Comorbidities may play a greater role than genetics women with gout, although this appears not to be true for men, Nicholas Sumpter, MSc, of the University of Alabama at Birmingham said at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).
Mr. Sumpter was among the authors of a recent paper in Arthritis & Rheumatology that suggested that earlier gout onset involves the accumulation of certain allelic variants in men. This genetic risk was shared across multiple ancestral groups in the study, conducted with men of European and Polynesian ancestry, Mr. Sumpter and colleagues reported.
“There might be more than one factor in gout in men, but in women we’ve been getting at this idea that comorbidities are the big thing,” he said.
During his presentation, Mr. Sumpter offered a hypothesis that in men there might be a kind of “two-pronged attack,” with increases in serum urate linked to genetic risk, but comorbidities also playing a role. “But that may not be the case for women.”
In his presentation, Mr. Sumpter noted a paper published in March 2022 from his University of Alabama at Birmingham colleagues, Aakash V. Patel, MD, and Angelo L. Gaffo, MD. In the article, Dr. Patel and Dr. Gaffo delved into the challenges of treating women with gout given “the paucity of appropriately well-powered, randomized-controlled trials investigating the efficacy” of commonly used treatments.
“This poses major challenges for the management of female gout patients since they carry a greater burden of cardiovascular and renal morbidity, which is known to modulate the pathophysiology of gout; as such, conclusions regarding the efficacy of treatments for females cannot be extrapolated from investigative studies that are predominantly male,” they wrote, calling for increased efforts to enroll women in studies of treatments for this condition.
There’s increased interest in how gout affects women, including findings in a paper published in September in Arthritis & Rheumatology that found people with gout, especially women, appear to be at higher risk for poor COVID-19 outcomes, including hospitalization and death, regardless of COVID-19 vaccination status.
Gout has become more common in women, although this remains a condition that is far more likely to strike men.
The age-standardized prevalence of gout among women rose from 233.52 per 100,000 in 1990 to 253.49 in 2017, a gain of about 9%, according to a systematic analysis of the Global Burden of Disease Study.
That topped the roughly 5% gain seen for men in the same time frame, with the rate going from 747.48 per 100,000 to 790.90. With the aging of the global population, gout’s burden in terms of prevalence and disability is expected to increase.
Impact of obesity and healthy eating patterns
Obesity, or excess adiposity, appears to be of particular concern for women in terms of gout risk.
While obesity and genetic predisposition both are strongly associated with a higher risk of gout, the excess risk of both combined was higher than the sum of each, particularly among women, Natalie McCormick, PhD, of Massachusetts General Hospital, Boston, and coauthors reported in Annals of the Rheumatic Diseases.
These findings suggested that “addressing excess adiposity could prevent a large proportion of female gout cases in particular, as well as its cardiometabolic comorbidities, and the benefit could be greater in genetically predisposed women,” they wrote.
In general, there’s a need to re-examine the advice given by many clinicians in the past that people with gout, or those at risk for it, should follow a low-protein diet to avoid purines, Dr. McCormick said in an interview.
“Now we’re finding that a healthier diet that balances protein as well as fat intake can actually be better both for cardiovascular health and for gout prevention,” she said.
Dr. McCormick’s research on this topic includes a 2022 JAMA Internal Medicine article, and a 2021 article in Current Rheumatology Reports. In the latter article, Dr. McCormick and colleagues examined the benefits of changing habits for patients, such as following one of several well-established healthy eating patterns, including the Mediterranean and DASH diets.
With excess weight and associated cardiovascular and endocrine risks already elevated among people with gout, especially women, the “conventional low-purine (i.e., low-protein) approach to gout dietary guidance is neither helpful nor sustainable and may lead to detrimental effects related to worsening insulin resistance as a result of substitution of healthy proteins with unhealthy carbohydrates or fats,” they wrote. “Rather, by focusing our dietary recommendations on healthy eating patterns which have been proven to reduce cardiometabolic risk factors, as opposed to singular ‘good’ or ‘bad’ food items or groups, the beneficial effects of such diets on relevant gout endpoints should naturally follow for the majority of typical gout cases, mediated through changes in insulin resistance.”
Mr. Sumpter and Dr. McCormick had no competing interests to declare.