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Perception of metabolic diseases related to blood stasis: A survey of Korean medicine doctors
European Journal of Integrative Medicine 35 (2020) 101103
Contents lists available at ScienceDirect
European Journal of Integrative Medicine journal homepage: www.elsevier.com/locate/eujim
Research paper
Perception of metabolic diseases related to blood stasis: A survey of Korean medicine doctors
T
Soobin Janga, Mi Mi Kob, Byoung-Kab Kangb, Jeeyoun Junga,* a b
Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
A R T I C LE I N FO
A B S T R A C T
Keywords: Blood stasis Metabolic disease Cardiovascular disease Herbal medicine East Asian medicine Traditional Korean medicine doctors
Introduction: Blood stasis is defined as slowing or stagnation of blood and is regarded as a cause of metabolic disease. The aim of this study was to explore the opinions of traditional Korean medicine (TKM) doctors on blood stasis in metabolic disease. Methods: An email with a link to an online survey was sent by the Association of Korean Medicine to all registered TKM doctors in October 2018. The questionnaire was developed and piloted by four Korean medicine doctors and included items on KMDs’ demographic characteristics, their perceptions on blood stasis and current treatment. Results: Of the 908 TKM doctors participating in the survey, 836 (92.1 %) reported that they thought metabolic disease was highly associated with blood stasis or that blood stasis was the cause of metabolic disease. Most frequently reported to be associated with blood stasis was vascular disease (n = 405, 44.6 %). Over three quarters of respondents thought that herbal medicine combined with conventional medication was good for managing blood pressure, blood sugar, and blood lipids (n = 724, 79.7 %). The higher cost compared to conventional drugs (n = 463, n = 51.0 %) was thought to be the reason that Korean medicine was not being used for the treatment of metabolic disease. Gyejibongnyeong-hwan and Cardiotonic pills were chosen as the appropriate herbal medicines for treating metabolic diseases as they were covered under herbal medicine insurance. Conclusions: This study suggests that further blood stasis research is required, particularly clinical studies in order to determine the strength of the association between blood stasis and metabolic diseases.
1. Introduction Blood stasis, one of the most common pathological patterns in traditional East Asian medicine, and is characterized by blood circulation problems or the accumulation of blood in certain parts of the body. Manifestations of blood stasis vary depending on its cause and the affected location, however the disease commonly affects patients with diseases related to blood circulation or with hemorrhagic diseases [1]. Heat in the blood, thick blood or blood stasis circulating in the whole body are considered the cause of metabolic diseases including hyperlipidemia and atherosclerosis [2,3]. Also, previous studies have reported that herbal medicines for treating blood stasis are effective for metabolic diseases [4–6]. There are several diagnostic tools for blood stasis and Korea Institute of Oriental Medicine (KIOM) integrated and summarized the diagnostic questionnaires used in South Korea, China and Japan [7–9].
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Doctors may use these diagnostic tools for blood stasis when choosing the correct treatment for patients. However, blood stasis is not recognized as an official diagnosis in South Korea. It is difficult to identify through electronic medical record data the clinical status such as the herbal medicines frequently used for blood stasis and the name of the metabolic diseases which most commonly use blood stasis prescriptions. In order to build supporting evidence for blood stasis in metabolic diseases, the current situation of the diagnosis and treatment of metabolic diseases with blood stasis should be understood. Accordingly, this study surveyed in detail the opinion of blood stasis related to metabolic disease by targeting traditional Korean medicine (TKM) doctors. The survey was focused on herbal medicines to identify herbal medicines with a high clinical value. This study aimed to present the current status of the treatment of metabolic diseases with blood stasis in South Korea and to collect the opinion of Korean medical doctors, and to provide practical evidence for blood stasis research.
Corresponding author. E-mail address: [email protected] (J. Jung).
https://doi.org/10.1016/j.eujim.2020.101103 Received 26 August 2019; Received in revised form 10 March 2020; Accepted 10 March 2020 1876-3820/ © 2020 Published by Elsevier GmbH.
European Journal of Integrative Medicine 35 (2020) 101103
S. Jang, et al.
2. Methods
Table 1 Demographic characteristics of responders.
2.1. Study design and setting
Demographic information
This study was a survey of TKM doctors' perceptions of metabolic diseases with blood stasis in South Korea. The survey was conducted by a KIOM research team via Mediresearch, (http://www.mediresearch. co.kr), which is an online research company in South Korea. Participants were recruited with the help of the Association of Korean Medicine (AKOM) office, which managed the personal information on TKM doctors. KIOM sent a letter to the AKOM requesting cooperation and AKOM sent an email twice informing members about the reserach survey.Those who had voluntarily agreed were enrolled. The survey was conducted anonymously between October 2 and 18, 2018.
Sex Age (years)
Time being a Korean medical doctor (years) Type of license Working region
2.2. Participants There was no special method for determining the sample size; we only sought to have as many people as possible to complete the survey during the survey period. Since the total number of TKM doctors is approximately 21,000 [10], the minimum number of participants was determined to be 700 (3.3 % of 21,000) based on previous surveys targeted on TKM doctors. Additional on-going recruitment continued until the end of the study period even if enrolled people exceeded 700. Those who did not belong to medical institute at the time of the survey for reasons such as working as researchers, or career break were excluded.
