ST-Elevation Myocardial Infarction (STEMI) remains a critical manifestation of coronary artery disease, accounting for a significant proportion of cardiovascular morbidity and mortality worldwide. Despite advancements in reperfusion therapies, the global burden of STEMI is still substantial, with post-infarction complications and mortality posing clinical challenges (1,2). The pathophysiology of STEMI involves not only plaque rupture and thrombus formation but also a robust inflammatory response that contributes to myocardial damage and adverse outcomes (3).

Inflammation is now recognized as a central player in the initiation, progression, and complications of atherosclerosis and myocardial infarction. Several pro-inflammatory cytokines, notably Interleukin-6 (IL-6), C-reactive protein (CRP), and Tumor Necrosis Factor-alpha (TNF-α), have been implicated in the modulation of vascular endothelial function, plaque instability, and myocardial injury (4,5). Elevated levels of these biomarkers are frequently observed in acute coronary syndromes and have been linked to larger infarct sizes, reduced left ventricular ejection fraction (LVEF), and poorer prognosis (6,7).

IL-6, a pleiotropic cytokine produced by activated leukocytes, endothelial cells, and cardiomyocytes, stimulates the hepatic synthesis of acute-phase proteins like CRP and promotes vascular inflammation (8). CRP, an established marker of systemic inflammation, has been shown to correlate with both the extent of myocardial necrosis and risk of recurrent ischemic events (9). TNF-α, another critical mediator, contributes to cardiomyocyte apoptosis, negative inotropic effects, and remodeling after infarction (10,11).

Although previous studies have explored the association of these inflammatory markers with cardiovascular outcomes, few have concurrently evaluated IL-6, CRP, and TNF-α in a prospective design specific to STEMI populations. This study aims to investigate the correlation between these inflammatory biomarkers and infarct severity, in-hospital complications, and short-term outcomes in patients with STEMI. Understanding these relationships could enhance early risk stratification and potentially guide anti-inflammatory therapeutic strategies.

A total of 120 consecutive patients aged 30–75 years, diagnosed with ST-Elevation Myocardial Infarction (STEMI) as per the standard criteria of chest pain lasting >20 minutes, ST-segment elevation ≥1 mm in two contiguous ECG leads, and elevated cardiac biomarkers, were included. Patients presenting within 12 hours of symptom onset were eligible. Exclusion criteria included prior myocardial infarction, chronic inflammatory diseases, malignancy, severe hepatic or renal dysfunction, and current use of immunosuppressive therapy.

Data Collection

Baseline demographic data, cardiovascular risk factors (such as smoking, hypertension, diabetes mellitus, and dyslipidemia), and clinical characteristics were recorded at admission. A standard 12-lead electrocardiogram and echocardiographic assessment were performed for all patients. Blood samples were collected at admission (within 12 hours of symptom onset) for routine investigations and measurement of inflammatory markers.

Biomarker Analysis

Serum levels of IL-6, CRP, and TNF-α were quantified using enzyme-linked immunosorbent assay (ELISA) kits (BioLegend, USA), following the manufacturer’s protocols. All samples were processed in duplicate to ensure accuracy. Peak serum troponin I levels were measured to estimate infarct size. Left ventricular ejection fraction (LVEF) was assessed via transthoracic echocardiography within 48 hours of admission using the modified Simpson’s method.

Outcome Measures

The primary outcome was the correlation of IL-6, CRP, and TNF-α levels with infarct severity, defined by peak troponin I and LVEF. Secondary outcomes included in-hospital adverse events (such as arrhythmias, heart failure, cardiogenic shock, and reinfarction) and 30-day mortality. Patients were followed up for 30 days post-discharge through outpatient visits or telephonic interviews.

Statistical Analysis

Data were analyzed using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. Pearson or Spearman correlation coefficients were used to assess the relationship between biomarker levels and infarct severity indicators. Logistic regression was performed to evaluate the association between high biomarker levels (upper tertile) and adverse outcomes. A p-value < 0.05 was considered statistically significant.

A total of 120 patients diagnosed with ST-Elevation Myocardial Infarction (STEMI) were included in the study. The mean age of participants was 58.3 ± 10.2 years, with a male predominance (n = 92; 76.7%). Common cardiovascular risk factors included hypertension (62.5%), diabetes mellitus (40.8%), and smoking (53.3%).

Serum Biomarker Levels and Infarct Severity

The mean serum levels of the inflammatory biomarkers were as follows: IL-6: 48.6 ± 12.3 pg/mL, CRP: 28.4 ± 9.1 mg/L, and TNF-α: 22.7 ± 7.4 pg/mL. These values were analyzed for correlation with peak troponin I and left ventricular ejection fraction (LVEF). Patients in the highest tertile of IL-6 had significantly higher troponin I values (27.8 ± 6.2 ng/mL) and lower LVEF (38.1 ± 6.4%) compared to those in the lowest tertile (troponin I: 16.4 ± 4.5 ng/mL; LVEF: 49.3 ± 7.2%) (Table 1).

