European Journal of Cardiovascular Medicine

According to the World Health Organisation (WHO), a stroke is defined as "rapidly developing clinical evidence of focal (or global) impairment of brain function, with symptoms lasting 24 hours or more or leading to death, with no evident cause other than vascular origin" (1). Strokes are broadly classified into two types: ischemic and hemorrhagic. Ischemic strokes, resulting from obstruction of blood flow to the brain, account for approximately 85% of all cases, whereas hemorrhagic strokes—caused by the rupture of blood vessels—constitute about 10–20% (2). Thrombotic cerebral infarctions arise due to atherosclerotic occlusion of major cervical or intracranial arteries, leading to localized ischemia. In contrast, hemorrhagic strokes, including subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), are associated with significant morbidity and mortality (3,4).

Inflammation plays a pivotal role in the pathophysiology of stroke. The activation of proinflammatory cytokines and recruitment of immune cells contribute to secondary neuronal injury (5). Elevated white blood cell (WBC) counts and neutrophilia have been linked with more severe strokes and larger infarct volumes. Additionally, inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width (RDW), and mean platelet volume (MPV) have emerged as useful indicators of stroke severity and prognosis (6). Among these, serum ferritin has recently gained interest as a potential prognostic marker in acute ischemic stroke. While traditionally known as an intracellular iron storage protein, serum ferritin also acts as an acute-phase reactant during systemic inflammation (7). Elevated ferritin levels have been associated with larger infarct sizes, poorer neurological recovery, and increased mortality in AIS patients. Iron overload-induced oxidative stress may worsen neuronal damage by generating reactive oxygen species (ROS) and promoting lipid peroxidation. Furthermore, hyperferritinemia has been implicated in promoting a prothrombotic state, potentially aggravating vascular occlusion and impeding neurological recovery (8).

Despite advances in thrombolytic therapy for AIS, a significant proportion of patients remain ineligible due to delayed presentation, contraindications, or limited access to specialized care. Identifying reliable prognostic biomarkers like serum ferritin could facilitate early risk stratification and aid in tailoring individualized treatment strategies. The present study aims to investigate the prognostic utility of serum ferritin in patients with acute ischemic stroke by measuring its levels at admission, day 7, and discharge, and analyzing its association with stroke severity and clinical outcomes. These insights may deepen our understanding of ferritin’s prognostic significance and its role in improving stroke management and patient outcomes.

A tertiary care hospital served as the site of this prospective observational investigation. Convenient sampling was used to enlist 120 individuals with acute ischaemic stroke (AIS) based on predetermined inclusion and exclusion criteria. Eligible participants were adults aged 18 years or older with a clinical diagnosis of AIS confirmed by neuroimaging (CT or MRI). Patients were excluded if they had hemorrhagic stroke, chronic inflammatory conditions, disorders of iron metabolism, chronic kidney or liver disease, malignancies, or were receiving iron supplementation.

Upon admission, detailed demographic information, medical history, and clinical parameters were recorded. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Serum ferritin levels were measured at three time points: on admission, day 7, and at discharge. Venous blood samples were collected and analyzed using enzyme-linked immunosorbent assay (ELISA). Additional investigations included complete blood count (CBC), inflammatory markers, and lipid profile assessments.

Data were analyzed using IBM SPSS Statistics Version 26.0. Descriptive statistics summarized baseline characteristics. Comparative analyses assessed changes in serum ferritin levels over time and their association with stroke severity and clinical outcomes. A p-value of <0.05 was considered statistically significant. The study protocol was approved by the Institutional Ethics Committee. Written informed consent was obtained from all patients or their legally authorized representatives. Patient confidentiality was strictly maintained throughout the study by anonymizing data and ensuring secure data handling.

The main conclusions of our investigation into serum ferritin as a prognostic indicator in individuals suffering from acute ischaemic stroke (AIS) are presented in this section. Serum ferritin levels at various time points, clinical profiles, demographic traits, and their relationship to patient outcomes and stroke severity (as determined by the NIHSS) are all included in the analysis. The statistical findings show noteworthy correlations that highlight serum ferritin's predictive significance in AIS.

