SCHRES-06667; No of Pages 6 Schizophrenia Research xxx (2016) xxx–xxx
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Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey Takuro Sugai a,b, Yutaro Suzuki a,b, Manabu Yamazaki c, Kazutaka Shimoda b,d, Takao Mori c, Yuji Ozeki b,d, Hiroshi Matsuda c, Norio Sugawara b,e, Norio Yasui-Furukori b,e, Yoshitake Minami c, Kurefu Okamoto c, Toyoaki Sagae f, Toshiyuki Someya a,b,⁎ a
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan c Japan Psychiatric Hospital Association, Tokyo, Japan d Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Japan e Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan f Department of Health and Nutrition, Yamagata Prefectural Yonezawa University of Nutrition Sciences Faculty of Health and Nutrition, Yonezawa, Japan b
a r t i c l e
i n f o
Article history: Received 22 May 2015 Received in revised form 4 January 2016 Accepted 10 January 2016 Available online xxxx Keywords: Metabolic syndrome Japanese mental health care system Prevalence The adapted adult treatment panel III (ATP III-A) criteria The Japan Society for the Study of Obesity (JASSO) definition Hospitalisation
a b s t r a c t Patients with schizophrenia have a higher risk of metabolic syndrome (MetS). MetS prevalence varies with ethnicity. Although environmental factors, such as lack of physical activity and unbalanced diet, can lead to MetS, these may differ between outpatients and inpatients with schizophrenia. The Japanese mental health care system differs from that in other countries. However, few studies have investigated the prevalence of MetS in Japanese patients with schizophrenia. Therefore, we conducted a nationwide survey to clarify the prevalence of MetS in Japanese outpatients and inpatients with schizophrenia. We investigated the risk of MetS by questionnaire in 520 facilities for outpatients and 247 facilities for inpatients. There were 7655 outpatients and 15,461 inpatients with schizophrenia. MetS prevalence was based on the National Cholesterol Education Program Adult Treatment Panel III (ATP III-A) and the Japan Society for the Study of Obesity (JASSO). The overall MetS prevalence in outpatients using the ATP III-A definition was 34.2%, with 37.8% in men and 29.4% in women, compared with 13.0% in inpatients, with 12.3% in men and 13.9% in women. MetS prevalence in outpatients was approximately 2- to 3-fold higher than in inpatients. In conclusion, MetS prevalence in Japanese outpatients was approximately 3-fold higher than in inpatients. Therefore, we should pay more attention to the risk of physical disease in Japanese patients with schizophrenia, considering the difference in health characteristics between outpatients and inpatients. © 2016 Published by Elsevier B.V.
1. Introduction Patients with schizophrenia have a reduced life expectancy compared with the general population (Druss et al., 2011; Laursen et al., 2007). One reason is that patients with schizophrenia have nearly twice the normal risk of dying from cardiovascular disease (Saha et al., 2007; Capasso et al., 2008). Many studies in Europe and North America have found a higher prevalence of metabolic syndrome (MetS) in patients with schizophrenia compared with the general population (Casey, 2005; Gurpegui et al., 2012). According to a metaanalysis of 25,692 subjects, the MetS prevalence rate was 32.5% ⁎ Corresponding author at: Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 9518510, Japan. E-mail address: [email protected] (T. Someya).
overall, and there were no significant differences due to the inpatient– outpatient status or country (Mitchell et al., 2013). In contrast, in a study in Japan, the MetS prevalence rates in outpatients and inpatients with schizophrenia were 48.1% and 15.8%, respectively (Sugawara et al., 2011). Our previous study revealed that the prevalence of underweight in Japanese inpatients with schizophrenia may be higher than that in the general population (Suzuki et al., 2014). Another study showed that obesity in Japanese inpatients with schizophrenia was associated with b3 months hospitalisation, whereas underweight was associated with ≥3 months hospitalisation (Inamura et al., 2012). The mental health care system in Japan remains hospital based, and has the largest number of psychiatric beds per person in the world. In Japan, the average length of stay is 8.5 years, and 71% of psychiatric inpatients remain in hospital for ≥1 year (Ministry of Health and Welfare, 1999). In addition, there has been a gradual ageing of inpatients, with 29.5% of patients aged N65 years and 64.6% aged N50 years (Zenkaren
http://dx.doi.org/10.1016/j.schres.2016.01.016 0920-9964/© 2016 Published by Elsevier B.V.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
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T. Sugai et al. / Schizophrenia Research xxx (2016) xxx–xxx
Health and Welfare Research Institute, ZHWRI, 2000). This aspect of the mental health system in Japan may be related to the difference in physical health between outpatients and inpatients with schizophrenia. There have been no large investigations of the prevalence of MetS in Japanese patients with schizophrenia, and such data are required to establish the risk of MetS. The most common definitions for MetS are the adapted Adult Treatment Panel III (ATP III-A) criteria proposed by the American Heart Association and the National Cholesterol Education Program. These definitions include waist circumference (WC), blood pressure (BP), triglyceride (TG), high-density lipoprotein cholesterol (HDL) and fasting plasma glucose (FPG) (Alberti et al., 2010). WC has been proposed as the most useful predictor of MetS in various populations with or without schizophrenia (Jin et al., 2010; Wang et al., 2009). However, it is difficult to use the same WC criterion as with European patients because of the smaller physique of Japanese people. In the present investigation, we also used the definition established by Japanese Society for the Study of Obesity (JASSO) (Examination Committee of the Criteria for Metabolic Syndrome in Japan, 2005). In the JASSO definition, the cut-off value for WC is 85 cm for men and 90 cm for women (Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the study of Obesity, 2002). However, the prognostic utility of MetS remains controversial because the different criteria and definitions provide differing results according to cohorts and settings (Zimmet et al., 2005; Alberti et al., 2005). In Japan, most psychiatric care is entrusted to private psychiatric hospitals; most of which belong to the Japan Psychiatric Hospital Association. The joint project with the cooperation of the Japan Psychiatric Hospital Association and the Japanese society of clinical neuropsychopharmacology to protect patients with schizophrenia was started in Japan in December 2012. In the present study, we used the large questionnaire survey in the joint project to establish the prevalence of MetS in Japanese patients with schizophrenia. This is believed to be the largest study investigating the prevalence of MetS in Japanese patients with schizophrenia.
