Lateral Pharyngoplasty Reduces Nocturnal Blood Pressure in Patients With Obstructive Sleep Apnea

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1 The Laryngoscope VC 2013 The American Laryngological, Rhinological and Otological Society, Inc. Lateral Pharyngoplasty Reduces Nocturnal Blood Pressure in Patients With Obstructive Sleep Apnea Carolina F. de Paula Soares, MD; Luciano Cavichio, MD; Michel B. Cahali, MD, PhD Objectives/Hypothesis: To compare the values of 24-hour ambulatory blood pressure monitoring (ABPM) in patients with obstructive sleep apnea (OSA), before and after lateral pharyngoplasty, and to investigate the influence of pre- and posttreatment polysomnographic and anthropometric variations on changes in ABPM. Study Design: Prospective study. Methods: Arterial blood pressure with 24-hour ABPM and nocturnal polysomnography were measured before and 6 months after surgery in 18 consecutively evaluated adults with OSA at a tertiary center. Results: A total of 83.3% were normotensive patients. Nocturnal measurements showed a decrease of 5.3 mmhg in mean arterial pressure (MAP; P 5.01), 7.4 mmhg in mean arterial systolic pressure (SP; P 5.006), and 4.2 mmhg in mean arterial diastolic pressure (DP; P 5.03), leading to significant reductions in all 24-hour measurements: 3.6 mmhg in MAP, 4.8 mmhg in SP, and 2.9 mmhg in DP. There were also significant mean reductions in the apnea hypopnea index (AHI), from 33.5 to 20.9 (P 5.02), arousal index, from 31.6 to 16.7 (P 5.005), and percentage of total sleep time with oxyhemoglobin saturation < 90%, from 10.6% to 0.9% (P 5.008). No correlations were noted between the measurements of arterial blood pressure and polysomnographic or anthropometric variations. Conclusions: In this small case series, lateral pharyngoplasty reduced the values obtained in the 24-hour ABPM due to a significant reduction of blood pressures during sleep in patients with OSA 6 months after surgery. Although the patients presented with reductions in AHI, arousals, and desaturation time, this was not correlated with the improvement in arterial blood pressure. Key Words: Obstructive sleep apnea, blood pressure, therapy, otorhinolaryngological surgical procedures, lateral pharyngoplasty. Level of Evidence: 4 Laryngoscope, 124: , 2014 INTRODUCTION The prevalence of obstructive sleep apnea (OSA) is higher in populations with systemic arterial hypertension (SAH), given a series of common risk factors, such as obesity and male gender. 1 In middle-aged and elderly individuals without previous diagnosis of SAH, dyslipidemia, or diabetes, the presence of OSA is associated with increased prevalence of SAH. Once the main confounding factors have been corrected (age, gender, and body mass index [BMI]), along with other potentially relevant variables (alcohol consumption, smoking), an increase in the apnea hypopnea index (AHI) and a longer drop in oxyhemoglobin saturation < 90% upon polysomnography were associated with a higher risk for SAH. 2 From the Department of Otolaryngology (C.F.D.P.S., M.B.C.) and Department of Cardiology (L.C.), Hospital do Servidor Publico Estadual de Sao Paulo; and Department of Otolaryngology, Hospital das Clinicas, University of Sao Paulo Medical School of the University of S~ao Paulo (M.B.C.), S~ao Paulo, Brazil Editor s Note: This Manuscript was accepted for publication June 27, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Carolina Ferraz de Paula Soares, R. Dom Pedro II 2099/901, , Cascavel-Parana, Brazil. naliroca@hotmail.com DOI: /lary Changes in blood pressure following treatment for OSA were studied with the use of continuous positive airway pressure (CPAP) 3,4 and intraoral appliances. 5 Only one article in English on blood pressure variations in adults following surgical treatment could be found in the PubMed database. 6 A new technique for pharyngeal surgery was proposed in 2003: lateral pharyngoplasty. 7 By proposing the myotomy of the superior pharyngeal constrictor muscle and the palatopharyngeal muscle to remove the passive constriction of the pharynx and support the lateral pharyngeal wall, this technique resulted in improved clinical and polysomnographic results compared to the classic and widespread uvulopalatopharyngoplasty (UPPP). 8 Lateral pharyngoplasty (LP) has been routinely used in our institution for the treatment of OSA since The aim of this study was to assess the values of 24-hour ambulatory blood pressure monitoring in patients with OSA, before and after surgical treatment with LP. Furthermore, the influences of polysomnographic and anthropometric variations on changes in ABPM were investigated. MATERIALS AND METHODS This research project was approved by the ethics committee of our institution and registered under Clinical Trials with the number NCT

