The association of cadmium and lead exposures with red cell distribution width.
ABSTRACT: Elevated red blood cell distribution width (RDW), traditionally an indicator of anemia, has now been recognized as a risk marker for cardiovascular disease incidence and mortality. Experimental and acute exposure studies suggest that cadmium and lead individually affect red blood cell production; however, associations between environmental exposures and RDW have not been explored. We evaluated relationships of environmental cadmium and lead exposures to RDW. We used data from 24,607 participants aged ?20 years in the National Health and Nutrition Examination Survey (2003-2016) with information on blood concentrations of cadmium and lead, RDW and socio-demographic factors. In models adjusted for age, sex, race/ethnicity, education, poverty income ratio, BMI, alcohol consumption, smoking status and serum cotinine, RDW was increasingly elevated across progressively higher quartiles of blood cadmium concentration. A doubling of cadmium concentration was associated with 0.16 higher RDW (95% CI: 0.14, 0.18) and a doubling of lead concentration with 0.04 higher RDW (95% CI: 0.01, 0.06). Also, higher cadmium and lead concentrations were associated with increased odds of high RDW (RDW>14.8%). The associations were more pronounced in women and those with low-to-normal mean corpuscular volume (MCV) and held even after controlling for iron, folate or vitamin B12 deficiencies. In analysis including both metals, cadmium remained associated with RDW, whereas the corresponding association for lead was substantially attenuated. In this general population sample, blood cadmium and lead exposures were positively associated with RDW. The associations may indicate hemolytic or erythropoietic mechanisms by which exposure increases mortality risk.
Project description:BACKGROUND:Environmental factors contributing to diabetic kidney disease are incompletely understood. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. MATERIAL AND METHODS:In a cross-sectional analysis in 231 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1), blood cadmium and lead concentrations were determined using inductively coupled plasma mass spectrometry. The associations between diet (derived from food frequency questionnaire), smoking and cadmium and lead were determined using multivariate linear regression. The associations between cadmium and lead and diabetic kidney disease (albumin excretion >30 mg/24 h and/or creatinine clearance <60 mL/min/1.73 m2) were determined using multivariate logistic regression. RESULTS:Median blood concentrations were 2.94 nmol/L (interquartile range (IQR): 1.78-4.98 nmol/L) for cadmium and 0.07 µmol/L (IQR: 0.04-0.09 µmol/L) for lead, i.e., below acute toxicity values. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11-2.74) times higher risk for albuminuria. In addition, both cadmium (odds ratio (OR) 1.50 95% CI: 1.02-2.21) and lead (OR 1.83 95% CI: 1.07-3.15) were associated with an increased risk for reduced creatinine clearance. Both passive smoking and active smoking were positively associated with cadmium concentration. Alcohol intake was positively associated with lead concentration. No positive associations were found between dietary intake and cadmium or lead. CONCLUSIONS:The association between cadmium and lead and the prevalence of diabetic kidney disease suggests cadmium and lead might contribute to the development of diabetic kidney disease. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption.
Project description:Infant exposures to metals are a concern for mining-impacted communities, although limited information is available to assess residential exposures over the first year of life. We measured lead (Pb), manganese, arsenic, and cadmium in indoor air, house dust, yard soil, and tap water from 53 infants' homes near the Tar Creek Superfund Site (Oklahoma, USA) at two time points representing developmental stages before and during initial ambulation (age 0-6 and 6-12 months). We measured infant metal biomarkers in: umbilical cord blood (n=53); 12- (n=43) and 24- (n=22) month blood; and hair at age 12 months (n=39). We evaluated cross-sectional and longitudinal associations between infant residential and biomarker concentrations. A doubling of mean dust Pb concentration was consistently associated with 36-49% higher 12-month blood Pb adjusting for cord blood Pb (P?0.05). Adjusted dust concentration explained 29-35% of blood Pb variance, and consistent associations with other media were not observed. Although concentrations in dust and blood were generally low, strong and consistent associations between dust and body burden suggest that house dust in mining-impacted communities may impact children's health. These relationships were observed at a young age, typically before blood Pb levels peak and when children's development may be particularly vulnerable to toxic insult.
