Age 3 Gender Interaction Effect on Resuscitation Outcomes in Patients With Out-of-Hospital Cardiac Arrest Akihito Hagihara, DMSca,*, Daisuke Onozuka, PhDa, Junko Ono, MSa, Takashi Nagata, MDb, and Manabu Hasegawa, MDc Although an interaction between gender and age has been shown to influence resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA), this interaction has not been investigated in Asian populations. In this prospective, observational study, data from all cases of OHCA in Japan between 2005 and 2012 were obtained from the Japanese National Registry. We determined the relative excess risk due to interaction and the ratio of odds ratios (ORs) to assess the interaction effect of gender and age on the incidence of return of spontaneous circulation (ROSC) before hospital arrival, 1-month survival, and neurologically intact survival 1 month after OHCA. Male gender was associated with decreased ROSC and lower 1-month survival rates in patients with OHCA of presumed cardiac origin. Older age was associated with lower 1-month and neurologically intact survival rates in male patients with OHCA of presumed cardiac and noncardiac origin and with increased ROSC in male patients with OHCA of presumed cardiac origin. The relative excess risk due to interaction for ROSC in patients with OHCA of presumed cardiac origin was statistically significant (OR 0.19, 95% confidence interval [CI] 0.06 to 0.32). The ratio of ORs for ROSC was statistically significant in patients with OHCA of presumed cardiac origin (OR 1.25, 95% CI 1.05 to 1.47) and of noncardiac origin (OR 0.40, 95% CI 0.17 to 0.92). In conclusion, the interaction effect between age and gender on ROSC was positive in OHCA cases of presumed cardiac origin and negative in those of noncardiac origin. Ó 2017 Elsevier Inc. All rights reserved. (Am J Cardiol 2017;120:387e392) Gender-related differences might play a role in the cause and resuscitation outcomes of out-of-hospital cardiac arrest (OHCA). Female patients with OHCA are more likely to be older,1 and are less likely to have a witnessed collapse,2 an arrest in a public place,3 cardiopulmonary resuscitation (CPR) by a bystander,4 and a shockable initial rhythm.1,3 Despite these unfavorable conditions, the survival to hospital arrival rate is higher in female than in male patients.5,6 It has been revealed that female patients of reproductive age are more likely to survive to hospital discharge than are male patients in the same age range because of protective effects of endogenous estrogen on the cardiovascular and a Department of Health Services Management and Policy, Kyushu University Graduate School of Medicine, Fukuoka, Japan; bDepartment of Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan; and cDepartment of Welfare, Shimonoseki, Japan. Manuscript received March 10, 2017; revised manuscript received and accepted May 1, 2017. Author Contributions: Hagihara made substantial contributions to conception and design. Hagihara and Onozuka analyzed data. Hagihara wrote the manuscript. Onozuka, Ono, Nagata, and Hasegawa were involved in drafting the manuscript and critically revising it for important intellectual content. Funding: This work was supported by Grants 15K08714 and 16H05247 from the Japan Society for the Promotion of Science. The funding source had no role in the study design, data collection, data analysis, data interpretation, or preparation of the manuscript. See page 392 for disclosure information. *Corresponding author: Tel: þ(81) 92-642-6950; fax: þ(81) 92-6426961. E-mail address: [email protected] (A. Hagihara).

0002-9149/17/$ - see front matter Ó 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2017.05.003

nervous system.7e11 A recent study found that the probability of survival for women continually decreased with age from the age of 18 years, whereas the probability of survival for men with OHCA of presumed cardiac origin increased steadily from 18 to 65 years of age and decreased thereafter.12 The higher early mortality in men was attributed to an interaction between gender hormones and age-specific physiology.12 Although an interaction between gender and age has been shown to influence resuscitation outcomes in patients with OHCA, this interaction has not been investigated in Asian populations. Thus, we obtained data from all cases of OHCA in Japan between 2005 and 2012 to investigate the interaction effect between gender and age on resuscitation outcomes according to OHCA origin. Methods Detailed information on the emergency medical service (EMS) system in Japan is published elsewhere.13,14 Briefly, during the study period, municipal governments provide EMS through approximately 800 fire stations with dispatch centers in Japan. Because EMS providers are not allowed to terminate resuscitation in the field by the Japanese guidelines, all patients with OHCA who are treated by EMS personnel are then transported to medical facilities.15 Based on a standardized Utstein-style template, the Fire and Disaster Management Agency (FDMA) has developed a registry of all OHCA cases in Japan which is in a prospective, nationwide, and population-based manner. In cooperation with the physicians in charge of patients with OHCA, EMS personnel use a standardized Utstein style, and summarize each OHCA case.16 Data from the www.ajconline.org

