1. Study design and patient selection
This observational multicenter study, which was conducted at 274 centers in China between June 2001 and July 2004, enrolled 7510 consecutive patients diagnosed with acute STEMI who were admitted within 12 hours of symptom onset. The diagnostic criteria for acute STEMI included typical chest pain or ischemic symptoms; dynamic changes in the electrocardiogram (ECG) showing elevation of ST-segment more than 0.2 mV in two adjacent leads (V1, V2, and V3) or more than 0.1 mV in other leads; new left bundle branch block (LBBB); and elevated levels of cardiac injury biomarkers (troponin I and creatine kinase MB). The exclusion criteria consisted of contraindications to anticoagulants, a history of hemorrhagic stroke in the last year, pregnancy, cancer, and an inability to finish the follow-up period. The ethics committees at Fuwai Hospital and each participating center approved the study protocols in accordance with the Declaration of Helsinki. All patients provided written consent.
After hospitalization, patients received treatment according to clinical guidelines applicable at the time of the study and local healthcare standards for managing STEMI. Reperfusion treatment, such as primary percutaneous coronary intervention (PCI) or thrombolytic therapy, was utilized. Primary PCI procedures were conducted through radial or femoral artery access using established techniques by experienced cardiologists at specialized facilities. A total of 374 patients were excluded due to incomplete data, leaving 7136 patients for inclusion in the final analysis of the study.
2. Data collection and laboratory measurements
Upon admission, baseline patient data were collected, encompassing variables such as sex, age, weight, heart rate, blood pressure (BP), hemoglobin, blood glucose (BG), blood potassium, blood sodium, location of myocardial infarction(MI), Killip class, cardiovascular history [including MI, hypertension, heart failure(HF), DM, and stroke], reperfusion therapy (PCI and thrombolysis), and medication regimens consisting of antiplatelets, β-blockers, statins, nitrates, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARBs), and diuretics.
The admission Thrombolysis in Myocardial Infarction Risk Score (TRS) was determined utilizing a scoring system that assigned points based on specific criteria[16]. Furthermore, detailed laboratory information was collected, such as three venous BG values within 24 hours and glycosylated hemoglobin (HbA1c) levels at the time of admission. Experienced researchers thoroughly reviewed the medical records of patients and addressed any inconsistencies in data collection through consultation.
Venous blood samples were consistently obtained from the antecubital vein of participants using a 21-gauge sterile syringe and collected in either EDTA-treated or plain tubes for laboratory testing. Venous BG levels were assessed upon admission, as well as at 6 ± 2 hours and 24 ± 2 hours post-admission, utilizing the glucose oxidase method for each patient. Blood samples were obtained from the cubital vein upon admission for the HbA1c test and then sent to the central laboratory of Fuwai Hospital in Beijing, where high-performance liquid chromatography was used. Consistent with standardized protocols, all participating centers adhered to identical blood collection procedures and testing methodologies. DM was characterized by an HbA1c level of ≥ 6.5%, whereas non-DM was indicated by an HbA1c level of < 6.5%.
Admission blood glucose (ABG) was assessed according to the BG levels of patients within 6 ± 2 hours of admission. The mean blood glucose (MBG) level was computed as the average of three BG values recorded within 24 hours after admission for each patient. The standard deviation (SD) of MBG was calculated as follows:
SD =√[((ABG – MBG)༾2 +(BG at 6 ± 2 hours – MBG)༾2 + (BG at 24 ± 2 hours – MBG)༾2)/3]. GV was assessed using the coefficient of variation of the BG level, calculated as MGL divided by SD for each patient, reflecting the degree of BG fluctuation within the 24-hour period.
3. Study outcomes and follow-up
All patients underwent a 30-day follow-up period, which involved interviews conducted in the clinic, telephone conversations with patients or their family members, or a review of medical documentation. The primary outcome was all-cause death within 30 days of enrollment, and the secondary outcome was major adverse cardiovascular events (MACEs). MACEs was evaluated as a composite outcome, encompassing all-cause death, cardiac arrest, cardiogenic shock, reinfarction, stroke, and major bleeding. Trained research personnel, unaware of the study's objectives, carried out the assessment of these outcome events.
All-cause death included deaths from cardiovascular and non-cardiovascular causes. Cardiac arrest was defined as ventricular fibrillation or pulseless ventricular tachycardia, or scenarios of clinical pulselessness characterized by pulseless electrical activity or bradycardia necessitating cardiopulmonary resuscitation and/or emergency defibrillation. Cardiogenic shock was identified by the presence of systolic arterial hypotension (< 90 mmHg) persisting for more than 30 minutes, along with symptoms of inadequate blood flow that did not improve with fluid adjustments, necessitating the use of intravenous drugs or mechanical devices to support BP. Reinfarction was characterized by recurrent typical chest pain accompanied by new ischemic ECG changes (such as ST-segment re-elevation, depression, or new Q waves), and further elevation in enzyme levels (reaching double the normal upper limit if they had previously returned to normal, or increasing by 50% if already elevated).
4. Statistical analysis
Continuous variables are expressed as the means ± SD for data that followed a normal distribution, or as quartiles for data that did not follow a normal distribution, with normality assessed using the Kolmogorov-Smirnov test. Categorical variables are presented as frequencies (percentages). Group comparisons utilized analysis of variance or the Mann-Whitney U test for continuous variables and Pearson’s chi-square test or Fisher’s exact test for categorical variables. Outcome estimates were calculated using the Kaplan-Meier method and analyzed with the log-rank test. Cox proportional hazards models were used for outcome analysis. Well-established risk factors and variables with p < 0.05 were included in multivariable analyses. Adjusted hazard ratios (HRs) and their respective 95% confidence intervals (CIs) were calculated relative to the reference group, where HRs was set to 1. Statistical significance was set at p < 0.05, and all tests were two-sided. Statistical analysis was conducted with SPSS 26.0 (IBM Corporation, New York, NY, USA) and GraphPad Prism 9.0 (GraphPad Software, Boston, MA, USA).