Stroke is one of the important causes of morbidity and mortality worldwide. The World Health Organization estimates about 15 million people suffer from stroke each year. Approximately 85 – 90% of all ischemic strokes occur due to compromised blood supply [1, 2]. It has been found that 75% of all ischemic strokes occur in people aged 65 and above. Most commonly affected are males as compared to females. However, the incidence of death is higher in females who suffer from stroke. Recently it appears that inflammatory processes are involved in causing cerebral ischemia. [3]. Ischemic brain injury is marked by acute local inflammation and changes in levels of C reactive protein and inflammatory cytokines. It has been found that elevated stroke risk is associated with high levels of C-reactive protein. Studies have shown that stroke risk is positively correlated with high levels of C-reactive proteins. Many patients with elevated CRP levels within a period of 72 hours of stroke have increased chances of death. [4] therefore, CRP may be used as a biomarker for grading systemic inflammation. Vascular inflammation is directly correlated to values of high sensitive CRP (HsCRP). [5] there is the possibility that elevated hs-CRP could be a direct reflection of cerebral tissue injury/inflammation. [2] HsCRP is an acute-phase protein produced by the liver and also by the vascular smooth muscles and adipocytes. It is also a novel plasma marker for athero-thrombotic disease. Although elevated plasma levels of HsCRP are not disease-specific however, they are sensitive markers elevated in response to tissue injury and inflammation. The size of the infarct and stroke severity are major determinants of the prognosis of ischemic stroke, and HsCRP could be used to predict prognosis. [6] based on this background we in the current study tried to evaluate the pattern of changes of HsCRP in acute ischemic stroke patients and the ability of HsCRP to determine prognosis based on the NIHSS scoring system in cohort presenting to hour hospital.

This prospective observational study was conducted at the Department of General Medicine, Govt Medical College and Hospital, Wanaparthy, Telangana. Institutional Ethical approval was obtained for the study. Written consent was obtained from the patients/relatives included in the study after explaining the nature of the study in vernacular language.

Inclusion Criteria 

1. Patients aged ≥18 years
2. Males and Females
3. Diagnosed with acute ischemic stroke (confirmed by MRI/CT within 24–48 hours of symptom onset)
4. Willing to provide informed consent

Exclusion Criteria

1. History of recent infection/inflammation (within 4 weeks)
2. Chronic inflammatory diseases (e.g., rheumatoid arthritis, lupus)
3. Active malignancy or immunosuppressive therapy
4. Hemorrhagic stroke or transient ischemic attack (TIA)

Demographic, clinical, and biochemical parameters were collected at enrolment, discharge, and at the end of the study. The study duration was 90 days. A detailed history was obtained at enrolment; clinical examination and battery of investigations were done on admission, discharge, and at completion of the study. Baseline Data Collection was done on admission demographic details, and risk factors (hypertension, diabetes, smoking, dyslipidemia) were noted. A detailed history was obtained and a clinical examination was done. The severity of the stroke was assessed using the National Institutes of Health Stroke Scale (NIHSS) at admission. 

Laboratory investigations included estimation of HsCRP levels measured with high-sensitivity ELISA/immunoturbidimetric assay within 24 hours of admission. Other relevant biomarkers (lipid profile, fasting glucose, renal function tests).  Clinical Outcomes: Short-term outcomes (at discharge): Modified Rankin Scale (mRS) score (favorable outcome: mRS 0–2; poor outcome: mRS 3–6). Mortality rate. Long-term outcomes (3-month follow-up), Functional recovery (mRS) Recurrent stroke or cardiovascular events 

Statistical Analysis: Continuous variables expressed as mean ± SD or median (IQR); categorical variables as percentages. Pearson/Spearman correlation to assess the relationship between HsCRP and stroke severity (NIHSS). Multivariate logistic regression to determine if HsCRP is an independent predictor of poor outcomes (adjusting for age, comorbidities, NIHSS).  Receiver operating characteristic (ROC) curve analysis to determine the optimal HsCRP cutoff for predicting poor outcomes.  P-values <0.05 were considered statistically significant (using SPSS 22 software).  

