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1 Service d'Exploration Fonctionnelle Multidisciplinaire and 2 Département de Biostatistiques, Hôpital Ambroise Paré (Assistance Publique - Hôpitaux de Paris), Université Paris, Boulogne, France
CORRESPONDENCE: C. Planès, Service d'Exploration Fonctionnelle, Hôpital Ambroise Pare, 92104, Boulogne, Cedex France. Fax: 33 149095906. E-mail: carole.planes@apr.ap-hop-paris.fr
Keywords: aging, blood pressure, sleep, sleep apnoea syndrome
Received: August 30, 2001
Accepted January 29, 2002
| Abstract |
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Twenty-nine subjects with newly-diagnosed untreated OSAS were categorised into three groups: normotensive subjects aged <50 yrs (n=10); subjects aged <50 yrs with untreated hypertension (n=8); and normotensive subjects aged >50 yrs (n=11). Beat-by-beat BP was recorded with a Finapres device during polysomnography. The average values±sd of apnoea-related BP elevations and the values of the frequency distribution of all BP variations during sleep were assessed to estimate short-term BP variability.
Apnoea-related systolic (or diastolic) BP elevations were significantly greater in hypertensives than in normotensives aged <50 yrs (50.3±4.88 versus 30.7±2.14 mmHg, p<0.001), as was the sd of systolic (or diastolic) BP variations during sleep (I9.6±2.22 versus 11.1±0.73, p<0.001). Short-term BP variability was not significantly increased in normotensive elderly patients.
To conclude, the results suggested that systemic hypertension is associated with a greater exacerbation of short-term variability during sleep in obstructive sleep apnoea syndrome patients.
Systemic hypertension (HT) is highly prevalent in patients with obstructive sleep apnoea syndrome (OSAS) 1, and recent epidemiological studies 24 suggest that this association is not entirely explained by known confounding factors such as obesity, age and sex. It has been speculated that the cardiovascular morbidity of OSAS may, in part, be related to the oscillations in systemic blood pressure (BP) and increases in sympathetic discharges that occur repeatedly during the night 5, 6. Indeed, BP falls in time with inspiratory efforts at the beginning of each obstructive episode and rises abruptly at apnoea termination, reaching a peak during the first postapnoeic breaths. Moreover, whereas in normal subjects sympathetic activity decreases during the night, measurements with microneurographical techniques have shown a progressive increase in sympathetic nerve activity during obstructive apnoea with a peak near the end of apnoea 5, 7. Consequently, the significant decrease in the level and variability of BP normally observed during nonrapid eye movement (NREM) sleep is blunted in OSAS patients 7.
In subjects with untreated essential HT, arterial baroreceptor reflex operates at higher pressures and baroreceptor heart-rate reflex has been reported to be decreased 8. The resulting increase in short-term variability of BP may play a role in the alteration of function and structure of the cardiovascular system, since in subjects with untreated systemic HT, target-organ damage has been shown to be related not only to the level of 24-h mean intraarterial BP, but also to BP variability 9, 10. As nocturnal BP variability has been reported to be increased in patients with essential systemic HT, it led the authors to consider whether the association of systemic HT with OSAS could exacerbate the fluctuations of BP related to apnoeic episodes.
To address this question and examine the effect of age, which has been shown to be associated with an increase in sympathetic nerve activity 11, the BP variability during sleep of three groups of subjects with OSAS was compared using a prospective study. The three groups included: subjects aged <50 yrs with normal daytime BP; subjects aged <50 yrs with untreated daytime systemic HT; and subjects aged >50 yrs with normal daytime BP. Using a photoplethysmographic device (Finapres; Ohmeda Inc., Englewood, NJ, USA) to record beat-to-beat BP, the amplitude of apnoea-related BP elevations measured manually were first averaged, and then the short-term variability of nocturnal BP was assessed by computing the sd of the distribution of BP variations according to their amplitude 12.
