The study population comprised patients admitted to Iwate Medical University Hospital between January 2012 and December 2017 due to AMI, specifically those who met the criteria outlined in the 3rd universal definition of MI (7).

AMI was diagnosed based on the evidence of myocardial necrosis in patients with acute myocardial ischemia in a clinical setting. The criteria for detection included the presence of a rise and/or fall in cardiac biomarker values, with at least one value exceeding the 99th percentile upper reference limit. In addition, at least one of the following conditions had to be met: 1) symptoms of ischemia; 2) new or presumed new significant ST-segment-T wave changes or new left bundle branch block; 3) development of a pathological Q wave on an electrocardiogram (ECG); 4) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; and 5) identification of an intracoronary thrombus by angiography or autopsy. Furthermore, in accordance with the classification of MI (types 1 to 5) as defined by the 3rd universal definition (7), the patients were classified as either type 1, spontaneous MI; type 2, MI secondary to an ischemia imbalance; or MI resulting in death when biomarker values were unavailable.

The exclusion criteria for the study subjects were as follows: 1) patients with AMI classified into two categories [type 4, including MI related to PCI or stent thrombosis; and type 5, including MI related to coronary artery bypass grafting (CABG)]; 2) patients transported after an unexplained cardiac arrest who died without resuscitation or admission, making the involvement of myocardial ischemia unclear; and 3) patients who declined to participate in the study via an opt-out mechanism.

The study was conducted in accordance with the ethical provisions of the Helsinki Declaration (2013 Brazil revision) and approved by the Ethics Committee of Iwate Medical University (MH2023-013). In this retrospective observational study, eligible patients were provided an opportunity to opt out (https://iwate-heart.jp/public_information/).

The definition of each parameter used in this study was established by referring to previous studies that are widely regarded as representative in the field. Hypertension was defined (in accordance with the ACC/AHA Stage 2 hypertension guidelines) as a systolic blood pressure of ≥140 mmHg, a diastolic blood pressure of ≥90 mmHg upon admission, or the use of antihypertensive medication (8). Diabetes was defined as a blood sugar level ≥200 mg/dL upon admission, an HbA1c level of ≥6.5%, or the administration of diabetes medication (9). For cases that did not meet this definition, fasting blood sugar, daily blood sugar fluctuation, and glucose tolerance tests were not conducted. Dyslipidemia was defined in line with the guidelines in Japan as low-density lipoprotein (LDL)-cholesterol ≥140 mg/dL or high-density lipoprotein (HDL)-cholesterol <40 mg/dL (10) and included a total cholesterol level of ≥240 mg/dL or the administration of lipid-lowering drugs. A history of ischemic heart disease was defined as a history of AMI or revascularization (PCI or CABG). A current smoking habit was defined as smoking within the year prior to admission. A history of stroke was defined as any past stroke that required hospitalization, including cerebral infarction and intracranial hemorrhaging. Consequently, incidental asymptomatic lacunar infarctions identified on imaging were excluded. Atrial fibrillation was defined as any history of treatment, regardless of whether it was chronic or paroxysmal, or any evidence of atrial fibrillation found on previous Holter monitoring or a 12-lead ECG. Cases of transient paroxysmal atrial fibrillation observed during hospitalization without a previous record were not included. However, those with consistent atrial fibrillation waveforms upon admission, even without prior records, were included. Obesity was defined as a body mass index (BMI) ≥25.0 kg/m² or higher upon admission (11). Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m² upon admission (12) or dialysis.

The primary outcome measure was in-hospital mortality, and a thorough examination of the underlying causes of death was conducted. Secondary outcome measures included acute-phase complications that occurred during hospitalization, such as heart failure, shock, arrhythmias, bleeding, mechanical complications, and infections.

All statistical analyses were performed using the SPSS^Ⓡ 28.0 software program for Windows (IBM, Chicago, USA). The patients were divided into two groups based on the presence or absence of DM, and the analyses were conducted accordingly. For comparisons between the two groups, the chi-squared and Mann-Whitney U tests were employed. The Kaplan-Meier method was used to calculate the cumulative event occurrence rate. The hazard ratio (HR) for event occurrence was assessed using a Cox proportional hazards model. Statistical significance was set at p<0.05.

A total of 1,140 patients with AMI met the enrollment criteria, and 408 patients (35.8%) were categorized as having DM. The mean age of the patients was 68.2±12.8 years old, and 75% were men.

The participants were stratified into two groups based on the presence of DM. Table 1 shows a comparison of the baseline clinical characteristics between the DM and non-DM groups. The DM group had a significantly higher BMI and a higher prevalence of hyperlipidemia than the non-DM group. In contrast, a current smoking habit and hypertension were significantly more prevalent in the non-DM group than in the DM group. Regarding the history of major vascular diseases, a history of coronary artery disease or stroke was significantly more frequent in the DM group than in the non-DM group. Importantly, the frequency of cardiac arrest on admission was significantly higher in the DM group than in the non-DM group, despite no apparent differences in systolic and diastolic blood pressure values on admission between the two groups.

