For Gout, a Triad of Risk Factors

Obesity, hypertension, and use of diuretic medications are independent risk factors for incident gout, with each factor more than doubling the risk, a new report confirmed.

In a meta-analysis, the multivariate-adjusted relative risk for gout was 2.24 (95% CI 1.76 to 2.86) in adults whose body mass index (BMI) was 30 kg/m² or higher, according to James A. Prior, PhD, and colleagues from Keele University in England.

And the adjusted relative risks were 2.11 (95% CI 1.64 to 2.72) in patients with hypertension and 2.39 (95% CI 1.57 to 3.65) for those taking diuretics, the researchers reported online in Arthritis Research & Therapy.

The incidence of gout is on the rise worldwide, and treatment is suboptimal. Identifying patients at risk -- particularly in primary care, where most gout management occurs -- is therefore an important goal.

Both obesity and hypertension have been linked with gout in large epidemiologic studies, but the magnitude of risk is unclear. "Obesity promotes insulin resistance which in turn reduces renal urate excretion resulting in hyperuricemia. Hypertension predisposes to gout by reducing renal urate excretion due to glomerular arteriolar damage and glomerulosclerosis," Prior and colleagues explained.

Diuretics can increase the reabsorption of uric acid while decreasing its renal secretion, but it's unclear whether these drugs' influence on gout risk is through effects on uric acid or relates to the comorbidities such as hypertension they are used to treat.

Therefore, to further explore the role of these three risk factors -- all potentially modifiable -- the researchers conducted a systematic review of the literature, identifying 14 studies that met their criteria. Sample sizes in the articles ranged from 923 to 60,181 and incident gout cases from 43 to 1,341, while follow-up time ranged from 8 to 52 years. A total of 11 of the studies were suitable for inclusion in the meta-analysis.

Two of the studies included only men, who were health professionals or medical students, while one focused only on women. In the majority of studies, most participants were white, and adjustment was made for age, sex, comorbidities, and diet. Most studies took place in the United States or the United Kingdom and involved general populations.

Most studies on obesity adjusted for hypertension and diuretic use, while most studies on hypertension adjusted for BMI and exposure to diuretics and all studies looking at diuretic use adjusted for BMI and blood pressure.

Four studies addressed obesity as a risk factor for gout, and provided an unadjusted relative risk of 2.84 (95% CI 2.15 to 3.76). There was little heterogeneity between the studies (I ²=21.4%, P=0.278).

Ten studies focused on hypertension as a risk factor, and the unadjusted relative risk was almost three times higher than for individuals with normal blood pressure (RR 2.98, 95% CI 2.63 to 3.37). Again, no evidence of heterogeneity was seen (I ²=48.3%, P=0.122).

Diuretic use as a risk factor for gout was examined in three studies, which together showed an unadjusted relative risk of 3.59 (95% CI 3.06 to 4.21), but significant heterogeneity was seen for the multivariate-adjusted relative risks (I ²=79.1%, P=0.008).

The study adds to the evidence suggesting that weight reduction should be a focus of gout prevention, and that diuretics should be avoided in patients at risk whenever possible, according to the authors.

"Future research should consist of prospective studies that consider the interaction between comorbidities and examine how certain clusters of comorbidities influence the risk of developing gout," they concluded.

Limitations of the analysis included the studies' reliance on self-report of gout and the use of specific population samples such as health professionals.