Obstructive Sleep Apnea and Blood Pressure

Transcription

1 AJH 2004; 17: Original Contributions Obstructive Sleep Apnea and Blood Pressure Interaction Between the Blood Pressure Lowering Effects of Positive Airway Pressure Therapy and Antihypertensive Drugs Jan Börgel, Bernd Martin Sanner, Fatih Keskin, Andrea Bittlinsky, Nina Karen Bartels, Nikolaus Büchner, Anika Huesing, Lars Christian Rump, and Andreas Mügge Background: There is increasing evidence that obstructive sleep apnea is an independent risk factor for arterial hypertension. Previous studies on the antihypertensive effects of positive airway pressure therapy on daytime blood pressure (BP) revealed inconsistent results. Methods: The relations between the apnea/hypopnea index (AHI) and BP or heart rate (HR) were investigated in a cohort of 540 consecutive patients (age, years) with moderate or severe obstructive sleep apnea (OSA). The mean AHI was events/h before OSA therapy. A group of 196 patients in whom antihypertensive medication was kept unchanged was followed for 6 months during bilevel or continuous positive airway pressure (Bi-/CPAP) therapy. Results: Significant associations were found between AHI and systolic BP ( 0.078, P.014), diastolic BP ( 0.056, P.003), HR ( 0.096, P.001), and the prevalence of arterial hypertension (odds ratio 0.015, P.003), independent of age, body mass index, and gender. During the follow-up period with effective Bi-/ CPAP therapy, the mean daytime systolic BP decreased from mm Hg to mm Hg (P.051), diastolic BP from mm Hg to mm Hg (P.001), and HR from to beats/min (P.001). Multiple linear regression analysis revealed that the absence of antihypertensive drugs and the level of the initial BP are significant and independent predictors for the lowering effect of Bi-/CPAP therapy on systolic and diastolic BP. Conclusions: This study confirms an independent relationship between the severity of OSA and BP/HR. Absence of BP-lowering medication and BP values before treatment are independent predictors for the reduction of BP with Bi-/CPAP therapy. Am J Hypertens 2004;17: American Journal of Hypertension, Ltd. Key Words: Obstructive sleep apnea, continuous positive airway pressure therapy, hypertension, antihypertensive medication, blood pressure. Obstructive sleep apnea (OSA) is a common disorder in adults and is characterized by repetitive apneas and hypoxia caused by upper airway collapse during sleep. It is estimated that 2% of women and 4% of men meet the diagnostic criteria for this disorder. 1 In obese men with or without any primary sleep complaint OSA can be diagnosed in up to 40% of the cases. 2 There is increasing evidence that OSA is an independent risk factor for arterial hypertension. 3,4 This association may contribute to the clinical observation that patients with OSA are at higher risk for cardiovascular complications than patients without OSA. 5 8 Continuous positive airway pressure (CPAP) and bilevel positive airway pressure (Bi-PAP) therapy are established and effective treatments for OSA. It is well known that Bi-/CPAP therapy improves the quality of life. 9 Furthermore, Bi-/CPAP therapy reduces apnea-associated blood pressure (BP), which increases during sleep. 10,11 The question whether nocturnal Bi-/CPAP therapy also reduces BP during Received April 8, First decision June 12, Accepted June 28, From the Medical Clinic II, Cardiology & Angiology, St. Josef- Hospital/Bergmannsheil, Ruhr-University Bochum (JB, FK, AB, NKB, AM), Bochum; Medical Clinic, Bethesda-Hospital (BMS), Wuppertal; Medical Clinic I, Marien-Hospital Herne, Ruhr-University Bochum (NB, LCR), and Institute for Biomedical Informatics, Ruhr-University Bochum (AH), Bochum, Germany. This study was supported by FoRUM (Forschungsförderung der Ruhr-Universität Bochum, Medizinische Fakultät). Address correspondence and reprint requests to Dr. Jan Börgel, Medical Clinic II Cardiology & Angiology, St. Josef-Hospital/Bergmannsheil, Gudrunstrasse 56, Bochum, Germany; jan.boergel@ruhr-uni-bochum.de 2004 by the American Journal of Hypertension, Ltd. Downloaded from Published by Elsevier Inc /04/$30.00 doi: /j.amjhyper

