Obstructive sleep apnoea and 24-h blood pressure in patients
with resistant hypertension
PATRICIA LLOBERES1 , 2, LOURDES LOZANO1 , 2, GABRIEL SAMPOL1 , 2,
ODILE ROMERO3, MARI´A J. JURADO3, JOSE´ RI´OS4, MARI´A D.
UNTORIA1 , 2and JOSE´ L. TOVAR5
1Department of Pulmonology (Sleep Unit), Hospital Universitari Vall d?Hebron, Universitat Auto ` noma de Barcelona, Barcelona, Spain,2CIBER
de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain,3Department of Neurophysiology (Sleep Unit), Hospital
Universitari Vall d?Hebron, Universitat Auto ` noma de Barcelona, Barcelona, Spain,4Unitat de Suport a l?Estadı´stica i Metodologia (IDIBAPS),
Barcelona, Spain and5Department of Nephrology, Hospital Universitari Vall d?Hebron, Universitat Auto ` noma de Barcelona, Barcelona, Spain
Accepted in revised form 18 January 2010; received 1 September 2009
Obstructive sleep apnoea (OSA) is common in patients with resistant hypertension, but
understanding of the pathogenic mechanisms linking both conditions is limited. This
study assessed the prevalence of OSA and the relationships between OSA and 24-h
blood pressure (BP) in 62 consecutive patients with resistant hypertension, defined as
clinic BP values ‡ 140 ⁄90 despite the prescription of at least three drugs at adequate
doses, including a diuretic. In order to exclude a ?white coat effect?, only patients with
ambulatory 24-h BP values ‡ 125 ⁄80 were recruited. Patients underwent polysomnog-
raphy, 24-h ambulatory BP monitoring and completed the Epworth sleepiness scale
(ESS). OSA was defined as an apnoea–hypopnoea index (AHI) ‡ 5 and excessive
daytime sleepiness (EDS) by an ESS ‡ 10. A multiple linear regression analysis was
used to assess the association of anthropometric data, OSA severity measures and ESS
with 24-h systolic and diastolic BP. Mean 24-h BP values were 139.14⁄80.98 mmHg.
Ninety per cent of patients had an AHI ‡ 5 and 70% had an AHI ‡ 30. Only the ESS
was associated with 24-h diastolic BP [slope 0.775, 95% confidence interval (CI) 0.120–
1.390, P < 0.02); age was associated negatively with 24-h diastolic BP (slope )0.64,
95% CI )0.874 to )0.411, P < 0.001). Compared with those without EDS, patients
with EDS showed a significantly higher frequency of diastolic non-dipping pattern
(69.2% versus 34.7%, P < 0.032). Our results demonstrate a high prevalence of severe
OSA in patients with resistant hypertension and suggest that EDS could be a marker of
a pathogenetic mechanism linking OSA and hypertension.
excessive daytime sleepiness, obstructive sleep apnoea, resistant hypertension
ambulatory blood pressure monitoring, blood pressure predictors,
Resistant hypertension is defined as blood pressure (BP) that
remains above the goal despite prescription of at least three
drugs in adequate doses (European Society of Hypertension,
2003). Patients with this condition constitute a special risk
group in the hypertensive population because they are more
likely to have target-organ damage and higher long-term
cardiovascular risk than patients with controlled hypertension
(Cuspidi et al., 2001). Several studies have reported a high
prevalence of obstructive sleep apnoea (OSA) in patients with
resistant hypertension (Cadaval Gonc ¸ alves et al., 2007; Lavie
and Hoffstein, 2001; Logan et al., 2001; Martı´nez-Garcı´a
et al., 2006; Pratt-Ubunama et al., 2007), and some authors
Correspondence: Dra Patricia Lloberes, Servei de Pneumologia,
Hospital Universitari Vall d?Hebron, Passeig Vall d?Hebron, 119–
129, 08035 Barcelona, Spain. Tel. ⁄fax: +34-93-2746083; e-mail:
J. Sleep Res. (2010) 19, 597–602
Sleep and blood pressure
? 2010 European Sleep Research Society
have suggested an association between the measures of OSA
severity and BP (Cadaval Gonc ¸ alves et al., 2007; Logan et al.,
2001; Martı´nez-Garcı´a et al., 2006; Nieto et al., 2000).
