As a traditional medical model shifts to a social-psychological-biological model of modern medicine, much attention is paid to the effects of psychological stress and mental disorders on coronary heart disease (CHD) [
As a branch of traditional Chinese medicine, Five-Animal Frolics Exercise (FAE) follows the social-psychological-biological model of modern medicine and coordinates the limbs and body by imitating animal gait [
This study belongs to a single-blind randomized trial. All procedures were approved by human research ethics committee of our hospital and conform to the provisions of the Declaration of Helsinki [
The cases included in this study were the patients who were discharged at our hospital from March 1, 2017, to March 1, 2018.
The patients who met diagnostic criteria for CHD, anxiety, and depression were included. CHD was diagnosed according to the “Diagnostic Criteria for Coronary Atherosclerotic Heart Disease” issued by the Ministry of Health of the People’s Republic of China in 2010; the diagnostic criteria for anxiety and depression refers to the Chinese Classification of Mental Disorders (Revision 3, CCMD-3) [
The patients who could not take some exercise and did not provide consent written form or history clinical data were excluded.
The sample size estimation of this study was due to the fact that there are few clinical studies on the therapy based on a FAE. Therefore, considering the sample size of each group, 100 cases of the lowest sample size of clinical research were the initial targets. Based on the actual situation, two aspects were considered. According to the estimated number of inpatients in our hospital, it was estimated that the number of patients who were diagnosed with CHD and met the inclusion and exclusion criteria in the annual inpatients was more than 100. The subjects who voluntarily joined the clinical study may be lower than the 100 cases. According to the period of the clinical study, the total duration was one year, and the follow-up period was 3 months; the shedding rate was set at 20%. Therefore, the final sample size of each group was 60, and the final number of total sample size was 120.
A total of 120 patients were assigned into the control group (CG, normal nursing care) and the experimental group (EG, FAE intervention), and the allocation ratio was 1 : 1 according to a random number produced by computer (Figure
CONSORT flow diagram. EG, the patients received FAE. CG, the patients received routine nursing care. The follow-up was three months.
The therapy was performed in the EG group based on conventional treatment of the CG group. FAE were trained as follows: training time was selected at 4 pm daily during the patient’s hospital stay. The location was selected in the open space of ward corridor. The exercise video was provided by our hospital for Loop Playback. The patients in the EG group were guided by five presentational trainers to learn FAE and mimic the movements of five different animals (tiger, deer, bear, monkey, and bird) and focused on massaging and strengthening specific internal organs. The patient’s breath required a nasal suction, when the inhalation touched the upper tip of the tongue, the tongue tip was flat when exhaling, and the respiratory rate was 8–10 beats/min. The patients were practiced regularly, and meditation time was 30–60 min at one time with low-decibel meditation light music background and professional guidance.
The test periods were 3 months in total, including 1 month of treatment and 3 months of observation. Follow-up was performed at 1 month and 3 months after the enrollment. Weekly telephone follow-up was performed to strengthen the subject’s compliance and minimize the subject. The rate of dropout of the tester was also promptly excluded from subjects with poor compliance. There were 4 on-site visits at the month 0, 1, and 3. The telephone interviews determined the number of monthly telephone follow-ups based on the subject’s compliance at our hospital.
General conditions included the current medical therapy, history, diagnosis, vital signs, physical examination, and the type, amount, and start and end time of the combined medication. Safety indicators included blood routine, urine routine, liver and kidney functions, blood lipids, blood sugar, BNP, 6-minute walk test, and Brog sensor score. Disease evaluation indicators included the HAMD, HAMA, Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), Short Form 36 Health Survey Questionnaire (SF-36), and Pittsburgh Sleep Quality Index (PSQI).
The statistical scale was measured at baseline and after 1 month and 3 months of treatment, and the amount of change in the score and the improvement rate were calculated; the improvement rate was given as (pretreatment score−treatment score)/pretreatment score × 100%; total effective rate = cure rate + significant efficiency + effective. The following criteria were used: recovery, improvement rate of 75%; markedly effective, 50% < improvement rate < 75%; effective, 25% < improvement rate < 50%; and invalid, improvement rate <25%.