2 1082 OBSTRUCTIVE SLEEP APNEA AND BP AJH December 2004 VOL. 17, NO. 12, Part 1 daytime remains controversial. Although four controlled studies found no 12,13 or only minor 14,15 BP reduction, two recent prospective trials demonstrated a pronounced effect of CPAP therapy on daytime BP in cohorts of and patients with moderate-to-severe OSA. In the present study the association between OSA and daytime BP was assessed in a collective of 540 consecutive in-hospital patients with moderate-to-severe OSA. Effects of positive airway pressure therapy on daytime BP and heart rate (HR) were analyzed in a group of 196 patients with a control polysomnography after 6 months. In this group any BP-lowering medication remained unchanged between the initial polysomnography and the control polysomnography after 6 months. Furthermore, we looked into factors that predict the BP-lowering effect of Bi-/CPAP therapy. Methods Patients Patients (n 540) were consecutively enrolled between 1999 and 2001 at the sleep laboratory of the Marienhospital, Herne, a hospital of the Ruhr-University of Bochum. Patients with Bi-/CPAP therapy for their obstructive sleep apnea were seen for control polysomnography every 6 months after establishing the initial diagnosis. After written consent for participation, clinical data relating to the cardiovascular risk profile from the time of the initial diagnosis of OSA were determined. This assessment included a standardized questionnaire, polysomnography, physical examination, electrocardiography, echocardiography, a blood analysis, and BP (measured by noninvasive inflatable cuff according to Riva Rocci). Blood pressure and HR measurements were measured three times per day during the hospital stay. The mean values of these three daytime measurements, before the initial polysomnography was performed, were used for further calculations. Patients were admitted to the sleep monitoring unit because of previous nocturnal apneas, snoring, symptoms of hypersomnia (such as daytime sleepiness) or due to cognitive dysfunction. The severity of OSA was assessed by the apnea/hypopnea index (AHI). The diagnosis of hypertension was established if patients were either on antihypertensive drugs or if the mean of three measured systolic BP was 140 mm Hg or the diastolic BP 90 mm Hg. The study protocol was approved by the Institutional Review Board of the Ruhr-University of Bochum. Follow-Up During Positive Airway Pressure Therapy All patients that were treated with Bi-/CPAP therapy due to OSA were re-evaluated by polysomnography after 6 months. A cohort of 196 consecutive symptomatic patients with unchanged BP-lowering medication between the first and second polysomnography was followed to investigate the influence of Bi-/CPAP treatment on BP and HR. If the cardiovascular medication was changed during the first or between the first and the second visit, patients were excluded from the analysis. Polysomnography All patients underwent overnight polysomnography (Somnostar 4100, Sensor Medics, Yorba Linda, CA), according to a standardized protocol. 18 Patients were monitored by continuous polygraphic recordings from surface leads for electroencephalography (C3/A1, C4/A2), bilateral electrooculography, submental and leg electromyography, electrocardiography, oxyhemoglobin saturation (finger pulse oximetry), chest and abdominal excursion (inductance plethysmography), nasal and oral airflow from noninvasive sensors, body position, tracheal sounds (microphone), and thoracic and abdominal respiratory movement (inductance plethysmography). Recordings were continuously supervised by a technician to ensure that the transducers and lead wires permitted normal positional changes during sleep. Bedtime and awakening time were at each subject s discretion. Polysomnographic recordings were scored in 30-sec periods for sleep, breathing, and oxygenation. A breathing event during sleep was defined as abnormal if either a complete cessation of airflow lasting 10 sec was seen (apnea) or a reduction in respiratory airflow of 50% of the tidal volume lasting 5 sec could be discerned (hypopnea). 