Circulation Journal
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Print ISSN : 1346-9843
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Predictors and Prognostic Impact of Post-Traumatic Stress Disorder After the Great East Japan Earthquake in Patients With Cardiovascular Disease
– Report From the CHART-2 Study –
Takeo OnoseKotaro NochiokaYasuhiko SakataMasanobu MiuraSoichiro TadakiRyoichi UshigomeTakeshi YamauchiKenjiro SatoKanako TsujiRuri AbeSatoshi MiyataJun TakahashiHiroaki Shimokawaon behalf of the CHART-2 Investigators
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Supplementary material

2015 Volume 79 Issue 3 Pages 664-667

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Abstract

Background: We examined the prevalence, predictors and prognostic impact of post-traumatic stress disorder (PTSD) after the Great East Japan Earthquake in patients with cardiovascular disease (CVD) in the CHART-2 study.

Methods and Results: The prevalence of PTSD was 14.7% at 6 months after the Earthquake. Female sex, experiencing the Tsunami, property loss, poverty, and insomnia medication use were associated with PTSD. The patients with PTSD more frequently experienced a composite of death, acute myocardial infarction, stroke and heart failure (18.5% vs. 15.0%, P=0.035).

Conclusions: PTSD was frequent in CVD patients after the Earthquake and had an adverse prognostic impact. (Circ J 2015; 79: 664–667)

In March 2011, the Great East Japan Earthquake, followed by a devastating tsunami and Fukushima-Daiichi nuclear power plant explosion, destroyed 370,780 houses and killed 15,785 people in the Tohoku District of Japan.13 Our observational study, the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2),46 which enrolled 10,219 patients with cardiovascular disease (CVD) in the disaster area, has provided a unique opportunity to examine the prognostic impact of disaster-related mental stress in survivors with CVD.

Methods

The CHART-2 study is a multicenter observational study of Japanese patients with CVD (Identifier: NCT00418041).46 Briefly, the study enrolled 10,219 consecutive Japanese patients older than 20 years with heart failure (HF) in Stages B/C/D or those with coronary artery disease (Stage A) between October 2006 and March 2010. Stages of HF were defined according to the ACC/AHA guidelines.7 Information on medical history and baseline demographics, including medication and echocardiographic data, was collected at the time of enrollment and thereafter annually by clinical research coordinators. The CHART-2 study was approved by the local ethics committees and written informed consent was provided by all patients. In September 2011, we sent a self-administered questionnaire including the Japanese version of the Impact of Event Scale-Revised (IES-R-J, Cronbach’s Alpha; 0.95)8 to 8,823 patients registered in the CHART-2 study. The IES-R-J score ranges from 0 to 88, and post-traumatic stress disorder (PTSD) is defined as a score ≥25.8 The primary endpoint was a composite of all-cause mortality and hospitalization for acute myocardial infarction, angina pectoris, stroke and HF. The present study was approved by the ethics committee of each participating hospital. All analyses were performed using R version 3.0.3 (R Foundation for Statistical Computing, Vienna, Austria).

Results

By December 2011, we obtained 3,620 valid responses, among which 534 (14.7%) patients were diagnosed as having PTSD. The patients with PTSD were characterized by female sex, higher age, lower diastolic blood pressure, lower prevalence of ischemic heart disease, higher prevalence of stroke and, particularly, a higher frequency of a past or current history of insomnia medication use (Table). The prevalence of PTSD was highest in the hospitals in the area directly affected by the Tsunami or within close proximity (<30 km) to the Fukushima-Daiichi nuclear power plant, and decreased in association with the reduction in seismic intensity (Figure A). The patients who experienced the Tsunami had the highest prevalence of PTSD (Figure B). Multivariate logistic regression analysis revealed that PTSD was significantly associated with several factors, including female sex (adjusted odds ratio (adOR) 1.27; 95% confidence interval (CI) 1.02–1.57; P=0.02), dyslipidemia (adOR 0.58; 95% CI 0.38–0.93; P=0.02), past or current insomnia medication use (adOR 8.57; 95% CI 5.76–12.76; P<0.001), experiencing the Tsunami (adOR 1.95; 95% CI 1.00–3.67; P=0.04), major property loss (adOR 1.65; 95% CI 1.14–2.38; P<0.01) and economic poverty after the Earthquake (adOR 3.22; 95% CI 1.73–5.91; P<0.001). Interestingly, dyslipidemia (adOR 0.52; 95% CI 0.31–0.92; P=0.02), major property loss (adOR 1.78; 95% CI 1.15–2.72; P<0.01) and economic poverty (adOR 4.64; 95% CI 2.33–9.12; P<0.001) were more likely associated with PTSD in males, whereas experiencing the Tsunami (adOR 4.40; 95% CI 1.26–14.7; P=0.02) was in females. Past or current insomnia medication use had comparable effect between the sexes (adOR 8.80; 95% CI 5.30–14.1; P<0.001, and adOR 10.00; 95% CI 5.00–20.4; P<0.001 for male and female, respectively). Importantly, during the median follow-up of 2 years, the patients with PTSD, as compared with those without it, more frequently experienced the primary endpoint (18.5% vs. 15.0%, adOR 1.26; 95% CI 1.02–1.57, P=0.035) (Figure C), regardless of age, sex, HF etiology or stage. Corporeal damages by the Tsunami and/or by the Earthquake did not influence the incidence of the primary endpoint (adOR 0.99; 95% CI 0.80–1.23, P=0.93) regardless of the presence or absence of PTSD.