Although the pathogenic mechanisms linking these two
conditions remain unclear, increased sympathetic tone and
catecholamine excretion are cited as probable mechanisms
(Jennum et al., 1989), being a consequence of hypoxia,
hypercapnia, pleural pressure fluctuation and sleep fragmen-
tation (Parish and Somers, 2004), all of which occur in patients
with OSA. Excessive daytime sleepiness (EDS), a key symptom
in many patients with OSA, may also be an important
mechanism, as has been suggested by the absence of a BP fall
in non-hypersomnolent patients with OSA (Barbe ´ et al., 2001;
Robinson et al., 2006). Along these lines, sleep deprivation
experiments have reported disturbances in BP regulation
(Knutson et al., 2007), and recent work suggests that elevated
night ⁄day BP may be a consequence of fragmented and light
sleep, regardless of the presence of apnoea (Matthews et al.,
2008) Although EDS is a common symptom in patients with
OSA, in a preliminary study we observed that most patients
with resistant hypertension do not report EDS. The purpose of
this study is to determine the prevalence of OSA and to analyse
the association between 24-h BP values and OSA measures in a
series of patients with resistant hypertension.
PATIENTS AND METHODS
Sixty-two consecutive patients were referred by the Hyperten-
sion Unit of our hospital with a diagnosis of resistant
hypertension from March 2004 to April 2006. Resistant
hypertension was defined as clinic BP values ‡140 ⁄90 despite
the prescription of at least three drugs at adequate doses,
including a diuretic (European Society of Hypertension.,
2003). In order to exclude a ?white coat effect?, only patients
with ambulatory 24-h BP values ‡125 ⁄80 were enrolled into
the study (European Society of Hypertension., 2003). Patients
had maintained consistent treatment and followed the usual
non-pharmacological measures for the previous 30 days.
Treatment compliance was assessed by the Haynes–Sackett
test (Haynes et al., 1976). Exclusion criteria were known OSA,
upper airway malformation, a history of poor treatment
compliance and congestive heart failure and secondary causes
of hypertension, such as renovascular hypertension, pheochro-
mocytoma or Cushing?s syndrome, excluded by laboratory
analysis and ⁄or radiological imaging as indicated clinically.
All participating patients underwent ambulatory blood pres-
sure monitoring (ABPM) (SpaceLabs 90217, Medical Inc.,
Redmon, WA, USA) 1 month before polysomnography. A
trained nurse fitted an appropriately sized cuff on the patient?s
non-dominant arm, which was worn for the subsequent 24 h
during normal daily activities. Monitors were programmed to
record BP every 20 min during the daytime period (07:00–
23:00 hours) and every 30 min during the night-time period
(23:00–07:00 hours). Studies were considered adequate if the
percentage of measurements was higher than 70%, and at least
one measurement per hour was recorded. The ambulatory
monitoring criteria for resistant hypertension were mean 24-h
BP values ‡125 ⁄80 (European Society of Hypertension., 2003).
Mean daytime, night-time, 24-h systolic and 24-h diastolic BP
were considered for the analysis. Patients were classified as
showing a dipping or a non-dipping pattern if the systolic or
the diastolic BP sleep ⁄wake ratio were lower or higher than
At the patient?s first visit, hypertension treatment, age, sex
and body mass index (BMI) were recorded. The presence of
EDS was defined as a value of ‡10 on the Spanish version of
the Epworth sleepiness scale (ESS) (Chiner et al., 1999).
Full-night polysomnography was performed at the sleep
laboratory, with monitoring
(C4-A1, O3-A2), submental electromyography, electrooculog-
raphy, thoracoabdominal motion (strain gauges), oronasal
flow using a thermistor and nasal cannula, finger pulse
oximetry and body position (Compumedics E Series, Abbots-
ford, Vic. Australia). Sleep stages were scored according to
standard criteria (Rechtschaffen and Kales, 1968). Apnoea was
defined as a total absence of oronasal flow for at least 10 s.
