European Journal of Cardiovascular Medicine

Acute myocardial infarction (AMI), commonly known as a heart attack, remains a significant global health burden and one of the leading causes of mortality worldwide¹. This condition, characterized by myocardial necrosis due to sustained ischemia, requires urgent diagnosis and intervention to improve outcomes. While biomarkers like cardiac troponins and creatine kinase-MB remain pivotal for diagnosing AMI, emerging evidence suggests that markers reflecting systemic inflammation and oxidative stress, such as serum ferritin could enhance risk stratification and prognostic accuracy^2-3. Serum ferritin serves as a crucial marker of iron storage and also functions as an acute-phase reactant during inflammatory states⁴. In the context of AMI, systemic inflammation is a key driver of pathogenesis, influencing plaque instability and myocardial damage. Studies have shown that elevated ferritin levels in AMI patients are associated with worse cardiovascular outcomes, including impaired left ventricular function and higher mortality rates. This elevation reflects not only an acute inflammatory response but also potential dysregulation in iron metabolism, which can exacerbate oxidative damage and contribute to myocardial injury⁵. Conversely, low serum ferritin, often indicative of iron deficiency, may impair oxygen delivery to ischemic myocardial tissues, underscoring the dual implications of ferritin in cardiovascular health. Integrating serum ferritin measurements into traditional diagnostic frameworks for acute myocardial infarction (AMI) may improve clinical risk stratification by providing insight into the underlying inflammatory status. While cardiac troponins and CK-MB effectively detect myocardial injury, they do not reflect systemic inflammation⁶, which plays a critical role in patient prognosis. Elevated ferritin levels, when assessed alongside troponin, may help identify AMI patients at increased risk of complications due to a hyperinflammatory state, enabling more targeted monitoring and timely therapeutic interventions. In addition to their diagnostic value, serum ferritin holds significant promise as prognostic markers in AMI. Prospective studies have consistently linked elevated ferritin levels with long-term adverse outcomes, including recurrent myocardial infarction and cardiovascular mortality. In addition to its diagnostic value, serum ferritin shows strong potential as a prognostic marker in acute myocardial infarction (AMI). Because ferritin reflects underlying inflammation, its dynamic changes may also serve as a tool for therapeutic monitoring, with reductions indicating response to anti-inflammatory interventions^7-8. Therapeutically, targeting serum ferritin pathways presents promising opportunities in acute myocardial infarction (AMI)⁹. Anti-inflammatory interventions, such as iron chelators or cytokine-specific therapies, may help modulate elevated ferritin levels and thereby improve outcomes in patients with heightened inflammatory responses¹⁰. As a marker of systemic inflammation, ferritin offers both diagnostic and therapeutic utility, potentially guiding personalized anti-inflammatory strategies in AMI care. Its integration into clinical practice could enhance risk stratification, support targeted treatment decisions, and improve prognostic accuracy^11-12 As evidence grows, serum ferritin is emerging as a key biomarker in the evolving field of precision cardiology^3,13.

AIM

Study of relationship of Serum Ferritin in Acute Myocardial Infarction.

This hospital-based observational case-control study was conducted in the Department of Medicine at Mahatma Gandhi Medical College and Hospital, Jaipur, a tertiary care centre, over a period of 18 months from April 2023 to September 2024. The study included a total of 320 participants, comprising 160 patients diagnosed with acute myocardial infarction (MI) and 160 age- and sex-matched healthy controls. All participants were between 18 and 65 years of age and were either admitted to or attended the outpatient or emergency services of the hospital during the study period. Diagnosis of AMI was based on European Society of Cardiology/ American College of Cardiology- fourth universal definition of myocardial infarction- 2018 guidelines, which included clinical symptoms such as chest pain and shortness of breath, electrocardiographic changes (ST- elevation/ depression) suggestive of infarction, elevated cardiac biomarkers (troponin – T/I, CK-MB), development of pathological Q wave or new-onset bundle branch block. For the evaluation of serum ferritin as a biomarker in MI, patients with conditions known to influence ferritin levels were excluded to minimize confounding. These included individuals with hemochromatosis, porphyria, chronic inflammatory disorders, liver malignancy, recent blood transfusion, or those receiving iron supplementation therapy. Additionally, patients with a past history of acute MI were excluded to ensure accurate assessment of serum ferritin in the context of new-onset myocardial infarction.

Each participant, both cases and controls, was enrolled after obtaining informed written consent following a thorough explanation of the study protocol in their preferred language. A structured data collection proforma was used to ensure uniformity and completeness. Demographic details (age, gender), lifestyle habits (smoking, alcohol intake, physical activity), comorbidities (diabetes mellitus, hypertension, dyslipidaemia), and family history of cardiovascular disease were recorded meticulously.

