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(Chest. 2002;122:1125-1132.)
© 2002 American College of Chest Physicians

The Effect of Correction of Sleep-Disordered Breathing on BP in Untreated Hypertension*

K. Mae Hla, MD, MHS; James B. Skatrud, MD; Laurel Finn, MS; Mari Palta, PhD and Terry Young, PhD

* From the Departments of Medicine (Drs. Hla and Skatrud) and Population Health Sciences (Ms. Finn and Drs. Hla, Palta, and Young), University of Wisconsin Medical School, Madison, WI.

Correspondence to: K. Mae Hla, MD, MHS, Department of Medicine, Section of General Internal Medicine, University of Wisconsin Medical School, 2828 Marshall Ct, Suite 100, Madison, WI 53705


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objectives: To compare BP response to 3 weeks of nasal continuous positive airway pressure (CPAP) in hypertensive patients with and without sleep-disordered breathing (SDB).

Design: A controlled, interventional trial of nasal CPAP in patients with and without SDB.

Participants and setting: Twenty-four men, aged 30 to 60 years, with mild to moderate untreated hypertension recruited from employee health and primary care clinics.

Methods: Based on in-laboratory polysomnography, 14 hypertensive patients had SDB, defined by five or more episodes of apnea and hypopnea per hour of sleep (apnea-hypopnea index [AHI], >= 5), and 10 had no SDB (AHI, < 5). We performed 24-h ambulatory BP monitoring on all patients at baseline, during CPAP, and after CPAP treatment. In patients with an AHI >= 5, nasal CPAP was titrated to reduce the AHI to < 5. Patients with an AHI < 5 received CPAP of 5 cm H2O to control for any potential effect of CPAP per se on BP. Both groups received CPAP for 3 weeks.

Results: After adjusting for age and body mass index, the mean nocturnal systolic and diastolic BP changes after CPAP treatment in the SDB group were significantly different from those in the no-SDB group: -7.8 vs +0.3 mm Hg (p = 0.02), and -5.3 vs -0.7 mm Hg (p = 0.03), respectively. There was a similar, although statistically insignificant, difference in the adjusted mean daytime systolic and diastolic BP changes after CPAP treatment between the two groups (-2.7 vs +0.4 mm Hg and -2.3 vs -1.7 mm Hg, respectively).

Conclusions: Three weeks of nasal CPAP treatment of SDB in hypertensive men caused the lowering of nocturnal systolic and diastolic BP values, suggesting that increased nocturnal BP in persons with hypertension was causally related to the apnea and hypopnea events of SDB.

Key Words: BP • hypertension • sleep apnea • sleep-disordered breathing treatment


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Hypertension is a polygenic disorder that can be influenced by a variety of environmental factors. Cross-sectional studies demonstrating the association between sleep-disordered breathing (SDB) and hypertension1 have led to the hypothesis that SDB causes hypertension.1 2 3 Findings from the only prospective study to date provide evidence that SDB leads to hypertension.4 Clinical trials of nasal continuous positive airway pressure (CPAP), a therapy that eliminates the events of SDB, represent another line of investigation into the causal role of sleep apnea in hypertension.5 6 7 8 9 10 Some, but not all, of these studies suggest that CPAP lowers BP in patients referred to a sleep clinic with symptomatic sleep apnea. Results from these CPAP interventional trials have been taken as evidence for or against a causal role of SDB in hypertension. However, the CPAP intervention studies overlook the possibility that nasal CPAP by itself could possibly have an effect on BP that is independent of its effect through eliminating sleep apnea. A major limitation of previous studies that attempted to establish a causal link between hypertension and sleep apnea has been the failure to use an adequate level of nasal CPAP in a control group of patients who do not have SDB. Without such a control group, we cannot be sure that the BP changes observed in the treatment groups were due to the effect of CPAP on eliminating apnea and hypopnea events as opposed to an independent effect of CPAP on other determinants of arterial pressure. The few studies that attempted to control for a CPAP effect used inadequate controls such as placebo tablets5 or the use of a mask with minimal levels of CPAP.9 In addition, because these studies were performed only among patients with sleep apnea, they lacked a control group of patients without SDB.