2. Methods 2.1. Study participants The questionnaire survey was conducted between January 2012 and July 2014. We obtained 7655 (outpatients) and 15,461 (inpatients) answers from 520 facilities for outpatients and 247 facilities for inpatients belonging to the Japan Psychiatric Hospital Association. All of the subjects were diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) or International Statistical Classification of Diseases and Related Health Problems version 10 (ICD-10). We excluded individuals aged b20 years and whose sex data were not assessed in the survey (n = 738). We also excluded individuals who could not be assessed for MetS (n = 13,389). We analysed a final total of 8989 subjects (2983 outpatients and 6006 inpatients) (Fig. 1). The survey was approved by the Ethics Committee at the Japan Psychiatric Hospitals Association. 2.2. Materials and methods A brief questionnaire was compiled to cover demographic data (age and sex), height, weight, WC, BP, HDL, TG and FPG after reviewing the relevant literature and guidelines. Body mass index (BMI) was determined as the ratio of weight to height (kg/m2). Standardised health questionnaires were used to determine behaviour, including current smoking status. BP was measured twice while the individual was in the seated position after at least 5 min rest, using a standard mercury sphygmomanometer. HDL, TG and FPG were also measured using standard analytical techniques. As detailed in the ATP III-A report, participants with ≥3 of the following criteria were defined as having MetS: (1) abdominal obesity: WC ≥90 cm in men and ≥80 cm in women; (2) high BP: ≥130/85 mm Hg; (3) low HDL cholesterol: HDL b 40 mg/dl in men and b 50 mg/dl in women; (4) hypertriglyceridemia: TG ≥150 mg/dl; and (5) high fasting glucose: FPG ≥100 mg/dl.
Fig. 1. Flow diagram of participant inclusion and exclusion.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
T. Sugai et al. / Schizophrenia Research xxx (2016) xxx–xxx
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Table 1 Demographic and clinical characteristics of subjects according to sex and type of care. Total
Age (years) BMI (kg/m2) Waist (cm) Systolic BP (mm Hg) Diastolic BP (mm Hg) LDL-cholesterol (mg/dl) HDL-cholesterol (mg/dl) TG (mg/dl) FPG (mg/dl) HbA1c Status of antipsychotic therapy (%) No treated Antipsychotic monopharmacy Antipsychotic polypharmacy Ratio of SGA therapy (%) Total CP equivalence (mg) Smoking (%)
Male
Female
Outpatients (n = 2983)
Inpatients (n = 6006)
p value
Outpatients (n = 1695)
Inpatients (n = 3283)
p value
Outpatients (n = 1288)
Inpatients (n = 2723)
p value
52.6 ± 13.6 25.3 ± 4.6 87.3 ± 13.0 126.0 ± 18.5 77.6 ± 12.6 116.3 ± 34.0 56.6 ± 19.1 140.6 ± 106.8 106.3 ± 40.3 5.5 ± 1.2
59.6 ± 13.0 21.7 ± 3.9 81.3 ± 11.2 116.9 ± 16.1 72.5 ± 11.5 103.9 ± 33.1 57.0 ± 19.5 94.3 ± 56.7 89.9 ± 22.5 5.6 ± 1.0
b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a NSa b0.001a b0.001a NSa
52.4 ± 12.9 25.4 ± 4.3 90.1 ± 11.6 127.9 ± 18.3 79.1 ± 12.6 115.9 ± 34.9 51.6 ± 16.2 155.0 ± 120.0 108.5 ± 41.3 5.6 ± 1.3
58.3 ± 12.8 21.8 ± 3.7 83.4 ± 10.4 117.6 ± 16.0 73.3 ± 11.4 98.4 ± 32.3 52.9 ± 18.8 95.4 ± 60.1 89.9 ± 20.6 5.6 ± 1.1
b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a 0.046a b0.001a b0.001a NSa
52.8 ± 14.4 25.1 ± 5.0 83.3 ± 13.9 123.4 ± 18.5 75.6 ± 12.4 116.9 ± 32.8 62.9 ± 20.6 121.7 ± 82.7 103.3 ± 38.7 5.5 ± 1.2
61.2 ± 13.0 21.7 ± 4.2 78.6 ± 11.7 116.1 ± 16.2 71.5 ± 11.5 110.2 ± 32.9 61.9 ± 19.2 92.9 ± 52.3 89.8 ± 24.3 5.5 ± 1.0
b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a NSa b0.001a b0.001a NSa
5.2 48.8 46.0 76.1 564.7 ± 486.6 35.9
6.4 39.7 53.9 77.5 729.3 ± 652.3 23.1
b0.001b
4.8 45.8 49.4 76.0 590.0 ± 483.1 48.0
6.3 37.9 55.8 76.2 762.3 ± 684.3 33.8
b0.001b
5.7 52.7 41.6 76.4 531.3 ± 489.3 20.0
6.7 42.1 51.2 78.7 689.5 ± 609.2 10.2
b0.001b
NSa b0.001a b0.001b
NSb b0.001a b0.001b
NSb b0.001a b0.001b
Data are expressed as mean ± SD. CP, chlorpromazine; HbA1c, haemoglobin A1c; SGA, second-generation antipsychotic. N.S.; not significant. a Data are analysed using unpaired Student's t test between outpatients and inpatients. b Data are analysed using χ2 test between outpatients and inpatients.
To compare the prevalence of MetS in patients with schizophrenia and the Japanese general population, we used a definition established by JASSO. As detailed in the JASSO report, MetS was diagnosed in participants with WC ≥ 85 cm in men and ≥ 90 cm in women, plus two of the following criteria: (1) high BP: BP ≥ 130/85 mm Hg; (2) low HDL cholesterol: HDL b 40 mg/dl; (3) hypertriglyceridemia: TG ≥150 mg/dl; and (4) high fasting glucose: FPG ≥110 mg/dl. 2.3. Statistical analysis To compare the main demographic and clinical characteristics between the groups, the unpaired Student's t test was performed to analyse continuous variables, and the χ2 test was performed to analyse categorical variables. The threshold for significance was set at p b 0.05. SPSS for Windows version 19.0 (IBM Japan, Tokyo, Japan) was used for statistical calculations. 3. Results There were 7655 Japanese outpatients with schizophrenia and 15,461 inpatients enrolled in the present survey at baseline, and 2983 outpatients and 6006 inpatients had sufficient data for assessment of MetS using the ATP III-A definition, compared with 2753 outpatients and 5776 inpatients for the JAASO definition.
3.1. Demographic and clinical characteristics The demographic and clinical characteristics of the study subjects are shown in Table 1. Inpatients were significantly older, and had lower BMI than outpatients. Outpatients had higher WC, BP, TG and FPG than inpatients had (all p b 0.001). There was no significant difference in HDL between outpatients and inpatients. The ratio of combination drug therapy and total chlorpromazine equivalent doses was higher in inpatients.
3.2. Prevalence of MetS based on ATP III-a definition The overall prevalence of MetS in outpatients using the ATP III-A definition was 34.2%, with 37.8% in men and 29.4% in women. The overall prevalence of MetS in inpatients was 13.0%, with 12.3% in men and 13.9% in women (Table 2). MetS prevalence in outpatients was 2–3-fold higher than in inpatients. In age-specific analysis, MetS prevalence in total outpatients aged N 30 years was significantly higher than in the total inpatients group. In particular, the prevalence of MetS in male outpatients aged 40–59 years was the highest, and reached N40%, despite a total MetS prevalence of 34.2%. Female outpatients had the highest prevalence of MetS in patients aged N 60 years.
