American Journal of Epidemiology Advance Access originally published online on February 17, 2008
American Journal of Epidemiology 2008 167(6):752-753; doi:10.1093/aje/kwn008
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LETTERS TO THE EDITOR |
RE: "PLASMA URATE AND RISK OF PARKINSON'S DISEASE"
Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA 02118
(e-mail: barton.wise{at}bmc.org)
In their recent article, Weisskopf et al. (1) reported that risk of Parkinson's disease was decreased by 57 percent among subjects in the highest quartile of plasma urate level (7.0–9.7 mg/dl) in comparison with those in the lowest quartile (<5.3 mg/dl). In the abstract, the authors stated that their results "raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's disease" (1, p. 561). We feel that this recommendation is premature.
First, the study was designed to examine the association between plasma urate level and the risk of development of Parkinson's disease, not the risk of disease progression. While the authors cited a recent conference report which suggested that a high plasma urate level may decelerate the progression of Parkinson's disease (2), there is a paucity of evidence to support a potential beneficial effect of high urate levels on disease progression. On the other hand, as the authors pointed out, several recent studies have shown that high levels of urate are associated with increased risk of cardiovascular disease mortality (3, 4). Furthermore, there is ample evidence that hyperuricemia (urate levels 
6.8 mg/dl) increases the risk of gout attacks (5). Given the well-established harmful effects of hyperuricemia and the meagerness of knowledge about the effect of urate on the central nervous system, one must wonder whether there exists any practical clinical potential for slowing the progression of Parkinson's disease by increasing urate levels.
Second, the authors hypothesized that the putative protective effect of plasma urate on the risk of Parkinson's disease is due to its antioxidant properties. However, other studies have suggested that uric acid is also prooxidative under certain conditions (6). Even if the proposed biologic mechanism were real, it would perhaps be more prudent to explore the possibility of a therapeutic effect on progression of Parkinson's disease of other antioxidants which do not carry the same level of recognized risk as does urate.
As an aside, there appears to be a discrepancy between the text and part A of figure 1 (1, p. 564). In the text and abstract, the rate ratio for Parkinson's disease for the highest quartile of urate level compared with the lowest is 0.43 (95 percent confidence interval: 0.18, 1.02). However, in figure 1, part A, the upper limit of the 95 percent confidence interval appears to be lower than 1.00, leaving readers with the impression that there is a statistically significant difference in the risk of developing Parkinson's disease when comparing subjects in the highest quartile of urate level with those in the lowest quartile.
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ACKNOWLEDGMENTS |
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Conflict of interest: none declared.
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References |
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 TOP References |
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- Weisskopf MG, O'Reilly E, Chen H, et al. Plasma urate and risk of Parkinson's disease. Am J Epidemiol (2007) 166:561–7.
[Abstract/Free Full Text] - Schwarzschild MA, Schwid SR, Mare kK, et al. Serum urate level predicts progression of Parkinson's disease. (Abstract). Presented at the 36th Annual Meeting of the Society for Neuroscience, Atlanta, Georgia, October 14–18. (2006) (http://www.sfn.org/am2006).
- Niskanen LK, Laaksonen DE, Nyyssonen K, et al. Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med (2004) 164:1546–51.
[Abstract/Free Full Text] - Fang J, Alderman MH. Serum uric acid and cardiovascular mortality: the NHANES I Epidemiologic Follow-up Study, 1971 –1992. JAMA (2000) 283:2404–10.
[Abstract/Free Full Text] - Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med (1987) 82:421–6.[CrossRef][Medline]
- Bagnati M, Perugini C, Cau C, et al. When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid. Biochem J (1999) 340:143–52.[CrossRef][Web of Science][Medline]
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  M. G. Weisskopf, E. O'Reilly, H. Chen, M. A. Schwarzschild, and A. Ascherio THE AUTHORS REPLY Am. J. Epidemiol., March 15, 2008; 167(6): 753 - 754. [Full Text] [PDF]
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