Integrative Biomedical Research

1. Introduction

Acute ischemic stroke continues to impose an enormous burden on global health systems, not only because of its high mortality but also due to the long-term neurological disability that frequently follows survival. Despite considerable advances in neuroimaging, thrombolytic therapy, and endovascular intervention, the clinical course of ischemic stroke often remains unpredictable during the early phase of hospitalization. Some patients recover with only minimal deficits, whereas others rapidly deteriorate despite receiving similar standards of care. This variability has encouraged ongoing efforts to identify reliable biological markers capable of reflecting disease severity, predicting outcome, and perhaps even guiding early therapeutic decisions. Among the many proposed candidates, inflammatory and coagulation-related biomarkers have drawn particular attention because they appear to mirror several of the underlying pathological mechanisms involved in cerebral ischemia.

The pathophysiology of acute ischemic stroke is far more complex than a simple interruption of cerebral blood flow. Once vascular occlusion occurs, a cascade of biochemical and cellular events begins almost immediately. Neuronal energy failure, oxidative stress, endothelial dysfunction, activation of coagulation pathways, and inflammatory responses collectively contribute to progressive tissue injury beyond the initial infarct core. In many patients, this secondary injury process evolves over hours to days and may significantly influence functional recovery. Interestingly, it is within this evolving inflammatory-thrombotic environment that circulating biomarkers may offer clinically meaningful insights. Rather than functioning merely as laboratory abnormalities, these markers may reflect the intensity of ongoing vascular injury and systemic response to cerebral ischemia.

Among these biomarkers, C-reactive protein (CRP) has been extensively investigated as an indicator of systemic inflammation. CRP is an acute-phase reactant synthesized primarily by hepatocytes in response to inflammatory cytokines, particularly interleukin-6. Elevated CRP levels have long been associated with atherosclerosis, endothelial dysfunction, and cardiovascular disease progression (Black et al., 2004; Weinhold et al., 1997). In the context of ischemic stroke, increased CRP concentrations may indicate not only preexisting vascular inflammation but also the inflammatory amplification that follows cerebral infarction. Several studies have suggested that elevated CRP levels are associated with increased stroke severity, poorer neurological recovery, and unfavorable clinical outcomes. Yet the precise prognostic value of CRP in acute ischemic stroke remains somewhat debated, partly because inflammatory responses may vary according to infarct size, comorbid conditions, and timing of measurement.

At the same time, growing interest has emerged regarding the role of coagulation markers, particularly D-dimer, in ischemic stroke prognosis. D-dimer is a degradation product formed during fibrin breakdown and serves as an indirect marker of thrombin generation and fibrinolytic activity. Because ischemic stroke is fundamentally a thromboembolic disorder in many patients, elevated D-dimer levels may reflect active intravascular thrombosis or ongoing clot turnover. Earlier investigations demonstrated that increased D-dimer concentrations were associated with cerebral venous thrombosis, pulmonary embolism, coronary artery disease, and ischemic stroke severity (Montaner et al., 2008; Hiltunen et al., 2013; Matsumoto et al., 2013). Furthermore, several reports indicated that elevated D-dimer levels may correlate with larger infarct volume, early neurological deterioration, and poor short-term prognosis following acute ischemic stroke (Park et al., 2011; Barber et al., 2004). Still, the consistency of these findings across different patient populations has remained variable, and the integration of D-dimer into routine prognostic assessment is not yet firmly established.

Another biomarker that has recently gained attention is procalcitonin (PCT). Traditionally recognized as a marker of bacterial infection and sepsis, PCT has increasingly been explored in noninfectious inflammatory conditions, including acute ischemic stroke. Although its precise biological role in stroke is not fully understood, elevated PCT levels may indicate heightened systemic inflammatory activation after cerebral injury. Some investigators have suggested that PCT may even outperform conventional inflammatory markers in predicting disease severity and adverse outcomes (Tian et al., 2015). Experimental and clinical evidence further indicates that post-stroke inflammatory activation may contribute to blood-brain barrier disruption, secondary neuronal injury, and increased susceptibility to complications, all of which could influence recovery trajectories (Jin et al., 2010). Consequently, evaluating PCT alongside CRP and D-dimer may provide a broader picture of the inflammatory and thrombotic processes occurring during the acute phase of ischemic stroke.