Table 2 Age-specific Prevalence of MetS in subjects by ATP III-A definition. Age (years)
Total Outpatients % (n)
Inpatients % (n)
p value
Male Outpatients % (n)
Inpatients % (n)
p value
Female Outpatients % (n)
Inpatients % (n)
p value
20–29 30–39 40–49 50–59 60–69 ≥70 Total
15.4 (20/130) 28.2 (124/440) 35.6 (238/669) 36.5 (265/726) 36.3 (255/702) 37.3 (118/316) 34.2 (1020/2983)
9.2 (11/121) 11.0 (40/362) 14.4 (118/818) 14.8 (195/1321) 12.2 (252/2068) 12.7 (167/1316) 13.0 (783/6006)
NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a
15.1 (8/53) 32.3 (80/248) 40.6 (165/406) 42.0 (182/433) 37.6 (151/402) 35.9 (55/153) 37.8 (641/1695)
10.4 (8/77) 12.9 (29/225) 14.1 (68/482) 13.9 (109/786) 11.4 (129/1129) 10.6 (62/584) 12.3 (405/3283)
NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a
15.6 (12/77) 22.9 (44/192) 27.8 (73/263) 28.3 (83/293) 34.7 (104/300) 38.7 (63/163) 29.4 (379/1288)
6.8 (3/44) 8.0 (11/137) 14.9 (50/336) 16.1 (86/535) 13.1 (123/939) 14.3 (105/732) 13.9 (378/2723)
NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a
NS, not significant. a Data are analysed using χ2 test between outpatients and inpatients.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
NSa NSa 0.023a b0.001a b0.001a b0.001a b0.001a 0.0 (0/48) 2.2 (3/134) 4.1 (13/320) 4.6 (25/546) 3.7 (38/1041) 3.3 (27/821) 3.6 (106/2910) 7.2 (5/69) 6.1 (12/196) 8.7 (22/252) 12.5 (34/272) 10.0 (30/301) 11.5 (19/165) 9.7 (122/1255) 3.0 6.1 13.1 24.6 32.0 33.7 24.7 NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a b
a
1.3 3.0 6.7 13.6 20.8 24.8 15.6 NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a 7.0 (8/114) 9.1 (28/308) 10.4 (74/713) 10.6 (131/1239) 7.6 (155/2042) 6.3 (86/1360) 8.3 (482/5776) 10.6 (13/123) 18.5 (77/417) 25.9 (159/615) 26.4 (171/647) 22.9 (151/660) 20.6 (60/291) 22.9 (631/2753) 20–29 30–39 40–49 50–59 60–69 ≥70 Total
Data are analysed using χ2 test between outpatients and inpatients. Data of general population are quoted from a national survey by the Ministry of Health and Welfare.
12.1 (8/66) 14.4 (25/174) 15.5 (61/393) 15.3 (106/693) 11.7 (117/1001) 10.9 (59/539) 13.1 (376/2866)
Female
Outpatients % (n) Inpatients % (n)
p value
General population %b Male
Outpatients % (n) General population %b Inpatients % (n)
Age (years)
Table 3 Age-specific Prevalence of MetS in subjects by JASSO definition, compared with Japanese general population.
The present study is believed to be the largest to investigate the prevalence of MetS in Japanese outpatients and inpatients with schizophrenia. Outpatients with schizophrenia had a higher risk of developing MetS. This study demonstrated that the prevalence of MetS using ATP III-A was 34.2% and 13.0% in Japanese outpatients and inpatients with schizophrenia, respectively. MetS prevalence of outpatients was significantly higher compared with inpatients and the general population (The National Health and Nutrition Examination Survey in Japan, 2014). Our outpatient results correspond with those of previous population studies that have reported a 2- to 3-fold higher prevalence of MetS in patients with schizophrenia compared with the general population (McEvoy et al., 2005). The results for inpatients did not contradict those in a previous study in Japan (Sugawara et al., 2011). It is thought that environmental factors, such as lack of physical activity and unbalanced diet, can lead to development of MetS. As a result of negative symptoms, patients with schizophrenia have a higher risk of developing obesity and glucose-lipid abnormalities. It is also reported that the prevalence of underweight in Japanese inpatients with schizophrenia may be higher than in the general population (Suzuki et al., 2014; Inamura et al., 2012). The mental health care system in Japan remains hospital based, and has the largest number of psychiatric beds in the world, and patients with schizophrenia frequently remain in hospital for long periods (Ministry of Health and Welfare, 1999; Zenkaren Health and Welfare Research Institute, ZHWRI, 2000). However, serious discussion about deinstitutionalisation began several years ago. Under these original Japanese mental health care systems, inpatients were at low risk of MetS because an appropriate lifestyle was promoted. This may account for the difference in Mets prevalence among outpatients, inpatients and the general population. In the present study, inpatients had higher polypharmacy and total CP equivalence (Table 1). However, inpatients had lower prevalence of MetS than outpatients had. Although some previous studies have shown the effect of polypharmacy on development of MetS (Correll et al., 2007; Misawa et al., 2011), clear evidence is still lacking. Long-term hospitalisation and antipsychotic therapy lead to lack of exercise and reduced gastrointestinal motility (Berger et al., 2010). In addition, inpatients receive constant lifestyle management. We thought that these findings may be partly explained by these conditions resulting in lower prevalence of MetS in inpatients with schizophrenia. Although it has been proposed that WC is potentially the most useful predictor of MetS in various populations with or without schizophrenia (Jin et al., 2010; Wang et al., 2009), we suggest that the HDL is also an important factor for predicting MetS onset. In the present study, the prevalence of MetS was higher in outpatients than inpatients. However, contrary to our expectations, there was no difference in HDL between outpatients and inpatients. It is reported that the most likely
Outpatients % (n)
4. Discussion
Total
Inpatients % (n)
p value
The prevalence of MetS according to the JASSO definition was lower than by the ATP III-A definition. The overall prevalence of MetS in outpatients was 22.9%, with 34.0% in men and 9.7% in women. The overall prevalence of MetS in inpatients was 8.3%, with 13.1% in men and 3.6% in women (Table 3). The prevalence of MetS in outpatients was also 2–3-fold higher than in inpatients using the JASSO definition. According to the National Health and Nutrition Examination Survey in Japan, the overall prevalence of MetS in the Japanese general population using the JASSO definition was 15.6%.20 Compared with the Japanese general population, outpatients with schizophrenia were found to be at higher risk of developing MetS. The risk of developing MetS in inpatients was lower than in the Japanese general population. This tendency was similar regardless of age.
