Abstract
Background
Patients with acute coronary syndrome (ACS) remain at high risk for recurrent adverse cardiovascular events after discharge. Patient adherence to secondary prevention is poor. This study proposes a follow-up center-based secondary prevention program to assess whether a structured cardiologist-led follow-up and reexamination protocol influences ACS patient prognosis.
Methods
A total of 9,534 ACS patients undergoing coronary angiography were retrospectively included and divided into a reexamination group (n = 6,804) and a non-reexamination group (n = 2,730) according to whether they were reexamined within one year or not. The patients were followed up after discharge for 3 years, and clinical outcomes were recorded. The primary outcome was cardiac death.
Results
Reexamination within 12 months was significantly associated with a reduced risk of cardiac death (adjusted hazard ratio [aHR], 0.58; 95% confidence interval [CI], 0.44–0.75) at 3 years after ACS. Among patients who underwent reexamination, the risk of cardiac death was 50% lower (aHR, 0.50; 95% CI, 0.35–0.70) and 63% lower (aHR, 0.37; 95% CI, 0.20–0.67) in the high-frequency (more than or equal to 2 times within one year) and long-term (continued reexamination after the first year of follow-up) reexamination groups, respectively. Similar results were observed after propensity score matching analysis.
Conclusions
Participation in a structured follow-up and reexamination programme significantly reduces the risk of cardiac death among ACS survivors. Establishing a follow-up center could be of great significance in improving patient prognoses.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12916-025-04346-x.
Keywords: Acute coronary syndrome, Follow-up center, Reexamination, Cardiac death
Background
Acute coronary syndrome (ACS), characterized by acute myocardial ischemia, is a leading cause of death and disability worldwide [1, 2]. Secondary prevention after ACS is crucial for improving life quality and prolonging survival [3–7]. However, the reality is that patient adherence to secondary prevention is poor [8, 9]. Adherence to long-term therapies in chronic conditions in Western countries averaged 50% and was even lower in developing countries [10]. Strategies to improve ACS patients’ adherence to secondary prevention programs remain a focus of clinical research. The regular reexamination method led by the follow-up center and cardiologists still has significant potential in yielding greater clinical benefits. Therefore, a secondary prevention program based on a follow-up center was established, aiming at exploring to what extent a structured follow-up and reexamination plan (including risk assessment, pharmacological management, lifestyle guidance, and further appropriate intervention) would improve the prognosis of ACS patients as well as providing a theoretical basis for medical systems at all levels to establish cardiologist-led follow-up centers and implement effective secondary prevention programs more effectively.
Methods
Study design and population
This was a single-center, retrospective cohort study. Patients 18 years or older with ACS who underwent coronary angiography at the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020 were retrospectively selected. The main exclusion criteria included in-hospital death, post-discharge death within 12 months, and loss to follow-up after one year of discharge. We divided ACS patients into a reexamination (RE) group and a non-reexamination (NRE) group according to whether they were reexamined within one year. In the reexamination group, two hypotheses that may affect the prognosis of ACS patients were tested: the reexamination frequency and duration. According to the ESC Guidelines for the management of acute coronary syndromes [2, 11, 12] and the median reexamination frequency, the reexamination group was divided into the low-frequency reexamination group (LFR, with a reexamination frequency of less than 2 times within one year) and the high-frequency reexamination group (HFR, with a reexamination frequency of more than or equal to 2 times within one year). Meanwhile, the reexamination group was stratified into the short-term reexamination (STR) group and the long-term reexamination (LTR) group based on whether there was a reexamination after one year of follow-up [2, 11, 12]. The study flow chart is shown in Fig. 1. The clinical diagnosis of ACS and definitions of traditional coronary risk factors are presented in the Additional file 1 [13–15]. The study complied with the provisions of the Declaration of Helsinki and was approved by the institutional ethics committee of the Second Affiliated Hospital of Harbin Medical University (Approval number: KY2015-182). All patients gave written informed consent.
Fig. 1.
Flow chart of the study process. ACS: acute coronary syndrome; HFR: high-frequency reexamination; LFR: low-frequency reexamination; LTR: long-term reexamination; STR: short-term reexamination
Composition of follow-up center
The follow-up center of the Cardiology Department of the Second Affiliated Hospital of Harbin Medical University has a complete follow-up system consisting of a health advisory team, a digital management system, and a standardized working process. Figure 2 shows the detailed composition and specific process.
Fig. 2.
