We explored the notion that social disadvantage increases vulnerability to the health effects of environmental hazards. Specifically, we examined (1) whether race modifies the association between blood lead and blood pressure and (2) whether socioeconomic status (SES) plays a role in this modifying effect.
Using the National Health and Nutrition Examination Survey (2001–2008) and linear regression, we estimated the association between blood lead and blood pressure. Using interactions among race, SES, and lead, we estimated this association by levels of social disadvantage.
Black men and women showed a 2.8 (P < .001) and 4.0 (P < .001) millimeters mercury increase in SBP, respectively, for each doubling of blood lead. White adults showed no association. This lead–SBP association exhibited by Blacks was primarily isolated to Blacks of low SES. For example, poor but not nonpoor Black men showed a 4.8 millimeters mercury (P < .001) increase in SBP for each doubling of blood lead.
Our results suggest that social disadvantage exacerbates the deleterious health effects of lead. Our work provides evidence that social and environmental factors must be addressed together to eliminate health disparities.
The objective of this study is to investigate the mobilization of lead from bone to blood (endogenous exposure) in a large epidemiologic population.
Study subjects were 776 participants in the Normative Aging Study. The subjects had their tibia lead, patella lead, blood lead, and/or urinary N-telopeptide (NTx) levels measured 1-4 times from 1991 to 2002. Regression models were estimated to quantify the association between tibia and patella lead and blood lead. We studied nonlinearity of the association, and explored possible factors that may modify it, including age and NTx levels.
Results and conclusions
There is significant association between bone lead and blood lead, and the association is non-linear. The non-linear associations between blood lead and bone lead are not significantly modified by age and NTx.
The identification of susceptible periods to Pb-induced decrements in childhood cognitive abilities remains elusive.
To draw inferences about windows of susceptibility using the pattern of associations between serial childhood blood lead (BPb) concentrations and children’s cognitive abilities at 4 years of age among 1035 mother–child pairs enrolled in 4 prospective birth cohorts from Mexico City.
Multiple longitudinally collected BPb measurements were obtained from children (1, 2, 3, and 4 years) between 1994 and 2007. Child cognitive abilities were assessed at 4 years using the general cognitive index (GCI) of the McCarthy Scales of Children’s Abilities. We used multivariable linear regression to estimate the change in cognitive abilities at 4 years of age with a 10 μg/dL increase in childhood BPb concentrations adjusting for maternal IQ, education, marital status, child sex, breastfeeding duration, and cohort.
In separate models for each BPb measurement, 2 year BPb concentrations were most strongly associated with reduced GCI scores at 4 years after adjusting for confounders (β: −3.8; 95% confidence interval CI: −6.3, −1.4). Mutual adjustment for other BPb concentrations in a single model resulted in larger, but less precise estimate between 2 year BPb concentrations and GCI scores at 4 years of age (β: −7.1; 95% CI: −12, −2.0). The association between 2 year BPb and GCI was not heterogeneous (p = 0.89), but some BPb and GCI associations varied in magnitude and direction across the cohorts. Additional adjustment for child hemoglobin, birth weight, gestational age, gestational BPb concentrations, or test examiner did not change the pattern of associations.
Higher BPb concentrations at 2 years of age were most predictive of decreased cognitive abilities among these Mexico City children; however, the observed pattern may be due to exposure, outcome, or cohort related factors. These results may help developing countries more efficiently implement childhood Pb prevention strategies.
Lead; Children; Epidemiology; Cognitive abilities; Windows of development
To evaluate forced expiratory volume in 1 second (FEV1, a measure of overall lung function), long-term average FEV1, and rate of decline in FEV1 in relation to cognition and cognitive decline in older men.
Prospective observational study.
Eight hundred sixty-four older men from the Normative Aging Study.
Starting in 1984, participants underwent triennial clinical evaluations. Lung function assessments provided estimates of FEV1. Cognitive assessments entailing tests of several cognitive abilities began in 1993. FEV1 measured approximately 12 years before baseline cognitive testing, average FEV1 over the 12-year period, and rate of change in FEV1 were all evaluated in relation to baseline and change in performance on the cognitive tests.