2 From May 2009 to February 2010, 29 patients underwent the lateral pharyngoplasty procedure to treat primary snoring (three cases) or OSA (AHI > 5, 26 cases) at our institution. After having received the recommendation for surgical treatment with lateral pharyngoplasty, we prospectively and consecutively recruited those patients with OSA to participate in the study. Twenty-three male and female adult patients with OSA agreed in participate in the study. All of them failed to tolerate or refused therapy with continuous positive airway pressure or mandibular repositioning devices, and they all signed an informed consent form. Patients with or without a history of SAH, with no prior pharyngeal surgery, with clearly identifiable posterior tonsillar pillars, and with no major facial skeletal deformities at inspection were included in the study. Patients with BMIs > 35 kg/m 2 and chronic users of benzodiazepines, neuroleptics, or other drugs that alter sleep structure were not candidates for lateral pharyngoplasty. Patients with SAH refractory to medical treatment where excluded from the study because it was a relative contraindication for surgical treatment. Those presenting with diastolic pressure (DP) > 120 mmhg during office baseline measurement or arterial blood pressure monitoring (ABPM), pre- or postoperatively, were also excluded due to likely failure of medical therapy for SAH. Our protocol included evaluations with 24-hour ABPM and nocturnal polysomnography in the laboratory, on separate days, before and 6 months after surgery. Preoperative polysomnography and ABPM were done between 2 and 12 months apart (polysomnography was always the first test), whereas postoperative examinations were done between 4 days and 2 months apart. Patients undergoing treatment for SAH were instructed to maintain the same medication until the postoperative evaluations. All patients were asked about the presence and maintenance of smoking habits throughout the study. Ambulatory Blood Pressure Monitoring ABPM is based on the indirect and intermittent measurement of arterial blood pressure, with minimum discomfort to the patient, for a continuous period of 24 hours. Indirect measurements were obtained by oscillometry. The test was always performed on business days, on a day that was representative of the patient s everyday activities; scheduled readings were set to be taken every 20 minutes between 7 AM and 10 PM and every 30 minutes between 10 PM and 7 AM. Tests were considered valid when at least 14 readings had been recorded during the day period and seven during the night period. After baseline measurement of blood pressure with mercury sphygmomanometer, the recording device (TM-2430; A&D company, Tokyo, Japan) and ABPM cuff were placed on the patients in the institution s Electrocardiography Department. Patients were requested to write down details regarding the times at which they woke up and went to sleep, activities performed during the evaluation period, medications used, and the presence of symptoms, such as pain or irritation. 9 Preoperative ABPM was performed between 7 and 2 days before surgery. Postoperative ABPM was performed, on average, for 187 days after surgery (ranging from 95 to 262 days). Due to scheduling difficulties, three patients performed the postoperative ABPM for between 95 and 118 days after surgery, whereas the others completed these examinations 6 months after the surgery. The ABPM report was made by a cardiologist who was blinded to the patient s identification as a participant in this study. Mean systolic pressure (SP) and DP were assessed in each test, over 24 hours and, separately, during the wakefulness and sleep periods referred by the patients. Additionally, mean heart rate and the presence or absence of decreased blood pressure during sleep (>10% decreases in SP and DP, known as the nocturnal dip) were measured. With these measurements, mean arterial pressure (MAP 5 SP DP / 3) over 24 hours and during wakefulness and sleep were calculated for each patient. Polysomnography Patients underwent all-night assisted polysomnography in a sleep laboratory between 2 and 12 months before surgery and between 6 and 9 months after surgery. The monitored parameters were: electroencephalogram, electro-oculogram (right and left), electromyogram (submentonian and tibial), electrocardiogram, oronasal airflow (thermistor and nasal cannula), thoracic and abdominal movement (inductance plethysmography), oxyhemoglobin saturation (pulse oximetry), and record of the position on the bed. The polysomnograms were staged according to standardized criteria following the updates made on the manual by Rechtschaffen and Kales 10 and were analyzed by doctors blinded to the patient s status (pre- or postoperative). The respiratory events were scored according to the criteria established by the American Academy of Sleep Medicine in 2007, using the recommended definition for hypopneas. 