Associations between co­exposure to heavy metals and vertebral compression fracture, as well as femoral neck bone mineral density: A cross-sectional study from NHANES data.

OBJECTIVE: Accumulating evidence showed that exposure to heavy metals was harmful to human health. Little is known regarding the mixing effects of multiple metal exposures on vertebral compression fracture (VCF) and femoral neck bone mineral density (BMD). This study aimed to explore the individual and joint effects of four heavy metals [manganese (Mn), lead (Pb), cadmium (Cd) and mercury (Hg)] on VCF risk and femoral neck BMD. METHODS: This cross-sectional study included 1,007 eligible individuals with vertebral fractures from National Health and Nutrition Examination Survey 2013-2014. The outcome was the risk of VCF and femoral neck BMD. Weighted multivariate logistic regression was used to explore the individual effect of four heavy metals on the VCF risk, separately. Weighted multivariate linear regression was used to explore the individual effect of four heavy metals on the femoral neck BMD, separately. Adopted bayesian kernel machine regression (BKMR) model and quantile-based g computation (qgcomp) to examine the joint effects of four heavy metals on the VCF risk and femoral neck BMD. RESULTS: Among the population, 57 individuals developed VCF. After adjusting covariates, we found no statistical differences regarding the individual effects of four heavy metals on the risk of VCF. BKMR model and qgcomp indicated that there were no statistical differences regarding the joint effects between four heavy metals on the VCF risk. In addition, we found that Cd was associated with femoral neck BMD, and an increase in the mixture of heavy metal exposures was associated with a decreased risk of femoral neck BMD. CONCLUSION: No significant correlation was observed between co-exposure to Mn, Pb, Cd and Hg and VCF risk. But co-exposure to Mn, Pb, Cd and Hg may be associated with femoral neck BMD.

Association between maternal heavy metal exposure and Kawasaki Disease, the Japan Environment and Children's Study (JECS).

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting young children, with an unclear etiology. We investigated the link between maternal heavy metal exposure and KD incidence in children using the Japan Environment and Children's Study, a large-scale nationwide prospective cohort with approximately 100,000 mother-child pairs. Maternal blood samples collected during the second/third trimester were analyzed for heavy metals [mercury (Hg), cadmium (Cd), lead (Pb), selenium (Se), manganese (Mn)], divided into four quartiles based on concentration levels. KD incidence within the first year of life was tracked via questionnaire. Among 85,378 mother-child pairs, 316 children (0.37%) under one year were diagnosed with KD. Compared with the lowest concentration group (Q1), the highest (Q4) showed odds ratios (95% confidence interval) for Hg, 1.29 (0.82-2.03); Cd, 0.99 (0.63-1.58); Pb, 0.84 (0.52-1.34); Se, 1.17 (0.70-1.94); Mn, 0.70 (0.44-1.11), indicating no concentration-dependent increase. Sensitivity analyses with logarithmic transformation and extended outcomes up to age 3 yielded similar results. No significant association was found between maternal heavy metal levels and KD incidence, suggesting that heavy metal exposure does not increase KD risk.

Association of blood metals with anxiety among adults: A nationally representative cross-sectional study.

BACKGROUND: Previous evidence demonstrated the inconsistent associations between metals and anxiety. The purpose of this study was to evaluate the individual and joint effects of blood lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se) and manganese (Mn) on anxiety in the general population. METHODS: Data of 4000 participants (aged≥20 years) in the study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Multiple logistic regression, restricted cubic splines (RCS) logistic analysis, and weighted quantile sum (WQS) regression were fitted to explore the possible effects of single and mixed metal exposures on anxiety. Moreover, this association was assessed by smoking group. RESULTS: In the study, 24.60 % of participants were in an anxiety state. In logistic regression, blood Pb, Cd, Hg, Se and Mn were not significantly associated with anxiety in all participants. After stratified by smoking group, blood Cd was positively associated with anxiety in the current smoking group [P = 0.029, OR (95 %): 1.708(1.063, 3.040)], whereas not in other groups. In RCS regression, we observed a linear dose-response effect of blood Cd on anxiety stratified by smoking group. In WQS analysis, mixed metal exposures were positively associated with anxiety [P = 0.033, OR (95 %): 1.437(1.031, 2.003)], with Cd (33.69 %) contributing the largest weight to the index. CONCLUSIONS: Our study showed that excessive exposure to Cd is a significant risk factor for anxiety, and the co-exposures to Pb, Cd, Hg, Se and Mn were positively related with the risk of anxiety in current smokers.