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The American Journal of Cardiology (www.ajconline.org)

Figure 1. OHCA cases evaluated in the study.

approximately 800 fire stations with dispatch centers in the 47 prefectures are then integrated into a national registry system on the FDMA database server after an electronic data check by FDMA. This is a prospective observational study using national registry data. The study was approved by the ethics committee at Kyushu University Graduate School of Medicine. Because the registry data were anonymous, the requirement for written informed consent was waived. There were 8 inclusion/exclusion criteria for study subjects. Specifically, the subjects (1) had an OHCA before the arrival of EMS personnel, (2) were 18 to 65 years of age, (3) were not resuscitated by public automated external defibrillator, (4) had an initial ventricular fibrillation/ventricular tachycardia rhythm, (5) were defibrillated by EMS personnel, (6) were of presumed cardiac or noncardiac origin, (7) experienced time from call to arrival at the scene or to the hospital of 52 years), and 95% confidence intervals (CIs) were derived by the delta method.19 All analyses were performed using the STATA software (version 14.1; Stata Corporation, College Station, Texas). The significance level for all tests was p 56 years, men aged 56 years, and men aged >56 years are presented in Table 2, with women

Coronary Artery Disease/Interaction Between Gender and Age in OHCA Patients

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Table 1 Baseline characteristics of patients with OHCA according to origin of cardiac arrest and gender, 2005 to 2012, Japan (n ¼ 25,431) Characteristics

Non-cardiac Females (n ¼ 296)

(OHCA Patients) Cases by year 2005 2006 2007 2008 2009 2010 2011 2012 Season January-March April-June July-September October-December Age, mean (SD), years Bystander eyewitness (yes) Relationship between bystander and patient (family member) (Cardiopulmonary resuscitation initiated by bystander) Chest compressions (yes) Rescue breathing (yes) (Life support by emergency medical service personnel) Emergency life-saving technician in ambulance (yes) Medical doctor in ambulance (yes) Advanced life support by physician (yes) Time from call to arrival at scene, mean (SD), min Time from call to arrival at hospital, mean (SD), min Number of defibrillations (1) Advanced airway management (yes) Insertion of intravenous line (yes) Epinephrine use (yes) (Endpoints) ROSC before hospital arrival (yes) 1-month survival (yes) CPC (1 or 2)

p

Males (n ¼ 919)

Presumed-cardiac

p

Females (n ¼ 3,212)

Males (n ¼ 21,004)

38 33 34 29 34 44 43 41

(12.8%) (11.2%) (11.5%) (9.8%) (11.5%) (14.9%) (14.5%) (13.9%)

118 127 114 115 114 119 108 104

(12.8%) (13.8%) (12.4%) (12.5%) (12.4%) (13.0%) (11.8%) (11.3%)

0.526

347 402 389 408 437 407 411 411

(10.8%) (12.5%) (12.1%) (12.7%) (13.6%) (12.7%) (12.8%) (12.8%)

2404 2510 2657 2700 2714 2650 2681 2687

(11.5%) (12.0%) (12.7%) (12.9%) (12.9%) (12.6%) (12.8%) (12.8%)

0.840

106 61 58 71 46.81 153 65

(35.8%) (20.6%) (19.6%) (24.0%) (14.77) (51.7%) (22.5%)

260 206 207 246 47.70 544 186

(28.3%) (22.4%) (22.5%) (26.8%) (14.25) (59.2%) (20.6%)

0.108

(27.3%) (23.0%) (23.5%) (26.1%) (11.05) (73.4%) (43.9%)

5475 5072 5176 5280 53.14 16,035 7,644

(26.1%) (24.2%) (24.6%) (25.1%) (10.36) (76.3%) (36.7%)

0.129

0.344 0.023 0.487

878 739 756 839 52.32 2,359 1,397