Study design and setting
From January 2021 to December 2021, a double-blind, randomized, parallel controlled clinical trial was conducted in the Department of Cardiology at Dongjie and Jinshan hospitals, Fujian Provincial Hospital, Fuzhou, China. This trial was registered as ChiCTR2300072730.
Inclusion and exclusion criteria
A total of 200 patients with ACS who were recruited to Dongjie Hospital and Jinshan Hospital of Fujian Provincial Hospital between January 1 and December 31, 2021, consented to participate in the trial. The inclusion criteria were as follows: (1) successful coronary angiography (the smooth execution of the procedure without adverse events or complications); (2) age between 18 and 79 years; (3) participants or their statutory guardians signed written informed consent to participate. The exclusion criteria were as follows: (1) severe liver, brain, kidney, digestive, respiratory system diseases, or any other serious systemic illnesses (impact has reached a level where they pose a significant threat to the patient’s health or substantially impair daily functioning); (2) NYHA functional class 4; (3) abnormal electrocardiograms (ECGs) (deviations from the normal ECG pattern), particularly when symptoms worsen or become unstable; (4) cardiogenic shock; (5) history of mental illness, including but not limited to schizophrenia (ICD-10: F20.x), schizoaffective disorder (ICD-10: F25.x), bipolar disorder (ICD-10: F31.x), or any previous diagnosis of depression; (6) sedative drug use; (7) presence of cognitive impairment or uncooperativeness; (8) Parkinson’s disease or anxiety disorder; (9) acute onset of various acute infections (a swift onset of microbial invasion, leading to sudden and severe symptoms, with a brief duration and an immediate immune response), fevers (an increase in body temperature beyond the normal range), or other systemic diseases.
Randomization and blinding
In this study, we utilized computer-generated randomization to assign participants to either the early exercise intervention group or the standard treatment group. The randomization sequence was generated by a statistician who was not involved in the study, using SAS software’s PLAY PLAN program. This sequence was then securely sealed within opaque envelopes, each consecutively numbered, and was overseen by another researcher not participating in the subsequent assessments. Once eligible participants had completed their baseline measurements, these sealed envelopes were handed over to the implementing researchers, ensuring the confidentiality of the random allocation process. The random sequence was only accessible to the coordinator, ensuring blinding of physicians and study personnel regarding the hypothesis, group assignment, intervention protocols, and study endpoints.
During the intervention implementation, those responsible for conducting the exercise programs were unable to be blinded, as they performed the interventions. However, efforts were made to maintain blinding for the principal investigator, who remained unaware of the assigned treatments throughout the data collection period, ensuring the integrity of the double-blind design. Participants were explicitly instructed not to engage in discussions about their treatments with the principal investigator or the interventionists. Instead, they were encouraged to seek guidance from an independent second exercise program implementer, further preserving the integrity of the double-blind nature of the study.
Ethical considerations
Our study was approved by the Ethics Committee of Fujian Provincial Hospital (Ethics Approval No. 202101041). All research subjects were ensured that they were volunteering and that they could leave the study anytime. The confidentiality of their data was strictly maintained.
Methods
All eligible patients underwent a demographic survey and baseline measurements, including the administration of the PHQ-9 questionnaire and blood pressure assessment upon admission. After admission, patients in both the early exercise training group and the control group received bedside ECG monitoring, oxygen inhalation, and routine nursing care, which included drug therapy, routine examinations, cardiac rehabilitation education, psychological counseling, and education.
Control group
In addition to receiving normal nursing care, the patients in the control group followed routine activity guidance, which included the following measures: (1) absolute bed rest for 3 days after admission to ensure the stability of the patient’s condition and facilitate adjustment to the new environment; (2) during bed rest, patients were advised to assume a supine or semisitting position to reduce cardiac load; (3) nurses and family members assisted patients in the control group with daily activities such as washing, eating, turning over, and defecating; and (4) starting from the third day after admission, patients were encouraged to engage in mobilization and exercise, gradually increasing the level of activity based on their individual condition. The duration of bed rest was extended if serious complications arose.
