Comment on: Gout: an independent risk factor for all-cause and cardiovascular mortality
Year: 2010
Type: letter
Abstract: Sir, Kuo et al. [1] found that gout, but not hyperuricaemia, was an independent risk factor for all-cause and cardiovascular mortality independent of age, gender, metabolic syndrome and proteinuria. However, the mechanisms underlying this association were not clearly defined. A plausible pathophysiological mechanism might be related to inflammation, which represents the characteristic difference between gout and hyperuricaemia. Indeed, it is well known that hyperuricaemia and/or crystal deposition are not sufficient to cause gouty attacks. We propose that iron may represent a factor that triggers inflammation and heightens cardiovascular risk in gouty patients. Accumulating evidence suggests that gout is a disease of iron overload. Uric acid accumulation, as both an anti-oxidant and an iron chelator [2], has been found in response to iron overload [3, 4]. In fact, human tophi and the SM contain iron [5]. Furthermore, it has been shown that some portion of the gouty inflammation after urate crystal deposition could result from the incomplete complexation of iron with subsequent catalytic generation of reactive oxygen species [3]. On the other hand, mounting evidence suggests a link between abnormal iron storage and the development of coronary artery disease [6]. Interestingly, it was found that iron depletion prevented the relapse of the acute arthritis of primary gout in 58% of gouty patients and markedly reduced its frequency and severity in the remaining 42% [7]. Although a study of iron depletion in the primary prevention of cardiovascular disease has not been performed so far, it is highly plausible that the protection against ischaemic cardiovascular disease in individuals with severely impaired haemostasis might be related to the decrease in stored tissue iron caused by recurrent bleeding [8]. Iron depletion may prevent cardiovascular disease and gouty arthritis through multiple cooperating mechanisms [7, 9]. A general mechanism with multiple consequences is an effect of stored iron on the availability of redox-active iron. In fact, the amount of free iron available at sites of oxidative or inflammatory injury appears to be a function of the stored iron level [7, 10]. Therefore, iron may represent an important biological link between gout and cardiovascular disease. Disclosure statement: The authors have declared no conflicts of interest.
Source: Lara D. Veeken
Authors: L. Mascitelli, F. Pezzetta, M. R. Goldstein
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2101609679