Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion


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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.MethodsTwenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0 mg/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 6 h following a placebo infusion of 500 mL normal saline and 1.2% dextrose, and for 6 h following a 3 g 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.ResultsThe 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. 2580 μg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase).ConclusionsEdetate 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.HighlightsLead and cadmium are associated with a higher incidence of adverse cardiovascular outcomes.An EDTA-based infusion increases the urinary excretion of lead and cadmium.MI survivors randomized to EDTA chelation demonstrated improved cardiac outcomes compared to placebo.Lead and cadmium may be modifiable risk factors for cardiovascular disease.TACT2 seeks to replicate the results of TACT and investigate mechanisms, including establishing a biorepository.

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