We appreciate the thoughtful comments by Reyes regarding our recent article.1 Reyes hypothesizes that an increase in the serum uric acid level induced by the use of diuretics may benefit the heart, blood vessels, and the brain. Diuretics, in addition to antihypertensive effect, were often prescribed for the treatment of symptoms of heart failure. Clinical trials have confirmed that, among patients with hypertension, low-dose diuretics are superior to other classes of antihypertensive agents (eg, calcium channel blockers and β-blockers) in reducing the risk of heart failure.2 The use of diuretics is known to increase serum uric acid concentration. Indeed, because uric acid could act as a powerful antioxidant, mild hyperuricemia might confer potential beneficial effects in reducing the risk of dementia including Alzheimer disease. However, Reyes's hypothesis remains in debate,3 and strong evidence in support of his hypothesis is lacking. Among the few studies addressing this issue, the follow-up data from the Atherosclerosis Risk in the Communities study4 demonstrated an independent moderate positive association between serum uric acid concentration and the risk of incident ischemic stroke. Although such an association was mainly restricted to subjects who did not use diuretics, no significant inverse association between the level of serum uric acid and incidence of stroke was suggested among those receiving diuretics. Furthermore, in the diuretic-based clinical trial of the Systolic Hypertension in the Elderly Program,5 the increase in serum uric acid level related to the use of diuretics was not associated with the risk of developing stroke, whereas the benefits of the active treatment on coronary events were offset in individuals who had a greater increase in serum uric acid concentration.
Qiu C, Winblad B, Fratiglioni L. Heart Failure, Dementia, and Diuretics: Is Uric Acid Involved?—Reply. Arch Intern Med. 2006;166(20):2287. doi:10.1001/archinte.166.20.2287-a