Composition of the follow-up center. The “Follow-up Center” has been introduced: with the following specific processes: Health Advisory Team. The health advisory team comprises two cardiologists: three cardiology nurses: and two senior return visitors. The cardiologists are responsible for making medical interventions and adjustments for patients. The nurses are responsible for providing medical education for patients and assisting patients in completing a series of preventive interventions: such as reexamination. Our hospital has established a strict feedback mechanism for return visits: requiring visitors to collect and organize relevant information under regulations and procedures. Reexamination Approach. Telephones and computers are connected to the hospital intranet. Upon discharge: ACS patients who have undergone coronary angiography automatically gain access to the follow-up service platform. Continuous nursing records or nursing return visit registration forms are then established: and centralized telephone follow-up is conducted for each discharged patient after coronary angiography. Digital Management System. Data and indicators of discharged ACS patients after coronary angiography: such as return visit workload: visit success rate: follow-up success rate: and patient satisfaction: are digitally analyzed monthly. The analysis results are summarized and discussed at a meeting. The quality of the return visit service is continuously improved based on digital analysis. Standardized Working Process. Patients are recommended to return to the hospital for reexaminations at 1: 3: 6: and 12 months after discharge. The entire process needs to be completed based on effective communication between the health advisory team and patients
Reexamination
According to the risk assessment results, a detailed and clear post-discharge follow-up plan and reexamination guidance were formulated before discharge. The recommended reexamination times were 1 month, 3 months, 6 months, 12 months, 24 months, and 36 months after discharge, following our center’s standardized procedures (Additional file 1: Fig. S1). Laboratory tests including lipid profile, glycaemic status, renal function, liver function, a complete blood count, and possibly biomarkers, were conducted. A 12-lead electrocardiogram should be part of every visit to detect changes suggestive of silent ischaemia/infarction. The choice of reexamination approach was left to the patient’s discretion. When patients could not visit the hospital in person, a remote physician consultation system based on a mobile application (WeChat) was provided. The cardiologist assessed the patient’s overall clinical status, medication compliance, and risk profile (reflected by risk scores) to optimize the medication plan on time and improve their medication adherence by further educating. Once the patient experienced chest pain, chest tightness, or an abnormal electrocardiogram, hospitalization or coronary angiography was recommended to evaluate the coronary stenoses when non-invasive testing was inconclusive. The specific assessment process is shown in Fig. 3.
Fig. 3.
Post-discharge reexamination guidance of ACS patients. ACS patients are recommended to undergo laboratory tests (a lipid profile: glycaemic status: renal function: liver function: a complete blood count: and possibly biomarkers) and a 12-lead ECG at 1: 3: 6: 12: 24: and 36 months after discharge. When patients experience chest pain: chest tightness: or have an abnormal electrocardiogram: hospitalization or coronary angiography is recommended to detect lesions early. ACS: acute coronary syndrome
Clinical follow-up and outcome definitions
The patients were followed up at 1, 3, 6, 12, 24, and 36 months sequentially after discharge via telephone, remote consultation system, or outpatient visits, according to our center’s standardized procedures (Additional file 1: Fig. S1). The median follow-up duration was 3 years. The primary outcome was cardiac death during the follow-up. Other secondary outcomes were all-cause death, non-fatal myocardial infarction (MI), unplanned revascularization, and re-hospitalization for cardiac causes. The detailed definitions of each adverse event are summarized in the Additional file 1.
Statistical analysis
All analyses were conducted with IBM SPSS Statistics 26.0 (IBM Corp., Armonk, NY, USA) and R version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria). After assessing data distribution by the Kolmogorov-Smirnov test, continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range) and compared via the Student’s t-test or the Mann–Whitney U test. Categorical variables were expressed as counts (percentages) and compared using the χ [2] or Fisher exact test. Missing data were handled using imputation, using the most frequent category for categorical variables and mean value for continuous variables. We used multivariable Cox proportional hazards regression models to model differences in the hazard of all-cause death. Fine-Gray subdistribution proportional hazard models were utilized to evaluate the relationship between reexamination and the incidence of post-discharge non-fatal MI, unplanned revascularisation, re-hospitalisation, or cardiac death. Death without non-fatal MI, death without unplanned revascularisation, death without re-hospitalisation, and noncardiac death were regarded as competing risks, respectively. The results were expressed in hazard ratio (HR) and 95% confidence interval (CI) with the non-reexamination group as the reference. We implemented several models to evaluate the impact of potential confounders. Model 1 was unadjusted; Model 2 was adjusted for age and sex; Model 3 was adjusted for age, sex, body mass index, diagnosis on admission, current smoker, hypertension, hyperlipidemia, diabetes, previous MI, previous percutaneous coronary intervention (PCI), chronic kidney disease, previous stroke, urban, educational attainment, economic status, family history of coronary heart disease (CHD), medications history, and medications at discharge. Model 4 was further adjusted for all covariates associated at the P ≤ 0.10 level with clinical outcomes in univariable analyses. A two-tailed P value < 0.05 was considered statistically significant. Propensity score 1:1 matching (with nearest neighbor matching and a caliper width of 0.20) was used to create cohorts with matched baseline characteristics. The corresponding covariates are provided in the Additional file 1. Baseline characteristics with a standardized mean difference (SMD) between cohorts ≤ 0.1 were considered well-balanced and comparable [16].
Results
Baseline clinical characteristics
The clinical baseline characteristics of the patients are summarized in Table 1. We initially enrolled 10,015 ACS patients and excluded 34 in-hospital deaths, 405 post-discharge deaths within 12 months, and 42 patients lost to follow-up after one year post-discharge. Ultimately, 9,534 ACS patients who underwent coronary angiography were included. The age was 60.4 ± 11.1 years, and 6,692 (70.2%) patients were male. Among all the patients, 6,804 patients were assigned to the RE group and 2,730 patients were assigned to the NRE group. Within one year after discharge, 71.4% of the patients underwent reexamination. Compared with patients in the NRE group, patients in the RE group were more likely to be young adults, current smokers and have a higher prevalence of hypertension, hyperlipidemia, diabetes and the family history of CHD, and have higher levels of cardiac troponin I, creatine kinase isoenzyme, total cholesterol, low-density lipoprotein cholesterol and hypersensitive C-reactive protein (all P < 0.05). Overall, patients in the RE group showed a higher baseline risk profile. In addition, patients in the RE group had a higher level of education (P < 0.001), a better economic status (P < 0.001), and tended to reside in urban areas (P < 0.001). No significant difference was observed between the two groups in baseline medication use. Notably, compared with NRE patients, patients who underwent reexamination within one year showed improved medication adherence at the one-year follow-up (all P < 0.001). The clinical baseline characteristics of patients in each RE subgroup are presented in Additional file 1: Table S1 and Table S2.