14.8 (8/54) 29.4 (65/221) 37.7 (137/363) 36.5 (137/375) 33.7 (121/359) 32.5 (41/126) 34.0 (509/1498)
General population %b
3.3. Prevalence of MetS based on JASSO definition compared with Japanese general population
0.1 1.3 3.2 7.2 12.0 17.9 9.4
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p value
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Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
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improvement in the lipid profile induced by physical activity is an increase in HDL cholesterol (Mann et al., 2014). In hospital, where physical activity is relatively confined, it may be difficult to increase the value of HDL. The prevalence of MetS reported in several previous studies varied considerably due to different definitions of MetS. In this study, we established the prevalence of MetS using the JASSO definition. In both outpatients and inpatients, the prevalence of MetS was low compared with that using the ATP III-A definition. Specifically, MetS prevalence in female patients using the JASSO definition was less than half of that with the ATP III-A definition. This may have been due to the effect of increasing the WC criterion to 90 cm (Examination Committee of the Criteria for Metabolic Syndrome in Japan, 2005). Although the effective cut-off value for WC is still controversial, the ATP III-A criteria might be suitable for making international comparisons because of the availability of data among different ethnic groups. The prevalence of MetS in our study did not differ from that in most European and Asian countries, such as 35% in The Netherlands (Schorr et al., 2009) and 32.3% in Belgium (De Hert et al., 2006). However, our results were less frequent than those in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) using the same definition of MetS (42.7%) (McEvoy et al., 2005). In previous studies, the prevalence of MetS in women was usually equal to or greater than that in men (McEvoy et al., 2005; Haack et al., 2009). When we examined MetS prevalence in each age group, it was high in men in each age groups. In male outpatients and inpatients, the prevalence of MetS was highest in those aged 40–59 years who are production populations. The interpretation of such trends is complex and needs to be done with caution, especially given the cross-sectional nature of the current study. The mechanism of increased prevalence is not known. Patients with schizophrenia are at risk for developing obesity due to lack of exercise, poor dietary habits, and limited activity due to negative symptoms. In addition, antipsychotic medication has direct metabolic effects (Basu et al., 2004). MetS is associated with diabetes and cardiovascular risk factors. The prevalence of diabetes in this population was three times higher than in the general population (Hanley et al., 2005). A prospective study showed that MetS was associated with a threefold increased risk of coronary heart disease and stroke over a median of 6.2 years follow-up (Isomaa et al., 2001). Therefore, our results demonstrate that we should carefully monitor patients with schizophrenia to minimise the risk of developing MetS. Although the prevalence of MetS in outpatients aged b59 years was higher than in the general population, the prevalence in outpatients aged N60 years was similar to that in the general population. It is difficult to clarify the reason for there being no difference in MetS prevalence between older outpatients and the older general population. One possibility is that the stabilisation of psychotic symptoms with ageing corrected irregular eating habits and led to a decrease in waist circumference and improvement of lipid abnormalities. Inpatients aged N 50 years had a considerably lower prevalence of MetS compared with the general population. We previously reported that the prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia was higher than in outpatients and the general population (Sugai et al., 2015). Most Japanese inpatients under long-term hospitalisation are old. Underweight and undernutrition in Japanese inpatients are serious problems. This may be related to lower prevalence of MetS in old inpatients. This study had limitations similar to those of other cross-sectional surveys of patients with schizophrenia and MetS. Because there was no information about the duration of illness and medication, we did not consider the influence of antipsychotics. In conclusion, we conducted a large questionnaire survey, and observed that Japanese outpatients with schizophrenia were more likely to have MetS than inpatients. The focus of psychiatric services in Japan is being shifted from hospital to community care, and the Ministry of Health, Labour and Welfare aims for the prompt discharge of newly
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admitted patients. As a result, it is expected that there will be an increase in Japanese outpatients with schizophrenia in the future. The long-term hospitalisation is a severe problem, and may lead to pressure of the medical economic cost. However, it may affect the low prevalence in Japanese inpatients with schizophrenia. Therefore, the physical risk in patients with schizophrenia may be affected by environmental parameters such as type of care (ambulatory or hospitalised). As for psychiatric care in Japan, treatment of outpatients should include day care and nutritional control, and more attention should be paid to the physical risk Japanese patients with schizophrenia.
Declaration of interest Toshiyuki Someya has received research support or honoraria from Asahi Kasei Pharma Corp., Astellas Pharma Inc., Daiichi Sankyo Co. Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co. Ltd., Eli Lilly Japan, K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Meiji Seika Pharma Co. Ltd., Mitsubishi Tanabe Pharma Co. Ltd., Mochida Pharmaceutical Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Shionogi & Co., Ltd., Tsumura & Co, and Yoshitomi Pharmaceutical Industries. Yutaro Suzuki has received research support or honoraria from Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co. Ltd., and Otsuka Pharmaceutical Co. Ltd. The other authors declare no potential conflict of interest. Kazutaka Shimoda has received research support or honoraria from Daiichi Sankyo Co. Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan, K.K., GlaxoSmithKline K.K., Meiji Seika Pharma Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Shionogi & Co., Ltd., Takeda Pharmaceutical Co., Ltd., Tsumra & Co., Yoshitomi Pharmaceutical Industries, Ltd., Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Janssen Pharmaceutical K.K., Kowa Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Mitsubishi Tanabe Pharma Corporation, Ltd., MSD K.K., Novartis Pharma K.K., and Ono Pharmaceutical Co., Ltd. Norio Yasui-Furukori has received research support or honoraria from Astellas Pharma Inc., Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan, K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Meiji Seika Pharma Co., Mochida Pharmaceutical Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and Yoshitomi Pharmaceutical Industries. Norio Sugawara has received grant/research support from Grant-in-Aid for Young Scientists (B)., The Ministry of Education, Culture, Sports, Science and Technology, Japan Grant B., Karoji Memorial Fund for Medical Research Grant and SENSHIN Medical Research Foundation. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the Schizophrenia Research policies on sharing data and materials, as detailed online in the guide for authors. The other authors declare no potential conflicts of interest.
Funding This work was partially supported by Eisai Co. Ltd., Yoshitomi Pharmaceutical Industries, Dainippon Sumitomo Pharma Co. Ltd., Astellas Pharma Inc., Meiji Seika Pharma Co. Ltd., Eli Lilly Japan, K.K., Otsuka Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., MSD K.K., Shionogi & Co. Ltd., Asahi Kasei Pharma Corp., Novartis Pharma Co. Ltd., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., and Tsumura & Co. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Contributors Author Takuro Sugai is the principal author and the main contributor to the design of the present study. Authors Takuro Sugai, Yutaro Suzuki, Kazutaka Shimoda, Yuji Ozeki, Norio Sugawara, Norio Yasui-Furukori and Toshiyuki Someya contributed in the study conception and design. Authors Manabu Yamazaki, Takao Mori, Hiroshi Matsuda, Yoshitake Minami, Kurefu Okamoto and Toyoaki Sagae were involved in the acquisition of data. Takuro Sugai and Yutaro Suzuki contributed in the drafting of the manuscript. Kazutaka Shimoda, Yuji Ozeki, Norio Sugawara, Norio Yausi-Furukori and Toshiyuki Someya were involved in the critical revision. All the authors were involved in the analysis and interpretation of the data; and gave their final approval.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
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Acknowledgements We are grateful to the study participants and the facilities belonging to Japan Psychiatric Hospital Association which cooperated with the present investigation. We would like to thank all our co-workers for their contributions to the data collection and management.
