Case-cohort study of styrene exposure and ischemic heart disease

Recent epidemiologic studies have consistently reported increased daily mortalities and hospital admissions associated with exposure to particulate air pollution. Ischemic heart disease (IHD*, International Classification of Diseases, Eighth Revision [ICD-8], codes 410-414) is among those diseases that contribute in large measure to this excess mortality. Some occupational studies have suggested elevated risk of IHD among workers exposed for short periods to styrene, which can be emitted from fossil fuel combustion, aircraft exhausts, and motor vehicle exhausts. Styrene is found in ambient air at average concentrations of a few micrograms per cubic meter or less but may reach very high concentrations at particular locations and times. Unmeasured aerosols of styrene may also increase population exposures. This case-cohort study explored a possible association and dose-response relation between styrene exposure and risk of acute IHD in an occupational setting. The population under study was 6587 male workers employed between 1943 and 1982 in two US plants manufacturing styrene-butadiene polymers used in synthetic rubber. The study assessed all 498 subjects who died from IHD along with a subcohort of twice that size, 997 subjects, selected as a 15% random sample of the full target cohort. IHD deaths during the study led to some overlap between cases and the subcohort, leaving 1424 unique subjects. Job histories were collected for all subjects. Industrial hygienists and engineers from the industry estimated relative exposures for all jobs. Exposure data were collected for many of the jobs from different sources. For any job with no available exposure measurements, z scores were used to estimate job exposure in each plant from the relative exposure level for that job in similar plants and the measurement distribution parameters of the study plant. Standardized mortality ratio (SMR) analyses were used to examine the overall risk of dying from IHD among study subjects compared with the US general population. A significantly elevated SMR of 1.47 with a 95% confidence interval (95% CI) of 1.17 to 1.77 for chronic IHD was found among black workers who had left the plants. A modification of the Cox proportional hazard regression model was used to control for confounders and examine dose-response relations between styrene exposure and the risk of IHD. Employment time-weighted average (TWA) styrene concentration intensity for the most recent 2 years was found significantly associated with death from acute IHD among active workers with a relative hazard of 3.26 to 6.60, depending on duration of employment. In this analysis, the highest relative hazard of 6.60 (95% CI, 1.78-24.54) was among active workers who had been employed for at least 5 years. The results suggest that the exposure intensity was more important than duration of exposure. On the basis of the dose-response relation established in this study, we estimate that for each 10 microg/m3 increase in ambient styrene, acute IHD mortality might increase 0.4%. At normal ambient styrene levels, the relative risk would be increased, at most, 0.1% compared with no exposure. At certain locations and times, however, ambient styrene could reach levels that would result in a relative hazard for acute IHD mortality as high as 3.386-fold the risk at no exposure.