11 The variables assessed in these tests were AHI, minimum oxyhemoglobin saturation, percentage of total sleep time with oxyhemoglobin saturation < 90%, arousal index (per hour of sleep), and percentage of total sleep time spent in rapid eye movement sleep and slow-wave sleep (N3). Surgery All patients underwent reconstruction of the upper airway with lateral pharyngoplasty. Performed under general anesthesia, the surgery consists of tonsillectomy, removal of the mucosa from the palatal corner to expose the lateral muscular wall of the pharynx, cross section of the palatopharyngeal muscle in its most caudal portion, and vertical myotomy of the superior pharyngeal constrictor muscle within the tonsillar fossa. Unlike the previously published technique, 7 we mobilized the palatopharyngeal muscle before sectioning it, detaching its insertion from the posterior wall of the pharynx. Therefore, the passive constriction of the pharynx was eliminated, and we were able to freely reposition the muscle flaps laterally to expand the pharyngeal tube. The dead space formed by the closure of the tonsillar fossa, deeply to the sutured pillars, was sealed with fibrin glue. Moreover, the central portion of the soft palate and uvula were fully preserved. Statistical Analysis Most of the variables assessed in this study did not present a normal distribution. Therefore, the data were subjected to nonparametric statistical tests. Consistent with this analysis, the measure of central tendency adopted was the median, followed by the respective interquartile range. For the purpose of comparison with other studies, some of the results were also presented as the mean values of the variables. The significance of anthropometric, polysomnographic, and ABPM alterations before and after surgery was verified by the nonparametric Wilcoxon test. To determine the influence of anthropometric and polysomnographic alterations on the differences obtained on the ABPM, Spearman correlation coefficient R was calculated for the variables with significant differences between the pre- and postoperative periods. A level of significance.05 was adopted. The statistical analysis was performed using BioEstat

3 TABLE I. Twenty-Four-Hour, Sleep and Wake Ambulatory Blood Pressure Monitoring: Pre- and Postoperative Values for the Whole Group. Mean, mmhg Median (Quartile Range), mmhg Measure Pre Post Difference, mmhg* Pre Post P 24-hour MAP (12.2) 91.2 (10.1) hour SP (13.8) (11.5) hour DP (8.0) 76.5 (10.0).03 MAP sleep (15.4) 78.2 (13.4).01 SP sleep (21.3) (18.5).006 DP sleep (13.0) 65.0 (10.5).03 MAP awake (11.5) 94.5 (8.8).15 SP awake (13.5) (8.5).07 DP awake (7.8) 79.5 (8.8).29 *Mean variation from pre- to postoperative. P <.05. DP 5 mean arterial diastolic pressure; MAP 5 mean arterial pressure; SP 5 mean arterial systolic pressure. software (Belem, Brazil). Statistically significant differences are identified in the tables with an asterisk. RESULTS Among the 23 patients who underwent surgery, four gave up on performing postoperative ABPM, two refused to perform the postoperative polysomnography, and one was excluded for presenting a hypertensive crisis, that is, headaches associated with DP > 120 mmhg during postoperative ABPM. Therefore, our final study group was composed of 13 men and five women. Mean age was 44.7 years, ranging from 24 to 61 years (median years; interquartile range ). Most patients were overweight before the surgery, with an average BMI of 29.2 kg/m 2, ranging from 23 to 34 kg/m 2 (median kg/m 2 ; interquartile range 5 4.5), and 61% had severe OSA (AHI > 30), with an average AHI of 34.9, ranging from 9.4 to 85 (median ; interquartile range ). Three patients presented with hypertension controlled by medication and maintained the same medication throughout the study period. The remaining 15 patients were normotensive, according to the office baseline measurement of blood pressure. Only one patient smoked, and the patient maintained the smoking