Interaction Effects between Insomnia and Depression on Incidence of Out-of-Hospital Cardiac Arrest: Multi-center study

doi:10.21203/rs.3.rs-1734977/v1

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Interaction Effects between Insomnia and Depression on Incidence of Out-of-Hospital Cardiac Arrest: Multi-center study

https://doi.org/10.21203/rs.3.rs-1734977/v1

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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.

Methods

This prospective multicenter case-control study was performed using Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiology Surveillance (CAPTURES-II) 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]).

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.

Insomnia

Depression

OHCA

Incidence

Current Knowledge/Study nationale: 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. Therefore, it is important to understand whether insomnia and depression may by associated with OHCA incidence both independently and in conjunction

Study impact: In the young age group, insomnia and depression together increased the risk of OHCA significantly. Early and active medical intervention for insomnia patients with depression may contribute to lowering the risk of OHCA.

Out-of-hospital cardiac arrest (OHCA) is a major public health burden because of its high incidence and low survival rates. The average global incidence of OHCA 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 OHCA patients, survival outcomes after OHCA remain poor ³.

The approach to OHCA 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 OHCA; however, the risk of OHCA is also associated with classical factors, such as hypertension, diabetes mellitus, and dyslipidemia ^{4, 5}.

Insomnia, the most common sleep disorder, is characterized by difficulty initiating and maintaining sleep and early-morning awakening ⁶. 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 ^7–9. 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 ¹⁰, ¹¹, ¹².

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 ¹³,¹⁴.

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 ¹⁵, ¹⁶. Consequently, it can impair an individual’s ability to adapt and respond to illness ¹⁷, ¹⁸.

Therefore, it is important to understand whether insomnia and depression may by associated with OHCA incidence both independently and in conjunction. We hypothesized that insomnia affects the incidence of OHCA through several processes and that these effects may vary depending on whether or not depression is present. The purpose of this study, therefore, was to determine the association of insomnia with the incidence of OHCA and identify if its effect is influenced by depression.

Study design, setting, and data source

This prospective multi-center case-control study was performed using Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES-II) project database in Korea.

The CAPTURES project aimed to identify risk factors for OHCA and evaluate prognostic factors with long-term follow-up. Phase I CAPTURES was performed in 27 hospitals in 2014. A detailed description of Phase I CAPTURES has been previously reported ¹⁹.

The CAPTURES-II project was a prospective hospital-based patient cohort study conducted at 17 university hospitals from September 2017 to December 2020. Patients who suffered OHCA who had a presumed cardiac etiology and were transported to the participating emergency department (ED) by emergency medical service (EMS) were included this project. Each patient was identified by the emergency physicians in each ED.

The CAPTURES-II registry included face-to-face interview for demographics, comorbidities assessment, health behaviors monitoring, medical record review including laboratory test results, short- and long-term follow-up (1 month, 6 months, and 12 months after hospital discharge), and blood sample collection for biomarker evaluation. For community-based controls, face-to-face interview and medical record review were conducted to obtain the same information concerning OHCA, and blood sample collection was performed. The data collected from all participating hospitals were transferred to the Quality Management Committee (QMC), where quality control and statistical analysis were performed. The QMC provided feedback to research coordinators on data quality control through monthly meetings. If the research coordinator was unable to define a coding element, they consulted the emergency physicians in the QMC for clarification.

Study population

Cases were defined as adult EMS-treated OHCA patients who had a presumed cardiac etiology and visited participating hospitals from September 2017 to December 2020.

Community-based controls were recruited from two hospitals (one metropolitan and one non-metropolitan). By cooperating with various community centers or public health centers, the CAPTURES-II control recruitment was promoted, with voluntary applicants being recruited as the control group. The controls were randomly matched within the strata, including age (10-year intervals), sex, and type of residence (metropolitan vs. urban or rural), with a 1:1 ratio of controls to cases.

Variables and measurements

The main exposure was history of insomnia as measured via face-to-face interviews with the patients or their families. Insomnia history was defined as a positive case of answering “yes” to the question “Have you ever suffered or been diagnosed with insomnia?” Depression history was defined in the same way.

The CAPTURES-II registry used the same questionnaire for cases and controls. We collected information on patient demographics (age, sex, residence area [metropolis vs. urban or rural]), insurance, education level), comorbidities (hypertension, diabetes, dyslipidemia, stroke), health behaviors (smoking, alcohol, coffee, physical activity), and sleep-related variables, as well as obesity, work type, sleeping medication, snoring, and sleep apnea.