Figure.

(A) Location of the epicenter of the Great East Japan Earthquake, the Fukushima-Daiichi nuclear power plants, and the study sites, and the proportions of patients with post-traumatic stress disorder (PTSD). (B) The questionnaire-based prevalence of PTSD in patients who experienced the Tsunami plus Earthquake, the Earthquake alone, or neither. (C) Kaplan-Meyer survival curves for the primary endpoint. Adjusted hazard ratio (HR) was determined by a stepwise Cox proportional hazard model with the following variables: PTSD, disaster-related experience, age, sex, systolic blood pressure, diastolic blood pressure, heart rate, body mass index, HF stage, hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, history of cancer, stroke, HF hospitalization, ischemic heart disease, valvular heart disease, left ventricular ejection fraction, B-type natriuretic peptide level, and use of renin-angiotensin system inhibitors, β-blockers, loop diuretics and calcium-channel blockers.

Table. Baseline Characteristics of the Patients
  PTSD P value
Yes (n=534) No (n=3,086)
Age at questionnaire, mean (SD), years 68.2 (10.9) 66.6 (11.4) 0.002
Female sex, n (%) 205 (38.4) 756 (24.5) <0.001
Height, mean (SD), cm 159.2 (8.9) 161.5 (8.9) <0.001
Body weight, mean (SD), kg 61.4 (12.3) 63.2 (11.6) 0.002
Body mass index, mean (SD), kg/m2 24.1 (4.2) 23.9 (4.2) 0.417
SBP, mean (SD), mmHg 127.5 (18.2) 128.1 (17.1) 0.504
DBP, mean (SD), mmHg 72.8 (11.5) 74.2 (11.5) 0.01
Heart rate, mean (SD), beats/min 69.5 (13.5) 70.2 (13.7) 0.253
Current or past smoking, n (%) 222 (44.6) 1,446 (49.4) 0.047
Echocardiography and laboratory findings
 LVEF, mean (SD), % 62.2 (14.1) 62.0 (13.8) 0.84
 LVEF <50% 100 (20.0) 560 (19.1) 0.624
 Left atrial dimension, mean (SD), mm 40.3 (8.4) 40.4 (7.8) 0.86
 Hemoglobin, mean (SD), g/dl 13.4 (2.1) 13.7 (1.8) <0.001
 Total protein, mean (SD), g/dl 7.3 (2.8) 7.2 (0.6) 0.305
 Albumin, mean (SD), g/dl 4.2 (0.4) 4.2 (0.4) 0.348
 Total cholesterol, mean (SD), mg/dl 184.8 (35.5) 184.7 (34.8) 0.963
 HbA1c, mean (SD), % 5.8 (11.5) 5.9 (2.5) 0.712
 eGFR, mean (SD), ml·min−1·1.73 m−2 64.6 (28.3) 65.8 (22.8) 0.383
 BNP, median (25th, 75th percentiles), pg/ml 59.2 (24.5, 129.6) 50.4 (21.6, 119.8) 0.025
Medical history, n (%)
 Heart failure in Stage C/D 234 (43.8) 1,272 (41.2) 0.274
 Hypertension 394 (73.8) 2,348 (76.1) 0.251
 Diabetes mellitus 127 (23.8) 756 (24.5) 0.744
 Dyslipidemia 385 (72.1) 2,386 (77.3) 0.009
 Hemodialysis 5 (0.9) 23 (0.7) 0.594
 Stroke 94 (17.6) 434 (14.1) 0.039
 Atrial fibrillation 138 (26.0) 716 (23.3) 0.184
 Cancer 49 (9.2) 313 (10.1) 0.601
 COPD 9 (4.6) 35 (2.8) 0.175
 Ischemic heart disease 272 (50.9) 1,764 (57.2) 0.008
 Valvular heart disease 96 (18.0) 502 (16.3) 0.344
 Cardiomyopathy 67 (12.5) 422 (13.7) 0.537
Medications, n (%)
 ACEI or ARB 335 (62.7) 1,967 (63.7) 0.661
 Loop diuretics 133 (24.9) 632 (20.5) 0.025
 Aldosterone antagonists 67 (12.5) 346 (11.2) 0.376
 Calcium-channel blockers 242 (45.3) 1,422 (46.1) 0.778
 Digitalis 72 (13.5) 407 (13.2) 0.836
 β-blockers 209 (39.1) 1,293 (41.9) 0.235
 Past or current insomnia medication use 194 (36.3) 171 (5.5) <0.001
Disaster experience, n (%)
 No effect from the Earthquake 60 (11.2) 733 (23.8) <0.001
 Tsunami evacuation or being trapped 82 (15.4) 144 (4.7) <0.001
 Own hospitalization 43 (8.1) 65 (2.1) <0.001
 Hospitalization of close relatives 102 (19.1) 223 (7.2) <0.001
 Major property loss 238 (44.6) 857 (27.8) <0.001
 Economic poverty 69 (12.9) 96 (3.1) <0.001
 Change of residence 58 (10.9) 102 (3.3) <0.001
 Unemployment or job change 22 (4.1) 43 (1.4) <0.001

