The results of this multicenter case-control study demonstrated that insomnia and depression are not associated with an increased risk of OHCA. However, in the interaction analysis of insomnia and depression, insomnia with depression increased the incidence of OHCA after adjusting for demographic characteristics and lifestyle behaviors, and this trend was significant only in the younger age group without insomnia medication. This research contributes to understanding the complex effects of insomnia and depression related to OHCA risk and will help develop strategies to reduce OHCA in the general population.
Sleep disturbance, including insomnia, has been reported as a risk factor of coronary heart disease and mortality in previous studies 20–22. Insomnia has been shown to adversely influence physiological metabolism and endocrine function similar to that in premature aging, including altering the hypothalamic-pituitary-adrenal axis, reducing endogenous testosterone levels, and elevating biomarkers of chronic inflammation 7, 8, 23. Contrary to the results of previous studies, insomnia alone did not increase OHCA incidence in our study.
Previous studies suggested that depression and depressive symptoms are associated with an increased risk of coronary heart disease and OHCA 14, 24, 25. Depression is associated with atherosclerosis, alteration of the cardiac autonomic response, and a decrease in heart rate variability 26, 27. Additionally, low red blood cell membrane levels of omega-3 polyunsaturated fatty acids, which is associated with an increased risk of sudden cardiac death, have been reported in patients with depressive disorders 28. However, our findings are in agreement with those of the prior studies, indicating that depression does not have an independent effect on OHCA incidence.
Insomnia and depression, though separate disorders, have been shown to be highly interrelated in several previous studies. In a 2016 meta-analysis that analyzed the risk of depression in insomnia patients, the risk ratio of depression was 2.27 (95% CI: 1.89—2.71) among those with insomnia 29. Additionally, symptoms of disturbed night-time sleep in individuals with depression have been suggested extensively in both clinical and epidemiological studies. In clinical studies, difficulty in initiating or maintaining sleep or both have been reported in about three-quarters of all depressive patients 30, 31. In epidemiological studies examining insomnia and depression, sleep symptoms, including insomnia and hypersomnia, occurred in 50–60% in young adults 32. In our study populations, 14.2% of insomnia patients had depression, while 52.7% of depression patients complained of insomnia. Regarding OHCA risk, insomnia and depression showed an interaction effect, and when insomnia was accompanied by depression, the OHCA risk was 2.33 times higher than when insomnia was not comorbid with depression, and this trend was maintained only in the young population under 65 years of age. A previous study on patients with coronary heart disease 33 reported that depression may be associated with mortality through negative health behaviors such as reduced physical activity. Thus, presence of depression are associated with a high possibility of neglecting health care, and, as insomnia and depression are closely interrelated, this could have a synergistic effect. Additionally, there is a possibility that insomnia and depression may intensify the effects of increasing OHCA incidence; further, because insomnia and depression can lead to one another, it may lead to a vicious cycle of exacerbation of each disease.
A study was conducted in the UK on the incidence of insomnia in a wide range of patients of varying ages with depression. Overall, 83% of patients with depression had insomnia, which varied from 77% in the 16–24-year age group to 90% in the 55–64-year age group 34. In our study, insomnia and depression showed a high trend in the elderly (those over 70 years of age); however, insomnia and depression did not increase the OHCA incidence either alone or together in the elderly population.
In this study, neither insomnia nor depression alone increased the OHCA risk; however, insomnia with depression was associated with increased OHCA incidence, and the effect of increased OHCA incidence was maintained only in the young population that did not consume insomnia medication. This may provide a theoretical basis for the need for early diagnosis and active treatment for insomnia patients with depression for lowering OHCA risk.
This study has several limitations. First, because histories of insomnia and depression were determined through self-report or through information obtained from the next of kin, rates of insomnia and depression may have been under- or over-estimated. Second, we did not investigate the treatment of depression in our registry questionnaire. There may be differences in the effect on OHCA risk depending on whether the disease is treated or not, which may have influenced the results of our study. Third, insomnia treatment other than medication could not be investigated in our registry. Finally, the study design was not a randomized controlled trial. There may have been a significant potential bias that was not controlled.