Table 1.
Baseline characteristics of patients
| Variables | Total (N = 9534) |
NRE (n = 2730) |
RE (n = 6804) |
P value |
|---|---|---|---|---|
| Age: years | 60.4 ± 11.1 | 61.6 ± 10.8 | 59.9 ± 11.1 | < 0.001 |
| Male: n (%) | 6692 (70.2) | 1888 (69.2) | 4804 (70.6) | 0.170 |
| BMI: kg/m2 | 25.1 ± 3.8 | 24.9 ± 3.4 | 25.3 ± 3.9 | < 0.001 |
| Current smoker: n (%) | 4100 (43.0) | 1038 (38.0) | 3062 (45.0) | < 0.001 |
| Urban: n (%) | 5657 (59.3) | 1447 (53.0) | 4210 (61.9) | < 0.001 |
| Educational attainment | < 0.001 | |||
| Primary school or below: n (%) | 3212 (33.7) | 1164 (42.6) | 2048 (30.1) | |
| Junior high school: n (%) | 2921 (30.6) | 840 (30.8) | 2081 (30.6) | |
| High school or vocational college: n (%) | 2075 (21.8) | 471 (17.3) | 1604 (23.6) | |
| University graduation or higher: n (%) | 1326 (13.9) | 255 (9.3) | 1071 (15.7) | |
| Economic status | < 0.001 | |||
| Low: n (%) | 5372 (56.3) | 1821 (66.7) | 3551 (52.2) | |
| Medium: n (%) | 2747 (28.8) | 636 (23.3) | 2111 (31.0) | |
| High: n (%) | 1415 (14.8) | 273 (10.0) | 1142 (16.8) | |
| Diagnosis | < 0.001 | |||
| STEMI: n (%) | 5052 (53.0) | 1168 (42.8) | 3884 (57.1) | |
| NSTEMI: n (%) | 2776 (29.1) | 719 (26.3) | 2057 (30.2) | |
| UA: n (%) | 1706 (17.9) | 843 (30.9) | 863 (12.7) | |
| Past medical history | ||||
| Hypertension: n (%) | 4954 (52.0) | 1372 (50.3) | 3582 (52.6) | 0.035 |
| Hyperlipidemia: n (%) | 6273 (65.8) | 1693 (62.0) | 4580 (67.3) | < 0.001 |
| Diabetes mellitus: n (%) | 3084 (32.3) | 843 (30.9) | 2241 (32.9) | 0.052 |
| Previous MI: n (%) | 1068 (11.2) | 383 (14.0) | 685 (10.1) | < 0.001 |
| Family history of CHD: n (%) | 2587 (27.1) | 544 (19.9) | 2043 (30.0) | < 0.001 |
| Previous PCI: n (%) | 1268 (13.3) | 608 (22.3) | 660 (9.7) | < 0.001 |
| Previous CABG: n (%) | 26 (0.3) | 16 (0.6) | 10 (0.1) | < 0.001 |
| Previous stroke: n (%) | 1765 (18.5) | 520 (19.0) | 1245 (18.3) | 0.394 |
| Previous HF: n (%) | 221 (2.3) | 82 (3.0) | 139 (2.0) | 0.005 |
| CKD: n (%) | 1554 (16.3) | 465 (17.0) | 1089 (16.0) | 0.219 |
| Laboratory test | ||||
| cTnI: μg/L | 19.9 (2.4–72.0) | 8.5 (0.4–57.5) | 24.6 (4.8–78.3) | < 0.001 |
| CK-MB: μg/L | 60.2 (4.8–192.0) | 20.0 (1.5–139.4) | 80.0 (9.3–208.2) | < 0.001 |
| BNP: pg/mL | 958.5 (293.2–2556.0) | 963.0 (244.0–2556.0) | 955.0 (310.0–2473.2) | 0.920 |
| TC: mg/dL | 176.5 ± 42.4 | 171.9 ± 42.2 | 178.4 ± 42.3 | < 0.001 |
| TG: mg/dL | 128.3 (88.5–168.2) | 132.8 (89.4–168.2) |
126.6 (87.6–168.2) |
0.087 |
| LDL-C: mg/dL | 110.5 ± 35.8 | 105.4 ± 35.3 | 112.6 ± 35.7 | < 0.001 |
| HDL-C: mg/dL | 45.8 ± 11.0 | 45.5 ± 11.2 | 45.9 ± 11.0 | 0.134 |
| Scr: μmol/L | 81.0 (69.0–94.0) | 81.0 (69.0–94.0) | 81.0 (69.0–94.0) | 0.958 |
| BUN: mmol/L | 5.7 (4.6–7.0) | 5.8 (4.7–7.1) | 5.7 (4.6–6.9) | 0.009 |
| Hs-CRP: mg/dL | 5.2 (2.0–11.1) | 4.8 (1.7–10.4) | 5.3 (2.1–11.3) | < 0.001 |
| HbA1C: % | 6.4 ± 1.3 | 6.5 ± 1.3 | 6.4 ± 1.3 | 0.191 |
| LVEF: % | 57.4 ± 7.5 | 57.4 ± 7.5 | 57.3 ± 7.5 | 0.662 |
| Medications history | ||||
| Aspirin: n (%) | 1968 (20.6) | 568 (20.8) | 1400 (20.6) | 0.802 |
| P2Y12 receptor inhibitors: n (%) | 614 (6.4) | 187 (6.8) | 427 (6.3) | 0.302 |
| Statins: n (%) | 936 (9.8) | 281 (10.3) | 655 (9.6) | 0.323 |
| Beta blocker: n (%) | 680 (7.1) | 177 (6.5) | 503 (7.4) | 0.119 |
| ACEI/ARB: n (%) | 511 (5.4) | 138 (5.1) | 373 (5.5) | 0.403 |
| Medications at discharge | ||||
| Aspirin: n (%) | 9284 (97.4) | 2554 (93.6) | 6730 (98.9) | < 0.001 |
| P2Y12 receptor inhibitors: n (%) | 9323 (97.8) | 2554 (93.6) | 6769 (99.5) | < 0.001 |
| Statins: n (%) | 9231 (96.8) | 2510 (91.9) | 6721 (98.8) | < 0.001 |
