The Prognostic Value of Homocysteine in Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis

Abstract

Background: This comprehensive meta-analysis aimed to assess whether an increased homocysteine (Hcy) level is an independent predictor of unfavorable outcomes in acute ischemic stroke (AIS) patients.Methods: A comprehensive literature search was conducted up to August 1, 2020 to collect studies reporting Hcy levels in AIS patients. We analyzed all the data using Review Manager 5.3 software.Results: Seventeen studies with 15,636 AIS patients were selected for evaluation. A higher Hcy level was associated with a poorer survival outcome (OR 1.43, 95% CI: 1.25–1.63). Compared with the AIS group, Hcy levels were significantly lower in the healthy control patients, with an SMD of 5.11 and 95% CI (1.87–8.35). Analysis of the different subgroups of AIS demonstrated significant associations between high Hcy levels and survival outcomes only in Caucasian and Asian patients. Moreover, whereas high Hcy levels were closely associated with gender, B12 deficiency, smoking, and patients who received tissue plasminogen activator treatment, no significant difference was found between increased Hcy levels and age, drinking, hypertension, diabetes mellitus, and hyperlipidemia. In addition, the cut-off value (20.0 μmol/L) might be an optimum cut-off index for AIS patients in clinical practice.Conclusion: This meta-analysis reveals that the Hcy level may serve as an independent predictor for unfavorable survival outcomes in AIS patients, particularly in Caucasian and Asian AIS patients. Further studies can be conducted to clarify this relationship.

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

“…The meta-analysis of Huang et al (2020) investigated the prognostic utility of Hcy in individuals with acute ischemic stroke (AIS) in terms of all-cause mortality, poor functional outcome, and recurrent stroke. Independently elevated Hcy levels were linked with an increased risk of all-cause mortality but not poor functional outcome and recurrent stroke in subjects with AIS [91]. Another study revealed a causal association between plasma Hcy levels and ischemic stroke (IS) induced by small artery occlusion.…”

“…Hcy levels were significantly lower in the healthy control patients than in the AIS group with an SMD of 5.11 and 95% CI (1.87-8.35). Significant links between higher Hcy levels and the subject's survival were observed only in Caucasians and Asians [91]. In a meta-analysis of prospective cohort studies, Wu et al ( 2020) assessed the quantitative dose-response link of plasma Hcy levels with IS and stroke.…”

“…To mitigate the adverse effects of HHcy to wound healing, the supplementation of cofactors (B vitamins, folic acid) or other agents (IL-10) seems to be perspective in the treatment of several diseases, especially in type 2 diabetic patients, patients with various types of ulcers, fractures, or inflammatory bowel diseases. This supplementation has the potential Hcy induced a calcium-mediated disruption of dynamics and mitochondrial function due to overexpression of the mitochondrial calcium uniporter and the IP3R-Grp75-VDAC complex in mitochondria-associated membranes [86] Table 1 Elevated Hcy levels were linked with an increased risk of all-cause mortality but not poor functional outcome and recurrent stroke in subjects with acute ischemic stroke [91] Ischemic stroke Plasma Meta-analysis Causal association between plasma Hcy levels and ischemic stroke induced by small artery occlusion [92] Acute ischemic stroke Plasma Acute ischemic stroke patients (n = 15.636) Elevated Hcy plasma levels were linked with poorer survival of subjects; significant links between higher Hcy levels and the subject's survival were observed only in Caucasians and Asians Elevated Hcy plasma levels are associated with a higher risk for IS and recurrent strokes but Hcy had no distinct linkage with hemorrhagic strokes [94] Pregnancy complications PE Plasma PE (n = 32) and controls without pregnancy complications (n = 64) Pregnant women with HHcy have a 7.7-fold risk for PE vs normal controls (Hcy and folate higher in PE vs control in third trimester) [101] Maternal blood (plasma) collected three times during pregnancy: 16th-20th weeks (T1), 26th-30th weeks (T2), at delivery (T3) NC (n = 126) and PE (n = 62)…”

Gender difference in association between H-type hypertension and subcortical ischemic vascular disease

“…BA for females, but not for males. Previous researches had shown that the prevalence of hypertension and tHcy level were higher in males than in females (Doumas et al, 2013;Huang et al, 2021), the associations between hypertension, tHcy, cardiovascular and cerebrovascular diseases were also different between genders (Wang et al, 2015;Zhong et al, 2017). A recent study had reported that the association between the increased hypertension severity and the onset of ischemic stroke was almost twice as strong in women as in men (Madsen et al, 2019).…”

Distribution characteristics and influencing factors of homocyteine in an apparently healthy examined population

“…In this study, the average concentration of Hcy was 10.2 (8.3–12.8) μmol/L, and males were much higher than females. In addition, smoking can indirectly lead to the reduction or lack of folic acid and vitamin B12 levels in the blood and affect the decomposition and metabolism of Hcy [ 15 ]. This may also be the reason why the level of Hcy in men is higher than that in women.…”