Hypopnoea was defined as a clear decrease in the amplitude of
oronasal flow for at least 10 s followed by 3% oxygen
desaturation and ⁄or arousal. Differentiation was made be-
tween obstructive and central apnoeas according to the
respiratory effort channels (presence or absence of a thoraco-
abdominal movement). Mean SaO2was recorded.
The apnoea–hypopnoea index (AHI) was obtained by
dividing the total number of apnoeas and hypopnoeas by the
total hours of sleep time, and OSA was defined as an AHI ‡ 5.
The protocol was approved by the hospital ethics committee
Data are expressed as the mean and SD. Categorical and
ordinal variables are described as frequencies and percentages.
Differences in quantitative variables were analysed with
Student?s t-test for unpaired data. The Fisher exact test for
qualitative variables or the Mann–Whitney U-test for ordinal
variables were applied in inferential analysis. Stepwise multiple
linear regression was used to estimate potential independent
associations of OSA severity variables (AHI and SaO2) and
EDS with the mean 24-h systolic and diastolic BP, after
adjusting for age, BMI and sex. Version 15 of spss for
Windows (SPSS Inc, Chicago, IL, USA) was used for the
analyses. Significance was set at a two-tailed P value of 0.05.
Most patients were men and obese. The mean number of drugs
used for treating resistant hypertension was 3.51 (0.08).
598 P. Lloberes et al.
? 2010 European Sleep Research Society, J. Sleep Res., 19, 597–602
Patients? characteristics and cardiovascular comorbid condi-
tions are shown in Table 1. All patients used diuretics, 72%
calcium-channel blockers, 92.2% angiotensin-converting en-
zyme inhibitors, 50% b-blockers and 24% a-blockers. Fifty-
eight per cent of patients were treated with three drugs, 36.8%
with four drugs and 5.3% with five drugs. There were no
significant differences between patients with or without EDS
regarding the kind of anti-hypertensive drugs used.
Polysomnography results are shown in Table 2. The AHI
was ‡ 5 in 56 of 62 (90.3%) patients and severe OSA
(AHI > 30) was documented in 43 of 62 (70%) patients.
The mean ESS of our population was 6.44 (0.43). Only 13
patients (20.9%) reported EDS (ESS ‡ 10). Differences be-
tween patients with and without EDS are shown in Table 3.
Compared with those without EDS, patients with EDS showed
a higher AHI and a higher prevalence of a diastolic non-
dipping pattern (55.9 ± 27.5 versus 41.05 ± 23.9, P < 0.04
and 64.3% versus 39.6%, P < 0.03, respectively); in addition
they showed higher ABPM measurements and lower SaO2
values, but these differences did not reach statistical signifi-
cance. The prevalence of dyslipidaemia and diabetes was
similar in patients with and without EDS. However, the
number of patients with ischaemic heart disease was signif-
icantly higher among patients without than in those with EDS.
BMI, AHI and mean SaO2, the ESS was associated indepen-
dently with mean 24-h diastolic BP (slope 0.775, 95% CI 0.120–
1.390, P < 0.02), and age was associated negatively with mean
24-h diastolic BP (slope )0.64, 95% CI )0.874 to )0.411,
P < 0.001) (Table 4). For each increasing point on the ESS,
diastolic BP increased by 0.775 mmHg and for each increasing
year of age, diastolic BP decreased by 0.64 mmHg. None of the
variables were associated significantly with the mean 24-h
systolic BP. To assess the potential contribution of comorbid-
ities (dyslipidaemia, diabetes and ischaemic heart disease), a
no significant effect of these comorbidities and did not change
the results of the first model.
Data from this study showed a high prevalence of OSA and
severe OSA in patients with resistant hypertension. The
ESS was associated with the mean 24-h diastolic BP,
regardless of other indices of OSA severity (AHI and mean
SaO2). In addition, the frequency of a diastolic non-dipping
pattern was higher in patients with EDS than in those
The high prevalence of OSA in our population is in keeping
with data from previous clinical studies (Cadaval Gonc ¸ alves
et al., 2007; Lavie and Hoffstein, 2001; Logan et al., 2001;
Martı´nez-Garcı´a et al., 2006; Pratt-Ubunama et al., 2007).
