European Journal of Cardiovascular Medicine

Stroke is one of the leading causes of mortality and long-term disability worldwide. According to the World Health Organization (WHO), stroke is defined as “rapidly developing clinical signs of focal or global disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than vascular origin.(1). Among the types of stroke, acute ischemic stroke (AIS), caused by the sudden occlusion of cerebral arteries, accounts for approximately 85% of all cases (2). Despite advances in thrombolytic therapies and acute care, AIS continues to pose a significant challenge due to its high rates of morbidity and functional impairment. Therefore, early identification of prognostic biomarkers is crucial for timely risk stratification, targeted therapy, and improved post-stroke care. In recent years, inflammation and oxidative stress have emerged as key mechanisms in the pathophysiology of AIS, drawing attention to biomarkers that reflect these processes (3,4).

Serum ferritin, primarily known as an iron storage protein, also functions as an acute-phase reactant. Its levels rise significantly in response to inflammation, infection, and oxidative stress (5). Elevated serum ferritin has been observed in various neurological disorders and is increasingly being investigated as a potential prognostic biomarker in stroke. Ferritin contributes to oxidative neuronal injury by catalyzing the formation of reactive oxygen species, thereby worsening ischemic damage and impairing recovery (6).

The Modified Rankin Scale (mRS) is a widely accepted tool used to assess functional outcomes and degree of disability following a stroke. It provides a simple yet effective scale ranging from 0 (no symptoms) to 6 (death), allowing clinicians to classify post-stroke recovery and long-term prognosis (7). While several studies have evaluated the relationship between serum ferritin and stroke severity, few have specifically focused on its association with functional outcomes as measured by the mRS (8,9).

Given this background, the present study aims to assess the prognostic value of serum ferritin in patients with acute ischemic stroke by correlating its levels at admission, on day 7, and at discharge with functional outcomes using the modified Rankin Scale. By evaluating this relationship, the study seeks to determine whether serum ferritin can serve as a predictive marker of disability and recovery in AIS, thereby aiding in early intervention and individualized patient care.

This prospective observational study was conducted at a tertiary care hospital to evaluate the prognostic value of serum ferritin in patients with acute ischemic stroke (AIS), with functional outcomes assessed using the modified Rankin Scale (mRS). A total of 120 patients diagnosed with AIS were included based on predefined inclusion and exclusion criteria, using a convenient sampling method.

Inclusion criteria were patients aged 18 years and above, presenting with symptoms of AIS confirmed by clinical examination and neuroimaging (CT/MRI). Exclusion criteria included patients with hemorrhagic stroke, chronic inflammatory conditions, disorders of iron metabolism, chronic liver or kidney disease, malignancy, or those currently receiving iron supplementation. Demographic details, clinical history, and baseline laboratory parameters were recorded at admission. Functional outcomes were assessed using the modified Rankin Scale (mRS) at three time points: on admission, on day 7 of hospital stay, and at the time of discharge or death.

Patients were classified into three outcome groups based on their scores on the modified Rankin Scale (mRS). Group A included patients with a good functional outcome, defined as an mRS score of 0 to 2, indicating no symptoms to slight disability but overall independence. Group B comprised those with moderate to severe disability, with mRS scores ranging from 3 to 5, reflecting varying degrees of dependence in daily activities. Group C included patients who died during hospitalization, corresponding to an mRS score of 6. This classification allowed for a structured evaluation of the association between serum ferritin levels and functional outcomes following acute ischemic stroke. Venous blood samples were collected to measure serum ferritin levels at admission, on day 7, and at discharge or death. Ferritin levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Other laboratory investigations included complete blood count (CBC), inflammatory markers, and lipid profile.

Data were compiled and analyzed using IBM SPSS Statistics version 26.0. Descriptive statistics such as mean, standard deviation, frequency, and percentage were used to summarize baseline characteristics. Comparative analysis of serum ferritin levels across different mRS outcome groups was conducted using appropriate statistical tests. A p-value < 0.05 was considered statistically significant. Ethical clearance for the study was obtained from the Institutional Ethics Committee. Written informed consent was collected from all participants or their legal guardians. All data were anonymized to ensure confidentiality and compliance with ethical standards.

This section presents the findings of our study on serum ferritin as a prognostic marker in acute ischemic stroke (AIS) among 120 patients, with a focus on functional outcomes assessed using the modified Rankin Scale (mRS). The results include demographic characteristics, clinical risk factors, and serum ferritin levels measured at three time points—at admission, on day 7, and at discharge or death. Patients were categorized into outcome groups based on mRS scores to evaluate the association between serum ferritin levels and stroke-related disability or mortality. Statistical analyses revealed significant differences in ferritin levels across the mRS outcome groups, supporting the utility of serum ferritin as a reliable prognostic biomarker for functional outcome in AIS patients.

