Association Between Serum Metal And Cardiovascular Risk Among Schizophrenia Patients And Mediation Role Of Visceral Adiposity

Background: Schizophrenia is a severe mental illness.It is estimated that the life expectancy of schizophrenia has an average of 15-20 years shorter than the general population.Cardiovascular disease is the leading cause of premature death in people with schizophrenia,and cardiovascular-related deaths alone more than double in people with mental illness.In recent years,an increasing number of studies have found that environmental metal exposure is associated with cardiovascular disease morbidity and mortality.However,evidence of the relationship between metal exposure and CVD risk in SCZ patients is rare,and the potential mechanism remains unclear.The purpose of this study was to investigate:(1)the relationship between single metal exposure and CVD risk in patients with schizophrenia,(2)the relationship between multiple metal co-exposure and CVD risk in patients with schizophrenia,to identify the main risk metals,and to explore whether an interactive effect exists in metals;(3)to further explore the potential mediating effect of visceral adiposity.Methods: Based on a schizophrenia-specific cohort established by Anhui Mental Health Center and Anhui Province,49 patients with chronic stable schizophrenia were recruited from three community health service centers in Hefei,China for a panel study with three repeated measures.In this study,the plasma atherosclerosis index(AIP)was used to assess the risk of cardiovascular disease in patients with schizophrenia,and China visceral fat Index(CVAI)was applied to evaluate visceral adiposity in patients with schizophrenia.Linear mixed effects model(LME),Bayesian kernel regression model(BKMR),and weighted quantile sum(WQS)models were used to evaluate the relationship between single and multiple serum metal exposure and CVD risk.Mediation analysis was employed to assess the medication role of CVAI.Results: We found that single exposure to serum silver(Ag),aluminum(Al),chromium(Cr),manganese(Mn),and vanadium(V)was positively associated with CVD risk and CVAI in patients with schizophrenia.LME models showed the strongest correlation between logarithmic(ln)transformed serum V and AIP(β=2.1055,95% confidence interval(CI): 0.4297-3.7813).Both BKMR and WQS models found that mixed metal exposure could increase the risk of CVD in schizophrenia patients.The overall effect was primarily dominated by V,and an increase of 1 unit in the WQS index was significantly correlated with an increase of0.1090(95CI: 0.0180,0.2000)in AIP.And we also found that there was some interaction between the metals.In addition,mediation analysis found that "Ag-CVAI-AIP","Al-CVAI-AIP","Cr-CVAI-AIP","Mn-CVAI-AIP" and "V-CVAI-AIP" all existed.CVAI had a significant mediating effect between the five metals and AIP in schizophrenia patients(P<0.05),and the mediating proportions were 31.63%,33.15%,34.28%,93.09%,and 33.48%,respectively.Conclusions: Our results suggest that environmental metal exposure increases the risk of CVD in schizophrenia,and the up-regulation of CVAI may play a potential mediating role in environmental metal exposure to CVD risk in schizophrenia.The intervention of visceral obesity is beneficial to reduce the harmful effect of environmental metal exposure on cardiovascular disease in patients with schizophrenia.