Maternal exposure to metals and time-to-pregnancy: The MIREC cohort study.

OBJECTIVE: To study the association between maternal exposure to arsenic, cadmium, lead, manganese and mercury, time-to-pregnancy (TTP) and infertility. DESIGN: Pregnancy-based retrospective TTP cohort study. SETTING: Hospitals and clinics from ten cities across Canada. POPULATION: A total of 1784 pregnant women. METHODS: Concentrations of arsenic, cadmium, lead, manganese and mercury were measured in maternal whole blood during the first trimester of pregnancy as a proxy of preconception exposure. Discrete-time Cox proportional hazards models generated fecundability odds ratios (FOR) for the association between metals and TTP. Logistic regression generated odds ratios (OR) for the association between metals and infertility. Models were adjusted for maternal age, pre-pregnancy body mass index, education, income, recruitment site and plasma lipids. MAIN OUTCOME MEASURES: TTP was self-reported as the number of months of unprotected intercourse to become pregnant. Infertility was defined as TTP longer than 12 months. RESULTS: A total of 1784 women were eligible for the analysis. Mean ± SD maternal age and gestational age at interview were 32.2 ± 5.0 years, and 11.6 ± 1.6 weeks, respectively. Exposure to arsenic, cadmium, manganese or mercury was not associated with TTP or infertility. Increments of one standard deviation of lead concentrations resulted in a shorter TTP (adjusted FOR 1.09, 95% CI 1.02-1.16); however, the association was not linear when exposure was modelled in tertiles. CONCLUSION: Blood concentrations of metals at typical levels of exposure among Canadian pregnant women were not associated with TTP or infertility. Further studies are needed to assess the role of lead, if any, on TTP.

Blood cadmium is associated with increased fracture risk in never-smokers - results from a case-control study using data from the Malmö Diet and Cancer cohort.

BACKGROUND: Several studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers. METHODS: The study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991-1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression. RESULTS: Median B-Cd was 0.22 µg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08-2.31, per µg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 µg/L; OR 1.21; 95 % confidence interval 1.01-1.45). CONCLUSION: Even modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures.

Cadmium exposure is associated with chronic kidney disease in a superfund site lead smelter community in Dallas, Texas.

Background: The study was conducted in a Dallas lead smelter community following an Environmental Protection Agency (EPA) Superfund Cleanup project. Lead smelters operated in the Dallas community since the mid-1930s.Aim: To test the hypothesis that cadmium (Cd) exposure is associated with chronic kidney disease (CKD) ≥ stage 3.Subjects and methods: Subjects were African American residents aged ≥19 to ≤ 89 years (n=835). CKD ≥ stage 3 was predicted by blood Cd concentration with covariates.Results: In logistic regression analysis, CKD ≥ stage 3 was predicted by age ≥ 50 years (OR = 4.41, p < 0.0001), Cd level (OR = 1.89, p < .05), hypertension (OR = 3.15, p < 0.03), decades living in the community (OR = 1.34, p < 0.003) and T2DM (OR = 2.51, p < 0.01). Meta-analysis of 11 studies of Cd and CKD ≥ stage 3 yielded an ORRANDOM of 1.40 (p < 0.0001). Chronic environmental Cd exposure is associated with CKD ≥ stage 3 in a Dallas lead smelter community controlling covariates.Conclusion: Public health implications include screening for heavy metals including Cd, cleanup efforts to remove Cd from the environment and treating CKD with newer renal-sparing medications (e.g., SGLT-2 inhibitors, GLP-1s).

Blood Cadmium and Abdominal Aortic Calcification in Population with Different Weight Statuses: a Population-Based Study.