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Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
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Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey Takuro Sugai a,b, Yutaro Suzuki a,b, Manabu Yamazaki c, Kazutaka Shimoda b,d, Takao Mori c, Yuji Ozeki b,d, Hiroshi Matsuda c, Norio Sugawara b,e, Norio Yasui-Furukori b,e, Yoshitake Minami c, Kurefu Okamoto c, Toyoaki Sagae f, Toshiyuki Someya a,b,⁎ a
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan c Japan Psychiatric Hospital Association, Tokyo, Japan d Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Japan e Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan f Department of Health and Nutrition, Yamagata Prefectural Yonezawa University of Nutrition Sciences Faculty of Health and Nutrition, Yonezawa, Japan b
a r t i c l e
i n f o
Article history: Received 22 May 2015 Received in revised form 4 January 2016 Accepted 10 January 2016 Available online xxxx Keywords: Metabolic syndrome Japanese mental health care system Prevalence The adapted adult treatment panel III (ATP III-A) criteria The Japan Society for the Study of Obesity (JASSO) definition Hospitalisation
a b s t r a c t Patients with schizophrenia have a higher risk of metabolic syndrome (MetS). MetS prevalence varies with ethnicity. Although environmental factors, such as lack of physical activity and unbalanced diet, can lead to MetS, these may differ between outpatients and inpatients with schizophrenia. The Japanese mental health care system differs from that in other countries. However, few studies have investigated the prevalence of MetS in Japanese patients with schizophrenia. Therefore, we conducted a nationwide survey to clarify the prevalence of MetS in Japanese outpatients and inpatients with schizophrenia. We investigated the risk of MetS by questionnaire in 520 facilities for outpatients and 247 facilities for inpatients. There were 7655 outpatients and 15,461 inpatients with schizophrenia. MetS prevalence was based on the National Cholesterol Education Program Adult Treatment Panel III (ATP III-A) and the Japan Society for the Study of Obesity (JASSO). The overall MetS prevalence in outpatients using the ATP III-A definition was 34.2%, with 37.8% in men and 29.4% in women, compared with 13.0% in inpatients, with 12.3% in men and 13.9% in women. MetS prevalence in outpatients was approximately 2- to 3-fold higher than in inpatients. In conclusion, MetS prevalence in Japanese outpatients was approximately 3-fold higher than in inpatients. Therefore, we should pay more attention to the risk of physical disease in Japanese patients with schizophrenia, considering the difference in health characteristics between outpatients and inpatients. © 2016 Published by Elsevier B.V.
1. Introduction Patients with schizophrenia have a reduced life expectancy compared with the general population (Druss et al., 2011; Laursen et al., 2007). One reason is that patients with schizophrenia have nearly twice the normal risk of dying from cardiovascular disease (Saha et al., 2007; Capasso et al., 2008). Many studies in Europe and North America have found a higher prevalence of metabolic syndrome (MetS) in patients with schizophrenia compared with the general population (Casey, 2005; Gurpegui et al., 2012). According to a metaanalysis of 25,692 subjects, the MetS prevalence rate was 32.5% ⁎ Corresponding author at: Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 9518510, Japan. E-mail address: [email protected] (T. Someya).
overall, and there were no significant differences due to the inpatient– outpatient status or country (Mitchell et al., 2013). In contrast, in a study in Japan, the MetS prevalence rates in outpatients and inpatients with schizophrenia were 48.1% and 15.8%, respectively (Sugawara et al., 2011). Our previous study revealed that the prevalence of underweight in Japanese inpatients with schizophrenia may be higher than that in the general population (Suzuki et al., 2014). Another study showed that obesity in Japanese inpatients with schizophrenia was associated with b3 months hospitalisation, whereas underweight was associated with ≥3 months hospitalisation (Inamura et al., 2012). The mental health care system in Japan remains hospital based, and has the largest number of psychiatric beds per person in the world. In Japan, the average length of stay is 8.5 years, and 71% of psychiatric inpatients remain in hospital for ≥1 year (Ministry of Health and Welfare, 1999). In addition, there has been a gradual ageing of inpatients, with 29.5% of patients aged N65 years and 64.6% aged N50 years (Zenkaren
http://dx.doi.org/10.1016/j.schres.2016.01.016 0920-9964/© 2016 Published by Elsevier B.V.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
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Health and Welfare Research Institute, ZHWRI, 2000). This aspect of the mental health system in Japan may be related to the difference in physical health between outpatients and inpatients with schizophrenia. There have been no large investigations of the prevalence of MetS in Japanese patients with schizophrenia, and such data are required to establish the risk of MetS. The most common definitions for MetS are the adapted Adult Treatment Panel III (ATP III-A) criteria proposed by the American Heart Association and the National Cholesterol Education Program. These definitions include waist circumference (WC), blood pressure (BP), triglyceride (TG), high-density lipoprotein cholesterol (HDL) and fasting plasma glucose (FPG) (Alberti et al., 2010). WC has been proposed as the most useful predictor of MetS in various populations with or without schizophrenia (Jin et al., 2010; Wang et al., 2009). However, it is difficult to use the same WC criterion as with European patients because of the smaller physique of Japanese people. In the present investigation, we also used the definition established by Japanese Society for the Study of Obesity (JASSO) (Examination Committee of the Criteria for Metabolic Syndrome in Japan, 2005). In the JASSO definition, the cut-off value for WC is 85 cm for men and 90 cm for women (Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the study of Obesity, 2002). However, the prognostic utility of MetS remains controversial because the different criteria and definitions provide differing results according to cohorts and settings (Zimmet et al., 2005; Alberti et al., 2005). In Japan, most psychiatric care is entrusted to private psychiatric hospitals; most of which belong to the Japan Psychiatric Hospital Association. The joint project with the cooperation of the Japan Psychiatric Hospital Association and the Japanese society of clinical neuropsychopharmacology to protect patients with schizophrenia was started in Japan in December 2012. In the present study, we used the large questionnaire survey in the joint project to establish the prevalence of MetS in Japanese patients with schizophrenia. This is believed to be the largest study investigating the prevalence of MetS in Japanese patients with schizophrenia.
2. Methods 2.1. Study participants The questionnaire survey was conducted between January 2012 and July 2014. We obtained 7655 (outpatients) and 15,461 (inpatients) answers from 520 facilities for outpatients and 247 facilities for inpatients belonging to the Japan Psychiatric Hospital Association. All of the subjects were diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) or International Statistical Classification of Diseases and Related Health Problems version 10 (ICD-10). We excluded individuals aged b20 years and whose sex data were not assessed in the survey (n = 738). We also excluded individuals who could not be assessed for MetS (n = 13,389). We analysed a final total of 8989 subjects (2983 outpatients and 6006 inpatients) (Fig. 1). The survey was approved by the Ethics Committee at the Japan Psychiatric Hospitals Association. 2.2. Materials and methods A brief questionnaire was compiled to cover demographic data (age and sex), height, weight, WC, BP, HDL, TG and FPG after reviewing the relevant literature and guidelines. Body mass index (BMI) was determined as the ratio of weight to height (kg/m2). Standardised health questionnaires were used to determine behaviour, including current smoking status. BP was measured twice while the individual was in the seated position after at least 5 min rest, using a standard mercury sphygmomanometer. HDL, TG and FPG were also measured using standard analytical techniques. As detailed in the ATP III-A report, participants with ≥3 of the following criteria were defined as having MetS: (1) abdominal obesity: WC ≥90 cm in men and ≥80 cm in women; (2) high BP: ≥130/85 mm Hg; (3) low HDL cholesterol: HDL b 40 mg/dl in men and b 50 mg/dl in women; (4) hypertriglyceridemia: TG ≥150 mg/dl; and (5) high fasting glucose: FPG ≥100 mg/dl.