| Beta blocker: n (%) | 5633 (59.1) | 1387 (50.8) | 4246 (62.4) | < 0.001 |
| ACEI/ARB: n (%) | 4325 (45.4) | 983 (36.0) | 3342 (49.1) | < 0.001 |
| Medications at follow-up | ||||
| Aspirin: n (%) | 8990 (94.3) | 2425 (88.8) | 6565 (96.5) | < 0.001 |
| P2Y12 receptor inhibitors: n (%) | 8583 (90.0) | 2058 (75.4) | 6525 (95.9) | < 0.001 |
| Statins: n (%) | 8988 (94.3) | 2355 (86.3) | 6633 (97.5) | < 0.001 |
| Beta blocker: n (%) | 5439 (57.0) | 1155 (42.3) | 4284 (63.0) | < 0.001 |
| ACEI/ARB: n (%) | 4027 (42.2) | 733 (26.8) | 3294 (48.4) | < 0.001 |
Data are presented as mean ± SD: median (interquartile range): or number (%)
Low economic status: defined as an average monthly income per person of less than 2,500 RMB. Medium economic status: defined as an average monthly income per person between 2,500 and 5,000 RMB. High economic status: defined as an average monthly income per person of 5,000 RMB or more
BMI body mass index, UA unstable angina, NSTEMI non-ST segment elevation myocardial infarction, STEMI ST-segment elevation myocardial infarction, MI myocardial infarction, CHD coronary heart disease, PCI percutaneous coronary intervention, CABG coronary artery bypass grafting, HF heart failure, CKD chronic kidney disease, cTNI cardiac troponin I, CK-MB creatine kinase-MB, BNP B-type natriuretic peptide, TC total cholesterol, TG triglyceride, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Scr serum creatinine, BUN blood urea nitrogen, Hs-CRP hypersensitive C-reactive protein, LVEF left ventricular ejection fraction, ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, RE reexamination, NRE non-reexamination
Reexamination and mortality
The median follow-up time was 36 months. During the follow-up period, 434 patients (4.6%) experienced all-cause death, of which 246 (2.6%) were due to cardiovascular causes. The Kaplan–Meier analysis showed that the RE group had a lower mortality rate than the NRE group (Fig. 4). Table 2 summarizes the risk of outcomes in the RE and NRE groups. In the unadjusted analysis, reexamination demonstrated a robust association with the outcome, patients in the RE group had approximately 50% lower risks of all-cause death (HR, 0.55; 95% CI, 0.45–0.66, P < 0.001; Table 2, Additional file 1: Table S3) and cardiac death (HR, 0.49; 95% CI, 0.38–0.63, P < 0.001; Table 2, Additional file 1: Table S4) compared with patients in the NRE group. This association remained significant for the risk of all-cause death (HR, 0.63; 95% CI, 0.52–0.77, P < 0.001) and risk of cardiac death (HR, 0.58; 95% CI, 0.44–0.75, P < 0.001) after full adjustment (Table 2). Among patients in the RE group, the prognosis of ACS patients was further assessed according to the frequency and duration of reexamination in Table 3. HFR was associated with significantly lower all-cause mortality (HR, 0.56; 95% CI, 0.43–0.72, P < 0.001) and cardiac mortality (HR, 0.50; 95% CI, 0.35–0.70, P < 0.001). Similarly, patients with long-term reexamination were associated with a 63% lower risk of all-cause death (HR, 0.37; 95% CI, 0.24–0.58, P < 0.001) and cardiac death (HR, 0.37; 95% CI, 0.20–0.67, P = 0.001) compared with patients with short-term reexamination.
Fig. 4.
Kaplan–Meier curves for all-cause and cardiac mortality in ACS patients. There were significant differences between the groups in the cumulative rates of all-cause death (A) and cardiac death (B): with the reexamination group showing a significantly reduced risk of death. RE: reexamination; NRE: non-reexamination; HR: hazard ratio; CI: confidence interval
Table 2.