| Material and methods |
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3 weeks; 3) no symptoms of cardiac failure or arrhythmia; and 4) no previous treatment by hypnotic drugs or treatment stopped for
3 weeks. The patients were divided into the following three groups according to their age and their daytime BP measured with a sphygmomanometer on three separate occasions. Group 1: patients aged <50 yrs without systemic HT (defined as systolic BP (SBP)
140 mmHg, diastolic BP (DBP)
90 mmHg) (n=10); group 2: patients aged <50 yrs with untreated systemic HT (n=8); group 3: patients aged >50 yrs without systemic HT (n=11). Among the eight subjects in group 2, two had stage 1 hypertension (140
SBP<159 mmHg or 90
DBP<99 mmHg), three had stage 2 hypertension (160
SBP<179 mmHg or 100
DBP<109 mmHg) and three had stage 3 hypertension (SBP
180 mmHg or DBP
110 mmHg) according to the classification of the World Health Organization. Clinical characteristics of the subjects are given in table 1
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Polysomnography
The polysomnographic data were recorded with a 16-channel polygraph (Reega 2000, Alvar, Paris, France), as previously described 12. Sleep staging was performed according to the criteria of Rechtschaffen and Kales 13. Electroencephalographic (EEG) arousals were scored according to standard criteria of the American Sleep Disorder Association (ASDA) 14. Apnoea was defined as cessation of oronasal airflow for >10 s and hypopnoea as a reduction of oronasal airflow to
50% of the value prevailing during preceding normal breathing for
10 s followed by transient EEG arousal.
Recording blood pressure during polysomnography
Beat-by-beat photoplethysmographic BP was monitored continuously with Finapres, with the exception of 10-min periods every 2 h where the system was turned off for patient comfort 12. All systolic and diastolic BP values as well as pulse oximetry values (Criticare 504, Critcare Systems Inc., Waukeste, WI, USA; averaging time: 3 s) were synchronised with polysomnography and analysed on a personal computer using software developed by the authors.
| Results |
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Sa,O2) at the termination of every selected event were noted, as well as the event duration.
Statistical analysis
Results are expressed as means±sem. Between-group comparisons were performed using a Kruskal-Wallis test. When a significant difference was observed, multiple pairwise comparisons were performed with the Bonferroni/Dunn procedure. Comparisons of percentages of total sleep time (TST) spent in stages 12 or with a Sa,O2, of <90% were performed with a Chi-squared test. Relationships between variables were evaluated by a Spearman's rank correlation test. A p<0.05 was considered statistically significant.
Polysomnography data and blood pressure values during sleep
There were no significant differences between the degree of sleep disturbance in the three groups as assessed by AHI, arousal index, sleep structure and percentage of nocturnal time spent with a Sa,O2 of <90%, or mean Sa,O2, during TST (table 2
). Only four subjects (two from group 2 and two from group 3) displayed severe oxygen desaturations at the end of apnoea, with an average minimal Sa,O2 of <75%, and a mean Sa,O2 during TST of <90%, while Sa,O2 did not decrease <85% in the remaining 25 subjects.
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Sa,O2 during apnoeas (p=0.19 and 0.24, respectively), or the mean duration of apnoeas (p=0.31). However, the two hypertensive subjects with the most profound desaturations (minimal Sa,O2 <75%) also had the highest values of apnoea-related BP elevations, suggesting that the latter could be influenced by the severity of hypoxaemia. Nevertheless, when these two subjects were excluded, the average value of apnoea-related SBP (DBP) elevations remained significantly higher in the group of hypertensive subjects without severe desaturation (mean minimal Sa,O2 at apnoea termination: 90.3±1.44 versus 91.2±1.00% in normotensives, ns) than in the normotensives (44.7±4.06 versus 30.7±2.14 mmHg, respectively, p<0.01). Neither systolic nor diastolic apnoea-related BP elevations were significantly correlated with age.
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| Discussion |
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The present study population comprised exclusively of patients with moderate-to-severe OSAS, who were free of cardiovascular medication. Normotensive and hypertensive OSAS patients aged <50 yrs were comparable in age, body masss index (BMI), AHI and arousal index and sleep structure. This ruled out several confounding factors that could influence BP variability such as obesity, aging and sleep fragmentation, all of which have been shown to be associated with an increase in sympathetic drive 11, 16. Nocturnal beat-by-beat BP was recorded with a Finapres system synchronised with polysomnography, a noninvasive technique that has been shown to be an accurate method for monitoring fast BP changes 17 and induces only minimal sleep disturbance 5, 7. When compared with measurements from a brachial-artery catheter, the Finapres may slightly overestimate SBP and its variability 18. However, as this overestimation is not related to BP level, the Finapres may be satisfactory for comparing BP variability between subjects.
