European Journal of Cardiovascular Medicine

Stroke remains a major public health challenge globally, particularly affecting ageing populations in developing nations like India [1]. As life expectancy improves, the incidence of stroke is expected to increase dramatically [2]. Ischemic strokes, caused by arterial occlusion, constitute the majority of strokes and often result in substantial long-term disability or death [3].The cascade of ischemic injury involves cellular energy failure, excitotoxicity, oxidative stress, and intracellular calcium overload [4]. Calcium plays a central role, activating enzymes such as phospholipases, proteases, and endonucleases, which ultimately lead to irreversible neuronal injury [5].Recent studies have highlighted the importance of serum calcium as a potential prognostic marker in acute stroke [6]. Lower serum calcium levels have been linked with larger infarcts and poorer outcomes [7]. However, data from the Indian population are limited. Considering the potential clinical significance, this study aims to evaluate the association between serum calcium levels and infarct size in patients with acute ischemic stroke.

This cross-sectional descriptive analytical study was conducted at Government Vellore Medical College and Hospital over a 12-month period (June 2019 to May 2020)

Inclusion and Exclusion Criteria:
Patients aged above 40 years with CT-confirmed acute ischemic stroke were enrolled after informed consent. Patients with hemorrhagic stroke, cortical venous thrombosis, hepatic or renal dysfunction, or unwillingness to participate were excluded.

Clinical and Laboratory Evaluation:
Detailed clinical histories focusing on vascular risk factors such as hypertension, diabetes, smoking, and alcoholism were recorded. Serum calcium and albumin were measured using automated chemistry analyzers [9].Corrected serum calcium was calculated using the formula:

Corrected Calcium (mg/dL) = Serum Calcium + 0.8 × (4.0 - Serum Albumin)

Radiological Assessment:
Non-contrast CT brain imaging was performed. Infarct size was estimated using the ABC/2 method, a validated method for estimating infarct volume on CT scans [10].

Statistical Analysis:
Data were analyzed using SPSS software version 22. Continuous variables were expressed as mean ± SD, and categorical variables as percentages. Pearson’s correlation coefficient was used to study the relationship between serum calcium parameters and infarct size, with p-values <0.05 considered statistically significant.

Demographic Description:

In the present study comprising 50 patients diagnosed with acute ischemic stroke, males constituted the majority with 62% of the study population, while females accounted for 38%. The mean age was 61.3 ± 10.4 years, with a significant clustering of cases between 51–70 years of age. The age and gender distribution are detailed below.

Table 1: Demographic Characteristics of the Study Population

Figure 1: Age and Gender Distribution of Stroke Patients

Bar graph representing the distribution of male and female patients across different age groups among the study population.

Risk Factors:

Among the study participants, hypertension was the most prevalent comorbidity, affecting 56% of patients, followed by diabetes mellitus (38%), smoking (28%), and alcohol consumption (24%). The frequency distribution of risk factors observed is summarized as follows.Among the study participants, hypertension was the most prevalent comorbidity, affecting 56% of patients, followed by diabetes mellitus (38%), smoking (28%), and alcohol consumption (24%). The frequency distribution of risk factors observed is summarized as follows.

Table 2: Risk Factors Distribution among Patients

Frequency and percentage of common vascular risk factors in the study cohort

Serum Calcium Distribution:Serum calcium analysis revealed that around 25% of patients had lower calcium levels (8.1–8.9 mg/dL), while approximately 43% had normal levels (9–9.4 mg/dL), and 31% had higher levels (9.5–11 mg/dL). Notably, female patients demonstrated a greater tendency towards lower calcium levels and larger infarct sizes compared to male counterparts. The detailed distribution is given below.

Table 3: Serum Calcium Distribution and Infarct Size by Gender

Association between serum calcium levels and the corresponding infarct sizes among males and females

Infarct Size and Serum Calcium Group:

On analyzing the relationship between serum calcium groups and infarct size, it was observed that patients with lower serum calcium levels had larger infarct volumes, whereas those with higher serum calcium demonstrated relatively smaller infarcts. The comparative data between calcium levels and infarct size is graphically represented below.