Hazard ratio of clinical outcomes between the reexamination group and the non-reexamination group
| No. of events/no. of patients (%) | HR (95% CI) | ||||
|---|---|---|---|---|---|
| Model 1 | Model 2 | Model 3 | Model 4 | ||
| All-cause Death | |||||
| NRE | 180/2730 (6.6) | 1 (Reference) | 1 (Reference) | 1 (Reference) | 1 (Reference) |
| RE | 254/6804 (3.7) | 0.55 (0.45–0.66)** | 0.60 (0.50–0.73)** | 0.61 (0.50–0.75) ** | 0.63 (0.52–0.77)** |
| Cardiac Death | |||||
| NRE | 109/2730 (4.0) | 1 (Reference) | 1 (Reference) | 1 (Reference) | 1 (Reference) |
| RE | 137/6804 (2.0) | 0.49 (0.38–0.63)** | 0.53 (0.41–0.68)** | 0.57 (0.44–0.75) ** | 0.58 (0.44–0.75) ** |
| Non-fatal MI | |||||
| NRE | 43/2730 (1.6) | 1 (Reference) | 1 (Reference) | 1 (Reference) | 1 (Reference) |
| RE | 133/6804 (2.0) | 1.23 (0.87–1.74) | 1.27 (0.90–1.79) | 1.37(0.95–1.82) | 1.36 (0.95–1.96) |
| Unplanned Revascularization | |||||
| NRE | 101/2730 (3.7) | 1 (Reference) | 1 (Reference) | 1 (Reference) | 1 (Reference) |
| RE | 722/6804 (10.6) | 2.98 (2.42–3.66)** | 2.94 (2.39–3.62)** | 2.80 (2.26–3.47)** | 2.79 (2.26–3.45) ** |
| Re-hospitalization | |||||
| NRE | 401/2730 (14.7) | 1 (Reference) | 1 (Reference) | 1 (Reference) | 1 (Reference) |
| RE | 1286/6804 (18.9) | 1.31 (1.17–1.47)** | 1.36 (1.21–1.52)** | 1.35 (1.20–1.53)** | 1.35 (1.20–1.52) ** |
Model 1: Unadjusted
Model 2: Adjusted for age: sex
Model 3: Adjusted for age: sex: body mass index: diagnosis on admission: current smoker: hypertension: hyperlipidemia: diabetes: previous MI: previous percutaneous coronary intervention: chronic kidney disease: previous stroke: urban: educational attainment: economic status: family history of coronary heart disease: medications history: and medications at discharge
Model 4: Adjusted for all covariates (age: sex: body mass index: current smoker: urban: educational attainment: economic status: diagnosis on admission: hypertension: hyperlipidemia: diabetes mellitus: previous MI: family history of coronary heart disease: previous percutaneous coronary intervention: previous coronary artery bypass grafting: previous stroke: previous heart failure: chronic kidney disease: laboratory test: medications history: and medications at discharge) associated at the P ≤ 0.10 level with clinical outcomes in unadjusted analyses
RE reexamination, NRE non-reexamination, MI myocardial infarction, HR hazard ratio, CI confidence interval
*P < 0.05 and **P < 0.001
Table 3.
Hazard ratio of clinical outcomes in each subgroup of reexamination
| No. of events/no. of patients (%) | HR (95% CI) | |
|---|---|---|
| All-cause Death | ||
| STR | 231/5251 (4.4) | 1 (Reference) |
| LTR | 23/1553 (1.5) | 0.37 (0.24–0.58) ** |
| LFR | 134/2391 (5.6) | 1 (Reference) |
| HFR | 120/4413 (2.7) | 0.56 (0.43–0.72) ** |
| Cardiac Death | ||
| STR | 125/5251 (2.4) | 1 (Reference) |
| LTR | 12/1553 (0.8) | 0.37 (0.20–0.67) * |
| LFR | 75/2391 (3.1) | 1 (Reference) |
| HFR | 62/4413 (1.4) | 0.50 (0.35–0.70) ** |
| Unplanned Revascularization | ||
| STR | 478/5251 (9.1) | 1 (Reference) |
| LTR | 244/1553 (15.7) | 1.73 (1.48–2.03) ** |
| LFR | 186/2391 (7.8) | 1 (Reference) |
| HFR | 536/4413 (12.1) | 1.60 (1.35–1.90) ** |
| Re-hospitalization | ||
| STR | 941/5251 (17.9) | 1 (Reference) |
| LTR | 345/1553 (22.2) | 1.23 (1.09–1.40) * |
| LFR | 462/2391 (19.3) | 1 (Reference) |
| HFR | 824/4413 (18.7) | 1.04 (0.93–1.17) |
Adjusted for all covariates (age: sex: body mass index: current smoker: urban: educational attainment: economic status: diagnosis on admission: hypertension: hyperlipidemia: diabetes mellitus: previous MI: family history of coronary heart disease: previous percutaneous coronary intervention: previous coronary artery bypass grafting: previous stroke: previous heart failure: chronic kidney disease: laboratory test: medications history: and medications at discharge) associated at the P ≤ 0.10 level with clinical outcomes in unadjusted analyses
STR short-term reexamination, LTR long-term reexamination, LFR low-frequency reexamination, HFR high-frequency reexamination, HR hazard ratio, CI confidence interval
*P < 0.05 and **P < 0.001
Reexamination and unplanned revascularization
Univariate Cox proportional hazards models for non-fatal MI and unplanned revascularization are reported in Additional file 1: Table S5 and Table S6. In model 3, patients in the RE group had a 2.80-fold increased risk of undergoing unplanned revascularization compared with patients in the NRE group (HR, 2.80; 95% CI, 2.26–3.47, P < 0.001; Table 2, model 3), with PCI being the predominant type (P < 0.001, Additional file 1: Table S7). The adjusted analysis results were robust after controlling for all covariates associated at the P ≤ 0.10 level with clinical outcomes (HR, 2.79; 95% CI, 2.26–3.45, P < 0.001; Table 2, model 4). In the RE group, unplanned revascularization showed a trend toward reducing the risk of all-cause death (HR, 0.67; 95% CI, 0.42–1.06, P = 0.089), though there was no significant difference (Additional file 1: Fig. S2). Moreover, long-term and high-frequency reexamination significantly increased the primary risk of unplanned revascularization by 1.73-fold (HR, 1.73; 95% CI, 1.48–2.03, P < 0.001; Table 3) and 1.60-fold (HR, 1.60; 95% CI, 1.35–1.90, P < 0.001; Table 3), respectively. Furthermore, patients in the RE group had approximately 58% higher risks of MACE (HR, 1.58; 95% CI, 1.36–1.84, P < 0.001; Additional file 1: Table S8), while the risks of MACE in the RE group were conversely 22% lower when unplanned revascularization was excluded (HR, 0.78; 95% CI, 0.63–0.97, P = 0.023; Additional file 1: Table S8), compared with patients in the NRE group. The results can also be observed in the HFR and LTR groups (Additional file 1: Table S9), compared with the LFR and STR groups, respectively.
