In this paper, we report an increased risk of IHD with chronic B(a
)P exposure, but not acute B(a
)P exposure, in an occupational cohort of aluminum smelter workers. Two previous smelter studies have shown an increased risk of heart disease with potroom work (7
) and cumulative coal tar exposure (6
). Environmental studies of air pollution, with much lower particulate matter and PAH exposure levels (19
), have found consistent associations between particulate matter and IHD mortality with both short- and long-term exposure (3
). Our strongest associations were with chronic B(a
)P exposure and all IHD combined. Our separate analyses of AMI and non-AMI causes suggested that the association may be limited to AMI, although nonsignificant risks were observed in all exposure categories for both outcomes. PAHs have been found to enhance the progression of atherosclerosis in toxicologic studies (20
), which is relevant to both AMI and non-AMI causes of IHD. We could not determine whether there was a latency period for the effects of chronic exposure, since cumulative metrics with lags ranging from 0 years through 5 years provided nearly identical results.
)P, a specific PAH, was used as a surrogate for the complex mixture of PAHs and other compounds emitted from the coal tar pitch used in the anode in the electrolytic process of aluminum smelting. The emissions in aluminum smelters include coal tar pitch volatiles such as PAHs, fluorides, sulfur dioxide, and carbon monoxide, among other substances (25
); however, in Söderberg smelters, these exposures are highly related. Previous analyses in this and other smelters have found B(a
)P to be a good surrogate measure of coal tar pitch volatile emissions for evaluation of cancer outcomes (16
). The causal components for heart disease are unknown; however, PAHs have been implicated in toxicologic studies (20
The development of quantitative exposure estimates is a major strength of this cohort study and a substantial improvement over the semiquantitative estimates used in the original study of this cohort (11
). Although we used sophisticated statistical models to maximize the use of exposure measurements, the nonlinear relations observed between cumulative B(a
)P and disease suggest that some exposure misclassification remained. Backwards extrapolation of pre-1977 levels was necessary for 44% of the person-years in the IHD analyses and may have resulted in underestimated exposure levels for this earlier period. However, the exposure measurements covered the time periods in which the majority of the technological improvements occurred (18
). Although measurements anchored the exposure estimates wherever possible, interpolation based on proportion of time spent in exposed work areas was required for jobs without measurements. These jobs generally fell within the low exposure category and were primarily jobs held by maintenance workers who worked in multiple plant and workshop areas.
For the hypothesized inflammation pathways for particulate matter and cardiovascular disease, the most relevant size fractions have been the fine (<2.5 μm) and ultrafine (<0.1 μm) particles (1
). The B(a
)P metric, however, was based on PAHs bound on particles collected using 37-mm cassettes (18
), which has a >50% sampling efficiency for particles with mean aerodynamic diameter less than 30 μm (28
). A study characterizing the particulates from smelter emissions have found several different types of particles that are less than 3 μm in diameter, including soot, but the predominant ultrafine particulates were fluoride-containing agglomerates in the 0.1- to 1-μm range (29
). We were unable to develop exposure metrics specific to these small particle sizes and thus assumed that the respirable fraction was a constant proportion of the measured particulate. If the proportion varied by job or time, exposure misclassification would have been introduced.
Other exposures relevant to an aluminum smelter environment, such as noise, heat, and high energy expenditures (30
), have also been associated with heart disease but were not evaluated in this study. Confounding by these exposures is unlikely, since our nonexposed reference group (50% of the cohort) included persons who worked in other noisy and high-physical-activity areas such as electrical operations, nonpotroom maintenance areas, the wharves, and the casting department, which also had high heat exposures.
We previously reported differences in exposure levels between smokers and nonsmokers (mean cumulative B(a
)P exposure of 30.9 μg/m3
-year and 20.9 μg/m3
-year, respectively) (36
). To account for the potential confounding from smoking, we adjusted for smoking status (ever smoker, never smoker, or unknown) in all analyses. Our internal comparisons for COPD, another disease with smoking as a risk factor, did not show an association with B(a
)P exposure, further supporting our findings of only modest confounding by smoking. Although residual confounding may remain, since we could not adjust for the workers’ pack-years of smoking, it is unlikely to account for the entirety of the elevated risk of heart disease mortality seen here, as previous studies have shown only modest confounding by smoking in occupational cohorts (37
A strength of our study was the use of internal comparisons to reduce bias due to the healthy worker effect. External comparisons of occupational cohorts with the general population have rarely shown an elevated SMR with cardiovascular disease, because of the healthy hire effect (39
). That was indeed the case with heart disease in our external comparisons. There is no simple way to address residual bias in the other component of the healthy worker effect, the healthy worker survivor effect. When people leave work or change to less-exposed jobs as their health declines, the healthier workers accrue the largest exposures while symptomatic persons truncate their exposures, resulting in attenuated exposure-response associations (40
). In light of the healthy worker survivor effect, we generally see weaker associations among active workers, since less healthy workers typically leave behind a survivor population of healthier employed subjects. We found the opposite, with higher hazard ratios for chronic B(a
)P exposure in our analyses restricted to active employment than in our full analyses; albeit the restricted analyses had much wider confidence intervals from the reduced power. The lower hazard ratios in the full cohort compared with the actively employed suggest that cardiovascular effects may be reversible with time away from exposure.
Although our a priori interest was heart disease outcomes, we also examined external comparisons for other nonmalignant chronic diseases and internal comparisons for cerebrovascular disease and COPD. The decreased all-cause mortality rate in this cohort is typical in an occupational cohort (39
). Cerebrovascular disease was elevated in the cohort's women (SMR = 1.64, 95% CI: 0.71, 3.23) but was not elevated in the men; no association with PAH exposure was observed in our internal comparisons. COPD mortality was lower than that of the province's population for both men and women, and we found no indication of a trend with PAH exposure in the internal comparisons. Other studies of aluminum smelter workers and of asphalt pavers have shown some weak evidence for an increased risk of respiratory symptoms and COPD mortality with PAH exposure (42
). In a Norwegian aluminum smelter study, Romundstad et al. (46
) found elevated COPD mortality with fluoride exposure, a coexposure in Söderberg smelters that was not examined in this study.
A limitation of our study was the use of mortality rather than morbidity for cardiopulmonary outcomes. We expected nearly complete ascertainment of mortality causes with the linkage of this cohort to the national mortality database, to the national cancer incidence database, and to tax data for confirmation of vital status. However, the good survival rates for cardiopulmonary outcomes indicated that we captured only a portion of the cardiopulmonary outcomes that might have arisen from occupational exposures. Further studies of cardiopulmonary morbidity and PAH exposure are warranted.
In summary, our results support those of previous environmental studies by finding exposure-response relations between chronic PAH exposure and heart disease in a highly exposed occupational cohort. Given the widespread prevalence of workplace exposure to PAHs and particulate matter and the high prevalence of heart disease worldwide, even modest associations can result in a high burden of heart disease. Our results provide additional evidence that the downward bias due to the healthy worker survivor effect in occupational studies requires the development and incorporation of more sophisticated analytical approaches, such as causal models that can account for variables (e.g., leaving work) that are both confounders and intermediates on the causal pathway (40