Working institution
Men Women 20-29 30-39 40-49 50-59 Over 60 Under 10 Over 10 under 20 Over 20 General practitioner Specialist Seoul Incheon, Gyeonggi-do, Gangwon-do Daejeon, Sejong, Chungcheong-do Busan, Daegu, Ulsan, Gyeongsang-do Gwangju, Jeolla-do, Jeju Clinic Hospital Public health institute
Total All data are in N (%)
N
%
696 212 118 352 319 99 20 418 352 138 703 205 228 251
76.7 23.3 13.0 38.8 35.1 10.9 2.2 46.0 38.8 15.2 77.4 22.6 25.1 27.6
108
11.9
195
21.5
126 639 200 69 908
13.9 70.4 22.0 7.6 100.0
2.6. Ethical considerations All participants were briefed with an explanation of the study’s purpose prior to the initiation of the survey. Only those who voluntarily agreed to participate and have their collected data to be published were enrolled in the study. This survey was conducted anonymously. This survey was approved by the Institutional Review Board of Woosuk University (IRB No. WSOH IRB H1901-01). All participants voluntarily agreed to participate in this survey.
2.3. Questionnaire The questionnaire was developed by four Korean medicine doctor (KMD) experts consisting of two researchers in blood stasis and two TKM doctors who specialised in cardiovascular disease. A draft questionnaire was developed through two rounds of reviews, placing emphasis on the easy comprehension of the questionnaire geared toward general responders. The experts examined the face reliability as well as readability of the questionnaire. Then, a pilot test was conducted targeting 10 people who were general clinical TKM doctors. A group of experts collected feedback and completed the final version of the questionnaire. The questionnaire is shown in Appendix A (in Supplementary material).
3. Results 3.1. Opinions on metabolic disease with blood stasis A total of 908 Korean medical doctors were enrolled and completed the questionnaire after excluding data from 7 subjects who were currently on leave or doing research. Demographic information on respondents is described in Table 1. Of the total respondents, 227 (25.0 %) TKM doctors responded that blood stasis is the cause of metabolic diseases. Of the remaining participants, 609 (67.1 %) thought that metabolic diseases are highly associated with blood stasis, 59 (7.6 %) thought that they are poorly associated, and 3 (0.3 %) thought that they are rarely associated. The diseases most associated with blood stasis were vascular disease (405, 44.6 %), heart disease (275, 30.3 %), hyperlipidemia (157, 17.3 %), diabetes mellitus (39, 4.3 %), and hypertension (32, 3.5 %). Most respondents (724, 79.7 %) considered that herbal medicine combined with conventional drugs is appropriate for managing blood pressure, blood sugar, and blood lipids; 156 (17.2 %) thought that there are some aspects that can be managed by herbal medicine alone. Only 28 (3.1 %) participants responded that the conventional medical system is wellestablished for managing metabolic diseases and there is no need for Korean medical treatment. The reasons for the low usefulness of herbal medicines for metabolic disease treatment were classified as follows: high cost compared to conventional drugs, 463 (51.0 %); no immediate effect as that observed with conventional drugs, 179 (19.7 %); lack of publicity with patients, 146 (16.1 %); and lack of evidence of clinical effectiveness, 120 (13.2 %) (Table 2).
2.4. Study variables The variables included were as follows: Demographic information: sex, age, duration of Korean medical practice, type of license, working region, and working institution Perception of metabolic diseases related to blood stasis: the association between metabolic disease and blood stasis, metabolic disease most associated with blood stasis, opinion on herbal medicine for treating metabolic disease, reason why herbal medicine is not frequently used for metabolic disease treatment, appropriate herbal medicine for treating each metabolic disease, most necessary herbal medicine to be covered by herbal insurance Current state of the treatment of metabolic diseases and blood stasis: proportion of patients with metabolic diseases, proportion of patients with blood stasis among the patients with metabolic diseases. 2.5. Statistical analyses A frequency analysis was performed for all variables. A chi-squared test was employed in order to examine the differences in the proportion of patients by type of institute. R 3.4.3 software was used for the analysis. 2
European Journal of Integrative Medicine 35 (2020) 101103
S. Jang, et al.
Table 2 Opinions on metabolic disease related to blood stasis. Question
Response
N (%)
Do you think that metabolic disease is associated with blood stasis?
Blood stasis is the cause of metabolic disease Highly associated Lowly associated Rarely associated Vascular disease (e.g. atherosclerosis, varicose veins, aneurysms) Heart disease (e.g. myocardial infarction, angina pectoris) Hyperlipidemia Diabetes mellitus Hypertension Herbal medicine combined with conventional drugs is good for managing blood pressure, blood sugar, and blood lipid. There are some parts that can be managed by herbal medicines without conventional drugs. The conventional medical system for managing metabolic disease is well-established and there is no need for Korean medical treatment. Expensive cost compared to conventional drugs No immediate effect like conventional drugs Lack of publicity among patients Lack of evidence of clinical effectiveness
227 (25.0) 609 (67.1) 69 (7.6) 3 (0.3) 405 (44.6) 275 (30.3) 157 (17.3) 39 (4.3) 32 (3.5) 724 (79.7)
What disease do you think is the most associated with blood stasis?
How do you feel about using herbal medicine for metabolic diseases?
Why do you think herbal medicine is not frequently used for metabolic disease treatment?