The aim of our study was to assess the effect of blood cadmium levels (B-Cd) on abdominal aortic calcification (AAC). We used the data from the 2013-2014 NHANES database. A total of 1530 participants were included in our study, with a mean AAC score of 1.40 ± 0.10, and a prevalence of severe AAC of 7.98%. Participants with higher B-Cd quartiles showed a higher prevalence of severe AAC. B-Cd was positively associated with higher AAC scores and increased risk of severe AAC. In the obese population, blood cadmium levels showed a positive association with the risk of severe AAC. There may be a positive correlation between B-Cd levels and AAC scores and risk of severe AAC, and this correlation is more pronounced in the obese population. Therefore, the cadmium load in AAC patients in the obese population should be considered in clinical work.

Association of blood cadmium with all-cause and cause-specific mortality in patients with hypertension.

Background: Cadmium is a commonly found heavy metal with a prolonged biological half-life, which results in long-term health burden for the population. Prior studies have demonstrated an association between blood cadmium and hypertension. However, few studies examined the relationship between blood cadmium and long-term health outcomes in patients with hypertension. This study aimed to investigate the association of blood cadmium with mortality in patients with hypertension. Methods: This study analyzed data from the National Health and Nutrition Examination Survey 1999-2012. Complex sampling-weighted multivariate Cox proportional hazards models were used to evaluate the hazard ratios (HRs) of all-cause, cardiovascular, and Alzheimer's disease mortality in patients with hypertension classified by blood cadmium concentrations' quantiles. Results: The study included 12,208 patients with hypertension with a median follow-up duration of 10.8 years. During this period, there were 4,485 all-cause deaths, including 1,520 cardiovascular deaths and 180 Alzheimer's disease deaths. Compared with the lowest quintile of blood cadmium (≤0.25 µg/L) group, the highest quintile of blood cadmium (≥0.80 µg/L) group's adjusted HRs were 1.85 (95% CI, 1.59-2.14) for all-cause mortality, 1.76 (95% CI, 1.33-2.34) for cardiovascular mortality, and 3.41 (95% CI, 1.54-7.51) for Alzheimer's disease mortality. Additionally, the adjusted HR for cardiovascular mortality was 2.12 (95% CI, 1.36-3.30) in never-smoking patients with hypertension. Conclusion: Higher blood cadmium is associated with increased risks of all-cause, cardiovascular, and Alzheimer's disease mortality in patients with hypertension. The effect of blood cadmium on cardiovascular mortality may be more pronounced in never-smoking hypertensive patients.

Contaminant Metals as Cardiovascular Risk Factors: A Scientific Statement From the American Heart Association.

Exposure to environmental pollutants is linked to increased risk of cardiovascular disease. Beyond the extensive evidence for particulate air pollution, accumulating evidence supports that exposure to nonessential metals such as lead, cadmium, and arsenic is a significant contributor to cardiovascular disease worldwide. Humans are exposed to metals through air, water, soil, and food and extensive industrial and public use. Contaminant metals interfere with critical intracellular reactions and functions leading to oxidative stress and chronic inflammation that result in endothelial dysfunction, hypertension, epigenetic dysregulation, dyslipidemia, and changes in myocardial excitation and contractile function. Lead, cadmium, and arsenic have been linked to subclinical atherosclerosis, coronary artery stenosis, and calcification as well as to increased risk of ischemic heart disease and stroke, left ventricular hypertrophy and heart failure, and peripheral artery disease. Epidemiological studies show that exposure to lead, cadmium, or arsenic is associated with cardiovascular death mostly attributable to ischemic heart disease. Public health measures reducing metal exposure are associated with reductions in cardiovascular disease death. Populations of color and low socioeconomic means are more commonly exposed to metals and therefore at greater risk of metal-induced cardiovascular disease. Together with strengthening public health measures to prevent metal exposures, development of more sensitive and selective measurement modalities, clinical monitoring of metal exposures, and the development of metal chelation therapies could further diminish the burden of cardiovascular disease attributable to metal exposure.

Global DNA methylation and the association between metal exposure and chronic kidney disease.