A second problem in attributing BP change to CPAP treatment is that previous trials of CPAP have been conducted with patients who had symptomatic sleep apnea severe enough to be referred for polysomnographic evaluation. These patients could have changes in their BP response as a result of excessive daytime sleepiness, sleep fragmentation, or the chronicity of the sleep apnea that might not be relevant in patients with hypertension who do not present with sleep complaints or symptoms impairing daytime function. Thus, populations of patients with clinically diagnosed sleep apnea and coexistent hypertension form the basis of much of our present knowledge linking sleep apnea to hypertension. The contribution of SDB to daytime hypertension has been infrequently studied in patient populations with clinically established hypertension.

To overcome these gaps in understanding the role of SDB in hypertension from previous CPAP intervention studies, we selected a population of hypertensive patients to investigate whether there was a BP response to 3 weeks of nasal CPAP treatment in those who had undiagnosed, occult SDB. The main purpose of our study was to determine whether there was an independent, causal effect of SDB on BP. We also used CPAP treatment in the hypertensive patients with no SDB to control for any other effect that CPAP itself potentially might have on BP independent of its effect through correction of SDB.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patient Selection
Male patients seen in the University of Wisconsin Hospital Employee Health and Primary Care outpatient clinics, aged 30 to 60 years, were screened prospectively for hypertension using a random-zero sphygmomanometer by a trained observer on three separate occasions. Three BP readings were taken over a period of about 6 min at each occasion. Patients with two of the three measurements of systolic BP >= 135 mm Hg or diastolic BP >= 85 mm Hg were asked to return for subsequent measurements. Individuals whose difference in BP was > 10 mm Hg for systolic BP and > 5 mm Hg for diastolic BP between the last two visits were excluded from the study because of concern related to labile BP and measurement error issues. In patients with mild hypertension that was being controlled with minimal antihypertensive therapy with single agents (n = 2), medication was tapered off over a 3-week period. All newly identified hypertensive patients and those who tapered off of medications with an untreated average systolic BP of >= 135 mm Hg or diastolic BP of >= 85 mm Hg were selected for further 24-h ambulatory BP measurements. All patients gave informed consent.

Patients were excluded from the study for the following reasons: (1) screening BP > 180/110 mm Hg, which would warrant definite antihypertensive therapy; (2) self-reported (and documented by chart review, when available) underlying comorbid diseases such as known coronary artery disease, cerebrovascular diseases, diabetes mellitus requiring pharmacologic treatment, congestive heart failure, COPD, renal disease, atrial fibrillation, and malignancy; (3) current use of adrenergic-augmenting psychotropic drugs including antidepressants, ephedrine, and other stimulants; (4) history of severe alcohol abuse sufficient to interfere with compliance; or (5) unstable weight (self-reported weight change of > 4.5 kg in preceding 6 months) or participation in a weight-reduction program or diet.

Protocol
The study consisted of three phases: a baseline pre-CPAP phase, an interventional CPAP phase, and a post-CPAP phase (Fig 1 ).



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  		Figure 1.. Study protocol flowchart. pt = patient.

 
In the pre-CPAP phase, patients seen in the Employee Health and Primary Care clinics at the University of Wisconsin Hospital with documented mild and moderate hypertension (defined as untreated average BP over three screening visits ranging from 135/85 to 180/110 mm Hg) were evaluated for SDB by full in-laboratory polysomnography. Patients were then categorized into hypertensive persons with SDB and hypertensive persons without SDB depending on their apnea-hypopnea index (AHI), a summary measure of SDB, using a cut-point of >= 5 events per hour of sleep. Baseline 24-h ambulatory BP measurements, weight, and medication history were recorded for all patients.

