Migraine and sleep apnea in the general population
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Objective is to investigate the relationship between migraine and obstructive sleep apnea in the general population. A cross-sectional population-based study. A random age and gender stratified sample of 40,000 persons aged 20–80 years residing in Akershus, Hedmark or Oppland County, Norway, were drawn by the National Population Register. A postal questionnaire containing the Berlin Questionnaire was used to classify respondents to be of either high or low risk of obstructive sleep apnea. 376 persons with high risk and 157 persons with low risk of sleep apnea aged 30–65 years were included for further investigations. They underwent an extensive clinical interview, a physical and a neurological examination by physicians, and in-hospital polysomnography. Those with apnea hypopnoea index (AHI) ≥5 were classified with obstructive sleep apnea. Migraine without aura (MO) and migraine with aura (MA) was diagnosed according to the International Classification of Headache Disorders. MO and MA occurred in 12.5 and 6.8% of the participants with obstructive sleep apnea. The logistic regression analyses showed no relationship between the two types of migraine and obstructive sleep apnea, with adjusted odds ratios for MO 1.15 (0.65–2.06) and MA 1.15 (0.95–2.39). Further, estimates using cutoff of moderate (AHI ≥ 15) and severe (AHI ≥ 30) obstructive sleep apnea, did not reveal any significant relationship between migraine and the AHI. Migraine and obstructive sleep apnea are unrelated in the general population.
KeywordsMigraine Migraine without aura Migraine with aura Obstructive sleep apnea Polysomnography and epidemiology
A relationship between headache and sleep has been recognized for a long time . Migraine attacks may be precipitated by sleep deprivation and patients with migraine often experience relief of their pain with sleep, while rest without sleep has been shown to be less effective [2, 3]. A recent study showed a significant association between primary headaches including migraine and severe sleep disturbances measured by two validated sleep questionnaires . One of the most common sleep disorders is obstructive sleep apnea syndrome, with an estimated prevalence of 2–4% among middle-aged adults [5, 6].
Obstructive sleep apnea syndrome is defined as at least five apneas or hypopneas per hour of sleep in conjunction with symptoms such as excessive daytime sleepiness. When obstructive sleep apnea is defined solely by an apnea hypopnea index (AHI) of ≥5, the estimated prevalence among middle-aged adults is approximately 20% in the general population [5, 7, 8]. This is a disorder with partial or complete obstruction of the upper airways during sleep which constitutes hypopnea and apnea and will typically result in repeated airflow cessation, oxygen desaturation and sleep disruption. The disruption of sleep may then result in one or more of the following: excessive daytime sleepiness, unrefreshing sleep, daytime fatigue or reduced cognitive function .
Sleep apnea headache is recognized in the in the International Classification of Headache Disorders (ICHD II) as a brief recurrent morning headache in the presence of an apnea hypopnea index (AHI) of ≥5 . There is however, still controversy regarding the association between primary headaches and obstructive sleep apnea. The apnea-related headache may present itself as migraine, tension-type, cluster or a non-specific headache, and several studies have found it to merely be a non-specific symptom with no clear relationship with obstructive sleep apnea [11, 12, 13, 14].
The aim of the present study was to investigate the relationship between migraine without aura (MO) and migraine with aura (MA), and obstructive sleep apnea in the general population.