habit in the postoperative period. Regarding pharyngeal anatomy, one patient was classified as Friedman stage I, six patients as stage II, and 11 as stage III. 12 Only two patients had large tonsils (i.e., size 3 or 4). Table I shows the mean arterial blood pressure values measured in the pre- and postoperative ABPM in the whole group. Arterial blood pressure was reduced in all measures of ABPM. The reductions were significant in all of the 24-hour measurements (MAP, SP, and DP) and in all measurements taken during sleep (MAP, SP, and DP). No significant changes were observed in blood pressure measurements during wakefulness. Tables II and III show the detailed mean systolic and diastolic measurements in each subject, before and after the surgeries. Demographic data and polysomnographic, anthropometric, and blood pressure alterations observed for each patient are presented in Tables IV and V. One hundred percent of Friedman stage I, 60% of Friedman stage II, and 40% of Friedman stage III patients obtained a reduction of at least 50% in AHI and an AHI < 20 postoperatively. Regarding the nocturnal dip, eight patients exhibited no decreases in preoperative SP or DP; among these, three began exhibiting the dipping pattern after surgery. One patient who was a blood pressure dipper became a nondipper after surgery. Significant reductions in AHI, arousals per hour, and percentage of total sleep time with oxyhemoglobin saturation < 90% were noted. There were no correlations TABLE II. Detailed Mean Systolic Pressure Values in Each Subject, Before and After Surgery (mmhg). 24-Hour Awake Sleep Patient No. Before After Before After Before After

4 TABLE III. Detailed Mean Diastolic Pressure Values in Each Subject, Before and After Surgery (mmhg). 24-Hour Awake Sleep Patient No. Before After Before After Before After between the reductions obtained in AHI (s 5.11; P 5.65), arousals per hour (s 5.11; P 5.66), percentage of total sleep time with oxyhemoglobin saturation < 90% (s 5.06; P 5.86), and the reduction observed in 24-hour MAP. There were also no correlations between the reduction in MAP during sleep and the reductions in AHI (s 5.06; P 5.82), arousals per hour (s 5.15; P 5.57), and percentage of total sleep time with oxyhemoglobin saturation < 90% (s 5.30; P 5.34). Moreover, reductions in SP or DP during sleep did not correlate with reductions in AHI (s 5.13; P 5.61 and s 5.01; P 5.96, respectively), arousals per hour (s 5.18; P 5.49 and s 5.11; P 5.66, respectively), or percentage of total sleep time with oxyhemoglobin saturation < 90% (s 5.29; P 5.37 and s 52.24; P 5.45, respectively). Because the reduction in BMI approached statistical significance (P 5.06), we also performed a correlation analysis between these data and blood pressure reductions; no correlations were observed with 24-hour MAP (s 52.03; P 5.88), MAP during sleep (s 5.007; P 5.97), SP during sleep (s 5.004; P 5.98), or DP during sleep (s 5.05; P 5.84). DISCUSSION This study revealed a significant association between the lateral pharyngoplasty treatment for OSA TABLE IV. Demographic Data and Polysomnographic, Anthropometric, and Blood Pressure Alterations of All Patients Before and After Surgery. AHI, Events/hr BMI, kg/m 2 Mean Difference in BP After Surgery, mmhg Patient No. Age, yr Gender Before After Before After 24-Hour MAP SP Sleep DP Sleep 1* 43 M F M M , 42 M F M , 61 F F , 47 F M * 51 M M M M M M * 51 M *Nocturnal dip of blood pressure absent in the preoperative period and present in the postoperative period. Nocturnal dip of blood pressure present in the pre- and postoperative periods. Nocturnal dip of blood pressure present in the preoperative period and absent in the postoperative period. Nocturnal dip of blood pressure absent in the pre- and postoperative period. Patients with systemic arterial hypertension controlled by medication. 24-Hour MAP 5 mean arterial pressure over 24 hours; AHI 5 apnea hypopnea index; BMI 5 body mass index; BP 5 blood pressure; DP 5 diastolic pressure; F 5 female; M 5 male; SP 5 systolic pressure. 314

