High Uric Acid Linked to Gout in Women
March 30, 2010
Elevated levels of uric acid increase the risk of gout in women, a finding that has not previously been reported, researchers said.
The risk of gout among women whose uric acid level was 8 mg/dL or greater was 46 times higher than for those whose level was below 5 mg/dL (RR 45.75, 95% CI 19.17 to 109.21), according to Vidula Bhole, MD, and colleagues from Boston University.
Other risk factors independently associated with incident gout in women were increasing age, obesity, alcohol consumption, hypertension, and diuretic use (P<0.05 for all), the researchers reported in the April issue of Arthritis & Rheumatism.
* Explain to interested patients that elevated levels of uric acid are associated with an increased risk of gout in both men and women.
* Explain that the risk is further increased for women with older age, obesity, heavy alcohol consumption, hypertension, and diuretic use.
Gout has historically been considered a male disease, and most research has been limited to men. However, the disease burden among women has been growing, with the incidence doubling in the past two decades.
Because risk factors for gout have not previously been investigated for women or compared with those for men, Bohle and colleagues turned to the Framingham Heart Study, examining data from 1950 to 2002 for 2,476 women and 1,951 men.
Mean ages at baseline were 47 and 46 years for women and men, respectively, and mean baseline serum uric acid levels were 4 mg/dL and 5.1 mg/dL.
All subjects were free of gout at the time of enrollment.
During a median follow-up of 28 years there were 104 cases of gout among women and 200 in men.
The incidence was 1.4 per 1,000 person-years for women, compared with 4 per 1,000 person-years for men.
The incidence rates for women per 1,000 person-years and relative risks according to serum uric acid levels were:
* <5 mg/dL, 0.8
* 5 to 5.9 mg/dL, incidence rate 2.5, RR 3.29 (95% CI 1.98 to 5.45)
* 6 to 6.9 mg/dL, incidence rate 4.2, RR 5.49 (95% CI 2.9 to 10.42)
* 7 to 7.9 mg/dL, incidence rate 13.1, RR 22.09 (95% CI 10.98 to 44.43)
* ³8 mg/dL, incidence rate 27.3 (P for trend <0.0001)
Although risks of gout were elevated for women in a graded fashion according to uric acid level, the risk was significantly lower than for men. The relative risks according to levels of uric acid above 5 mg/dL for men were 4.54, 12.05, 31.01, and 61.27.
Multivariate relative risks of gout for women according to risk factors were:
* Age (per five years), 1.24 (95% CI 1.08 to 1.43)
* Body mass index ³30 kg/m2, 2.74 (95% CI 1.65 to 4.58)
* Heavy alcohol consumption, 3.10 (95% CI 1.69 to 5.68)
* Hypertension, 1.82 (95% CI 1.06 to 3.14)
* Diuretic use, 2.39 (95% CI 1.53 to 3.74)
The magnitude of associations with these risk factors for women were similar to those for men, except for a stronger age effect (P for interaction = 0.02).
The age-adjusted relative risk of gout conferred by menopause was 4.18 (95% CI 0.55 to 31.86).
The associations of obesity and hypertension with gout seen in this study are consistent with previous observations for men.
The link between obesity and gout is likely to derive from increased insulin levels, which can reduce renal excretion of urate.
Diuretics also play an important role in the development of gout in women, independent of hypertension, through combined effects of volume depletion and increased tubular resorption of uric acid.
"Previous retrospective case series of gout in women showed that a higher proportion of women than men with gout had hypertension and were treated with diuretics, suggesting that these risk factors may be more important among women," the authors observed.
The researchers also looked at relative risks for both sexes associated with specific types of alcohol. For women, these were:
* Heavy beer consumption, 7.10 (95% CI 1.70 to 29.62)
* Heavy spirit consumption, 2.66 (95% CI 1.24 to 5.72)
* Moderate or heavy wine consumption, 1.46 (95% CI 0.80 to 2.65)
The corresponding relative risks for men were 2, 1.82, and 1.24.
These data suggest that women may be more susceptible than men to beer and spirits as a risk factor for gout, a finding that should be confirmed by future studies.
"Our data provide support for a substantial role of alcohol intake in the risk of incident gout among women, independent of the presence of other risk factors," the researchers wrote. "To our knowledge, our findings provide the first prospective, quantitative data on the relationship between serum uric acid levels and the risk of incident gout among women."
Strengths of the study include its use of community-based prospective data, so its findings are likely to be generalizable. Also, recall bias was avoided.
Limitations were its reliance on clinical diagnosis of gout, rather than detection of urate crystals in synovial fluid, and the unavailability of creatinine measurements during the early years of the study.
The study was also observational and unmeasured factors may have contributed to the observed associations, the authors said.
The study and investigators were supported by the National Institutes of Health, the Canadian Arthritis Network/The Arthritis Society of Canada, the Michael Smith Foundation for Health Research, and the Canadian Institutes of Health Research.
One investigator has received consulting and other fees from Savient Pharmaceuticals, UCB Pharma, and Takeda Pharmaceuticals, and has served as a paid consultant to Cowan and Associates.
A second investigator has received honoraria for serving on the advisory boards of Savient Pharmaceuticals and TAP Pharmaceuticals.
Primary source: Arthritis & Rheumatism
Bhole V, et al "Epidemiology of gout in women: fifty-two-year followup of a prospective cohort" Arthritis Rheum 2010; 62: 1069-76.