Statistical analysis

Demographic findings of the OHCA case group and community-based control group have been described. Categorical variables were analyzed using the chi-square test, and continuous variables with normal distribution were analyzed using the t-test. Case-control matching was performed based on age, sex, and residence (metropolis vs. urban or rural). For the case-control dataset, conditional logistic regression analysis was conducted to estimate the effect of insomnia and depression on the risk of OHCA incidence and to calculate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) after adjusting for potential confounders identified in directed acyclic graph models. We also conducted interaction analysis between history of insomnia and history of depression according to age group. Finally, subgroup analysis was performed in the patients with insomnia. In subgroup analysis, we conducted interaction analysis between history of depression and insomnia medication. All variables in the final model were assessed for multicollinearity, which was not detected in this analysis.

All statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). All p-values were two tailed, and p < 0.05 was considered statistically significant.

Ethic statements

The study was approved by the ethics committees of all 17 participating university hospitals (IRB No: Chonnam National University Hospital, CNUH-2017-285; Chungbuk National University Hospital, CBNUH2017-09-009-001; Chungnam National University Hospital, CNUH2017-10-027; Dankook University Hospital, DKUH2018-12-019; Hallym University Kangnam Sacred Heart Hospital, HKS2018- 02-016; Hallym University Dongtan Sacred Heart Hospital, HDT2017-10-002; Korea University Anam Hospital, 2018AN0148; Korea University Ansan Hospital, AS17174; Kyungpook National University Hosptial, KNUH2017-10-035-006; Seoul National University Boramae Medical Center, 20171123/30-2017-66/123; Seoul National University Bundang Hospital, B-1711/430 − 304; Seoul National University Hospital, H-1709-053-883; Soonchunhyang University Bucheon Hospital, SCHBC2018-02-014-002; Sungkyunkwan University Samsung Medical Center, SMC2018-08-121; Ulsan University Asan Medical Center, S2018-1805-0001; Yonsei University Severance Hospital, 4-2017-1201; Yonsei University Wonju Severance Christian Hospital, CR317101). Informed consent was obtained from all subjects and/or their legal guardian(s). This study is registered at ClinicalTrials.gov (NCT03700203). All methods were performed in accordance with relevant guidelines and regulations.

Demographic findings

A total of 1014 OHCA cases and 1014 community-based controls were included in this analysis.

The characteristics of the OHCA cases and community-based controls are shown in Table 1. Of cases and matched controls, 26.8% (272/1014) and 26.7% (271/1014) had a history of insomnia (p-value = 0.96) and 7.3 (74/1014) and 7.1 (72/1014) had history of depression (p-value < 0.01).

Table 1

Characteristics of the out-of-hospital cardiac arrest case group and age-, sex-, and urbanization level-matched control group.
Variables	All	OHCA case	Community control
Variables	N (%)	N (%)	N (%)	p-value
All	2,028 (100.0)	1,014 (100.0)	1,014 (100.0)
Age				1.00
18—29	38 (1.9)	19 (1.9)	19 (1.9)
30—39	114 (5.6)	57 (5.6)	57 (5.6)
40—49	276 (13.6)	138 (13.6)	138 (13.6)
50—59	512 (25.2)	256 (25.2)	256 (25.2)
60—69	544 (26.8)	272 (26.8)	272 (26.8)
70—120	544 (26.8)	272 (26.8)	272 (26.8)
Gender, female	554 (27.3)	277 (27.3)	277 (27.3)	1.00
Metropolis, yes	1,028 (50.7)	514 (50.7)	514 (50.7)	1.00
Comorbidity
Hypertension	823 (40.6)	454 (44.8)	369 (36.4)	< 0.01
Diabetes mellitus	411 (20.3)	274 (27.0)	137 (13.5)	< 0.01
Dyslipidemia	365 (18.0)	130 (12.8)	235 (23.2)	< 0.01
Stroke	115 (5.7)	85 (8.4)	30 (3.0)	< 0.01
Insurance, medical aid	210 (10.4)	110 (10.8)	100 (9.9)	0.47
Education level, high	646 (31.9)	253 (25.0)	393 (38.8)	< 0.01
Obesity, yes	146 (7.2)	35 (3.5)	111 (10.9)	< 0.01
Married, yes	1,544 (76.1)	705 (69.5)	839 (82.7)	< 0.01
Work type
Night work	362 (17.9)	100 (9.9)	262 (25.8)	< 0.01
Shift work	178 (8.8)	32 (3.2)	146 (14.4)	< 0.01
Physical activity				< 0.01
Vigorous	365 (18.0)	115 (11.3)	250 (24.7)
Moderate	365 (18.0)	115 (11.3)	250 (24.7)
No	549 (27.1)	159 (15.7)	390 (38.5)
Coffee, yes	697 (34.4)	202 (19.9)	495 (48.8)	< 0.01
Smoking				< 0.01
Current smoker	536 (26.4)	343 (33.8)	193 (19.0)
Ex-smoker	597 (29.4)	252 (24.9)	345 (34.0)
Non-smoker	895 (44.1)	419 (41.3)	476 (46.9)
Alcohol drinking				< 0.01
Heavy	617 (30.4)	309 (30.5)	308 (30.4)
Moderate	661 (32.6)	246 (24.3)	415 (40.9)
No	750 (37.0)	459 (45.3)	291 (28.7)
Sleeping pill, yes	95 (4.7)	60 (5.9)	35 (3.5)	< 0.01
Sleep disorder
Insomnia	543 (26.8)	272 (26.8)	271 (26.7)	0.96
Snoring	1,073 (52.9)	493 (48.6)	580 (57.2)	< 0.01
Sleep apnea	350 (17.3)	188 (18.5)	162 (16.0)	0.13
Depression, Yes	146 (7.2)	74 (7.3)	72 (7.1)	< 0.01
OHCA, out-of-hospital cardiac arrest

