In our study, mercury exposure as assessed by an objective biomarker measurement was not associated with an increased risk of cardiovascular disease among men or women in two separate U.S. cohorts. An increased risk with greater mercury exposure was also not evident among participants with lower selenium concentrations, in analyses restricted to the first 10 years of follow-up and analyses stratified according to the duration of follow-up, or in analyses restricted to those participants without substantial changes in fish consumption over time and analyses stratified according to the level of fish consumption. These findings provide no support for clinically relevant adverse effects of typical levels of dietary methylmercury exposure on cardiovascular disease in U.S. adults.
Higher mercury exposures were actually associated with trends toward lower cardiovascular disease risk, although these trends were not significant in the fully adjusted models. To our knowledge, there is no biologic explanation for why mercury would induce cardiovascular benefits. These results plausibly reflect the extent to which mercury levels are an indirect, but nonetheless objective, biomarker of fish consumption and its correlates and thus probably provide independent information on how much fish a person consumes, even after adjustment for estimated consumption. Trends toward lower risk with higher mercury exposure appeared to be confined to women, but this sex difference was not significant and is probably due to chance. Trends toward lower cardiovascular disease risk with higher mercury levels have also been seen in some prior studies.7,11
Of six prior studies of the relationship between mercury exposure and cardiovascular disease,6–11
only two showed positive associations.6,7
The largest study (684 cases) included only nonfatal myocardial infarction and was retrospective,6
raising concern about possible selection bias. A smaller, prospective study (282 cases) showed a positive association with total coronary events but without a clear dose– response relationship or significant associations with coronary or cardiovascular mortality.7
The remaining four studies were prospective and did not show significant associations; however, they included participants with occupational exposure to mercury vapor,8
the health effects of which differ from those of methylmercury12
; they assessed erythrocyte mercury levels, which reflect a more recent exposure than do toenail or hair concentrations9
; or they had small numbers of cases (<100).10,11
Several of the prior studies also did not evaluate stroke6–8,11
or include women.6–8
The investigation we describe here was designed to overcome these limitations.
With respect to generalizability, it is important to consider how mercury exposures in the present study compare with those in prior studies and with average population exposures. In our highest exposure quintile, the median toenail mercury concentration was 0.68 µg per gram, and in our highest decile, 1.00 µg per gram, corresponding to hair concentrations of about 1.84 and 2.70 µg per gram, respectively, calculated from a reported toenail-to-hair ratio of mercury of about 0.37.32–35
These exposure levels are similar to those seen in two smaller studies, in which mercury levels were positively associated with coronary heart disease risk,6,7
and are also similar to higher U.S. exposures (in the 95th percentile).36
Differences in population selenium levels have been hypothesized to explain discrepant findings of prior studies with respect to mercury and cardiovascular risk — in particular, a study from Finland.7
Before soil supplementation was begun in the 1980s, selenium levels in Finland were among the lowest in Europe (mean serum level, <70 µg per liter).37
In the Finnish mercury study, average serum selenium levels at baseline (from 1984 through 1989, after soil supplementation began) were higher (117 µg per liter)7
but still below average U.S. levels (138 µg per liter).38
In our study, we found no evidence of an increased risk with higher mercury levels, even among participants with selenium levels in the lowest decile (<0.64 µg per gram in toenails, approximately equivalent to <91 µg per liter in serum39
). We also found no evidence that mercury was harmful among participants in different strata of fish consumption, including those with low fish consumption, in whom higher mercury levels would suggest more exclusive consumption of mercury-contaminated fish.
Our analysis cannot exclude the possibility of mercury-related cardiovascular toxicity at higher exposures than those observed in our cohorts or in the setting of frank selenium deficiency, which would be rare in U.S. cohorts. Ecologic or small cross-sectional studies in more highly exposed populations in the Amazon,40
the Faroe Islands,32
suggest that methylmercury exposure may be associated with higher blood pressure or lower parasympathetic activity; ecologic evidence of an increased risk of clinical cardiovascular events is lacking.43
Our analysis has potential limitations. Although toenail concentrations of mercury provide an excellent biomarker of integrated, usual methylmercury exposure during the previous year, changes in dietary exposure over time could attenuate true relationships toward null. Toenail mercury concentration serves as a marker of fish consumption, and our findings may be partly confounded by the beneficial effects of fish intake, despite adjustment for responses to the dietary questionnaire; this might account for trends toward lower risk. Although the findings were similar in the two independent cohorts and there is little reason to believe that biologic effects of methylmercury in these populations would be different from those in the general population of women and men, these cohorts comprised largely white, educated U.S. adults, potentially limiting generalizability.
The absence of any association between mercury exposure and increased cardiovascular disease risk in adults should not alter ongoing public health and policy efforts to reduce mercury contamination in fish and the environment, which could still have the potential to offset, at least in part, the net cardiovascular benefits of fish consumption. Our findings should also not alter advisories directed toward women who are or may become pregnant or who are nursing, since methylmercury exposure from consumption of specific fish species could cause neurodevelopmental harm, or at least partly offset the neurodevelopmental benefits of fish consumption, in their children.
In summary, this prospective study of two large cohorts of men and women in the United States showed no evidence of a relationship between mercury exposure and increased cardiovascular disease risk.