The amplitude of BP elevations at the termination of obstructive respiratory events was markedly increased in the hypertensive group and was correlated with daytime as well as night-time BP levels. The apnoeas or hypopnoeas used for measurements were selected randomly during stages 1 or 2 of NREM sleep and ended with a typical cortical EEG arousal, thus ruling out differences in sleep stage 7, 12, 19 or in the type and duration of EEG arousal 20 that might influence the amplitude of apnoea-related BP surges. The degree of arterial hypoxaemia is another factor that might influence systemic BP during apnoea 21. Studying intra-individual correlations between BP and Sa,O2, Shepard 22 previously showed that the degree of desaturation modulated the surge in pressure at apnoea termination, accounting for
30% of its amplitude. In contrast, the present study examined interindividual correlations and found that the amplitude of apnoea-related SBP (DBP) elevation was not significantly correlated with Sa,O2 nadir at the end of apnoea. This may be explained by the fact that all of the study subjects, with the exception of two (belonging to the hypertensive group), had only mild-to-moderate nocturnal oxygen desaturations (Sa,O2, nadir >85%). Moreover, the average value of apnoea-related SBP (DBP) elevation was still significantly higher in the subgroup of hypertensive subjects without severe desaturation than in the normotensive subjects. These observations argue against the possibility that the greater BP fluctuations observed in the hypertensive population could simply be a reflection of the more profound hypoxaemia. However, it is likely that the severity of hypoxemia might in some way influence the amplitude of apnoea-related BP elevation.
In the present study, the sd of beat-by-beat SBP and DBP values during TST, an estimate of short- and long-term variability of BP, was significantly increased in the hypertensive compared with the normotensive apnoeics. Mancia et al. 23 previously reported that the absolute variability of BP was increased during sleep in subjects with mild and severe essential HT. Since
30% of patients with essential HT may be expected to have OSAS 24, 25, it is likely that their study population included both apnoeic and nonapnoeic subjects. The present results showed that the sd of the distribution of all-night SBP (DBP) variations according to their amplitude was also markedly increased in hypertensive subjects, and was significantly correlated with both the daytime SBP (or DBP) value and mean SBP (or DBP) during sleep. This computerised index was specifically designed to assess BP variability during sleep in patients with sleep-disordered breathing, as it can be computed even during nonstationary periods of varying durations. It reflected short-term variability of BP since all the BP changes computed lasted <20 s and were influenced by sleep fragmentation 12, 26. However, a difference in OSAS severity could not account for the difference between the normotensive and hypertensive groups as both populations had comparable AHI, arousal index and sleep structure. It was found that the sd of the distribution of SBP (DBP) variations was significantly correlated with mean Sa,O2 during sleep, suggesting that hypoxaemia could influence short-term variability of BP during sleep in OSAS. However, this index was also significantly higher in the subgroup of hypertensive subjects without severe nocturnal hypoxemia (mean Sa,O2 >90%) than in normotensive subjects with comparable nocturnal Sa,O2. Therefore, hypoxaemia alone was probably not sufficient to explain the greater short-term variability of BP in the hypertensive group.
As systemic hypertension is very common in obstructive sleep apnoea syndrome the present results, highlighting as they do the greater short-term variability of blood pressure during sleep in apnoeic patients with untreated systemic hypertension, may have important clinical relevance. Since excessive blood-pressure variability has been linked to target-organ damage, sleep apnoea patients with systemic hypertension might be at particular risk. The computation of the sd of the distribution of blood-pressure variations during sleep, a computerised index of short-term blood-pressure variability with a good correlation with the amplitude of apnoea-related blood-pressure elevations, might be helpful in appreciating the effect of obstructive sleep apnoea syndrome treatment or antihypertensive medication on nocturnal blood-pressure variability in hypertensive patients with sleep apnoea.
| Acknowledgements |
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| References |
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