Comparisons between groups were performed by the Welch’s t-test for continuous variables, and by the Fisher’s exact test for dichotomous variables. All analyses were performed using R version 3.0.3. P<0.05 was considered to be statistically significant. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BNP, B-type natriuretic peptide; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HbA1c, hemoglobin A1c; LVEF, left ventricular ejection fraction; SBP, systolic blood pressure.

Discussion

To the best of our knowledge, this is the first study demonstrating the prevalence, predictors and adverse prognostic impact of psychological stress caused by a major earthquake. Although the overall prevalence of PTSD (11.4%) was comparable with that reported in the general population after major disasters,9,10 the present study demonstrates for the first time that the intensity of the Earthquake, experiencing the Tsunami and proximity to the nuclear power plants were independently associated with the incidence of PTSD. PTSD was more frequently observed in females than in males,11 and furthermore, sex differences were suggested in the mechanisms of PTSD after the Earthquake; dyslipidemia, major property loss and economic poverty were mainly associated with PTSD in males, whereas the Tsunami experience was the main factor for females. Thus, corporeal and spiritual losses differently influence mental disorders in males and females after a major natural disaster. In contrast, the prognostic effect of the Earthquake was comparable between the sexes in patients with PTSD.

In conclusion, PTSD was frequently noted in CVD patients at 6 months after the Great East Japan Earthquake and associated with subsequent adverse prognostic impact. Furthermore, the present study demonstrates the importance of a sex-based approach to preventing PTSD after major disasters when victims experience several types of stress.12 Further studies are needed to generalize the present findings to other cohorts.

Acknowledgments

We thank all the CHART-2 study investigators (Appendix S1) and the staff of the Department of Evidence-based Cardiovascular Medicine for their contributions.

Funding

This study was supported in part by Grants-in-Aid from a Research Grant from the Ministry of Health, Labour, and Welfare (H.S. and Y.S.) and by a research grant from Banyu Life Science Foundation International (Y.S.).

Conflict of Interest

H.S. received lecture fees from Bayer Yakuhin, Ltd (Osaka, Japan), Daiichi Sankyo Co, Ltd (Tokyo, Japan) and Novartis Pharma K.K. (Tokyo, Japan). The Department of Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, is supported in part by the unrestricted research grants from Daiichi Sankyo Co, Ltd (Tokyo, Japan), Bayer Yakuhin, Ltd (Osaka, Japan), Kyowa Hakko Kirin Co, Ltd (Tokyo, Japan), Kowa Pharmaceutical Co, Ltd (Tokyo, Japan), Novartis Pharma K.K. (Tokyo, Japan), Dainippon Sumitomo Pharma, Co, Ltd (Osaka, Japan), and Nippon Boehringer Ingelheim Co, Ltd (Tokyo, Japan).

Supplementary Files

Supplementary File 1

Appendix S1. The CHART-2 Study Investigators

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-14-1403

References
 
© 2015 THE JAPANESE CIRCULATION SOCIETY
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