18 Obstructive apnea was defined as absence of tidal volume in the presence of paradoxical chest or abdominal wall motion. The average number of episodes of apnea and hypopnea per hour of sleep (AHI) was calculated. When the AHI was 5 events/h associated with typical clinical features, OSA syndrome was diagnosed. Sleep was staged manually by the methods of Rechtschaffen and Kales. 19 Patients with central sleep apneas were excluded from the study. Further parameters such as arousal index and sleep efficiency were identified according to the recommendations of the American Sleep Disorders Association. 20 Statistical Analysis Results are presented as means SD. All reported P values are two-tailed. Statistical analyses were performed with the computer software SPSS for Windows (SPSS, Chicago, IL). The relationships between BP, HR, and the AHI were first explored by bivariate regression analysis. In line with our (parametric) regression analyses the Pearson s correlation coefficient was calculated as well for this association as a measure of determination to qualify further regression analysis. To determine the independent associations of the AHI on these parameters in the presence of body mass index (BMI), age, and gender, multiple linear regressions were calculated. The odds ratio between the severity of OSA represented by the AHI and the prevalence of arterial

3 AJH December 2004 VOL. 17, NO. 12, Part 1 OBSTRUCTIVE SLEEP APNEA AND BP 1083 Table ) Demographics of full study cohort (n Mean age (y SD) Female, n (%) 85 (15.7) Mean BMI (kg/m 2 SD) Results of polysomnography Mean AHI (events/h SD) Mean O 2 saturation (% SD) Mean max. O 2 desaturation (% SD) Sleep efficiency (% SD) Blood pressure (BP)/heart rate Mean systolic BP (mm Hg SD) Mean diastolic BP (mm Hg SD) Mean heart rate (beats/min SD) Additional cardiovascular risk factors Systemic hypertension (n [%]) 315 (58.3) Type 2 diabetes mellitus 89 (16.5) (n [%]) Current smoking (self-reported) 148 (27.4) (n [%]) Cardiovascular history Coronary artery disease (n 67 (12.4) [%]) Myocardial infarction (n [%]) 33 (6.1) Stroke/TIA (n [%]) 27 (5.0) Atrial fibrillation (n [%]) 32 (5.9) BMI body mass index; AHI apnea/hypopnea index; BP blood pressure; TIA transient ischemic attack. hypertension was calculated with multiple logistic regression analysis using BMI, age, and gender as covariates. Differences in BP/HR after Bi-/CPAP therapy were analyzed with the t test for paired samples. To determine independent predictors for BP/HR reduction during Bi-/CPAP therapy, a multivariate linear regression analysis was performed. Results Untreated Patients With Obstructive Sleep Apnea Table 1 summarizes the demographic findings in all patients (n 540). Arterial hypertension was diagnosed in 315 (58%) patients. Antihypertensive medication consisted of (n; % of full cohort): angiotensin-converting enzyme (ACE) inhibitors (164; 30.4%), -receptor blockers (115; 21.3%), diuretics (90; 16.7%), calcium channel blockers (98; 18.1%), nitrates (49; 9.1%), central antihypertensive drugs (22; 4.1%), and -adrenergic antagonist (1;0.2%). Two hundred fifty-eight patients (47.8%) did not take any BP-lowering medication (33 patients had untreated arterial hypertension). We found a linear relationship between the relative risk for hypertension and the numbers of nocturnal apneas independent of age, BMI, and gender. The relative risk for FIG. 1. Linear regression between apnea/hypopnea index (AHI) and blood pressure (BP)/heart rate in all patients and in the group not taking BP-lowering drugs (BPLD). arterial hypertension increased by 15% (odds ratio [OR] 1.15, confidence interval ; P.003) if the AHI increased by 10 events per hour. Bivariate linear regression showed a significant relationship between AHI and systolic BP, diastolic BP, or HR in the full study group