Sampling and representativeness
The participants were all admitted to Akershus University Hospital (Stensby Hospital), Norway, and underwent an extensive clinical interview including a semi-structured headache interview and a physical and a neurological examination by one of three physicians. The physicians were blinded regarding the participants replies on the questionnaire. The International Classification of Headache Disorders (ICHD II) was applied . The Hospital Anxiety and Depression Scale (HADS) was used to screen for depression . The replies were dichotomized and depression was defined by a score of ≥8 on the subscale of depression (HADS-D) . Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale . The results were dichotomized into scores ≤10 and >10, the latter is considered to represent clinically significant excessive daytime sleepiness . Body mass index (kg/m2) was calculated from measured weight and height. All participants then underwent in-hospital polysomnography (PSG) performed on standard, multichannel, EmblaTM, PSG devices (ResMed Corp Poway, CA, USA). The recordings included a two-channel electroencephalograph (C4/A1, C3/A2 according to the 10-20 international electrode placement system), a two-channel electrooculogram, a one-channel submental electromyogram, leg EMG (tibialis), SaO2, breathing movements (Respitrace; Ambulatory Monitoring, Ardsley, NY, USA), air flow (Pro-Tech, Woodinville, WA, USA) and body position. All electrophysiological signals were pre-amplified, stored and subsequently scored (30-s epochs using Somnologica 3.2 software package, Flaga-Medcare, Buffalo, NY, USA) according to the Rechtshaffen and Kales scoring manual by two US board certified PSG technicians who were blinded to the result of the Berlin Questionnaire . Arousals were documented and classified . Obstructive apneas were scored when at least a 90% decrease of flow occurred for more than 10 s. Hypopneas were defined as a 30% decrease in flow for more than 10 s with subsequent oxygen desaturation of at least 4%. The apnea hypopnoea index (AHI) was calculated as the average of total number of apneas and hypopneas per hour of sleep. In this study the participants with apnea hypopnoea index (AHI) ≥5 were classified with obstructive sleep apnea.
Statistical analyses were performed using SPSS Base System for Windows 16.0. Chi-square tests and logistic regression modeling with 5% level of significance were used. Fisher’s exact test was used when appropriate. The Student’s t test and Mann–Whitney U test were used in comparing normally and non-normally distributed continuous variables. In our multivariate logistic regression model obstructive sleep apnea was used as the dependent variable, while migraine, depression, gender, body mass index and age were independent variables.
The project was approved by The Regional Committees for Medical Research Ethics and the Norwegian Social Science Data Services.
Participants and non-participants were not significantly different regarding self-reported migraine (31.0 vs. 28.8%, p = 0.43), depression (10.1 vs. 11.9%, p = 0.34), simple snoring (89.8 vs. 87.2%, p = 0.37), gender (male, 54.3 vs. 50.1%; p = 0.16) or age (mean age 48.6 vs. 48.8 years, p = 0.75), while simple snoring was overrepresented in the low-risk group, as compared to all low-risk respondents of the questionnaire (82.2 vs. 45.1%, p < 0.001).
Demographic and clinical characteristics of the study sample
Male (N = 291)
Female (N = 242)
All (N = 533)
30 and 35
40 and 45
50 and 55
60 and 65
Body mass index (kg/m2)
Excessive daytime sleepiness
Obstructive sleep apnea (AHI ≥ 5)
AHI ≥ 15
AHI ≥ 30
Migraine without aura, n (%)
Migraine with aura, n (%)
Clinical characteristics of migraine without aura and migraine with aura
Migraine without aura (N = 71)
Migraine with aura (N = 38)
Lifetime number of attacks
Frequency (days per month)
Daily activity inhibited
Migraine age at onset, mean (SD)
Polysomnographic characteristics of the study sample
Migraine without aura (N = 71)
Migraine with aura (N = 38)
No migraine (N = 431)
Total sleep time (min)
Sleep efficiency (%)
S1 of total sleep time (%)
S2 of total sleep time (%)
S3 of total sleep time (%)
S4 of total sleep time (%)
REM of total sleep time (%)
Sleep latency (min)
REM latency from sleep onset (min)
Apnea hypopnoea index (AHI)
Oxygen desaturation index (ODI)
Average oxygen saturation (%)
Lowest oxygen saturation (%)
Average desaturation (%)
Crude and adjusted odds ratios (cOR and aOR) with 95% confidence intervals (CI) for obstructive sleep apnea by migraine without aura, depression, gender, body mass index and age
Migraine without aura
Body mass index
Crude and adjusted odds ratios (cOR and aOR) with 95% confidence intervals (CI) for obstructive sleep apnea by migraine with aura, depression, gender, body mass index and age
Migraine with aura
Body mass index
The main finding in this population-based cross-sectional study was the lack of relationship between MO, MA and all migraine, and obstructive sleep apnea. This is in concurrence with two previous clinical population studies from France and Norway [14, 23]. In the French study which recruited patients referred to a sleep laboratory because of snoring, the prevalence of migraine was higher among snorers (40.7%) than in patients with sleep apnea syndrome (28.3%), but the difference was not statistically significant (p = 0.18) . The Norwegian study recruited patients referred to a neurologist because of headache. They also found a higher prevalence of migraine among patients without obstructive sleep apnea (40%) than among patients with obstructive sleep apnea (29%), but the result was not statistically significant (p = 0.39) .
