Hyperhomocysteinemia Associates with Small Vessel Disease More Closely Than Large Vessel Disease

Abstract

Background: Hyperhomocysteinemia was believed to be an independent risk factor for stroke and associate with small vessel disease (SVD) related stroke and large vessel disease (LVD) related stroke differently. However it's still unclear which type of stroke associated with homocysteine (HCY) more strongly because the conclusions of previous studies were contradictory. In this study we focused on the subclinical angiopathies of stroke, i.e., SVD and LVD instead of stroke subtypes and sought to compare the associations between HCY level and different angiopathies. Methods: 324 non-stroke patients were enrolled. Sex, age, HCY level and other vascular risk factors were collected. MRI and angiographies were used to determine the type of angiopathies and their severity, i.e., the scores of leukoaraiosis (LA), plaques and numbers of silent brain infarctions (SBI). LVD was defined as the presence of atherosclerotic plaques of cerebral arteries. SVD was defined as the presence of either LA or SBI. 230 patients were deemed to have LVD; 180 patients were deemed to have SVD. Spearman's correlation test and logistic regression were used to analyze the association between HCY level and different angiopathies. Results: The correlation between HCY level and scores of plaques was weaker than that of the scores of LA and numbers of SBI. Hyperhomocysteinemia was an independent risk factor for SVD (OR = 1.315, P <0.001), whereas the association between HCY level and LVD was not that significant (OR = 1.058, P = 0.075). Conclusion: HCY level associated with SVD more strongly than LVD.

Homocysteine and small vessel stroke: A mendelian randomization analysis

“…Although it did not reduce cognitive decline in the same study, this may be because cognitive testing has been shown to be insensitive to detect changes over a 2‐ to 3‐year period in this cerebral small vessel disease . Furthermore, several case‐control studies have shown that elevated tHcy levels are a stronger risk factor for SVS than other ischemic stroke subtypes and that tHcy levels are higher in patients with cerebral small vessel disease than in healthy controls, although such studies only show associations and cannot exclude confounding.…”

Potential serum biomarkers in the pathophysiological processes of stroke

“…Hyperhomocysteinemia (Hcy level ≥15.90 µmol/l) was more common in patients with large-vessel atherosclerotic stroke and CE stroke in the Turkish population [60]. By contrast, a study found that Hcy level was associated with SVDrelated stroke more strongly than LVD-related stroke [61]. Hyperhomocysteinemia was an independent risk factor for SVD [62].…”

Homocysteine, Alcoholism, and Its Potential Epigenetic Mechanism

“…Excess production of Hcy can occur as a result of impaired metabolism due to a deficiency in cofactors (vitamin B6, B12, folate) or to genetic alteration in metabolic enzymes (methionine synthase [MS], methyltetrahydrofolate reductase [MTHFR], cystathionine‐ β ‐synthase [CBS], and cystathionine‐ γ ‐lyase). HHcy is commonly seen in about 5 to 12% of the general population and is recognized as a risk factor for cerebrovascular diseases (Clarke, ; Feng et al., ; Okura et al., ), diabetes, obesity, and hepatic steatosis (Dara et al., ; Ji and Kaplowitz, ). Various epidemiological and longitudinal studies suggested a causal link between Hcy and cognitive impairment (Nurk et al., ).…”