If an adverse event occurred, it should be recorded in time, and the corresponding method was taken according to the severity of the adverse event. The final result was recorded and analyzed if the adverse event disappeared. They should be reported to the responsible person for discussion and treatment if serious adverse events occurred.
5 mL blood was obtained from each participant, and serum was prepared via centrifugation at
The data were analyzed by using SPSS 20.0 statistical software. Count data were examined by using the Pearson 2 test. The two groups were compared by the LSD method if the data were in accordance with the normal distribution and expressed by the mean standard deviation (S.D.); they were represented by median (P25 and P75) and analyzed by a nonparametric test if they were not normally distributed. The data were compared in a single group before and after treatment, and a paired sample
In this study, no subjects were excluded from the study, and 120 subjects finished the present experiment, and the follow-up was 3 months (Figure
Clinical baseline characteristics between two groups.
Parameters | EG ( | CG ( | |
---|---|---|---|
Gender (male) | 24 (40%) | 24 (40%) | — |
Age (yr) | 61.00 ± 8.93 | 63.10 ± 10.04 | 0.763 |
Combined with hypertension | 45 (75%) | 42 (70%) | 0.816 |
Combined with diabetes | 24 (40%) | 24 (40%) | — |
Combined with tuberculosis | 57 (95%) | 51 (85%) | 0.615 |
Abnormal ECG check | 33 (55%) | 36 (60%) | 0.805 |
Total cholesterol | 3.89 ± 1.32 | 3.82 ± 1.03 | 0.965 |
Triglyceride | 1.50 ± 0.92 | 1.82 ± 0.78 | 0.328 |
Low-density lipoprotein | 2.04 ± 1.06 | 1.91 ± 0.63 | 0.877 |
Fasting blood sugar | 6.60 ± 1.40 | 7.28 ± 2.62 | 0.372 |
BNP | 87.02 ± 79.40 | 99.96 ± 138.24 | 0.868 |
6-minute walk test | 527.78 ± 49, 77 | 539.25 ± 57.59 | 0.135 |
Brog feels the score | 11.89 ± 1.61 | 11.25 ± 1.68 | 0.409 |
HAMD, HAMA, SAS, and SDS were measured in the two groups. The anxiety and depression scales were scored at baseline (month 0), the first follow-up (month 1, primary outcomes), and the last follow-up (month 3, secondary outcomes). The first follow-up and baseline were calculated as the amount of change (I). The change in the final follow-up from the baseline was calculated as the amount of change (II).
Before intervention, the statistical difference for HAMD, HAMA, SAS, and SDS was insignificant between the two groups (
Comparison of four anxiety depression scales between two groups.
Parameters and time points | EG | CG | ||
---|---|---|---|---|
HAMD | 0 month | 12.0 (10.0, 14.0) | 11.5 (8.3, 14.8) | 0.908 |
1 month | 7.5 (5.3, 10.0) | 9.5 (7.0, 12.0) | ||
3 months | 5.0 (4.0, 6.0) | 8.0 (5.3, 10.0)# | ||
Amounts of change (I) | 4.0 (2.3, 6.8)# | 2.0 (0.3, 3.8) | 0.015 | |
Amounts of change (II) | 7.0 (5.3, 8.8)# | 3.0 (2.3, 5.8) | 0.002 | |
HAMA | 0 month | 17.0 (15.0, 19.0) | 15.0 (12.0, 17.0) | 0.095 |
1 month | 10.0 (7.0, 12.0) | 12.0 (10.0, 14.0) | ||
3 months | 5.5 (5.0, 7.8)# | 9.0 (7.0, 12.0)# | ||
Amounts of change (I) | 8.0 (5.3, 9.0)# | 2.0 (2.0, 4.0) | <0.001 | |
Amounts of change (II) | 11.0 (9.0, 12.0)# | 5.0 (4.0, 7.8) | <0.001 | |
SDS | 0 month | 41.0 (39.3, 47.5) | 40.5 (35.3, 49.0) | 0.770 |
1 month | 34.0 (31.0, 36.0) | 35.0 (32.0, 44.3) | ||
3 months | 30.0 (29.3, 32.0)# | 34.0 (30.3, 40.8)# | ||
Amounts of change (I) | 7.0 (5.0, 10.0)# | 3.0 (1.0, 6.8) | 0.012 | |
Amounts of change (II) | 10.0 (8.3, 14.8)# | 5.5 (3.3, 8.0) | 0.005 | |
SAS | 0 month | 50.0 (51.0, 55.5) | 50.0 (50.0, 52.0) | 0.106 |
1 month | 41.0 (34.0, 43.5) | 45.0 (39.5, 48.8) | ||
3 months | 32.0 (31.0, 37.5)# | 40.0 (32.8, 44.3)# | ||
Amounts of change (I) | 14.5 (10.3, 18.0)# | 4.5 (3.0, 8.8) | <0.001 | |
Amounts of change (II) | 20.0 (15.3, 22.8)# | 8.5 (6.3, 17.0)# | <0.001 |
The PSQI scores of the two groups were recorded at baseline (month 0), the first follow-up (month 1), and the last follow-up (month 3). The statistical difference for PSQI scores at baseline was insignificant between the two groups (Table
Comparison of PSQI between two groups.
