title: Association between hyperhomocysteinemia and stroke with atherosclerosis and small artery occlusion depends on homocysteine metabolism-related vitamin levels in Chinese patients with normal renal function.
abstract: This study was conducted to investigate the role of different homocysteine metabolism-related vitamin (HMRV) levels in the correlation between hyperhomocysteinemia (HHCY) and ischemic stroke (IS) subtypes. Three hundred and forty-eight IS patients manifesting different vascular subtypes were subclassified on the basis of HMRV deficiencies. Correlation between HHCY and IS subtypes was investigated in all the subgroups. In this study, HHCY was significantly correlated with the IS subtypes in large artery atherosclerosis (OR 1.126, 95%CI: 1.051 ~ 1.206, P = 0.001) and small artery occlusion (OR 1.105, 95%CI: 1.023 ~ 1.193, P = 0.012). Subgroup analysis revealed a correlation between HHCY and IS subgroup (OR 1.201, 1.178, 95%CI: 1.081 ~ 1.334, 1.058 ~ 1.313, P = 0.001, P = 0.003, respectively) in HMRV deficiency, but not significantly with the IS subgroup in normal HMRV levels. Serum vitamin B12 concentrations are inversely correlated with both IS subtypes in HMRV deficiency subgroups (OR 0.992, 0.995, 95%CI: 0.987 ~ 0.996, 0.991 ~ 0.999, P < 0.001, P = 0.007, respectively), which may contribute to HHCY incidence in these populations. The correlation between HHCY and IS subtypes is affected by HMRV levels in this case-control study. Our findings are helpful to understand the inconsistency in prior homocysteine studies. Serum vitamin B12 levels may play a critical role in HHCY incidence in this Chinese population.Cerebrovascular disease has emerged as the leading cause of disability and mortality in both urban and rural areas of China (Neurology branch of Chinese Medical Association 2015). Ischemic stroke (IS) constitutes 60% to 80% of all cerebrovascular disease (Neurology branch of Chinese Medical Association 2014). Among a variety of risk factors, hyperhomocysteinemia (HHCY) has been closely correlated with IS due to intracranial small-vessel disease and extracranial large-artery disease (Selhub et al. 1995; Eikelboom et al. 2000; Alvarez et al. 2012; Jeon et al. 2014). However, the failure to lower homocysteine (HCY) via homocysteine metabolism-related vitamin (HMRV, including folic acid and vitamin B12 but not vitamin B6 in this study) supplementation to reduce stroke morbidity questions the role of HCY as a risk factor for stroke (Lonn et al. 2006; Hankey et al. 2010). Theoretically, HMRV supplementation merely lowers the incidence of stroke induced by HHCY resulting from HMRV deficiency, whereas HHCY-induced stroke concomitant with normal HMRV levels may be refractory to treatment. The correlation between HCY varying with HMRV levels and IS subtypes is still unclear. In this study, we investigated the impact of variation in HMRV levels on the correlation between HHCY and IS subtypes in 348 acute IS patients with large and small vessel diseases. We sought to determine the factors underlying the conflicting results associated with lowering HCY by HMRV supplementation to reduce stroke incidence.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.|Department of Neurology, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, 215002, China.
authors.forename: Guan-Hui
authors.initials: GH
authors.lastname: Wu
authors.affiliation: Department of Clinical Psychology, Suzhou Psychiatric Hospital, 286 Guangji Road, Suzhou, 215008, China.
authors.forename: Fan-Zhen
authors.initials: FZ
authors.lastname: Kong
authors.affiliation: Department of Neurology, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, 215002, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Dong
authors.affiliation: Department of Neurology, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, 215002, China.
authors.forename: De-Feng
authors.initials: DF
authors.lastname: Wu
authors.affiliation: Department of Neurology, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, 215002, China.
authors.forename: Qian-Zhu
authors.initials: QZ
authors.lastname: Guo
authors.affiliation: Department of Neurology, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, 215002, China.
authors.forename: Ai-Rong
authors.initials: AR
authors.lastname: Shen
authors.affiliation: Department of Neurology, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, 215002, China.
authors.forename: Qing-Zhang
authors.initials: QZ
authors.lastname: Cheng
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Luo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology; D002681:China / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D002537:Intracranial Arteriosclerosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D007668:Kidney / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020521:Stroke / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Atherosclerosis; Hyperhomocysteinemia; Small artery occlusion; Stroke; Vitamin