Biomarker Of Long-term Exposure Research Articles

Circulating lung-cancer-related non-coding RNAs are associated with occupational exposure to hexavalent chromium – A cross-sectional study within the SafeChrom project

BackgroundHexavalent chromium (Cr(Ⅵ)) is classified as a group 1 human carcinogen and increases the risk of lung cancer. Non-coding RNAs (ncRNAs) have key regulatory roles in lung cancer, but less is known about their relation to Cr(Ⅵ) exposure. ObjectivesWe aimed to 1) measure the expression of lung cancer-related circulating ncRNAs in exposed workers and controls; 2) assess associations between ncRNAs expression and Cr concentrations in red blood cells (RBC) and urine; and 3) evaluate correlations between the ncRNAs. MethodsThe study included 111 Cr(VI) exposed workers and 72 controls recruited from the SafeChrom project. Cr concentrations were measured in RBC (biomarker of long-term exposure) and urine (biomarker of short-term exposure) samples. Long ncRNA (lncRNA) and microRNA (miRNA) were extracted from plasma followed by deoxyribonuclease treatment, complementary DNA synthesis, and quantitative real‐time polymerase chain reaction using target-specific assays for three lncRNAs (H19, MALAT1, NORAD), and four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a). ResultsExpression levels of lncRNAs MALAT1 and NORAD, and all four miRNAs, were significantly lower in Cr(VI) exposed workers compared with controls, and correlated significantly with RBC-Cr concentrations (rS = −0.16 to −0.38). H19 was non-significantly increased in exposed workers but significantly correlated with miR-142-3p (rS = −0.33) and miR-15b-5p (rS = −0.30), and NORAD was significantly positively correlated with all four miRNAs (rS = 0.17 to 0.46). In multivariate regression models adjusting for confounders, expressions of lncRNAs MALAT1 and NORAD and all miRNAs were still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr concentrations. ConclusionsCr(VI) exposure was inversely and in a dose–response manner associated with the expression of circulating non-coding RNA, which suggests ncRNAs as potential biomarkers for Cr(VI)-induced toxicity. Correlations between miRNAs and lncRNAs suggest that they participate in the same lncRNA-miRNA-messenger RNA regulatory axes, which may play important roles in Cr(VI) carcinogenesis.

Biomarkers of arsenic exposure in biogeochemical provinces

Introduction. One of the direct methods of assessing the impact of contaminants on public health is the use of biological markers that allow determining the presence of a substance or its metabolite in human biological tissues and the dose received from all sources of this substance. 
 The purpose of this study was to determine the dependence of arsenic content in biological samples (hair) 
 of exposed residents on the level of its content in drinking water and to substantiate the effectiveness of the use of this biomarker in the conditions of a hydrogeochemical province in the Republic of Dagestan.
 Material and methods. During this research the arsenic content in the hair of the exposed residents was measured with further comparison of the data obtained with its content in drinking groundwater. To determine the arsenic content in the hair of the exposed residents, an atomic absorption method was used with preliminary preparation of biosubstrate samples. Socio-demographic data were obtained from a questionnaire. Statistical data processing was carried out using Microsoft Excel.
 Results. In the course of this study, a correlation was revealed between the arsenic content in the hair of the exposed residents and its content in the drinking water consumed, and a direct proportional relationship between these values was also revealed. Thus, with an increase in the concentration of arsenic in water by 
 0.1 mg/l, the arsenic content in the hair increases by 0.14 mkg/g. So, using of the hair of exposed residents as a biomarker of long-term exposure is recommended to small doses of arsenic in a biogeochemical province.
 limitation of the study is the small sample size. However, this does not prevent the assessment of the effectiveness of using hair as a biomarker of arsenic exposure and preliminary conclusions for subsequent in-depth analysis of biomonitoring in the conditions of biogeochemical provinces.
 Conclusion. As a rule, the content of natural toxic elements is characterized by trace amounts in the conditions of biogeochemical provinces. Biomonitoring will reveal the level of stress on the body and timely apply preventive methods before the clinical signs of intoxication are revealed.