The characteristics according to the history of insomnia and depression are reported Table 2 and Table 3. Insomnia did not increase OHCA incidence (50.1% vs. 50.0, p value = 0.17), whereas history of depression lowered the OHCA incidence (50.7% vs. 57.6%, p value < 0.01).

Table 2

Characteristics of the study population according to the insomnia
Variables	All	Insomnia (+)	Insomnia (-)
Variables	N (%)	N (%)	N (%)	p-value
All	2,028 (100.0)	543 (100.0)	1,485 (100.0)
Case-control				0.17
OHCA case	1,014 (50.0)	272 (50.1)	742 (50.0)
Community control	1,014 (50.0)	271 (49.9)	743 (50.0)
Age				< 0.01
18—29	38 (1.9)	7 (1.3)	31 (2.1)
30—39	114 (5.6)	29 (5.3)	85 (5.7)
40—49	276 (13.6)	80 (14.7)	196 (13.2)
50—59	512 (25.2)	112 (20.6)	400 (26.9)
60—69	544 (26.8)	159 (29.3)	385 (25.9)
70—120	544 (26.8)	156 (28.7)	388 (26.1)
Gender, female	554 (27.3)	183 (33.7)	371 (25.0)	< 0.01
Metropolis, yes	1,028 (50.7)	297 (54.7)	731 (49.2)	0.86
Comorbidity
Hypertension	823 (40.6)	249 (45.9)	574 (38.7)	< 0.01
Diabetes	411 (20.3)	140 (25.8)	271 (18.2)	< 0.01
Dyslipidemia	365 (18.0)	126 (23.2)	239 (16.1)	< 0.01
Stroke	115 (5.7)	45 (8.3)	70 (4.7)	< 0.01
Insurance, medical aid	210 (10.4)	66 (12.2)	144 (9.7)	0.47
Education level, high	646 (31.9)	162 (29.8)	484 (32.6)	< 0.01
Obesity, yes	146 (7.2)	55 (10.1)	91 (6.1)	< 0.01
Married, yes	1,544 (76.1)	415 (76.4)	1,129 (76.0)	< 0.01
Work type
Night work	362 (17.9)	91 (16.8)	271 (18.2)	< 0.01
Shift work	178 (8.8)	57 (10.5)	121 (8.1)	< 0.01
Physical activity				< 0.01
Vigorous	365 (18.0)	78 (14.4)	287 (19.3)
Moderate	549 (27.1)	141 (26.0)	408 (27.5)
No	1,114 (54.9)	324 (59.7)	790 (53.2)
Coffee, yes	697 (34.4)	157 (28.9)	540 (36.4)	< 0.01
Smoking				< 0.01
Current smoker	536 (26.4)	142 (26.2)	394 (26.5)
Ex-smoker	597 (29.4)	156 (28.7)	441 (29.7)
Non-smoker	895 (44.1)	245 (45.1)	650 (43.8)
Alcohol drinking				< 0.01
Heavy	617 (30.4)	170 (31.3)	447 (30.1)
Moderate	661 (32.6)	162 (29.8)	499 (33.6)
No	750 (37.0)	211 (38.9)	539 (36.3)
Sleeping pill, yes	95 (4.7)	91 (16.8)	4 (0.3)	< 0.01
Sleeping disorder
Snoring	1,073 (52.9)	339 (62.4)	734 (49.4)	< 0.01
Sleep apnea	350 (17.3)	119 (21.9)	231 (15.6)	0.13
Depression, yes	146 (7.2)	77 (14.2)	69 (4.6)	< 0.01
OHCA, out-of-hospital cardiac arrest