Fig. 1. Flow diagram of participant inclusion and exclusion.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
T. Sugai et al. / Schizophrenia Research xxx (2016) xxx–xxx
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Table 1 Demographic and clinical characteristics of subjects according to sex and type of care. Total
Age (years) BMI (kg/m2) Waist (cm) Systolic BP (mm Hg) Diastolic BP (mm Hg) LDL-cholesterol (mg/dl) HDL-cholesterol (mg/dl) TG (mg/dl) FPG (mg/dl) HbA1c Status of antipsychotic therapy (%) No treated Antipsychotic monopharmacy Antipsychotic polypharmacy Ratio of SGA therapy (%) Total CP equivalence (mg) Smoking (%)
Male
Female
Outpatients (n = 2983)
Inpatients (n = 6006)
p value
Outpatients (n = 1695)
Inpatients (n = 3283)
p value
Outpatients (n = 1288)
Inpatients (n = 2723)
p value
52.6 ± 13.6 25.3 ± 4.6 87.3 ± 13.0 126.0 ± 18.5 77.6 ± 12.6 116.3 ± 34.0 56.6 ± 19.1 140.6 ± 106.8 106.3 ± 40.3 5.5 ± 1.2
59.6 ± 13.0 21.7 ± 3.9 81.3 ± 11.2 116.9 ± 16.1 72.5 ± 11.5 103.9 ± 33.1 57.0 ± 19.5 94.3 ± 56.7 89.9 ± 22.5 5.6 ± 1.0
b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a NSa b0.001a b0.001a NSa
52.4 ± 12.9 25.4 ± 4.3 90.1 ± 11.6 127.9 ± 18.3 79.1 ± 12.6 115.9 ± 34.9 51.6 ± 16.2 155.0 ± 120.0 108.5 ± 41.3 5.6 ± 1.3
58.3 ± 12.8 21.8 ± 3.7 83.4 ± 10.4 117.6 ± 16.0 73.3 ± 11.4 98.4 ± 32.3 52.9 ± 18.8 95.4 ± 60.1 89.9 ± 20.6 5.6 ± 1.1
b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a 0.046a b0.001a b0.001a NSa
52.8 ± 14.4 25.1 ± 5.0 83.3 ± 13.9 123.4 ± 18.5 75.6 ± 12.4 116.9 ± 32.8 62.9 ± 20.6 121.7 ± 82.7 103.3 ± 38.7 5.5 ± 1.2
61.2 ± 13.0 21.7 ± 4.2 78.6 ± 11.7 116.1 ± 16.2 71.5 ± 11.5 110.2 ± 32.9 61.9 ± 19.2 92.9 ± 52.3 89.8 ± 24.3 5.5 ± 1.0
b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a NSa b0.001a b0.001a NSa
5.2 48.8 46.0 76.1 564.7 ± 486.6 35.9
6.4 39.7 53.9 77.5 729.3 ± 652.3 23.1
b0.001b
4.8 45.8 49.4 76.0 590.0 ± 483.1 48.0
6.3 37.9 55.8 76.2 762.3 ± 684.3 33.8
b0.001b
5.7 52.7 41.6 76.4 531.3 ± 489.3 20.0
6.7 42.1 51.2 78.7 689.5 ± 609.2 10.2
b0.001b
NSa b0.001a b0.001b
NSb b0.001a b0.001b
NSb b0.001a b0.001b
Data are expressed as mean ± SD. CP, chlorpromazine; HbA1c, haemoglobin A1c; SGA, second-generation antipsychotic. N.S.; not significant. a Data are analysed using unpaired Student's t test between outpatients and inpatients. b Data are analysed using χ2 test between outpatients and inpatients.
To compare the prevalence of MetS in patients with schizophrenia and the Japanese general population, we used a definition established by JASSO. As detailed in the JASSO report, MetS was diagnosed in participants with WC ≥ 85 cm in men and ≥ 90 cm in women, plus two of the following criteria: (1) high BP: BP ≥ 130/85 mm Hg; (2) low HDL cholesterol: HDL b 40 mg/dl; (3) hypertriglyceridemia: TG ≥150 mg/dl; and (4) high fasting glucose: FPG ≥110 mg/dl. 2.3. Statistical analysis To compare the main demographic and clinical characteristics between the groups, the unpaired Student's t test was performed to analyse continuous variables, and the χ2 test was performed to analyse categorical variables. The threshold for significance was set at p b 0.05. SPSS for Windows version 19.0 (IBM Japan, Tokyo, Japan) was used for statistical calculations. 3. Results There were 7655 Japanese outpatients with schizophrenia and 15,461 inpatients enrolled in the present survey at baseline, and 2983 outpatients and 6006 inpatients had sufficient data for assessment of MetS using the ATP III-A definition, compared with 2753 outpatients and 5776 inpatients for the JAASO definition.
3.1. Demographic and clinical characteristics The demographic and clinical characteristics of the study subjects are shown in Table 1. Inpatients were significantly older, and had lower BMI than outpatients. Outpatients had higher WC, BP, TG and FPG than inpatients had (all p b 0.001). There was no significant difference in HDL between outpatients and inpatients. The ratio of combination drug therapy and total chlorpromazine equivalent doses was higher in inpatients.
3.2. Prevalence of MetS based on ATP III-a definition The overall prevalence of MetS in outpatients using the ATP III-A definition was 34.2%, with 37.8% in men and 29.4% in women. The overall prevalence of MetS in inpatients was 13.0%, with 12.3% in men and 13.9% in women (Table 2). MetS prevalence in outpatients was 2–3-fold higher than in inpatients. In age-specific analysis, MetS prevalence in total outpatients aged N 30 years was significantly higher than in the total inpatients group. In particular, the prevalence of MetS in male outpatients aged 40–59 years was the highest, and reached N40%, despite a total MetS prevalence of 34.2%. Female outpatients had the highest prevalence of MetS in patients aged N 60 years.