Introduction: Prior studies indicate that exposure to metals may alter DNA methylation. Evidence also shows that global DNA methylation is associated with chronic kidney disease (CKD). This study aimed to examine the association between CKD and 5-methyl-2-deoxycytidine (5mdC, %), a marker of global DNA methylation, and to evaluate the interaction between metal exposures and 5mdC (%) on CKD. We also explored the mediation effect of 5mdC (%) on the association between metal exposures and renal function (i.e., estimated glomerular filtration rate, eGFR). Methods: A total of 218 CKD patients and 422 controls were recruited in this case-control study. 5mdC (%), concentrations of blood lead and cadmium, plasma selenium, and total urinary arsenic were measured. CKD cases were clinically defined among patients with eGFR <60 mL/min/1.73 m2 for at least 3 months and without hemodialysis. Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to examine the association between metal exposures, 5mdC (%), and CKD, adjusted for confounders. Multivariable linear regression models were used to examine associations between metal exposures, 5mdC (%), and eGFR. Results and Discussion: CKD cases compared to controls had 6.06-fold (95% CI: 3.11-11.81) higher odds of having high blood cadmium and high 5mdC (%) levels. A positive interaction on an additive scale was identified between blood cadmium and 5mdC (%) on CKD. Cases compared to controls had 4.73-fold (95% CI: 2.65-8.45) higher odds of having low plasma selenium and high 5mdC (%) levels; and a significant multiplicative interaction between plasma selenium and 5mdC (%) on CKD was observed. In addition, we found that blood lead and cadmium concentrations were positively associated, while plasma selenium concentrations were inversely associated, with 5mdC (%). The associations of blood lead and plasma selenium with eGFR were partially mediated by 5mdC (%). Our results suggest that 5mdC (%) may interact with plasma selenium and blood cadmium to influence the risk of CKD. The 5mdC (%) also potentially mediates the associations between exposure to metals and renal function.

Chronic exposure to Cadmium in drinking water: effect on kidneys and long bones / Exposición crónica a Cadmio en agua potable: efecto sobre riñones y huesos largos

Over the last years, cadmium (Cd) contamination has become a worldwide problem as a result of its increasing use in industry, its long half-life inside the body, and its deleterious health effects. The aim of the present work was to evaluate the effect of chronic exposure to Cd on the kidneys and long bones. To this end, 16 young male Wistar rats were assigned to one of two groups: control and Cd. Rats in the Cd group were given drinking water containing 25 mg/L of CdCl2 for six months and control rats were given drinking water. After euthanasia, the kidneys, tibiae, and femurs were resected, processed histologically, and embedded in paraffin or methyl methacrylate. Urinary Cd, histopathological evaluation of kidney tissue, determination of catalase, superoxide dismutase, glutathione content, lipid peroxidation levels and the area of the proximal tubules expressing alkaline phosphatase were analyzed. Static and dynamic histomorphometric parameters of tibia and femur were determined. The data were statistically analyzed using Student’s t test (p<0.05). The Cd group showed greater urinary Cd excretion, glomerular and tubular damage, a significant decrease in alkaline phosphatase activity in the proximal tubules, and lower renal superoxide dismutase activity. The Cd group showed significantly more yellow bone marrow, fewer tartrate-resistant acid phosphatase positive osteoclasts and a lower percentage of runt-related transcription factor 2 in the growth plate than in controls. (AU)

En los últimos años, la contaminación por cadmio (Cd) se ha convertido en un problema mundial debido a su creciente uso en la industria, su larga vida media dentro del cuerpo y sus efectos nocivos para la salud. El objetivo del presente trabajo fue evaluar el efecto de la exposición crónica a Cd en riñones y huesos largos. Para ello, se asignaron 16 ratas Wistar macho jóvenes a uno de dos grupos: control y Cd. Las ratas del grupo Cd recibieron agua potable que contenía 25 mg/l de CdCl2 durante seis meses y las ratas de control recibieron agua potable. Después de la eutanasia, los riñones, las tibias y los fémures fueron resecados, procesados histológicamente e incluidos en parafina o metacrilato de metilo. Se analizó Cd urinario, evaluación histopatológica del tejido renal, determinación de catalasa, superóxido dismutasa, contenido de glutatión, niveles de peroxidación lipídica y área de los túbulos proximales que expresan fosfatasa alcalina. Se determinaron parámetros histomorfométricos estáticos y dinámicos de tibia y fémur. Los datos se analizaron estadísticamente mediante la prueba t de Student (p<0,05). El grupo Cd mostró una mayor excreción urinaria de Cd, daño glomerular y tubular, una disminución significativa de la actividad de la fosfatasa alcalina en los túbulos proximales y una menor actividad de la superóxido dismutasa renal. El grupo Cd mostró significativamente más médula ósea amarilla, menos osteoclastos positivos a la fosfatasa ácida resistentes al tartrato y un porcentaje más bajo de factor de transcripción 2 relacionado con el runt e n la placa de crecimiento que en los controles. (AU)

National analysis of urinary cadmium concentration and kidney stone: Evidence from NHANES (2011-2020).