Although numerous studies have independently examined CRP, D-dimer, or procalcitonin in stroke patients, comparatively fewer investigations have evaluated these biomarkers simultaneously within a single clinical framework. Moreover, evidence regarding their relationship with both stroke severity and short-term functional outcomes remains limited in many South Asian populations. Given the growing need for accessible, inexpensive, and rapidly measurable prognostic indicators, further investigation appears warranted.

Therefore, the present study aimed to evaluate the association of admission plasma D-dimer, serum procalcitonin, and C-reactive protein levels with the severity and short-term outcomes of patients presenting with acute ischemic stroke. By correlating these biomarkers with established neurological assessment scales, including the Scandinavian Stroke Scale and Modified Rankin Scale, this study sought to determine whether these laboratory parameters could serve as useful prognostic tools during the early phase of stroke management.

2. Materials and Methods

2.1 Study Design and Clinical Setting

This multicenter observational study was conducted to explore the relationship between admission plasma D-dimer, serum procalcitonin (PCT), and C-reactive protein (CRP) levels with stroke severity and short-term clinical outcomes in patients with acute ischemic stroke. Although the investigation primarily followed an observational framework, patients were prospectively evaluated during hospitalization and subsequently followed for short-term outcome assessment. The study was carried out across several tertiary-level hospitals in Dhaka, Bangladesh, including the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka Medical College Hospital (DMCH), and Sir Salimullah Medical College & Mitford Hospital.

Patient recruitment was performed over different study periods according to institutional accessibility and departmental collaboration. Enrollment was conducted at the Department of Neurology, BSMMU, and the Department of Internal Medicine, DMCH, from July 2015 to March 2017; at the Department of Neurology and Medicine, Sir Salimullah Medical College & Mitford Hospital, from January 2018 to December 2018; and at the Department of Neurology, DMCH, from August 2017 to July 2019. The multicenter nature of the study was intended to minimize institutional bias and improve the representativeness of patients presenting with acute ischemic stroke in routine clinical practice.

2.2 Study Population

A total of 260 adult patients diagnosed with acute ischemic stroke were consecutively enrolled according to predefined eligibility criteria. Patients aged 18 years or older, irrespective of sex, were considered eligible if they presented within the acute phase of ischemic stroke and the diagnosis was confirmed clinically along with neuroimaging findings. Stroke diagnosis was established on the basis of detailed neurological evaluation and computed tomography (CT) imaging of the brain performed during admission.

Patients were excluded if they had conditions likely to influence inflammatory or coagulation biomarkers independently of ischemic stroke. These included hemorrhagic stroke, cerebral venous thrombosis, bacterial sepsis, localized bacterial infections such as pneumonia, meningitis, or peritonitis, chronic liver disease, renal dysfunction, and medullary thyroid carcinoma. To reduce confounding laboratory variability, patients with serum glutamic pyruvic transaminase (SGPT) levels >88 U/L or serum creatinine >1.5 mg/dL were also excluded. Since procalcitonin is known to rise substantially in bacterial infections and systemic inflammatory states, exclusion of infectious conditions was considered particularly important for preserving the interpretability of biomarker measurements (Tian et al., 2015; Massaro et al., 2007).

A non-randomized purposive sampling technique was employed during patient enrollment. After screening and confirmation of eligibility, informed written consent was obtained either directly from the patient or from legally authorized family members in cases where neurological impairment limited communication.

2.3 Ethical Considerations

The study protocol was reviewed and approved by the ethical review authorities of the participating institutions prior to initiation of patient recruitment. All procedures were conducted in accordance with the ethical standards of institutional research committees and with the principles outlined in the Declaration of Helsinki. Confidentiality of patient information was strictly maintained throughout data collection, analysis, and reporting.

2.4 Clinical Evaluation and Neurological Assessment

Detailed demographic and clinical data were collected at admission using a structured data collection form. Information regarding age, sex, occupation, vascular risk factors, smoking history, and associated comorbidities was recorded systematically. Clinical examination included comprehensive neurological assessment, general physical examination, and systemic evaluation.

