Variability Of Association Between Homocysteine And Incidence Of Cerebral Infarction Based On Differences Of Serum Folic Acid And Vitamin B12 Levels

BackgroundCerebral infarction(CI)is the most common cerebral stroke type,accounting for 60-80% of the whole cerebrovascular disease and has been the first cause of death in China with high rate of morbidity,disability,mortality and recurrence.The increase of homocysteine(HCY)contributes to the atherosclerosis pathological changes and epidemiological investigation demonstrated its close relationship to the increasing incidence of cardio-cerebral vascular disease(CCVD)like CI.While some studies found that there was no correlation between the increase of HCY and the incidence of the incidence of CI,or such correlation was limited to certain subtypes.The supplement of folic acid(FA),vitamin B12(vit B12),vitamin B6 could not reduce the incidence of CCVD is conflicted with previous studies.Present researches targeted on the factors influencing on the effect of vitamin families such as age,genotype,kidney function,anti-platelet drugs and FA fortification dietary etc,and they have not yet reached a widely recognized consensus.The inconsistency of previous studies on the correlation between HCY and CI indicated there might be some difference of the casual relationship.The remarkable impact of vitamin family on HCY level relied on FA and vit B12 as substrate and cofactor for methylation to form methionine to complete the methionine cycle.Although prospective studies have not proven the benefit of vitamin B family supplement on preventing the recurrence of CCVD,their effect on reducing HCY are consistent.This suggested that baseline vitamin level might be an important impact factor for HCY level,and the inclusion of FA and vit B12 are more accurate to investigate the relationship between HCY and CI.ObjectiveThis study aims to analyze the influence of FA and vit B12 on the relationship between HCY and CI,and to explore the cause that why previous epidemic investigations and prospective researches suggested increasing HCY is a risk factor of CI,but the application of FA and vit B12 could not reduce CCVD by decreasing the HCY.MethodsThe admitted patients with acute CI,aged between 45 to 90 years old were collected from October 2012 to March 2016 were collected.The patients with benign paroxysmal positional vertigo(BPPV)at the same age group and from the same period were selected as the control group.1.A total of 497 cases and 317 controls in compliance with inclusion criteria were finally selected to analyze the alternation of the relationship between the HCY and CI before and after inclusion of FA,vit B12 to investigate their influence on the relationship.2.According to the concentration of serum FA and vit B12,the patients were divided into the normal vitamin group(354 cases vs 241 ones as the control group),and the vitamin deficiency group(143 cases vs 76 ones as the control group).The alternation of the relationship between the HCY and CI before and after inclusion of FA,vit B12 in both groups was investigated to observe their influence on that relationship.3.In those FA normal patients,the CI patients were further divided into the vit B12 normal group(354 cases vs 241 ones in the control group),and the vit B12 deficiency group(88 cases vs 55 ones in the control group)based on the vitamin concentration.The alternation of the relationship between the HCY and CI before and after inclusion of FA,vit B12 in both groups was investigated to observe the effect of vitamin at normal FA level on the relationship.ResultsOur study showed that the relationship between HCY and CI was affected by the level of FA and vit B12,and the results were summarized as follows:1.The increasing HCY was positively correlated to the incidence of CI(OR: 1.043,95%CI: 1.013-1.073,P=0.005)by adjustment for other risk factors before inclusion of FA and vit B12.After inclusion of FA and vit B12 and adjustment for other risk factors,such correlation was not relevant.The FA and vit B12 level were negatively correlated with the incidence of CI(OR 0.934,0.998,95%CI 0.901-0.968,0.996-0.999,all P<0.001).2.The increasing HCY was positively correlated to the incidence of CI in the vitamin deficiency group(OR: 1.070,95%CI: 1.019-1.123,P=0.006)by adjustment for other risk factors before inclusion of FA and vit B12.After inclusion of FA and vit B12 and adjustment of other risk factors,such correlation was not obvious in both vitamin normal and deficiency group.The level of FA(OR 0.947,95%CI 0.907-0.990,P=0.015),vit B12(OR 0.997,95%CI 0.995-0.998,P=0.000)was negatively correlated to the incidence of CI in the vitamin normal group.In the vitamin deficiency group,the level of FA(OR 0.911,95%CI 0.855-0.970,P=0.004)was negatively correlated with the incidence of CI.3.The increasing HCY was positively correlated to the incidence of CI in the vitamin deficiency group(OR: 1.102,95%CI 1.028-1.182,P=0.006)by adjustment for other risk factors before inclusion of FA and vit B12.In the vit B12 normal group,such correlation was not obvious.After inclusion of FA and vit B12 and adjustment of other risk factors,the increasing HCY(OR 1.102,95%CI 1.028-1.182,P=0.006)was positively correlated to CI in the vitamin deficiency group,and not correlated in the vitamin normal group.The level of FA(OR: 0.947,95%CI:0.907-0.990,P=0.015),vit B12(OR: 0.997,95%CI: 0.995-0.998,P=0.000)was negatively correlated to the incidence of CI in the vitamin normal group.ConclusionOur study showed that the relation between HCY and CI was affected by FA and vit B12 levels.The conclusions were listed as follows:1.For general patients,the relationship between HCY and CI was affected by FA and vit B12.The increasing HCY enlarged the CI risk before inclusion of FA and vit B12 into the analysis.After inclusion of those factors,the correlation between increasing HCY and the enlarged CI risk disappeared.Instead,the decreasing FA and vit B12 increased the CI risk.2.Before inclusion of FA and vit B12,there is no correlation between increasing HCY and CI in the vitamin normal group but increasing HCY increased CI risk in the vitamin deficiency group according to the subgroup analysis by the level of FA and vit B12.After inclusion of above two vitamins,the correlation disappeared,suggesting that the increase of HCY might stem from the deficiency of FA and vit B12.3.The subgroup analysis by vit B12 level in those FA normal patients before and after inclusion of FA and vit B12 all indicated that increasing HCY enlarged the risk of CI,and such correlation was not obvious in the vit B12 normal group.