The interventional phase consisted of CPAP treatment, which was titrated during overnight polysomnography in the sleep laboratory to eliminate apnea, hypopnea, snoring, and flow limitation. During the 3 weeks of CPAP intervention, patients recorded daily compliance diaries regarding the use of CPAP. On the last day of CPAP treatment, 24-h overnight (night 21) and daytime (days 21 and 22 inclusive) ambulatory BP monitoring was performed to obtain measurements with CPAP use.

The post-CPAP measurements included overnight BP measurements during sleep on the night without CPAP use (night 22) and daytime ambulatory BP measurements during wakefulness the following morning (day 23). Most patients removed their BP monitoring unit early in the day on day 23. The few available post-CPAP daytime waking BP values were insufficient for analysis and thus were not reported.

Measurements
BP: Screening BP measurements were performed in accordance with recommendations of the American Heart Association,11 using appropriate cuff size, on the left arm, in the seated position, with the random-zero sphygmomanometer by a research assistant who was trained to accurately record readings without end-digit bias. A 24-h ambulatory monitor (Accutracker II; Suntech Medical Instruments/Eutectics Electronics; Raleigh, NC) was used to record 24-h ambulatory BPs in all patients who fulfilled the inclusion criteria for the diagnosis of borderline/mild hypertension after screening BP measurements. The monitor utilizes a modified auscultatory method of BP measurement. The frequency of cuff inflation was preset to automatically record at intervals of 15 to 20 min during waking hours (6 AM to 11 PM) and every 30 min during periods of sleep (11 PM to 6 AM). The ambulatory BP data record for each patient included readings of systolic pressure, diastolic pressure, mean arterial pressure, and heart rate. A detailed diary of activities of daily living, including specific times each patient went to bed, turned lights off, and woke up, was kept by all patients throughout all 24 h BP monitoring periods. Daytime and nighttime mean systolic and diastolic pressures were categorized using the patients’ recorded sleeping and waking times.

On the last day of CPAP treatment (day 21), ambulatory BP measurements were repeated for 48 h to determine the change in pressures from baseline (pre-CPAP) to during CPAP (the first 24 h with use of CPAP) and post-CPAP (the second 24 h without use of CPAP) treatments. The change in mean systolic and diastolic pressures during sleep and wakefulness (as defined by the times recorded on individual diaries) from before to after 3 weeks of CPAP treatment was calculated for each patient.

Sleep Evaluation: In-laboratory polysomnography was performed using a multichannel polygraph (model 78; Grass Instrument Co; Quincy, MA). EEG (C3/A2, C4/A1, O1/A2, and O2/A1 leads), electrooculogram, and submental and tibial electromyelograms were obtained. Airflow was measured with nasal and oral thermistors (ProTec thermocouple; ProTec; Woodinville, WA). Movement of the chest wall and abdomen was measured with respiratory inductance plethysmography (Respitrace Ambulatory Monitoring; Ardsley, NY). Calibration was performed with an isovolume maneuver followed by a spirometric volume calibration. Oxygen saturation was measured using pulse oximetry (Datex Ohmeda; Madison, WI). Sleep stages were analyzed using the method of Rechtschaffen and Kales.12 The polysomnogram records were scored by trained technicians. All scored records were checked and errors adjudicated for consistency by the sleep laboratory manager.

Respiratory events were defined as follows: apnea was the cessation of airflow at the nose and mouth for >= 10 s; and hypopnea was a discernible reduction in respiratory effort accompanied by a decrease of >= 4% in oxygen saturation. Patients then were classified into two experimental groups. Patients who had >= 5 events of apnea or hypopnea per hour of sleep (ie, AHI, >= 5) were classified as patients with SDB. Patients with an AHI of < 5 were categorized as patients without SDB.