Total
156 (17.2) 28 (3.1) 463 179 146 120 908
(51.0) (19.7) (16.1) (13.2) (100.0)
Gyejibongnyeong-hwan (292, 32.2 %) was selected as the most necessary herbal medicine to be covered by health insurance, followed by Cardiotonic pills (236, 26.0 %) and Dangguixu-san (203, 22.4 %). The exact details are shown in Table 4.
3.2. Current state of treatment of metabolic diseases and blood stasis The proportion of patients with metabolic diseases in the entire population was mostly distributed in the ‘0–20 %’ section followed by the ‘20–40 %’ section regardless of working institution. However, the results showed that patients with metabolic diseases tend to visit hospitals and public health institutes compared to clinics (p < 0.001). Most TKM doctors reported that 20–40 % of patients with metabolic diseases presented with blood stasis. (Table 3). There were no significant differences associated with place of work (p = 0.1629).
4. Discussion This study described the opinions of TKM doctors regarding the association between metabolic diseases and blood stasis. As shown in Table 1, data on basic characteristics such as sex, age, and region of 908 respondents were reviewed. The proportion of patients with metabolic diseases was less than 40 % in general; the proportion was higher in public health institutes than in clinics or hospitals. The proportion of those who had blood stasis among patients with metabolic diseases was 20–40 % regardless of the type of the medical institute (Table 3). Most TKM doctors thought that metabolic diseases are highly associated (609, 67.1 %) with blood stasis or blood stasis is the cause of metabolic diseases (227, 25.0 %) (Table 2). This result corresponds with the opinion of Chinese experts that cardiovascular disease is related to blood stasis and further research on cardiovascular diseases and blood stasis is needed [11]. Based on a previous survey [12], more than 70 % of the 678 TKM doctors responded that the most relevant pathological mechanism of blood stasis was thrombosis or abnormalities in hemorheology. Therefore, this study focused on metabolic diseases, not diseases such as gynecological disease or pain diseases which are also related to blood stasis. Severe conditions such as vascular diseases
3.3. Appropriate herbal medicines for metabolic diseases with blood stasis This questionnaire surveyed herbal medicines that were appropriate for each metabolic disease. All respondents selected three herbal medicines in the descending order. The selected herbal medicines for hypertension were as follows: Cardiotonic pills 304 (33.5 %), Gyejibongnyeong-hwan 191 (21.0 %), Xuefu-xhufu decoction 142 (15.6 %). Herbal medicines for diabetes mellitus were as follows: Gyejibongnyeong-hwan 223 (24.6 %), Shu-Jing-Huo-Xie-Tang 159 (15.6 %), Xuefu-zhufu decoction 490 (54.0 %). Herbal medicines for hyperlipidemia were as follows: Cardiotonic pills 239 (26.3 %), Gyejibongnyeong-hwan 190 (20.9 %), Xuefu-zhufu decoction 152 (16.7 %). However, the results of the sum of the 1-3rd place in hyperlipidemia were as follows: Gyejibongnyeong-hwan 490 (54.1 %), Xuefuzhufu decoction 485 (53.4 %), and Cardiotonic pills 450 (49.6 %). Table 3 Proportion of patients with metabolic disease and blood stasis. Question
Proportion of patients with metabolic disease in entire population
Proportion of patients with blood stasis in patients with metabolic disease
Response
Type of institute
0–20 % 20–40 % 40-60 % 60–80 % 80–100 % Total 0–20 % 20–40 % 40-60 % 60-80 % 80–100 % Total
* Fisher’s exact test was performed. 3
P-value*
Clinic (n, (%))
Hospital (n, (%))
Public health institute (n, (%)
301 (47.1) 208 (32.6) 96 (15.0) 33 (5.2) 1 (0.2) 639 (100.0) 177 (27.7) 208 (32.6) 160 (25.0) 79 (12.4) 15 (2.3) 639 (100.0)
76 (38.0) 69 (34.5) 31 (15.5) 18 (9.0) 6 (3.0) 200 (100.0) 61 (30.5) 79 (39.5) 41 (20.5) 17 (8.5) 2 (1.0) 200 (100.0)
20 (29.0) 21 (30.4) 14 (20.3) 10 (14.5) 4 (5.8) 69 (100.0) 18 (26.1) 26 (37.7) 21 (30.4) 3 (4.3) 1 (1.4) 69 (100.0)