The consistency of our results is further emphasized by the fact that mild (AHI ≥ 5), moderate (AHI ≥ 15) and severe (AHI ≥ 30) obstructive sleep apnea showed exactly the same. This lack of dose–response relationship between headache and severity of obstructive sleep apnea has previously been reported in two case–control studies from USA and Norway, respectively [12, 24].
In contrast, another Norwegian population-based survey found that severe sleep disturbances were five times more likely among migraineurs than in headache-free individuals . Sleep disturbances in that survey was based on the Karolinska Sleep Questionnaire with a score in the upper quartile. This questionnaire assesses snoring, apnea, insomnia, daytime sleepiness and restless legs syndrome, and in the analysis of the separate items they did not find any differences in the prevalence of snoring or apnea between migraineurs and headache-free individuals. Their finding that excessive daytime sleepiness is more likely among migraineurs was confirmed in our study.
The strengths of this study were the use of interview and examination by physicians regarding the diagnoses of MO and MA as well as the use of PSG in diagnosing obstructive sleep apnea in participants from the general population. Although the response rate to the questionnaire was relatively low, similar replies to the first and second issued questionnaire as well as the electronic responses suggest that responders and non-responders are not different. A previous Danish epidemiological survey found no significant difference in the frequency of migraine among responders and non-responders . In addition, the response rate is comparable to that of other sleep-related epidemiologic studies [26, 27].
The relatively low participation rate may introduce a selection bias. However, participants and non-participants were not significantly different regarding self-reported migraine, depression, simple snoring, gender or age. Another possible selection bias is the fact that respondents with high risk of obstructive sleep apnea were oversampled. As expected, this resulted in a high prevalence of obstructive sleep apnea (55.5%) and excessive daytime sleepiness (32.2%) in our sample. However, we do not believe that increased sleepiness has influenced the estimated relationship between migraine and obstructive sleep apnea, since no significant associations were found. Regarding the difference between the participants and the study population, we discovered that self-reported simple snoring was overrepresented in the low-risk group in the study sample, as compared to all respondents of the questionnaire with low risk. Since there may be a relationship between snoring and headache, this may have introduced a misclassification bias which contributed to a slight overestimation of headache in participants without obstructive sleep apnea in the current study [28, 29]. This will not, however, influence our finding that migraine and the AHI was non-significantly related. Finally, it cannot be completely ruled out that the use of single in-patient PSG may be a potential limitation to our study . Although the mean total sleep time in this sample was 411.7 min, which may represent a first night effect, we believe the latter is more important in measuring of the sleep quality than in diagnosing of obstructive sleep apnea.
There seems to be no clear relationship between migraine without and with aura, and obstructive sleep apnea in the general population.
This study was supported by a grant from South-East Norway Regional Health Authority, grant number 2004219. The Faculty Division Akershus University Hospital kindly provided technical support. Thanks to Akershus University Hospital for providing research facilities.
Conflict of interest
None of the authors have any financial or other relationships that might lead to a conflict of interest.
This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.
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