For cases, detailed history was taken at admission, focusing on the onset, duration, nature, and radiation of chest pain, associated symptoms, and past cardiac events. A thorough clinical examination was performed including vital signs, cardiovascular system examination, and systemic assessment. A 12-lead electrocardiogram (ECG) was recorded for all patients on admission and repeated as necessary. Blood samples were drawn within the first 24 hours of admission for laboratory evaluation.

All study participants underwent the following laboratory investigations: Complete Blood Count (CBC), Liver Function Tests (LFTs), Renal Function Tests (RFTs), Fasting and Postprandial Blood Glucose, Lipid Profile (Total cholesterol, LDL, HDL, Triglycerides), Serum Ferritin, Serum Creatine Kinase-MB (CK-MB), Troponin-T (Trop-T) assay.

Serum samples were analysed using standardized automated analysers following institutional quality control protocols. Data from both groups were tabulated and processed for statistical comparison of biochemical and clinical variables. All data collection was performed by trained physicians and lab personnel under the supervision of senior investigators, ensuring adherence to ethical and scientific standards. Statistical testing was conducted with the statistical package for the social science system version SPSS 20.0. Continuous variables were presented as Mean ± SD or median (IQR) for non-normally distributed data. Categorical variables were expressed as frequencies and percentages. The comparison of normally distributed continuous variables between the groups was performed using Student‘s t test else Mann Whitney U test was used for non-normal distribution data. Nominal categorical data between the groups were compared using Student t-test, Chi-squared test, Fisher‘s exact test or as appropriate. Multivariate analysis was done in the end. For all statistical tests, a p value less than 0.05 were taken to indicate a significant difference. Results were graphically represented where deemed necessary. Graphical representation was done in MS Excel 2010.

Table 1: Age Distribution in MI and Non-MI Groups

The MI group had significantly fewer individuals aged <40 years and more individuals aged ≥61 years compared to the non-MI group (p<0.0001), indicating higher MI occurrence in older age. Most participants in both groups were aged 40–60 years, with a slightly higher proportion in the non-MI group.

Table 2: Distribution of Affected Cardiac Wall in MI Patients

 Among MI patients, the Inferior Wall was most commonly affected (40%), followed by the Septal Wall (31.9%), indicating these regions are more prone to infarction. The Lateral (14.4%) and Anterior (13.7%) Walls were less frequently involved.

Table 3: Distribution of Co-Morbidities in MI and Non-MI Groups

Hypertension and diabetes mellitus were significantly more prevalent in MI patients than in non-MI individuals, highlighting their strong association with myocardial infarction risk (p < 0.0001).

Table 4: Distribution of Mean BMI in MI and Non-MI Groups

The mean BMI was significantly higher in the MI group (26.72 ± 4.34 kg/m²) compared to the non-MI group (23.62 ± 3.06 kg/m²) (p < 0.0001), indicating a strong association between increased BMI and MI

Table 5: Comparison of Haematological Between MI and Non-MI Groups

Table 5 highlights significant differences in key biochemical markers between MI and Non-MI groups. While haemoglobin and ESR levels showed no statistically significant variation, LDH and hs-CRP were significantly elevated in MI patients, reflecting myocardial damage and systemic inflammation. Troponin-I levels were markedly higher in the MI group, underscoring its diagnostic accuracy in identifying myocardial infarction (p<0.0001).

Table 6: Comparison of abnormal Serum Ferritin Levels between MI and Non-MI Groups

Table 6 shows that elevated serum ferritin levels (≥200 μg/L) were significantly more prevalent in MI patients (63.8%) compared to non-MI individuals (18.2%) (p < 0.0001). The mean ferritin concentration was also markedly higher in the MI group, indicating a strong association between elevated ferritin and increased cardiovascular risk.

Table 7: Comparison of Mean Abnormal Serum Ferritin Levels Between MI and Non-MI Groups

The mean serum ferritin concentration was significantly higher in the MI group (220.78 ± 17.98 ng/mL) compared to the non-MI group (154.39 ± 45.76 ng/mL) (p < 0.0001), indicating a potential role of ferritin in cardiovascular risk.

Table 8: Distribution of Serum Ferritin Levels in MI and Non-MI Groups

Table 8 reveals that elevated (200–299 μg/L) and very high (≥300 μg/L) serum ferritin levels were significantly more prevalent among MI patients, while low and moderate levels were more common in non-MI individuals (p < 0.0001). This distribution underscores a strong association between higher ferritin concentrations and increased risk of myocardial infarction.

Table 9: Correlation of Serum Ferritin with Established Markers of Acute Myocardial Infarction

Table 9 shows that serum ferritin had strong, statistically significant positive correlations with Troponin-I (r = 0.68), CK-MB (r = 0.72), and hs-CRP (r = 0.60), highlighting its association with myocardial injury and inflammation (p < 0.0001). Its correlation with LDH was moderate (r = 0.64) but not statistically significant (p = 0.342), suggesting limited utility with this marker.