5 TABLE V. Pre- and Postoperative Polysomnographic and Anthropometric Alterations for the Entire Group. Median Mean Value (Quartile Range) Value Measure Before After Before After P AHI, events/hr (25.5) 15.7 (21.1).02* O 2 nadir, % (7.8) 84.3 (7.5).38 O 2 < 90%, % (12.5) 0.7 (1.5).008* Arousals, (28.9) 15.7 (10.5).005* events/hr REM, % (7.0) 18.7 (10.2).93 N3, % (7.7) 22.0 (9.4).12 Heart rate, (14.3) 78.4 (6.9).08 beats/min BMI, kg/m (4.5) 29.0 (5.3).06 AHI 5 apnea hypopnea index; BMI 5 body mass index; N3 5 N3 sleep phase; O 2 < 90% 5 percentage of total sleep time with oxyhemoglobin saturation < 90% O 2 nadir 5 minimum oxygen saturation; REM 5 rapid eye movement sleep. *P <.05. and blood pressure reduction in 24-hour MAP, caused by a particularly significant reduction in MAP during sleep. Both systolic and diastolic components decreased significantly within 24 hours and during sleep, but not during wakefulness, during an average follow-up of 187 days after surgery. Significant reductions in AHI, percentage of total sleep time with oxyhemoglobin saturation < 90% and arousal index were also noted. There was no correlation between polysomnographic alterations and blood pressure reductions, and there were no significant anthropometric differences after surgery. To the best of our knowledge, this is the first medium-term study showing the effect of upper airway reconstructive surgery in OSA on sleep blood pressures. Lateral pharyngoplasty produced a reduction of 3.6 mmhg in 24-hour MAP. A meta-analysis of 16 studies on the effect of CPAP on blood pressure 4 reported a mean reduction of 2.53 mmhg in 24-hour MAP. In 10 of the 16 studies, these measurements were performed after only 1 month of treatment with CPAP, and only one study conducted a follow-up 6 months after adaptation to CPAP. Because the effect of CPAP on blood pressure seems to be greater in patients with SAH, and that meta-analysis included normotensive and hypertensive patients, 4 this may have diminished the reported results of that therapy on blood pressure. Hence, because 83.3% of our cases were normotensives, the lateral pharyngoplasty effect on blood pressure definitely deserves further studies. Twenty-five percent of the patients in this study achieved an AHI < 5 after surgery, and 50% reached an AHI < 20, with a reduction of at least 50% in AHI, a criterion that is often used to define a favorable response to surgery. It should be noted that all surgeries were performed by different resident physicians during supervised learning of the surgical technique, and all but two patients had tonsil size 1 or 2, which may explain the lower polysomnographic results when compared to those previously reported. 8 Despite this, 13 patients (72.2%) obtained a reduction in 24-hour MAP. In these 13 cases, the reduction in 24-hour MAP was, on average, 6.7 mmhg, and 84.6% of the group was composed of normotensive individuals. These data compare favorably with reported blood pressure measurements in patients using CPAP. 4 The correlation between AHI and the incidence of SAH remains controversial. The first prospective study on this subject indicated a correlation between baseline AHI and the incidence of SAH 4 years later. 13 This study played an important role in defining the severity parameters of OSA according to AHI. However, subsequent prospective studies with longer follow-up periods and larger numbers of participants 14,15 did not show a correlation between AHI and the development of SAH. Our study showed no correlations between reductions in AHI or arousals and blood pressure. Due to our small sample size, it is probable that our study was not powered sufficiently to detect the effect of intermediate polysomnographic changes on blood pressure. We believe that the significant reduction in arousals may have reduced sympathetic activity, contributing to lower blood pressure. Also, the reduction of the percentage of total sleep time with oxyhemoglobin saturation < 90% may have accounted for a reduction of the oxidative stress and the release of inflammatory mediators. Another factor that could explain the great reduction in ABPM observed in our cases would be a feasible effect of surgery on the reduction of respiratory effort, 16 duetodecreasedupper airway resistance. Although this resistance was not measured in this study and is not usually measured in a conventional polysomnography, the improvement of OSA may indicate reduced upper airway resistance, which, due to the effect of intrathoracic pressure on the heart, may correlate better with blood pressure than AHI. In a study with the revised UPPP technique, 6 the authors obtained reductions in mean blood pressure of 5.6 mmhg for 24-hour SP and 4.4 mmhg for 24-hour DP; additionally, they noted significant reductions in mean blood pressure during sleep. In this study, patients with arterial hypertension underwent surgery and presented significant weight loss during the 4-week period in which the study was conducted. This is a significant difference compared to our study, which presented a longer follow-up period (6 months) and no significant differences in weight or BMI during the study period. Another study using oral appliances with a follow-up period of only 1 month reported average reductions of 1.6 mmhg in SP and 1.8 mmhg in 24-hour DP; the differences were predominant during wakefulness. 