Ivan A Arenas1, Ana Navas-Acien2, Ian Ergui1, Gervasio A Lamas3. 1. The Columbia University Division of Cardiology at Mount Sinai Medical Center, Miami Beach, FL, USA. 2. Columbia University Mailman School of Public Health, New York, NY, USA. 3. The Columbia University Division of Cardiology at Mount Sinai Medical Center, Miami Beach, FL, USA. Electronic address: Gervasio.Lamas@msmc.com.
Abstract
Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. METHODS:Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. RESULTS:The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). CONCLUSIONS: Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events.
RCT Entities:
Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. METHODS: Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. RESULTS: The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). CONCLUSIONS:Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events.
Authors: Francisco Ujueta; Ivan A Arenas; Esteban Escolar; Denisse Diaz; Robin Boineau; Daniel B Mark; Patrick Golden; Lauren Lindblad; Hwasoon Kim; Kerry L Lee; Gervasio A Lamas Journal: J Diabetes Complications Date: 2019-04-14 Impact factor: 2.852
Authors: Gervasio A Lamas; Kevin J Anstrom; Ana Navas-Acien; Robin Boineau; Hwasoon Kim; Yves Rosenberg; Mario Stylianou; Teresa L Z Jones; Bonnie R Joubert; Regina M Santella; Esteban Escolar; Y Wady Aude; Vivian Fonseca; Thomas Elliott; Eldrin F Lewis; Michael E Farkouh; David M Nathan; Ana C Mon; Leigh Gosnell; Jonathan D Newman; Daniel B Mark Journal: Am Heart J Date: 2022-05-19 Impact factor: 5.099
Authors: Rossana Calderon Moreno; Ana Navas-Acien; Esteban Escolar; David M Nathan; Jonathan Newman; John F Schmedtje; Denisse Diaz; Gervasio A Lamas; Vivian Fonseca Journal: J Clin Endocrinol Metab Date: 2019-07-01 Impact factor: 6.134
Authors: Zenith H Alam; Francisco Ujueta; Ivan A Arenas; Anne E Nigra; Ana Navas-Acien; Gervasio A Lamas Journal: Int J Environ Res Public Health Date: 2020-06-29 Impact factor: 3.390