Reexamination and re-hospitalization
Reexamination was associated with a higher risk of re-hospitalization than non-reexamination in the unadjusted model (HR, 1.31; 95% CI, 1.17–1.47, P < 0.001; Table 2, Additional file 1: Table S10). The adjusted analysis results remained robust after controlling for all covariates (HR, 1.35; 95% CI, 1.20–1.52, P < 0.001; Table 2). Unstable or progressive angina (P < 0.001) was the primary reason for the increased re-hospitalization risk in the RE group (Additional file 1: Table S7). The HRs for re-hospitalization were 1.23 (HR, 1.23; 95% CI, 1.09–1.40, P = 0.001; Table 3) and 1.04 (HR, 1.04; 95% CI, 0.93–1.17, P = 0.510; Table 3) for patients with long-term and high-frequency reexamination, respectively.
Baseline characteristics and clinical outcomes in the PSM cohort
After conducting propensity score matching (PSM), the baseline characteristics were well balanced for the entire cohort (SMD ≤ 0.1), as summarized in Additional file 1: Table S11. Ultimately, 2,413 pairs of patients were matched, with an average age of 61.5 ± 10.8 years, and 67.9% were male (Additional file 1: Table S11). Within the PSM cohort, during the 3-year follow-up, patients in the RE group had lower all-cause mortality and cardiac mortality, and higher rates of non-fatal MI, unplanned revascularization, and re-hospitalization than those in the NRE group (all P < 0.05; Additional file 1: Table S12). This increase was predominantly attributed to a significant rise in unplanned PCI and re-hospitalization for unstable or progressive angina. The Kaplan–Meier curve also indicated that the RE group had a lower cumulative rate of all-cause death (4.4% vs. 7.7%, P < 0.001) and cardiac death (2.1% vs. 4.6%, P < 0.001) compared with the NRE group (Additional file 1: Fig. S3). Furthermore, after repeating PSM in the subgroup of patients who underwent reexamination, the baseline characteristics were also well balanced (SMD ≤ 0.1, Additional file 1: Table S13 and Table S14), the risk of all-cause death and cardiac death remained lower in both the LTR subgroup (Additional file 1: Table S15) and the HFR subgroup (Additional file 1: Table S16). These findings were consistent with those of the primary analysis.
Discussion
ACS is a disease with high morbidity and mortality in the cardiovascular system [1, 2]. Our study is the first to explore the prognostic value of a reexamination protocol within and after the first year of follow-up. In the secondary prevention program based on a follow-up center, the main findings of this study were as follows: Reexamination within 12 months was significantly associated with a reduced risk of death 3 years after ACS. The risk of all-cause death and cardiac death decreased by 37% and 42%, respectively, in patients who had a reexamination compared with those who did not. Among patients who underwent reexamination, the risk of all-cause death in the high-frequency reexamination group was 44% lower, and the risk of cardiac death was 50% lower than that in the low-frequency reexamination group. Furthermore, patients who continued to reexamine after the first year of follow-up had a 63% lower risk of cardiac death and all-cause death. This is strong evidence favoring regular and scientific reexamination of ACS patients after discharge, even if the patient is asymptomatic. During follow-up, cardiologists can adjust and optimize the patients’ overall status in the following ways:
Firstly, weigh the benefits of antithrombotic and anticoagulant therapy against the risk of bleeding, including severe, life-threatening bleeding [17–19]. Cardiologists should adjust the antithrombotic and anticoagulant treatment according to the patients’ clinical status, such as skin purpura, melena, hematuria, as well as the results of blood routine and coagulation function tests. Secondly, lipid-lowering treatment should be initiated as early as possible after an ACS event, as it is associated with lower cardiovascular event rates [20–23]. In all cases, lipid levels should be re-evaluated 4–6 weeks after each treatment or dose adjustment to determine whether treatment goals have been achieved and to check for any safety issues. Thirdly, the liver and kidney function of the patients should be monitored. In a prospective study, administering atorvastatin was found to have the risk of causing acute liver injury [24]. In addition, inappropriate diuretic use may lead to electrolyte disturbances and further cause kidney injury [25, 26]. Fourthly, cardiologists should combine echocardiography, cardinal symptoms, and B-type natriuretic peptide to assess patients with suspected heart failure, and anti-heart failure therapy should be administered when necessary. In patients with ST-segment elevation myocardial infarction after primary PCI, heart failure hospitalization within 1 year was independently associated with a higher risk of all-cause death and heart failure hospitalization beyond 1 year [27]. Therefore, timely adjustment of anti-heart failure treatment is essential. Fifthly, diabetes confers approximately a two-fold increased risk of coronary artery disease [28], and ACS patients with diabetes may more often present with non-specific symptoms, which may lead to delays in accessing care [29, 30]. A recent study has shown that better glycemic control can be achieved with more frequent follow-up in patients with type 2 diabetes [31]. Finally, other systemic diseases should also be focused on. The process above requires the follow-up center to guide patients to undergo reexamination at appropriate times and regularly, which is conducive to timely adjustment of drugs and intervention, thereby effectively reducing the risk of adverse events.
