The role of homocysteine levels as a risk factor of ischemic stroke events: a systematic review and meta-analysis

Rengaraj. G

Physician Assistant, Kauvery Hospital, Cantonment, Trichy, Tamil Nadu

Abstract

Background

Epidemiological research has shown that increased total homocysteine (tHcy) levels are associated with an increased risk of thromboembolic disease; however, controversy still exists over which subtype of stroke is allied to hyperhomocysteinemia. This study aimed to investigate whether elevated tHcy is an independent risk factor for ischemic stroke and to compare tHcy levels in patients with ischemic stroke subtypes.

Methods

This prospective study was conducted on young ischemic stroke patients in Kauvery Hospital, Trichy. Ischaemic stroke patients of age < 50 years were selected from both the outpatient and inpatient departments. A fasting venous blood sample was sent for analysis. Data was collected through a structured proforma and was analyzed. A period of 12 months, from January 2024 to December 2024 at Kauvery Hospital cantonment, Tamil Nadu, India.

Results

We have taken 196 patients who had a recent stroke for this study among the population 76 (38.7%) cases had hyper-homocysteinemia and 120 patients has normal homocysteine levels. The frequency was significantly higher in males and in the age group 18-50 years (22.9%).

1). Age

Variables (Age (Years)	Frequency	Percentage among 196 (100%) patients
<18	4	0.02
18-50	45	22.9
>50	27	13.7

2). Gender

Variables	Frequency	Percentage among 196 (100%) patients
Male	72	36.7
Female	4	0.02

3). Homocysteine Levels (mmol/l)

Variables	Frequency	Percentage among 196 (100%) patients
< 15 (Normal)	120	61.2
15-30	50	25.5
> 30	26	13.2

4). Risk Factors

Variables	Frequency	Percentage among 196 (100%) patients
Hypertension	23	11.7
Diabetes	70	35.7

5). Type of Stroke (TOAST Classification)

Variables	Frequency	Percentage among 196 (100%) patients
Large Artery Atherosclerosis	12	0.06
Small Vessel Disease	34	0.17
Cardiac embolism	18	0.09
Stroke of Undetermined Etiology	12	0.06

Exclusion Criteria for Cases and Controls

The exclusion criteria were concomitant history of previous ischemic strokes, cerebral venous infarcts, ischemic heart disease, peripheral vascular disease, hypothyroidism, epilepsy, renal impairment, pregnancy, postpartum state, consumption of oral contraceptives or drugs that might affect serum vitamin B12, folate, and Hcy levels, brain mass or any malignancy, history of migraine, and vitamin B12 and folate deficiencies.

Stroke Subtypes

According to the TOAST criteria, stroke subtypes were classified into large artery, cardioembolic, small artery/lacunar strokes, and strokes of other undetermined etiology 196 All the patients were subtyped using a modified TOAST criterion.

Discussion

This study has some important limitations. First, intracranial atherosclerosis can give rise to lacunar infarcts indistinguishable from lacunar and may result in small vessel/lacunar misclassification. Furthermore, small cardioembolic embolism can cause lacunar syndromes, acting as a confounding factor in the analysis of the relation between HHcy and stroke subtypes. We also could not omit HHcy as an acute-phase reactant and possible genetic propensity of our patients to HHcy.

In our study, we tried to match all the previously known traditional risk factors of cerebrovascular disease in the selection of controls. However, it was achieved only for age, sex, DM, and smoking and we resolved the confounding actions of HTN and HLP with statistical methods.

Conclusion

This study showed that an elevated Hcy level was an independent risk factor for ischemic stroke in patients. In addition, there was a significant relationship between increased Hcy levels and the risk of cardio embolic strokes.

Kauverian Bookshelf

Applied Medical Statistics

The role of homocysteine levels as a risk factor of ischemic stroke events: a systematic review and meta-analysis