In 12 of the patients who showed SDB, nasal CPAP was administered via a nasal mask (Respironics, Inc; Murrysville, PA) and titrated during a full polysomnography. In the remaining two patients who showed sleep apnea or hypopnea during the first 4 h of the initial screening sleep study, titration of the appropriate level of CPAP was performed during the second half of the initial screening polysomnography. The mask was fitted with a small pneumotachograph to measure flow during CPAP titration. CPAP was titrated in 2.5 cm H2O increments until the apneas, hypopneas, and snoring were eliminated. Further adjustment in the CPAP level was made to eliminate evidence of dynamic inspiratory flow limitation and to return the inspiratory flow pattern to the appearance during wakefulness. The mean (± SD) AHI after optimal CPAP titration was 0.9 ± 1 event per hour, with a range of 0 to 4 events per hour of sleep.

All patients used either the therapeutic or sham nasal CPAP at night for 3 weeks. Patients with SDB received the therapeutic level of CPAP that had been shown to eliminate all apneas, hypopneas, flow limitation, and audible snoring during the previous nocturnal polysomnography. Patients with no SDB received sham CPAP that was arbitrarily set at a pressure of 5 cm H2O. Patients were not told of their SDB status or the CPAP setting. In 16 patients, compliance was monitored by recording the time that the mask pressure was within 2 cm H2O of the prescribed pressure.13

Body Mass Index: Body weight and height were measured on all patients to calculate the body mass index (BMI). All patients maintained the same weight during 3 weeks of CPAP.

Data Analysis
Using 24-h BP measurements, mean BP during sleep and wakefulness for each patient was compared before and after 3 weeks of CPAP treatment. The main outcome measure was the paired difference in systolic and diastolic BP from baseline to during and after CPAP treatment. To control for important baseline differences in covariables between groups, all outcome data on BP results were analyzed both with and without adjusting for BMI and age. Univariate and multivariate (controlling for age and BMI) linear regressions were used with these mean differences as the dependent variables. Comparisons were made across SDB groups, dichotomized with a cut-point AHI of 5. A p value of <= 0.05 was considered to indicate statistical significance. If a significant difference in the paired differences was found between SDB status groups, the mean paired difference for each group was assessed for significance from zero. This was examined by performing a t test, which utilized the overall pooled SD from the regression model. All data were analyzed with an intention-to-treat design regardless of compliance with CPAP use.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Hypertensive patients with SDB (AHI, >= 5) were older and heavier, and had higher systolic and diastolic BP values during both wakefulness and sleep compared with hypertensive men who did not have SDB (AHI < 5) [Table 1 ]. Because of the expected and important baseline differences in mean age and BMI between groups, all outcome data on BP results are reported both with and without adjustment for age and BMI. The CPAP level used in the group without SDB was 5 cm H2O. The median CPAP level used in the SDB group was 9 cm H2O (range, 7 to 15 cm H2O).


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  		Table 1.. Characteristics of Study Subjects*

 
CPAP Effect on Nighttime BP
After 3 weeks of CPAP treatment, hypertensive patients with SDB had significant decreases in nocturnal systolic and diastolic pressures from baseline, while those without SDB did not demonstrate a BP change (within-group changes). There was also a significant difference between the two groups in the mean decrease of nocturnal systolic and diastolic pressures after CPAP treatment (between-group comparisons).

Figure 2 shows the raw unadjusted mean systolic and diastolic pressures of each patient in the two groups during sleep in the pre-CPAP, CPAP, and post-CPAP periods. The unadjusted mean nighttime systolic BP decreased by 10.4 mm Hg with CPAP treatment in the SDB group (AHI, >= 5), while it increased by 1.9 mm Hg in the control group with AHI < 5 (p = 0.0003). The unadjusted mean nighttime diastolic pressure decreased 5.2 mm Hg in the SDB group compared with an increase of 0.3 mm Hg in the control patients without SDB (p = 0.024). On both the nights with CPAP usage and those without CPAP usage (ie, post-CPAP usage), the mean nocturnal systolic and diastolic BP in the SDB group was significantly reduced compared with the pre-CPAP BP (p < 0.05) [Fig 2 ].