Additionally, it is interesting that in this study, patients who underwent reexamination experienced a higher incidence of unplanned revascularization, which may be attributed to the gradual progression of lesions, namely in-stent restenosis, unstable plaque progression in non-culprit lesions, increased lipid accumulation, and luminal narrowing [32]. These high-risk factors can be identified during the reexamination process. However, few studies have evaluated whether the increased revascularization was beneficial [33]. Therefore, the findings of our study may bring about further discussion regarding the added value of performing unplanned revascularization after PCI.
Moreover, structured reexamination may increase medical resource investment and patient costs, resulting in higher initial costs. Nevertheless, previous studies have shown that long-term, continuous, and coordinated post-hospital management can reduce potential costs from both societal and healthcare perspectives, while significantly improving patients’ quality of life [34]. This long-term cost-effectiveness can be achieved by preventing adverse events and reducing subsequent high-cost treatments [35]. Moreover, in the future, the development of a standardized individualized follow-up protocol will further contribute to reducing patients’ costs, thus enhancing overall cost-effectiveness.
Although the long-term cost-effectiveness has been confirmed [35], limited economic conditions, poor educational and cognitive level [36–38], as well as strained doctor-patient relationships [39] are closely associated with patients’ poor adherence to reexaminations, resulting in patients being unable to seek medical intervention in time, ultimately leading to poorer prognoses [40]. Thus, health education and lifestyle management by cardiologists should be emphasized to increase patients’ adherence and persistence to reexamination, ultimately preventing recurrent adverse events after ACS in the long term [40]. Based on the above needs, the intervention of the medical system and cardiologists is crucial, which can guide patients to have regular and appropriate reexaminations, and provide medical education to improve patients’ adherence.
Based on the discussion above, to ensure high-quality follow-up care, it is crucial for centers with limited resources to establish a medical consortium that can help incorporate grassroots and rural areas into the overall prevention and control system for ACS, thereby optimizing the follow-up care. Moreover, the application of digital health tools facilitate expanding our work at multiple levels and from various perspectives, which is based on the application “Cardiovascular Diseases Digital Management Center”, through measures such as science popularization, individualized rehabilitation plans adjustment, cardiopulmonary and specialized assessments, it enables comprehensive as well as dynamic management of ACS patients and increases patients’ adherence to follow-up care. Although wearable monitoring devices are not yet widely adopted, our center actively recommends their use on patients to monitor various vital signs.
By establishing the follow-up center, our institution has educated and guided patients to have regular reexaminations actively and persistently. As a result, 71% of patients chose to undergo reexaminations after discharge, and 22% showed higher adherence. This approach ensures timely reexamination, crucial for improving the currently low secondary prevention measures implementation rate. The follow-up center enhances patients’ awareness of postoperative health management by providing senior return visitors to assist with reexamination consultations, making the process more scientific and safer. Our findings indicate that most ACS patients can benefit from reexaminations. Therefore, we call on cardiovascular hospitals to establish dedicated follow-up centers and standardize medical management processes throughout the post-discharge period. This initiative can improve patients’ quality of life and significantly reduce the mortality rate.
Strengths and limitations
This analysis boasts several strengths that contribute to its overall robustness. First, the study presents robust statistical analyses and leverages a large sample size to provide strong evidence. The findings align with current evidence on secondary prevention. Second, the cohorts were further matched according to baseline characteristics, thus enhancing the homogeneity of the two groups and improving internal validity. Third, the significant relationship between ACS patients’ prognosis and reexamination frequency and duration provides crucial insights for high-risk subgroups, emphasizing the necessity of regular interventions.
Limitations, naturally, also exist. Despite employing a robust analysis, this study remains limited by its design, which is single-center, retrospective, and observational. First, the sample primarily represents ACS patients from China, which may limit its generalizability to other populations. Second, this study excluded patients who died within 12 months or were lost to follow-up after one year post-discharge. Although subgroup analyses based on the follow-up duration supported the results’ robustness, this selection bias may have overestimated the benefits of reexamination. Third, although we adjusted for a variety of covariates and performed PSM, residual confounding from unmeasured factors (such as diet, psychosocial stressors, and insurance coverage) may still exist. Further extensive research that provides detailed insights into these potential confounders is essential. Fourth, our study did not account for individuals with limited access to follow-up care (such as those who do not attend due to socioeconomic obstacles or live in rural areas), the impact of periprocedural ischemic events on the decision-making process for follow-up reexaminations [41], as well as the patient’s intrinsic adherence (such as health care awareness), which might lead to an overestimation of the reexamination benefits. Fifth, our present analysis emphasized the impact of medical interventions and communication education on patient outcomes. However, it paid less attention to the benefits of social support outside the hospital during the follow-up period, which may affect the patient’s prognosis. Sixth, the relatively small sample size for non-fatal MI outcomes may limit the statistical power required for complex causal analyses. Finally, external validation of the results based on national or international databases was not conducted, potentially restricting the generalizability of our findings. Future large-scale multicenter prospective randomized clinical trials are necessary to eliminate potential biases, enhance generalizability, and validate our conclusions.
