Cadmium Exposure and All-Cause and Cardiovascular Mortality in the U.S. General Population

Abstract

Background: Urine cadmium concentrations were associated with all-cause and cardiovascular mortality in men in the 1988–1994 U.S. National Health and Nutrition Examination Survey (NHANES) population. Since 1988, cadmium exposure has decreased substantially in the United States. The associations between blood and urine cadmium and cardiovascular disease (CVD) mortality at more recent levels of exposure are unknown.Objectives: We evaluated the prospective association of blood and urine cadmium concentrations with all-cause and CVD mortality in the 1999–2004 U.S. population.Methods: We followed 8,989 participants who were ≥ 20 years of age for an average of 4.8 years. Hazard ratios for mortality end points comparing the 80th to the 20th percentiles of cadmium distributions were estimated using Cox regression.Results: The multivariable adjusted hazard ratios [95% confidence intervals (CIs)] for blood and urine cadmium were 1.50 (95% CI: 1.07, 2.10) and 1.52 (95% CI: 1.00, 2.29), respectively, for all-cause mortality, 1.69 (95% CI: 1.03, 2.77) and 1.74 (95% CI: 1.07, 2.83) for CVD mortality, 1.98 (95% CI: 1.11, 3.54) and 2.53 (95% CI: 1.54, 4.16) for heart disease mortality, and 1.73 (95% CI: 0.88, 3.40) and 2.09 (95% CI: 1.06, 4.13) for coronary heart disease mortality. The population attributable risks associated with the 80th percentile of the blood (0.80 μg/L) and urine (0.57 μg/g) cadmium distributions were 7.0 and 8.8%, respectively, for all-cause mortality and 7.5 and 9.2%, respectively, for CVD mortalityConclusions: We found strongly suggestive evidence that cadmium, at substantially low levels of exposure, remains an important determinant of all-cause and CVD mortality in a representative sample of U.S. adults. Efforts to further reduce cadmium exposure in the population could contribute to a substantial decrease in CVD disease burden.

Kidney Cadmium Toxicity, Diabetes and High Blood Pressure: The Perfect Storm

“…In a follow-up of NHANES III (1988-1994 participants, Adams et al (2012) found increases in death from lung cancer among men who had urinary Cd ≥ 0.58 µg/g creatinine (HR 3.22, 95% CI 1.26-8.25), while Hyder et al (2013) found increases in death from non-malignant, liver-related diseases among women with urinary Cd ≥ 0.83 μg/g creatinine and men with urinary Cd ≥ 0.65 μg/g creatinine (HR 3.42, 95% CI 1.12-10.47). Consistent with the Japanese findings, Tellez-Plaza et al (2012) found increases in death from cardiovascular disease (CVD) (HR 1.74, 95% CI 1.07-2.83), from ischemic heart disease (HR 2.53 95% CI 1.54-4.16), and from coronary heart disease (HR 2.09, 95%, 1.06-4.13) among those with urinary Cd ≥ 0.57 vs. 0.14 μg/g creatinine. Population attributed risks predict that a 25% reduction in Cd exposure (a fall of urinary Cd from 0.57 to 0.14 μg/g creatinine) will prevent 8.8% overall deaths and 9.2% from CVD deaths.…”

Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke

“…The general population is exposed to cadmium through food such as rice, wheat, and potatoes from contaminated agricultural soil; tobacco smoking further increases cadmium exposure 1. Cadmium has many adverse health effects, including increased risk of cardiovascular disease 2, 3. A recent study from the population‐based Malmö Diet and Cancer study (MDC) reported that cadmium in blood was associated with incidence of cardiovascular diseases, including ischemic stroke.…”

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

“…Environmental exposure to cadmium in the general population is associated with a range of chronic ailments and various types of cancers. Associations of cadmium exposure and increased all-cause mortality and cancer mortality were observed (Menke et al 2009;Adams et al 2012;Tellez-Plaza et al 2012b).…”

“…A bolus of liver cadmium, previously bound to MT, can be displaced by nitric oxide and is released during infection and sepsis, where cellular nitric oxide synthesis is enhanced (Satarug et al 2000a). This may explain an increase in all-cause mortality among persons who had elevated cadmium body burden with or without pre-existing signs of cadmium-related kidney toxicity (Menke et al 2009;Adams et al 2012;Tellez-Plaza et al 2012b) Metabolic and carcinogenic effects Type-2 diabetes: In 1980, Merali and Singhal demonstrated the ability of cadmium to induce diabetic symptoms in neonatal rats. They found the liver of these cadmiumexposed neonatal rats contained low levels of glycogen and showed evidence of enhanced gluconeogenesis (increased activity of enzymes in gluconeogenesis: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose1,6-biphosphatase and glucose-6-phosphatase).…”

“…Waalkes and Rehm (1994) demonstrated cadmium carcinogenesis in mice. Almost three decades after these reports of hypertensive, diabetogenic and carcinogenic effects of cadmium in experimental animals, cadmium exposure in the general population of the USA has been found to be associated with increased risks of pre-diabetes, type-2 diabetes (Schwartz et al 2003), hypertension (Tellez-Plaza et al 2008) and cancer mortality (Adams et al 2012;Tellez-Plaza et al 2012b). In addition, cadmium exposure has been associated with learning disability in children (Ciesielski et al 2012) and hearing disability in adolescents (Shargorodsky et al 2011) and adults in the USA (Choi et al 2012).…”