< 0.001
0.1629
European Journal of Integrative Medicine 35 (2020) 101103
S. Jang, et al.
Table 4 Appropriate herbal medicine for treating each metabolic disease and most necessary to be covered by health insurance. Appropriate herbal medicine
Gyejibongnyeong-hwan Cardiotonic pills Xuefu-zhufu decoction Shu-Jing-Huo-Xie-Tang Dangguixu-san Do-In-Seung-Gi-Tang Samchil-san Tongdo-san Others
Hypertension with blood stasis
Diabetes mellitus with blood stasis
Hyperlipidemia with blood stasis
To be covered by health insurance
1st place (n, (%))
1-3rd place (n, (%))
1st place (n, (%))
1-3rd place (n, (%))
1st place (n, (%))
1-3rd place (n, (%))
1st place (n, (%))
1-3rd place (n, (%))
191 (21.0) 304 (33.5) 142 (15.6) 92 (10.1) 60 (6.6) 57 (6.3) 21 (2.3) 15 (1.7) 26 (2.9)
522 (57.5) 580 (63.9) 490 (54.0) 380 (41.9) 236 (26.0) 281 (30.9) 125 (13.8) 75 (8.3) 35 (3.9)
223 (24.6) 112 (12.3) 149 (16.4) 159 (17.5) 61 (6.7) 77 (8.5) 63 (6.9) 32 (3.5) 32 (3.5)
532 (58.6) 320 (35.2) 469 (51.7) 494 (54.4) 245 (27.0) 271 (29.8) 211 (23.2) 138 (15.2) 44 (4.8)
190 (20.9) 239 (26.3) 152 (16.7) 118 (13.0) 65 (7.2) 64 (7.0) 36 (4.0) 18 (2.0) 26 (2.9)
491 (54.1) 450 (49.6) 485 (53.4) 439 (48.3) 252 (27.8) 253 (27.9) 212 (23.3) 106 (11.7) 36 (4.0)
292 (32.2) 236 (26.0) 56 (6.2) 59 (6.5) 203 (22.4) 33 (3.6) 14 (1.5) 7 (0.8) 8 (0.9)
683 (75.2) 485 (53.4) 332 (36.6) 341 (37.6) 536 (59.9) 203 (22.4) 85 (9.4) 49 (5.4) 10 (1.1)
not suitable for the treatment of metabolic diseases. There are some limitations in this study. First, a recall bias may exist when answering the questions regarding the proportion of patients. It is currently not possible to calculate the exact number of patients using the National Health Insurance Service data. Second, although Do-InSeung-Gi-Tang was included in the item ‘it is necessary for health insurance to cover herbal medicine’, it is already covered under health insurance. Third, there are several questionnaires for diagnosing bloodstasis, therefore it would been better to have investigated how TKM doctors diagnosed blood stasis. Nonetheless, this study attempted to collect as many opinions of TKM doctors as possible on the association between blood stasis and metabolic diseases.
(405, 44.6 %) and heart diseases (275, 30.3 %) were regarded as diseases related to blood stasis, and hyperlipidemia had the highest association with blood stasis among hypertension, hyperlipidemia and diabetes mellitus. Hyperlipidemia is a condition involving abnormally increased levels of blood lipids and lipoproteins. The excess lipids in the walls of the arteries form blood clots thus leading to blood stasis [13,14]. Approximately 80 % of the 908 respondents supported the belief that ‘Herbal medicines combined with conventional drugs are good for managing blood pressure, blood sugar, and blood lipids.’ There are several previous clinical trials of herbal medicines combined with Western medicine for the treatment of metabolic diseases [15,16]. In Wang’s study [15], Yiqi Huaju Qingli Herb Formula combined with Western medicine significantly lowered blood glucose and improved lipid metabolism in metabolic syndrome patients. In Xian’s study [16], Shenmai injection, which is extracted from Panax ginseng, and Ophipogon japonicas in addition to standard medicines improved chronic heart disease and coronary artery disease compared to placebo with standard medicines. Regarding the appropriate herbal medication, Gyejibongnyeonghwan and Cardiotonic pills were selected by a high percentage of participants for each disease. Gyejibongnyeong-hwan has been used mainly for treating primary dysmenorrhea or uterine myoma with blood stasis [17]. On the other hand this formula is also regarded as a therapeutic drug for decreasing blood lipids or preventing heart diseases [18]. Cardiotonic pills, such as the Danshen dripping pill, is a representative herbal medicine for stable angina pectoris in some countries [19,20]. It is now undergoing phase III clinical trials for drug development in the United States under the lead of a Chinese pharmaceutical company [21]. Salvia miltiorrhiza, the main herb of Cardiotonic pills is effective to remove blood stasis and promote blood circulation [22]. Xuefu-zhufu decoction was also selected as the appropriate herbal medicine by a high percentage of participants. It has been widely used in China for the treatment of heart diseases such as coronary artery disease and atherosclerosis and is helpful for dissipating blood stasis [23,24]. Gyejibongnyeong-hwan and Cardiotonic pills were also ranked first and second among the most necessary herbal medicine to be covered by health insurance. Dangguixu-san ranked third since it is an effective drug for treating the pain caused by blood stasis rather than metabolic diseases [25]. Most respondents (n = 463, 51.0 %) thought that the expensive cost compared to conventional drugs was the biggest reason why herbal medicine is not frequently used for metabolic disease treatment. Accordingly, it is important to have insurance coverage and provide patients medical service at a low cost to raise herbal medicine prescription rate. Only two prescriptions (i.e. DaehwangmokdanpiTang, Do-In-Seung-Gi-Tang) for blood stasis were included in the 56 herbal medicines covered by health insurance [26], however they are
5. Conclusions This study investigated the opinion of TKMs on the association between metabolic diseases and blood stasis. Most experts agreed that metabolic diseases were highly associated with blood stasis and that herbal medicines combined with conventional drugs were effective for the treatment of metabolic diseases. The results of this survey may provide basic data for future clinical studies and health policy research.
Funding This study was supported by a grant from the Korea Institute of Oriental Medicine, Republic of Korea (KSN2013210).
Availability of data and materials The data used for this study are available from the corresponding author upon request.
Consent for publication Not applicable.