5 Our study has several limitations. Our small sample size and the lack of a control group preclude generalizations about the impact of lateral pharyngoplasty on SAH. The selection bias of surgical cases makes comparisons with other studies difficult, as we excluded cases of morbid obesity or with more pronounced cardiovascular comorbidities, which represent populations typically assessed by other studies with CPAP. 4 ABPM and the polysomnography were done on different nights, which can be seen as a weakness of the study because the sleep periods were not objectively measured but only reported by the patients during ABPM. The literature already 315

6 showed that monitoring blood pressure during sleep can interfere with the sleep test by increasing the arousals, 17 which is not desirable. We could verify that there was little or no difference in the subjects weight between those examinations, either before or after the surgeries, but we cannot be sure that the OSA has not worsened between the preoperative sleep studies and the surgeries. The proximity of preoperative ABPM to the day of the surgery, which is a stressful time for the patient, could have increased that blood pressure measurement, falsely improving the results of postoperative ABPM. However, given the significant reduction in blood pressure observed during sleep but not during wakefulness, we believe that this factor had little interference with our results. CONCLUSION We concluded that, in this small case series with 83.3% normotensive subjects, lateral pharyngoplasty significantly reduced the measurements obtained in 24- hour ABPM due to a significant reduction in MAP during sleep in patients with OSA 6 months after surgery. Although the patients exhibited reductions in AHI, arousals, and percentage of total sleep time with oxyhemoglobin saturation < 90%, these changes did not correlate with blood pressure improvement in these patients. BIBLIOGRAPHY 1. Silverberg DS, Oksenberg A, Iaina A. Sleep related breathing disorders are common contributing factors to the production of essential hypertension but are neglected, underdiagnosed, and undertreated. Am J Hypertens 1997;10: Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000;283: Barbe F, Duran-Cantolla J, Capote F, et al. Long-term effect of continuous positive airway pressure in hypertensive patients. Am J Respir Crit Care Med 2010;181: Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 2007;50: Gotsopoulos H, Kelly JJ, Cistulli PA. Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial. Sleep 2004;27: Yu S, Liu F, Wang Q, et al. Effect of revised UPPP surgery on ambulatory BP in sleep apnea patients with hypertension and oropharyngeal obstruction. Clin Exp Hypertens 2010;32: Cahali MB. Lateral pharyngoplasty: a new treatment for obstructive sleep apnea hypopnea syndrome. Laryngoscope 2003;113: Cahali MB, Formigoni GG, Gebrim EM, Miziara ID. Lateral pharyngoplasty versus uvulopalatopharyngoplasty: a clinical, polysomnographic and computed tomography measurement comparison. Sleep 2004;27: Nobre F, Mion D. Monitorizacao ambulatorial da pressao arterial. Rev Ass Med Brasil 1998;44: Thorpy MJ. International Classification of Sleep Disorders: Diagnostic and Coding Manual. American Sleep Disorders Association, Rochester, MN; Iber C, Ancoli-Israel S, Chesson A Jr, Quan S. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Westchester, IL: American Academy of Sleep Medicine; Friedman M, Ibrahim H, Bass L. Clinical staging for sleep-disordered breathing. Otolaryngol Head Neck Surg 2002;127: Peppard PE, Young T, Palata M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342: O Connor GT, Caffo B, Newman AB, et al. Prospective study of sleep disordered breathing and hypertension: the Sleep Heart Health Study. Am J Respir Crit Care Med 2009;179: Cano-Pumarega I, Duran-Cantolla J, Aizpuru F, et al. Obstructive sleep apnea and systemic hypertension. Longitudinal study in the general population: the Vitoria Sleep Cohort. Am J Respir Crit Care Med 2011; 184: Bradley TD, Floras JS. Treating obstructive apnea. Is there more to the story than 2 millimeters of mercury? Hypertension 2007;50: Lenz MC, Martinez D. Awakenings change results of nighttime ambulatory blood pressure monitoring. Blood Press Monit 2007;12: