Stroke is a major public health problem globally, ranking as the second leading cause of death and a primary cause of long-term neurological disability [1]. In India, the incidence of stroke is rising, with significant implications for healthcare systems and families [2]. Ischemic stroke, resulting from thrombotic or embolic occlusion of cerebral arteries, constitutes approximately 80-85% of all strokes.

While traditional vascular risk factors such as hypertension, diabetes mellitus, dyslipidemia, and smoking are well-established, they do not fully explain the pathogenesis of all strokes. In recent decades, hyperhomocysteinemia has garnered attention as an independent, modifiable risk factor for atherosclerosis and thromboembolic events [3].

Homocysteine is a sulfur-containing amino acid formed during methionine metabolism. Elevated levels can arise from genetic polymorphisms (e.g., MTHFR C677T) or nutritional deficiencies in vitamin B12, folate, and vitamin B6 [4]. The proposed mechanisms linking hyperhomocysteinemia to ischemic stroke include endothelial injury, smooth muscle proliferation, oxidative stress, and activation of the coagulation cascade [5, 6].

The prevalence of hyperhomocysteinemia and its association with stroke varies across populations due to dietary habits, genetic factors, and nutritional status. This study was undertaken to investigate the correlation of serum homocysteine with ischemic stroke and to provide a detailed clinical, radiological, and biochemical profile of stroke patients in the Jodhpur region.

2. Objectives

1. To determine the baseline level of serum homocysteine in normal, healthy individuals (control group).
2. To determine the serum homocysteine level in patients diagnosed with ischemic stroke (case group).
3. To study the correlation of serum homocysteine levels in patients with ischemic stroke compared to healthy controls.
4. To analyze the detailed demographic profile, risk factors, clinical features, and investigation findings (including biochemical, radiological, and ECG) in patients with ischemic stroke.

3.1 Study Design and Setting This was a hospital-based, analytical case-control study conducted in the Department of Medicine at Vyas Medical College, Jodhpur. 3.2 Study Population Subjects were recruited from patients attending the medical outpatient department (OPD) and those admitted to various medical wards. 3.3 Inclusion Criteria • Group 1 (Control Group): 50 age- (±5 years) and sex-matched healthy individuals selected from hospital staff and attendants, with no history of stroke, transient ischemic attack (TIA), or any major systemic illness. • Group 2 (Case Group): 50 patients diagnosed with a first-ever episode of acute ischemic stroke. Diagnosis was confirmed by history, neurological examination, and neuroimaging (NCCT head or MRI brain) showing an acute infarct in a vascular distribution. 3.4 Exclusion Criteria • History of previous stroke or TIA. • Hemorrhagic stroke confirmed by imaging. • Chronic renal failure, liver disease, or hypothyroidism. • Patients on medications affecting homocysteine (methotrexate, phenytoin, vitamin B supplements). • Pregnant women. • Patients with malignancy. 3.5 Data Collection and Investigations A detailed proforma was used to collect: • Demographic data (age, sex). • Risk factors: hypertension, diabetes mellitus, smoking, alcohol, dyslipidemia, atrial fibrillation. • Clinical features: symptoms at onset and neurological signs. • Biochemical investigations: fasting blood sugar, lipid profile, renal function tests. • Imaging: Chest X-ray PA view, NCCT head/MRI brain. • Electrocardiogram (ECG). • Anthropometry: Body Mass Index (BMI) calculated as weight (kg)/height (m²). 3.6 Homocysteine Measurement After obtaining written informed consent, a 5 mL fasting venous blood sample was collected in an EDTA vacutainer. Plasma was separated by centrifugation. Serum homocysteine levels were measured using a chemiluminescence immunoassay (CLIA) method in the central laboratory. 3.7 Statistical Analysis Data were entered into Microsoft Excel and analyzed using SPSS version 20.0. Descriptive statistics (mean, standard deviation, frequency, percentage) were calculated. The unpaired Student's t-test was used to compare means between groups. A p-value < 0.05 was considered statistically significant.

4.1 Demographic Profile of Cases (n=50)

Table 1: Age and Sex Distribution of Ischemic Stroke Patients

Source: Survey Data

The mean age of cases was 59.5 ± 11.2 years, with the largest proportion (34%) of patients in the 61-70 years age group. This finding is consistent with epidemiological data showing that the risk of stroke increases exponentially with advancing age, primarily due to age-related vascular changes including arterial stiffness, endothelial dysfunction, and the cumulative burden of traditional risk factors.

