Plasma Multiple Metal Concentrations With Incident Stroke And Hypertension In Chinese Adults

Part I Plasma Circulating Multiple Metals and Incident Stroke in Chinese Adults: the Dongfeng-Tongji CohortObjectives: Circulating metals synchronously reflect multiple metal exposures,which may be linked with the risk of stroke.Previous studies have evaluated the associations of single metal exposures with stroke risk,whereas the findings were inconsistent.Moreover,it is lack of prospective studies investigating the associations of multiple metal exposures with incident stroke.Methods: We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008.A total of 1304 incident stroke cases(1035 ischemic strokes and 269 hemorrhagic strokes)were prospectively identified by December 31,2016,and matched to incidence density sampled controls according to age(within 1 year),sex and blood sampling date(within 1 month).We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model.Results: After adjusted for potential confounders,three metals(copper,molybdenum and titanium)were significantly associated with higher risk of ischemic stroke,and ORs according to per IQR increase were 1.29(95% CI: 1.13,1.46),1.19(95% CI: 1.05,1.35)and 1.30(95% CI: 1.07,1.59),respectively.Two metals(rubidium and selenium)were associated with lower risk of hemorrhagic stroke,and ORs according to per IQR increase were 0.66(95% CI: 0.50,0.87)and 0.69(95% CI: 0.51,0.91).The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke,and the adjusted ORs according to per IQR increase were 1.37(95% CI: 1.20,1.56)and 1.53(95% CI: 1.16,2.01).Conclusions: This study found the plasma copper,molybdenum,and titanium were associated with higher risk of ischemic stroke,whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke.Additional research is needed to confirm these findings in other populations.Part II Plasma Circulating Multiple Metals and Incident Hypertension in Chinese Adults: the Dongfeng-Tongji CohortObjectives: Hypertension is the most important risk factor of stroke.Previous cross-sectional studies have evaluated the associations of single metal exposures with hypertension risk.To better understand the potential mechanism of multiple metal exposures on stroke,we conducted a prospective study to examine the associations of multiple plasma metal levels with incident hypertension.Methods: We conducted a prospective analysis within the Dongfeng-Tongji cohort launched in 2008.After the exclusion of coronary heart disease and stroke cases,a total of 2274 subjects free of hypertension at baseline were enrolled.We determined plasma concentrations of 24 metals and evaluated the associations of plasma multiple metals with incident hypertension using logistic regression models.Results: After adjusted for potential confounders,plasma copper was significantly associated with higher risk of hypertension,while plasma nickel and zinc were associated with lower risk of hypertension in the single metal models.The adjusted ORs comparing extreme quartiles of copper and nickle were 1.34(95% CI: 1.07,1.67;P-trend=0.011)and 0.74(95% CI: 0.60,0.93;P-trend=0.005),and OR according to per IQR increase of zinc were 0.90(95% CI: 0.83,0.98;P-trend=0.012).When included the three metals in the same model,the association of plasma zinc and hypertension was close to the null,whereas associations of copper and nickel were similar to estimates from single metal models,and ORs comparing extreme quartiles were 1.34(95% CI: 1.07,1.69;P-trend=0.008)and 0.75(95% CI: 0.60,0.94;P-trend=0.015),respectively.Conclusions: This study found the plasma copper was associated with higher risk of hypertension.Plasma nickel may not be a reliable biomarker to reflect chronic exposure.Therefore,further investications are warranted to explore the association of nickel exposure with hypertension risk.