Arce Domingo-Relloso1,2,3, Maria Grau-Perez1,2, Laisa Briongos-Figuero4, Jose L Gomez-Ariza5, Tamara Garcia-Barrera5, Antonio Dueñas-Laita6, Jennifer F Bobb7, F Javier Chaves8,9, Marianthi-Anna Kioumourtzoglou3, Ana Navas-Acien3, Josep Redon-Mas1,10,11, Juan C Martin-Escudero4, Maria Tellez-Plaza1,12,13. 1. Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research INCLIVA, Valencia, Spain. 2. Department of Statistics and Operational Research, University of Valencia, Valencia, Spain. 3. Department of Environmental Health Sciences, Columbia University, New York, NY, USA. 4. Department of Internal Medicine, Hospital Universitario Rio Hortega, Valladolid, Spain. 5. Department of Chemistry, University of Huelva, Huelva, Spain. 6. Department of Toxicology, Hospital Universitario Rio Hortega, Valladolid, Spain. 7. Biostatistics Unit, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA. 8. Genotyping and Genetic Diagnosis Unit, Institute for Biomedical Research INCLIVA, Valencia, Spain. 9. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Institute of Health Carlos III, Madrid, Spain. 10. Department of Internal Medicine, Hospital Clínico de Valencia, Valencia, Spain. 11. CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health CarlosIII, Madrid, Spain. 12. Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Institute of Health Carlos III, Madrid, Spain. 13. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Abstract
BACKGROUND: The association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain. METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting. RESULTS: In single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities. CONCLUSIONS: Urine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.
BACKGROUND: The association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain. METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting. RESULTS: In single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities. CONCLUSIONS: Urine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.
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