Abstract 1443: Environmental heavy metal toxicity and mammographic breast density in a Mississippi Delta southern state

Abstract Importance: Increased mammographic density (MD) is a strong independent risk factor for breast carcinoma. Ubiquitous environmental heavy metal (HM) exposure/toxicity appears pro-carcinogenic in several human cancers. However, studies in the current scientific literature have not elucidated specific connections between HM exposure and mammographically detected increases in breast density. Objective: To determine whether increases in heavy metals (ie, chromium, arsenic and cadmium) measured in urine as a biomarker for long-term exposure, associate with increased MD in a female study cohort in Arkansas. Design, Setting, Participants: One hundred thirty-nine participants in the Arkansas Rural Community Health (ARCH) study cohort, recruited through a mobile mammography unit at baseline, were included in this pilot study. Demographic/health history questionnaire data, urine, blood and saliva samples and incident mammograms classified by BI-RADS were ascertained after informed consent. Study protocol was approved by the Institutional Review Board at the University of Arkansas for Medical Sciences (UAMS). Main Outcome and Measures: Urinary chromium, arsenic and cadmium levels were determined using inductively coupled plasma mass spectrometry. The concentrations of HM were adjusted for urinary creatinine and specific gravity and the results categorized into tertiles. Multivariable logistic regression models were used to evaluate the association between HM exposure and MD. Association of both continuous and categorical variables were examined. Confounding variables in the multivariable models including age, race, BMI, age at menarche and smoking history were determined by a priori knowledge and statistical assessment. Results: Odds ratios (OR) and 95% confidence intervals (CI) for the association between each tertile of HM exposure and MD were used for the assessment. For the unadjusted model, increasing ORs for MD were noted with increased levels of both Chromium and Arsenic exposure. Increased ORs for MD were observed with increased levels of Chromium, Arsenic and Cadmium exposure in the multivariable adjusted model. However, none of these associations demonstrated statistical significance in this limited pilot study. Conclusion: Positive associations between HM exposure and MD were noted after adjusting for age, sex, BMI, age at menarche and smoking history in this pilot study. However, the association did not reach statistical significance at α = 0.05. Citation Format: Bobbie Dean Fine, Shelbie Stahr, Lora J. Rogers, Gail A. Runnells, Tung-Chin Chiang, Lihchyun J. Su. Environmental heavy metal toxicity and mammographic breast density in a Mississippi Delta southern state [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1443.

Epigenome-wide Association Study of DNA Methylation and Specific Pesticide Use Among U.S. Farmers

Background: Pesticide exposure is associated with certain cancers and neurologic diseases, but the underlying mechanisms are not fully understood. DNA methylation, an epigenetic modification, may play a role. DNA methylation patterns likely differ by specific pesticide, but no epigenome-wide association studies have evaluated methylation patterns across different pesticides. We conducted epigenome-wide analyses of DNA methylation in relation to several pesticides used among U.S. farmers.Methods: The Agricultural Lung Health Study (ALHS) is a case-control study of asthma, nested within the Agricultural Health Study (AHS). For 1,170 ALHS male farmers, blood DNA methylation was measured with Illumina’s MethylationEPIC array. Participants self-reported pesticide use in the AHS (past use) and ALHS (current use, defined as past 12 months). Pesticides were grouped by chemical class and active ingredients. Using robust linear regression, we analyzed 13 chemical classes and 16 active ingredients with 30+ exposed men. Analyses were adjusted for age, smoking status, packyears, state, asthma status, and estimated cell type proportions.Results: Participants who reported past and current use of pesticide class or active ingredient were compared to those who never reported use. Using family-wise error rate (p<9×10-8) or false discovery rate (p<0.05), we identified differentially methylated C-phosphate-G (CpG) sites for 10 chemical classes and 9 active ingredients. Most differentially methylated CpG sites were unique to each active ingredient. For 5 of the 9 active ingredients, lifetime days of use was available and there was evidence of a dose-response at most differentially methylated CpG sites. Significant CpG sites were enriched for transcription factor motifs. We plan to correlate significant CpG sites with gene expression in external data.Conclusions: We observed differential methylation associated with several chemical classes and active ingredients. These differential methylation patterns could be biomarkers of long-term exposure and may provide additional biological insight into health effects of pesticide exposure.

