European Journal of Cardiovascular Medicine

Stroke constitutes a significant global health concern and ranks as the second foremost cause of disability globally. It is anticipated that 80% to 87% of cases are categorised as ischaemia. In recent decades, recent studies indicate, inflammatory response is crucial in the pathophysiology of ischaemic stroke aetiology. During the acute phase, inflammation may exacerbate secondary brain injury by stimulating glial cells, increasing pro- inflammatory cytokine concentrations, and compromising the integrity of the blood-brain barrier.So inflammation might be an effective approach for avoiding future strokes. 1,2

Plasma C-reactive protein (CRP) is primarily produced by the liver in response to tissue injury and serves as a very sensitive indicator of inflammatory activity. Previous research has established a correlation between CRP-based inflammatory markers and inflammatory disorders, including DM nephropathy, subacute thyroiditis, and hepatitis. Given the association between stroke and inflammation, it is essential to measure the levels of C-reactive protein (CRP) in people who have experienced a stroke. The relationship between C-reactive protein (CRP) levels and clinical outcomes in stroke patients has been thoroughly investigated; yet, the findings remain ambiguous.Certain studies have indicated a correlation between CRP levels and functional results following a stroke; though, many studies have found no significant relationship between these variables. 3,4 This study sought to evaluate serum C-reactive protein (CRP) as a short- term prognostic indicator in individuals with acute ischaemic stroke.

This single-center prospective study was carried out among 100 Patients attending Department of Medicine OPD, Governement General Hospital, Srikakulam. Duration of study was  18 Months (June 2023- December 2024).

Inclusion Criteria

Patients presenting within 48 hours of stroke onset and providing informed permission for research participation were included.

Exclusion Criteria

1. Subdural haemorrhage, intracerebral haemorrhage and subarachnoid haemorrhage were excluded
2. Patients having repeated history of stroke
3. Patients having infections and malignancies during study were excluded
4. Patients with rheumatic heart disease & collagen vascular problems
5. Patients with past history of transient ischemic attacks or reversible ischemic neurological deficits.

Methodology

Clinical Examination:

Patients were examined for hypertension, obesity, and the existence of carotid artery thrill and bruit. A thorough evaluation of the cardiovascular and central neurological systems was performed, and  the  findings  were  recorded. An  electrocardiogram  and  a posteroanterior chest X-ray were performed to rule out AF , VHD, and acute myocardial infarction. Blood pressure was measured at admission, and body mass index was calculated. Individuals with a BMI over 30 were categorised as obese.

Investigations: Hb%, Total count, differential count, Random blood sugar, urea , creatinine. Fasting total cholesterol (TC), Fasting high density lipoprotein cholesterol(HDL-C). CT brain plain at the time of admission and Hs CRP test was done within 24-48 hours of stroke onset.

Assessing Functional Outcome: On seventh day patients clinical and functional status were assessed using GLASGOW OUTCOME SCALE.

GLASGOW OUT COME SCALE:

Note: The scale presented here is based on the original article by Jennett and Bond.

SCORE DESCRIPTION

• Death
• Persistent vegetative state Patient exhibits no obvious cortical function.
• Severe Disability (Conscious but disabled). Patient depends upon others for daily support due to mental or physical disability or both
• Moderate Disability (Disabled but independent). Patient is independent as far as daily life is concerned. The disabilities found include varying degrees of dysphasia, hemiparesis, or ataxia, as well as intellectual and memory deficits and personality changes.
• Good Recovery, Resumption of normal activities even though there may be minor neurological or psychological deficits.

This study examined 100 people to investigate the relationships among comorbid conditions, inflammatory indicators, lipid profiles, and neurological outcomes. The gender distribution revealed a significant male predominance, with 82% of the sample population identified as male and only 18% as female, yielding a male-to-female ratio of around 4.5:1.

Lifestyle Risk Factors

Regarding lifestyle factors, 57% of participants reported smoking, while 43% identified as non-smokers. Alcohol consumption was negligible, with only 15% admitting to usage, while the remaining 85% denied any intake. These findings highlight the superiority of smoking over alcohol use as a potential lifestyle-related risk factor in this cohort.

