Dietary Mercury Exposure Unlikely to Raise CVD Risk

Megan Brooks

March 23, 2011

March 23, 2011 — Typical levels of dietary mercury exposure in the United States do not increase the risk for cardiovascular disease (CVD) in adults, a new study suggests.

The findings stem from a nested case-control study of data on 51,529 men enrolled in the Health Professionals Follow-up Study (HPFS) and 121,700 women in the Nurses' Health Study (NHS).

"This is by far the largest study of this important research question," first author Dariush Mozaffarian, MD, DrPH, from Harvard School of Public Health in Boston told Medscape Medical News. The findings, he said, "provide fairly definitive evidence for no harm" at typical mercury exposure levels in the United States.

Dr. Dariush Mozaffarian

The study is published in the March 24 issue of The New England Journal of Medicine.

Reached for comment, Jyrki Virtanen, PhD, nutritional epidemiologist at the University of Eastern Finland Kuopio campus, said, "This is a very well done study and indeed a very interesting and important paper, considering the mixed results from the prior smaller studies."

Dr. Jyrki Virtanen

"Important Area of Uncertainty"

Fish has long been viewed as a heart-healthy food because it contains high levels of omega-3 fatty acids. But fish is also the major source of exposure to methylmercury. Chronic, low-level mercury exposure appears to cause subtle but measurable neurodevelopmental delay in infants.

In adults, the main health concern is potential cardiovascular harms, Dr. Mozaffarian and colleagues note in their report. The Institute of Medicine and other US agencies have identified the effect of mercury exposure on CVD as an "important area of uncertainty that warrants further investigation," they point out.

To investigate further, the researchers identified a total of 3427 participants in the HPFS and NHS with incident cardiovascular disease, including 1532 nonfatal myocardial infarctions, 831 fatal cases of coronary heart disease (CHD), and 1064 strokes. These case participants were then matched to 3427 controls who did not develop CVD during the same period of follow-up.

Median mercury concentrations in stored toenail clippings were 0.23 µg/g among cases (interdecile range, 0.06 - 0.94 µg/g) and 0.25 µg/g among controls (interdecile range, 0.07 - 0.97 µg/g). The median follow-up interval from the time of toenail sampling to the time of incident CVD was 11.3 years; follow-up time was identical in controls.

In multivariate analysis, there was no increased risk for CHD, stroke, or total CVD in participants in the highest quintile of mercury exposure relative to those in the lowest quintile.

Table. Relative Risk for CVD in the 5th vs 1st Quintile of Mercury Exposure

Endpoint Number of Cases Adjusted RR (95% CI) P Value for Trend
CHD 2363 0.85 (0.69 - 1.04) .10
Stroke 1064 0.84 (0.62 - 1.14) .27
Total CVD 3427 0.85 (0.72 - 1.01) .06

CI = confidence interval; RR = relative risk.

The trace element selenium may protect against mercury toxicity. But when Dr. Mozaffarian's team restricted their analysis to participants with lower selenium concentrations, they still failed to see a link between mercury exposure and increased CVD risk.

They also say there is "no biologic" explanation for the suggestion in this study that mercury may somehow be protective against CVD.

Findings Specific to United States

What's not addressed in the current study, Dr. Mozaffarian emphasized, is "whether harm might be seen at higher exposure levels, such as those present in very specific regions in some countries outside the US."

This is an important point, echoed by Dr. Virtanen. He noted that a mercury-CVD link was seen in men in the Kuopio Ischemic Heart Disease Risk Factor Study in 1995 (Circulation. 1995;91:645-655) and again in 2005 (Arterioscler Thromb Vasc Biol. 2005;25:228-233).

"Interestingly," the Finnish researcher said, in studies from neighboring Sweden, mercury has not been associated with the risk for CVD. "One possible explanation is that mercury exposure is not harmful until a certain (currently unknown) threshold level is exceeded."

"The threshold may be different in different populations due to, for example, differences in the population intake of dietary antioxidants and selenium, or differences in their genetic-based defenses," Dr. Virtanen noted.

Dr. Mozaffarian and colleagues say their reliance on toenail mercury concentrations as an exposure measure is one potential limitation of the study. Although an "excellent" biomarker of mercury exposure during the previous year, changes in dietary exposure over time could attenuate true mercury-CVD ties toward null, they say.

They further emphasize in their report that their results should not alter ongoing public health and policy efforts to curb mercury contamination of fish and the environment. The findings also should not alter advisories directed toward women who are or may become pregnant or who are nursing to eat no more than 2 servings of fish per week and limit their intake of selected species of fish because of their high mercury content, such as shark, swordfish, king mackerel, and tilefish.

The study was funded by the National Institutes of Health. Dr. Mozaffarian and Dr. Virtanen have disclosed no relevant financial relationships.

N Engl J Med. 2011;364:1116-1125.

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