Background: The association between urinary cadmium and kidney stone risk is inconsistent in previous studies, which needs further exploration. This study was performed to explore the association between urinary cadmium and kidney stone. Materials and methods: Data from the National Health and Nutrition Examination Survey (2011-2020) were included and further analyzed. Urinary cadmium was stratified into quartiles with quartile 1 (Q1: 0.025-0.104 µg/L) and quartile 4 (Q4: 0.435-7.581 µg/L). Further weighted logistic regression was adopted to evaluate the association between urinary cadmium and kidney stone. A subgroup analysis was used to verify the findings. The non-linear association was examined using the restricted cubic spline (RCS) regression. Results: A total of 9,056 adults aged 20 years and above were included in this study. In the fully adjusted model, an increased risk of kidney stones was identified for quartile 2 (OR = 1.40, 95% CI = 1.06-1.84, P < 0.05), quartile 3 (OR = 1.18, 95% CI = 0.88-1.59, P > 0.05), and quartile 4 (OR = 1.54, 95% CI = 1.10-2.06, P < 0.05). A similar association was found between continuous cadmium increase and OR of kidney stones in the fully adjusted model (OR = 1.13, 95% CI = 1.01-1.26, P < 0.05). The RCS also indicated a non-linear association between urinary cadmium concentration and kidney stone risk (P for non-linear < 0.001). Conclusion: In summary, cadmium exposure is identified as a risk factor for kidney stones in this study. Their non-linear association makes demands on early intervention for the cadmium-exposed population. Medical interventions for kidney stone prevention should take cadmium exposure into account.

Association of multi-metals with the risk of hypertension and the interaction with obesity: A cross-sectional study in China.

Background: Environmental exposure to multiple metals have been inconsistently associated with hypertension. Obesity is an important independent risk factor for hypertension, and few studies have assessed the interaction between obesity and metals in this context. We aimed to clarify their association and interaction. Methods: This cross-sectional study included 3,063 adults from 11 districts or counties, Guangdong. We measured the whole blood levels of 13 metals and used multipollutant-based statistical methods to analyze the association of metals with hypertension. The interaction between metals and obesity on hypertension was assessed on additive and multiplicative scales. Results: Four metals (manganese, arsenic, cadmium, and lead) were significantly associated with hypertension risk, five metals (manganese, zinc, arsenic, cadmium, and lead) were related to elevated SBP levels, five metals (manganese, zinc, selenium, cadmium, and lead) were associated with elevated DBP levels in single-metal model. Manganese remained significantly related to hypertension risk [odds ratio, 1.35 (1.02-1.78)] after adjusting for these four metals. Significant positive dose-response relationships between manganese, arsenic, cadmium, lead and hypertension risk were observed (P for overall < 0.001, P for non-linearity > 0.05). Compared with those in the lowest quartile, participants in the highest manganese quartile had a 2.83 mmHg (95% Cl: 0.71-4.96) (P FDR = 0.040) higher level of SBP. Individuals in the highest quartiles of zinc and lead had a 1.45 mmHg (0.10-2.81) (P FDR = 0.033) and 2.06 mmHg (0.59-3.53) (P FDR = 0.020) higher level of DBP, respectively. The negative interactions between cadmium, lead and obesity influences hypertension risk. BKMR analysis showed a significant joint effect of manganese, arsenic, cadmium and lead on hypertension when the concentrations of four metals were at or above their 55th percentile compared to their median values. Conclusions: The combined effect of four metals (manganese, arsenic, cadmium and lead) were associated with the prevalence of hypertension. Potential interaction effects of cadmium, lead and obesity on hypertension risk may exist. Further cohort studies in larger population are needed to clarify these findings.

Association between dietary intake of α-tocopherol and cadmium related osteoporosis in population ≥ 50 years.