In multivariable-adjusted analyses, associations between FEV1 and baseline cognitive scores were mixed, although average FEV1 predicted significantly better performance on tests of visuospatial ability (P =.04) and general cognition (P =.03). Higher FEV1 was more consistently associated with slower cognitive decline, but only the association between historical FEV1 and attention was significant (difference per standard deviation in FEV1 = 0.056, P =.05). Rate of FEV1 decline was not consistently associated with cognitive function or decline. Findings were generally similar or stronger in men who had never smoked. To account for potential bias due to selective attrition, inverse probability of censoring weights were applied to the cognitive decline analyses, yielding slightly larger estimates; the inadequate prognostic power of the censoring models limited this approach.
Overall, the data provide limited evidence of an inverse association between FEV1 and cognitive aging.
lung function; cognition; cognitive decline; epidemiology; aging
Limited epidemiologic data are available concerning the cardiovascular effects of cadmium exposure, although recent studies suggest associations with myocardial infarction and peripheral arterial disease. We examined the associations of cadmium exposure with cardiovascular disease in nationally representative general Korean adults.
We used cross-sectional data on blood cadmium and self-reported diagnoses of ischemic heart disease (IHD), stroke, and hypertension in a sub-sample of 1908 adults, aged 20 years and older, who participated in the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). We used survey logistic regression models accounting for the complex sampling design to estimate the odds ratios (OR), adjusting for age, education, income, alcohol, smoking, body mass index, waist circumference, family history of hypertension, blood pressure, and blood lead.
The geometric mean of blood cadmium was 1.53 μg/L. After adjusting for potential confounders, an interquartile range (IQR) increase in blood cadmium (0.91 μg/L) was found to be associated with an increased risk for IHD (OR 2.1, 95% confidence interval (CI) 1.3–3.4). An IQR increase in blood cadmium was found to be associated with an elevated risk for hypertension only among men (OR 1.4, 95% CI 1.1–1.8) but not among women. No association was observed with stroke in both genders.
These findings suggest that cadmium in blood may be associated with an increased risk for IHD and hypertension in the general Korean adult population.
Blood cadmium; Cardiovascular disease; Ischemic heart disease; Hypertension; KNHANES
To examine longitudinal association of prenatal, infancy, and early childhood lead exposure during sensitive periods with height and BMI.
The 773 participants were recruited between 1994 and 2005 in Mexico City. We constructed lead exposure history categories for prenatal (maternal patella lead), infancy and childhood periods (mean child blood lead between birth to 24 months and 30 to 48 months, respectively). Linear regression models were used to study lead exposure history with height and BMI at 48 months.
Children with blood lead levels higher than the median during infancy attained a mean height at 48 months that was significantly shorter (−0.84 cm, 95% CI= −1.42 to −0.25) than children with levels lower than the median. Prenatal lead exposure was not associated with height at 48 months. Results for attained BMI were in general in the same direction as for height.
Our study suggests an effect of early life lead exposure on height attainment at 48 months with an exposure window of greatest sensitivity occurring in infancy.
To characterize the relation between an exposure and a continuous outcome, the sampling of subjects can be done much as it is in a case-control study, such that the sample is enriched with subjects who are especially informative. In an outcome dependent sampling (ODS) design, observations made on a judiciously chosen subset of the base population can provide nearly the same statistical efficiency as observing the entire base population. Reaping the benefits of such sampling, however, requires use of an analysis that accounts for the ODS design. In this report, the authors examined the statistical efficiency of a plain random sample analyzed with standard methods, compared with that of data collected with an ODS design and analyzed by either of two appropriate methods. In addition, three real datasets were analyzed using an ODS approach. The results demonstrate the improved statistical efficiency obtained by using an ODS approach and its applicability in a wide range of settings. An ODS design, coupled with an appropriate analysis, can offer a cost-efficient approach to studying the determinants of a continuous outcome.
biased sampling; continuous outcome; empirical likelihood; epidemiologic methods; epidemiologic research design; semiparametric
We evaluated the modifying influence of a δ-aminolevulinic acid dehydratase (ALAD) polymorphism on the relation between lead burden and cognition among older men.
