Study On The Relationship Between Multi-metal Exposure And Blood Pressure Level And Biological Mechanisms In Young People

Objectives Hypertension is the most common chronic disease and has become the most important risk factor for cardiovascular disease(CVD)and all-cause mortality worldwide.Elevated blood pressure in young adults is not only harmful to short-term cardiovascular health,but also increases the risk of CVD in future.Metal exposure is a potential risk factor for elevated blood pressure.However,previous studies mainly focused on single metal exposure,and there are few available studies on the effect of exposure to multiple metals on blood pressure.Additionally,it is unclear about the biological mechanism of metal exposure on blood pressure.This study aims to analyze the effects of single and combined exposure to multiple metals on blood pressure levels in young people,and to explore the potential biological mechanisms of the association between metal exposure and blood pressure.Methods A panel study was conducted with 45 healthy college participants from the Caofeidian campus of North China University of Science and Technology.These participates were followed up in 4 seasons for physical examination and blood and urine samples collection.The concentrations of 12 urinary metals of subjects were determined by inductively coupled plasma mass spectrometry,including aluminum,vanadium,chromium,manganese,copper,zinc,arsenic,selenium,molybdenum,cadmium,antimony,and lead.Enzyme-linked immunosorbent assay was used to determine the levels of urinary8-hydroxy-2’-deoxyguanosine(8-OHd G)and 8-iso-prostaglandin(8-iso-PGF2α)and plasma C-reactive protein(CRP),interleukin-6(IL-6),transforming growth factor-β1(TGF-β1),endothelin-1(ET-1),and vascular endothelial growth factor(VEGF).Subsequently,linear mixed effects models(LME)and Bayesian kernel machine regression(BKMR)were used to analyze the associations of 12 urinary metals with blood pressure levels;the mediation effect models were used to explore the potential mediating roles of biomarkers of oxidative stress(8-OHd G and 8-iso-PGF2α),inflammation(CRP,IL-6,and TGF-β1),and endothelial dysfunction(ET-1 and VEGF)in the associations of urinary metals with blood pressure.Results 1 After correction for false discovery rate,the LME models showed that systolic blood pressure(SBP)increased by 3.25 mm Hg(95%CI: 1.18,5.32),2.52 mm Hg(95%CI:0.53,4.51),2.76 mm Hg(95%CI: 0.97,4.55),3.64 mm Hg(95%CI: 1.55,5.72),3.07 mm Hg(95%CI: 1.11,5.02),2.57 mm Hg(95%CI: 0.87,4.26),2.01 mm Hg(95%CI: 0.48,3.53),2.45 mm Hg(95%CI: 0.76,4.14),2.71 mm Hg(95%CI: 1.14,4.28),3.57 mm Hg(95%CI: 1.35,5.79),and 2.13 mm Hg(95%CI: 0.50,3.77)with a one-unit increase in the ln-transformed level of urinary aluminum,vanadium,chromium,manganese,copper,zinc,arsenic,selenium,molybdenum,antimony,and lead;a one-unit increase in the lntransformed level of aluminum and manganese was associated with an increase of 2.97 mm Hg(95%CI: 0.94,5.00)and 3.32 mm Hg(95%CI: 1.30,5.35)in diastolic blood pressure(DBP);pulse pressure(PP)increased by 2.08 mm Hg(95%CI: 0.46,3.69),1.92 mm Hg(95%CI: 0.51,3.33),1.98 mm Hg(95%CI: 0.57,3.39),and 1.70 mm Hg(95%CI:0.35,3.06)with a one-unit growth in the ln-transformed level of urinary copper,zinc,selenium,and molybdenum.2 The BKMR models showed that manganese might be the key metal that caused the elevation of DBP,however,the key metal that causes the change of SBP and PP was not found.The overall effect of the metal mixture was significantly and positively associated with SBP when the levels of 12 metal were above their 55 th percentile;when the levels of 12 metal were above the 65 th percentile,the overall effect of the metal mixture was significantly and positively associated with DBP;however,no significant association was found between the overall effect of metal mixture and PP.3Urinary 8-iso-PGF2α was significantly and positively associated not only with manganese,chromium,and molybdenum,but also with SBP.The mediation effect models showed that8-is-PGF2α significantly mediated the positive association of manganese,chromium,and molybdenum with SBP,with the mediating proportions of 24.6%,17.4%,and 20.7%,respectively.However,no mediated effects were found for 8-OHd G,CRP,IL-6,TGF-β1,ET-1,and VEGF.Conclusions There was a significant positive association between metal exposure and SBP levels in young people in Caofeidian area,and oxidative stress may play an important role in the association of metal exposure with SBP.Figure 15;Table 15;Reference 196...