Among the 120 patients included in the study, 61.7% were male and 38.3% were female. A majority of patients (77.5%) were aged over 46 years, with 39.2% being older than 60 years. 58.3% of individuals had hypertension, which was the most common comorbidity. Diabetes mellitus was next, affecting 33.3% of patients. Regarding lifestyle risk factors, 25.8% of respondents said they had ever consumed alcohol, and 40.8% said they had ever smoked or chewed tobacco. Regarding clinical outcomes, the overall survival rate was 90.8%, while 9.2% of the patients succumbed to stroke-related complications. These baseline characteristics form the foundation for subsequent analyses of serum ferritin levels in relation to clinical severity and mortality in AIS. (Table 1)

A comparative analysis of serum ferritin levels between survivors and non-survivors revealed significantly higher ferritin concentrations in patients who succumbed to acute ischemic stroke. At the time of admission, the mean serum ferritin level among survivors was 127.42 ng/mL, whereas it was markedly elevated at 353.76 ng/mL in non-survivors (p = 0.002), indicating a strong association with poor prognosis. This pattern remained consistent over time. On day 7, non-survivors continued to exhibit elevated ferritin levels (343.19 ng/mL) compared to survivors (128.56 ng/mL, p < 0.001). Similarly, at discharge or death, the ferritin levels in non-survivors remained significantly higher (348.29 ng/mL vs. 130.15 ng/mL, p < 0.001). These statistically significant differences across all time points highlight the prognostic relevance of elevated serum ferritin and its association with increased mortality in AIS patients. (Table 2).

The distribution of patients according to stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS) at various time points, revealed a dynamic change in clinical status during hospitalization. At admission, the majority of patients presented with moderate to severe (NIHSS 16–20) strokes (43.3%), followed by moderate strokes (NIHSS 5–15) in 39.2% of cases. Severe strokes (NIHSS 21–42) accounted for 15.8%, while only 1.7% of patients had minor strokes (NIHSS 0–4). By day 7, a shift toward clinical improvement was observed, with a notable increase in patients categorized under moderate severity (69.2%) and a modest rise in minor stroke cases (5.0%). Concurrently, there was a reduction in the moderate to severe (12.5%) and severe stroke groups (13.3%), suggesting recovery in a subset of patients, while others remained critically ill. At discharge or death, this trend of improvement persisted. The proportion of patients with minor strokes rose to 12.5%, and the moderate category remained consistent at 69.2%. Meanwhile, moderate to severe cases decreased to 7.5%, and severe strokes slightly declined to 10.8%. These findings indicate that a significant number of patients experienced clinical improvement during hospitalization, while a smaller subset either deteriorated or did not survive. (Table 3)

Table 4 presents the comparison of serum ferritin levels across varying stroke severity categories, as defined by the NIHSS, at three different time points—admission, day 7, and discharge/death. The data reveal a consistent and statistically significant correlation between higher ferritin levels and greater stroke severity (p < 0.001 at all-time points).

At admission, patients with severe strokes (NIHSS 21–42) exhibited the highest mean serum ferritin levels (305.58 ± 167.18 ng/mL), followed by those in the moderate to severe group (NIHSS 16–20) with levels of 139.87 ± 71.63 ng/mL. Patients categorized as moderate (NIHSS 5–15) showed considerably lower levels (93.44 ± 57.13 ng/mL), while the minor stroke group (NIHSS 0–4) had an average level of 154.05 ± 24.75 ng/mL, possibly reflecting an early-phase inflammatory surge. On day 7, this trend persisted. Ferritin levels remained highest among patients with severe strokes (326.41 ± 141.78 ng/mL), followed by the moderate to severe (188.97 ± 55.56 ng/mL) and moderate groups (114.07 ± 59.56 ng/mL). In contrast, ferritin levels significantly declined in the minor stroke group (43.90 ± 17.76 ng/mL), likely indicating resolution of the acute inflammatory response. By discharge or death, patients with severe strokes continued to show elevated ferritin levels (331.62 ± 141.01 ng/mL), as did those in the moderate to severe category (193.47 ± 59.42 ng/mL). The moderate group had levels of 115.15 ± 59.66 ng/mL, while the minor group maintained the lowest ferritin concentrations (42.03 ± 16.46 ng/mL). These findings demonstrate a clear positive association between serum ferritin levels and stroke severity, with persistently elevated levels in more severe cases. The progressive increase in ferritin in patients with higher NIHSS scores underscores the role of ongoing inflammation and oxidative stress in poor neurological outcomes. Thus, serum ferritin may serve as a valuable biomarker for predicting stroke progression and clinical prognosis.