Trial group
The trial group followed an individualized early exercise rehabilitation program that was tailored to each patient’s cardiac function and progress in rehabilitation. The program included guidance on gradually increasing the exercise intensity and duration. Please refer to Table 1 for specific details of the program.
During early exercise rehabilitation nursing, close monitoring of the patient was essential. If any of the following situations occurred, immediate cessation of activity or reduction in future activity intensity was necessary: heart rate reaching or exceeding 120 beats per minute; systolic blood pressure decreasing by 20 mmHg (1 mmHg = 0.133 kPa) or increasing by 30 mmHg; elevation of the S-T segment on the electrocardiogram (ECG) by 2 mm or depression by 1 mm, along with severe arrhythmia; and excessive fatigue or the presence of symptoms such as dyspnea and chest pain reported by the patient.
Collection of baseline feature data
Data collection for the study was conducted using the hospital’s electronic information system. The collected data encompassed a wide range of variables, including (1) Demographic information: Sex; Age; Education level; Marital status; (2) Medical history: (Preexisting conditions such as hypertension, diabetes, heart failure, and malignant tumors); (3) Lifestyle factors: Smoking history; Drinking history; (4) Medical interventions: History of coronary intervention; (5) Admission details: Mode of admission; (6) Physiological parameters: Blood pressure measurements; (7) Laboratory test results: Results of relevant laboratory tests.
Collection of laboratory inspection data
Centrifugation of peripheral venous blood from both groups of patients (2000 revolutions per minute for 5 min) was followed by freezing the supernatant at -80 °C. The automatic biochemical analyzer Atellica, manufactured by Siemens Corporation, and the fluorescent immunoanalyzer MINI-VIDAS, manufactured by Biomeerier in France, were used in the analysis. The glucose oxidase method was utilized for fasting blood glucose determination, and the.
ELISA technique was employed for NT-proBNP and TnI measurements. All specimens were tested by the Clinical Laboratory of Fujian Provincial Hospital.
Measurement data
There were five researchers, each with specific responsibilities and following a blind approach: one was responsible for the assessment of PHQ-9 questionnaires before and after the intervention, one was responsible for the entry of baseline and laboratory indicators, one was responsible for the early exercise rehabilitation intervention, one was the early exercise program second implementer, and one was responsible for statistics and other analysis of the data.
Observation indicators
Baseline data of the two groups
The Patient Health Questionnaire-9 (PHQ-9) is an internationally recognized and widely used depression screening tool. It consists of nine questions that ask participants about the frequency and severity of specific depression symptoms they may have experienced over the past two weeks. On the usual depression scale, the PHQ-919 has the highest sensitivity (95%). It has 5 severity levels: “none” (total score of 0–4), “mild” (total score of 5–9), “moderate” (PHQ-9: total score of 10–14), “severe” (PHQ-9: total score of 15–19), and “very severe” (PHQ-9: total score of 20–27).
Primary outcomes
PHQ-9 score, fasting blood glucose, BNP, and troponin I at discharge. Changes in these parameters compared to baseline were evaluated.
Secondary outcomes
Analyzing subgroup variations and assessing the incidence of adverse events during the study period.
Adverse events
Adverse events were defined as cardiovascular events, such as arrhythmia, heart failure, and angina, caused by early exercise rehabilitation training. Such sequelae were recorded during the intervention period.
Statistical methods
The data were analyzed by SPSS 26.0. Data were described as frequencies, percentages (%), means and SD, or medians and ranges. Continuous variables that followed a normal distribution are herein described using x ± s (mean ± standard deviation); differences between the groups were determined by the t test. Continuous variables with a nonnormal distribution are described by M (P25, P75), which represents the median with the interquartile range. Differences between the groups were determined by the nonparametric Mann‒Whitney U test. To compare the changes in PHQ-9 scores and fasting blood glucose levels within the intervention group and control group before and after the intervention, the paired sample t test or the Wilcoxon test of two related samples was used. All tests were 2-tailed, and significance was set at a two-sided P value of less than 0.05.
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