The severe OSA detected in most of our patients contrasts with
previous studies reporting a mean AHI below 30. Two of these
studies used methods different from ours (unattended level III
Table 1 Characteristics of the population with ambulatory blood
pressure monitoring (ABPM)-confirmed resistant hypertension
Characteristicsn = 62
BMI (Kg m)2)
Current or ex-smokers (%)
Cumulative tobacco use, packs per year
Ischaemic heart disease
CVE or TIA
Time since diagnosis of hypertension, years
Number of antihypertensive drugs
Epworth Sleepiness Scale (0–24)
Office BP (mmHg)
24-hour ambulatory BP (mmHg)
Mean daytime systolic BP
Mean daytime diastolic BP
Mean night-time systolic BP
Mean night-time diastolic BP
Mean 24-h daytime systolic BP
Mean 24-h night-time diastolic BP
Sleep BP pattern (n, %)
Dipping systolic BP
Non-dipping systolic BP
Rising systolic BP
Dipping diastolic BP
Non-dipping diastolic BP
Rising diastolic BP
Data are presented as mean (SD). Categorical variables are
presented as the median, or n (%).
BMI, body mass index; BP, blood pressure; CVE, cardiovascular
event; TIA, transient ischaemic attack.
Table 2 Polysomnography results in patients with ambulatory
blood pressure monitoring (ABPM)-confirmed resistant hyperten-
Polysomnographic resultsn = 62
AHI ‡ 5 (n, %)
AHI > 30 (n, %)
Stage 1 (%)
Stage 2 (%)
Stage 3 (%)
Stage 4 (%)
Sleep efficiency (%)
Total sleep time (min)
Data are presented as mean (SD); median or n (%) for categorical
AHI, apnoea–hypopnoea index; REM, rapid eye movement sleep;
SaO2,arterial oxygen saturation.
Obstructive sleep apnoea in patients with resistant hypertension 599
? 2010 European Sleep Research Society, J. Sleep Res., 19, 597–602
portable monitors) (Cadaval Gonc ¸ alves et al., 2007; Martı´nez-
Garcı´a et al., 2006) and two others used full polysomnography
(Logan et al., 2001; Pratt-Ubunama et al., 2007). One study
described an association between the AHI and systolic BP
(Logan et al., 2001) and another reported an association
between the AHI and systolic and diastolic BP (Martı´nez-
Garcı´a et al., 2006). In contrast, we did not document any
association between the AHI and BP levels. This discrepancy
can be explained by differences in the characteristics of the
study populations and, possibly, by the extremely high
prevalence of OSA and severe OSA in our patients. However,
another case–control study showed no relationship between
the AHI and BP in patients with systemic hypertension
(Campos Rodriguez et al., 2006).
This study is the first to identify an association between EDS
and diastolic BP in patients with resistant hypertension. We
found no associations of anthropometric or OSA severity
indices with 24-h SBP. One study reported that in newly
diagnosed apnoeic patients without a history of hypertension,
an increase in diastolic blood pressure was the most frequent
pattern encountered (Baguet et al., 2005). Sympathetic hyper-
activity, both night-time and daytime, increases peripheral
vascular resistance, which is related to mean BP. Previous
studies did not adjust for the ESS, the most widely used
measure for assessing subjective EDS, which in our series
showed a linear association with 24-h diastolic BP, regardless
of the AHI. The Spanish version of the ESS has been validated
Table 3 Characteristics of resistant hypertension patients with or without excessive daytime sleepiness
CharacteristicsNo EDS (n = 49)EDS (n = 13)P
Office systolic BP (mmHg)
Office diastolic BP (mmHg)
Total sleep time
ABPM measurements (mmHg)
Mean 24-h systolic
Mean 24-h diastolic
Non-dipping systolic (n, %)
Non-dipping diastolic (n, %)
Dyslipidaemia (n, %)
Diabetes (n, %)
Ischaemic heart disease (n, %)
Data are presented as mean (SD); median or n (%) for categorical variables.
APBM, ambulatory blood pressure monitoring; AHI, apnoea-hypopnoea index; BMI, body mass index; BP, blood pressure; EDS, excessive
daytime sleepiness; REM, rapid eye movement sleep; SaO2,arterial oxygen saturation.