and the group of patients not taking antihypertensive drugs (Fig. 1). The adjustment for age, BMI, and gender disclosed an independent influence of the AHI on these parameters, as shown in Table 2. The BMI was the strongest confounding factor in this model. In the 258 of 540 patients who did not take any antihypertensive drugs, the adjusted (BMI, age, gender) and P values remained similar compared to all patients: systolic BP: 0.078, P.048; diastolic BP: 0.080, P.003; HR: 0.109, P.001. Follow-Up During Positive Airway Pressure Therapy Of the 540 patients seen in the initial polysomnography, 295 were treated with Bi-/CPAP therapy and could be restudied after a 6-month follow-up period. Of these, 99 patients had to be excluded for analysis because the BP-

4 1084 OBSTRUCTIVE SLEEP APNEA AND BP AJH December 2004 VOL. 17, NO. 12, Part 1 Table 2. Multivariate regression between apnea/hypopnea index (AHI) and blood pressure (BP)/heart rate (HR) adjusted for body mass index (BMI), age, and gender AHI Adjusted for BMI Adjusted for BMI and Age Adjusted for BMI, Age, and Gender P P P P Mean systolic BP Mean diastolic BP Mean HR lowering medication was changed during the follow-up period. In 55 of those patients, one or more substances were added, in 29 patients one or more substances were reduced, and in 15 patients substances or doses were changed. The characteristics for the follow-up group (n 196) are summarized in Table 3. Of 196 patients in the follow-up cohort, 91 (46.4%) were on BP-lowering drugs at the time of the initial visit. In these patients the medication with BP-lowering properties consisted of (n; % of follow-up cohort 196 patients): ACE inhibitors (52; 26.5%), -receptor blockers (41; 20.9%), diuretics (26; 16.7%), calcium channel blockers (32; 18.1%), nitrates (15; 7.7%), and central antihypertensive drugs (6; 3.1%). None of our patients received -adrenergic antagonists. Of those subjects on BP-lowering treatment, 77 (85%) patients had the diagnosis of hypertension and were treated an average of 9.2 ( 8.8) years before OSA was diagnosed (results from patient s questionnaire). The remaining 14 patients on BP-lowering drugs received this therapy because of coronary heart disease or heart failure ( -blockers, ACE inhibitors, nitrates, diuretics). In the group not taking BP-lowering drugs (n 105), 22 (20.9%) patients were diagnosed with arterial hypertension. Effective Bi- (n 7) /CPAP (n 189) therapy reduced the mean AHI from to events/h during the 6-month follow-up. Except for the sleep efficiency, all other sleep parameters also improved significantly with positive airway pressure therapy. The average BP and HR decreased after 6 months of Bi-/CPAP therapy. The mean systolic BP decreased from to mm Hg (P.051), mean diastolic BP from to mm Hg (P.001), and mean HR from to mm Hg (P.001). Table 3 shows the BP and HR reductions with Bi-/ CPAP therapy for the groups taking or not taking BP- Table 3. Effect of Bi-/CPAP therapy on polysomnographic data, blood pressure (BP), heart rate, and body mass index (BMI) in 196 patients with obstructive sleep apnea (OSA) Untreated OSA, Mean ( SD) After 6 Months of Bi-/CPAP Therapy, Mean ( SD) Mean of Difference (95% confidence interval) Polysomnography: AHI events/hour 31.4 (21.5) 2.2 (2.3) 29.1 ( 32.2, 26.1).001 Mean O 2 saturation 92.2 (3.6) 93.8 (2.3) 1.6 (1.12, 2.1).001 Max. O 2 desaturation 80.5 (9.2) 88.3 (6.9) 7.8 (6.2, 9.3).001 Arousal index 19.4 (10.6) 8.8 (7.0) 10.7 ( 14.7, 6.5).001 Sleep efficiency 87.3 (10.1) 87.7 (9.7) 0.4 ( 1.7, 2.5).7 BMI, full cohort (n 196) 31.5 (5.8) 31.4 (5.5) 0.09 ( 0.3, 0.6).458 Mean systolic BP, full cohort (15.5) (15.9) 2.0 ( 4.1, 0.01).051 (n 196) Group with BPLD (n 91) (16.4) (14.7) 1.2 ( 4.5, 2.1).465 Group without BPLD (n 105) (13.9) (15.7) 2.8 ( 5.3, 0.2).037 Mean diastolic BP, full cohort 80.2 (9.3) 77.5 (9.5) 2.7 ( 4.2, 1.1).001 (n 196) Group with BPLD (n 91) 81.1 (9.2) 79.6 (8.7) 1.5 ( 3.9, 9.2).223 Group without BPLD (n 105) 79.4 (9.4) 75.7 (9.7) 3.7 ( 5.7, 1.7).001 Mean heart rate, full cohort 77.7 (8.8) 75.7 (8.1) 2.0 ( 3.2, 0.8).001 (n 196) Group with BPLD (n 91) 77.2 (9.0) 75.1 (7.7) 2.1 ( 3.9, 0.3).022 Group without BPLD (n 105) 78.2 (8.6) 76.3 (8.4) 1.9 ( 3.6, 0.3).024 Bi-/CPAP bilevel/continuous positive airway pressure; BPLD BP-lowering drugs. Other abbreviations as in Table 1. P