CRediT authorship contribution statement Soobin Jang: Conceptualization, Methodology, Validation, Investigation, Writing - original draft, Visualization. Mi Mi Ko: Methodology, Formal analysis, Data curation, Writing - review & editing. Byoung-Kab Kang: Software, Validation, Formal analysis, Writing - review & editing. Jeeyoun Jung: Investigation, Resources, Writing - review & editing, Supervision, Project administration, Funding acquisition. 4
European Journal of Integrative Medicine 35 (2020) 101103
S. Jang, et al.
Declaration of Competing Interest
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Research paper
Perception of metabolic diseases related to blood stasis: A survey of Korean medicine doctors
T
Soobin Janga, Mi Mi Kob, Byoung-Kab Kangb, Jeeyoun Junga,* a b
Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
A R T I C LE I N FO
A B S T R A C T
Keywords: Blood stasis Metabolic disease Cardiovascular disease Herbal medicine East Asian medicine Traditional Korean medicine doctors
Introduction: Blood stasis is defined as slowing or stagnation of blood and is regarded as a cause of metabolic disease. The aim of this study was to explore the opinions of traditional Korean medicine (TKM) doctors on blood stasis in metabolic disease. Methods: An email with a link to an online survey was sent by the Association of Korean Medicine to all registered TKM doctors in October 2018. The questionnaire was developed and piloted by four Korean medicine doctors and included items on KMDs’ demographic characteristics, their perceptions on blood stasis and current treatment. Results: Of the 908 TKM doctors participating in the survey, 836 (92.1 %) reported that they thought metabolic disease was highly associated with blood stasis or that blood stasis was the cause of metabolic disease. Most frequently reported to be associated with blood stasis was vascular disease (n = 405, 44.6 %). Over three quarters of respondents thought that herbal medicine combined with conventional medication was good for managing blood pressure, blood sugar, and blood lipids (n = 724, 79.7 %). The higher cost compared to conventional drugs (n = 463, n = 51.0 %) was thought to be the reason that Korean medicine was not being used for the treatment of metabolic disease. Gyejibongnyeong-hwan and Cardiotonic pills were chosen as the appropriate herbal medicines for treating metabolic diseases as they were covered under herbal medicine insurance. Conclusions: This study suggests that further blood stasis research is required, particularly clinical studies in order to determine the strength of the association between blood stasis and metabolic diseases.
1. Introduction Blood stasis, one of the most common pathological patterns in traditional East Asian medicine, and is characterized by blood circulation problems or the accumulation of blood in certain parts of the body. Manifestations of blood stasis vary depending on its cause and the affected location, however the disease commonly affects patients with diseases related to blood circulation or with hemorrhagic diseases [1]. Heat in the blood, thick blood or blood stasis circulating in the whole body are considered the cause of metabolic diseases including hyperlipidemia and atherosclerosis [2,3]. Also, previous studies have reported that herbal medicines for treating blood stasis are effective for metabolic diseases [4–6]. There are several diagnostic tools for blood stasis and Korea Institute of Oriental Medicine (KIOM) integrated and summarized the diagnostic questionnaires used in South Korea, China and Japan [7–9].
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Doctors may use these diagnostic tools for blood stasis when choosing the correct treatment for patients. However, blood stasis is not recognized as an official diagnosis in South Korea. It is difficult to identify through electronic medical record data the clinical status such as the herbal medicines frequently used for blood stasis and the name of the metabolic diseases which most commonly use blood stasis prescriptions. In order to build supporting evidence for blood stasis in metabolic diseases, the current situation of the diagnosis and treatment of metabolic diseases with blood stasis should be understood. Accordingly, this study surveyed in detail the opinion of blood stasis related to metabolic disease by targeting traditional Korean medicine (TKM) doctors. The survey was focused on herbal medicines to identify herbal medicines with a high clinical value. This study aimed to present the current status of the treatment of metabolic diseases with blood stasis in South Korea and to collect the opinion of Korean medical doctors, and to provide practical evidence for blood stasis research.
Corresponding author. E-mail address: [email protected] (J. Jung).
https://doi.org/10.1016/j.eujim.2020.101103 Received 26 August 2019; Received in revised form 10 March 2020; Accepted 10 March 2020 1876-3820/ © 2020 Published by Elsevier GmbH.
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2. Methods
Table 1 Demographic characteristics of responders.
2.1. Study design and setting
Demographic information
This study was a survey of TKM doctors' perceptions of metabolic diseases with blood stasis in South Korea. The survey was conducted by a KIOM research team via Mediresearch, (http://www.mediresearch. co.kr), which is an online research company in South Korea. Participants were recruited with the help of the Association of Korean Medicine (AKOM) office, which managed the personal information on TKM doctors. KIOM sent a letter to the AKOM requesting cooperation and AKOM sent an email twice informing members about the reserach survey.Those who had voluntarily agreed were enrolled. The survey was conducted anonymously between October 2 and 18, 2018.
Sex Age (years)
Time being a Korean medical doctor (years) Type of license Working region
2.2. Participants There was no special method for determining the sample size; we only sought to have as many people as possible to complete the survey during the survey period. Since the total number of TKM doctors is approximately 21,000 [10], the minimum number of participants was determined to be 700 (3.3 % of 21,000) based on previous surveys targeted on TKM doctors. Additional on-going recruitment continued until the end of the study period even if enrolled people exceeded 700. Those who did not belong to medical institute at the time of the survey for reasons such as working as researchers, or career break were excluded.