The distribution of study subjects according to demographic characteristics, comorbidities, lifestyle risk factors, and clinical outcomes is summarized below. Among the 120 patients with acute ischemic stroke (AIS), 61.7% were male and 38.3% were female, indicating a male predominance. A significant proportion of patients (77.5%) were aged above 46 years, with 39.2% being over 60 years of age. Hypertension was the most prevalent comorbidity, observed in 58.3% of patients, followed by diabetes mellitus in 33.3%. Regarding lifestyle-related risk factors, 40.8% of patients had a history of smoking or tobacco chewing, and 25.8% reported alcohol consumption. The overall survival rate was 90.8%, while 9.2% of the patients succumbed during the course of hospitalization. These findings reflect the high burden of vascular and lifestyle-related risk factors among AIS patients and underscore the importance of early risk assessment and preventive strategies. (Table 1)

The comparison of serum ferritin levels between survivors and non-survivors at different time points revealed significantly higher ferritin concentrations among patients who died. At admission, the mean serum ferritin level was 127.42 ng/mL in survivors, compared to 353.76 ng/mL in non-survivors (p = 0.002), indicating a strong association between elevated ferritin levels and poor prognosis. This pattern persisted on day 7 (128.56 ng/mL vs. 343.19 ng/mL, p < 0.001) and at discharge or death (130.15 ng/mL vs. 348.29 ng/mL, p < 0.001). These statistically significant differences across all three time points suggest that persistently elevated serum ferritin levels are strongly correlated with increased mortality in AIS patients, highlighting its potential utility as a prognostic biomarker in clinical practice (Table 2).

The modified Rankin Scale (mRS) was used to assess stroke severity and functional outcomes at admission, on Day 7, and at discharge/death. At admission, the majority of patients (98.3%) were in Group B (mRS 3-5), indicating significant disability, while only 1.7% had good functional status (Group A, mRS 0-2). By Day 7, the proportion of patients in Group A improved to 34.2%, while 64.1% remained in Group B, and 0.83% had died (Group C, mRS 6). At discharge, functional outcomes further improved, with 57.5% in Group A, while 33.3% remained moderately to severely disabled (Group B) and 9.2% did not survive (Group C). (Table 3)

The comparison of serum ferritin levels across the modified Rankin Scale (mRS) score groups at different time points reveals a significant association between higher ferritin levels and poorer prognosis in acute ischemic stroke patients. At admission, there was no statistically significant difference in ferritin levels between Group A (good prognosis) and Group B (bad prognosis) (p = 0.94), indicating that initial ferritin levels did not significantly distinguish between the groups. However, by day 7, serum ferritin levels showed a marked increase in Group B (180.40 ± 112.09 ng/mL) and Group C (worst prognosis/death) (263.30 ± 32.10 ng/mL) compared to Group A (82.21 ± 46.63 ng/mL), with a statistically significant difference between Groups A and B (p < 0.001) and Groups A and C (p = 0.009), suggesting that increasing ferritin levels were associated with worsening outcomes. By the time of discharge or death, serum ferritin levels remained significantly elevated in Group B (188.65 ± 84.43 ng/mL) and Group C (348.29 ± 154.47 ng/mL) compared to Group A (96.24 ± 48.42 ng/mL), with all intergroup comparisons showing highly significant differences (p < 0.001). This indicates that persistently elevated serum ferritin levels correlate strongly with stroke severity and poor prognosis, supporting its potential role as a prognostic biomarker in acute ischemic stroke. (Table 4)

Acute ischemic stroke (AIS) is a major cause of mortality and long-term disability, primarily resulting from the obstruction of cerebral blood flow. Early identification of reliable prognostic markers is essential for predicting clinical outcomes and guiding appropriate therapeutic interventions. Among emerging biomarkers, serum ferritin—traditionally known as an iron-storage protein—has gained attention for its additional role as an acute-phase reactant involved in inflammation and oxidative stress, both of which are central to AIS pathophysiology. Several studies have demonstrated a positive correlation between elevated serum ferritin levels and poor functional outcomes in stroke patients. These outcomes are commonly measured using the modified Rankin Scale (mRS), which quantifies post-stroke disability. Higher ferritin levels at admission and throughout hospitalization have been associated with increased degrees of disability, highlighting its potential as a valuable prognostic tool. However, the interpretation of serum ferritin must be approached with caution, as its levels can be influenced by confounding factors such as infections, chronic inflammatory conditions, liver dysfunction, and malignancy. Despite these limitations, serum ferritin remains a promising biomarker for functional outcome prediction in AIS.

