ABSTRACT
Background
In China, on more than 100 weekends or holidays, only on-duty cardiologists are available during admissions. This study aimed to analyze the impact of admission time on major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI).
Methods
This prospective observational study enrolled patients with AMI between October 2018 and July 2019. The patients were assorted into off-hour (admitted on weekends or national holidays) and on-hour groups. The outcome was MACEs at admission and 1 year after discharge.
Results
A total of 485 patients with AMI were enrolled in this study. The occurrence of MACEs was significantly higher in the off-hour group compared with the on-hour group (P < .05). Multivariate regression analysis showed that age (HR = 1.047, 95% CI: 1.021–1.073), blood glucose level (HR = 1.029, 95% CI: 1.009–1.050), multivessel disease (HR = 1.904, 95% CI: 1.074–3.375), and off-hour hospital admission (HR = 1.849, 95% CI: 1.125–3.039) were all independent risk factors for in-hospital MACEs, while percutaneous coronary intervention (HR = 0.210, 95% CI: 0.147–0.300) and on-hour admission (HR = 0.723, 95% CI: 0.532–0.984) were protective factors for MACEs 1 year after discharge.
Conclusion
The “off-hour effect” still existed in patients with AMI, and the risk of MACEs in the hospital and 1 year after discharge was higher for off-hour admission.
In China, the prevalence of coronary heart disease (CHD) continues to increase, and CHD remains the leading cause of death in both urban and rural areas (Citation1,Citation2). A pronounced tendency toward younger-age CHD has been reported due to anxiety symptoms and occupational stress among young workers, with progressing economic impact on society (Citation3). The timely and effective opening of the infarct-related blood vessels can reduce not only the incidence and mortality of heart failure in patients with acute myocardial infarction (AMI) and ST-segment elevation myocardial infarction (STEMI) but also improve the quality of life and prognosis (Citation4).
Previous studies pointed out that the mortality rate of patients admitted during weekends was often higher, and such patients were more often associated with complications (Citation5,Citation6). Part of the reason for the high mortality rate of patients with AMI is that the incidence of vascular reconstruction surgery on holidays is low; also, fewer medical personnel are available on duty, while patients need to wait longer to provide informed consent (Citation7). This phenomenon is called a “weekend effect” or “holiday effect,” meaning that patients with AMI admitted to the hospital on holidays have a higher risk of death and a poorer prognosis compared with patients admitted on weekdays (Citation8).
However, other studies reported no difference in the long-term clinical results of patients with AMI/STEMI, regardless of the admission time (Citation9–11). Although patients admitted to the hospital on holidays underwent cardiac catheter surgery with a delay compared with those on working days, it did not affect the prognosis of some patients with non-ST-segment elevation myocardial infarction (NSTEMI) (Citation12). Moreover, the duty form of cardiologists did not affect the prognosis of patients with AMI who were admitted on nonworking days, as clinical medical staff provided high-quality treatment for patients on nonworking days (Citation13). Therefore, it is essential to re-assess the most recent developments in this field, especially during the COVID-19 pandemic, when medical professionals need to find a balance between timely treatment and infection control procedures (Citation14).
Therefore, this study aimed to analyze the impact of admission time on major adverse cardiovascular events (MACEs) in patients with AMI.
Materials and methods
Study design and participants
This prospective observational study included patients with AMI in Tianjin Baodi District People’s Hospital between October 2018 and July 2019. The AMI was diagnosed according to the fourth edition of the “General Definition of Myocardial Infarction” (Citation15) as follows (Citation1): serum troponin increased more than 99%ile of the normal reference value (Citation2); clinical symptoms of acute myocardial ischemia (Citation3); new ischemic electrocardiogram changes and formation of pathological Q wave (Citation4); imaging changes of newly developed segmental ventricular wall motion disorder; and (Citation5) coronary angiography – or autopsy-confirmed coronary thrombosis. The exclusion criteria were as follows (Citation1): patients with a serious lack of clinical data (Citation2); multiple organ failure (Citation3); inability to cooperate with treatment (Citation4); transfer to another hospital within 12 h of admission (Citation5); hospital stays more than 14 days (Citation6); malignant tumor or congenital coronary artery malformation; and (Citation7) patients with a history of percutaneous coronary intervention (PCI) or coronary artery bypass grafting. The study protocol was approved by the Human Ethics Committee of Tianjin Baodi District People’s Hospital. All patients signed the informed consent form.