Working institution
Men Women 20-29 30-39 40-49 50-59 Over 60 Under 10 Over 10 under 20 Over 20 General practitioner Specialist Seoul Incheon, Gyeonggi-do, Gangwon-do Daejeon, Sejong, Chungcheong-do Busan, Daegu, Ulsan, Gyeongsang-do Gwangju, Jeolla-do, Jeju Clinic Hospital Public health institute
Total All data are in N (%)
N
%
696 212 118 352 319 99 20 418 352 138 703 205 228 251
76.7 23.3 13.0 38.8 35.1 10.9 2.2 46.0 38.8 15.2 77.4 22.6 25.1 27.6
108
11.9
195
21.5
126 639 200 69 908
13.9 70.4 22.0 7.6 100.0
2.6. Ethical considerations All participants were briefed with an explanation of the study’s purpose prior to the initiation of the survey. Only those who voluntarily agreed to participate and have their collected data to be published were enrolled in the study. This survey was conducted anonymously. This survey was approved by the Institutional Review Board of Woosuk University (IRB No. WSOH IRB H1901-01). All participants voluntarily agreed to participate in this survey.
2.3. Questionnaire The questionnaire was developed by four Korean medicine doctor (KMD) experts consisting of two researchers in blood stasis and two TKM doctors who specialised in cardiovascular disease. A draft questionnaire was developed through two rounds of reviews, placing emphasis on the easy comprehension of the questionnaire geared toward general responders. The experts examined the face reliability as well as readability of the questionnaire. Then, a pilot test was conducted targeting 10 people who were general clinical TKM doctors. A group of experts collected feedback and completed the final version of the questionnaire. The questionnaire is shown in Appendix A (in Supplementary material).
3. Results 3.1. Opinions on metabolic disease with blood stasis A total of 908 Korean medical doctors were enrolled and completed the questionnaire after excluding data from 7 subjects who were currently on leave or doing research. Demographic information on respondents is described in Table 1. Of the total respondents, 227 (25.0 %) TKM doctors responded that blood stasis is the cause of metabolic diseases. Of the remaining participants, 609 (67.1 %) thought that metabolic diseases are highly associated with blood stasis, 59 (7.6 %) thought that they are poorly associated, and 3 (0.3 %) thought that they are rarely associated. The diseases most associated with blood stasis were vascular disease (405, 44.6 %), heart disease (275, 30.3 %), hyperlipidemia (157, 17.3 %), diabetes mellitus (39, 4.3 %), and hypertension (32, 3.5 %). Most respondents (724, 79.7 %) considered that herbal medicine combined with conventional drugs is appropriate for managing blood pressure, blood sugar, and blood lipids; 156 (17.2 %) thought that there are some aspects that can be managed by herbal medicine alone. Only 28 (3.1 %) participants responded that the conventional medical system is wellestablished for managing metabolic diseases and there is no need for Korean medical treatment. The reasons for the low usefulness of herbal medicines for metabolic disease treatment were classified as follows: high cost compared to conventional drugs, 463 (51.0 %); no immediate effect as that observed with conventional drugs, 179 (19.7 %); lack of publicity with patients, 146 (16.1 %); and lack of evidence of clinical effectiveness, 120 (13.2 %) (Table 2).
2.4. Study variables The variables included were as follows: Demographic information: sex, age, duration of Korean medical practice, type of license, working region, and working institution Perception of metabolic diseases related to blood stasis: the association between metabolic disease and blood stasis, metabolic disease most associated with blood stasis, opinion on herbal medicine for treating metabolic disease, reason why herbal medicine is not frequently used for metabolic disease treatment, appropriate herbal medicine for treating each metabolic disease, most necessary herbal medicine to be covered by herbal insurance Current state of the treatment of metabolic diseases and blood stasis: proportion of patients with metabolic diseases, proportion of patients with blood stasis among the patients with metabolic diseases. 2.5. Statistical analyses A frequency analysis was performed for all variables. A chi-squared test was employed in order to examine the differences in the proportion of patients by type of institute. R 3.4.3 software was used for the analysis. 2
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Table 2 Opinions on metabolic disease related to blood stasis. Question
Response
N (%)
Do you think that metabolic disease is associated with blood stasis?
Blood stasis is the cause of metabolic disease Highly associated Lowly associated Rarely associated Vascular disease (e.g. atherosclerosis, varicose veins, aneurysms) Heart disease (e.g. myocardial infarction, angina pectoris) Hyperlipidemia Diabetes mellitus Hypertension Herbal medicine combined with conventional drugs is good for managing blood pressure, blood sugar, and blood lipid. There are some parts that can be managed by herbal medicines without conventional drugs. The conventional medical system for managing metabolic disease is well-established and there is no need for Korean medical treatment. Expensive cost compared to conventional drugs No immediate effect like conventional drugs Lack of publicity among patients Lack of evidence of clinical effectiveness
227 (25.0) 609 (67.1) 69 (7.6) 3 (0.3) 405 (44.6) 275 (30.3) 157 (17.3) 39 (4.3) 32 (3.5) 724 (79.7)
What disease do you think is the most associated with blood stasis?
How do you feel about using herbal medicine for metabolic diseases?
Why do you think herbal medicine is not frequently used for metabolic disease treatment?
Total
156 (17.2) 28 (3.1) 463 179 146 120 908
(51.0) (19.7) (16.1) (13.2) (100.0)
Gyejibongnyeong-hwan (292, 32.2 %) was selected as the most necessary herbal medicine to be covered by health insurance, followed by Cardiotonic pills (236, 26.0 %) and Dangguixu-san (203, 22.4 %). The exact details are shown in Table 4.