Stroke severity at admission was quantified using the National Institutes of Health Stroke Scale (NIHSS), which is widely accepted for assessing neurological impairment in acute ischemic stroke. In addition, the Glasgow Coma Scale (GCS) was used to evaluate the level of consciousness during initial presentation. Functional disability and neurological outcomes were assessed using both the Scandinavian Stroke Scale (SSS) and the Modified Rankin Scale (mRS). Baseline scoring was performed during admission, while follow-up outcome evaluation was conducted at 30 days after stroke onset.

The use of these standardized scales allowed comparison of biomarker levels with objective clinical severity measures and functional outcomes. Previous investigations have similarly utilized these scales while examining prognostic markers in ischemic stroke populations (Zi & Shuai, 2014; Yang et al., 2014).

2.5 Laboratory Investigations and Biomarker Measurement

Venous blood samples were collected from all enrolled patients under aseptic precautions shortly after hospital admission and before initiation of major therapeutic interventions whenever feasible. Blood specimens were processed according to standard laboratory procedures.

Plasma D-dimer estimation was performed in the Department of Hematology laboratory at Dhaka Medical College Hospital. D-dimer was selected because it reflects ongoing fibrin degradation and intravascular thrombotic activity, mechanisms closely associated with ischemic cerebrovascular events (Montaner et al., 2008; Barber et al., 2004). Serum CRP assay was performed within 24 hours of hospitalization to minimize variability related to delayed inflammatory responses. CRP levels below 6 mg/dL were considered negative, whereas levels above this threshold were categorized as positive.

For serum procalcitonin analysis, additional blood samples were collected during the acute admission period. Procalcitonin was evaluated as an inflammatory biomarker because previous evidence suggested its potential association with ischemic stroke severity and prognosis (Shenhar-Tsarfaty et al., 2015; Tian et al., 2015). Routine laboratory investigations including complete blood count, fasting or random blood glucose, serum creatinine, lipid profile, and other clinically indicated biochemical tests were also performed.

Neuroimaging evaluation primarily included CT scanning of the brain to differentiate ischemic stroke from hemorrhagic stroke and to support diagnostic confirmation. Imaging protocols followed standard institutional emergency stroke assessment practices (Scott & Barsan, 1999; Wintermark & Bogousslavsky, 2003).

2.6 Outcome Assessment

Short-term outcome evaluation was conducted at both 7 days and 30 days following stroke onset. Mortality status was recorded during follow-up, and functional outcome was reassessed using the Modified Rankin Scale and Scandinavian Stroke Scale. Poor outcome was generally interpreted as severe disability or death during the short-term follow-up period.

The primary outcome variables included:

1. Stroke severity at admission,
2. Functional disability at 30 days,
3. Short-term mortality,
4. Correlation between biomarker levels and neurological outcome scales.

2.7 Statistical Analysis

All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as frequency and percentage distributions.

Comparisons between groups were conducted using Student’s t-test for continuous variables and Chi-square test for categorical variables. Correlation analyses between biomarker levels and stroke severity scales were performed using Spearman or Pearson correlation coefficients as appropriate according to data distribution

Table 1: Distribution of the study population according to age (N=260)

Table 2: Distribution of the study population according to sex (N=260)

Table 3: Distribution of the study population according to Occupation (N=260)

Table 4: Distribution of the study population according to Risk factors (N=260)

characteristics. Univariate and multivariate logistic regression analyses were further performed to identify predictors associated with short-term mortality following ischemic stroke.

A two-tailed p-value <0.05 was considered statistically significant, and confidence intervals were calculated at the 95% level throughout the analysis.

3. Results

3.1 Baseline Demographic Characteristics of the Study Population

A total of 260 patients with acute ischemic stroke were included in the final analysis. For comparative purposes, patients were categorized according to CRP status into two equal groups: CRP-positive patients (Group A, n=130) and CRP-negative patients (Group B, n=130).