Table 2 Age-specific Prevalence of MetS in subjects by ATP III-A definition. Age (years)
Total Outpatients % (n)
Inpatients % (n)
p value
Male Outpatients % (n)
Inpatients % (n)
p value
Female Outpatients % (n)
Inpatients % (n)
p value
20–29 30–39 40–49 50–59 60–69 ≥70 Total
15.4 (20/130) 28.2 (124/440) 35.6 (238/669) 36.5 (265/726) 36.3 (255/702) 37.3 (118/316) 34.2 (1020/2983)
9.2 (11/121) 11.0 (40/362) 14.4 (118/818) 14.8 (195/1321) 12.2 (252/2068) 12.7 (167/1316) 13.0 (783/6006)
NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a
15.1 (8/53) 32.3 (80/248) 40.6 (165/406) 42.0 (182/433) 37.6 (151/402) 35.9 (55/153) 37.8 (641/1695)
10.4 (8/77) 12.9 (29/225) 14.1 (68/482) 13.9 (109/786) 11.4 (129/1129) 10.6 (62/584) 12.3 (405/3283)
NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a
15.6 (12/77) 22.9 (44/192) 27.8 (73/263) 28.3 (83/293) 34.7 (104/300) 38.7 (63/163) 29.4 (379/1288)
6.8 (3/44) 8.0 (11/137) 14.9 (50/336) 16.1 (86/535) 13.1 (123/939) 14.3 (105/732) 13.9 (378/2723)
NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a
NS, not significant. a Data are analysed using χ2 test between outpatients and inpatients.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
NSa NSa 0.023a b0.001a b0.001a b0.001a b0.001a 0.0 (0/48) 2.2 (3/134) 4.1 (13/320) 4.6 (25/546) 3.7 (38/1041) 3.3 (27/821) 3.6 (106/2910) 7.2 (5/69) 6.1 (12/196) 8.7 (22/252) 12.5 (34/272) 10.0 (30/301) 11.5 (19/165) 9.7 (122/1255) 3.0 6.1 13.1 24.6 32.0 33.7 24.7 NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a b
a
1.3 3.0 6.7 13.6 20.8 24.8 15.6 NSa b0.001a b0.001a b0.001a b0.001a b0.001a b0.001a 7.0 (8/114) 9.1 (28/308) 10.4 (74/713) 10.6 (131/1239) 7.6 (155/2042) 6.3 (86/1360) 8.3 (482/5776) 10.6 (13/123) 18.5 (77/417) 25.9 (159/615) 26.4 (171/647) 22.9 (151/660) 20.6 (60/291) 22.9 (631/2753) 20–29 30–39 40–49 50–59 60–69 ≥70 Total
Data are analysed using χ2 test between outpatients and inpatients. Data of general population are quoted from a national survey by the Ministry of Health and Welfare.
12.1 (8/66) 14.4 (25/174) 15.5 (61/393) 15.3 (106/693) 11.7 (117/1001) 10.9 (59/539) 13.1 (376/2866)
Female
Outpatients % (n) Inpatients % (n)
p value
General population %b Male
Outpatients % (n) General population %b Inpatients % (n)
Age (years)
Table 3 Age-specific Prevalence of MetS in subjects by JASSO definition, compared with Japanese general population.
The present study is believed to be the largest to investigate the prevalence of MetS in Japanese outpatients and inpatients with schizophrenia. Outpatients with schizophrenia had a higher risk of developing MetS. This study demonstrated that the prevalence of MetS using ATP III-A was 34.2% and 13.0% in Japanese outpatients and inpatients with schizophrenia, respectively. MetS prevalence of outpatients was significantly higher compared with inpatients and the general population (The National Health and Nutrition Examination Survey in Japan, 2014). Our outpatient results correspond with those of previous population studies that have reported a 2- to 3-fold higher prevalence of MetS in patients with schizophrenia compared with the general population (McEvoy et al., 2005). The results for inpatients did not contradict those in a previous study in Japan (Sugawara et al., 2011). It is thought that environmental factors, such as lack of physical activity and unbalanced diet, can lead to development of MetS. As a result of negative symptoms, patients with schizophrenia have a higher risk of developing obesity and glucose-lipid abnormalities. It is also reported that the prevalence of underweight in Japanese inpatients with schizophrenia may be higher than in the general population (Suzuki et al., 2014; Inamura et al., 2012). The mental health care system in Japan remains hospital based, and has the largest number of psychiatric beds in the world, and patients with schizophrenia frequently remain in hospital for long periods (Ministry of Health and Welfare, 1999; Zenkaren Health and Welfare Research Institute, ZHWRI, 2000). However, serious discussion about deinstitutionalisation began several years ago. Under these original Japanese mental health care systems, inpatients were at low risk of MetS because an appropriate lifestyle was promoted. This may account for the difference in Mets prevalence among outpatients, inpatients and the general population. In the present study, inpatients had higher polypharmacy and total CP equivalence (Table 1). However, inpatients had lower prevalence of MetS than outpatients had. Although some previous studies have shown the effect of polypharmacy on development of MetS (Correll et al., 2007; Misawa et al., 2011), clear evidence is still lacking. Long-term hospitalisation and antipsychotic therapy lead to lack of exercise and reduced gastrointestinal motility (Berger et al., 2010). In addition, inpatients receive constant lifestyle management. We thought that these findings may be partly explained by these conditions resulting in lower prevalence of MetS in inpatients with schizophrenia. Although it has been proposed that WC is potentially the most useful predictor of MetS in various populations with or without schizophrenia (Jin et al., 2010; Wang et al., 2009), we suggest that the HDL is also an important factor for predicting MetS onset. In the present study, the prevalence of MetS was higher in outpatients than inpatients. However, contrary to our expectations, there was no difference in HDL between outpatients and inpatients. It is reported that the most likely
Outpatients % (n)
4. Discussion
Total
Inpatients % (n)
p value
The prevalence of MetS according to the JASSO definition was lower than by the ATP III-A definition. The overall prevalence of MetS in outpatients was 22.9%, with 34.0% in men and 9.7% in women. The overall prevalence of MetS in inpatients was 8.3%, with 13.1% in men and 3.6% in women (Table 3). The prevalence of MetS in outpatients was also 2–3-fold higher than in inpatients using the JASSO definition. According to the National Health and Nutrition Examination Survey in Japan, the overall prevalence of MetS in the Japanese general population using the JASSO definition was 15.6%.20 Compared with the Japanese general population, outpatients with schizophrenia were found to be at higher risk of developing MetS. The risk of developing MetS in inpatients was lower than in the Japanese general population. This tendency was similar regardless of age.