EG | CG | ||
---|---|---|---|
0 month | 14.0 (10.3, 15.0) | 11.0 (9.0, 13.8) | 0.100 |
1 month | 9.0 (6.5, 11.8) | 9.0 (7.3, 12.0) | |
3 months | 7.0 (5.0, 7.8)# | 8.0 (6.0.1 5)# | |
Amounts of change (I) | 3.0 (1.3, 6.8)# | 1.0 (0.0, 1.8) | 0.003 |
Amounts of change (II) | 6.0 (4.0, 8.0) | 2.5 (1.0, 4.0)# | 0.001 |
The percentage of total effectiveness of the PSQI efficacy of the two groups is described in Table
Comparison of curative effect of PSQI.
Groups | Therapeutic results | Total effective | ||||
---|---|---|---|---|---|---|
Healing | Significant effective | Effective | Invalid | |||
EG | 7 (35%) | 13 (65%) | 100%# | <0.001 | ||
CG | 1 (5%) | 2 (10%) | 6 (30%) | 11 (55%) | 45% |
The scores of the simple quality of life scale (SF-36) of the two groups were measured at baseline (month 0), the first follow-up (month 1), and the last follow-up (month 3). Except for body pain, the scores of the other factors were insignificant before intervention (Table
The comparison of life quality of SF-36 between two groups.
Parameters and time points | EG | CG | ||
---|---|---|---|---|
Physical functioning | 0 month | 88.0 (84.0, 100.0) | 85.0 (85.0, 95.0) | 0.430 |
1 month | 94.0 (88.0, 100.0) | 85.0 (80.0, 95.0) | ||
3 months | 100.0 (100.0, 100.0)# | 87.5 (81.3, 95.0)# | ||
Amounts of change (I) | 3.8 (0.0, 5.0)# | 0.0 (0.0, 0.0) | 0.295 | |
Amounts of change (II) | 5.0 (0.0, 10.0) | 0.2 (0.0, 5.0) | 0.003 | |
Physical role functioning | 0 month | 12.9 (0.0, 18.8) | 11.3 (0.0, 75.0) | 0.925 |
1 month | 25.0 (25.0, 50.0) | 0.0 (0.0, 87.5) | ||
3 months | 50.0 (50.0, 100.0)# | 37.5 (6.3, 100.0)# | ||
Amounts of change (I) | 21.0 (0.0, 25.0)# | 0.0 (0.0, 0.0) | 0.049 | |
Amounts of change (II) | 50.0 (25.0, 50.0)# | 12.5 (0.0, 43.8) | 0.003 | |
Body pain | 0 month | 84.0 (75.0, 100.0) | 79.0 (74.0, 100.0) | 0.042 |
1 month | 95.0 (88.0, 100.0) | 84.0 (74.0, 100.0) | ||
3 months | 92.0 (74.0, 100.0)# | 89.0 (76.5, 100.0)# | ||
Amounts of change (I) | 2.0 (0.0, 9.0) | 0.0 (0.0, 0.0) | 0.109 | |
Amounts of change (II) | 3.1 (0.0, 15.0) | 3.3 (0.0, 26.0) | 0.274 | |
General health perceptions | 0 month | 30.0 (25.0, 45.0) | 32.5 (20.0, 40.0) | 0.579 |
1 month | 45.0 (26.8, 53.8) | 32.5 (25.0, 45.0) | ||
3 months | 56.0 (45.0, 70.3)# | 52.5 (35.0, 67.0)# | ||
Amounts of change (I) | 3.6 (0.0, 13.8) | 1.2 (0.0, 3.8) | 0.637 | |
