Toxic metals have been associated with cardiovascular mortality and morbidity (1). The Trial to Assess Chelation Therapy (TACT) reported that treatment with an edetate disodium-based infusion reduced cardiac events in post-MI patients (2-5). We hypothesized enhanced excretion of toxic metals epidemiologically linked to cardiovascular disease as a possible mechanism.
Twenty four patients (post-MI, age >50 years, creatinine ≤ 2.0 mg/dL) were included. Urinary concentrations of 20 toxic metals normalized to urinary creatinine excretion were measured at baseline, for 6 hours following a placebo infusion of 500 mL normal saline and 1.2% dextrose, and for 6 hours following a 3 gram edetate disodium-based infusion as used in TACT (2).
Mean age was 65 years (Range 51 to 81 years). All patients were male. 60% had history of diabetes mellitus and 65% were former smokers. Serum creatinine was 0.97±0.31 mg/dl. Toxic metals were very prevalent in the spontaneous urine of post MI patients (Table 1). After placebo infusion there was only a mild increase in Cesium excretion with not significant changes in total urinary metal excretion (1.40 vs. 1.42 mg/g creatinine; 1.6% increase; P=0.2). After edetate treatment, total urinary metal excretion increased by 60% (1.40 mg/g vs. 2.25 mg/g creatinine; P<0.0001). Edetate effect was particularly large for Pb (3,887% increase) and Cd (670% increase)(Figure 1). There was also a moderate increase in Ni (157% increase), Al (246% increase) and Tl (50%) (Figure 2). Gd appeared in the urine of patients who had a contrast MRI in the past.
Edetate disodium-based infusion markedly increased excretion of lead and cadmium, two toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events. Metal burden may be an under-recognized and modifiable risk factor for atherosclerotic disease.
This study was funded by Mounta Sinai Medical Center and the JAmes P. Carter Memorial Grant for EDTA Chelation Research.
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