Comorbidities

Among the research participants, 24% were classified as diabetic, whereas the majority (76%) lacked a documented history of diabetes mellitus. Hypertension impacted over half of the population (54%), signifying a considerable prevalence of this cardiovascular risk factor.  Ischaemic heart disease (IHD) was observed in 5% of individuals, whereas obesity was recorded in 8%, suggesting a somewhat lower prevalence of both conditions in the current cohort.

Lipid Profile

The evaluation of lipid profiles revealed that 30% of patients displayed elevated total cholesterol levels (>200 mg/dL), whilst the other 70% sustained values within the normal range. A major finding was the prevalence of low high-density lipoprotein (HDL) levels, with 84% demonstrating HDL values under 45 mg/dL. Only 16% had HDL levels surpassing this threshold. Furthermore, the TC/HDL ratio above 4 in 89% of cases, signifying atherogenic risk, whereas just 11% had a favourable ratio below 4.

C-Reactive Protein (CRP) Distribution

The CRP readings were classified into nine intervals, ranging from 1 to 10 mg/L. The highest proportions of patients had CRP levels in the ranges of 6-7 mg/L (23%), 7-8 mg/L (21%), and 3-4 mg/L (21%). Only 1% of individuals had CRP levels between 1-2 mg/L, signifying that the majority of participants demonstrated moderately elevated to high inflammatory markers.

Table 1: Distribution of Study Subjects based on CRP Distribution

Neurological Status and Outcome (Glasgow Coma Scale)

The assessment of neurological condition using the Glasgow Coma Scale (GCS) categorised patients into three groups: mild/good outcome (34%), vegetative/severe impairment (61%), and death (5%). The frequency of negative neurological consequences underscores the severity of illness in the studied cohort.

Table 2: Distribution of Study Subjects based on GLASGOW Scale

Association of GCS with CRP

A statisticaly signifcant association was found between GCS scores and CRP levels (Fisher’s Exact Value = 57.54, p < 0.001).  Patients demonstrating adverse neurological outcomes (vegetative condition, severe disability, or fatality) exhibited increased CRP levels, whereas those with intermediate or favourable outcomes displayed comparably lower CRP values. This validates CRP as an effective prognostic marker in neurological injury.

Table 3: Association of GLASGOW Scale and Hs-CRP

Association of GCS with Lipid Parameters

Total cholesterol had a significant connection with neurological outcomes (p = 0.002). Increased serum cholesterol values were more common among those with inadequate GCS scores.  HDL levels exhibited a significant connection (p = 0.04), with increased HDL linked to enhanced neurological outcomes. The TC/HDL ratio had a strong connection with GCS status (p = 0.002), with elevated ratios correlated with bad neurological outcomes.

Table 4: Association of GLASGOW Scale and Total Cholesterol

Table 5: Association of GLASGOW Scale and TCL/HDL Ratio

Association of GCS with Comorbidities

Relationships between smoking, alcohol use, DM,HTN,IHD, obesity and GCS scores were evaluated. However, none of these comorbid conditions showed statistically significant associations with GCS scores (all p > 0.05), indicating that while these comorbidities are prevalent, they may not independently predict neurological outcomes.

Table 6: Comparison between Variables and Hs-CRP

Gender and CRP

No significant association between CRP values was noted between male and female subjects (p = 0.9), suggesting gender did not influence systemic inflammation as measured by CRP.

CRP Associations with Lifestyle and Clinical Parameters

The stratification of CRP by various risk factors shown no significant differences associated with smoking (p = 0.7), alcohol use (p = 0.9), diabetes (p = 0.7), hypertension (p = 0.9), ischaemic heart disease (IHD) (p = 0.9), or obesity (p = 0.1). A comparative examination of lipid parameters revealed significantly higher CRP levels in individuals with total cholesterol over 200 mg/dL (p <0.001), HDL below 45 mg/dL (p = 0.02), and a TC/HDL ratio >4 (p < 0.001), showing a link between dyslipidemia& systemic inflammation.