Cadmium Exposure and Ovarian Reserve in Women Aged 35-49 Years: The Impact on Results From the Creatinine Adjustment Approach Used to Correct for Urinary Dilution.

Cadmium is toxic to the ovaries in animal studies, but its association with diminished ovarian reserve in women is not established. We investigated urinary cadmium, a biomarker of long-term exposure, in relation to diminished ovarian reserve, as indicated by elevated serum follicle-stimulating hormone concentrations (≥10 IU/L), in women aged 35-49 years (unweighted n=1,681). Using data from the Third National Health and Nutrition Examination Survey (1988-1994), we conducted Poisson regression to estimate adjusted relative risks and 95% confidence intervals. Because the best approach to correcting for urinary dilution in spot samples with creatinine remains controversial, we employed 3 approaches: standardization, covariate adjustment, and covariate-adjusted standardization. Our data suggested a modest association with standardization (highest quartile vs. lowest: relative risk (RR) = 1.3, 95% confidence interval (CI): 0.8, 1.9; P for trend=0.06) and covariate-adjusted standardization (highest quartile vs. lowest: RR = 1.3, 95% CI: 0.9, 1.9; P for trend=0.05) and a stronger association with covariate adjustment (highest quartile vs. lowest: RR = 1.8, 95% CI: 1.2, 2.9; P for trend=0.01). The stronger association with covariate adjustment may reflect bias from conditioning on urinary creatinine, a collider in the hypothesized causal pathway. We conclude that cadmium may contribute to ovarian aging in women and that careful consideration of the creatinine adjustment approach is needed to minimize bias.

Peripheral Arterial Disease and Its Association With Arsenic Exposure and Metabolism in the Strong Heart Study.

At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45-74 years in 1989-1991 were reexamined in 1993-1995 and 1997-1999, respectively, for incident PAD defined as either ABI <0.9 or ABI >1.4. A total of 286 and 206 incident PAD cases were identified for ABI <0.9 and ABI >1.4, respectively. The sum of inorganic and methylated urinary arsenic species (∑As) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of ∑As with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI <0.9 and 2.24 (95% CI: 1.01, 4.32) for ABI >1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI >1.4 (hazard ratio=2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate ∑As and increased arsenic methylation were associated with ABI >1.4 but not with ABI <0.9. Further studies are needed to clarify whether diabetes and enhanced arsenic metabolism increase susceptibility to the vasculotoxic effects of arsenic exposure.

Dietary Intake Estimates and Urinary Cadmium Levels in Danish Postmenopausal Women.

BackgroundCadmium is a known carcinogen that can disrupt endocrine signalling. Cigarette smoking and food are the most common routes of non-occupational exposure to cadmium. Cadmium accumulates in the kidney and can be measured in urine, making urine cadmium (U-Cd) a biomarker of long-term exposure. However dietary-cadmium (D-Cd) intake estimates are often used as surrogate indicator of cadmium exposure in non-smoking subjects. It is therefore important to investigate the concordance between D-Cd estimates obtained with Food Frequency Questionnaires and U-Cd.MethodsU-Cd levels were compared with estimated dietary-cadmium (D-Cd) intake in 1764 post-menopausal women from the Danish Diet, Cancer and Health cohort. For each participant, a food frequency questionnaire, and measures of cadmium content in standard recipes were used to judge the daily intake of cadmium, normalized by daily caloric intake. Cadmium was measured by ICP-MS in spot urine sampled at baseline and normalized by urinary creatinine. Information on diet, socio-demographics and smoking were self-reported at baseline.ResultsLinear regressions between U-Cd and D-Cd alone revealed minimal but significant positive correlation in never smokers (R2 = 0.0076, β = 1.5% increase per 1 ng Cd kcal-1, p = 0.0085, n = 782), and negative correlation in current smokers (R2 = 0.0184, β = 7.1% decrease per 1 ng Cd kcal-1 change, p = 0.0006, n = 584). In the full study population, most of the variability in U-Cd was explained by smoking status (R2 = 0.2450, n = 1764). A forward selection model revealed that the strongest predictors of U-Cd were age in never smokers (Δ R2 = 0.04), smoking duration in former smokers (Δ R2 = 0.06) and pack-years in current smokers (Δ R2 = 0.07). Food items that contributed to U-Cd were leafy vegetables and soy-based products, but explained very little of the variance in U-Cd.ConclusionsDietary-Cd intake estimated from food frequency questionnaires correlates only minimally with U-Cd biomarker, and its use as a Cd exposure indicator may be of limited utility in epidemiologic studies.