Information on ALAD genotype, lead measurements, potential confounders, and cognitive testing was collected from 982 participants. For each cognitive test and lead biomarker, we fit separate multiple linear regression models which included an interaction term for ALAD genotype and the lead biomarker, and adjusted for potential confounders.
With higher levels of tibia lead, ALAD 1-2/2-2 carriers exhibited worse performance on a spatial copying test in comparison with ALAD 1-1 carriers (pinteraction=0.03). However, there was no consistent pattern of an ALAD genotype-lead interaction for the other tests.
The results provide some evidence that ALAD genotype modifies the relation between lead burden and cognition among older men with low lead burden, particularly for cognitive domains sensitive to the effects of cumulative lead burden.
blood; bone and blood; lead; environmental; polymorphism; genetic; cognition; neuropsychological tests
Evidence supports a role for epigenetic mechanisms in the pathogenesis of late-onset Alzheimer’s disease (LOAD), but little has been done on a genome-wide scale to identify potential sites involved in disease. This study investigates human postmortem frontal cortex genome-wide DNA methylation profiles between 12 LOAD and 12 cognitively normal age- and gender-matched subjects. Quantitative DNA methylation is determined at 27,578 CpG sites spanning 14,475 genes via the Illumina Infinium HumanMethylation27 BeadArray. Data are analyzed using parallel linear models adjusting for age and gender with empirical Bayes standard error methods. Gene-specific technical and functional validation is performed on an additional 13 matched pair samples, encompassing a wider age range. Analysis reveals 948 CpG sites representing 918 unique genes as potentially associated with LOAD disease status pending confirmation in additional study populations. Across these 948 sites the subtle mean methylation difference between cases and controls is 2.9%. The CpG site with a minimum false discovery rate located in the promoter of the gene Transmembrane Protein 59 (TMEM59) is 7.3% hypomethylated in cases. Methylation at this site is functionally associated with tissue RNA and protein levels of the TMEM59 gene product. The TMEM59 gene identified from our discovery approach was recently implicated in amyloid-β protein precursor post-translational processing, supporting a role for epigenetic change in LOAD pathology. This study demonstrates widespread, modest discordant DNA methylation in LOAD-diseased tissue independent from DNA methylation changes with age. Identification of epigenetic biomarkers of LOAD risk may allow for the development of novel diagnostic and therapeutic targets.
DNA methylation; epigenetics; late onset Alzheimer’s disease; prefrontal cortex
Thyroid hormones are vital to a host of human physiological functions in both children and adults. Exposures to chemicals, including chlorpyrifos, have been found to modify thyroid signaling at environmentally relevant levels in animal studies. The aim of this study was to examine circulating T4 and TSH levels in relation to urinary concentrations of 3, 5, 6-trichloro-2-pyridinol (TCPY), a metabolite of the organophosphorus insecticides chlorpyrifos and chlorpyrifos-methyl, using data from individuals 12 years and older from the U.S. National Health and Nutrition Examination Surveys (NHANES). NHANES datasets from 1999–2000 and 2001–2002 were combined, and individuals with thyroid disease, those taking thyroid medications, and pregnant women were excluded (N=3249). Multivariable linear regression models for relationships between log-transformed urinary TCPY and serum total T4 or log (TSH) were constructed adjusting for important covariates. Models were stratified by sex and a categorical age variable (12–18, 18–40, 40–60, and >60 years). In male participants, an interquartile range (IQR) increase in urinary TCPY was associated with statistically significant increases in serum T4 of 3.8% (95th CI 0.75 to 7.0)among those 12–18 years of age and 3.5% (95th CI 0.13 to 7.0) in the 18–40 year age group., relative to median T4 levels using unweighted models. An IQR increase in TCPY was also associated with decreases in TSH of 10.7% (−18.7–2.05) among men 18–40 years old and 20.0% (95th CI −28.9 to −9.86) among men >60 years old. Conversely, urinary TCPY was positively associated with TSH in females >60 years of age. Further research to confirm these findings, elucidate mechanisms of action, and explore the clinical and public health significance of such alterations in thyroid hormones is needed.