Table 10: Relationship of Serum Ferritin with Established Risk Factors of Acute Myocardial Infarction

Table 10 shows that serum ferritin levels had a significant positive correlation with hypertension (r = 0.51, p < 0.0001) and dyslipidaemia (r = 0.62, p < 0.0001), indicating their potential role in cardiovascular risk. Correlations with diabetes, smoking, and obesity were moderate to weak but statistically insignificant, suggesting limited associations in these domains.

Table 11: Reliability of Serum Ferritin as Clinical Markers for Acute Myocardial Infarction

The AMI group exhibited a significantly higher serum ferritin level (220.78 ± 17.98 ng/mL) compared to the control group (154.39 ± 45.76 ng/mL) with a p-value of <0.001, indicating a statistically significant difference. The sensitivity of serum ferritin for diagnosing AMI was 84.2%, meaning that it correctly identified this percentage of AMI patients, while the specificity was 86.2%, indicating that this percentage of non-AMI individuals were accurately classified. The AUC value of 0.62 (95% CI: 0.55-0.70) suggests a moderate diagnostic performance for serum ferritin in distinguishing AMI patients from controls.

This hospital based cross sectional study analysed 160 MI patients and 160 healthy controls, aged 18–65 years, who attended or were admitted to the Department of Medicine, Mahatma Gandhi Hospital, Jaipur, between April 2023 and September 2024. The objective was to evaluate the role of serum ferritin as potential biomarkers for acute myocardial infarction (AMI) and their correlation with established cardiac, metabolic, and inflammatory markers.

The analysis revealed that individuals aged ≥61 years were more prevalent in the MI group (28.2%) compared to the non-MI group (3.7%), indicating a significant age-related risk (p < 0.0001).

The study highlights a strong association between elevated serum ferritin levels and acute myocardial infarction (AMI). A striking 63.8% of MI patients had serum ferritin levels ≥200 μg/L compared to only 18.2% in the non-MI group, and this difference was highly statistically significant (p < 0.0001). Ferritin, traditionally a marker of iron stores, also behaves as an acute-phase reactant and increases in response to inflammation and oxidative stress. In AMI, myocardial necrosis triggers a systemic inflammatory response, which can elevate serum ferritin levels irrespective of iron status. This dual role of ferritin—as a marker of both iron overload and inflammation—makes it particularly relevant in cardiovascular pathology. Supporting this observation, Rajapurkar et al¹⁵. reported that AMI patients had significantly higher median serum ferritin levels (220 µg/L) compared to controls (155 µg/L), and ferritin >200 µg/L was independently associated with MI (adjusted OR: 5.72). A meta-analysis by Wang et al¹⁵. found a consistent trend, indicating serum ferritin levels were significantly elevated in AMI across multiple studies (SMD: 0.78). The pathophysiological mechanisms proposed include ferritin’s role in catalysing the formation of reactive oxygen species (ROS) through Fenton reactions, contributing to lipid peroxidation, endothelial damage, and plaque instability—all critical events in atherosclerosis and MI.

In the present study, serum ferritin levels demonstrated significant positive correlations with established cardiac markers, underscoring its potential role as an acute-phase reactant in myocardial injury. Notably, serum ferritin showed a strong correlation with Troponin-I (r = 0.68, p < 0.0001), CK-MB (r = 0.72, p < 0.0001), and hs-CRP (r = 0.60, p < 0.0001), suggesting that elevated ferritin levels may reflect both the extent of myocardial necrosis and the accompanying inflammatory response. However, ferritin showed a weaker and statistically insignificant correlation with lactate dehydrogenase (LDH) (r = 0.64, p = 0.342), a non-specific marker of tissue injury. These findings are in line with previous studies, such as that by Aviram et al. (2008)¹⁶, which highlighted ferritin’s role in oxidative stress and cardiovascular risk due to its iron-mediated pro-oxidant properties. Overall, the significant associations between serum ferritin and key cardiac biomarkers support its potential utility as a prognostic indicator in acute myocardial infarction, reflecting both inflammation and myocardial damage.

In conclusion, this study demonstrates that serum ferritin levels are significantly elevated in patients with acute myocardial infarction compared to healthy controls. Serum ferritin showed strong positive correlations with established cardiac biomarkers such as Troponin-I, CK-MB, and hs-CRP, highlighting its role in the inflammatory and oxidative stress responses associated with myocardial injury. These findings suggest that serum ferritin may serve as a reliable adjunctive biomarker for the diagnosis and risk stratification of MI. Nonetheless, further large-scale studies are warranted to validate its clinical utility and establish standardized thresholds specific to acute coronary syndromes.

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