Table 3

Characteristics of the study population according to the depression
Variables	All	Depression (+)	Depression (-)
Variables	N (%)	N (%)	N (%)	p-value
All	1,748 (100.0)	146 (100.0)	1,602 (100.0)
Case-control				< 0.01
OHCA case	996 (57.0)	74 (50.7)	922 (57.6)
Community control	752 (43.0)	72 (49.3)	680 (42.4)
Age				1.00
18–29	34 (1.9)	1 (0.7)	33 (2.1)
30–39	98 (5.6)	11 (7.5)	87 (5.4)
40–49	242 (13.8)	35 (24.0)	207 (12.9)
50–59	448 (25.6)	19 (13.0)	429 (26.8)
60–69	472 (27.0)	37 (25.3)	435 (27.2)
70-	454 (26.0)	43 (29.5)	411 (25.7)
Gender, female	469 (26.8)	51 (34.9)	418 (26.1)	1.00
Metropolis, yes	890 (50.9)	101 (69.2)	789 (49.3)	0.86
Comorbidity
Hypertension	727 (41.6)	57 (39.0)	670 (41.8)	< 0.01
Diabetes	342 (19.6)	37 (25.3)	305 (19.0)	< 0.01
Dyslipidemia	339 (19.4)	29 (19.9)	310 (19.4)	< 0.01
Stroke	97 (5.5)	14 (9.6)	83 (5.2)	< 0.01
Insurance, medical aid	170 (9.7)	30 (20.5)	140 (8.7)	0.47
Education level, high	591 (33.8)	34 (23.3)	557 (34.8)	< 0.01
Obesity, yes	141 (8.1)	17 (11.6)	124 (7.7)	< 0.01
Married, yes	1,407 (80.5)	106 (72.6)	1,301 (81.2)	< 0.01
Work type
Night work	346 (19.8)	20 (13.7)	326 (20.3)	< 0.01
Shift work	171 (9.8)	11 (7.5)	160 (10.0)	< 0.01
Physical activity				< 0.01
Vigorous	347 (19.9)	20 (13.7)	327 (20.4)
Moderate	510 (29.2)	31 (21.2)	479 (29.9)
No	891 (51.0)	95 (65.1)	796 (49.7)
Coffee, yes	669 (38.3)	41 (28.1)	628 (39.2)	< 0.01
Smoking				< 0.01
Current smoker	451 (25.8)	41 (28.1)	410 (25.6)
Ex-smoker	539 (30.8)	42 (28.8)	497 (31.0)
Non-smoker	758 (43.4)	63 (43.2)	695 (43.4)
Alcohol drinking				< 0.01
Heavy	545 (31.2)	42 (28.8)	503 (31.4)
Moderate	597 (34.2)	47 (32.2)	550 (34.3)
No	606 (34.7)	57 (39.0)	549 (34.3)
Sleeping pill, yes	86 (4.9)	30 (20.5)	56 (3.5)	< 0.01
Sleep disorder
Insomnia	486 (27.8)	77 (52.7)	409 (25.5)	< 0.01
Snoring	989 (56.6)	79 (54.1)	910 (56.8)	< 0.01
Sleep apnea	328 (18.8)	32 (21.9)	296 (18.5)	0.13
OHCA, out-of-hospital cardiac arrest

Main results

The results of conditional logistic regression models, including AORs (95% CIs), for OHCA with history of insomnia and depression are shown in Table 4. Insomnia was not associated with increased OHCA risk (AOR [95% CI]: 0.95 [0.64—1.40]). Depression also was not a risk factor of OHCA (0.86 [0.67—1.10]).