3.2. Current state of treatment of metabolic diseases and blood stasis The proportion of patients with metabolic diseases in the entire population was mostly distributed in the ‘0–20 %’ section followed by the ‘20–40 %’ section regardless of working institution. However, the results showed that patients with metabolic diseases tend to visit hospitals and public health institutes compared to clinics (p < 0.001). Most TKM doctors reported that 20–40 % of patients with metabolic diseases presented with blood stasis. (Table 3). There were no significant differences associated with place of work (p = 0.1629).
4. Discussion This study described the opinions of TKM doctors regarding the association between metabolic diseases and blood stasis. As shown in Table 1, data on basic characteristics such as sex, age, and region of 908 respondents were reviewed. The proportion of patients with metabolic diseases was less than 40 % in general; the proportion was higher in public health institutes than in clinics or hospitals. The proportion of those who had blood stasis among patients with metabolic diseases was 20–40 % regardless of the type of the medical institute (Table 3). Most TKM doctors thought that metabolic diseases are highly associated (609, 67.1 %) with blood stasis or blood stasis is the cause of metabolic diseases (227, 25.0 %) (Table 2). This result corresponds with the opinion of Chinese experts that cardiovascular disease is related to blood stasis and further research on cardiovascular diseases and blood stasis is needed [11]. Based on a previous survey [12], more than 70 % of the 678 TKM doctors responded that the most relevant pathological mechanism of blood stasis was thrombosis or abnormalities in hemorheology. Therefore, this study focused on metabolic diseases, not diseases such as gynecological disease or pain diseases which are also related to blood stasis. Severe conditions such as vascular diseases
3.3. Appropriate herbal medicines for metabolic diseases with blood stasis This questionnaire surveyed herbal medicines that were appropriate for each metabolic disease. All respondents selected three herbal medicines in the descending order. The selected herbal medicines for hypertension were as follows: Cardiotonic pills 304 (33.5 %), Gyejibongnyeong-hwan 191 (21.0 %), Xuefu-xhufu decoction 142 (15.6 %). Herbal medicines for diabetes mellitus were as follows: Gyejibongnyeong-hwan 223 (24.6 %), Shu-Jing-Huo-Xie-Tang 159 (15.6 %), Xuefu-zhufu decoction 490 (54.0 %). Herbal medicines for hyperlipidemia were as follows: Cardiotonic pills 239 (26.3 %), Gyejibongnyeong-hwan 190 (20.9 %), Xuefu-zhufu decoction 152 (16.7 %). However, the results of the sum of the 1-3rd place in hyperlipidemia were as follows: Gyejibongnyeong-hwan 490 (54.1 %), Xuefuzhufu decoction 485 (53.4 %), and Cardiotonic pills 450 (49.6 %). Table 3 Proportion of patients with metabolic disease and blood stasis. Question
Proportion of patients with metabolic disease in entire population
Proportion of patients with blood stasis in patients with metabolic disease
Response
Type of institute
0–20 % 20–40 % 40-60 % 60–80 % 80–100 % Total 0–20 % 20–40 % 40-60 % 60-80 % 80–100 % Total
* Fisher’s exact test was performed. 3
P-value*
Clinic (n, (%))
Hospital (n, (%))
Public health institute (n, (%)
301 (47.1) 208 (32.6) 96 (15.0) 33 (5.2) 1 (0.2) 639 (100.0) 177 (27.7) 208 (32.6) 160 (25.0) 79 (12.4) 15 (2.3) 639 (100.0)
76 (38.0) 69 (34.5) 31 (15.5) 18 (9.0) 6 (3.0) 200 (100.0) 61 (30.5) 79 (39.5) 41 (20.5) 17 (8.5) 2 (1.0) 200 (100.0)
20 (29.0) 21 (30.4) 14 (20.3) 10 (14.5) 4 (5.8) 69 (100.0) 18 (26.1) 26 (37.7) 21 (30.4) 3 (4.3) 1 (1.4) 69 (100.0)
< 0.001
0.1629
European Journal of Integrative Medicine 35 (2020) 101103
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Table 4 Appropriate herbal medicine for treating each metabolic disease and most necessary to be covered by health insurance. Appropriate herbal medicine
Gyejibongnyeong-hwan Cardiotonic pills Xuefu-zhufu decoction Shu-Jing-Huo-Xie-Tang Dangguixu-san Do-In-Seung-Gi-Tang Samchil-san Tongdo-san Others
Hypertension with blood stasis
Diabetes mellitus with blood stasis
Hyperlipidemia with blood stasis
To be covered by health insurance
1st place (n, (%))
1-3rd place (n, (%))
1st place (n, (%))
1-3rd place (n, (%))
1st place (n, (%))
1-3rd place (n, (%))
1st place (n, (%))
1-3rd place (n, (%))
191 (21.0) 304 (33.5) 142 (15.6) 92 (10.1) 60 (6.6) 57 (6.3) 21 (2.3) 15 (1.7) 26 (2.9)
522 (57.5) 580 (63.9) 490 (54.0) 380 (41.9) 236 (26.0) 281 (30.9) 125 (13.8) 75 (8.3) 35 (3.9)
223 (24.6) 112 (12.3) 149 (16.4) 159 (17.5) 61 (6.7) 77 (8.5) 63 (6.9) 32 (3.5) 32 (3.5)
532 (58.6) 320 (35.2) 469 (51.7) 494 (54.4) 245 (27.0) 271 (29.8) 211 (23.2) 138 (15.2) 44 (4.8)
190 (20.9) 239 (26.3) 152 (16.7) 118 (13.0) 65 (7.2) 64 (7.0) 36 (4.0) 18 (2.0) 26 (2.9)
491 (54.1) 450 (49.6) 485 (53.4) 439 (48.3) 252 (27.8) 253 (27.9) 212 (23.3) 106 (11.7) 36 (4.0)
292 (32.2) 236 (26.0) 56 (6.2) 59 (6.5) 203 (22.4) 33 (3.6) 14 (1.5) 7 (0.8) 8 (0.9)
683 (75.2) 485 (53.4) 332 (36.6) 341 (37.6) 536 (59.9) 203 (22.4) 85 (9.4) 49 (5.4) 10 (1.1)
not suitable for the treatment of metabolic diseases. There are some limitations in this study. First, a recall bias may exist when answering the questions regarding the proportion of patients. It is currently not possible to calculate the exact number of patients using the National Health Insurance Service data. Second, although Do-InSeung-Gi-Tang was included in the item ‘it is necessary for health insurance to cover herbal medicine’, it is already covered under health insurance. Third, there are several questionnaires for diagnosing bloodstasis, therefore it would been better to have investigated how TKM doctors diagnosed blood stasis. Nonetheless, this study attempted to collect as many opinions of TKM doctors as possible on the association between blood stasis and metabolic diseases.
