Interaction effects between insomnia and depression on risk of out-of-hospital cardiac arrest: Multi-center study

PLOS ONE RESEARCH ARTICLE Interaction effects between insomnia and depression on risk of out-of-hospital cardiac arrest: Multi-center study Eujene Jung1, Hyun Ho Ryu ID1,2*, Sung Wan Kim3, Jung Ho Lee1, Kyoung Jun Song4, Young Sun Ro5, Kyoung Chul Cha6, Sung Oh Hwang6, Phase II Cardiac Arrest Pursuit Trial with Unique Registry and Epidemiologic Surveillance (CAPTURES-II investigators)¶ a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Jung E, Ryu HH, Kim SW, Lee JH, Song KJ, Ro YS, et al. (2023) Interaction effects between insomnia and depression on risk of out-of-hospital cardiac arrest: Multi-center study. PLoS ONE 18(8): e0287915. https://doi.org/10.1371/journal. pone.0287915 Editor: Billy Morara Tsima, University of Botswana School of Medicine, BOTSWANA 1 Department of Emergency Medicine, Chonnam National University Hospital, Gwangju, Korea, 2 Medicine, Chonnam National University, Gwangju, Korea, 3 Department of Psychiartry, Chonnam National University Medical School, Gwangju, Korea, 4 Department of Emergency Medicine, Seoul National University Boramae Medical Center, Seoul, Korea, 5 Department of Emergency Medicine, Seoul National University Hospital, Seoul, Korea, 6 Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea ¶ Membership of the Phase II Cardiac Arrest Pursuit Trial with Unique Registry and Epidemiologic Surveillance (CAPTURES-II investigators) is listed in the Acknowledgments. * Abstract Background Insomnia and depression have been known to be risk factors of several diseases, including coronary heart disease. We hypothesized that insomnia affects the out-of-hospital cardiac arrest (OHCA) incidence, and these effects may vary depending on whether it is accompanied by depression. This study aimed to determine the association between insomnia and OHCA incidence and whether the effect of insomnia is influenced by depression. Received: July 14, 2022 Accepted: June 15, 2023 Published: August 18, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0287915 Copyright: © 2023 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data were obtained from the Korea Disease Control and Prevention Agency. () Methods This prospective multicenter case-control study was performed using Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiology Surveillance (CAPTURESII) project database for OHCA cases and community-based controls in Korea. The main exposure was history of insomnia. We conducted conditional logistic regression analysis to estimate the effect of insomnia on the risk of OHCA incidence and performed interaction analysis between insomnia and depression. Finally, subgroup analysis was conducted in the patients with insomnia. Results Insomnia was not associated with increased OHCA risk (0.95 [0.64–1.40]). In the interaction analysis, insomnia interacted with depression on OHCA incidence in the young population. Insomnia was associated with significantly higher odds of OHCA incidence (3.65 [1.29– 10.33]) in patients with depression than in those without depression (0.84 [0.59–1.17]). In the subgroup analysis, depression increased OHCA incidence only in patients who were not taking insomnia medication (3.66 [1.15–11.66]). PLOS ONE | https://doi.org/10.1371/journal.pone.0287915 August 18, 2023 1 / 13 PLOS ONE Funding: This work was supported by the Korea Disease Control and Prevention Agency (Grant No: 2017NE3300600, 2017E3300601, 2019P330800). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Insomnia and depression on incidence of OHCA Conclusion Insomnia with depression is a risk factor for OHCA in the young population. This trend was maintained only in the population not consuming insomnia medication. Early and active medical intervention for patients with insomnia may contribute to lowering the risk of OHCA. Competing interests: The authors have declared that no competing interests exist. Introduction Sudden cardiac death (SCD) is a major public health burden because of its high incidence and low survival rates. The average global incidence of SCD among adults is approximately 55 per 100,000 person-years and 97.1 per 100,000 population in USA [1]. Survival to discharge rate is lower in Asia (4.5%) than that in North America (7.7%) and Europe (11.7%) [2]. Despite advances in resuscitation technology and post-resuscitation care for SCD patients, survival outcomes after SCD remain poor [3–5]. The approach to SCD risk stratification is difficult. Recent studies suggest that there are several unrecognized variables that directly affect cardiac function and the occurrence of arrhythmias related to the risk of SCD; however, the risk of SCD is also associated with classical factors, such as hypertension, diabetes mellitus, and dyslipidemia [6, 7]. Insomnia, the most common sleep disorder, is characterized by difficulty initiating and maintaining sleep. It may also take the form of early-morning awakening in which the individual awakens several hours early and is unable to resume sleeping [8]. The duration and continuity of sleep is associated with homeostasis of cardiovascular, metabolic, and immune systems, and insomnia has been shown to adversely influence metabolism and endocrine function, including altering the hypothalamic-pituitary-adrenal axis and elevating biomarkers of chronic inflammation [9–11]. Numerous previous studies have shown that insomnia is associated with an increased coronary heart disease and that it influences cardiovascular mortality; however, results to date have been inconsistent [12–14] Depression, which is often accompanied with insomnia, not only increases the risk of a new event of heart disease but also increases the risk of recurrent events in patients with heart disease through several biological pathways [15, 16]. Insomnia and depression are commonly comorbid and are associated with significant distress, daytime fatigue, and increased likelihood of day-time sleep, in addition to pathological effects [17, 18]. Consequently, it can impair an individual’s ability to adapt and respond to illness [19, 20]. Therefore, it is important to understand whether insomnia and depression may by associated with OHCA risk both independently and in conjunction. We hypothesized that insomnia affects the risk of OHCA (...truncated)