Table 1. Mean Inflammatory Biomarker Levels Across Tertiles and Their Correlation with Infarct Severity

Significant inverse correlations were observed between IL-6 and LVEF (r = -0.58, p < 0.001), and between TNF-α and LVEF (r = -0.42, p = 0.004). CRP showed a moderate positive correlation with peak troponin I (r = 0.47, p = 0.001). These findings are summarized in Table 2.

Table 2. Correlation between Biomarker Levels and Infarct Severity Indicators

Clinical Outcomes and Biomarker Association

In-hospital complications occurred in 37 patients (30.8%), with higher rates observed in the highest tertile of IL-6 (52.5%) compared to the lowest tertile (15%). Thirty-day mortality was recorded in 11 patients (9.2%), all of whom had elevated levels of at least two inflammatory biomarkers. Logistic regression analysis revealed that elevated IL-6 (>60 pg/mL) independently predicted 30-day mortality (OR: 4.9; 95% CI: 1.6–14.5; p = 0.006) and adverse events (OR: 3.4; 95% CI: 1.7–6.8; p = 0.002).

These data indicate that elevated IL-6, CRP, and TNF-α levels are significantly associated with greater myocardial damage and poorer early clinical outcomes in STEMI patients (Tables 1 and 2).

The present prospective cohort study demonstrated a significant association between elevated levels of inflammatory biomarkers—IL-6, CRP, and TNF-α—and increased infarct severity and adverse short-term outcomes in patients with ST-Elevation Myocardial Infarction (STEMI). These findings reinforce the growing understanding of the role of systemic inflammation not only in the pathogenesis of atherosclerosis but also in the extent of myocardial injury and the prognosis of acute coronary syndromes.

IL-6 was found to have the strongest correlation with both peak troponin I levels and reduced LVEF, underscoring its potential utility as a marker for myocardial necrosis. IL-6 is a pleiotropic cytokine involved in leukocyte activation, endothelial dysfunction, and hepatic production of acute-phase reactants, such as CRP (1). Elevated IL-6 levels have been previously linked to larger infarct sizes and adverse ventricular remodeling (2,3). Our findings are in line with Nishikawa et al., who reported that IL-6 levels within the first 24 hours of infarction predicted left ventricular dysfunction and clinical outcomes (4).

CRP, an acute-phase protein, showed a moderate positive correlation with troponin I and an inverse correlation with LVEF, consistent with prior studies indicating that CRP reflects ongoing inflammation and myocardial injury (5,6). Ridker et al. have emphasized the prognostic significance of CRP in post-infarction patients, particularly regarding recurrent ischemic events (7). Similarly, Suleiman et al. demonstrated that elevated CRP at admission was an independent predictor of 30-day mortality in STEMI patients (8).

TNF-α, another pro-inflammatory cytokine, also demonstrated significant inverse correlation with LVEF and was associated with poor outcomes. TNF-α has been implicated in the pathogenesis of ventricular dysfunction through its negative inotropic effects, induction of apoptosis, and promotion of extracellular matrix remodeling (9). Elevated TNF-α levels in acute MI have been correlated with increased infarct size and higher mortality risk (10,11).

Importantly, patients in the highest tertile of biomarker levels experienced a significantly greater incidence of in-hospital complications and 30-day mortality. These findings support the hypothesis that inflammatory activity directly contributes to myocardial injury and may amplify adverse cardiovascular events. Such results are consistent with studies by Miettinen et al. and Biasucci et al., which showed elevated cytokine levels in high-risk acute coronary syndrome populations (12,13).

The prognostic value of combining multiple inflammatory markers also warrants attention. In our study, individuals with elevated IL-6, CRP, and TNF-α concurrently had worse outcomes than those with elevations in a single marker, a finding echoed by Liuzzo et al., who proposed that biomarker clustering enhances risk stratification (14,15).

Despite these insights, the study has certain limitations. The relatively small sample size and single-center design may limit the generalizability of the findings. Furthermore, serial measurement of biomarkers and long-term follow-up were not conducted, which could have provided additional information on chronic inflammation and its effect on cardiac remodeling. Nevertheless, the strength of the study lies in its prospective design and focused evaluation of three key inflammatory markers using standardized assays.

Elevated levels of IL-6, CRP, and TNF-α are significantly associated with increased infarct severity and poorer short-term outcomes in STEMI patients. These inflammatory biomarkers can serve as valuable adjuncts for early risk stratification and may guide future therapeutic strategies targeting inflammation in acute myocardial infarction.

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