Biomarker; Endocrine Disruption; Exposure; Pesticides; Human
Several lines of evidence indicate that the etiology of late-onset Alzheimer’s disease (LOAD) is complex, with significant contributions from both genes and environmental factors. Recent research suggests the importance of epigenetic mechanisms in defining the relationship between environmental exposures and LOAD. In epidemiologic studies of adults, cumulative lifetime lead (Pb) exposure has been associated with accelerated declines in cognition. In addition, research in animal models suggests a causal association between Pb exposure during early life, epigenetics, and LOAD. There are multiple challenges to human epidemiologic research evaluating the relationship between epigenetics, LOAD, and Pb exposure. Epidemiologic studies are not well-suited to accommodate the long latency period between exposures during early life and onset of Alzheimer’s disease. There is also a lack of validated circulating epigenetics biomarkers and retrospective biomarkers of Pb exposure. Members of our research group have shown bone Pb is an accurate measurement of historical Pb exposure in adults, offering an avenue for future epidemiologic studies. However, this would not address the risk of LOAD attributable to early-life Pb exposures. Future studies that use a cohort design to measure both Pb exposure and validated epigenetic biomarkers of LOAD will be useful to clarify this important relationship.
DNA methylation; epigenetics; epidemiology; Late-onset Alzheimer’s disease; lead exposure; Pb
Background: Blacks have higher hypertension rates than whites, but the reasons for these disparities are unknown. Differential vulnerability, through which stress alters vulnerability to the effects of environmental hazards, is an emergent notion in environmental health that may contribute to these disparities.
Objectives: We examined whether blacks and whites exhibit different associations between blood lead (BPb) and blood pressure (BP) and whether depressive symptoms may play a role.
Methods: Using the National Health and Nutrition Examination Survey 2005–2008, we regressed BP on the three-way interaction among race/ethnicity, BPb, and depressive symptoms in blacks and whites ≥ 20 years of age.
Results: Blacks but not whites showed a positive association between BPb and systolic blood pressure (SBP). The disparity in this association between blacks and whites appeared to be specific to the high depressive symptoms group. In the low depressive symptoms group, there was no significant black–white disparity (βinteraction = 0.9 mmHg; 95% CI: –0.9, 2.7). However, of those with high depressive symptoms, blacks and whites had 5.6 mmHg (95% CI: 2.0, 9.2) and 1.2 mmHg (95% CI: –0.5, 2.9) increases in SBP, respectively, in association with each doubling of BPb (βinteraction = 4.4 mmHg; 95% CI: 0.5, 8.3). The pattern of results was similar for diastolic blood pressure.
Conclusions: Our results suggest that depressive symptoms may contribute to the black–white disparity in the association between BPb and BP. Depressive symptoms may result, in part, from psychosocial stress. Our results support the notion that stress increases vulnerability to the health effects of environmental hazards and suggest that stress-related vulnerability may be an important determinant of racial/ethnic health disparities.
African Americans; depressive symptoms; health status disparities; hypertension; lead; psychosocial stress
Paralleling the rapid growth in computers and internet connections, adolescent internet addiction (AIA) is becoming an increasingly serious problem, especially in developing countries. This study aims to explore the prevalence of AIA and associated symptoms in a large population-based sample in Shanghai and identify potential predictors related to personal characteristics.
In 2007, 5,122 adolescents were randomly chosen from 16 high schools of different school types (junior, senior key, senior ordinary and senior vocational) in Shanghai with stratified-random sampling. Each student completed a self-administered and anonymous questionnaire that included DRM 52 Scale of Internet-use. The DRM 52 Scale was adapted for use in Shanghai from Young’s Internet Addiction Scale and contained 7 subscales related to psychological symptoms of AIA. Multiple linear regression and logistic regression were both used to analyze the data.