(405, 44.6 %) and heart diseases (275, 30.3 %) were regarded as diseases related to blood stasis, and hyperlipidemia had the highest association with blood stasis among hypertension, hyperlipidemia and diabetes mellitus. Hyperlipidemia is a condition involving abnormally increased levels of blood lipids and lipoproteins. The excess lipids in the walls of the arteries form blood clots thus leading to blood stasis [13,14]. Approximately 80 % of the 908 respondents supported the belief that ‘Herbal medicines combined with conventional drugs are good for managing blood pressure, blood sugar, and blood lipids.’ There are several previous clinical trials of herbal medicines combined with Western medicine for the treatment of metabolic diseases [15,16]. In Wang’s study [15], Yiqi Huaju Qingli Herb Formula combined with Western medicine significantly lowered blood glucose and improved lipid metabolism in metabolic syndrome patients. In Xian’s study [16], Shenmai injection, which is extracted from Panax ginseng, and Ophipogon japonicas in addition to standard medicines improved chronic heart disease and coronary artery disease compared to placebo with standard medicines. Regarding the appropriate herbal medication, Gyejibongnyeonghwan and Cardiotonic pills were selected by a high percentage of participants for each disease. Gyejibongnyeong-hwan has been used mainly for treating primary dysmenorrhea or uterine myoma with blood stasis [17]. On the other hand this formula is also regarded as a therapeutic drug for decreasing blood lipids or preventing heart diseases [18]. Cardiotonic pills, such as the Danshen dripping pill, is a representative herbal medicine for stable angina pectoris in some countries [19,20]. It is now undergoing phase III clinical trials for drug development in the United States under the lead of a Chinese pharmaceutical company [21]. Salvia miltiorrhiza, the main herb of Cardiotonic pills is effective to remove blood stasis and promote blood circulation [22]. Xuefu-zhufu decoction was also selected as the appropriate herbal medicine by a high percentage of participants. It has been widely used in China for the treatment of heart diseases such as coronary artery disease and atherosclerosis and is helpful for dissipating blood stasis [23,24]. Gyejibongnyeong-hwan and Cardiotonic pills were also ranked first and second among the most necessary herbal medicine to be covered by health insurance. Dangguixu-san ranked third since it is an effective drug for treating the pain caused by blood stasis rather than metabolic diseases [25]. Most respondents (n = 463, 51.0 %) thought that the expensive cost compared to conventional drugs was the biggest reason why herbal medicine is not frequently used for metabolic disease treatment. Accordingly, it is important to have insurance coverage and provide patients medical service at a low cost to raise herbal medicine prescription rate. Only two prescriptions (i.e. DaehwangmokdanpiTang, Do-In-Seung-Gi-Tang) for blood stasis were included in the 56 herbal medicines covered by health insurance [26], however they are
5. Conclusions This study investigated the opinion of TKMs on the association between metabolic diseases and blood stasis. Most experts agreed that metabolic diseases were highly associated with blood stasis and that herbal medicines combined with conventional drugs were effective for the treatment of metabolic diseases. The results of this survey may provide basic data for future clinical studies and health policy research.
Funding This study was supported by a grant from the Korea Institute of Oriental Medicine, Republic of Korea (KSN2013210).
Availability of data and materials The data used for this study are available from the corresponding author upon request.
Consent for publication Not applicable.
CRediT authorship contribution statement Soobin Jang: Conceptualization, Methodology, Validation, Investigation, Writing - original draft, Visualization. Mi Mi Ko: Methodology, Formal analysis, Data curation, Writing - review & editing. Byoung-Kab Kang: Software, Validation, Formal analysis, Writing - review & editing. Jeeyoun Jung: Investigation, Resources, Writing - review & editing, Supervision, Project administration, Funding acquisition. 4
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Declaration of Competing Interest
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