INTRODUCTION: To analyze the association between α-tocopherol intake and cadmium (Cd) exposure and osteoporosis in population ≥ 50 years. MATERIALS AND METHODS: Sociodemographic data, physical examination, and laboratory indicators including serum Cd level and dietary α-tocopherol intake of 8459 participants were extracted from the National Health and Nutrition Examination Survey (NHANES) database in this cross-sectional study. The associations between α-tocopherol intake, serum Cd levels and osteoporosis were evaluated using univariate and multivariate logistic regression analyses, with the estimated value (ß), odds ratios (ORs) and 95% confidence intervals (CIs). We further explored the impact of α-tocopherol intake on Cd exposure and the bone mineral density (BMD) in total femur and femur neck. RESULTS: A total of 543 old adults suffered from osteoporosis. The serum Cd level (0.52 µg/L vs. 0.37 µg/L) and α-tocopherol intake (5.28 mg vs. 6.50 mg) were statistical different in osteoporosis group and non-osteoporosis group, respectively. High level of Cd exposure was related to the increased risk of osteoporosis [OR = 1.60, 95% CI (1.15-2.21)]. In the total femur, α-tocopherol intake may improve the loss of BMD that associated with Cd exposure [ß = - 0.047, P = 0.037]. Moreover, high α-tocopherol intake combined with low Cd exposure [OR = 0.54, 95% CI (0.36-0.81)] was linked to the decreased risk of osteoporosis comparing with low α-tocopherol intake combined with high Cd exposure. CONCLUSION: High α-tocopherol intake may improve the Cd-related osteoporosis and loss of BMD that could provide some dietary reference for prevention of osteoporosis in population ≥ 50 years old.

Association of urinary heavy metals co-exposure and adult depression: Modification of physical activity.

OBJECTIVE: This study aimed to evaluate the association between urinary heavy metal mixture exposure and depression, and the modifying role of physical activity in the effects of heavy metal mixture on depression risk was also considered. METHODS: Data of this study were derived from the National Health and Nutrition Examination Survey 2011-2016. Depression was measured by the Patient Health Questionnaire. We first selected 6 (cadmium, cobalt, tin, antimony, thallium, and mercury) from 14 heavy metals through elastic net regression for further analysis. Then binomial logistic regression, generalized additive model, environment risk score (ERS), and weighted quantile sum (WQS) regression were adopted to assess the effects of six metals individual and cumulative exposure on depression risk. Finally, we also examined whether physical activity could mitigate the effects of heavy metal co-exposure on depression risk. RESULTS: Totally, 4212 participants were included and 7.40% of subjects were with depression. We found urinary tin and antimony were separately associated with increased odds of depression (Sb: OR = 1.285, 95% CI: 1.064-1.553; Sn: OR = 1.281, 95% CI: 1.097-1.495), and a linear dose-response relationship between tin and depression was also noticed (P < 0.05). Meanwhile, urinary heavy metals co-exposure was positively related to depression risk (ERSQ4: OR = 2.691, 95% CI: 1.399-5.174; WQSpositive: OR = 1.465, 95% CI: 1.063-2.021), in which tin, antimony, and cadmium were identified with greater contributions to the overall mixture effect. In both ERS and WQS models, the significant positive association between the metal mixture and depression risk remained only in those who were inactive in physical activity. CONCLUSION: Our study concluded the detrimental effect of heavy metals in combined exposure on the risk of depression, which might be attenuated by physical activity.

Race and Gender Differences in the Associations Between Cadmium Exposure and Bone Mineral Density in US Adults.

Several previous studies have found the deleterious effects of cadmium exposure on bone. However, studies on the effects of cadmium exposure on bone mineral density (BMD) in gender- and race-specific groups are still lacking. The aim of this study was to investigate the relationship between cadmium exposure and BMD in adults and the gender and racial differences therein. Weighted multivariate regression, generalized weighted model, and smoothed curve fitting were used to explore the relationship between lumbar BMD with blood cadmium (B-Cd) and urine cadmium (U-Cd) based on data from the National Health and Nutrition Examination Survey (NHANES). In addition, subgroup analyses were further used to investigate the differential associations across gender and race. Of the 4335 adult participants. After adjusting for primary demographic variables, B-Cd [- 0.018 (- 0.028, - 0.008)] and U-Cd [- 0.010 (- 0.020, - 0.001)] were shown to be negatively related to lumbar BMD. In the fully adjusted model, the negative association between B-Cd and lumbar BMD was maintained [- 0.010 (- 0.018, - 0.002)]. In the subgroup analysis stratified by gender and race, this relationship was retained in females and non-Hispanic blacks. Furthermore, these negative associations were most pronounced among non-Hispanic black women [B-Cd and lumbar BMD, - 0.046 (- 0.076, - 0.017); U-Cd and lumbar BMD, -0.034 (- 0.063, - 0.006)]. Our findings suggest that there are significant sex and race differences in the negative association between cadmium exposure and BMD. This negative association was most prominent in non-Hispanic black females.

