Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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 μg/L (3.65 nmol/L) and 1.58 μg/dL (0.076 μmol/L), respectively, in 14,778 adults aged ≥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 (≥30 mg/g creatinine), reduced estimated glomerular filtration rate (eGFR) (<60 mL/minute/1.73 m²), 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.

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Introduction: Cadmium induces hypertension in animal models. Epidemiologic studies of cadmium exposure and hypertension, however, have been inconsistent. Objective: We aimed to investigate the association of blood and urine cadmium with blood pressure levels and with the prevalence of hypertension in U.S. adults who participated in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Methods: We studied participants ≥ 20 years of age with determinations of cadmium in blood (n = 10,991) and urine (n = 3,496). Blood and urine cadmium were measured by atomic absorption spectrometry and inductively coupled plasma–mass spectrometry, respectively. Systolic and diastolic blood pressure levels were measured using a standardized protocol. Results: The geometric means of blood and urine cadmium were 3.77 nmol/L and 2.46 nmol/L, respectively. After multivariable adjustment, the average differences in systolic and diastolic blood pressure comparing participants in the 90th vs. 10th percentile of the blood cadmium distribution were 1.36 mmHg [95% confidence interval (CI), −0.28 to 3.00] and 1.68 mmHg (95% CI, 0.57–2.78), respectively. The corresponding differences were 2.35 mmHg and 3.27 mmHg among never smokers, 1.69 mmHg and 1.55 mmHg among former smokers, and 0.02 mmHg and 0.69 mmHg among current smokers. No association was observed for urine cadmium with blood pressure levels, or for blood and urine cadmium with the prevalence of hypertension. Conclusions: Cadmium levels in blood, but not in urine, were associated with a modest elevation in blood pressure levels. The association was stronger among never smokers, intermediate among former smokers, and small or null among current smokers. Our findings add to the concern of renal and cardiovascular cadmium toxicity at chronic low levels of exposure in the general population.

Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective was to conduct a systematic review of epidemiologic studies evaluating the association between environmental chemicals with DNA methylation levels in adults. After excluding arsenic, recently evaluated in a systematic review, we identified a total of 17 articles (6 on cadmium, 4 on lead, 2 on mercury, 1 on nickel, 1 on antimony, 1 on tungsten, 5 on persistent organic pollutants and perfluorinated compounds, 1 on bisphenol A, and 3 on polycyclic aromatic hydrocarbons). The selected articles reported quantitative methods to determine DNA methylation including immunocolorimetric assays for total content of genomic DNA methylation, and microarray technologies, methylation-specific quantitative PCR, Luminometric Methylation Assay (LUMA), and bisulfite pyrosequencing for DNA methylation content of genomic sites such as gene promoters, LINE-1, Alu elements, and others. Considering consistency, temporality, strength, dose-response relationship, and biological plausibility, we concluded that the current evidence is not sufficient to provide inference because differences across studies and limited samples sizes make it difficult to compare across studies and to evaluate sources of heterogeneity. Important questions for future research include the need for larger and longitudinal studies, the validation of findings, and the systematic evaluation of the dose-response relationships. Future studies should also consider the evaluation of epigenetic marks recently in the research spotlight such as DNA hydroxymethylation and the role of underlying genetic variants.