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Action Points
Diuretics -- a class of drugs
known to raise serum urate levels -- independently increased the risk
for gout in patients with high blood pressure, a prospective cohort
study revealed.
After adjustment for blood pressure and potential confounders such as glomerular filtration rate, exposure to a diuretic led to a 1.48-fold increased likelihood of incident gout (95% CI 1.11 to 1.98), according to Mara A. McAdams DeMarco, PhD, of Johns Hopkins University in Baltimore, and colleagues. However, further adjustment for the level of serum urate nullified this association (HR 0.96, 95% CI 0.71 to 1.28), "suggesting that serum urate level may be a key intermediate on the pathway between diuretic use and incident gout," the researchers wrote in the January issue of Arthritis & Rheumatism. A possible link between diuretic use and gout was identified more than 25 years ago, but it has remained unclear whether the diuretic or the underlying hypertension is the main culprit. So DeMarco and colleagues analyzed data from the population-based Atherosclerosis Risk in Communities studies, focusing on 5,789 participants with hypertension, but not gout, at baseline. Men represented 42% of the cohort and African-Americans 31%. Mean age at the time of enrollment was 55, and mean body mass index was 29. A total of 37% of participants used diuretics during nine years of follow-up. The cumulative incidence of gout overall was 3.9%, but was higher in men than in women (5.3% versus 2.8%). The cumulative incidence of gout was significantly higher among those taking diuretics than among those not taking the drugs (5.5% versus 2.9%, P<0.001), the researchers reported. Any diuretic use also was associated with a three-fold higher risk of gout compared with untreated hypertension (HR 3.35, 95% CI 2.49 to 4.51). The risk of gout was elevated with both thiazide (HR 1.44, 95% CI 1 to 2.10) and loop (HR 2.31, 95% CI 1.36 to 3.91) diuretics, they noted. A total of 63 patients on thiazide diuretics developed gout, which represented a cumulative incidence of 5%; 23 cases occurred with loop diuretics, for an incidence of 7%. However, once again the association was lost after adjustment for serum urate levels for both thiazide (HR 0.94, 95% CI 0.64 to 1.38) and loop (HR 1.35, 95% CI 0.78 to 2.34) diuretics. In contrast to diuretics, treatment with other types of antihypertensive decreased the risk of gout (HR 0.64, 95% CI 0.49 to 0.86), and the risk was unchanged after adjustment for urate levels. Among patients who began diuretic treatment after enrollment in the study, serum urate levels were 0.72 mg/dL higher than in patients not taking the drugs, while initiation of a nondiuretic antihypertensive led to a decrease of 0.21 mg/dL. "Future studies should not only confirm the risk of gout associated with diuretic-induced hyperuricemia but also further elucidate the complicated relationship of hypertension, diuretics, uric acid, and gout," DeMarco and colleagues stated. Limitations of the study included self-report of gout, possible selection bias or confounding by indication, and a lack of information on specific brands of medication.
This
work was supported by the National Institutes of Health, the Donald B.
and Dorothy Stabler Foundation, and the Ira T. Fine Discovery Fund. The
authors reported no relationships with industry.
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Saturday, January 21, 2012
Increased Gout Risk With Diuretic Use Confirmed
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