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Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study.

ABSTRACT: Long-term exposure to high levels of arsenic is associated with increased risk for cardiovascular disease, whereas risk from long-term exposure to low to moderate arsenic levels (< 100?g/L in drinking water) is unclear.To evaluate the association between long-term exposure to low to moderate arsenic levels and incident cardiovascular disease.Prospective cohort study.The Strong Heart Study baseline visit between 1989 and 1991, with follow-up through 2008.3575 American Indian men and women aged 45 to 74 years living in Arizona, Oklahoma, and North and South Dakota.The sum of inorganic and methylated arsenic species in urine at baseline was used as a biomarker of long-term arsenic exposure. Outcomes were incident fatal and nonfatal cardiovascular disease.A total of 1184 participants developed fatal and nonfatal cardiovascular disease. When the highest and lowest quartiles of arsenic concentrations (> 15.7 vs. < 5.8 ?g/g creatinine) were compared,the hazard ratios for cardiovascular disease, coronary heart disease, and stroke mortality after adjustment for sociodemographic factors, smoking, body mass index, and lipid levels were 1.65 (95%CI, 1.20 to 2.27; P for trend < 0.001), 1.71 (CI, 1.19 to 2.44; P for trend < 0.001), and 3.03 (CI, 1.08 to 8.50; P for trend = 0.061),respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, and stroke were 1.32 (CI,1.09 to 1.59; P for trend = 0.002), 1.30 (CI, 1.04 to 1.62; P for trend = 0.006), and 1.47 (CI, 0.97 to 2.21; P for trend = 0.032).These associations varied by study region and were attenuated after further adjustment for diabetes, hypertension, and kidney disease measures.Direct measurement of individual arsenic levels in drinking water was unavailable.Long-term exposure to low to moderate arsenic levels was associated with cardiovascular disease incidence and mortality.

SUBMITTER: Moon KA

PROVIDER: S-EPMC4157936 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study.

Moon Katherine A KA Guallar Eliseo E Umans Jason G JG Devereux Richard B RB Best Lyle G LG Francesconi Kevin A KA Goessler Walter W Pollak Jonathan J Silbergeld Ellen K EK Howard Barbara V BV Navas-Acien Ana A

Annals of internal medicine 20131101 10

<h4>Background</h4>Long-term exposure to high levels of arsenic is associated with increased risk for cardiovascular disease, whereas risk from long-term exposure to low to moderate arsenic levels (< 100μg/L in drinking water) is unclear.<h4>Objective</h4>To evaluate the association between long-term exposure to low to moderate arsenic levels and incident cardiovascular disease.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>The Strong Heart Study baseline visit between 1989 and 1991, wi ...[more]

PMID: 24061511

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Project description:BACKGROUND:High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity. OBJECTIVE:We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance. METHODS:We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (?As). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up. RESULTS:Median ?As, iAs%, MMA%, and DMA% was 4.4 ?g/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ?As was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ?As was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants. CONCLUSIONS:Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.

Project description:ObjectiveTo evaluate the association between arsenic exposure and mortality from cardiovascular disease and to assess whether cigarette smoking influences the association.DesignProspective cohort study with arsenic exposure measured in drinking water from wells and urine.SettingGeneral population in Araihazar, Bangladesh.Participants11,746 men and women who provided urine samples in 2000 and were followed up for an average of 6.6 years.Main outcome measureDeath from cardiovascular disease.Results198 people died from diseases of circulatory system, accounting for 43% of total mortality in the population. The mortality rate for cardiovascular disease was 214.3 per 100,000 person years in people drinking water containing <12.0 µg/L arsenic, compared with 271.1 per 100,000 person years in people drinking water with ≥ 12.0 µg/L arsenic. There was a dose-response relation between exposure to arsenic in well water assessed at baseline and mortality from ischaemic heart disease and other heart disease; the hazard ratios in increasing quarters of arsenic concentration in well water (0.1-12.0, 12.1-62.0, 62.1-148.0, and 148.1-864.0 µg/L) were 1.00 (reference), 1.22 (0.65 to 2.32), 1.35 (0.71 to 2.57), and 1.92 (1.07 to 3.43) (P = 0.0019 for trend), respectively, after adjustment for potential confounders including age, sex, smoking status, educational attainment, body mass index (BMI), and changes in urinary arsenic concentration since baseline. Similar associations were observed when baseline total urinary arsenic was used as the exposure variable and for mortality from ischaemic heart disease specifically. The data indicate a significant synergistic interaction between arsenic exposure and cigarette smoking in mortality from ischaemic heart disease and other heart disease. In particular, the hazard ratio for the joint effect of a moderate level of arsenic exposure (middle third of well arsenic concentration 25.3-114.0 µg/L, mean 63.5 µg/L) and cigarette smoking on mortality from heart disease was greater than the sum of the hazard ratios associated with their individual effect (relative excess risk for interaction 1.56, 0.05 to 3.14; P = 0.010).ConclusionsExposure to arsenic in drinking water is adversely associated with mortality from heart disease, especially among smokers.

