Nested Case-Control Study On Plasma Spermidine And Cardio-cerebral Vascular Diseases

Objective:Cardio-cerebral Vascular Diseases（CVD）hold on to the first cause of death overall,it was reported in 2015 China cardiovascular disease,CVD accounts for residents of deaths in rural areas constitute 44.60 percent,42.51 percent for the city,and every five deaths in two cases have died from CVD.There is a significant correlation between dietary spermine（SPD）and CVD incidence.However,there is no prospective data confirmed that correlation between plasma SPD and CVD.The purpose of this study was to demonstrate the relationship plasma SPD levels and CVD in prospective cohort study.Methods:This is a nested case-control study from a prospective cohort design.CVD incident was selected as the case group during the follow-up period,and matched gender,age,and hypertension in a 1:1 ratio by risk-set sampling.Baseline plasma SPD levels were measured by lquid chromatography-tandem mass spectrometry（HPLC-MS/MS）.Using conditional logistic regression model was used to assess the SPD for OR and 95%confidence interval（CI）of risk of CVD.We constructed two models:in model 1,we adjusted age and ethnicity;in model 2,we further adjusted SBP,DBP,BMI,e GFR,TC、TG,HDL＿C,smoking,drinking,anti-hypertensive drugs,and the history of diabetes.In these multivariate logic models,SPD was entered into the model with continuous variables（1μg/L）or quartiles（the lowest quartile was selected as the reference group）.To assess the impact on the predictive value of the model of adding in risk factors,the change in-2 log likelihood was calculated for each consecutive model and compared with aχ² distribution,with the degrees of freedom reflecting the parameters in each model.In addition,receiver operating characteristic（ROC）curves were constructed,and the areas under the curves（AUC）were calculated to assess the additional discriminant power of each consecutive logistic model.Results:This study included 78 cases of newly diagnosed cases of CVD and median follow-up was 4.66 years old,78 cases matched controls were selected for this analysis.We found that SPD baseline levels was higher in newly diagnosed CVD cases than in the control group[median（inter quarter range）:76.41（25.23-94.71）vs 89.26（69.72-103.25）)μg/L,P=0.023].Q1<31.1μg/L)was used as a control.After multivariate adjustment,Q3:81.8～100.3μg/L compared with Q1,the risk of CVD was 0.436;95%CI:0.213-0.894;P=0.024.Furthermore,after SPD was added to the traditional risk factor model,the-2log likelihood change was 14.612（degree of freedom is 1）,P<0.001,indicating that SPD can significantly improve the predictive power of the model;The AUC₁ was 0.616（95%CI:0.528-0.703）,and the AUC₂ was 0.715（95%CI:0.636-0.795）,AUC₁vs AUC_2:P=0.018.Conclusion:This study firstly revealed that there is a negative association between SPD and CVD incidence in the community-based general population.SPD can increase the prediction of CVD incidence beyond traditional risk factors.It is recommended to validate this conclusion in a larger and more representative population with a view to providing a new approach to the diagnosis and treatment of CVD.