Conclusions
In the secondary prevention program based on the follow-up center, better clinical outcomes were observed in the reexamination group, including lower cardiac and all-cause mortality. We identified several factors that significantly affected the reexamination outcomes: the risk of cardiac death and all-cause death decreased with increasing reexamination frequency. Furthermore, patients who continued reexamination after the first year of follow-up had a 63% lower risk of cardiac death and a 63% lower risk of all-cause death. The high reexamination coverage rate among patients in our hospital may be attributed to the reexamination strategy led by the follow-up center. Therefore, establishing a follow-up center may be significant in improving patient prognosis.
Supplementary Information
Additional file 1: Figures S1-S3: Tables S1-S16. Fig. S1-The standardized reexamination procedure for acute coronary syndrome. Fig. S2-Mortality risk of the revascularization subgroup versus the non-revascularization subgroup in the reexamination group. Fig. S3-Kaplan–Meier curves for all-cause and cardiac mortality after propensity score matching. Table S1-Baseline characteristics of patients with long-term or short-term reexamination. Table S2-Baseline characteristics of patients with low-frequency or high-frequency reexamination. Table S3-Univariate Cox regression analysis for all-cause death. Table S4-Univariate Cox regression analysis for cardiac death. Table S5-Univariate Cox regression analysis for non-fatal MI. Table S6-Univariate Cox regression analysis for unplanned revascularization. Table S7-The primary reasons for unplanned revascularization and re-hospitalization. Table S8-Hazard ratio of MACE between the reexamination group and the non-reexamination group. Table S9-Hazard ratio of MACE in each subgroup of reexamination. Table S10-Univariate Cox regression analysis for re-hospitalization. Table S11-Baseline characteristics of patients after propensity score matching. Table S12-Clinical outcomes at 3 years after propensity score matching. Table S13-Baseline characteristics of patients with long-term versus short-term reexamination after propensity score matching. Table S14-Baseline characteristics of patients with low-frequency versus high-frequency reexamination after propensity score matching. Table S15-Clinical outcomes at 3 years of patients with long-term versus short-term reexamination after propensity score matching. Table S16-Clinical outcomes at 3 years of patients with low-frequency versus high-frequency reexamination after propensity score matching.
Acknowledgements
The authors sincerely thank all the colleagues and patients who participated in this study.
Abbreviations
- ACS
Acute coronary syndrome
- RE
Reexamination
- NRE
Non-reexamination
- LFR
Low-frequency reexamination
- HFR
High-frequency reexamination
- STR
Short-term reexamination
- LTR
Long-term reexamination
- MI
Myocardial infarction
- SD
Standard deviation
- HR
Hazard ratio
- CI
Confidence interval
- PCI
Percutaneous coronary intervention
- CHD
Coronary heart disease
- SMD
Standardized mean difference
- PSM
Propensity score matching
Authors' contributions
CW, LC, XM, MS, YW1, FD, and YW2 conceptualized and designed the study. CW, XT, HZ, TC, XH, JD, DW, HJ, and BY performed data acquisition, analysis, and interpretation. CW, LC, XM, MS, CZ, YW2, JW, and SH drafted and edited the first manuscript. All authors contributed to the critical revision of the manuscript and approved the final draft. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no specific grant from funding agencies in the public: commercial: or not-for-profit sectors.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
The study complied with the provisions of the Declaration of Helsinki and was approved by the institutional ethics committee of the Second Affiliated Hospital of Harbin Medical University (Approval number: KY2015-182). All patients gave written informed consent.
Consent for publication
All authors give their consent to the publication of this manuscript.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Chao Wang, Lina Cui and Xianqin Ma contributed equally to this work.
Contributor Information
Haibo Jia, Email: jhb101180@163.com.
Bo Yu, Email: yubodr@163.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Additional file 1: Figures S1-S3: Tables S1-S16. Fig. S1-The standardized reexamination procedure for acute coronary syndrome. Fig. S2-Mortality risk of the revascularization subgroup versus the non-revascularization subgroup in the reexamination group. Fig. S3-Kaplan–Meier curves for all-cause and cardiac mortality after propensity score matching. Table S1-Baseline characteristics of patients with long-term or short-term reexamination. Table S2-Baseline characteristics of patients with low-frequency or high-frequency reexamination. Table S3-Univariate Cox regression analysis for all-cause death. Table S4-Univariate Cox regression analysis for cardiac death. Table S5-Univariate Cox regression analysis for non-fatal MI. Table S6-Univariate Cox regression analysis for unplanned revascularization. Table S7-The primary reasons for unplanned revascularization and re-hospitalization. Table S8-Hazard ratio of MACE between the reexamination group and the non-reexamination group. Table S9-Hazard ratio of MACE in each subgroup of reexamination. Table S10-Univariate Cox regression analysis for re-hospitalization. Table S11-Baseline characteristics of patients after propensity score matching. Table S12-Clinical outcomes at 3 years after propensity score matching. Table S13-Baseline characteristics of patients with long-term versus short-term reexamination after propensity score matching. Table S14-Baseline characteristics of patients with low-frequency versus high-frequency reexamination after propensity score matching. Table S15-Clinical outcomes at 3 years of patients with long-term versus short-term reexamination after propensity score matching. Table S16-Clinical outcomes at 3 years of patients with low-frequency versus high-frequency reexamination after propensity score matching.
Data Availability Statement
No datasets were generated or analysed during the current study.