The overall mean age of the study population was 61.73±10.49 years. Patients in Group A had a mean age of 61.69±10.51 years, whereas those in Group B demonstrated a nearly similar mean age of 61.78±10.52 years. No statistically significant age difference was observed between the two groups (p=0.948) (Table 1). Interestingly, the largest proportion of patients in both groups belonged to the 61–70 years age category, accounting for 38.85% of the total population, suggesting that ischemic stroke occurred predominantly among older adults within this cohort (Table 1).

Sex distribution also appeared relatively balanced between the two study groups. Male patients represented 63.46% of the overall population, while females accounted for 36.54%. Although men were more frequently affected than women, the distribution pattern did not differ significantly between CRP-positive and CRP-negative patients (p=0.521) (Table 2).

Regarding occupational background, service holders comprised the largest subgroup (31.54%), followed by housewives (20.00%), businessmen (17.31%), farmers (12.69%), and day laborers (11.54%) (Table 3). A smaller proportion of patients belonged to miscellaneous occupational categories, including retired individuals. Again, occupational distribution between the two groups showed no statistically meaningful variation (p>0.05), indicating comparable socioeconomic representation across the study population.

3.2 Distribution of Vascular Risk Factors

Hypertension emerged as the most common vascular risk factor among study participants, affecting nearly half of the total population (49.62%). Diabetes mellitus was present in 28.85% of patients, while smoking history was identified in 25.77%. Dyslipidemia and obesity were observed in 15.77% and 10.00% of cases, respectively (Table 4).

Although CRP-positive patients tended to demonstrate slightly higher frequencies of hypertension, dyslipidemia, and obesity, these differences did not reach statistical significance. Overall, the vascular risk factor profile appeared broadly similar between the two groups (p>0.05), suggesting that baseline cardiovascular comorbidity burden was relatively comparable at enrollment.

3.3 Clinical Presentation of Acute Ischemic Stroke

The neurological presentation of ischemic stroke varied considerably among patients, though several clinical manifestations were particularly prominent. Hemiplegia or hemiparesis was by far the most frequent presentation, occurring in 89.62% of patients overall (Table 5). Cranial nerve palsy and dysphagia were also commonly encountered, affecting 61.54% and 60.77% of patients, respectively.

Other neurological manifestations included sphincter disturbances (39.23%), sensory deficits (37.31%), facial nerve palsy (28.08%), altered consciousness (27.31%), dysphasia (23.46%), headache (21.92%), and convulsions (18.08%). Less common symptoms included hiccup, vomiting, vertigo, and neck rigidity.

Interestingly, although certain symptoms such as sensory loss and convulsions appeared somewhat more frequent among CRP-negative patients, none of the clinical manifestations demonstrated statistically significant differences between groups (p>0.05). Thus, the overall neurological presentation at admission remained broadly comparable regardless of CRP status.

3.4 Distribution of Serum CRP Levels

Serum CRP concentrations differed substantially between the two study groups (Table 6). CRP-positive patients demonstrated a markedly elevated mean CRP level of 14.35±5.17 mg/dL, whereas the CRP-negative group showed a much lower mean value of 3.07±1.27 mg/dL. The overall mean CRP concentration for the entire cohort was 8.71±6.79 mg/dL.

Table 5: Clinical features of the study population (N=260)

Table 6: CRP level of the study population (N=260)

Table 7: GCS of the study population in relation to CRP (N=260)

Table 8: NIHSS score of the study population in relation to CRP (N=260)

Table 9: Outcome of study population at day 7 after stroke in relation to CRP (N=260)

Table 10: CRP level in relation to admission NIHSS score and outcome of patients (N=260)

Median CRP values were 13.00 mg/dL in Group A and 3.00 mg/dL in Group B, further emphasizing the substantial inflammatory difference between the two populations. CRP values below 6 mg/dL were considered negative according to the predefined study criteria.

3.5 Association Between CRP Status and Level of Consciousness

Neurological status at admission, assessed using the Glasgow Coma Scale (GCS), demonstrated a significant relationship with CRP positivity (Table 7). Among CRP-positive patients, 25.38% presented with severe impairment of consciousness (GCS ≤8), whereas only 11.54% of CRP-negative patients fell within this category.