Amounts of change (II) | 20.0 (5.5, 30.0) | 17.0 (5.0, 30.3) | 0.949 | |
Vitality | 0 month | 45.0 (41.0, 50.0) | 55.0 (45.0, 65.0) | 0.117 |
1 month | 55.0 (50.0, 68.8) | 55.0 (45.0, 65.0) | ||
3 months | 62.5 (55.0, 70.0)# | 57.5 (51.3, 73.8)# | ||
Amounts of change (I) | 10.0 (0.0, 18.8) | 0.0 (0.0, 0.0) | ≤0.001 | |
Amounts of change (II) | 15.0 (5.3, 23.8) | 5.0 (0.0, 10.0) | 0.073 | |
Social functioning | 0 month | 88.0 (75.0, 100.0) | 88.0 (65.3, 100.0) | 0.610 |
1 month | 88.0 (88.0, 100.0) | 88.0 (78.3, 100.0) | ||
3 months | 100.0 (100.0, 100.0)# | 100.0 (100.0, 100.0)# | ||
Amounts of change (I) | 5.0 (0.0, 12.8) | 0.0 (0.0, 0.0) | 0.172 | |
Amounts of change (II) | 12.0 (0.0, 13.0) | 12.0 (0.0, 34.0) | 0.728 | |
Emotional wellbeing | 0 month | 0.0 (0.0, 91.8) | 0.0 (0.0, 100.0) | 0.942 |
1 month | 50.0 (33.0, 100.0) | 0.0 (0.0, 100.0) | ||
3 months | 100.0 (67.0, 100.0)# | 33.0 (8.3, 100.0)# | ||
Amounts of change (I) | 23.0 (0.0, 33.0)# | 0.0 (0.0, 0.0) | 0.012 | |
Amounts of change (II) | 67.0 (8.3, 100.0)# | 0.0 (0.0, 33.0) | 0.003 | |
Mental health | 0 month | 50.0 (42.0, 60.0) | 48.0 (42.5, 56.0) | 0.073 |
1 month | 60.0 (49.0, 68.0) | 48.0 (42.5, 55.8) | ||
3 months | 68.0 (60.0, 72.0)# | 56.0 (48.0, 64.0)# | ||
Amounts of change (I) | 8.0 (0.0, 18.5)# | 0.0 (0.0, 0.0) | 0.001 | |
Amounts of change (II) | 17.0 (1.0, 24.0) | 4 (−0.8, 13.5) | 0.062 | |
Perception of changes in health | 0 month | 25.0 (25.0, 25.0) | 25.0 (25.0, 50.0) | 0.666 |
1 month | 37.5 (25.0, 50.0) | 25.0 (25.0, 50.0) | ||
3 months | 50.0 (25.0, 50.0)# | 50.0 (25.0, 50.0) | ||
Amounts of change (I) | 0.0 (0.0, 25.0) | 0.0 (0.0, 0.0) | 0.322 | |
Amounts of change (II) | 15.0 (0.0, 25.0) | 0.0 (0.0, 25.0) | 0.002 |
All subjects had no abnormalities in both groups during blood tests, urine routine, and liver and kidney function tests during the clinical study. Combined with BNP, the 6-minute walk test, and Brog sensory score at baseline (month 0), the subjects of two groups had better cardiac function and performed the exercises or regular exercise (walking, cycling, and jogging.).
During the 0-week period, the number of adverse events was two, the symptom was diarrhea, one was from the EG group, and the other occurred during the taking medicine. The tester did not have any further adverse events. There were no serious adverse events between the two groups.