Project description:Lead and cadmium exposures have markedly declined in the USA following the implementation of large-scale public health policies and could have contributed to the unexplained decline in cardiovascular mortality in US adults. We evaluated the potential contribution of lead and cadmium exposure reductions to explain decreasing cardiovascular mortality trends occurring in the USA from 1988-94 to 1999-2004.Prospective study in 15?421 adults ?40 years old who had participated in the National Health and Nutrition Examination Survey 1988-94 or 1999-2004. We estimated the amount of change in cardiovascular mortality over time that can be independently attributed to the intermediate pathway of changes in blood lead and urine cadmium concentrations.There was a 42.0% decrease in blood lead and a 31.0% decrease in urine cadmium concentrations. The cardiovascular mortality rate ratio [95% confidence intervals (CIs)] associated with a doubling of metal levels was 1.19 (1.07, 1.31) for blood lead and 1.20 (1.09, 1.32) for urine cadmium. The absolute reduction in cardiovascular deaths comparing 1999-2004 to 1988-94 was 230.7 deaths/100?000 person-years, in models adjusted for traditional cardiovascular risk factors. Among these avoided deaths, 52.0 (95% CI 8.4, 96.7) and 19.4 (4.3, 36.4) deaths/100?000 person-years were attributable to changes in lead and cadmium, respectively.Environmental declines in lead and cadmium exposures were associated with reductions in cardiovascular mortality in US adults. Given the fact that lead and cadmium remain associated with cardiovascular disease at relatively low levels of exposure, prevention strategies that further minimize exposure to lead and cadmium may be needed.
Project description:Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005-2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02-2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91-2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37-8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40-5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn.
Project description:Background:The ubiquitous metals cadmium and lead are immunotoxic, but little is known about their relations to cytomegalovirus (CMV), a widespread herpesvirus. Although CMV infections are mostly asymptomatic, congenital infections are a leading cause of birth defects. In otherwise healthy individuals, there is also some evidence linking subclinical reactivations to accelerated age-related declines in immune function and chronic disease. Methods:Our objective was to evaluate associations of blood cadmium and lead biomarkers with CMV infection in a representative sample of the United States population. In seropositive individuals, we also examined associations with CMV-specific immunoglobulin G (IgG) antibody levels and suspected CMV recurrences. Using cross-sectional data from the 1999-2004 National Health and Nutrition Examination Surveys, we fit multivariable survey-weighted regression models accounting for potential confounding by sociodemographic and lifestyle factors and stratifying by age group to allow for heterogeneity. CMV recurrences were defined according to (1) the presence of either CMV-specific immunoglobulin M in sera or CMV viral DNA in urine, and (2) high CMV-specific IgG avidity. Results:We observed null associations for blood cadmium. Increasing blood lead quartiles were related to CMV seropositivity and higher CMV IgG levels (both P trend < 0.01), but not CMV recurrence, only among individuals who were 20-29 years of age. Conclusion:Blood cadmium levels do not appear to be related to immunological markers of CMV infections. The possibility that lead exposures increase the risk of CMV infection and impair immune control of the virus in young adults was suggested. Prospective studies are needed to confirm.
Project description:PURPOSE OF REVIEW:This study aims to summarize the current body of literature on the relationship between various toxic metals exposures (i.e., aluminum, antimony, arsenic, beryllium, cadmium, chromium, lead, manganese, and nickel) and autism spectrum disorder (ASD), with a focus on potential sex differences in these associations. RECENT FINDINGS:Sex differences in ASD diagnosis and mutagenic effects of toxic exposures indicate that sex differences may play a major part in the causal relationship of any potential associations seen; however, we were only able to find three studies that reported on sex differences in observed associations with toxic metals exposure and ASD. We also found several studies investigating associations between ASD and metals exposures, including 11 on aluminum, 6 on antimony, 15 on arsenic, 5 on beryllium, 17 on cadmium, 11 on chromium, 25 on lead, 14 on manganese, and 13 on nickel with markers of exposure in hair, urine, blood, teeth, fingernails, and air pollution. Results for each metal were conflicting, but studies on cadmium and lead yielded the highest proportion of studies with positive results (72% and 36%, respectively). Based on our examination of existing literature, the current evidence warrants a considerable need for evaluations of sex differences in future studies assessing the association between metals exposures and ASD. Additionally, failure to account for potential sex differences could result in bias and misinterpretation of exposure-disease relationships.
Project description:Although cadmium and lead are known risk factors for hearing loss in animal models, few epidemiologic studies have been conducted on their associations with hearing ability in the general population.We investigated the associations between blood cadmium and lead exposure and hearing loss in the U.S. general population while controlling for noise and other major risk factors contributing to hearing loss.We analyzed data from 3,698 U.S. adults 20-69 years of age who had been randomly assigned to the National Health and Nutrition Examination Survey (NHANES) 1999-2004 Audiometry Examination Component. Pure-tone averages (PTA) of hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz were computed, and hearing loss was defined as a PTA > 25 dB in either ear.The weighted geometric means of blood cadmium and lead were 0.40 [95% confidence interval (CI): 0.39. 0.42] µg/L and 1.54 (95% CI: 1.49, 1.60) µg/dL, respectively. After adjusting for sociodemographic and clinical risk factors and exposure to occupational and nonoccupational noise, the highest (vs. lowest) quintiles of cadmium and lead were associated with 13.8% (95% CI: 4.6%, 23.8%) and 18.6% (95% CI: 7.4%, 31.1%) increases in PTA, respectively (p-trends < 0.05).Our results suggest that low-level exposure to cadmium and lead found in the general U.S. population may be important risk factors for hearing loss. The findings support efforts to reduce environmental cadmium and lead exposures.