In our study, the majority of patients with acute ischemic stroke (AIS) were male (61.7%), while 38.3% were female, indicating a male predominance in stroke incidence. Most patients were from the elderly age group (>60 years), followed by those in the 46–60-year range. These findings are consistent with previous research. For instance, SankarBhuyan S et al. (10) reported that the majority of stroke patients in their study were aged between 51 and 70 years, with an age range of 32 to 80 years. Similarly, Sadek N et al. (11) observed a mean age of 65.66 years, with patients ranging from 35 to 94 years. In another study, Garg R et al. (5) found that 54% of patients fell within the 61–70 year age group, with a mean age of 66.62 years. These findings collectively underscore the fact that advancing age is a significant risk factor for AIS. Elderly patients are not only more susceptible to stroke but also tend to experience more severe neurological deficits and poorer functional outcomes.

Comorbidities play a significant role in influencing the prognosis of acute ischemic stroke (AIS). In the present study, hypertension (58.3%) emerged as the most prevalent comorbidity, followed by diabetes mellitus (33.3%). Additionally, 40.8% of patients had a history of smoking or tobacco chewing, and 25.8% reported alcohol consumption. These findings align with the study by SankarBhuyan S et al. (10),, who reported a higher prevalence of hypertension and diabetes among AIS patients, particularly in those with poor outcomes. Similarly, Sadek et al. (11) observed an even greater burden of these comorbidities, with 76% of patients having hypertension and 52% having diabetes. The presence of these risk factors—especially hypertension and diabetes—is strongly associated with increased stroke severity, while lifestyle factors such as smoking and alcohol use further contribute to adverse outcomes. These results underscore the importance of targeted risk factor modification and preventive strategies to mitigate the overall burden and long-term disability associated with AIS.

In the present study, the mortality rate was 9.2%, with 90.8% of patients surviving following acute ischemic stroke. This observed mortality is notably lower than that reported in previous studies. For instance, SankarBhuyan S et al. (10) documented a significantly higher mortality rate of 35%, with most deaths occurring in patients aged 51–70 years. Similarly, Chauhan DS et al. (12) reported a 23.3% mortality rate, with 24 patients deteriorating and 22 showing clinical improvement during hospitalization. The relatively lower mortality in our cohort may be attributed to factors such as early diagnosis, timely medical intervention, and improved stroke care protocols at our tertiary care center. Nonetheless, despite the high survival rate, stroke-related disability remains a considerable concern among survivors. This underscores the critical importance of early rehabilitation and structured post-stroke care strategies to improve long-term functional outcomes and quality of life.

Serum ferritin levels demonstrated a strong association with stroke prognosis in this study. Patients who survived had consistently lower ferritin levels across all measured time points compared to those who did not survive. At admission, the mean serum ferritin level among survivors was 127.42 ng/mL, significantly lower than the 353.76 ng/mL observed in non-survivors (p = 0.002). This trend persisted on day 7 (128.56 ng/mL vs. 343.19 ng/mL, p = 0.001) and at discharge or death (130.15 ng/mL vs. 348.29 ng/mL, p = 0.001), highlighting a sustained elevation of ferritin levels in patients with poor outcomes. These findings are consistent with previous literature. Mandal SK et al. (6) reported significantly higher ferritin levels in AIS patients (83.1 ng/mL) compared to healthy controls (41.3 ng/mL), supporting its role as an inflammatory marker in stroke. Similarly, Garg R et al. (5) found elevated ferritin levels in patients with severe stroke (282.77 ng/mL) compared to those with less severe presentations (205.12 ng/mL). Collectively, these observations reinforce the utility of serum ferritin as a prognostic biomarker in AIS, with elevated levels indicating greater inflammatory burden, more extensive neuronal injury, and worse clinical outcomes.

The modified Rankin Scale (mRS) was used to evaluate functional outcomes in AIS patients. At admission, 98.3% had poor prognosis (mRS 3–5), and only 1.7% had good prognosis (mRS 0–2). By day 7, 34.4% improved to a good prognosis, increasing to 57.5% at discharge, while 9.2% of patients died (mRS 6). These findings align with Sultana J et al. (9), who reported a higher ferritin level in patients with more severe strokes. Similarly, Koul RK (14) and Santhosh BT (14) found a positive correlation between elevated serum ferritin and greater disability, supporting the utility of mRS and ferritin as prognostic tools in AIS.

Serum ferritin is a potential prognostic biomarker in acute ischemic stroke (AIS), showing strong correlation with disability, poor outcomes, and mortality. It may aid in early risk stratification, though confounding factors like infection must be considered. Standardized measurement and further research are needed to validate its clinical utility and explore therapeutic targets related to iron metabolism.

Conflict of Interest: The authors declare no conflict of interest.

Source of Funding: This research received no external funding.

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