The age distribution reveals that 80% of patients were above 50 years of age, reflecting the degenerative nature of cerebrovascular disease. Only 6% of patients were below 40 years, suggesting that stroke in younger individuals is relatively uncommon and often associated with distinct etiologies such as cardiac embolism, vasculitis, hypercoagulable states, or substance abuse.

The male-to-female ratio in our study was 2.3:1, with males comprising 70% of the case group. This male predominance is a consistent finding across Indian stroke studies and can be attributed to several factors. First, males have higher exposure to traditional risk factors such as smoking, alcohol consumption, and occupational stress. Second, hormonal factors, particularly the protective effect of estrogen in premenopausal women, may delay the onset of atherosclerotic vascular disease in females. Third, cultural factors in India may lead to differential healthcare-seeking behavior, with males being brought to tertiary care centers more frequently than females.

4.2 Distribution of Risk Factors in 50 Patients of Acute Ischemic Stroke (Gender-Wise)

Table 2: Distribution of Risk Factors (Male/Female Wise)

Source: Survey Data

Hypertension: The most prevalent risk factor, present in 64% of patients. This finding aligns with the landmark INTERSTROKE study, which identified hypertension as the single most important modifiable risk factor for stroke, accounting for approximately 35-40% of the population-attributable risk [9]. The slightly higher prevalence in females (66.7% vs. 62.9%) is noteworthy and may reflect poorer blood pressure control in postmenopausal women or a higher prevalence of isolated systolic hypertension in elderly females. Chronic hypertension leads to hypertensive arteriolosclerosis, lipohyalinosis, and endothelial damage, predisposing to both large artery atherosclerosis and small vessel lacunar infarcts.

Diabetes Mellitus: Diabetes was present in 40% of patients, with equal distribution between males and females. Diabetes is a potent risk factor for stroke, increasing risk by 2-4 fold. The pathophysiological mechanisms include accelerated atherosclerosis, endothelial dysfunction, increased platelet aggregation, and impaired fibrinolysis. The high prevalence in our study reflects the rising epidemic of type 2 diabetes in India, which has one of the largest diabetic populations globally [10].

Smoking and Alcohol: Smoking was present in 51.4% of males and 0% of females, while alcohol consumption was seen in 42.9% of males and 0% of females. This stark gender disparity reflects cultural norms in Rajasthan, where tobacco and alcohol use are socially accepted among males but largely prohibited among females. Smoking contributes to stroke through multiple mechanisms: nicotine-induced vasoconstriction, carbon monoxide-mediated endothelial injury, increased oxidative stress, and promotion of a prothrombotic state. The risk of stroke is dose-dependent and decreases significantly after smoking cessation.

Dyslipidemia: Dyslipidemia was present in 34% of patients, with similar prevalence in both genders. The atherogenic lipid profile—elevated LDL cholesterol, low HDL cholesterol, and elevated triglycerides—promotes the formation of atherosclerotic plaques in the carotid arteries and cerebral vasculature. The relatively lower prevalence of diagnosed dyslipidemia compared to hypertension may be attributed to underdiagnosis, as lipid abnormalities are often asymptomatic and may not have been previously screened.

Atrial Fibrillation: Atrial fibrillation was present in 10% of patients. This is a critical finding because atrial fibrillation increases stroke risk by 5-fold and is associated with more severe strokes due to larger embolic burden. The slightly higher prevalence in females (13.3% vs. 8.6%) is consistent with literature showing that females with atrial fibrillation have a higher age-adjusted stroke risk compared to males. Patients with atrial fibrillation require anticoagulation for secondary prevention [11].

Family History of Stroke: A positive family history was noted in 12% of patients, suggesting a genetic predisposition. Family history may reflect inherited risk factors such as hypertension, diabetes, or hyperhomocysteinemia due to MTHFR gene polymorphisms.

4.3 Number of Risk Factors Present in 50 Infarct Patients

Table 3: Number of Risk Factors per Patient

Source: Survey Data

The majority of patients (44%) had 2-3 risk factors, highlighting the multifactorial nature of ischemic stroke. Only 8% of patients had no identifiable traditional risk factors, suggesting that in these individuals, other mechanisms such as hyperhomocysteinemia, hypercoagulable states, or cryptogenic embolism may be operative.