Data collection
The clinical data of patients were collected, including (Citation1) demographic data, previous history (diabetes, hypertension, smoking history, cerebral infarction, and hyperlipidemia), admission heart rate, blood pressure, echocardiography (left ventricular ejection fraction (LVEF) %, left anterior descending branch (LAD), and LA), door-to-balloon dilatation time (D-to-B), and hospital treatment, collected through the clinical electronic medical record system; and (Citation2) the first ECG, myocardial enzyme, and troponin results on admission. The diagnosis of AMI (STEMI and NSTEMI) was made using (Citation3) laboratory examination indicators during hospitalization (including Troponin T (TNT) peak, creatine kinase isoenzyme (CKMB) peak, NT-proBNP, low-density lipoprotein (LDL), D-dimer, and random blood glucose); and (Citation4) in-hospital revascularization treatment (PCI and drug thrombolysis). The number and location of diseased vessels were recorded if patients underwent PCI (Citation5). The malignant arrhythmia (except reperfusion arrhythmia), the major adverse cardiovascular events (MACE), and the application of an aortic balloon pump during hospitalization were recorded. The off-hour admission was defined as weekdays 17:01 p.m. to 7:59 a.m., weekends, and holidays. The rest of the time was defined as on-hour admission (weekdays 8:00 a.m. to 17:00 p.m.). All attending physicians, irrespective of the work shift, belong to the same team of physicians sharing the same practice guidelines and consensuses. Each shift includes at least an associate chief physician (with>10 years of experience) and an attending physician (with>5 years of experience). In addition, according to life and work shift circumstances, the physicians are interchangeable between the two groups.
Outcomes
The outcome of this study was MACEs, including the short-term incidence of MACEs in the hospital and the incidence of MACEs 1 year out of the hospital. MACEs included cardiac death, recurrent myocardial infarction, recurrent refractory angina attack, stent thrombosis, newly diagnosed acute congestive heart failure requiring hospitalization, malignant arrhythmia (except reperfusion arrhythmia), severe gastrointestinal bleeding, and cerebral infarction (Citation12,Citation16).
Telephone follow-up or outpatient follow-up was performed for patients with AMI 1 year after discharge by trained doctors or nurses blinded to the purpose of this study. The follow-up included analysis of electrocardiogram, dynamic electrocardiogram or patient medical history, and readmission data.
Statistical analysis
All data management and visualization were performed in SPSS 25.0 statistical software (IBM, NY, USA). The measurement data conforming to the normal distribution were expressed as X ± s, and the independent-samples t-test was used for comparison between the two groups. The enumeration data were expressed as rate or composition ratio, and the comparison between groups was performed using the χ2 test. The univariate and multivariate Cox regression analyses were used to analyze the influencing factors of MACEs in patients with AMI in the hospital and 1 year after discharge. Variables with P < .05 and clinically significant variables were further included in the multivariate Cox regression analysis (method: Wald forward, conditional). A P value<0.05 indicated a statistically significant difference
Results
A total of 485 patients were included in this study (323 male and 162 female). Of these, 277 had STEMI, and 208 had NSTEMI. The on-hour group consisted of 319 patients, whereas the off-hour group consisted of 166 patients. No significant difference was found in age, sex, type of myocardial infarction, smoking history, hypertension history, and cerebral infarction history between the two groups (P > .05). The analysis of risk factors for CHD revealed that the prevalence of diabetes (39.8% vs. 25.7%, P = .001) and hyperlipidemia (51.2% vs. 37.9%, P = .005) was higher in the off-hour group than in the on-hour group.