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  		Figure 2.. Systolic BP (•) and diastolic BP ({circ}) during sleep. Each data point represents an individual’s average BP recorded between sleep onset and awakening within each study period (pre-CPAP, during CPAP, and post-CPAP treatment); horizontal bars indicate mean BP values at each study period averaged within SDB groups defined by AHI (AHI < 5, no SDB; AHI >= 5, SDB). * = p < 0.05 for comparison of unadjusted mean pre-CPAP BP values with mean CPAP and post-CPAP BP values in patients with SDB.

 
As shown in Table 2 , after adjusting for age and BMI, the mean nighttime systolic BP decreased by 10.3 mm Hg with CPAP and by 7.8 mm Hg after CPAP treatment in the SDB group (p = 0.002 and p = 0.001, respectively, for within-group changes). In contrast, the mean nighttime systolic BP increased by 1.7 mm Hg with CPAP and by 0.3 mm Hg after CPAP therapy in the group without SDB (p = 0.55 and p = 0.91, respectively, for within-group changes). The mean changes in systolic BP with CPAP and after CPAP treatment were significantly different between the two study groups (p = 0.007 and p = 0.02, respectively, for between-group comparisons). The adjusted mean diastolic BP decreased by 4.5 mm Hg with CPAP therapy and by 5.3 mm Hg after CPAP therapy in the patients with SDB (p = 0.01 and p = 0.003, respectively, for within-group change), compared with a decrease of 0.7 mm Hg in those without SDB (p = 0.74 and p = 0.70, respectively, for within-group changes). The mean change in diastolic pressure after CPAP treatment differed significantly between the two groups (p = 0.03 for between-group comparison).


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  		Table 2.. Change in Nocturnal BP From Baseline to During CPAP and After CPAP Treatment Adjusted for Age and BMI*

 
CPAP Effect on Daytime BP
There was a similar trend for a decrease in mean daytime systolic and diastolic BP values from baseline to CPAP treatment noted in the SDB group (within-group change), as seen in Figure 3 and Table 3 . After controlling for age and BMI, the mean daytime systolic BP decreased by 2.7 mm Hg in the patients with SDB with CPAP treatment (p = 0.07), compared with an increase of 0.4 mm Hg in the control group (p = 0.8). Similarly, the mean decrease in daytime diastolic BP was 2.3 mm Hg in the SDB group (p = 0.08), compared with 1.7 mm Hg (p = 0.26) in the group without SDB. However, there were no statistically significant differences between the SDB and the control groups (between-group comparisons) in the mean change in daytime systolic and diastolic BP. The corresponding p values were p = 0.20 for systolic BP change and p = 0.81 for diastolic BP change (Table 3) .



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  		Figure 3.. Systolic BP (•) and diastolic BP ({circ}) during wakefulness. Each data point represents an individual’s average BP recorded during wakefulness within each study period (pre-CPAP and during CPAP treatment); horizontal bars indicate mean BP values at each study period averaged within SDB groups defined by AHI (AHI < 5, no SDB; AHI >= 5, SDB).

 

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  		Table 3.. Change in BP During Wakefulness From Baseline to CPAP Treatment Adjusted for Age and BMI*

 
Effect of Compliance With CPAP Treatment
Full compliance data, as measured by the time at pressure recordings, were available for eight patients in each group. The patients with SDB used nasal CPAP at the prescribed pressure for a mean (± SD) of 5.7 ± 1.7 h per night, whereas those who did not have SDB used CPAP for 3.5 ± 2.2 h per night (p = 0.04). Compliance was lower in patients without SDB during each night during the 3-week study period.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In our study of hypertensive men, the elimination of SDB with 3 weeks of nasal CPAP therapy produced the following results: (1) systolic and diastolic BP values decreased during the night after a 3-week trial of CPAP; (2) the BP-lowering effect persisted during the night after the CPAP trial was terminated; and (3) daytime BP showed a trend toward reduction after the 3-week CPAP trial. Our data indicate that the elimination of SDB events reduces nocturnal BP in hypertensive patients with occult, undiagnosed sleep apnea/hypopnea. This extends previous findings in indicating that even preclinical, undiagnosed SDB may have a causative role in elevating nocturnal BP.