The cumulative effect of multiple risk factors is well documented: the presence of two or more risk factors exponentially increases stroke risk beyond the sum of their individual risks. For example, a patient with hypertension and diabetes has a significantly higher risk than the additive risk of each condition alone, due to synergistic endothelial damage. This finding underscores the importance of comprehensive risk factor modification rather than targeting individual factors in isolation.

The 10% of patients with 4 or more risk factors constitute a very high-risk subgroup that requires aggressive multifactorial intervention, including strict blood pressure, glycemic, and lipid control, antiplatelet therapy, and lifestyle modifications.

4.4 Abnormal Biochemical Investigations in 50 Patients with Ischemic Infarcts (Gender-Wise)

Table 4: Abnormal Biochemical Investigations (Male/Female Wise)

Source: Survey Data

Fasting Blood Sugar: Elevated fasting blood glucose was observed in 52% of patients. This includes both patients with previously diagnosed diabetes and those with newly detected hyperglycemia. Acute hyperglycemia in stroke patients is associated with larger infarct size, poorer functional outcomes, and increased mortality. The mechanisms include exacerbation of oxidative stress, lactic acidosis in ischemic tissue, and impairment of collateral circulation.

Lipid Profile: Low HDL cholesterol was the most common lipid abnormality, present in 64% of patients. HDL cholesterol plays a crucial role in reverse cholesterol transport, removing excess cholesterol from arterial walls. Low HDL is a strong independent predictor of atherothrombotic stroke. Elevated LDL cholesterol (58%) and elevated triglycerides (46%) were also highly prevalent, reflecting the typical dyslipidemic pattern seen in metabolic syndrome—characterized by high LDL, high triglycerides, and low HDL.

The gender distribution shows slightly higher rates of dyslipidemia in females, particularly low HDL (66.7% vs. 62.9%) and elevated LDL (60.0% vs. 57.1%). This may be attributed to hormonal changes after menopause, which lead to a more atherogenic lipid profile.

Serum Creatinine: Elevated creatinine was noted in 10% of patients, indicating underlying chronic kidney disease. Renal impairment is an important risk factor for stroke, as it is associated with accelerated atherosclerosis, endothelial dysfunction, and altered coagulation. Patients with chronic kidney disease have a 2-3 fold increased risk of stroke compared to those with normal renal function.

4.5 Body Mass Index (BMI) of 50 Patients of Acute Ischemic Infarcts

Table 5: BMI Distribution in Cases

Source: Survey Data

A significant proportion of patients (60%) were either overweight or obese. Obesity contributes to stroke risk through multiple interrelated mechanisms: it promotes hypertension, diabetes, dyslipidemia, and obstructive sleep apnea—each an independent risk factor. Additionally, adipose tissue is metabolically active, secreting pro-inflammatory cytokines (adipokines) that promote systemic inflammation and endothelial dysfunction.

The classification used in this study follows the World Health Organization (WHO) Asia-Pacific guidelines, which define overweight as BMI ≥23 kg/m² and obesity as BMI ≥25 kg/m². These lower cutoffs are used for Asian populations because they have a higher percentage of body fat at lower BMI levels and develop metabolic complications at lower BMI thresholds compared to Caucasian populations [12].

The gender distribution shows a higher proportion of females (33.3%) in the obese category than males (31.4%), though the difference is not substantial. This may reflect differences in body composition and fat distribution, with females having higher rates of central obesity post-menopause.

The 6% of patients who were underweight represent a smaller subgroup where stroke may be related to other etiologies such as vasculitis, hypercoagulable states, or cardioembolism rather than atherosclerotic mechanisms.

4.6 Chest X-ray PA View Findings in 50 Patients of Acute Ischemic Infarcts

Table 6: Chest X-ray PA View Findings (Male/Female Wise)

Source: Survey Data

Chest X-ray is a routine investigation in stroke patients to evaluate for cardiac enlargement, pulmonary pathology, and potential sources of embolism. Cardiomegaly was the most common abnormal finding, present in 22% of patients. Cardiomegaly on chest X-ray typically indicates underlying left ventricular hypertrophy or dilatation, most commonly due to chronic hypertension or ischemic heart disease.