Of the 5,122 students, 449 (8.8%) were identified as internet addicts. Although adolescents who had bad (vs. good) academic achievement had lower levels of internet-use (p < 0.0001), they were more likely to develop AIA (odds ratio 4.79, 95% CI: 2.51-9.73, p < 0.0001) and have psychological symptoms in 6 of the 7 subscales (not in Time-consuming subscale). The likelihood of AIA was higher among those adolescents who were male, senior high school students, or had monthly spending >100 RMB (all p-values <0.05). Adolescents tended to develop AIA and show symptoms in all subscales when they spent more hours online weekly (however, more internet addicts overused internet on weekends than on weekdays, p < 0.0001) or when they used the internet mainly for playing games or real-time chatting.
This study provides evidence that adolescent personal factors play key roles in inducing AIA. Adolescents having aforementioned personal characteristics and online behaviors are at high-risk of developing AIA that may compound different psychological symptoms associated with AIA. Spending excessive time online is not in itself a defining symptom of AIA. More attention is needed on adolescent excessive weekend internet-use in prevention of potential internet addicts.
Adolescent; Internet addiction; Risk factors; China
Pessimism, a general tendency toward negative expectancies, is a risk factor for depression and also heart disease, stroke, and reduced cancer survival. There is evidence that individuals with higher lead exposure have poorer health. However, low socioeconomic status (SES) is linked with higher lead levels and greater pessimism, and it is unclear whether lead influences psychological functioning independently of other social factors. The authors considered interrelations among childhood and adult SES, lead levels, and psychological functioning in data collected on 412 Boston area men between 1991 and 2002 in a subgroup of the VA Normative Aging Study. Pessimism was measured by using the Life Orientation Test. Cumulative (tibia) lead was measured by x-ray fluorescence. Structural equation modeling was used to quantify the relations as mediated by childhood and adult SES, controlling for age, health behaviors, and health status. An interquartile range increase in lead quartile was associated with a 0.37 increase in pessimism score (P < 0.05). Low childhood and adult SES were related to higher tibia lead levels, and both were also independently associated with higher pessimism. Lead maintained an independent association with pessimism even after childhood and adult SES were considered. Results demonstrate an interrelated role of lead burden and SES over the life course in relation to psychological functioning in older age.
depression; lead; metals; orientation; psychology; socioeconomic factors
Background: 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.
Objectives: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
cadmium; epidemiology; hearing; lead; NHANES
To investigate the effects of pre- and postnatal lead exposure and polymorphisms in dopamine metabolism genes on neurocognitive development of Mexican children at 24 (n=220) and 48 months (n=186) of age.
We genotyped the dopamine transporter gene (DAT1; SLC6A3) variable nucleotide tandem repeat, and the dopamine receptor D2 (DRD2) Taq 1A single nucleotide polymorphism. Children were assessed at 24 mo with Bayley Scales of Infant Development (MDI, PDI) and at 48 mo with McCarthy Scales of Children’s Abilities.
Lead concentration (BLL) in umbilical cord was 6.6±3.3 μg/dL (measured in 1995-96), 8.1±4.4 μg/dL at 24, and 8.1±3.6 μg/dL at 48 months. Cord BLL was negatively associated with MDI (p<0.01) and PDI (p<0.1) but not McCarthy scores. The 48- but not 24-month BLL was negatively associated with children’s scores. Children with DRD2 TT genotype (variant) scored higher than those with CC genotype (wild type) on MDI and McCarthy memory scale. Neither polymorphism modified the relationship between BLL (either pre or post-natal) and neurocognitive development.
Lead exposure was adversely, whereas the DRD2 Taq 1A TT variant was positively associated with neurocognitive measures. We found no evidence of gene-environment interactions on developmental outcomes in early childhood.
