The present study utilized HIT-6 and ESS to study sleep apnea headache. This appears to be the first report on evaluating sleep apnea headache using HIT-6. Our main results can be summarized as follows. First, the prevalence of sleep apnea headache was higher among women than among men. Second, sleep apnea headache could develop in female patients with relatively mild OSA. Third, HIT-6 could offer a useful outcome measure for evaluating therapeutic efficacy for treatment of sleep apnea headache.
Comparison of HIT-6 scores in sleep apnea headache and migraine
Mean HIT-6 score in patients with sleep apnea headache was 55.0, which was categorized as moderate impact (HIT-6 score: 50–55). Several studies have investigated migraine using HIT-6. For example, mean HIT-6 scores in episodic and chronic migraine have been reported as 62.5 ± 7.8 and 60.2 ± 6.8, respectively9). A recent randomized controlled trial of erenumab showed baseline HIT-6 scores of 57.4–58.9 among Japanese patients with episodic migraine10), and scores of 62.7–63.3 for chronic migraine11). In refractory chronic migraine, HIT-6 was 67.612). HIT-6 scores in sleep apnea headache were thus generally lower than those seen in migraine.
We also found that HIT-6 scores in patients with sleep apnea headache could be improved by OA or CPAP therapy for OSA. The mean change in score was 10.0, reaching 14.1 in the good adherence group for CPAP. This reduction in the negative impact on patients QOL is not negligible, and these therapies should therefore be applied not only for the improvements in sleep breathing, but also to reduce the negative effects of morning headache on QOL.
The present study of sleep apnea headache patients did not include any with migraine. As sleep apnea could represent an aggravating factor for migraine, clarification of the relationship between sleep apnea and migraine using HIT-6 could be an avenue of future research.
Correlation between HIT-6 and N3 ratio in sleep apnea headache patients
A significant negative correlation between HIT-6 and N3 ratio was identified in patients with sleep apnea headache. The N3 ratio was higher in patients with relatively mild headache than in patients with either relatively severe headache or no headache at all, whereas ESS scores were similar in patients without headache and patients with relatively mild headache. An increase in slow-wave sleep and relatively mild daytime sleepiness might be characteristic of patients with mild headache. We speculate that the increase in slow-wave sleep may contribute to reducing the severity of headache and sleepiness. However, our results have at least two limitations. First, this study investigated a small cohort, and second, polysomnography was only performed for a single overnight stay. Further accumulation of cases is necessary to confirm the relationship between HIT-6 and slow-wave sleep. Consistent with a previous study4), ESS scores were high in our patients with relatively severe headache, suggesting that sleep apnea headache is closely related to daytime sleepiness.
Sex differences in sleep apnea headache
The current study showed a sex difference in the characteristics of sleep apnea headache. The prevalence of sleep apnea with morning headache was higher in women than in men. Female patients with sleep apnea headache showed a lower AHI than female patients without headache, suggesting that severity of sleep apnea was not important for the complication of sleep apnea headache. Such tendencies were not observed in male patients. Among male, patients with sleep apnea headache were relatively young. One might concern about small number of female patients, therefore, larger study is necessary to validate our results, especially in sex differences. Recently, the evidence of sex differences in sleep apnea has been growing13). Differences in hormones, structure and physiological behavior of the upper airway, craniofacial morphology, and patterns of fat deposition and respiratory stability may contribute to sex differences in sleep apnea14,15). The present study suggests that the headache induced by sleep apnea represents another important aspect of sex differences in sleep apnea.
ESS and HIT-6 as outcome measures to evaluate sleep apnea therapy
We studied sleep apnea headache using the ESS and HIT-6 questionnaires as quantitative evaluation scales. Both OA and CPAP treatment improved scores, and patients with good adherence to CPAP showed better improvements than those with poor adherence. Total ESS score changed from 9.0 to 5.3 with OA treatment, and from 9.6 to 3.6 with good adherence to CPAP. HIT-6 score changed from 56.4 to 45.9 in the OA treatment group, and from 58.1 to 44.0 with good adherence to CPAP. These results suggest that, in terms of improving sleep apnea headache, OA provides sufficient efficacy for mild to moderate OSA, while CPAP is effective for severe OSA as long as satisfactory adherence is achieved.
We also found that CPAP adherence was important for improving HIT-6 score. Several studies have examined the importance of CPAP use for ≥4 h/night in patients with hypertension16,17), cardiovascular disease18,19), and heart failure20). The present study provided evidence that, concordant with circulatory disorders, 4 h/night is the target duration for CPAP use among patients with sleep apnea headache.