Several strengths are evident in our study design. First, we studied patients with mild hypertension who were either untreated or who had stopped receiving their medications. Previous studies5 6 7 8 9 have all used the presence of sleep apnea rather than hypertension as the defining entry criteria. The selection of hypertensive patients in our study allowed us to answer the question concerning the role of SDB in causing reversible hypertension. Second, we used a CPAP control group to determine whether CPAP would have an effect on BP through an un-known mechanism, independent of its effect of eliminating SDB. If CPAP per se caused a decrease in BP unrelated to its effect on SDB, it could falsely accentuate the observed decrease in BP related to its effect on the elimination of SDB. On the other hand, if CPAP caused an increase in BP in the study patients related to discomfort or anxiety, it could potentially mask the effect on BP. We did not see a significant effect on the CPAP on BP in our control, nonapneic, hypertensive patients. Thus, we were able to safely assume that the effect on BP seen in subjects with apnea was mediated through the elimination of SDB. Third, we used a relatively long period of CPAP administration. Some studies9 have suggested that 1 week is insufficient to demonstrate a cardiovascular response to CPAP. Finally, we used in-laboratory nocturnal polysomnography to document the severity of sleep apnea/hypopnea and the efficacy of nasal CPAP. The use of EEG monitoring assured that we could make an accurate determination of respiratory events related to specific stages of sleep.

The mechanism of reduction in nocturnal BP during treatment with nasal CPAP is most likely related to its effect in eliminating apneas and hypopneas during sleep. Acute elevations in BP have been documented in association with abnormal respiratory events.14 It has been shown that during each apnea or hypopnea, chemoreflex stimulation occurs as a result of acute hypoxia and hypercapnia, which in turn causes increased peripheral vasoconstriction. The peripheral vasoconstriction and increased heart rate are the predominant determinants of the acute increase in BP.14 Arousal from sleep may also play a role in BP elevation, but its effect becomes less important in the presence of more severe levels of chemoreflex activation.14 Reductions in BP have been previously reported during nasal CPAP therapy in patients with sleep apnea5 6 7 8 9 and high upper airway resistance syndromes.15 Thus, the elimination of sleep apnea and hypopnea with nasal CPAP and the resulting reduction in chemoreflex stimulation and arousals is a plausible explanation for the reduction of nocturnal BP in our study population.

We observed that the reduction in nocturnal BP persisted on the first night following 3 weeks of consecutive nights of CPAP usage, even though CPAP had been discontinued. The most likely explanation is that nasal CPAP improved upper airway patency in a way that was maintained on the first night following the 3 weeks of CPAP usage. In previous studies, a reduction in the AHI persisted on the first night without CPAP therapy, while the upper airway caliber improved after commencing therapy in one study16 and was unchanged in another.17 The mechanism for this persistent effect included reduced edema,16 improved upper airway dilator muscle activity,18 reduced upper airway muscle fatigue,19 and reduced upper airway vascularity.20 We did not perform polysomnography on the night without CPAP to confirm this possibility. Alternatively, nasal CPAP therapy may have resulted in a carry-over effect due to the alteration in neurohumoral influences that regulate BP. During the 3 weeks of CPAP therapy, changes may have occurred in vascular responsiveness,21 baroreflex sensitivity,22 sympathetic nerve activity,23 and hormone levels.24 25 The reduction of nocturnal BP even in the absence of nasal CPAP supports the idea that the positive airway pressure associated with the CPAP did not have an independent effect in reducing the nocturnal BP.