Assessing human exposure to inorganic arsenic in high-arsenic areas of Latium: a biomonitoring study integrated with indicators of dietary intake.

In Latium (central Italy), arsenic concentrations exceeding the regulatory limit of 10 μg/L for drinking water are present in groundwater from a large area of volcanic origin. At least in part of the area, high arsenic concentrations have been detected also in soil and phytoavailable geogenic arsenic enters the food chain. As a result, local population may be exposed to inorganic arsenic via water and also through consumption of food with higher than background arsenic concentrations. A cross sectional study was conducted to assess inorganic arsenic exposure and metabolism in 269 residents of 27 municipalities in the provinces of Viterbo, Rome and Latina. Total arsenic in toenails and the sum of inorganic arsenic and methylated metabolites in urine, the latter determined by HPLC-ICP-MS, were used as biomarkers of inorganic arsenic exposure. All the subjects involved in the study provided samples of the water(s) used for drinking and cooking as well as detailed information on water use. To get an insight into dietary intake from locally-processed food, inorganic arsenic in bread samples collected in affected municipalities of the three provinces was determined and compared to background levels of samples from reference areas. 30% of the sample used bottled water or resorted to water treatment in order to lower the arsenic content <10 μg/L (Group 1), 51% of the sample drank bottled water and used tap water with an arsenic content exceeding 10 μg/L for cooking only (Group 2), 19% of the sample used tap water with an arsenic content exceeding 10 μg/L for both drinking and cooking (Group 3). Nail arsenic was higher for Group 2 and 3 compared to Group 1, whereas all groups had higher nail arsenic than the reference group. The sum of inorganic arsenic and related metabolites in urine was higher in Group 3 than in the other two groups, and higher in Group 2 compared to Group 1. White bread from the study area showed significantly higher inorganic arsenic levels compared to samples from reference areas. Use of toenail arsenic as biomarker of long-term exposure allowed to retrospectively reconstruct exposure irrespective of recent modifications due to changes in water use. In Group 3, urinary concentration of inorganic arsenic and metabolites exceeded the upper limit of the reference concentration range for the Italian population. Inter-individual variability of the efficiency of arsenic metabolism in the study population was substantial indicating that a subgroup of the population is more susceptible to the toxic effects of inorganic arsenic owing to a lower methylation capability.

Study of N-methylcarbamoylated hemoglobin in blood of being an exposure biomarker of N, N-dimethylformamide

To assess the value of blood N-methylcarbamoylated haemoglobin (NMHb) as a biomarker of N, N-dimethylformamide (DMF) exposure. Seventy-two DMF processing workers in a synthetic leather factory were included in the DMF exposure group, and 12 workers in a food factory without exposure to DMF were included in the control group. Long-time individual sampling in workplace was performed among 45 workers in the exposure group, accompanied by a questionnaire survey. Blood and urine were collected for the determination of urinary N-methylformamide (NMF), urinary creatinine, and blood NMHb. Air DMF and urinary NMF were determined by gas chromatography. NMHb in blood was degraded to 3-methyl-5-isopropylhydantoin by Edman degradation before it could be determined by gas chromatography/mass spectrometry. Air DMF in workplace and NMF in post-shift urine were both correlated with NMHb in blood, and the respective regression equations were LgNMHb (nmol/g globin) = 0.32×LgDMF (mg/m(3))+1.8 (r = 0.60, P < 0.005), and LgNMHb (nmol/g globin) = 0.47×LgNMF (mg/g Cr) + 1.4 (r = 0.56, P < 0.005). NMHb can be used as a biomarker of long-term exposure to DMF.