Table 4 Multiple linear regression analysis showing the association
of sex, BMI, age, ESS, AHI and mean SaO2with the mean systolic
and diastolic 24-h blood pressure values
SlopeP 95% CI
24-h systolic BP
24-h diastolic BP
ABPM, ambulatory blood pressure monitoring; AHI, apnoea–
hypopnoea index; BMI, body mass index; BP, blood pressure; ESS,
Epworth sleepiness scale; SaO2,oxygen saturation.
600 P. Lloberes et al.
? 2010 European Sleep Research Society, J. Sleep Res., 19, 597–602
and is equivalent to the original (Chiner et al., 1999). We also
found a trend towards higher BP values and a higher
percentage of patients with a diastolic non-dipping pattern in
subjects with EDS compared with those without EDS.
Therefore, our results suggest that EDS is associated with
higher diastolic BP and that daytime somnolence might be an
indicative marker of a pathogenetic mechanism linking OSA
and resistant hypertension. The relationship between EDS and
BP could be mediated through sleep fragmentation, poor sleep
quality and chronic sleep deprivation, all of which occur in
human OSA. Sleepiness, because of OSA, is required to
confirm sleep apnoea syndrome, but does not necessarily
correlate with it. The susceptibility to somnolence differs
between individuals and may be regulated by interdependent
mechanisms, including cytokines, which are also implicated in
inflammation pathways (Spiegel et al., 1999). However, in our
population, which was not recruited on the basis of clinical
suspicion of sleep apnoea syndrome, only 21% of patients
reported EDS. This concurs with Martı´nez-Garcı´a et al.
(2006), who described a similarly low mean ESS in a
population of patients with resistant hypertension, although
their patients had a lower AHI than ours. Interestingly, in two
studies showing that continuous positive airway pressure
(CPAP) has no effect on BP in patients without hypersomno-
lence (Barbe ´ et al., 2001; Robinson et al., 2006), the authors
concluded that treating non-hypersomnolent OSA patients for
potential effects on blood pressure and, possibly, cardiovas-
cular risk, cannot be supported. In these studies EDS was
assessed with the ESS, as did we. Previous studies support a
rationale for the association between restricted sleep and
total cardiovascular disease because of increased autonomic
activity, elevated blood pressure, hypercortisolaemia, impaired
glucose tolerance and increased inflammatory markers (Kapsi-
malis et al., 2008). Recently, Kapur et al. (2008) analysed
whether self-reported sleepiness modified the relationship
between sleep-disordered breathing and prevalent hyperten-
sion in the Sleep Heart Health Study cohort. They found that
the association of OSA with hypertension was stronger in
individuals who reported daytime sleepiness than in those
who did not. In this study, however, sleepiness as measured
by the ESS appeared to modify the AHI–hypertension
association less strongly than sleepiness measured by reported
frequency of daytime sleepiness. As discussed by the authors,
subjects who develop any clinical consequence of OSA may
have a higher susceptibility to the disruptive effects of OSA
or, alternatively, EDS may be a better marker of the
physiological significance of OSA than are polysomnographic
indices of OSA severity. Another recent study demonstrated
the association between EDS and impaired autonomic
cardiac modulation, indicating changes in cardiac sympath-
ovagal balance towards a predominance of sympathetic
modulation during sleep in patients with OSA (Lombardi
et al., 2008).
We found a negative association between age and diastolic
BP, with a decrease of 0.64 mmHg for every year of increasing
age. This may be derived, at least in part, from the age-related
increase in arterial stiffness that causes a diastolic BP decrease
in the general population beginning in the sixth decade
(Lakatta and Levy, 2003).