Based on the inclusion and exclusion criteria a total of 80 cases of acute ischemic stroke were included in the study during the duration of the study period. Table 1 depicts the baseline characteristics of 80 participants enrolled in a study. The patients were categorized into two groups based on their initial HsCRP levels: a low HsCRP group (< 1 mg/L, n=33) and a high HsCRP group (> 3 mg/L, n=47). The mean age of the total study population was 66.51 years (± 6.91). The high HsCRP group had a slightly higher mean age (70.22 ± 3.4 years) compared to the low HsCRP group (64.19 ± 3.5 years). However, the p-value of 0.225 indicates that this difference in age between the two groups was not statistically significant. The majority of the study participants were male (75%). The proportion of males was higher in the high HsCRP group (80.9%) compared to the low HsCRP group (66.7%). Conversely, the proportion of females was higher in the low HsCRP group (33.3%) compared to the high HsCRP group (19.1%). The p-value of 0.031 suggests that the difference in sex distribution between the two groups is statistically significant. A significantly higher proportion of participants in the high HsCRP group had a history of hypertension (89.4%) compared to the low HsCRP group (39.4%).

Table 1: Baseline characteristics of the study participants

      * Significant

The prevalence of diabetes was also significantly higher in the high HsCRP group (38.3%) compared to the low HsCRP group (24.2%). A very small proportion of the total study population were smokers (2.5%). All the smokers were in the high HsCRP group (4.3%), while there were no smokers in the low HsCRP group (0%). The NIHSS score, a measure of stroke severity at admission, was presented as the median (interquartile range). The median NIHSS score was numerically lower in the high HsCRP group [29.37 (26.7 – 37.5)] compared to the low HsCRP group [40.28 (33.54- 48.7)]. There was a highly significant difference in HsCRP levels between the two defined groups. The low HsCRP group had a median HsCRP of 0.94 mg/L (interquartile range: 0.87 – 1.21), which falls below the 1 mg/L threshold. The high HsCRP group had a median HsCRP of 2.82 mg/L (interquartile range: 2.06 – 3.51), which is above the 3 mg/L threshold. The p-value of <0.001* confirms that this difference in HsCRP levels between the groups was highly statistically significant, validating the group classification. The overall median HsCRP for the total population was 2.57 mg/L (interquartile range: 0.87 – 3.51).

Table 2: Association between HsCRP levels and clinical outcomes

Table 2 shows that poor Outcome (mRS 3-6): Patients with high HsCRP levels (> 3 mg/L) had a significantly higher risk of poor outcome (modified Rankin Scale 3-6) compared to those with low HsCRP levels (< 1 mg/L). The odds ratio was 4.27, indicating more than four times higher odds of poor outcomes in the high HsCRP group. This association was statistically significant (p = 0.021). Mortality at Discharge: There was a statistically significant difference in mortality at discharge between the two groups. No deaths occurred in the low HsCRP group (0.0%), while 10.6% of patients in the high HsCRP group died (p = 0.000). Poor Outcome at 3 Months: Similar to the outcome at discharge, patients with high HsCRP levels had a significantly higher risk of poor outcome at 3 months. The odds ratio was 4.23, suggesting more than four times higher odds of poor outcomes at 3 months in the high HsCRP group. This association was also statistically significant (p = 0.001). Recurrent Stroke/CV Events: While there was a trend towards a higher incidence of recurrent stroke or cardiovascular (CV) events in the high HsCRP group (6.4%) compared to the low HsCRP group (0.0%), this difference was not statistically significant (p = 0.075).

Table 3: Multivariate Regression Analysis for Predictors of Poor Outcome (mRS 3-6)

Table 3, presents the results of a multivariate regression analysis of the predictors of poor outcome (mRS 3-6). NIHSS score (OR 3.01) has the widest confidence interval, reflecting its clinical importance in stroke outcomes. HsCRP Significance: (2.37–3.94), confirming its independent association with poor outcomes. Elevated HsCRP (>3 mg/L) independently predicted poor functional outcome after adjusting for stroke severity and vascular risk factors, with nearly 2.7-fold increased odds of unfavorable outcome (mRS 3-6).