Project description:Rationale: Exposure to inorganic arsenic, through drinking naturally-contaminated water, is an established cause of lung cancer. Evidence on the impact of arsenic exposure on lung function, however, is less conclusive. The evidence available, mostly from populations exposed to water arsenic levels >100 ?g/L, suggests that arsenic exposure is associated with lower lung function. Prospective studies and studies examining low-to-moderate levels of water arsenic exposure (<50 ?g/L) the level relevant for U.S. populations, are very limited. Objectives: We evaluated the association between chronic low-to-moderate arsenic exposure with lung function and disease in an American Indian population. Methods: The Strong Heart Study is a multicenter prospective study of cardiovascular disease and its risk factors among American Indian adults. The present analysis, in 2,166 adults, used urinary arsenic measurements at baseline (1989–1991) and lung symptoms and function assessment by standardized spirometry at the second examination (1993–1995). We evaluated associations between arsenic exposure and airflow obstruction, defined as ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70, and restrictive pattern, defined as FEV1/FVC ratio greater than 0.70 and FVC less than 80% predicted; respiratory symptoms; and self-reported physician diagnosis of nonmalignant respiratory disease. Results: The prevalence of airflow obstruction between 1993 and 1995 was 21.4% (463/2,166); restrictive pattern was 14.5% (314/2,166). Median urinary arsenic concentrations were higher in participants with airflow obstruction (11.0 ?g/g creatinine) compared to those without obstruction (9.8 ?g/g creatinine), and higher in those with restrictive pattern (12.0 ?g/g) compared to those without restrictive pattern (9.4 ?g/g). The odds ratio (95% confidence interval) for obstructive and restrictive patterns comparing the 75th to 25th percentile of arsenic was 1.13 (0.96–1.32) and 1.27 (1.01–1.60), respectively, after adjustment for age, sex, education, study site, smoking status, smoking pack-year, estimated glomerular filtration rate, tuberculosis, and body mass index. Emphysema, cough 4–6 times a day, phlegm, and stopping for breath were also positively associated with arsenic. Conclusions: In this American Indian population, exposure to low-to-moderate levels of inorganic arsenic, as measured in urine, was positively associated with restrictive pattern as measured by spirometry, self-reported emphysema diagnosis, self-reported shortness of breath, and more frequent cough and phlegm among those with cough, independent of smoking status. These findings suggest that low-to-moderate arsenic exposure can contribute to nonmalignant lung disease, and may be associated with restrictive lung disease.

Project description:BackgroundChronic exposure to arsenic (As), a human toxicant and carcinogen, remains a global public health problem. Health risks persist after As exposure has ended, suggesting epigenetic dysregulation as a mechanistic link between exposure and health outcomes.ObjectivesWe investigated the association between total urinary As and locus-specific DNA methylation in the Strong Heart Study, a cohort of American Indian adults with low-to-moderate As exposure [total urinary As, mean (±SD) μg/g creatinine: 11.7 (10.6)].MethodsDNA methylation was measured in 2,325 participants using the Illumina MethylationEPIC array. We implemented linear models to test differentially methylated positions (DMPs) and the DMRcate method to identify regions (DMRs) and conducted gene ontology enrichment analysis. Models were adjusted for estimated cell type proportions, age, sex, body mass index, smoking, education, estimated glomerular filtration rate, and study center. Arsenic was measured in urine as the sum of inorganic and methylated species.ResultsIn adjusted models, methylation at 20 CpGs was associated with urinary As after false discovery rate (FDR) correction (FDR< 0.05). After Bonferroni correction, 5 CpGs remained associated with total urinary As (pBonferroni<0.05), located in SLC7A11, ANKS3, LINGO3, CSNK1D, ADAMTSL4. We identified one DMR on chromosome 11 (chr11:2,322,050-2,323,247), annotated to C11orf2; TSPAN32 genes.DiscussionThis is one of the first epigenome-wide association studies to investigate As exposure and locus-specific DNA methylation using the Illumina MethylationEPIC array and the largest epigenome-wide study of As exposure. The top DMP was located in SLC7A11A, a gene involved in cystine/glutamate transport and the biosynthesis of glutathione, an antioxidant that may protect against As-induced oxidative stress. Additional DMPs were located in genes associated with tumor development and glucose metabolism. Further research is needed, including research in more diverse populations, to investigate whether As-related DNA methylation signatures are associated with gene expression or may serve as biomarkers of disease development. https://doi.org/10.1289/EHP6263.

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Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study.

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Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study.

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