Conversely, patients with lower CRP levels more frequently demonstrated preserved consciousness, with 66.92% of CRP-negative patients showing GCS scores between 13–15 compared to 45.38% in the CRP-positive group. The difference in GCS distribution between groups was statistically significant (p=0.001), suggesting that elevated inflammatory burden may be associated with more severe neurological compromise during the acute phase of ischemic stroke.

3.6 Association Between CRP and Stroke Severity

Stroke severity, evaluated using the National Institutes of Health Stroke Scale (NIHSS), also differed significantly according to CRP status (Table 8). Severe stroke (NIHSS 21–42) was observed in 24.62% of CRP-positive patients compared with only 10.00% among CRP-negative individuals. Similarly, moderate-to-severe stroke scores (NIHSS 16–20) were more common in the CRP-positive group.

In contrast, mild stroke severity (NIHSS 1–4) was substantially more frequent among CRP-negative patients (30.77%) than CRP-positive patients (10.00%). Overall, the distribution of NIHSS scores demonstrated a statistically significant association with CRP positivity (p=0.001), indicating that higher inflammatory activity may parallel increasing neurological severity at presentation.

Further descriptive analysis revealed a progressive rise in mean CRP values with increasing NIHSS categories (Table 10). Patients with mild neurological impairment exhibited relatively low CRP concentrations, whereas individuals with severe stroke demonstrated markedly elevated CRP levels. Interestingly, although CRP values tended to be numerically higher among patients who died, this difference did not reach statistical significance (p=0.614).

3.7 Short-Term Outcome and Mortality

Short-term mortality analysis demonstrated a striking difference between the two groups (Table 9). At 7-day follow-up, mortality among CRP-positive patients reached 15.38%, compared with only 2.31% among CRP-negative patients. Conversely, survival rates were considerably higher in the CRP-negative population.

This difference was statistically significant (p=0.001), suggesting a potentially important association between elevated CRP levels and early mortality following acute ischemic stroke.

3.8 Correlation Between Biomarkers and Stroke Severity at Admission

Correlation analysis demonstrated significant associations between admission biomarker levels and neurological severity scales (Table 11). Plasma D-dimer, serum procalcitonin, and CRP all showed significant inverse correlations with the Scandinavian Stroke Scale (SSS), indicating that higher biomarker concentrations were associated with poorer neurological status.

Among these biomarkers, serum procalcitonin demonstrated the strongest negative correlation with SSS (r=-0.492, p<0.001), followed closely by D-dimer (r=-0.464, p<0.001). CRP also showed a statistically significant inverse relationship (r=-0.367, p<0.001).

Similarly, positive correlations were observed between biomarker levels and Modified Rankin Scale (mRS) scores at admission. Elevated D-dimer and procalcitonin levels demonstrated highly significant positive correlations with functional disability, while CRP exhibited a weaker but still statistically significant relationship.

3.9 Correlation Between Biomarkers and Thirty-Day Functional Outcome

At 30-day follow-up, biomarker levels continued to demonstrate significant associations with neurological outcome measures (Table 12). Higher D-dimer, procalcitonin, and CRP concentrations remained inversely correlated with Scandinavian Stroke Scale scores, indicating poorer neurological recovery among patients with elevated biomarker levels.

D-dimer demonstrated the strongest inverse correlation

Table 11: Spearman Correlation between D-dimer, serum procalcitonin, CRP and Scandinavian Stroke Scale and Modified Rankin Scale at admission. *Significant. **Highly significant

Table 12: Spearman Correlation between D-Dimer, Fibrinogen, CRP and the Outcome of the Stroke Using Scandinavian Stroke Scale and Modified Rankin Scale at 30 Days. *Significant. **Highly significant

Table 13: Univariate analysis risk factors for dying at 7 days after stroke (N=260)

Table 14: Multivariate analysis of risk factors for dying at 7 days after stroke (N=260)

with 30-day SSS (r=-0.496, p<0.001), followed by procalcitonin (r=-0.473, p<0.001) and CRP (r=-0.386, p<0.001). Likewise, all three biomarkers demonstrated positive correlations with Modified Rankin Scale scores, suggesting greater residual disability among patients with elevated inflammatory and coagulation marker levels.