Cord blood lead; postnatal lead exposure; DAT1; DRD2; gene polymorphisms; Mexico; child development
Lead exposure poses a major environmental hazard in India, but little information is available on the impact of lead exposure on neurobehavioral development in Indian children. We hypothesize that higher blood lead levels are associated with poorer visual-motor, visual-spatial and fine motor functioning among children. We conducted a cross-sectional study of 814 school children, aged 3–7 years. Lead in whole blood was measured using the LeadCare Analyzer. The Wide Range of Visual Motor Abilities Test (WRAVMA) was administered to each child by trained examiners. The mean blood lead level was 11.4 ± 5.3 μg//dL. In multivariate analyses adjusting for mother’s education level, fathers education level, average monthly income, hemoglobin and sex, WRAVMA scores were inversely related to blood lead level. An increase of 10 μg/dL was associated with a decrease of 2.6 points (95% CI: −4.5 to −0.7, P=0.006) in the Visual Motor Composite score and a decrease of 2.9 points (95% CI: −5.1 to −0.7, P=0.011) in the Drawing subtest. Exploration of the shape of the dose-effect relationships using spline functions indicated some non-linearities, with the steepest declines in visual-motor skills occurring at higher blood lead levels. Among urban Indian children, higher blood lead levels are associated with decreased visual-motor abilities, particularly visual-motor integration.
Lead levels; visual motor abilities; children
Bone lead is a cumulative measure of lead exposure that can also be remobilized. We examined repeated measures of bone lead over 11 years to characterize long-term changes and identify predictors of tibia and patella lead stores in an elderly male population.
Lead was measured every 3–5 years by k-x-ray fluorescence and mixed-effect models with random effects were used to evaluate change over time.
554 participants provided up to 4 bone lead measurements. Final models predicted a −1.4% annual decline (95%CI: −2.2,−0.7) for tibia lead and piecewise linear model for patella with an initial decline of 5.1% per year (95%CI: −6.2,−3.9) during the first 4.6 years but no significant change thereafter (−0.4% (95% CI: −2.4, 1.7)).
These results suggest that bone lead half-life may be longer than previously reported.
Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation.
Objective: We assessed whether bone lead—a biomarker of cumulative lead exposure—is associated with depression and anxiety symptoms among middle-age and elderly women.
Methods: Participants were 617 Nurses’ Health Study participants with K-shell X-ray fluorescence bone lead measures and who had completed at last one Mental Health Index 5-item scale (MHI-5) and the phobic anxiety scale of the Crown-Crisp Index (CCI) assessment at mean ± SD age of 59 ± 9 years (range, 41–83 years). With exposure expressed as tertiles of bone lead, we analyzed MHI-5 scores as a continuous variable using linear regression and estimated the odds ratio (OR) of a CCI score ≥ 4 using generalized estimating equations.
Results: There were no significant associations between lead and either outcome in the full sample, but associations were found among premenopausal women and women who consistently took hormone replacement therapy (HRT) between menopause and bone lead measurement (n = 142). Compared with women in the lowest tertile of tibia lead, those in the highest scored 7.78 points worse [95% confidence interval (CI): –11.73, –3.83] on the MHI-5 (p-trend = 0.0001). The corresponding OR for CCI ≥ 4 was 2.79 (95% CI: 1.02, 7.59; p-trend = 0.05). No consistent associations were found with patella lead.
Conclusions: These results provide support for an association of low-level cumulative lead exposure with increased depressive and phobic anxiety symptoms among older women who are premenopausal or who consistently take postmenopausal HRT.
anxiety; depression; environmental exposure; epidemiology; lead; longitudinal study
Background: Lead exposure has been associated with cardiovascular disease (CVD) in animal and human studies. However, the mechanisms of action have not been fully elucidated. We therefore examined the relationship between lead and multiple biomarkers of CVD.
Methods: Participants were older men from the Normative Aging Study without preexisting coronary heart disease, diabetes, or active infection at baseline (n = 426). Serum biomarkers included lipid profile [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides] and inflammatory markers [C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor receptor-2 (TNF-R2)]. We measured lead in blood and in bone by K-shell X-ray fluorescence. In this sample, 194 men (44.3%) had two or more repeated measures, resulting in 636 observations for analysis. We conducted analyses using mixed effects models with random subject intercepts.