Results of our study agrees with other studies emphasising the predictive importance of CRP in acute ischaemic stroke. Bian et al. (2023) showed that increased CRP levels within 24 hours of stroke onset were related with worse functional outcomes at three months. Their analysis revealed a substantial relation between CRP levels and baseline NIHSS scores, fasting hyperglycemia, and age, suggesting that CRP functions as a marker for both the inflammatory response and the severity of the stroke event. 5

Similarly, van Hertog et al. (2009) found that CRP values measured within 12 hours after the onset of ischaemic stroke were by itself tied to worse outcomes and mortality at three months. Findings points those with CRP levels ≥7 mg/L had a notable increased risk of negative consequences. 6

These research corroborate our findings, underscoring the importance of CRP as a crucial biomarker for early prognostication in AIS.

Our research revealed that 30% of participants had increased total cholesterol values (>200 mg/dL), and a significant proportion demonstrated low HDL levels (<45 mg/dL). A high TC/HDL ratio (>4) was prevalent among patients, correlated with worse neurological outcomes.

Numerous studies have examined the association between lipid profiles and CRP levels. Elevated CRP values are related to dyslipidemia, suggesting a synergistic effect that exacerbates stroke outcomes. A study by Elkind et al. (2009) showed that CRP levels forecast mortality but not recurrent stroke, underscoring the complex relationship among inflammation, lipid metabolism, and stroke prognosis. 7

Our research revealed no statistically positive relation between modifiable factors, i.e smoking and alcohol use, and comorbidities such as DM , HTN , IHD, and obesity, as well as CRP levels or GCS outcomes.

Our findings found that heightened CRP values were assosiated with worse neurological impairment and higher mortality rates. This aligns with the findings of van Hertog et al. (2009), who showed that high CRP levels within 12 hours of stroke onset were assosiatedwith high risk of negative outcomes and death at three months. 8

Bian et al. (2023) demonstrated a positive correlation between CRP levels and baseline NIHSS scores, indicating that CRP could be seen as a surrogate indicator of stroke severity. 5

Acute ischaemic stroke (AIS) remains a leading cause of illness and mortality worldwide, with its effects intensified in low- and middle-income countries. Inflammation has emerged as a pivotal element in the aetiology and prognosis of ischaemic strokes. C- reactive protein (CRP) is a significant inflammatory biomarker noted for its sensitivity, cost- effectiveness, and accessibility in routine clinical practice.

CRP is an acute-phase reactant synthesized by the liver, with levels rising in reaction to interleukin-6 (IL-6), particularly after tissue injury, infections, or systemic inflammation. In the case of AIS, infarcted cerebral tissue initiates an inflammatory flow, resulting in to the release of cytokines that subsequently facilitate the production of CRP. This biological process substantiates the use of CRP as a predictive biomarker for assessing the extent of neuroinflammatory injury.

The prognostic value of CRP in AIS is intricate. CRP levels measured during the acute phase—generally during the first 24–72 hours—are correlated with early neurological deterioration, infarct advancement, and worse functional outcomes. These associations highlight its potential use in clinical decision-making, including risk classification, monitoring intensity, and potential early interventions.

While CRP is a frequently employed biomarker, it is not the only inflammatory marker linked to stroke outcomes. Further biomarkers, such as interleukins (e.g., IL-6, IL-1β), tumour necrosis factor-alpha (TNF-α), serum amyloid A, and pentraxin-3 (PTX3), also had diagnostic and prognostic relevance. Nonetheless, these indicators sometimes need specialist assays, limiting their real-time application.

In contrast, CRP is one among few biomarkers that is cost-efficient, rapidly measurable, and widely available in most healthcare settings. High-sensitivity CRP (hs-CRP) tests provide enhanced accuracy in quantifying low concentrations, although traditional CRP evaluations still offer valuable predictive information, especially in acute situations.

Limitations:

Cross-Sectional Design:

Single-Center Study:

Limited Sample Size:

Limited Outcome Stratification

CRP functions as a promising and pragmatic biomarker for short-term prognosis in acute ischaemic stroke. Its ease of testing, robust connection with stroke severity, and potential therapeutic implications make it a valuable tool in the clinician's arsenal. However, meticulous interpretation and contextual integration with additional therapeutic aspects are prerequisite for the effective use of its potential. As our understanding of neuroinflammation in stroke progresses, CRP is anticipated to remain vital for biomarker research and clinical application.

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