Taken together, these findings indicate that increased admission levels of D-dimer, procalcitonin, and CRP were consistently associated with greater stroke severity, poorer neurological recovery, and increased functional disability during short-term follow-up.

3.10 Regression Analysis of Mortality Risk Factors

Univariate logistic regression analysis was performed to identify predictors associated with 7-day mortality after ischemic stroke (Table 13). Variables including advanced age (>60 years), male sex, CRP positivity, hypertension, diabetes mellitus, smoking, obesity, and dyslipidemia were examined individually.

Although several variables demonstrated elevated odds ratios, none reached statistical significance at the conventional 0.05 threshold. However, age above 60 years, diabetes mellitus, and CRP positivity approached significance at the more relaxed <0.1 significance level.

Subsequently, multivariate logistic regression analysis was conducted using variables identified in univariate analysis (Table 14). After adjustment for confounding variables, age above 60 years remained independently associated with mortality risk (p=0.023). CRP positivity also continued to demonstrate an association with poorer short-term outcome, although the statistical interpretation appeared somewhat limited by wide confidence intervals and model variability.

4. Discussion

4.1 Overview of the Principal Findings

The present study explored the relationship between admission plasma D-dimer, serum procalcitonin, and C-reactive protein levels with stroke severity and short-term outcomes in patients presenting with acute ischemic stroke. Overall, the findings suggest that inflammatory and coagulation-related biomarkers may carry meaningful prognostic value during the acute phase of ischemic stroke. Elevated levels of D-dimer, procalcitonin, and CRP were consistently associated with greater neurological impairment, poorer functional status, and less favorable short-term outcomes, particularly within the first 30 days after stroke onset (Tables 11–12).

What perhaps stands out most is not simply the elevation of these biomarkers themselves, but rather the way they appeared to parallel clinical deterioration. Patients with higher inflammatory and coagulation marker levels tended to present with more severe neurological deficits, lower Glasgow Coma Scale scores, higher NIHSS scores, and increased short-term mortality. Taken together, these findings reinforce the growing view that ischemic stroke is not merely a vascular occlusive event, but also a dynamic inflammatory and thrombotic disorder involving complex systemic responses.

4.2 Demographic Characteristics and Clinical Profile

In the current study, the mean age of patients was approximately 62 years, with the majority belonging to the 61–70 years age group (Table 1). This observation appears consistent with the established epidemiological pattern of ischemic stroke, where advancing age remains one of the strongest nonmodifiable risk factors. Similar age distributions have been reported in previous stroke studies conducted in South Asian populations (Siddique et al., 2009; Omkar Prasad et al., 2013). The predominance of older adults in this cohort likely reflects the cumulative burden of vascular risk factors and progressive endothelial dysfunction that accompany aging.

Male patients outnumbered female patients, with a male-to-female ratio of approximately 1.6:1 (Table 2). Although the sex distribution was not statistically different between study groups, this pattern aligns with several earlier regional studies demonstrating higher stroke incidence among men, particularly during the middle and older age decades (Siddique et al., 2009). The reasons behind this sex disparity are probably multifactorial, involving differences in smoking prevalence, occupational stress, vascular risk exposure, and possibly hormonal protection in women during earlier life stages.

Clinically, hemiplegia or hemiparesis emerged as the most common presenting feature, occurring in nearly 90% of patients (Table 5). This finding closely resembles observations reported by Siddique et al. (2009) and Omkar Prasad et al. (2013), who similarly identified hemiplegia as the dominant neurological presentation among acute ischemic stroke patients. Other common manifestations, including cranial nerve palsy, dysphagia, sensory deficits, and altered consciousness, further reflect the heterogeneous neurological involvement associated with cerebral ischemia.

4.3 Vascular Risk Factors and Stroke Burden

Hypertension and diabetes mellitus were highly prevalent among the study population (Table 4), reinforcing their well-established role in the development and progression of ischemic cerebrovascular disease. Chronic hypertension contributes to endothelial injury, vascular remodeling, and accelerated atherosclerosis, whereas diabetes mellitus promotes microvascular dysfunction, oxidative stress, and inflammatory activation. Together, these processes may predispose patients not only to stroke occurrence but also to worse neurological recovery afterward.