Investigating the Use of Hair to Assess Polybrominated Diphenyl Ether Exposure Retrospectively

Polybrominated diphenyl ethers (PBDEs) are chemicals that are added to a variety of consumer products as flame-retardants and have been classified as emerging endocrine disruptors. They are persistent and have been detected in humans. Previous studies have suggested that hair is a suitable matrix for examining human exposure to organic pollutants such as PBDEs. It is believed that the majority of exposure is from our indoor environment. The aim of this study was to investigate the changes in PBDE patterns and levels along the hair shaft, by using segmental analysis to retrospectively assess long-term exposure over a 1-year period. Questionnaires and hair samples from 65 women were collected at the Hospital for Sick Children, in Toronto, as part of a larger study. To assess long-term stability, hair samples were separated into 4- and 3-cm segments representing a 1-year period. Hair segments were analyzed for levels of 8 PBDE congeners, BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209 on gas chromatography-mass spectrometry (MS). A Friedman test was used to detect the differences in exposure among segments, and factors such as dietary habits, hair care routine, and site of residence were investigated to determine if they might affect hair levels. A significant increase (P < 0.0001) in total PBDEs was seen among segments moving from proximal (root end) to distal along the hair shaft (median in pg/mg): first (33.3), second (43.0), third (61.6), and fourth (75.5) segments. Significantly lower levels of PBDEs were observed in artificially colored hair samples (P = 0.032), and a significant increase in PBDE levels was observed in women who consumed meat on a daily basis as opposed to weekly consumption (P = 0.040). The increase in PBDEs along the hair shaft suggests that hair PBDEs may be influenced by diet and artificial coloring. More work is needed to validate the use of PBDEs in hair as a biomarker of long-term exposure.

Toenail as a biomarker of heavy metal exposure via drinking water: a systematic review.

Toenail is metabolic end product of the skin, which can provide information about heavy metal accumulation in human cells. Slow growth rates of toenail can represent heavy metal exposure from 2 to 12 months before the clipping. The toenail is a non-invasive biomarker that is easy to collect and store and is stable over time. In this systematic review, the suitability of toenail as a long-term biomarker was reviewed, along with the analysis and validation of toenail and confounders to heavy metal. This systematic review has included 30 articles chosen from a total of 132 articles searched from online electronic databases like Pubmed, Proquest, Science Direct, and SCOPUS. Keywords used in the search included "toenail", "biomarker", "heavy metal", and "drinking water". Heavy metal in toenail can be accurately analyzed using an ICP-MS instrument. The validation of toenail heavy metal concentration data is very crucial; however, the Certified Reference Material (CRM) for toenail is still unavailable. Usually, CRM for hair is used in toenail studies. Confounders that have major effects on heavy metal accumulation in toenail are dietary intake of food and supplement, smoking habit, and overall health condition. This review has identified the advantages and limitations of using toenail as a biomarker for long-term exposure, which can help future researchers design a study on heavy metal exposure using toenail.

Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy.