14.8 (8/54) 29.4 (65/221) 37.7 (137/363) 36.5 (137/375) 33.7 (121/359) 32.5 (41/126) 34.0 (509/1498)
General population %b
3.3. Prevalence of MetS based on JASSO definition compared with Japanese general population
0.1 1.3 3.2 7.2 12.0 17.9 9.4
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p value
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Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
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improvement in the lipid profile induced by physical activity is an increase in HDL cholesterol (Mann et al., 2014). In hospital, where physical activity is relatively confined, it may be difficult to increase the value of HDL. The prevalence of MetS reported in several previous studies varied considerably due to different definitions of MetS. In this study, we established the prevalence of MetS using the JASSO definition. In both outpatients and inpatients, the prevalence of MetS was low compared with that using the ATP III-A definition. Specifically, MetS prevalence in female patients using the JASSO definition was less than half of that with the ATP III-A definition. This may have been due to the effect of increasing the WC criterion to 90 cm (Examination Committee of the Criteria for Metabolic Syndrome in Japan, 2005). Although the effective cut-off value for WC is still controversial, the ATP III-A criteria might be suitable for making international comparisons because of the availability of data among different ethnic groups. The prevalence of MetS in our study did not differ from that in most European and Asian countries, such as 35% in The Netherlands (Schorr et al., 2009) and 32.3% in Belgium (De Hert et al., 2006). However, our results were less frequent than those in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) using the same definition of MetS (42.7%) (McEvoy et al., 2005). In previous studies, the prevalence of MetS in women was usually equal to or greater than that in men (McEvoy et al., 2005; Haack et al., 2009). When we examined MetS prevalence in each age group, it was high in men in each age groups. In male outpatients and inpatients, the prevalence of MetS was highest in those aged 40–59 years who are production populations. The interpretation of such trends is complex and needs to be done with caution, especially given the cross-sectional nature of the current study. The mechanism of increased prevalence is not known. Patients with schizophrenia are at risk for developing obesity due to lack of exercise, poor dietary habits, and limited activity due to negative symptoms. In addition, antipsychotic medication has direct metabolic effects (Basu et al., 2004). MetS is associated with diabetes and cardiovascular risk factors. The prevalence of diabetes in this population was three times higher than in the general population (Hanley et al., 2005). A prospective study showed that MetS was associated with a threefold increased risk of coronary heart disease and stroke over a median of 6.2 years follow-up (Isomaa et al., 2001). Therefore, our results demonstrate that we should carefully monitor patients with schizophrenia to minimise the risk of developing MetS. Although the prevalence of MetS in outpatients aged b59 years was higher than in the general population, the prevalence in outpatients aged N60 years was similar to that in the general population. It is difficult to clarify the reason for there being no difference in MetS prevalence between older outpatients and the older general population. One possibility is that the stabilisation of psychotic symptoms with ageing corrected irregular eating habits and led to a decrease in waist circumference and improvement of lipid abnormalities. Inpatients aged N 50 years had a considerably lower prevalence of MetS compared with the general population. We previously reported that the prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia was higher than in outpatients and the general population (Sugai et al., 2015). Most Japanese inpatients under long-term hospitalisation are old. Underweight and undernutrition in Japanese inpatients are serious problems. This may be related to lower prevalence of MetS in old inpatients. This study had limitations similar to those of other cross-sectional surveys of patients with schizophrenia and MetS. Because there was no information about the duration of illness and medication, we did not consider the influence of antipsychotics. In conclusion, we conducted a large questionnaire survey, and observed that Japanese outpatients with schizophrenia were more likely to have MetS than inpatients. The focus of psychiatric services in Japan is being shifted from hospital to community care, and the Ministry of Health, Labour and Welfare aims for the prompt discharge of newly
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admitted patients. As a result, it is expected that there will be an increase in Japanese outpatients with schizophrenia in the future. The long-term hospitalisation is a severe problem, and may lead to pressure of the medical economic cost. However, it may affect the low prevalence in Japanese inpatients with schizophrenia. Therefore, the physical risk in patients with schizophrenia may be affected by environmental parameters such as type of care (ambulatory or hospitalised). As for psychiatric care in Japan, treatment of outpatients should include day care and nutritional control, and more attention should be paid to the physical risk Japanese patients with schizophrenia.
Declaration of interest Toshiyuki Someya has received research support or honoraria from Asahi Kasei Pharma Corp., Astellas Pharma Inc., Daiichi Sankyo Co. Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co. Ltd., Eli Lilly Japan, K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Meiji Seika Pharma Co. Ltd., Mitsubishi Tanabe Pharma Co. Ltd., Mochida Pharmaceutical Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Shionogi & Co., Ltd., Tsumura & Co, and Yoshitomi Pharmaceutical Industries. Yutaro Suzuki has received research support or honoraria from Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co. Ltd., and Otsuka Pharmaceutical Co. Ltd. The other authors declare no potential conflict of interest. Kazutaka Shimoda has received research support or honoraria from Daiichi Sankyo Co. Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan, K.K., GlaxoSmithKline K.K., Meiji Seika Pharma Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Shionogi & Co., Ltd., Takeda Pharmaceutical Co., Ltd., Tsumra & Co., Yoshitomi Pharmaceutical Industries, Ltd., Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Janssen Pharmaceutical K.K., Kowa Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Mitsubishi Tanabe Pharma Corporation, Ltd., MSD K.K., Novartis Pharma K.K., and Ono Pharmaceutical Co., Ltd. Norio Yasui-Furukori has received research support or honoraria from Astellas Pharma Inc., Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan, K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Meiji Seika Pharma Co., Mochida Pharmaceutical Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and Yoshitomi Pharmaceutical Industries. Norio Sugawara has received grant/research support from Grant-in-Aid for Young Scientists (B)., The Ministry of Education, Culture, Sports, Science and Technology, Japan Grant B., Karoji Memorial Fund for Medical Research Grant and SENSHIN Medical Research Foundation. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the Schizophrenia Research policies on sharing data and materials, as detailed online in the guide for authors. The other authors declare no potential conflicts of interest.
Funding This work was partially supported by Eisai Co. Ltd., Yoshitomi Pharmaceutical Industries, Dainippon Sumitomo Pharma Co. Ltd., Astellas Pharma Inc., Meiji Seika Pharma Co. Ltd., Eli Lilly Japan, K.K., Otsuka Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., MSD K.K., Shionogi & Co. Ltd., Asahi Kasei Pharma Corp., Novartis Pharma Co. Ltd., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., and Tsumura & Co. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Contributors Author Takuro Sugai is the principal author and the main contributor to the design of the present study. Authors Takuro Sugai, Yutaro Suzuki, Kazutaka Shimoda, Yuji Ozeki, Norio Sugawara, Norio Yasui-Furukori and Toshiyuki Someya contributed in the study conception and design. Authors Manabu Yamazaki, Takao Mori, Hiroshi Matsuda, Yoshitake Minami, Kurefu Okamoto and Toyoaki Sagae were involved in the acquisition of data. Takuro Sugai and Yutaro Suzuki contributed in the drafting of the manuscript. Kazutaka Shimoda, Yuji Ozeki, Norio Sugawara, Norio Yausi-Furukori and Toshiyuki Someya were involved in the critical revision. All the authors were involved in the analysis and interpretation of the data; and gave their final approval.
Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
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T. Sugai et al. / Schizophrenia Research xxx (2016) xxx–xxx
Acknowledgements We are grateful to the study participants and the facilities belonging to Japan Psychiatric Hospital Association which cooperated with the present investigation. We would like to thank all our co-workers for their contributions to the data collection and management.
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Please cite this article as: Sugai, T., et al., Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.01.016