The high prevalence of non-dipping in our population is
consistent with the findings from two previous studies (Logan
et al., 2001; Martı´nez-Garcı´a et al., 2006) in patients with
resistant hypertension and OSA and might be relevant to the
pathogenesis of resistant hypertension and to the high cardio-
vascular risk described in patients with this condition. A recent
revision recommends that OSA should be suspected strongly
when morning BP cannot be controlled <135 ⁄85 mm Hg with
increased sleep ⁄wake ratios (Kario, 2009). Our finding of a
significantly higher diastolic non-dipping pattern in patients
with EDS compared with those without EDS was not reported
previously and supports a relationship between EDS and
Our study is one of the largest case series using full-night
polysomnography and ambulatory BP monitoring in patients
referred from a hypertension unit for resistant hypertension,
independently of clinically suspected OSA. Thus, it has the
strength of data from ambulatory BP monitoring and full
polysomnography in the patient assessment. The main limita-
tions of the study are its cross-sectional design and the high
prevalence of OSA, which may have underestimated the
relationship between OSA severity and BP that was observed
in other studies. Although the ESS is a subjective measure-
ment, it is the most widely used instrument for the assessment
of EDS in patients with OSA. EDS may be a consequence of
sleep fragmentation and nocturnal hypoxaemia occurring
during OSA (Roure et al., 2008) but other conditions, such
as obesity, poor sleep habits and depression, are also asso-
ciated with EDS (Bixler et al., 2005). However, our results were
controlled for obesity and other comorbidities (dyslipidaemia,
diabetes and ischaemic heart disease). As we do not count the
arousal index routinely when scoring polysomnography, the
possible influence of this measure of sleep fragmentation in the
pathophysiology of BP rise was not tested in our study;
however, no significant differences were found between sleep
efficiency and sleep stages distribution between patients with
and without EDS.
In summary, this study shows an extremely high prevalence
of severe OSA in patients with resistant hypertension and an
association of subjective daytime sleepiness with diastolic
hypertension. Our results raise the possibility that improving
daytime hypersomnolence in patients with OSA and resistant
hypertension might improve BP control.
The prevalence of OSA and severe OSA in patients with
resistant hypertension is extremely high. EDS is associated
with diastolic BP levels independently of other indices of
OSA severity, and with a higher frequency of a diastolic BP
non-dipping pattern. These findings suggest that sleep
disruption causing daytime sleepiness may play a role in BP
Obstructive sleep apnoea in patients with resistant hypertension 601
? 2010 European Sleep Research Society, J. Sleep Res., 19, 597–602
ACKNOWLEDGEMENTS Download full-text
This study was supported by the Fundacio ´
Pneumologia (FUCAP) 2004. The authors wish to thank the
technicians of the Sleep Unit for their assistance in the
performance of sleep studies, and Celine Cavallo and Rosa
LLoria for the editing and translation of the manuscript.
Baguet, J. P., Hammer, L., Levy, P. et al. Night-time and diastolic
hypertension are common and underestimated conditions in newly
diagnosed apnoeic patients. J. Hypertens., 2005, 23: 521–527.
Barbe ´ , F., Mayorales, L. R., Duran, J et al. Treatment with contin-
uous positive airway pressure is not effective in patients with sleep
apnea but no daytime sleepiness. Ann. Intern. Med., 2001, 134: 1015–
Bixler, E. O., Vgontzas, A. N., Lin, H. M., Calhoun, S. L., Vela-
Bueno, A. and Kales, A. Excessive daytime sleepiness in a general
population sample: the role of sleep apnea, age, obesity, diabetes,
and depression. J. Clin. Endocrinol. Metab., 2005, 90: 4510–4515.
Cadaval Gonc ¸ alves, S., Martinez, D., Gus, M. et al. Obstructive sleep
apnea and resistant hypertension. A case–control study. Chest, 2007,
Campos Rodriguez, F., Grilo Reina, A., Perez Ronche, J. et al. Effect
of continuous positive airway pressure on ambulatory BP in patients
with sleep apnea and hypertension: a placebo-controlled trial. Chest,
2006, 129: 1459–1467.
Chiner, E., Arriero, J. M., Signes-Costa, J., Marco, J. and Fuentes, I.
Validation of the Spanish version of the Epworth sleepiness scale in
patients with a sleep apnea syndrome. Arch. Bronconeumol., 1999,
Cuspidi, C., Macca, G., Sampieri, L. et al. High prevalence of cardiac
and extracardiac organ damage in refractory hypertension. J.
Hypertens., 2001, 19: 2063–2070.
European Society of Hypertension. European Society of Cardiology
Guidelines for the management of arterial hypertension 2003.
Guidelines Committee. J. Hypertens., 2003, 21: 1011–1053.