5 AJH December 2004 VOL. 17, NO. 12, Part 1 OBSTRUCTIVE SLEEP APNEA AND BP 1085 FIG. 2. Reduction of blood pressure (BP) and heart rate (HR) after 6 months of either bilevel or continuous positive airway pressure treatment in patients taking and not taking BP-lowering drugs (BPLD). SBP systolic BP; DBP diastolic BP. lowering drugs. The separate calculation for these groups revealed that BP reduction is only significant in the group not taking BP-lowering drugs. The HR decreased significantly in both groups (Table 3 and Fig. 2). Multivariate linear regression disclosed independent predictors for the BP-lowering effects in response to Bi-/ CPAP therapy: both the initial BP before OSA therapy and the absence of any BP-lowering medication were significant predictors for reduction of both systolic ( SBP) and diastolic ( DBP) BP. Pulse pressure, age, AHI at baseline, and the reduction of AHI ( AHI) were additional independent predictors for SBP. According to the HR reduction ( HR) with Bi-/CPAP therapy, only the HR at baseline was a significant predictor (Table 4). Discussion In summary, our study suggests that: 1. There is a linear and independent relationship between the frequency of nocturnal apneas/hypopneas and the prevalence of arterial hypertension in patients with OSA. 2. Daytime systolic and diastolic BP and HR correlate positively with the frequency of nocturnal apneas/ hypopneas, independently of BMI, age, and gender. 3. The level of BP before OSA therapy as well as the absence of antihypertensive medication are independent predictors for beneficial effects of Bi-/CPAP therapy on systolic and diastolic BP. Our results are supported by the recent results from the large cross-sectional trial Sleep Heart Health Study (SHHS). 5 In the SHHS a significant and independent relation was demonstrated between the severity of sleepdisordered breathing and daytime systolic/diastolic BP. Interestingly these correlations were more evident in the age group less than 65 years compared to the older patients. Our study shows important differences to the SHHS: 1) we enrolled inpatients with moderate-to-severe OSA (mean AHI 28 events/h v 4 events/h in the SHHS); 2) the mean age in our study is lower (55.4 v 62.1 years in the SHHS); 3) the cardiovascular risk profile is, on average, more severe in our study cohort; and 4) the ethnicity of our study population is homogenous; in contrast almost 25% of the patients enrolled in the SHHS are non-white. The pathomechanism for the association between OSA and elevated BP is still not fully understood, and several pathways may be involved. One major factor could be that patients with OSA have an elevated sympathetic activity during nighttime and daytime 21,22 and have a higher norepinephrine release rate in response to hypoxia than healthy controls. 23 In our study group we observed a positive correlation between the severity of OSA as assessed by the AHI and mean daytime HR. This correlation supports the hypothesis of an elevated sympathetic nerve activity in patients with OSA. Although the association between the severity of OSA and prevalence of arterial hypertension has been consistently shown in previous studies, 4,24,25 the hemodynamic short-term and long-term effects of Bi-/CPAP therapy have not been unequivocally clarified. Four controlled studies found no 12,13 or only minor (1.4 and 2.5 mm Table 4. Multivariate regression: predictors for the BP/HR lowering effect of Bi-/CPAP therapy SBP DBP HR Predictor P P P SBP baseline DBP baseline Pulse pressure HR baseline BP-lowering drugs AHI baseline AHI BMI baseline Age Gender SBP systolic blood pressure; DBP diastolic blood pressure; HR heart rate; other abbreviations as in Tables 1 through 3.