In terms of admission data, no significant difference was found in the heart rate, systolic blood pressure, and the first NT-proBNP, LDL, and D-dimer values between the two groups (P > .05). However, LVEF% was significantly lower, while the number of patients with Killip class II – IV and the peak value of TNT and CKMB were higher in the off-hour group than in the on-hour group (all P < .001). The results of coronary angiography showed that the incidence of combined three-vessel disease variables was similar in the off-hour and on-hour groups (P = .607). No difference was observed in the D-to-B time of PCI treatment between patients admitted on-hour and off-hour (P = .702), but the rate of PCI treatment in the on-hour group was higher than that in the off-hour group (P = .040) (). The D-to-B was similar between the two groups (65.65 ± 27.31 vs. 62.51 ± 11.38 min, P = .262).
Table 1. Baseline characteristics of the study patients.
One or more of the MACEs in the same patient were recorded as one MACE. One hundred-fifty patients had MACEs, which was significantly lower in the on-hour group [78 patients, 24.5% compared with 72 patients (43.4%) in the off-hour group, P < .001]. The incidence of acute heart failure, recurrent refractory angina pectoris, and severe gastrointestinal bleeding was significantly higher in the off-hour group than in the on-hour group, but the in-hospital mortality in the two groups was comparable (P = .632) ().
Table 2. Summary of major adverse cardiovascular events in hospital.
The multivariate cox logistic regression analysis showed that age (HR = 1.047, 95% CI: 1.021–1.073), random blood glucose (HR = 1.029, 95% CI: 1.009–1.050), multivessel disease (HR = 1.904, 95% CI: 1.074–3.375), Killip Class II – IV (HR = 2.811, 95% CI: 1.669–4.734), and off-hour hospital admission (HR = 1.849, 95% CI: 1.125–3.039) were all risk factors for MACEs in patients with AMI (P < .05, ). The off-hour admission was an independent risk factor for MACEs in patients with AMI (P < .05, ).
Table 3. Multivariate Cox regression analysis of risk factors for major adverse cardiovascular events during the hospital stay.
During the 1-year follow-up after discharge, 73 MACEs (44%) occurred in the off-hour group, and 98 MACEs (30.7%) occurred in the on-hour group (P = .004). Age (HR = 1.048, 95% CI: 1.031–1.065) and LDL (HR = 1.132, 95% CI: 1.050–1.221) were independent risk factors for MACEs, while PCI treatment (HR = 0.723, 95% CI: 0.532–0.984) and on-hour admission (HR = 0.723, 95% CI: 0.532–0.984) were protective factors for MACEs in patients with AMI ().
Table 4. Multivariate Cox regression analysis of risk factors for major adverse cardiovascular events 1 year after discharge.
During this time, 15 (3.17%) patients were lost to follow-up. The ratio of recurrent refractory angina pectoris was higher in the off-hour group than in the working-day group (13.3% vs. 6.9%). No difference was found in mortality, the incidence of recurrent myocardial infarction, the incidence of acute heart failure, the incidence of malignant arrhythmia, and the incidence of stroke between the two groups (P > .05, ).
Table 5. Summary of major adverse cardiovascular events 1 year after discharge.
Discussion
This study showed that the incidence of MACEs in the hospital and 1 year after discharge was higher for patients admitted off-hours. Furthermore, off-hour hospital admission was an independent risk factor for in-hospital MACEs, whereas on-hour admission was a protective factor for MACEs 1 year after discharge. These findings suggested that the “off-hour effect” still existed in patients with AMI in Tianjin, with the long-term and short-term prognoses being worse for patients admitted during the off-hours than those admitted during on-hours.
The observed differences could not be explained only by the lower number of specialists available during admission (Citation17). The possible reasons might also include delayed PCI treatment, higher symptom severity that prompted patients to seek help during holidays, and acute stress factors. Previous studies showed that a relatively higher incidence of adverse events during hospitalization on holidays might be related to the fact that off-hour patients had longer D-to-B (hospital door-to-balloon dilation time) and S-to-B (symptom onset to balloon dilation time) (Citation8). A study of 68 439 patients by Magid et al. (Citation7) reported that the outcomes of patients with STEMI onset on holidays were worse than the outcomes on workdays, which were explained by the delayed PCI treatment. A study by Kostis et al. (Citation18) included 23 164 patients and reported that the higher mortality rate in patients with AMI admitted on weekends was partly due to the lower incidence of invasive therapy in the acute phase of illness. A study by Rathore et al. (Citation19) showed that the delay in emergency PCI treatment for patients with AMI caused by any reason would lead to an increase in the mortality of patients, and every 1/4-h delay in D-to-B time would increase the mortality of patients by 10%–15%. In this study, no statistically significant difference was found in D-to-B time between the two groups, indicating no delay in interventional treatment for patients admitted off-hours. Still, the study found that the incidence of MACE events in the off-hour group was higher in the hospital and outside the hospital. At least partly, this difference might be related to the lower rate of PCI treatment in off-hour patients, which was in line with the conclusions reported by the studies by Magid and Rathore and the results of a recent meta-analysis by Yu et al. (Citation20). In addition, the results of the present showed that PCI treatment was a protective factor for MACEs 1 year after discharge. However, the decisive factor hypothesis needs to be further tested in the future due to the lack of S-to-B time in this study.
