Aslak Harbo Poulsen1, Clara G Sears2, James Harrington3, Chanelle J Howe2, Katherine A James4, Nina Roswall5, Kim Overvad6, Anne Tjønneland7, Gregory A Wellenius8, Jaymie Meliker9, Ole Raaschou-Nielsen10. 1. Danish Cancer Society Research Center, Copenhagen, Denmark. Electronic address: aslak@cancer.dk. 2. Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA. 3. Center for Analytical Science, Research Triangle Institute, Research Triangle Park, NC, USA. 4. Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, USA. 5. Danish Cancer Society Research Center, Copenhagen, Denmark. 6. Department of Public Health, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. 7. Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health University of Copenhagen. Copenhagen, Denmark. 8. Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA; Department of Environmental Health, Boston University, Boston, MA, USA. 9. Program in Public Health, Department of Family, Population, & Preventive Medicine, Stony Brook University, Stony Brook, NY, USA. 10. Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Environmental Science, Aarhus University, Roskilde, Denmark.
Abstract
BACKGROUND: and Purpose: Cadmium has been associated with risk of cardiovascular events, including stroke. Human cadmium exposure occurs primarily through diet and tobacco smoke. Recent cohort studies have found an association with stroke, but residual confounding from smoking, could not be ruled out. We therefore conducted a case-cohort study to evaluate whether cadmium is associated with stroke in never-smokers. METHODS: The Danish Diet Cancer and Health cohort consists of Danes 50-64 years old, recruited in 1993-1997. From never-smoking cohort members without previous cancer or stroke we sampled a sub-cohort of 1200 persons. We also identified all (n = 534) cases in the cohort with a validated stroke diagnosis between baseline and 2009. We quantified cadmium and creatinine concentrations from baseline urine samples and used cadmium per creatinine as our main exposure metric. We used Cox proportional hazards models to estimate hazard ratios (HRs) with age as time scale and adjusting for BMI, education and urinary cotinine with and without stratification by sex. RESULTS: The median urinary cadmium concentration was 0.21 μg cadmium/g creatinine in cases and 0.19 μg/g in the sub-cohort. The majority (83%) of stroke cases were diagnosed with ischemic stroke. The HR for stroke in the highest quartile of exposure (median 0.44 μg/g creatinine) was 1.11 (95% CI: 0.79-1.54) compared with the lowest quartile (median 0.10 μg/g creatinine). The HR per inter quartile range (IQR, 0.19 μg/g creatinine) was 1.02 (95% CI: 0.92-1.12). Among men, the HR per IQR higher levels of cadmium (0.16 μg/g creatinine) was 1.18 (95% CI: 0.92-1.52), and 1.00 (95% CI: 0.89-1.12) among women. Adjusting for creatinine or using osmolality instead of creatinine standardization generally attenuated observed relationships. CONCLUSIONS: Our results do not support that low levels of cadmium exposure among never-smokers are strongly associated with risk of stroke, although results varied somewhat by sex and method of accounting for urinary dilution.
BACKGROUND: and Purpose: Cadmium has been associated with risk of cardiovascular events, including stroke. Human cadmium exposure occurs primarily through diet and tobacco smoke. Recent cohort studies have found an association with stroke, but residual confounding from smoking, could not be ruled out. We therefore conducted a case-cohort study to evaluate whether cadmium is associated with stroke in never-smokers. METHODS: The Danish Diet Cancer and Health cohort consists of Danes 50-64 years old, recruited in 1993-1997. From never-smoking cohort members without previous cancer or stroke we sampled a sub-cohort of 1200 persons. We also identified all (n = 534) cases in the cohort with a validated stroke diagnosis between baseline and 2009. We quantified cadmium and creatinine concentrations from baseline urine samples and used cadmium per creatinine as our main exposure metric. We used Cox proportional hazards models to estimate hazard ratios (HRs) with age as time scale and adjusting for BMI, education and urinary cotinine with and without stratification by sex. RESULTS: The median urinary cadmium concentration was 0.21 μg cadmium/g creatinine in cases and 0.19 μg/g in the sub-cohort. The majority (83%) of stroke cases were diagnosed with ischemic stroke. The HR for stroke in the highest quartile of exposure (median 0.44 μg/g creatinine) was 1.11 (95% CI: 0.79-1.54) compared with the lowest quartile (median 0.10 μg/g creatinine). The HR per inter quartile range (IQR, 0.19 μg/g creatinine) was 1.02 (95% CI: 0.92-1.12). Among men, the HR per IQR higher levels of cadmium (0.16 μg/g creatinine) was 1.18 (95% CI: 0.92-1.52), and 1.00 (95% CI: 0.89-1.12) among women. Adjusting for creatinine or using osmolality instead of creatinine standardization generally attenuated observed relationships. CONCLUSIONS: Our results do not support that low levels of cadmium exposure among never-smokers are strongly associated with risk of stroke, although results varied somewhat by sex and method of accounting for urinary dilution.
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