Table 4: ROC Analysis for HsCRP in Predicting Poor Outcomes

The calculation of Youden's Index (Optimal cutoff) of HsCRP was 3.1 mg/L and a Positive Predictive Value: of 78.3%. Negative Predictive Value: 80.1% Accuracy: 79.2%. Figure 1 ROC curve demonstrating the predictive performance of HsCRP for poor functional outcome (mRS 3-6). The AUC of 0.81 (95% CI: 0.73–0.89) indicates good discriminatory ability. The dashed diagonal line represents chance prediction (AUC = 0.5). Optimal cutoff was >3 mg/L (sensitivity 82.5%, specificity 75.9%).  AUC >0.8 is considered "excellent" discrimination Significant p-value confirms predictive value. HsCRP demonstrated excellent predictive accuracy for poor outcomes (AUC 0.81, p<0.001). At the >3 mg/L cutoff, the test correctly identified 82.5% of patients who progressed to poor outcomes (mRS 3-6), while excluding 75.9% of those with favorable recovery.

This current study was designed to determine the significance of HsCRP in ischemic stroke. Our study shows a significant correlation between elevated high-sensitivity C-reactive protein levels and poor clinical outcomes in patients with acute ischemic stroke (AIS). The results of our study found that elevated 3 mg/L) was associated with poor short-term outcomes including increased disability (mRS 3–6). The multivariate analysis of this study further confirmed that HsCRP is an independent predictor of poor prognosis after adjusting for confounders such as age, stroke severity, and comorbidities. The findings of our study are in concordance with previous studies in this field highlighting the prognostic value of inflammatory markers particularly HsCRP in AIS. Di Napoli et al. [7] in a similar study reported a positive association between elevated CRP levels and poor 3-month outcomes in stroke patients. Similarly, Elkind et al. [8] reported that patients with higher baseline HsCRP were more likely to experience adverse outcomes which included recurrent stroke and vascular events within one year of the first event. Our study corroborates this evidence by showing that the HsCRP cutoff of >3mg/L is a reliable predictor of poor functional recovery with a sensitivity of 82.5% and specificity of 75.9%.

The analysis of AUC of 0.81 (95% CI: 0.73–0.89) shows the excellent discriminatory power of HsCRP in prediction. Similar findings have also been reported by Rodríguez-Yáñez et al. [9], who showed that AUC of 0.79 for HsCRP in predicting early neurological deterioration. The results of the study found that patients with high HsCRP had a lower median NIHSS score on admission, despite worse outcomes. This shows that systemic inflammation as reflected by HsCRP may influence recovery independently of initial stroke severity. Since HsCRP is known to mediate endothelial dysfunction, promote thrombosis, and exacerbate blood-brain barrier disruption. These mechanisms could potentially contribute to delay or incomplete neurological recovery [10]. The multivariate regression analysis shows the significance of HsCRP as an independent predictor. We found the adjusted odds ratio (OR) of 2.65 (95% CI: 2.37–3.94, p=0.001). Therefore, elevated HsCRP remains a reliable marker of poor outcomes. This is in concordance with studies of Vila et al. [11] and Whiteley et al. [12] where they found that HsCRP retained its predictive ability even after adjusting for stroke subtype and risk factors such as diabetes and hypertension. We found that hypertension and diabetes were more prevalent in the high HsCRP group and were independently associated with poor outcomes with (ORs of 2.67 and 2.29, respectively). This shows the synergistic relationship between inflammation and vascular risk. Rost et al. [13] showed that patients with multiple risk factors and elevated inflammatory markers are at a significantly higher risk of complications and recurrent events. In this study we found the optimal HsCRP cutoff identified by Youden’s Index was 3.1mg/L which is in close agreement with the cutoff used by other studies, such as the Northen Manhattan Stroke Study, which used >3 mg/L to define high cardiovascular risk [14]. This shows the ability of HsCRP to act as a diagnostic marker as well as a stratification tool for early therapeutic intervention. Our study is not without its limitations which included a moderate sample size (N=80) and single-center study which may limit the generalizability of the findings and the serial measurements of HsCRP were not performed which could be more useful in determining temporal trends of inflammation and outcome prediction.

In conclusion, this study reinforces the prognostic value of HsCRP levels in AIS. HsCRP >3 mg/L was independently associated with worse functional outcomes, higher mortality, and increased likelihood of recurrent vascular events. Since HsCRP is a low-cost diagnostic marker, it could be a valuable adjunct in stroke prognostication and risk stratification. Further studies with large sample sizes and serial estimation of HsCRP must be done to validate our findings and studies could explore whether anti-inflammatory interventions targeting CRP pathways could improve acute stroke outcomes.

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