6 1086 OBSTRUCTIVE SLEEP APNEA AND BP AJH December 2004 VOL. 17, NO. 12, Part 1 Hg) 14,15 daytime BP reduction after Bi-/CPAP therapy. In contrast, two recent studies 16,17 demonstrated a more pronounced effect of CPAP therapy on daytime BP. Sanner et al 16 reported a reduction of the mean arterial BP by an average of 4.6 mm Hg during CPAP therapy for 9 months in 52 patients with a mean AHI of 32 events/h. Becker et al 17 demonstrated for the first time in a controlled and randomized study including 32 patients with severe OSA (mean AHI 62.5 events/h) an even more pronounced reduction by an average of 9.9 mm Hg mean arterial BP during CPAP therapy. The discrepancy with previous studies on the same topic is not quite clear. It has been argued 14 that the percentage of hypertensive patients was higher in the latter studies (Sanner et al: of 52 patients (71%), mean BP 137/88 mm Hg; Becker et al: of 32 patients (66%), mean BP 140/86 mm Hg) compared to the former studies (Dimsdale et al: of 29 patients (34%), mean BP 128/82 mm Hg; Pepperell et al: of 104 patients (21%) patients, mean BP 134/85 mm Hg; Faccenda et al: normotensive, mean BP 127/78 mm Hg). These differences in the percentage of hypertensive OSA patients may influence the magnitude of the BP-lowering effects in response to CPAP therapy. Despite of a high percentage of arterial hypertension in our study cohort (58%), the reduction of the mean BP and mean HR by Bi-/CPAP therapy was only moderate (see Table 3). A conceivable reason for this might be that the mean daytime BP was lower in our group (130/79 mm Hg) than in the follow-up cohort of Becker et al 17 (140/86 mm Hg) or Sanner et al 16 (137/88 mm Hg). This matches our findings. We found that the level of BP and not the diagnosis of arterial hypertension in patients untreated for OSA is an independent predictor for the beneficial effects of Bi-/CPAP therapy on BP (Table 4). A new finding is that the beneficial effect of Bi-/CPAP therapy on daytime BP was prominent in those patients without any BP-lowering medication, and was not significant in those who were on BP-lowering drugs. Interestingly, the significant reduction of the mean daytime BP in the follow-up cohort was based on a BP decrease in the group not taking BP-lowering drugs, despite the lower initial BP in these patients (Table 3, Fig. 2). It is beyond the scope of our study to disclose the pathomechanism for our finding that Bi-/CPAP therapy does not reduce daytime BP significantly in those patients with OSA who were already on BP-lowering medication. Hedner et al 26 demonstrated a reduction in sympathetic activity after long-term CPAP treatment in patients with OSA. Other investigators reported an improvement of vascular reactivity. 27 A reduction of vasoconstrictive hormones, such as renin and plasma angiotensin II, 28 during CPAP therapy is also discussed. We speculate that the antihypertensive medication interacts with some of these pathophysiologic pathways, which are supposed to cause hypertension in patients with OSA. The Bi-/CPAP therapy in addition to an antihypertensive medication may not be sufficient to cause a further reduction in mean BP. The patient questionnaire revealed that those patients with treated hypertension were on antihypertensive drugs for an average of 9.2 years at the time when OSA was diagnosed. We cannot exclude the possibility that longstanding hypertension might have caused a perpetuated elevation of BP (eg, due to vascular remodeling). Thus, these patients may respond less well to Bi-/CPAP therapy as compared to patients without long-standing hypertension. In contrast to BP, we noted a beneficial effect of Bi-/ CPAP therapy on the HR, irrespective of whether the patients were treated or not with antihypertensive medication. This observation suggests that Bi-/CPAP therapy further reduces sympathetic nerve activity, despite the presence of antihypertensive medication. It should be noted, however, that only 45% of our group of patients taking BP-lowering drugs were on -blocking agents. Sanner et al 16 showed that pulse pressure and a high HR at baseline were predictors for BP reduction and CPAP therapy. In our model, pulse pressure only predicted the reduction of systolic BP, whereas a high HR at baseline only predicted the reduction of HR. The fact that AHI at baseline and the reduction of AHI during Bi-/CPAP therapy were significant predictors for the decline in systolic BP underlines the beneficial effect of Bi-/CPAP therapy on BP. However, we could not show such a significant association for diastolic BP and HR reduction. In summary, our study confirms, in a large cohort of patients, a linear and independent relationship between the frequency of nocturnal apneas/hypopneas and the level of BP and HR in patients with OSA. As a result Bi-/CPAP therapy had a beneficial effect on the daytime systolic and diastolic BP, as well as on the mean HR. This beneficial effect on the BP, however, was more evident in patients with elevated BP values at the start of Bi-/CPAP therapy and was restricted to those who were not on antihypertensive medication. Limitations Our prospective study was not controlled by a group of patients who was treated with subtherapeutic Bi-/CPAP. There is a controversy about such a control group. Even subtherapeutic CPAP therapy has a substantial impact on the AHI and sleep structure and therefore, does not resemble placebo treatment. We selected patients in whom the BP-lowering medication was kept unchanged during the hospital stay and during a 6-month follow-up period. Of the 540 patients, seen in the initial polysomnography, 295 patients were treated with Bi-/CPAP therapy and could be restudied after a 6-month follow-up period. Of these, 99 patients had to be excluded for analysis because the BP-lowering medication was changed during the follow-up period. This high number of dropouts, as well as this selection, may have been biased to patients with mild arterial hyperten-

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