Figure 2: Average Infarct Size by Serum Calcium Group

Bar graph comparing the average infarct size across different serum calcium levels (Low, Normal, High) among acute ischemic stroke patients

Correlation Analysis:

Statistical analysis using Pearson’s correlation demonstrated a significant negative correlation between serum calcium and infarct size (r = -0.2933, p = 0.04), and a stronger negative correlation when corrected calcium was considered (r = -0.6303, p = 0.01). Serum albumin levels showed no significant correlation. The results are detailed below.

Table 4: Correlation between Serum Calcium, Corrected Calcium, and Infarct Size

Pearson’s correlation analysis between biochemical markers and infarct size

Figure 3: Correlation between Serum Calcium and Infarct Size

Scatter plot illustrating the inverse relationship between serum calcium levels and infarct size among patients with acute ischemic stroke

The present study demonstrated a statistically significant inverse relationship between serum calcium levels and infarct size in patients presenting with acute ischemic stroke. These findings corroborate earlier observations by Borah et al. [11] and Kasundra et al. [12], who reported similar associations in Indian populations.The mean serum calcium levels were notably lower among patients with larger infarcts, suggesting that hypocalcemia may reflect more extensive neuronal injury. This is physiologically plausible given that calcium influx into neurons is a central mechanism of excitotoxicity during ischemic injury [4,5]. As the energy-dependent calcium pumps fail during ischemia, intracellular calcium overload triggers activation of destructive enzymatic cascades, leading to cell death [13].The higher proportion of large infarcts among female patients in this study, despite a lower overall incidence compared to males, is particularly noteworthy. This finding aligns with studies by Tziomalos et al. [8] and suggests possible gender-based differences in calcium metabolism or hormonal influences post-menopause. Moreover, comorbid conditions such as diabetes mellitus and hypertension, highly prevalent in our cohort, are known to exacerbate vascular damage and may have influenced the observed outcomes [14].Corrected calcium showed an even stronger negative correlation with infarct size compared to total serum calcium. This finding underscores the importance of adjusting for serum albumin when interpreting calcium levels, as hypoalbuminemia can falsely lower total serum calcium measurements [9]. Similar observations have been made by Ishfaq et al. [3] and Rodríguez-Luna et al. [10], emphasizing corrected calcium as a better prognostic marker.From a clinical standpoint, serum calcium measurement is inexpensive, widely available, and rapid. Its integration into routine stroke assessment protocols could enhance early risk stratification, guiding therapeutic decision-making. For instance, patients presenting with low serum calcium could be identified as high-risk for extensive cerebral injury, necessitating closer monitoring and possibly more aggressive interventions.Nevertheless, this study has certain limitations. It was confined to a single tertiary care center with a relatively small sample size, limiting generalizability. Only baseline calcium levels were assessed; dynamic changes in calcium levels during hospitalisation were not recorded. Future studies with larger sample sizes and longitudinal designs are warranted to validate these findings and explore potential interventional strategies.In summary, our results support the hypothesis that serum calcium, particularly corrected calcium, is inversely associated with infarct size in acute ischemic stroke. Incorporating serum calcium into early prognostic models may provide valuable clinical insights, aiding in the management of stroke patients.

This study highlights a significant negative correlation between serum calcium levels and infarct size in patients with acute ischemic stroke. Lower serum calcium and corrected calcium levels at admission were associated with larger infarct volumes, indicating poorer prognosis. Female patients exhibited a higher incidence of large infarcts despite being fewer in number. Risk factors such as diabetes and hypertension were prevalent among patients with lower calcium levels. Corrected calcium was found to be a superior predictor compared to total serum calcium. Routine measurement of serum calcium may thus serve as a simple, cost-effective tool for early risk stratification in acute stroke settings. Larger multicentric studies are recommended to confirm these findings and explore possible therapeutic interventions.

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