The presence of cardiomegaly is clinically significant because it serves as a marker of chronic cardiac strain and is often associated with left ventricular dysfunction, which increases the risk of cardioembolic stroke. Patients with cardiomegaly and atrial fibrillation (seen in 10% of our patients) are at particularly high risk for embolic strokes.

Pulmonary edema was seen in 6% of patients, indicating acute or chronic heart failure. This finding has important therapeutic implications, as volume overload can exacerbate neurological injury and requires careful fluid management during the acute stroke phase.

The overall normal chest X-ray in 70% of patients is expected, as acute ischemic stroke does not directly cause pulmonary changes. However, a normal chest X-ray does not exclude significant cardiac pathology, and echocardiography may be required for further evaluation in selected patients.

4.7 Signs and Symptoms in 50 Patients of Acute Ischemic Infarcts

Table 7: Presenting Signs and Symptoms (Male/Female Wise)

Source: Survey Data

Symptoms: Limb weakness was the most common presenting symptom, reported by 94% of patients. This is the hallmark symptom of stroke, reflecting involvement of the corticospinal tract. The predominance of limb weakness correlates with the high frequency of MCA territory involvement (68% in our study), as the MCA supplies the motor cortex and its descending fibers.

Facial weakness (80%) and slurred speech (74%) were also highly prevalent. Facial weakness in upper motor neuron type typically spares the forehead, distinguishing it from lower motor neuron facial palsy. Slurred speech (dysarthria) may result from weakness of the oral, lingual, or pharyngeal musculature and is often associated with swallowing difficulties, increasing the risk of aspiration pneumonia.

Altered sensorium was present in 22% of patients. This can range from mild confusion to coma and is more common in patients with large hemispheric strokes, brainstem involvement, or those with associated metabolic disturbances. The presence of altered sensorium at presentation is a poor prognostic indicator.

Headache was reported by only 16% of patients. Unlike hemorrhagic stroke, where headache is a prominent feature (present in 80-90% of cases), ischemic stroke typically presents without significant headache. When present, headache in ischemic stroke may indicate large artery dissection, posterior circulation involvement, or concomitant hypertension.

Signs: Hemiplegia (complete paralysis) was observed in 76% of patients, while hemiparesis (partial weakness) was seen in 20%. The predominance of hemiplegia suggests that many patients presented with severe deficits, likely due to delayed presentation or large vessel occlusion. The National Institutes of Health Stroke Scale (NIHSS) scores, though not formally recorded in this study, would be expected to be higher in patients with hemiplegia.

Upper motor neuron facial palsy was observed in 82% of patients, consistent with the high rate of contralateral facial weakness seen in MCA strokes. Dysarthria was present in 70% of patients, highlighting the frequency of speech impairment in stroke.

Gaze palsy was the least common sign (10%), typically indicating involvement of the frontal eye fields (conjugate gaze deviation toward the side of the lesion) or paramedian pontine reticular formation (conjugate gaze deviation away from the side of the lesion). Gaze palsy is often associated with larger infarcts and worse outcomes.

4.8 ECG Findings in 50 Patients of Acute Ischemic Infarcts

Table 8: ECG Findings (Male/Female Wise)

Source: Survey Data

Electrocardiography is an essential investigation in all stroke patients to identify cardiac sources of embolism and to detect underlying cardiac pathology that may influence management.

Left Ventricular Hypertrophy (LVH): LVH with strain pattern was the most common ECG abnormality, present in 40% of patients. LVH is a marker of chronic hypertension and is associated with increased cardiovascular morbidity and mortality. The strain pattern—characterized by ST-segment depression and T-wave inversion in the left precordial leads—indicates significant myocardial involvement. Patients with LVH have a higher risk of stroke due to associated hypertensive arteriopathy, increased left atrial size predisposing to atrial fibrillation, and potential for cardioembolism.

Atrial Fibrillation: Atrial fibrillation was detected in 10% of patients on ECG. This is a critical finding because atrial fibrillation is a major cause of cardioembolic stroke, which tends to be more severe and has a higher risk of recurrence. The slightly higher prevalence in females (13.3% vs. 8.6%) is consistent with literature showing that females with atrial fibrillation have a higher age-adjusted stroke risk. All patients with atrial fibrillation require long-term anticoagulation for secondary stroke prevention unless contraindicated.