Project description:Arsenic, cadmium, mercury, and lead are associated with cardiovascular disease in epidemiologic research. These associations may be mediated by direct effects of the metals on blood pressure (BP) elevation. Manganese is associated with cardiovascular dysfunction and hypotension in occupational cohorts.We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP.We conducted a cross-sectional analysis of associations between toenail metals and BP among older men from the Normative Aging Study (n = 639), using linear regression and adjusting for potential confounders.An interquartile range increase in toenail arsenic was associated with higher systolic BP [0.93 mmHg; 95% confidence interval (CI): 0.25, 1.62] and pulse pressure (0.76 mmHg; 95% CI: 0.22, 1.30). Positive associations between arsenic and BP and negative associations between manganese and BP were strengthened in models adjusted for other toenail metals.Our findings suggest associations between BP and arsenic and manganese. This may be of public health importance because of prevalence of both metal exposure and cardiovascular disease. Results should be interpreted cautiously given potential limitations of toenails as biomarkers of metal exposure.
Project description:Environmental cadmium and lead exposures are widespread, and both metals are nephrotoxic at high exposure levels. Few studies have evaluated the associations between low-level cadmium and clinical renal outcomes, particularly with respect to joint cadmium and lead exposure. The geometric mean levels of blood cadmium and lead were 0.41 microg/L (3.65 nmol/L) and 1.58 microg/dL (0.076 micromol/L), respectively, in 14,778 adults aged >or=20 years who participated in the National Health and Nutrition Examination Survey (1999-2006). After adjustment for survey year, sociodemographic factors, chronic kidney disease risk factors, and blood lead, the odds ratios for albuminuria (>or=30 mg/g creatinine), reduced estimated glomerular filtration rate (eGFR) (<60 mL/minute/1.73 m(2)), and both albuminuria and reduced eGFR were 1.92 (95% confidence interval (CI): 1.53, 2.43), 1.32 (95% CI: 1.04, 1.68), and 2.91 (95% CI: 1.76, 4.81), respectively, comparing the highest with the lowest blood cadmium quartiles. The odds ratios comparing participants in the highest with the lowest quartiles of both cadmium and lead were 2.34 (95% CI: 1.72, 3.18) for albuminuria, 1.98 (95% CI: 1.27, 3.10) for reduced eGFR, and 4.10 (95% CI: 1.58, 10.65) for both outcomes. These findings support consideration of cadmium and lead as chronic kidney disease risk factors in the general population and provide novel evidence of risk with environmental exposure to both metals.
Project description:BACKGROUND:Epidemiologic studies suggest toxic metals are linked with diabetes and cardiovascular disease, while experimental studies indicate nutritionally essential metals are involved in the metabolism of macronutrients and defense against oxidative stress. OBJECTIVES:We sought to evaluate how essential and toxic metals are cross-sectionally related to metabolic syndrome, a clustering of cardiometabolic conditions. METHODS:Using data from the 2011-2014 National Health and Nutrition Examination Survey (n?=?1088), we characterized metal concentrations as measured in spot urine (arsenic, cadmium, and inorganic/elemental mercury), whole blood (manganese, lead, methylmercury, and selenium), and serum (copper and zinc) samples. Principal component analysis was performed to derive patterns of exposures. Metabolic syndrome was defined according to the 2009 Joint Scientific Statement as the presence of ??3 of the following conditions: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, and abdominal obesity. RESULTS:After adjustment for potential confounders, prevalence ratios for metabolic syndrome comparing the highest to the lowest quartiles were 1.41 (95% CI: 1.18-1.67) for the arsenic-inorganic/elemental mercury pattern, 0.95 (0.78-1.16) for the methylmercury-manganese pattern, 0.73 (0.57-0.94) for the cadmium-lead pattern, 0.91 (0.76-1.10) for the copper pattern, and 1.36 (1.13-1.63) for the selenium-zinc pattern. The positive associations observed for the arsenic-inorganic/elemental mercury pattern were due to an elevated prevalence of high blood pressure, low HDL cholesterol, and high triglycerides among those with greater exposures. Associations for the selenium-zinc pattern were driven by a positive relationship with high triglycerides. Greater lead-cadmium co-exposures were related to a lower prevalence of dyslipidemia and abdominal obesity. CONCLUSIONS:These cross-sectional findings suggest both toxic and essential metal exposures may contribute to cardiometabolic health, but need to be confirmed with prospective data.