Acute ischaemic stroke (AIS), which is brought on by a disruption in cerebral blood flow, continues to be a leading cause of death and permanent disability worldwide. Finding trustworthy prognostic biomarkers is crucial for clinical decision-making, early risk assessment, and improving patient outcomes. Because of its dual function in iron metabolism and systemic inflammation, serum ferritin—most often recognised as an intracellular iron-storage protein—has become a promising biomarker. The pathogenesis of AIS is influenced by oxidative stress and inflammatory activity, both of which are reflected in elevated blood ferritin levels. According to the National Institutes of Health Stroke Scale (NIHSS), a number of studies have shown a positive association between higher ferritin levels and worse neurological outcomes. More severity of stroke and more disability are indicated by higher ferritin concentrations both at admission and during hospitalisation. Ferritin levels, however, should be interpreted with caution because they could be affected by confounding variables such as hepatic dysfunction, chronic inflammatory diseases, or concurrent infections. In our study, the majority of AIS patients were male (61.7%), while 38.3% were female. Most patients belonged to the elderly age group (>60 years), followed by the 46–60-year age group. These findings align with previous research by SankarBhuyan S et al.(9), where the majority of stroke patients were aged between 51 and 70 years, with a minimum age of 32 years and a maximum of 80 years. Similarly, Sadek N et al. (10) reported a mean age of 65.66 years in their study, with ages ranging from 35 to 94 years. In a separate study, Garg R et al.(7) observed that 54% of stroke patients were between 61 and 70 years, with a mean age of 66.62 years. These results reinforce that increasing age is a significant risk factor for AIS, with older patients more likely to experience severe strokes and worse outcomes.

Comorbidities play a crucial role in determining stroke prognosis. In our study, hypertension (58.3%) and diabetes (33.3%) were the most common comorbidities among AIS patients. Additionally, 40.8% had a history of smoking or tobacco chewing, and 25.8% consumed alcohol. In a similar study by SankarBhuyan S et al.(9), hypertension and diabetes were more common among patients with poor outcomes. Sadek et al.(10) reported an even higher prevalence of hypertension (76%) and diabetes (52%) among stroke patients. These findings suggest that hypertension and diabetes are strong predictors of stroke severity, while smoking and alcohol consumption further contribute to poor outcomes. Addressing these risk factors through preventive measures could reduce the overall burden of AIS.

The mortality rate in our study was 9.2%, with 90.8% of patients surviving. This is lower compared to other studies, such as SankarBhuyan S et al.(9), where the overall mortality rate was 35%, with most deaths occurring in the 51–70-year age group. Similarly, Chauhan DS et al.(11) reported 23.3% mortality, with 24 cases deteriorating and 22 cases showing improvement. The lower mortality in our study may reflect early diagnosis, improved stroke care, and timely interventions, which have contributed to better survival rates. However, even among survivors, stroke-related disability remains a significant challenge, reinforcing the need for effective rehabilitation strategies.

Serum ferritin levels showed a strong association with stroke severity and prognosis. Patients who survived had significantly lower ferritin levels at all time points compared to those who did not survive. At admission, mean ferritin levels were 127.42 ng/mL in survivors and 353.76 ng/mL in non-survivors (p = 0.002). By day 7, ferritin levels remained lower in survivors (128.56 ng/mL) compared to non-survivors (343.19 ng/mL, p = 0.001). At discharge, survivors had ferritin levels of 130.15 ng/mL, whereas non-survivors had significantly higher levels (348.29 ng/mL, p = 0.001). Similar trends have been reported in previous studies. Mandal SK et al.(12) found significantly higher ferritin levels in AIS patients (83.1 ng/mL) compared to controls (41.3 ng/mL). Garg R et al. (7) reported higher ferritin levels in severe stroke patients (282.77 ng/mL) compared to those with less severe strokes (205.12 ng/mL). These findings confirm that elevated ferritin levels are a marker of stroke severity and poor prognosis.

Stroke severity progression was assessed using the National Institutes of Health Stroke Scale (NIHSS). At admission, 15.8% of patients had severe strokes (NIHSS 21–42), 43.3% had moderate to severe strokes (NIHSS 16–20), and 39.2% had moderate strokes (NIHSS 5–15). By day 7, 69.7% of patients had moderate strokes, while severe strokes reduced to 12.6%. At discharge, severe strokes further declined, with 70.3% of patients classified as having moderate strokes. In a study by Sultana J et al. (13), 60% of high-ferritin patients had severe strokes, while those with normal ferritin levels had only moderate strokes. Koul RK et al. (14) reported a mean NIHSS score of 12.24, confirming that higher NIHSS scores are associated with increased ferritin levels and worse outcomes.

With a strong association to stroke severity, unfavourable clinical outcomes, and death, serum ferritin has shown great promise as a predictive biomarker in acute ischaemic stroke (AIS). Early risk assessment and patient care may benefit from its application in clinical practice. Standardised testing procedures and rigorous evaluation of confounding factors such infections, chronic inflammatory conditions, and hepatic dysfunction should, nevertheless, direct its interpretation. To confirm its predictive usefulness and look into focused treatment approaches that address iron metabolism and oxidative stress in AIS, more extensive, multicentric research is necessary.

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

Source of Funding: This research received no external funding.

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