Ischemic Changes: ST-T changes suggestive of myocardial ischemia were present in 16% of patients. These changes may represent underlying coronary artery disease, which frequently coexists with cerebrovascular disease due to shared risk factors (panvascular disease). In the acute stroke setting, these changes may also reflect neurocardiogenic injury—a phenomenon where acute brain injury leads to myocardial dysfunction and ECG changes.

Normal ECG: Only 34% of patients had a completely normal ECG, underscoring the high prevalence of underlying cardiac pathology in stroke patients.

4.9 Arterial Involvement on Neuroimaging

Table 9: Arterial Territory Involvement

Source: Survey Data

Middle Cerebral Artery (MCA): The MCA was the most commonly involved territory, accounting for 68% of strokes. This is consistent with the anatomical distribution of cerebral blood flow, as the MCA supplies approximately two-thirds of the hemispheric surface, including the motor and sensory cortices, language areas, and visual radiations. MCA strokes typically present with contralateral hemiparesis, hemisensory loss, facial weakness, and, if dominant hemisphere involved, aphasia. The high frequency of MCA involvement in our study explains the predominance of limb weakness (94%) and hemiplegia (76%) observed in Table 7.

Posterior Cerebral Artery (PCA): PCA involvement was seen in 12% of patients. PCA strokes affect the occipital lobe, presenting with contralateral homonymous hemianopia. If the thalamus is involved, patients may present with sensory deficits or thalamic pain syndromes. PCA strokes are sometimes misdiagnosed because motor deficits are less prominent than in MCA strokes.

Anterior Cerebral Artery (ACA): ACA involvement was seen in 8% of patients. ACA strokes affect the frontal lobe and parasagittal regions, presenting with contralateral leg weakness (greater than arm weakness), abulia, and urinary incontinence. The lower frequency of ACA strokes compared to MCA strokes is expected due to the smaller territory supplied by the ACA.

Lacunar Infarcts: Lacunar infarcts were seen in 8% of patients. These are small subcortical infarcts (≤1.5 cm) resulting from occlusion of a single penetrating artery, typically in the setting of hypertension. They are associated with specific clinical syndromes including pure motor hemiparesis, pure sensory stroke, and ataxic hemiparesis.

Brainstem/Cerebellar: Brainstem and cerebellar infarcts accounted for 4% of patients. These posterior circulation strokes can present with vertigo, ataxia, cranial nerve deficits, and cross findings (ipsilateral cranial nerve signs with contralateral limb weakness). They carry a high risk of morbidity due to potential for brainstem compression and hydrocephalus.

4.10 Blood Pressure at Presentation

Table 10: Blood Pressure Profile in Cases

Source: Survey Data

A total of 84% of patients had elevated blood pressure at presentation, underscoring the central role of hypertension in ischemic stroke. This high prevalence is consistent with the INTERSTROKE study, which identified hypertension as the most important modifiable risk factor for stroke globally [9].

The blood pressure profile in acute ischemic stroke is complex. In many patients, blood pressure is elevated at presentation due to various factors: pre-existing chronic hypertension, acute stress response to the stroke, increased intracranial pressure, and autoregulatory mechanisms attempting to maintain cerebral perfusion pressure.

The management of blood pressure in acute ischemic stroke requires careful consideration. While chronic hypertension is a risk factor, acute blood pressure reduction in the first 24-48 hours can be detrimental, particularly in patients with large vessel occlusion or significant stenosis, as it may compromise collateral circulation to the ischemic penumbra. Current guidelines recommend permissive hypertension with a threshold for treatment typically at >220/120 mmHg or in patients eligible for thrombolysis (>185/110 mmHg).

The finding that 40% of patients had Stage 2 hypertension (≥140/90 mmHg) and 44% had Stage 1 hypertension indicates that a significant proportion of patients had poorly controlled or newly detected hypertension, representing a missed opportunity for primary prevention.

4.11 Homocysteine Levels in Different Age Groups

Table 11: Mean Homocysteine Levels in Different Age Groups (Cases)

Source: Survey Data

The highest mean homocysteine levels were observed in the 61-70 years age group (20.5 ± 5.4 µmol/L), followed by the >70 years age group (19.4 ± 5.1 µmol/L). This age-related increase in homocysteine levels is well documented and can be attributed to several factors.