Aristolochic acid (AA) causes aristolochic acid nephropathy (AAN), first described in women in Belgium accidently prescribed Aristolochia fangchi in a slimming treatment, and also Balkan endemic nephropathy (BEN), through probable dietary contamination with Aristolochia clematitis seeds. Both nephropathies have a high risk of urothelial cancer, with AA being the causative agent. In tissues of AAN and BEN patients, a distinct DNA adduct, 7-(deoxyadenosin-N6-yl)-aristolactam I (dA-AAI), has been detected. DNA adducts can be removed through DNA repair, they can result in mutations through erroneous DNA replication or they can cause cell death. The dA-AAI adduct induces AT to TA transversions in the tumor-suppressor TP53 gene in experimental systems, matching TP53 mutations observed in urothelial tumors from AAN cancer cases. Using thin-layer chromatography 32P-postlabeling and mass spectrometric analysis we report the detection of dA-AAI in renal DNA from 11 Belgian AAN patients over 20 years after exposure to AA had ceased. Our results showed that dA-AAI is an established biomarker of AA exposure, and that this biomarker can be demonstrated to be persistent decades after a distinct AA exposure. Further, the persistence of dA-AAI adducts appears to be a critical determinant for the AA mutational fingerprint frequently found in oncogenes and tumor suppressor genes recently identified by whole genome sequencing of AA-associated urothelial tumors. The potential for exposure to AA worldwide is high; the unprecedented long-term persistence of dA-AAI provides a useful long-term biomarker of exposure and attests to the role of AA in human urothelial malignancy.

Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water.

BackgroundLimited data exist on the contribution of dietary sources of arsenic to an individual’s total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest.MethodsAssociations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations <1 μg/L versus ≥1 μg/L.ResultsAs expected, toenail arsenic concentrations increased with household water arsenic concentrations. Among the foods known to be high in arsenic, no clear relationship between toenail arsenic and rice consumption was detected, but there was a positive association with consumption of dark meat fish, a category that includes tuna steaks, mackerel, salmon, sardines, bluefish, and swordfish. Positive associations between toenail arsenic and consumption of white wine, beer, and Brussels sprouts were also observed; these and most other associations were not modified by exposure via water. However, consumption of two foods cooked in water, beans/lentils and cooked oatmeal, was more strongly related to toenail arsenic among those with arsenic-containing drinking water (≥1 μg/L).ConclusionsThis study suggests that diet can be an important contributor to total arsenic exposure in U.S. populations regardless of arsenic concentrations in drinking water. Thus, dietary exposure to arsenic in the US warrants consideration as a potential health risk.

Resolving the Enigma of the Mesoamerican Nephropathy: A Research Workshop Summary

The First International Research Workshop on Mesoamerican Nephropathy (MeN) met in Costa Rica in November 2012 to discuss how to establish the extent and degree of MeN, examine relevant causal hypotheses, and focus efforts to control or eliminate the disease burden. MeN describes a devastating epidemic of chronic kidney disease of unknown origin predominantly observed among young male sugarcane cutters. The cause of MeN remains uncertain; however, the strongest hypothesis pursued to date is repeated episodes of occupational heat stress and water and solute loss, probably in combination with other potential risk factor(s), such as nonsteroidal anti-inflammatory drug and other nephrotoxic medication use, inorganic arsenic, leptospirosis, or pesticides. At the research workshop, clinical and epidemiologic case definitions were proposed in order to facilitate both public health and research efforts. Recommendations emanating from the workshop included measuring workload, heat, and water and solute loss among workers; quantifying nephrotoxic agents in drinking water and food; using biomarkers of early kidney injury to explore potential causes of MeN; and characterizing social and working conditions together with methods for valid data collection of exposures and personal risk factors. Advantages and disadvantages of different population study designs were detailed. To elucidate the etiology of MeN, multicountry studies with prospective cohort design, preferably integrating an ecosystem health approach, were considered the most promising. In addition, genetic, experimental, and mechanistic methods and designs were addressed, specifically the need for kidney biopsy analysis, studies in animal models, advances in biomarkers, genetic and epigenetic studies, a common registry and repository of biological and demographic data and/or specimens, and other areas of potential chronic kidney disease experimental research. Finally, in order to improve international collaboration on MeN, workshop participants agreed to establish a research consortium to link these Mesoamerican efforts to other efforts worldwide.