Table 4

Multivariable conditional logistic regression analysis of insomnia and depression for out-of-hospital cardiac arrest
OHCA incidence	OHCA cases/Community controls	Model 1			Model 2			Model 3			Model 3 (subgroup)
OHCA incidence	(n/n)	AOR	95% CI		AOR	95% CI		AOR	95% CI		AOR	95% CI
Insomina (-)	742/743	1.00			1.00			1.00
Insomnia (+)	272/271	0.92	0.74	1.13	1.00	0.80	1.25	0.95	0.64	1.40
Depression (-)	900/937	1.00			1.00			1.00			1.00
Depression (+)	114/77	1.49	1.08	2.06	1.23	0.87	1.73	0.86	0.67	1.10	2.30	1.26	4.20
Younger age (18–64)	602/599	1.00			1.00			1.00			1.00
Older age (65–120)	412/415	1.07	0.75	1.53	1.18	0.81	1.70	1.40	0.93	2.12	1.19	0.57	2.48
OHCA, out-of-hospital cardiac arrest

Interaction analysis

We added an interaction term between history of insomnia and depression to the fully adjusted model. The AORs assessing the statistical interaction on OHCA incidence from the conditional logistic regression analysis are shown in Table 5. Insomnia interacted with depression on OHCA incidence in the young population (0.84 [0.59—1.17] for patients without depression, 3.65 [1.29—10.33] for patients with depression, p for interaction < 0.01). In subgroup analysis, history of depression was associated with significantly higher odds of OHCA incidence for patients taking insomnia medication (3.66 [1.15—11.66]) than those taking not insomnia medication (1.05 [0.99—12.22]) (p for interaction < 0.01).

Table 5

Interaction analysis for OHCA incidence of insomnia according to depression
OHCA incidence	Insomnia (-)	Insomnia (+)			p for interaction
OHCA incidence	AOR	AOR	95% CI
Whole population (18–120)					0.03
Depression (-)	1.00	0.89	0.70	1.13
Depression (+)	1.00	2.33	1.17	4.64
Young population (18–64)					< 0.01
Depression (-)	1.00	0.84	0.59	1.17
Depression (+)	1.00	3.65	1.29	10.33
Old population (65–120)					0.17
Depression (-)	1.00	0.87	0.60	1.27
Depression (+)	1.00	1.73	0.64	4.68
OHCA, out-of-hospital cardiac arrest

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.

In the young age group, insomnia and depression together increased the risk of OHCA significantly. This trend was maintained only in the population that did not take insomnia medication. Early and active medical intervention for insomnia patients with depression may contribute to lowering the risk of OHCA.

aOR: adjusted odd ratio

CAPTURES: Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveilance

CI: confidence interval

ED: Emergency department

EMS: emergency medical service

OHCA: out-of-hospital cardiac arrest

QMC: quality management committee

Acknowledgements

We would like to acknowledge and thank to investigators from all 17 participating university hospitals of the phase II Cardiac Arrest Pursuit Trial with Unique Registry and Epidemiologic Surveillance (CAPTURES-II): Sung Oh Hwang (Yonsei University Wonju Severance Christian Hospital), Sang Do Shin (Seoul National University Hospital), Mi Jin Lee (Kyungpook National University Hosptial), Jong-Hak Park (Korea University Ansan Hospital), Su Jin Kim (Korea University Anam Hospital), Sung Bum Oh (Dankook University Hospital), Jonghwan Shin (Seoul National University Boramae Medical Center), Seung Min Park (Seoul National University Bundang Hospital), Min Seob Sim (Sungkyunkwan University Samsung Medical Center), Won Young Kim (Ulsan University Asan Medical Center), In-Cheol Park (Yonsei University Severance Hospital), Hyun Ho Ryu (Chonnam National University Hospital), Yeonho You (Chungnam National University Hospital), Sang-Chul Kim (Chungbuk National University Hospital), Ju Ok Park (Hallym University Dongtan Sacred Heart Hospital).

Funding

This work was supported by the Korea Disease Control and Prevention Agency (Grant No: 2017NE3300600, 2017E3300601, 2019P330800).

Conflicts of interest

None

Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request ([email protected]).

Author Contributions

Dr. Ryu and Jung had full access to all the data used in the study and take responsibility for the integrity of the data as well as the accuracy of data analysis.

Study concept and design: Hwang, Shin, Song, and Cha

Acquisition, analysis, or interpretation of data: Ro and Jung

Drafting of the manuscript: Jung, Lee, Song, and Kim

Critical revision of the manuscript for important intellectual content: Ro, Shin, and Jung

Statistical analysis: Jung and Ryu

Obtained funding: Shin and Hwang

Administrative, technical, or material support: Ro, Kim, and Ryu

Study supervision: Ryu and Hwang

Manuscript approval: All authors

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No competing interests reported.

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Interaction Effects between Insomnia and Depression on Incidence of Out-of-Hospital Cardiac Arrest: Multi-center study

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