatorial da pressão arterial durante 24 h.

Variável explicativa	PAS		PAD
Variável explicativa	N. de estudos	p	N. de estudos	p
Pontuação na ESE	6	0,74	5	0,44
IMC	6	0,14	5	0,25
IAH	6	0,22	5	0,70
Idade	6	0,47	5	< 0,0001

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PAS: pressão arterial sistólica; PAD: pressão arterial diastólica; ESE: Escala de Sonolência de Epworth; IMC: índice de massa corporal; e IAH: índice de apneia-hipopneia.

A análise de sensibilidade foi realizada por meio da remoção de um estudo por vez do modelo dos efeitos combinados, a fim de observar a média de alteração dos efeitos e determinar se havia alguma diferença entre o modelo dos efeitos combinados e o modelo original no tocante à heterogeneidade e IC. Verificou-se que um estudo resultou em heterogeneidade. Foram usados diferentes desvios-padrão e coeficientes de correlação, mas os resultados não foram significativamente diferentes. Os gráficos de funil mostraram que não houve viés de publicação significativo (teste de Begg: p = 0,707; teste de Egger: p = 0,347).

DISCUSSÃO

Já se reconheceu que a AOS é um fator independente de risco de hipertensão,¹¹^,¹⁹^,²⁰ sendo um fator clínico adverso que torna impossível o controle da hipertensão; além disso, a AOS é o mais comum fator que leva à hipertensão resistente.²¹ Como o desempenho da CPAP na manutenção da pressão positiva contínua no trato respiratório é extraordinário e como a CPAP é eficaz na redução do IAH, da morbidade cardiovascular e da mortalidade cardiovascular,²²^,²³ é atualmente uma das maneiras mais eficazes de tratar a AOS leve, moderada e grave. No entanto, ainda há controvérsia a respeito da capacidade da CPAP de controlar de modo eficaz a pressão arterial.

A presente meta-análise mostrou que, em pacientes com AOS e hipertensão resistente submetidos a tratamento com CPAP, houve redução de 5,40 mmHg e 3,86 mmHg, respectivamente, nas médias de PAS e PAD (medidas por meio de MAPA durante 24 h). Além disso, houve redução das médias de PAS e PAD noturna após o tratamento com CPAP (2,11 mmHg e 1,55 mmHg, respectivamente). Embora tenha havido redução de 4,11 mmHg e 3,17 mmHg, respectivamente, nas médias de PAS e PAD diurna após o tratamento com CPAP, os efeitos combinados da CPAP na PAS foram estatisticamente significativos.

Encontramos dois estudos observacionais nos quais os autores mostraram os efeitos do tratamento com CPAP na pressão arterial em pacientes com AOS e hipertensão resistente. Dernaika et al.²⁴ observaram uma redução de 5,6 mmHg na pressão arterial média após o tratamento com CPAP (IC95%: 2,0-8,7; p = 0,03). Frenţ et al.²⁵ sugeriram que o tratamento em longo prazo com CPAP é capaz de controlar de maneira significativa a pressão arterial em pacientes com AOS e hipertensão resistente. Os achados dos dois estudos supracitados são coerentes com os do presente estudo.

Durán-Cantolla et al.²⁶ observaram redução de 2,1 mmHg (IC95%: 0,4-3,7; p = 0,01) e 1,3 mmHg (IC95%: 0,2-2,3; p = 0,02), respectivamente, nas médias de PAS e PAD (medidas por meio de MAPA durante 24 h). Barbé et al.²⁷ constataram que, após o tratamento com CPAP, houve redução de 1,89 mmHg (IC95%: −0,11 a 3,9; p = 0,0654) e 2,19 mmHg (IC95%: 0,93-3,46; p = 0,0008), respectivamente, nas médias de PAS e PAD. Portanto, pode-se inferir que o tratamento com CPAP tem efeitos significativos na pressão arterial de pacientes com AOS e hipertensão resistente. Iftikhar et al.²⁸ realizaram uma meta-análise dos efeitos da CPAP na pressão arterial em pacientes com hipertensão resistente e AOS e relataram que o risco de dano ao órgão-alvo e de complicações cardiovasculares é maior em pacientes com hipertensão resistente do que naqueles com hipertensão não resistente, tendo constatado que o tratamento com CPAP resultou em redução favorável da pressão sanguínea nos pacientes com hipertensão resistente.

No presente estudo, realizamos uma análise dos efeitos combinados da média de PAS/PAD diurna, e os resultados do teste de heterogeneidade revelaram heterogeneidade razoavelmente grande entre os estudos quanto à PAS/PAD diurna. A análise de sensibilidade revelou que a heterogeneidade foi principalmente causada por um estudo conduzido por Pedrosa et al.,¹⁸ que concluíram que o tratamento com CPAP não é capaz de melhorar de modo significativo a média de PAS/PAD noturna, mas é capaz de melhorar de modo significativo a média de PAS/PAD diurna. Esse achado é semelhante aos da presente meta-análise.

Encontramos dois estudos nos quais os pacientes receberam tratamento com CPAP, tratamento anti-hipertensivo convencional ou ambos. Lozano et al.¹⁵ constataram que o uso de tratamento com CPAP e tratamento anti-hipertensivo convencional resultou em uma redução mais significativa da média de PAD (medida por meio de MAPA durante 24 h) do que o uso de tratamento anti-hipertensivo convencional apenas. Os resultados obtidos por Litvin et al.²⁹ são coerentes com os obtidos por Lozano et al.¹⁵; eles constataram que o uso de CPAP e o tratamento anti-hipertensivo convencional resultaram em uma redução mais significativa da pressão arterial. Portanto, pacientes com hipertensão resistente devem receber tratamento anti-hipertensivo e tratamento com CPAP, cujos efeitos são mais significativos do que os do tratamento anti-hipertensivo apenas.