First, aging is associated with a progressive decline in renal function, even in the absence of overt kidney disease. Since homocysteine is primarily cleared by the kidneys, reduced glomerular filtration rate leads to its accumulation. Second, elderly individuals often have decreased dietary intake of vitamin B12 and folate, as well as reduced absorption of these vitamins due to atrophic gastritis, which is common in the aging population. Third, age-related changes in enzyme activity involved in homocysteine metabolism may contribute to its elevation.

The increase in homocysteine levels with age has important clinical implications. As age is itself an independent risk factor for stroke, the combination of advanced age and hyperhomocysteinemia creates a high-risk profile. The peak in the 61-70 years age group, followed by a slight decline in those over 70, may reflect survival bias—individuals with the highest homocysteine levels may have had earlier vascular events, leaving a cohort with relatively lower levels in the oldest age group.

The youngest age group (<40 years) had the lowest mean homocysteine level (14.3 µmol/L), though still elevated compared to healthy controls. This suggests that even in young stroke patients, hyperhomocysteinemia may play an etiological role, and screening should not be limited to older individuals.

4.12 Mean Homocysteine Levels in Cases vs. Controls

Table 12: Comparison of Mean Homocysteine Levels

*Statistically significant (p < 0.05)

Source: Survey Data

The mean serum homocysteine level in the case group (18.45 ± 5.2 µmol/L) was significantly higher than in the control group (10.25 ± 3.1 µmol/L; p < 0.001). This difference is highly statistically significant and establishes a strong positive correlation between elevated homocysteine levels and ischemic stroke.

Interpretation of Homocysteine Levels:

Normal homocysteine levels are generally considered to be between 5-15 µmol/L. Mild hyperhomocysteinemia is defined as 15-30 µmol/L, moderate as 30-100 µmol/L, and severe as >100 µmol/L. In our study, the mean level in cases (18.45 µmol/L) falls within the mild hyperhomocysteinemia range, while the control group mean (10.25 µmol/L) is within the normal range.

Pathophysiological Significance:

The 8.2 µmol/L difference between cases and controls is clinically meaningful. Each 5 µmol/L increase in homocysteine level is associated with an approximately 20-30% increase in the risk of stroke, according to meta-analyses [13]. The mechanisms underlying this association include:

1. Endothelial Dysfunction: Homocysteine impairs endothelial nitric oxide synthase (eNOS), reducing nitric oxide bioavailability and leading to vasoconstriction and platelet adhesion.
2. Oxidative Stress: Homocysteine auto-oxidizes, generating reactive oxygen species (ROS) that damage vascular endothelium and promote LDL oxidation.
3. Smooth Muscle Proliferation: Homocysteine stimulates the proliferation of vascular smooth muscle cells, contributing to intimal thickening and atherosclerosis.
4. Prothrombotic Effects: Homocysteine activates factor XII, promotes tissue factor expression, and inhibits thrombomodulin and protein C activation, creating a hypercoagulable state.
5. Inflammation: Homocysteine upregulates pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α, promoting vascular inflammation.

Clinical Implications:

The finding that hyperhomocysteinemia is significantly associated with ischemic stroke has important clinical implications. Unlike many other risk factors, hyperhomocysteinemia is readily modifiable through simple, inexpensive interventions. Vitamin B12 and folate supplementation can effectively lower homocysteine levels by 20-30% within weeks. While randomized controlled trials of homocysteine-lowering therapy have shown mixed results for secondary stroke prevention, subgroup analyses suggest that patients with high baseline homocysteine levels and those in regions without mandatory folate fortification may derive significant benefit [14].

In the Indian context, where folate fortification of food is not mandatory and vitamin B12 deficiency is highly prevalent due to vegetarian dietary patterns, homocysteine-lowering therapy may have particular relevance. Screening for homocysteine, along with vitamin B12 and folate levels, should be considered as part of the routine evaluation of stroke patients and high-risk individuals.

This study provides a comprehensive analysis of the clinical, biochemical, and radiological profile of patients with acute ischemic stroke and establishes a significant correlation with elevated serum homocysteine levels.

Demographic Profile: The mean age of 59.5 years and male predominance (70%) in our study are consistent with the findings of Pandian et al. and other Indian studies, which report a higher incidence of stroke in males, likely due to higher exposure to lifestyle risk factors like smoking and alcohol [8]. The peak incidence in the 61-70 years age group aligns with global epidemiological data.