Before FAE intervention, the statistical difference for miR-124 (Figure
Relative levels of miR-124 and miR-135 in the patients with coronary heart disease. EG and FAE were used. CG, a control group.
The Pearson correlation coefficient test showed that the increase in the levels of miR-124 and miR-135 would result in the increase in the scores of SAS (Figures
Pearson correlation coefficient analysis of the relationship between relative levels of miR-124 and miR-135 and the values of SAS and SDS. (a) The relationship between relative levels of miR-124 and the scores of SAS. (b) The relationship between relative levels of miR-135 and the scores of SAS. (c) The relationship between relative levels of miR-124 and the scores of SDS. (d) The relationship between relative levels of miR-135 and the scores of SDS. There is a strong positive relationship if rho value falls within 0.5 and 1. There is a strong negative relationship if rho value falls within −0.5 and −1.
The differences for the changes of HAMD, HAMA, SDS, SAS, and PSQI scores were significant between the two groups (
After a 3-month intervention, serum levels of miR-124 and miR-135 and the scores of the HAMD/HAMA, SAS, SDS, and PSQI in the EG group were lower than those in the CG group, while SF-36 scores in the EG group were higher than those in the CG group. Serum levels of miR-124 and miR-135 had a strong positive relationship with SAS and SDS. The results suggest that miR-124 and miR-135 may be candidate biomarkers in the diagnosis of the CHD patients with depression and anxiety. The study suggests that FAE can control the symptoms related to anxiety and depression and improve sleep quality and life quality in CHD patients by affecting serum levels of miR-124 and miR-135. The results were consistent with a previous report that FAE intervention improved anxiety and emotional disorders in the patients [
According to the anxiety and depression scores, the patients had different degrees of mild-to-moderate anxiety and depression before the intervention. After the implementation of FAE, the anxiety and depression of patients were alleviated and improved, further demonstrating that psychological intervention promoted the mental health of patients. The number of anxiety and depression in the two groups decreased after intervention, but the number of anxiety and depression in the EG group was significantly lower than that in the CG group (
There is increasing strong evidence supporting the integrated effectiveness of mind-body treatments (nonpharmacological interventions) for heart disease [
There were some limitations in the present work. The subjects were only included at our hospital, which had certain geographical restrictions, which led to some selection biases. The four anxiety scales used in this study were credible in the psychiatric reliability. However, for nonpsychiatric diseases and nonpsychiatric physicians, their reliability may be affected because they were not analyzed by psychiatrists, and the diagnosis of emotional disorders only included anxiety and depression. FAE is only popular in China and seldom known in other countries. The detailed molecular mechanism on how FAE can affect miRNA remains unclear. In the comparison of life quality of SF-36 between two groups, the difference of the amounts of change (I) of vitality and mental health was statistically significant between the EG group and the CG group. But the difference of the amounts of change (II) of vitality and mental health between the EG group and the CG group was statistically insignificant. The reasons may be caused by the following reasons: (1) the study was performed in the small population, and some bias will be induced (
The EG group has better improvement in the anxiety and depression scale (HAMD, HAMA, SAS, and JDS), PSQI, curative effects, and SF-36. Serum levels of miR-24 and miR-135 had a strong positive relationship with SAS and SDS scores. The study suggests that FAE inhibits the risk of anxiety and depression and improves sleep quality and life quality in CHD patients by affecting serum levels of miR-24 and miR-135. We recommend that the CHD patients should insist on practicing FAE to prevent the risk of mental diseases, such as depression and anxiety. On the other hand, a long-term study in a larger population is needed to confirm the present conclusion.
The data for the current study are available from the corresponding author upon reasonable request.
The authors declare that there are no conflicts of interest.
Jun Jiang, Qingbao Chi, Yuting Wang, and Xue Jin designed and performed the present experiments and analyzed all data. Shui Yu developed the overview and involved in writing the article. All authors agreed the final submission.
The authors are very grateful to all the patients in the study. The authors also thank Professor Qi Song and Chun Sun for supporting technique help. The study was performed by using the financial support from the Talent Creative Projects of the First Hospital of Jilin University (grant no. JLU2019CC).