Nossa análise de subgrupos revelou que o IAH, o IMC e a pontuação na ESE estavam no subgrupo de risco de AOS e podem ser fatores que resultam em heterogeneidade. É possível que isso ocorra em virtude do fato de que a gravidade da AOS afeta o tratamento da hipertensão.

A presente meta-análise apresenta algumas vantagens sobre duas meta-análises anteriores.²⁸^,³⁰ Em primeiro lugar, todos os 6 estudos incluídos em nossa meta-análise são ECCA. Em segundo lugar, compilamos um conjunto mais abrangente de estudos e, por isso, nossos resultados são mais convincentes. Finalmente, a fim de explorar o maior número possível de fatores que resultassem em heterogeneidade e fornecer uma explicação melhor para os resultados observados, adotamos uma variedade de abordagens para testar a heterogeneidade.

O presente estudo tem limitações. Em primeiro lugar, em virtude das limitações de nosso método de seleção de estudos, é possível que estudos relevantes tenham sido deixados de fora. Em segundo lugar, o número de ECCA incluídos em nossa meta-análise foi bastante pequeno. Em terceiro lugar, não controlamos fatores de confusão como média de idade dos pacientes, tipo de medicamento anti-hipertensivo, grau de obesidade e fatores genéticos. Finalmente, não houve homogeneidade entre os estudos no tocante aos grupos de controle. Apesar dessas limitações, os resultados do presente estudo podem ser usados para orientar futuros estudos.

Em suma, o tratamento com CPAP tem efeito em pacientes com AOS e hipertensão resistente. Ao tratar pacientes com hipertensão, os médicos podem prescrever tratamento com CPAP apenas ou tratamento com CPAP e tratamento anti-hipertensivo convencional para aqueles que também apresentem AOS.

Trabalho realizado na Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming, China

Apoio financeiro: Nenhum

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PERMALINK

Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a systematic review and meta-analysis of six randomized controlled trials

Qiang Lei

Yunhui Lv

Kai Li

Lei Ma

Guodong Du

Yan Xiang

Xuqing Li

ABSTRACT

Objective:

Methods:

Results:

Conclusions:

INTRODUCTION

METHODS

Inclusion criteria

Exclusion criteria

Literature retrieval

Literature screening

Quality assessment

Statistical analysis

Meta-analysis

Heterogeneity test

Sensitivity analysis

RESULTS

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the process of including studies in our meta-analysis.

Table 1. Basic characteristics of the six studies included in the meta-analysis.

Table 2. Baseline apnea-hypopnea index, Epworth Sleepiness Scale score, body mass index, systolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring), and diastolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring).a.

Figure 2. Forest plot of the mean change in systolic blood pressure as assessed by 24-h ambulatory blood pressure monitoring and its 95% CI.

Figure 3. Forest plot of the mean change in diastolic blood pressure as assessed by 24-h ambulatory blood pressure monitoring and its 95% CI.

Table 3. Subgroup analysis of mean changes in systolic blood pressure as assessed by 24-h ambulatory blood pressure monitoring.

Table 4. Subgroup analysis of mean changes in diastolic blood pressure as assessed by 24-h ambulatory blood pressure monitoring.

Table 5. Meta-regression of 24-h ambulatory blood pressure monitoring data.

DISCUSSION

REFERENCES

Efeitos da pressão positiva contínua nas vias aéreas na pressão arterial em pacientes com hipertensão resistente e apneia obstrutiva do sono: revisão sistemática e meta-análise de seis ensaios clínicos controlados aleatórios

Qiang Lei

Yunhui Lv

Kai Li

Lei Ma

Guodong Du

Yan Xiang

Xuqing Li

RESUMO

Objetivo:

Métodos:

Resultados:

Conclusões:

INTRODUÇÃO

MÉTODOS

Critérios de inclusão

Critérios de exclusão

Busca de estudos

Seleção de estudos

Avaliação da qualidade

Análise estatística

Meta-análise

Teste de heterogeneidade

Análise de sensibilidade

RESULTADOS

Figura 1. Fluxograma Preferred Reporting Items for Systematic Reviews and Meta-Analyses do processo de inclusão de estudos em nossa meta-análise.

Tabela 1. Características básicas dos seis estudos incluídos na meta-análise.

Figura 2. Gráfico de floresta (forest plot) da média de alteração da pressão arterial sistólica medida por meio de monitoração ambulatorial da pressão arterial durante 24 h e seu IC95%.

Figura 3. Gráfico de floresta (forest plot) da média de alteração da pressão arterial diastólica medida por meio de monitoração ambulatorial da pressão arterial durante 24 h e seu IC95%.

Tabela 3. Análise de subgrupos da média de alteração da pressão arterial sistólica medida por meio de monitoração ambulatorial da pressão arterial durante 24 h.

Tabela 4. Análise de subgrupos da média de alteração da pressão arterial diastólica medida por meio de monitoração ambulatorial da pressão arterial durante 24 h.

Tabela 5. Metarregressão dos dados obtidos por meio de monitoração ambulatorial da pressão arterial durante 24 h.

DISCUSSÃO

ACTIONS

PERMALINK

RESOURCES

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Cited by other articles

Links to NCBI Databases

Table 2. Baseline apnea-hypopnea index, Epworth Sleepiness Scale score, body mass index, systolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring), and diastolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring).^a.