Risk Factors: Hypertension was the most common risk factor (64%), similar to the INTERSTROKE study, which identified hypertension as the single most important modifiable risk factor for stroke globally [9]. The high prevalence of diabetes (40%) and dyslipidemia (low HDL in 64%) reflects the growing burden of metabolic syndrome in the Indian population. Notably, smoking and alcohol were exclusive to males, contributing to their higher stroke incidence. The finding that 44% of patients had 2-3 risk factors underscores the multifactorial nature of stroke and the need for comprehensive risk factor modification.

Clinical Features: Limb weakness (94%) and hemiplegia (76%) were the predominant presentations, correlating with the high frequency of MCA territory involvement (68%). This pattern is typical of supratentorial strokes and reflects the motor cortex and corticospinal tract involvement. The presence of altered sensorium in 22% of patients is a concerning finding, as it is associated with larger infarct size and worse prognosis.

Investigations: The high prevalence of abnormal biochemical findings—particularly dyslipidemia (64%) and impaired fasting glucose (52%)—highlights the importance of metabolic screening in stroke patients. ECG abnormalities, especially LVH (40%) and atrial fibrillation (10%), indicate significant underlying cardiac pathology that requires targeted intervention. The finding that 60% of patients were overweight or obese reflects the growing epidemic of obesity in India and its contribution to vascular disease.

Homocysteine Correlation: The mean homocysteine level in cases (18.45 µmol/L) was significantly higher than in controls (10.25 µmol/L) (p < 0.001). This finding aligns with the work of Sacco et al. in the NOMAS study and Kalita et al. in an Indian cohort, confirming hyperhomocysteinemia as an independent risk factor [13, 15]. The observed age-related increase in homocysteine levels (peaking in 61-70 years) is consistent with age-related decline in renal function and vitamin B12 absorption.

Strengths and Limitations:

Strengths:

Age- and sex-matched control group minimizes selection bias.

Comprehensive data collection including clinical, biochemical, and radiological parameters.

Diagnosis of ischemic stroke confirmed by neuroimaging.

Detailed gender-wise analysis of multiple parameters.

Limitations:

Case-control design establishes association but not causation.

Relatively small sample size (n=50 per group).

Vitamin B12 and folate levels were not measured, which would have helped clarify the etiology of hyperhomocysteinemia.

No long-term follow-up data on outcomes or recurrence.

This study demonstrates a strong and statistically significant positive correlation between elevated serum homocysteine levels and ischemic stroke. The mean homocysteine level was significantly higher in patients with ischemic stroke compared to healthy controls (18.45 ± 5.2 µmol/L vs. 10.25 ± 3.1 µmol/L, p < 0.001). Hyperhomocysteinemia appears to be a significant modifiable risk factor in the population of Jodhpur and surrounding regions. The detailed analysis of 50 stroke patients revealed: Male predominance (70%) with peak incidence in 61-70 years age group. Hypertension (64%) as the most prevalent risk factor. Majority of patients (44%) had 2-3 risk factors, highlighting multifactorial etiology. Limb weakness (94%) and hemiplegia (76%) as predominant clinical features. MCA territory involvement in 68% of cases. High prevalence of dyslipidemia (low HDL in 64%) and impaired fasting glucose (52%). LVH on ECG (40%) and cardiomegaly on chest X-ray (22%) indicating chronic hypertension. Age-related increase in homocysteine levels, peaking in 61-70 years age group. Clinical Implications and Recommendations: Screening: Given the strong association, screening for serum homocysteine levels should be considered as part of the routine workup for patients presenting with ischemic stroke and for those at high risk. Risk Factor Modification: Aggressive management of traditional risk factors—hypertension, diabetes, dyslipidemia, and obesity—must be combined with lifestyle modifications including smoking cessation and alcohol reduction. Homocysteine-Lowering Therapy: Since hyperhomocysteinemia can be effectively treated with vitamin B12 and folate supplementation, its identification offers a potential therapeutic target for secondary stroke prevention. In the Indian context, where vitamin B12 deficiency is highly prevalent, supplementation may be particularly beneficial. Comprehensive Evaluation: The high prevalence of cardiac abnormalities (LVH, atrial fibrillation) and renal impairment in this study underscores the need for comprehensive cardiovascular evaluation in all stroke patients. Future Research: Larger, prospective, multi-centric studies with measurement of vitamin B12 and folate levels are needed. Interventional trials evaluating the benefit of homocysteine-lowering therapy in reducing stroke burden in the Indian population are warranted.

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