Haynes, R. B., Sackett, D. L., Gibson, E. S. et al. Improvement of
medication compliance in uncontrolled hypertension. Lancet, 1976,
Jennum, P., Wildschiodtz, G., Christensen, N. J. and Schwartz, T.
Blood pressure, catecholamines, and pancreatic polypeptide in
obstructive sleep apnea with and without nasal continuous positive
airway pressure (nCPAP) treatment. Am. J. Hypertens., 1989, 2:
Kapsimalis, F., Basta, M., Varouchakis, G., Gourgoulianis, K.,
Vgontzas, A. and Kryger, M. Cytokines and pathological sleep.
Sleep Med., 2008, 9: 603–604.
Kapur, V. K., Resnick, H. E. and Gottlieb, D. J. Sleep disordered
breathing and hypertension: does self-reported sleepiness modify the
association? Sleep Heart Health Study Group Sleep, 2008, 31: 1127–
Kario, K. Obstructive sleep apnea and hypertension: ambulatory
blood pressure. Hypertens. Res., 2009, 32: 428–432.
Knutson, K. L., Spiegel, K., Penev, P. and Van Cauter, E. The
metabolic consequences of sleep deprivation. Sleep Med. Rev., 2007,
Lakatta, E. G. and Levy, D. Arterial and cardiac aging: major
shareholders in cardiovascular disease enterprises. Part I. Aging
Lavie, P. and Hoffstein, V. Sleep apnea syndrome: a possible
contributing factor to resistant hypertension. Sleep, 2001, 24:
Logan, A., Perlikowski, S., Mente, A. et al. High prevalence of
unrecognized sleep apnoea in drug-resistant hypertension. J. Hy-
pertens., 2001, 19: 2271–2277.
Lombardi, C., Parati, G., Cortelli, P. et al. Daytime sleepiness and
neural cardiac modulation in sleep-related breathing disorders. J.
Sleep Res., 2008, 17: 263–270.
Martı´nez-Garcı´a, M. A., Go ´ mez-Aldaravı´, R., Gil-Martı´nez, T.,
Soler-Catalun ˜ a, J. J., Berna ´ cer-Alpera, B. and Roma ´ n-Sa ´ nchez, P.
Sleep-disordered breathing in patients with difficult-to-control
hypertension. Arch. Bronconeumol., 2006, 42: 14–20.
Matthews, K. A., Kamarck, T. W., Hall, M. H. et al. Blood pressure
dipping and sleep disturbance in African-American and Caucasian
men and women. Am. J. Hypertens., 2008, 21: 826–883.
Nieto, F. J., Young, T. B., Lind, B. K. et al. Association of sleep-
disordered breathing, sleep apnea and hypertension in a large
community-based study. JAMA, 2000, 283: 1829–1836.
Parish, J. M. and Somers, V. K. Obstructive sleep apnea and
cardiovascular disease. Mayo Clin. Proc., 2004, 79: 1036–1046.
Pratt-Ubunama, M. N., Nishizaka, M. K., Boedefeld, R. L., Cofield,
S. S., Harding, S. M. and Calhoun, D. A. Plasma aldosterone is
related to severity of obstructive sleep apnea in subjects with
resistant hypertension. Chest, 2007, 131: 453–459.
Rechtschaffen, A. and Kales, A. A Manual of Standardized
Terminology, Techniques and Scoring System for Sleep Stages of
Human Subjects. U.S. Government Printing Office, Washington,
Robinson, G. V., Smith, D. M., Langford, B. A., Davis, R. J. and
Stradling, J. R. Continuous positive airway pressure does not reduce
blood pressure in non sleepy hypertensive OSA patients. Eur. Respir.
J., 2006, 27: 1229–1235.
Roure, N., Gomez, S., Mediano, O. et al. Daytime sleepiness and
polysomnography in obstructive sleep apnea patients. Sleep Med.,
2008, 9: 727–731.
Spiegel, K., Leproult, R. and Van Cauter, E. Impact of sleep debt on
metabolic and endocrine function. Lancet, 1999, 354: 1435–1439.
602 P. Lloberes et al.
? 2010 European Sleep Research Society, J. Sleep Res., 19, 597–602