Our demonstration of a trend only toward a reduction in daytime BP with CPAP therapy is consistent with the difference in results noted in previous studies. A decrease in BP has been reported in some,5 8 10 but not all studies.25 26 Several possible explanations may account for our observation of only a small reduction in daytime BP. First, the 3-week duration of CPAP therapy may have been insufficient to cause a reduction in sympathetic activity and a subsequent significantly greater lowering of BP. It has been suggested that any effect of CPAP treatment on sympathetic drive may be evident only after extended therapy lasting up to 6 to 12 months.27 Second, CPAP therapy may reverse the counterregulatory effects of SDB that serve to minimize BP elevation due to sleep apnea. For example, in patients with sleep apnea, nasal CPAP reduces the high levels of atrial natriuretic peptide and diuresis that are observed prior to therapy.28 Thus, the decreased diuresis may attenuate any reductions in daytime BP that otherwise might be observed. Third, our sample size may have been too small to detect a significant reduction in daytime BP. For example, given our data (sample size and SD of BP changes), using 90% power, and an {alpha} of 0.05, the minimum detectable drop in daytime systolic BP was 4.1 mm Hg. However, our observed changes in daytime systolic BP levels were similar to the difference in systolic BP levels seen between subjects with and without SDB in large, population-based, cross-sectional and longitudinal studies.4 Fourth, poor compliance with nasal CPAP may have limited a daytime BP effect. However, when compliance was measured using a time-at-pressure-measurement device in our patients, an adequate duration of usage suggested that poor compliance was not the source of our failure to detect a significant daytime reduction in BP. Also, the observed lower compliance with CPAP use in patients with no SDB could have a potential effect on BP change: if CPAP per se had a BP-lowering effect, the lesser use of it in patients without SDB could have minimized the actual difference in daytime BPs between the groups. Fifth, snoring without sleep apnea has been associated with a slight elevation in daytime BP.29 Five of our patients without SDB had self-reported snoring. CPAP may have slightly lowered their daytime BP and thereby prevented a statistically significant difference in daytime BP between the patients with and those without SDB. Finally, our patients may have had a milder degree of SDB than that seen in previous studies of patients selected on the basis of having a substantial degree of sleep apnea. The contribution of sleep apnea to hypertension is shown to be greater with more severe disease,4 and, consequently, the reduction in BP in our patients with occult, clinically undiagnosed SDB would be expected to be smaller. We concluded that the small lowering of daytime BP in our hypertensive patients is consistent with the relatively small independent contribution of sleep apnea to hypertension in patients with occult SDB. This finding does not minimize the important public health impact of a small elevation of BP on cardiovascular morbidity and mortality or the beneficial effects of small therapeutic reductions in arterial pressure.

Our results have several important clinical implications. First, the apnea and hypopnea events of SDB cause nocturnal hypertension, which is a risk factor for cardiovascular morbidity and mortality. Second, treatment of occult sleep apnea with nasal CPAP is associated with a substantial reduction in nighttime BP. A reduction in BP similar to that obtained with CPAP has been associated with a substantial reduction in the incidence of cerebrovascular accidents and myocardial infarction in previous studies.30 Therefore, the recognition and treatment of occult SDB may be relevant to improving long-term outcomes of patients with hypertension, especially in cases of refractory or poorly controlled BP.


   Acknowledgements
 
The authors thank Monica Kunesh, Joel Faith, Renee Arakawa, and the Sleep Laboratory personnel for technical assistance.


   Footnotes
 
Abbreviations: AHI = apnea-hypopnea index; BMI = body mass index; CPAP = continuous positive airway pressure; SDB = sleep-disordered breathing

This research was supported by National Institutes of Health grants P50 HL42242-06 and RO1 62252, National Institutes of Health Sleep Academic Award, General Clinical Research Center RR 03186, and the Veterans Affairs Research Service, University of Wisconsin, Madison, WI.

Received for publication October 4, 2001. Accepted for publication March 19, 2002.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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