Author Affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso.
Cardiovascular disease (CVD) remains the most common cause of morbidity and mortality in the United States. In 2008, the overall rate of deaths attributable to CVD was 244.8 per 100 000,1 and currently more than 2200 Americans die of CVD each day, an average of 1 death every 39 seconds.1 Although the large case-control study Effect of Potentially Modifiable Risk Factors Associated With Myocardial Infarction in 52 Countries (INTERHEART) suggested that lipid levels; smoking; hypertension; diabetes mellitus; abdominal obesity; psychosocial factors; consumption of fruits, vegetables, and alcohol; and degree of physical activity account for most (approximately 90%) of the risk for myocardial infarction worldwide in both sexes and at all ages in all regions,2 other novel risk factors may also play a role.
Shankar et al3 examined the independent relationship between serum perfluorooctanoic acid (PFOA) levels and cardiovascular outcomes and report that exposure to PFOA is associated with increased likelihood of CVD and peripheral arterial disease (PAD) independent of traditional cardiovascular risk factors. These results contribute to the evolving data on the adverse health effects of PFOA, suggesting that PFOA exposure may be potentially related to CVD. The study has several strengths, including its population-based nature, inclusion of a multiethnic sample, its moderate sample size, and the availability of data on confounders for multivariable adjustment. However, a major limitation is the cross-sectional nature of study. Given this significant limitation, causality or the temporal nature of the association between PFOA and CVD cannot be concluded from the current analysis.
Let us now examine the biology of PFOA in the context of the current analysis. Perfluorooctanoic acid does not occur naturally but is present in the serum of most residents of industrialized countries. In the United States, the median level is approximately 4 ng/mL.4 Drinking water is the primary route of exposure in most populations, but exposure sources are not completely understood, and breathing air containing these substances is another avenue of exposure, particularly among workers. Evidence of an association of elevated cholesterol and uric acid levels with PFOA exposure exists, although the magnitude of the effect is inconsistent across different exposure levels.5,6 Elevated serum PFOA levels have also been shown to be associated with altered glucose homeostasis and indicators of metabolic syndrome.7 The combination of metabolic alterations, including elevated cholesterol and uric acid levels, and altered glucose homeostasis with insulin resistance offers biological plausibility for a possible association of PFOA exposure with CVD. The data on CVD before the analysis by Shankar et al3 were limited in quantity and quality, consisting primarily of mortality studies among relatively small cohorts of workers. The mortality of workers (n = 4747) at a DuPont plant using PFOA showed no convincing evidence of increased CVD mortality risk for PFOA-exposed workers.8 In another study, compared with an internal referent population of nonexposed workers, moderate and high exposures to PFOA were positively associated with cerebrovascular disease (odds ratios, 1.8 [95% CI, 0.9-3.1] and 4.6 [1.3-17.0], respectively).9
The most consistent effect of PFOA appears to be association with modest increases in cholesterol and uric acid levels. However, these findings have been largely based on cross-sectional data and therefore cannot determine causality. Three longitudinal studies show that PFOA changes over time correlate with changes in cholesterol levels, and 1 longitudinal study shows a similar effect on uric acid levels, strengthening the case for a possible causal relationship.4
Given the pervasive nature of the exposure and unclear associations with CVD, what are clinicians and individuals to do? The Department of Health and Human Services Agency for Toxic Substances and Disease Registry provides some guidance on the topic. The registry suggests that families whose tap or well water contains PFOA may choose to drink and cook with bottled water or to install activated carbon water filters to minimize exposure. Furthermore, families may choose products that do not contain PFOA and avoid carpet and clothing treatments and coatings for paper and cardboard packaging with PFOA.
Although it seems clear that additional prospective research is needed to tease out the true adverse cardiovascular effects of PFOA, given the concerns raised by this and prior studies, clinicians will need to act now. From a societal point of view, it would make sense to limit or to eliminate the use of PFOA and its congeners in industry through legislation and regulation while improving water purification and treatment techniques to try and remove this potentially toxic chemical from our water supply. This procedure is particularly relevant in areas with factories that produce PFOA. For those individuals who have already been exposed and may have significant serum levels, removal of PFOA from their system appears to be more challenging. Although some data suggest that the use of a specific bile acid sequestrant (cholestyramine) facilitates excretion of PFOA in animals and significantly diminishes liver and plasma levels,10 colesevelam hydrochloride, another bile acid sequestrant, did not appear to be effective in diminishing serum PFOA values. At present, it does not appear that we have an agent that will consistently and effectively reduce PFOA levels in humans, and we need to focus on reducing exposure through regulation and improved technique to eliminate the chemical from water and other potential sources. Knowledge and awareness about novel cardiovascular risk factors, such as PFOA levels, should not dissuade us from aggressively managing known existing risk factors for CVD such as dyslipidemia, smoking, hypertension, diabetes, obesity, and lack of regular physical activity.
Correspondence: Dr Mukherjee, Division of Cardiovascular Medicine, Department of Internal Medicine, Texas Tech University, 4800 Alberta Ave, El Paso, TX 79905 (firstname.lastname@example.org).
Published Online: September 3, 2012. doi:10.1001/archinternmed.2012.3397
Financial Disclosure: None reported.
Mukherjee D. Perfluorooctanoic Acid Exposure and Cardiovascular DiseasePotential Role and Preventive Measures Comment on “Perfluorooctanoic Acid and Cardiovascular Disease in US Adults”. Arch Intern Med. 2012;172(18):1403-1405. doi:10.1001/archinternmed.2012.3397