What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Ischemic stroke (n=9947). Intervention: Homocysteine levels vs. Controls (without ischemic stroke). Primary outcome: Standardized mean difference of homocysteine levels (SMD 1.67, 95% CI 1.09-2.25, p=<0.01).

October 13, 2022PLoS ONE40 citationsOpen Access

Homocysteine is associated with higher risks of ischemic stroke: A systematic review and meta-analysis

Q: What are the key findings of this study?

Homocysteine levels were significantly higher in patients with ischemic stroke compared to controls, with a standardized mean difference of 1.67.

NRNícollas Nunes RabeloUniversidade de São Paulo JTJoão Paulo Mota TellesUniversidade de São Paulo LPLeonardo Zumerkorn PipekHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Key Result

Homocysteine levels were significantly higher in patients with ischemic stroke compared to controls, with a standardized mean difference of 1.67.

Study Design

Type

Meta-Analysis (n=9,947)

Structured PICO

Are homocysteine levels higher in patients with ischemic stroke compared to controls?

Population

9,947 participants (5,002 with ischemic stroke and 4,945 controls) from 13 observational studies were included in a meta-analysis to evaluate the association between homocysteine levels and ischemic stroke.

Exposure

Ischemic stroke (assessing homocysteine levels as an exposure/biomarker)

Comparator

Controls without ischemic stroke

Outcome

Standardized mean difference in homocysteine (Hct) levels between patients with ischemic stroke and controlssurrogate

Patients with ischemic stroke have significantly higher levels of homocysteine compared to controls, supporting its association as a potential risk factor or biomarker.

Main Result

Standardized Mean Difference: 1.67 (95% CI 1.09–2.25)

p-value: p=<0.01

Limitations

Retrospective design of some included studies might be subjected to artifact and bias
Significant heterogeneity among included studies (I2 = 99%)
Potential publication bias since only published data was used
Diverse detection methods used for elevated plasma homocysteine
Lack of data regarding follow-up duration in the included studies
Cross-sectional design makes it difficult to establish a causal link
Only included papers published in English

Abstract

BACKGROUND: High levels of homocysteine (Hct) have been associated with great risks of ischemic stroke. However, some controversy still exists. We performed a systematic review and meta-analysis to compare the levels of Hct between patients with ischemic stroke and controls. METHODS: We performed a systematic literature search for articles reporting Hct levels of patients with occurrence of ischemic stroke. We employed a random-effects inverse-variance weighted meta-analytical approach in order to pool standardized mean differences, with estimation of τ2 through the DerSimonian-Laird method. RESULTS: The initial search yielded 1361 studies. After careful analysis of abstracts and full texts, the meta-analysis included data from 38 studies, which involved almost 16 000 stroke events. However, only 13 studies reported means and standard deviations for cases and controls, and therefore were used in the meta-analysis. Those studies presented data from 5002 patients with stroke and 4945 controls. Standardized mean difference was 1.67 (95% CI 1.00-2.25, P < 0.01), indicating that Hct levels were significantly larger in patients with ischemic stroke compared to controls. Between-study heterogeneity was very large (I2 = 99%), particularly because three studies showed significantly large mean differences. CONCLUSION: This meta-analysis shows that patients with ischemic stroke have higher levels of Hct compared to controls. Whether this is a modifiable risk factor remains to be assessed through larger prospective cohorts.

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