Mediating effect of telomere length in a hypertension population exposed to cadmium: a case-control study.

Cadmium (Cd) is associated with telomere length and hypertension, respectively, but the mechanism behind its relationship is unclear. Our study aimed to clarify the role of telomere length in the relationship between Cd and hypertension. A 1:1 matched case-control study was conducted with 213 hypertensive patients and 213 normotensive controls in Taiyuan, Shanxi Province, China, from February and June 2016. General demographic characteristics information and lifestyle were collected using a structured questionnaire. Urine samples were collected to test urinary Cd (UCd) levels and corrected by urinary creatinine (UCr) levels. Peripheral leukocyte absolute telomere length (ATL) was measured using quantitative polymerase chain reaction. Logistic regression was used to screen the influencing factors of hypertension. A mediation effect analysis was used to explore the role of telomere length between Cd exposure and the risk of hypertension. We found that the hypertension group had a significantly higher UCd level compared to the control group (0.91 vs 0.80 µg/g Cr, P < 0.01), while ATL showed the opposite relationship (2.36 vs 2.65 kb, P < 0.01). The Regression analysis of hypertension identified these significant predictors: family history of hypertension (OR = 3.129, 95% confidence interval (95% CI): 1.767-5.540), Body mass index (BMI, OR = 1.088, 95% CI: 1.023-1.157), total cholesterol (TC, OR = 1.277, 95% CI: 1.024-1.592), UCd (OR = 2.092, 95% CI: 1.179-3.710), ATL (OR = 0.105, 95% CI: 0.025-0.453) and 8-hydroxy-2-deoxyguanosine (8-OHdG, OR = 7.864, 95% CI: 3.516-17.589). Mediating effect analysis revealed that ATL was a potential partial mediating factor between Cd and hypertension. Cd may induce hypertension by affecting telomere length, but this requires further exploration.

Cadmium, active smoking and renal function deterioration in patients with type 2 diabetes.

BACKGROUND: Cadmium is an established nephrotoxin, present in cigarette smoke. We investigated the hazards of cadmium concentration and smoking status on renal function deterioration. We furthermore discerned whether the association of cadmium concentration with renal function deterioration is attributable to smoking status. METHODS: Prospective analyses were performed in data of 226 patients of the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT). Cadmium concentrations were determined from EDTA whole-blood. Smoking status was determined via a self-administered questionnaire. Renal function deterioration was defined as need for renal replacement therapy or a persistent decline of ≥30% in estimated glomerular filtration rate from baseline for at least 3 months. Multivariable Cox regression models were performed to calculate hazard ratios (HRs) for the association between smoking status, cadmium concentration and renal function deterioration. RESULTS: Median (interquartile range) whole-blood cadmium was 2.9 (1.9-5.1) nmol/L. Active smokers had significantly higher cadmium [7.4 (3.3-11.7) nmol/L] compared with never smokers [2.6 (1.6-4.2) nmol/L] and former smokers [2.8 (1.8-4.8) nmol/L]. During median follow-up for 6 (4-8) years, renal function deterioration occurred in 60 persons (27%). Both cadmium and active smoking were associated with an increased hazard for renal function deterioration [HR 1.37, 95% confidence interval (95% CI) 1.06-1.78 and 3.77, 95% CI 1.72-8.29, respectively]. In a multivariable model with both smoking status and cadmium concentration included, active smokers have an increased risk for renal function deterioration (HR 3.00, 95% CI 1.22-7.40), while the association between cadmium and renal function deterioration lost statistical significance (HR 1.16, 95% CI 0.87-1.54). CONCLUSIONS: Active smoking is associated with progressive kidney disease in type 2 diabetes. The association between cadmium concentration and renal function deterioration in large part determined by smoking status. Extensive assessment of smoking status may be useful in patients with type 2 diabetesat high risk of kidney damage.

