Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy

Abstract

This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment.

Keywords: cadmium; coronary artery disease; lead; metal intoxication; myocardial infarction.

Figure 1. Primary Endpoint in the Overall Patient Population

TACT Kaplan-Meier estimates of the primary composite endpoint: EDTA chelation therapy versus placebo (2). The primary endpoint was a composite of death from any cause, reinfarction, stroke, coronary revascularization, or hospitalization for angina. CI = confidence interval; EDTA = edetate disodium; HR = hazard ratio; TACT = Trial to Assess Chelation Therapy.

Figure 2. Primary Endpoint in Patients With Diabetes

Kaplan-Meier estimates of the primary composite endpoint: EDTA chelation therapy versus placebo: subset of patients with diabetes (19). Abbreviations as in Figure 1.

Central Illustration. Heavy Metals as a Risk Factor for Atherosclerotic Cardiovascular Disease and the Benefits of Chelation Therapy

Major sources and routes of exposure, mechanisms at the molecular and cellular level, responses at the tissue and organ level, and subclinical and clinical cardiovascular effects on the basis of experimental and epidemiological evidence are shown for lead and cadmium. Arrows denote direction of flow. NO = nitric oxide.