The prevalence of ST-elevated MI was significantly lower in the DM group than in the non-DM group. Significant differences were observed between the two groups in terms of the ejection fraction on admission, serum creatinine level, eGFR, serum B-type natriuretic peptide (BNP) level, and Killip status. A blood examination of serum lipid profiles revealed a significantly higher triglyceride level and a significantly lower LDL-cholesterol level in the DM group than in the non-DM group.

A detailed comparison of the patient management strategies is presented in Table 2. In the DM group, emergent coronary angiography and PCI were performed significantly less frequently than in the non-DM group. In addition, the prevalence of lesions involving the left main coronary artery was significantly higher in the DM group than in the non-DM group. Furthermore, patients in the DM group underwent CABG significantly more frequently than in the non-DM group.

Regarding mechanical support, patients in the DM group received significantly more frequent treatments with mechanical ventilation, intra-aortic balloon pump, and veno-atrial extracorporeal membrane oxygenation than in the non-DM group. As a result, in-hospital mortality was significantly higher and the length of hospital stay significantly longer in the DM group than in the non-DM group. The Kaplan-Meier survival curve of in-hospital mortality (within 30 days after admission), illustrated in Fig. 1, shows a significant difference between the two groups. The HR for in-hospital mortality in the DM group was 1.87 (95% confidence interval: 1.19-2.93, p=0.007).

The in-hospital mortality rate of the 1,140 patients included in this study was 6.6%. A comparison of the causes of in-hospital death between the two groups is shown in Fig. 2. Nearly half of the causes were attributed to cardiogenic shock (CS) in both groups. However, the remaining causes of death appeared to differ between the two groups, particularly in terms of mechanical complications, infection, and malignant disease. When comparing the causes of death, a higher proportion of non-cardiac deaths (including infections, malignancies, strokes, and multiple organ failures) were observed in the DM group than in the non-DM group (32% vs. 14%, p=0.046, respectively). Deaths due to mechanical complications were more frequent in the non-DM group than in the DM group; however, the difference was not statistically significant (DM: 16% vs. non-DM: 32%, p=0.119). When examining the relationship between the timing of death and its causes, it was found that, for both groups, the majority of deaths until the third clinical day were predominantly due to CS or mechanical complications. However, regarding the causes of death after the tenth clinical day, in the DM group, the proportion of deaths attributed to CS or mechanical complications was <30%, with a greater number of patients dying from other causes, such as lethal arrhythmias, cerebral infarction, infections, and malignancies. In contrast, in the non-DM group, the proportion of patients dying from CS or mechanical complications remained high (65%).

Factors potentially associated with in-hospital mortality were individually compared between those who survived and those who died in both the DM and non-DM groups (Table 3). In the DM group, statistically significant differences were observed in the age, hypertension, current smoking habit, history of stroke, Killip status, ejection fraction on admission, renal dysfunction (eGFR <60 mL/min/1.73 m²), and serum BNP levels between the survival and in-hospital death subgroups. However, these factors showed slight variation in the non-DM group. Interestingly, the sex, history of atrial fibrillation, and ST elevation were also found to be significantly different factors in the non-DM group. Notably, in the non-DM group, a history of stroke no longer had a significant impact on in-hospital death when comparing the surviving and deceased patients.

The predictors of in-hospital mortality for both the DM and non-DM groups were analyzed separately using univariate analyses, and the results are shown in Table 4. Any factors found to be statistically significant in the univariate analyses in either group were included in the Cox's proportional hazards model to identify independent predictors of in-hospital death, as shown in Table 5. Consequently, CS, renal dysfunction, and a history of stroke independently predicted in-hospital mortality in the DM group. Conversely, CS and renal dysfunction were independent predictors of in-hospital mortality in the non-DM group. Furthermore, in the non-DM group, patients who underwent revascularization (emergency PCI or CABG) had a lower risk of in-hospital mortality than those who did not, but this difference was not statistically significant in the DM group. An interaction test for in-hospital death using a two-way analysis of variance showed that there was an interaction between “DM” and “a history of stroke” (p=0.006).

In addition, we focused on patients with CS (n=97) and compared in-hospital mortality between patients with DM (n=47) and those without DM (n=50). In-hospital deaths were observed in 23 CS cases in the DM group (48.9%) and 19 CS cases in the non-DM group (38.0%). The DM group had a higher mortality rate; however, these differences were not statistically significant (p=0.277).

Several limitations associated with the present study warrant mention. In this study, diabetes was defined according to criteria established from prior AMI research and existing literature. Intraday glucose variability and oral glucose tolerance tests were not performed, potentially leading to some cases of diabetes or impaired glucose tolerance being categorized as nondiabetic. This limitation was inherent to this study. Furthermore, despite the availability of the latest 4th version of the universal definition (24), we chose to apply the 3rd version of the universal definition (7) in this study. This decision was made because the 3rd definition was used during the recruitment period. However, it is important to acknowledge that the composition of the enrolled patient population may not have substantially differed; therefore, we employed the 3rd universal definition (25). Finally, the door-to-balloon time is a well-established mortality parameter in AMI patients (26). However, our study had a substantial proportion of NSTEMI patients (approximately 40%); therefore, we did not include this parameter in our analysis.