Compared with patients with STEMI in other countries, Chinese people are reported to be more pain tolerant (Citation21), and often only severe symptoms prompt them to seek help during holidays. Most of the admitted patients have their first episode of AMI, and therefore they may not quickly respond to emergencies and visit the hospital due to the lack of recognition (Citation20). This may explain why previous studies showed that patients with STEMI admitted to the hospital off-hours had more severe symptoms than others admitted on-hours, as measured by cardiogenic shock or the Killip scale (Citation7,Citation22). Accordingly, the prognosis of patients with STEMI is related to the difference in severity (Citation23). A study by Isogai et al. (Citation24) found that the complications in patients with AMI admitted to the hospital on holidays, such as particularly high mortality, were associated with increasing Killip class from grade II to grade IV. The selective bias is considered to be a potential mechanism of the “holiday effect,” that is, more critically ill patients may be admitted on weekends, while patients with relatively mild conditions may choose to wait for the working day, which is consistent with our research results. Moreover, the number of patients with cardiac function Killip class II – IV in the off-hour group in this study was significantly higher than that in the on-hour group, and the value of left ventricular ejection fraction indicated by echocardiography was lower. The peak value of TNT in the off-hour group was higher, indicating that the myocardial infarction area of patients was larger, and the condition was more often complicated with diabetes and hyperlipidemia, which are confirmed by many studies as the risk factors affecting the prognosis of patients with CHD (Citation25,Citation26).
Several lifestyle-related factors may have an additional impact on the MACE rate during holidays and thus influence the results in a time-effect manner. Sudden anger, anxiety, sadness, and stress all increase the risk of myocardial infarction (Citation27), and these external factors during holidays have been repeatedly confirmed to be related to the high-risk prevalence of myocardial infarction. In particular, Mohammad et al. (Citation28) conducted a study in 2018 on the number of daily myocardial infarction cases worldwide covering 16 years, showing that the incidence of AMI was high during Christmas and midsummer nights. Related activities and mood swings during holidays may lead to increased oxygen demand in older and more severe patients, resulting in myocardial infarction secondary to ischemia (Citation29). Moreover, irregular diet during holidays, irregular working hours, and other factors can often lead to an overall lower health level (Citation26). In this study, the incidence of gastrointestinal bleeding in the off-hour group was significantly higher, which might be related to the occurrence of gastrointestinal stress symptoms caused by irregular diet and irregular working and rest patterns during the holidays (Citation30). These findings might have important implications for clinical practice, suggesting that an appropriate management process is needed for patients with AMI admitted off-hours to take into account all potential factors influencing prognosis.
This study had several limitations. First, the sample size of this study was comparatively big, but it mainly comprised single-center data, leading to some bias in the data collection process. Second, this study lacked data on the time from onset to the first medical contact (SO-to-FMC), the number of white blood cells, and the platelet aggregation rate, as well as detailed information on active medical care. Finally, the results might be region specific and need to be further confirmed by large-scale, multi-center clinical studies.
In conclusion, the “holiday effect” still existed in patients with AMI in Tianjin, and the risk of MACE events in the hospital and 1 year after discharge was higher for off-hour admission.
Ethics approval and consent to participate
This work has been carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association. This study was approved by Tianjin Chest Hospital, and all participants provided written informed consent.
Availability of data and materials
All data generated or analyzed during this study are included in this published article
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
References
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