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.
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.1–3
Our observational study, the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2),4–6
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).4–6
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.
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
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