[Distribution Characteristics and Ecological Risk Assessment of Soil Heavy Metals in Baiyangdian Lake].

To understand the spatial distribution characteristics and potential ecological risk of heavy metals in soil of Baiyangdian Lake, 55 soil samples were collected and the contents of eight heavy metals (Mn, Cr, Cu, Zn, As, Cd, Pb, and Ni) were detected. The spatial variation structure and distribution pattern were analyzed using geostatistical methods (Moran index and semi-variance model). The degree of heavy metal pollution and its risk were assessed using the geoaccumulation index (Igeo) and potential ecological risk index (Eri and RI). The results showed that the average of ω(Mn), ω(Cr), ω(Cu), ω(Zn), ω(As), ω(Cd), ω(Pb), and ω(Ni) were 467.75, 43.59, 28.57, 89.04, 12.32, 0.18, 19.26, and 30.56 mg·kg-1, respectively, all of which were lower than the screening values of soil pollution risk in agricultural land. However, the contents of Cu, Zn, and Cd were significantly higher than their background values, with two highly variable elements of Cu (48.65%) and Cd (37.52%). The Moran index indicated that Mn, Cu, Cd, and Pb showed weak spatial autocorrelation. Nugget coefficients of both of Cd and Pb shown by the semi-variance model were 100%, suggesting random variation as a main spatial variation driven by anthropogenic factors. High values of soil heavy metals were mainly distributed in the southwest of Baiyangdian Lake with a significant correlation between the heavy metals. The Igeo of soil heavy metals from high to low was Cd>Cu>Zn>Ni>As>Pb>Mn>Cr. Cd pollution was the most common, in which 67.27% of the samples were lightly polluted. Ecological risk assessment revealed that the average Eri of Cd was 58.81, belonging to the middle ecological risk level, and the rest were at light ecological risk. As a whole, the RI of soil heavy metal pollution in Baiyangdian Lake was at a light ecological risk level (87.81), with the highest contribution rate of Cd to RI (66.39%). Thus, it is necessary to strengthen the control of soil heavy metal Cd pollution in Baiyangdian Lake in the future.

A systematic review and meta-analysis of the hyperuricemia risk from certain metals.

The relationship between exposure to certain metals and the risk of hyperuricemia (HUA) has biological plausibility, yet prior studies have presented inconsistent findings. We aim to clarify the relationship between exposure to certain metals and HUA using a systematic review and meta-analysis approach. We searched the Web of Science, Embase, MEDLINE, Pubmed, Corchrane and China National Knowledge Infrastructure databases from inception through December, 2021 in order to identify studies that assessed the relationships between metals and the risk of HUA. Data were pooled by random-effects models and expressed as pooled odds ratios (OR) and 95% confidence intervals (CIs). The risk of bias was assessed using a tool from Agency for Healthcare Research and Quality (AHRQ). Twenty eligible articles (nineteen cross-sectional studies and one cohort) were included in our analysis, involving 63,283 participants in total. The studies showed that arsenic (pooled OR = 1.702, 95% CI: 1.44, 2.011; n = 6, I2 = 29.5%), calcium (pooled OR = 1.765, 1.111, 2.804; 4, 82.3%), cadmium (pooled OR = 1.199,1.020, 1.410; 11, 38.5%) and lead (pooled OR = 1.564,1.205, 2.030; 11, 72.9%) exposure were, all linked to an increased risk of HUA. Exposure to molybdenum (pooled OR = 0.804, 0.724, 0.975, 3, 0%) was linked to a decreased risk of HUA, however. Exposure to arsenic, calcium, cadmium and lead is associated with an increased risk of HUA. Molybdenum exposure was associated with a decreased prevalence of HUA; however, aluminum, cobalt, copper, iron, magnesium, manganese, mercury, selenium, thallium and zinc are not associated with HUA risk. Further experimental studies are warranted to decipher the mechanisms by which exposure to the above metals affect HUA risk. The findings reinforced the importance of metals in the HUA risk, and provided a reference for legislation to prevent HUA and protect people's health.