Association between Benzene Exposure, Circulating Angiogenic Cell Levels, and Cardiovascular Disease Risk in the Louisville Healthy Heart Study

Background: Benzene is an aromatic hydrocarbon found in high amounts in vehicular exhaust and tobacco smoke. Exposure to traffic pollutants or chronic tobacco smoke exposure induces cardiovascular injury, suppresses circulating angiogenic cells (CACs), and increases thrombosis and atherogenesis. The purpose of this study was to examine whether benzene exposure is associated with CAC levels and cardiovascular injury in humans.

Methods: Benzene exposure was assessed in 240 participants of the Louisville Healthy Heart Study with cardiovascular disease (CVD) risk by measuring the urinary levels of the benzene metabolite – trans, trans-muconic acid (t,t-MA). Because benzene is both environmental pollutant and a tobacco smoke constituent, urine cotinine levels were also measured. Generalized linear models were used to assess the association between benzene exposure and parameters of CVD risk and injury and adjusted for potential confounders.

Results: The study population was 51±10 years old, 41% African American, 47% female, and 39% current smokers. As expected, urinary t,t-MA levels were higher in smokers than non-smokers and positively correlated with urinary cotinine levels. Urine t,t-MA level was inversely associated with residential proximity to roadways. Urinary t,t-MA levels are inversely related to both early (AC133⁺) and late (AC133^–) CACs. However, no association was observed between t,t-MA and inflammation or thrombosis. In non-smokers, t,t-MA levels were positively associated with increased Framingham Risk Scores.

Conclusions: Regardless of the source of benzene exposure (e.g., tobacco smoke, or traffic emissions), benzene may increase cardiovascular disease risk in part through decreased levels of CACs and subsequent suppression of vascular repair.