Cadmium Exposure and Incident Cardiovascular Disease

Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort. We conducted a prospective cohort study of 3348 American Indian adults 45-74 years of age from Arizona, Oklahoma, and North and South Dakota, who participated in the Strong Heart Study in 1989-1991. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through 31 December 2008. The geometric mean cadmium level in the study population was 0.94 μg/g (95% confidence interval [CI] = 0.92-0.96). We identified 1084 cardiovascular events, including 400 deaths. After adjustment for sociodemographic and cardiovascular risk factors, the hazard ratios (HRs) (comparing the 80th to the 20th percentile of urine cadmium concentrations) was 1.43 for cardiovascular mortality (95% CI = 1.21-1.70) and 1.34 for coronary heart disease mortality (1.10-1.63). The corresponding HRs for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.24 (1.11-1.38), 1.22 (1.08-1.38), 1.75 (1.17-2.59), and 1.39 (1.01-1.94), respectively. The associations were similar in most study subgroups, including never-smokers. Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality and increased incidence of cardiovascular disease. These findings support that cadmium exposure is a cardiovascular risk factor.

Abstract P038: Cadmium Exposure is Prospectively Associated to Cardiovascular Risk in the Strong Heart Study

Introduction: Cadmium is a widespread toxic metal with potential cardiovascular effects, but establishing cadmium as a cardiovascular risk factor has been limited by the lack of data on its association with incident cardiovascular events. Hypothesis: We tested the hypothesis that urine cadmium concentrations would be associated with cardiovascular disease mortality and incidence. Methods: Prospective cohort study of 3,347 American Indian adults 45-74 years old without prevalent cardiovascular disease from Arizona, Oklahoma and North and South Dakota who participated in the Strong Heart Study (SHS) in 1989-91 and had urine cadmium measures available. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through December 30 th 2007. Results: We identified 1,028 cardiovascular events, including 372 deaths. After adjustment for known cardiovascular risk factors, the hazard ratios (95% CI) for cardiovascular and coronary heart disease mortality, comparing the 80 th to the 20 th percentiles of urine cadmium concentrations, were 1.43 (1.21, 1.69) and 1.33 (1.09, 1.62), respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.16 (1.04, 1.29), 1.11 (0.98, 1.27), 1.50 (1.01, 2.22) and 1.22 (1.01, 1.47), respectively. The associations were similar in different study subgroups, including never-smokers. The figure shows increasing dose-response relations between urine cadmium concentrations and all cardiovascular disease mortality and incidence endpoints except for incident stroke. Conclusions: Urine cadmium, a biomarker of long-term exposure, was positively and consistently associated with cardiovascular disease mortality and incidence, overall and across subgroups. These findings support that cadmium exposure is a cardiovascular risk factor irrespective of the source of exposure. Efforts to reduce cadmium exposure in the population are needed.

Measurement of cortisol in human Hair as a biomarker of systemic exposure

Current methods for measuring long-term endogenous production of cortisol can be challenging due to the need to take multiple urine, saliva or serum samples. Hair grows approximately 1 centimeter per month, and hair analysis accurately reflects exposure to drug abuse and environmental toxins. Here we describe a new assay for measurement of cortisol in hair, and determined a reference range for non-obese subjects. For measurement of cortisol in hair we modified an immunoassay originally developed for measuring cortisol in saliva. We compared hair samples obtained from various parts of the head, and assessed the effect of hair dying. We analyzed hair samples from non-obese subjects, in whom we also obtained urine, saliva and blood samples for cortisol measurements. The mean extraction recovery for hair cortisol standards of 100 ng/ml, 50 ng/ml and 2 ng/ml (n=6) was 87.9%, 88.9% and 87.4%, respectively. Hair cortisol levels were not affected by hair color or by dying hair samples after they were obtained. Cortisol levels were decreased in hair that was artificially colored before taking the sample. The coefficient of variation was high for cortisol levels in hair from different sections of the head (30.5 %), but was smaller when comparing between hair samples obtained from the vertex posterior (15.6%). The reference range for cortisol in hair was 17.7-153.2 pg/mg of hair (median 46.1 pg/mg). Hair cortisol levels correlated significantly with cortisol in 24-hour urine (r=0.33; P=0.041). The correlation of hair cortisol with 24-hour urine cortisol supports its relevance as biomarker for long-term exposure.