Results: Lead levels were associated with several CVD biomarkers, including levels of TNF-R2 and lipid markers. Specifically, in multivariable models, a 50% increase in blood lead level was associated with 26% increased odds of high TNF-R2 levels (> 5.52 ng/mL; odds ratio = 1.26; 95% confidence interval: 1.09, 1.45). There were positive associations of blood lead level with total cholesterol and HDL levels, and these associations were more evident when modeled as continuous outcomes than when categorized using clinically relevant cut points. In addition, longitudinal analyses indicated a significant increase in TNF-R2 levels over time to be associated with high blood lead level at the preceding visit.
Conclusions: Blood lead level may be related with CVD in healthy older men through its association with TNF-R2 levels. In addition, the magnitude of the association of blood lead level with TNF-R2 level increased with age in the study population.
aging; biomarkers; cardiovascular; cholesterol; inflammation; lead; metals
Background: Lead exposure in adults is associated with hypertension. Altered prenatal nutrition is associated with subsequent risks of adult hypertension, but little is known about whether prenatal exposure to toxicants, such as lead, may also confer such risks.
Objectives: We investigated the relationship of prenatal lead exposure and blood pressure (BP) in 7- to 15-year-old boys and girls.
Methods: We evaluated 457 mother–child pairs, originally recruited for an environmental birth cohort study between 1994 and 2003 in Mexico City, at a follow-up visit in 2008–2010. Prenatal lead exposure was assessed by measurement of maternal tibia and patella lead using in vivo K-shell X-ray fluorescence and cord blood lead using atomic absorption spectrometry. BP was measured by mercury sphygmomanometer with appropriate-size cuffs.
Results: Adjusting for relevant covariates, maternal tibia lead was significantly associated with increases in systolic BP (SBP) and diastolic BP (DBP) in girls but not in boys (p-interaction with sex = 0.025 and 0.007 for SBP and DBP, respectively). Among girls, an interquartile range increase in tibia lead (13 μg/g) was associated with 2.11-mmHg [95% confidence interval (CI): 0.69, 3.52] and 1.60-mmHg (95% CI: 0.28, 2.91) increases in SBP and DBP, respectively. Neither patella nor cord lead was associated with child BP.
Conclusions: Maternal tibia lead, which reflects cumulative environmental lead exposure and a source of exposure to the fetus, is a predisposing factor to higher BP in girls but not boys. Sex-specific adaptive responses to lead toxicity during early-life development may explain these differences.
blood pressure; children; lead; prenatal exposure; sex
In-vivo measurement of bone lead by means of K-X ray fluorescence (KXRF) is the preferred biological marker of chronic exposure to lead. Unfortunately, considerable measurement error associated with KXRF estimations can introduce bias in estimates of the effect of bone lead when this variable is included as the exposure in a regression model. Estimates of uncertainty reported by the KXRF instrument reflect the variance of the measurement error and, although they can be used to correct the measurement error bias, they are seldom used in epidemiological statistical analyses. Errors-in-variables regression (EIV) allows for correction of bias caused by measurement error in predictor variables, based on the knowledge of the reliability of such variables. The authors propose a way to obtain reliability coefficients for bone lead measurements from uncertainty data reported by the KXRF instrument and compare, by use of Monte Carlo simulations, results obtained using EIV regression models versus those obtained by the standard procedures. Results of the simulations show that Ordinary Least Square (OLS) regression models provide severely biased estimates of effect, and that EIV provides nearly unbiased estimates. Although EIV effect estimates are more imprecise, their mean squared error is much smaller than that of OLS estimates. In conclusion, EIV is a better alternative than OLS to estimate the effect of bone lead when measured by KXRF.
Lead; KXRF; measurement error; errors-in-variables model; simulations
Background: 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.
Objectives: We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP.
Methods: 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.
Results: 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.
Conclusions: 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.
arsenic; blood pressure; cadmium; epidemiology; lead; manganese; mercury; metals