Interestingly, although the distributions of hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking were not statistically different between CRP-positive and CRP-negative groups, patients with these risk factors tended to demonstrate poorer neurological status and less favorable outcomes overall. This observation may suggest that inflammatory biomarkers and traditional vascular risk factors operate synergistically rather than independently during ischemic stroke progression.

4.4 Relationship Between CRP and Neurological Severity

One of the more notable findings of this study was the significant association between elevated CRP levels and stroke severity. Patients with CRP positivity demonstrated substantially worse GCS and NIHSS scores at admission compared with CRP-negative patients (Tables 7–8). Moreover, mean CRP concentrations progressively increased with higher NIHSS categories (Table 10), suggesting a possible dose-response relationship between systemic inflammation and neurological injury severity.

CRP is widely recognized as an acute-phase reactant synthesized in response to inflammatory cytokine signaling, particularly interleukin-6 (Black et al., 2004; Weinhold et al., 1997). In acute ischemic stroke, elevated CRP may reflect several overlapping pathological mechanisms, including endothelial dysfunction, tissue necrosis, activation of inflammatory cascades, and secondary ischemic injury. The present findings are broadly consistent with the systematic review by Hasan et al. (2012), which highlighted the potential utility of inflammatory biomarkers in acute stroke prognosis.

At the same time, it remains difficult to determine whether elevated CRP directly contributes to neurological worsening or simply mirrors the magnitude of tissue injury already present. It is plausible that both mechanisms coexist. Larger infarcts may provoke more intense inflammatory responses, while inflammation itself may amplify neuronal damage through disruption of the blood-brain barrier, leukocyte infiltration, and microvascular thrombosis.

4.5 Prognostic Significance of D-Dimer

The present study also demonstrated a strong association between elevated D-dimer levels and stroke severity as well as poor functional outcome (Tables 11–12). D-dimer showed significant inverse correlations with Scandinavian Stroke Scale scores and positive correlations with Modified Rankin Scale scores, both at admission and during 30-day follow-up.

These observations align closely with earlier reports by Lip et al. (2002), Ageno et al. (2002), and Zi and Shuai (2014), who similarly found elevated D-dimer concentrations among patients with acute ischemic stroke. D-dimer is generated during fibrin degradation and therefore serves as an indirect marker of thrombin generation and active coagulation. Elevated levels likely reflect ongoing intravascular thrombosis, clot turnover, and fibrinolytic activation occurring during acute cerebral ischemia.

From a pathophysiological perspective, the association between elevated D-dimer and poorer outcome appears biologically plausible. Larger or more unstable thrombi may produce greater cerebral infarction, resulting in more severe neurological impairment and reduced recovery potential. Barber et al. (2004) similarly reported that D-dimer predicted early clinical progression in ischemic stroke patients, while Yang et al. (2014) demonstrated its prognostic value for short-term mortality and poor outcome.

Interestingly, D-dimer exhibited one of the strongest correlations with functional outcome in the current study, perhaps suggesting that coagulation pathway activation plays a particularly important role during the early evolution of ischemic injury.

4.6 Role of Procalcitonin in Acute Ischemic Stroke

Another important observation from this study was the significant elevation of serum procalcitonin among patients with more severe stroke and poorer short-term outcomes (Tables 11–12). Traditionally, procalcitonin has been viewed primarily as a marker of bacterial infection and systemic inflammatory response. However, increasing evidence suggests that noninfectious inflammatory conditions, including ischemic stroke, may also trigger elevations in circulating PCT levels.

The present findings are broadly consistent with the work of Tian et al. (2015) and Ufuk et al. (2007), both of whom reported associations between elevated procalcitonin and increased stroke severity. Experimental evidence suggests that acute cerebral ischemia can induce systemic inflammatory activation involving cytokine release, leukocyte recruitment, and neuroimmune signaling (Jin et al., 2010). In this context, elevated procalcitonin may reflect the intensity of post-ischemic inflammatory activation rather than overt infection alone.

