| Objective:Herpes simplex virus(HSV)can promote the occurrence and development of atherosclerosis and relate to hypertension,diabetes and dyslipidemia.In addition,Cardiovascular disease with HSV infection is associated with an increased risk of adverse prognosis.At present,there are few reports about the relationship between HSV and the adverse prognosis of ischemic stroke.Since cardiovascular disease and ischemic stroke have similar risk factors of prognosis,we assumed that HSV infection can increase the risk of adverse prognosis of ischemic stroke.Therefore,a prospective cohort study was conducted to examine the association between HSV and adverse prognosis at 14 days(discharged)and 3 months after onset among ischemic stroke patients.And 1150 cases of first onset of ischemic stroke cases were collected from 14 hospitals in China.Subjects and methods1.A multi-center,prospective cohort study was conducted.And 1150 cases of the first onset,admission within 72 hours,age ≥ 40 years old ischemic stroke patients were continuous inclusion from 14 hospitals in seven provinces from June 2011 to December 2013.2.Demographic data,lifestyle factors,personal disease history,infectious diseases,physical examination data,treatment and hematology examination data of all cases were collected.Fasting venous blood of all the subjects were drawed within 24 hours.The HSV-1/2 IgG antibody levels were detected by using human herpes simplex virus type 1/2 IgG Elisa kit manufactured by Shanghai YuanMu Biotechnology Co.,Ltd.And the testing instrument was fully automatic enzyme-linked immunosorbent assay(FreedomEVOlyzer150 / 8).3.In this study,We followed up and observed the adverse outcomes within 14 days(or discharged)and 3 months.The outcomes were death,disability(mRS,3-5)as well as death or disability.4.SAS 9.4 software was used for statistical analysis,and all analysis were two-sided test.The significance level was α = 0.05.Covariance analysis and chi-square trend test were used to compare the baseline characteristics.To describe the distribution of outcomes from onset to 14 days(or discharge)and 3 months,the chi-square test or the Fisher exact test method were used to compare the incidence.Univariate and Multivariate Logistic Regression Model was used to analyze the relationship between HSV-1/2 IgG level and adverse outcomes.The level of IgG divided into four groups according to the quartile and the lowest group as the reference group.Risk was estimated by Odds ratio(OR)and its 95% confidence interval.In addition,the cases were grouped by the traditional risk factors.And the high value group was defined as above upper quartile of HSV-1/2 IgG level.Univariate and multivariate logistic regression model were used to analyze the relationship between HSV-1/2 IgG level and death and disability in each subgroup.The additive and multiplicative interaction model was used to analyze the effects of HSV-1/2 IgG and traditional risk factors on the risk of death and disability in 3 months among cases.Results1.A total of 1150 cases were included with an average age of 62.39 ± 11.19 years old,including 786 males(68.35%)and 364 females(31.65%).The results showed that cases with higher HSV-1 IgG levels had lower admission systolic blood pressure levels(P values for trend=0.043)and had higher admission NIHSS score and higher proportion of smoking and antibiotic treatment(P values for trend were 0.048,0.037,0.003,respectively).The high level HSV-2 IgG cases had lower levels of TC,TG and lower proportion of hyperlipidemia and family history of stroke(P values for trend,0.024,0.042,0.014,<0.001).The high level HSV-2 IgG cases are also had higher HDL-C levels and higher proportion of coronary heart disease(P values for trend,0.019 and 0.026).2.The number of death,disability,death and disability in 14 days(or discharge)were 19(1.65%),332(28.87%)and 351(30.52%).The incidence of death,disability as well as death or disability had no statistically significant.HSV-1 IgG or HSV-2 IgG had no association with the risk of death,disability,death or disability among the patients after adjustment(P > 0.05).3.Subgroup analysis found that the risk of death and disability in the high HSV-1 IgG group was not statistically significant higher than that in the low group among ischemic stroke patients with diabetes in 14 days(or discharge).High levels of HSV-2 IgG increased the risk of death and disability among ischemic stroke patients under 65 years old or female.The risk were 1.95 and 2.46 times than the low level groups,respectively(P <0.05 for all).4.Forty cases were lost to follow in three months(the follow-up rate: 96.52%).The number of death,disability,death and disability were 37(3.33%),231(20.81%)and 268(24.14%).The incidence of death(P = 0.008)or death and disability(P = 0.050)in patients with different HSV-1 IgG levels was statistically significant or nearly statistically significant.The incidence of death with different HSV-2 IgG levels was statistically significant(P = 0.036).With the increase of HSV-1 IgG or HSV-2 IgG levels,death,death or disability showed as an increasing trend(trend P <0.05).5.There was no statistically significant difference(P > 0.05)between the HSV-1 IgG and the risk of adverse outcomes after adjustment in 3 months.But for HSV-2,the fourth quartile group has 2.51 times risk for death and cardiovascular events as well as death and disability after adjustment(P = 0.006).6.Subgroup analysis of 3 months shown that the risk of death or disability was not statistically significant in the high levels of HSV-1 IgG group(P >0.05).And high level of HSV-2 IgG increased the risk of death and disability in patients under 65 years old,or male,or female,or smoking,or hypertensive,or diabetic,or dyslipidemia patients.The risks were 1.97,0.86,1.40,1.74,1.98,1.15,1.83 and 1.58 times than the low groups,respectively(P <0.05).7.There were not additive or multiplicative interaction between high-level HSV-1 IgG or high levels of HSV-2 IgG and traditional risk factors for death and disability from onset to 3 months among ischemic stroke patients(P >0.05).Conclusion1.High levels of HSV-1IgG had no association with the risk of death,disability as well as death or disability of the patients with ischemic stroke within 14 days(or discharge)or three months.2.High levels of HSV-2 IgG had no association with the risk of death,disability as well as death or disability of the patients with ischemic stroke within 14 days(or discharge).But high levels of HSV-2 IgG can increase the risk of death or disability within 3 months.3.High levels of HSV-2 IgG can increase the risk of death or disability in some subgroup of traditional risk factors within 14 days(or discharge)and 3 months.There were not additive or multiplicative interaction between high-level HSV-1 IgG or high levels of HSV-2 IgG and traditional risk factors for death and disability within 3 months among ischemic stroke patients(P >0.05). |
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