BHF Cardis Project

Cardiovascular diseases result from a complex interaction of genetic, lifestyle and environmental factors. Several personal risk factors for developing heart disease have been identified, including smoking, diabetes and dyslipidemia1. Much less is known of the contribution of environmental contaminants, despite accumulating evidence suggesting that exposure to certain pollutants and chemicals could elevate cardiovascular risk.

Up to now, the most widely reported associations between cardiovascular disease and pollutants have centred on exposure to air particulates and heavy metals. However, the general adult population is also exposed to many common, lipophilic chemical compounds in everyday life, which can accumulate in body tissues to create a toxic body burden. For the most part, the health consequences of this low level exposure to so-called ‘present organic pollutants’ (POPs) is unknown, although numerous adverse effects have been documented. Chronic accumulation of low concentrations of POPs within the body is associated with an increase in the incidence of insulin resistance, metabolic syndrome and diabetes in study populations. Elevated risk for mortality from ischemic heart disease has been identified in several cohorts, including those showing high occupational or accidental exposure to POPs and in the general population.

An important focus is on Bisphenol A (BPA), an organic compound classified as an ‘endocrine disruptor’: that is, a compound capable of causing dysfunction to hormonally regulated body systems. More than 2.2 million metric tonnes of BPA are produced worldwide each year for use mainly as a constituent monomer in polycarbonate plastics and epoxy resins. Widespread and continuous human exposure to BPA is primarily through food but also through drinking water, dental sealants, dermal exposure and inhalation of household dusts. It is one of the world’s highest production volume compounds and human biomonitoring data indicates that the majority (up to 95%) of the general population is exposed to BPA, evidenced by the presence of measurable concentrations of metabolites in the urine of population representative samples.

In 2008, our collaborator Professor David Melzer in Exeter published the first major epidemiological study to examine the health effects associated with Bisphenol A. They had proposed that higher urinary BPA concentrations would be associated with adverse human health effects, especially in the liver and in relation to insulin, cardiovascular disease and obesity. In their human study higher BPA concentrations were associated with cardiovascular diagnoses (OR per 1SD increase in BPA concentration 1.39, 95% CI 1.18-1.63; p=.001 with full adjustment). Higher BPA concentrations were also associated with diabetes (OR per 1SD increase in BPA concentration, 1.39;95% CI 1.21-1.60;p<.001) but not with other common diseases.

More recently, the British Heart Foundation funded our Cardis Project to investigate the association between exposure to BPA and heart disease in our MaGiCAD cohort. As well as attempting to replicate the earlier associations in a population with much better characterized cardiovascular disease status, the prospective component of MaGiCAD should allow the first indication of whether the observed associations are actually causal. If exposure to BPA really does increase the risk of heart disease, the implications for safety assessment of BPA and other POPs is significant: we may have to re-evaluate our use of BPA and introduce tighter controls on existing and new chemicals to which people are commonly exposed.

By the summer of 2010, we have measured the levels of BPA in urine samples from the entire MaGiCAD cohort, and statistical analysis of the data is underway. We hope to publish the results from these studies by the end of 2010. Watch this space for the first announcement of the findings.