What remains particularly interesting is that procalcitonin demonstrated correlations with both neurological severity and functional disability comparable to those observed for D-dimer. This raises the possibility that inflammatory biomarkers and coagulation biomarkers may together provide complementary prognostic information during the acute phase of ischemic stroke.

4.7 Biomarkers and Short-Term Mortality

Short-term mortality was substantially higher among CRP-positive patients compared with CRP-negative individuals (Table 9). Although multivariate analysis demonstrated some statistical instability, likely related to sample size and event distribution, elevated inflammatory status nevertheless appeared associated with increased early mortality risk.

This finding deserves careful interpretation. Mortality after ischemic stroke is influenced by numerous interacting variables, including infarct size, cerebral edema, aspiration pneumonia, cardiac complications, baseline frailty, and delayed neurological deterioration. Biomarkers such as CRP, D-dimer, and procalcitonin may not independently determine mortality; however, they may serve as biological indicators of patients already experiencing more extensive vascular and inflammatory injury.

4.8 Clinical Implications

From a practical standpoint, the findings of this study suggest that admission measurement of D-dimer, CRP, and serum procalcitonin may assist clinicians in early risk stratification of patients with acute ischemic stroke. These biomarkers are relatively accessible, minimally invasive, and widely available in routine clinical settings. Their integration into early stroke assessment protocols may help identify patients at higher risk for neurological deterioration, severe disability, or poor short-term outcome.

Importantly, these biomarkers should probably not be interpreted in isolation. Rather, their value may be greatest when combined with clinical severity scales, neuroimaging findings, and conventional vascular risk assessment.

4.9 Limitations of the Study

Several limitations should be acknowledged while interpreting the findings of this study. First, the observational design limits the ability to establish causal relationships between biomarker elevation and stroke outcome. Second, biomarker measurements were performed primarily during admission, and serial monitoring was not conducted. Consequently, dynamic changes in inflammatory and coagulation markers over time could not be evaluated.

The study also lacked detailed infarct volume analysis and stroke subtype classification, both of which might influence biomarker expression and prognosis. In addition, although infectious conditions were excluded clinically, subclinical inflammatory states may still have contributed to variability in biomarker levels. Finally, the study population was derived from tertiary hospitals within a single geographic region, which may limit broader generalizability.

Despite these limitations, the study provides important insight into the prognostic significance of inflammatory and coagulation biomarkers in acute ischemic stroke and contributes additional evidence supporting their potential clinical utility.

5. Conclusion

The findings of this study suggest that inflammatory and coagulation-related biomarkers may play a meaningful role in understanding the clinical course of acute ischemic stroke. Elevated admission levels of plasma D-dimer, serum procalcitonin, and C-reactive protein were consistently associated with greater neurological impairment, increased functional disability, and poorer short-term outcomes. Patients with higher biomarker levels tended to present with more severe stroke manifestations and demonstrated less favorable recovery during follow-up. Among these markers, D-dimer and procalcitonin showed particularly strong relationships with stroke severity and disability scales, while CRP positivity was associated with increased early mortality. Although ischemic stroke is fundamentally a vascular event, the present findings further emphasize the importance of systemic inflammation and coagulation activation during disease progression. Measurement of these biomarkers at admission may therefore provide a simple, accessible, and clinically valuable approach for early prognostic assessment, risk stratification, and individualized management of patients with acute ischemic stroke.

Author Contributions

M.R. conceived and designed the study, supervised data collection, interpreted the findings, and finalized the manuscript. T.J. contributed to laboratory analysis, data interpretation, and manuscript drafting. A.S.M.H.A.M. participated in patient recruitment, clinical evaluation, and data acquisition. M.W. contributed to neurological assessment, follow-up evaluation, and statistical interpretation. M.A.R. assisted in data collection, literature review, and manuscript preparation. S.M.A.A. participated in laboratory coordination, biomarker analysis, and manuscript revision. P.P. contributed to patient assessment, data verification, and critical revision of the manuscript. M.A.K. supervised the overall research process, critically reviewed the manuscript, and approved the final version for publication. All authors read and approved the final manuscript.

References