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“These observations suggest that the often-observed epidemiologic correlation between low serum urate and adverse health outcomes may be confounded."
Among patients with low serum urate (SU) concentrations, sarcopenia and weight loss are common symptoms. Body composition differences may help to explain the link between low SU and higher mortality, according to a study published in Arthritis & Rheumatology.1
“A number of observational studies have linked low SU concentrations to adverse outcomes such as dementia, Parkinson’s disease and early mortality,” investigators explained. “These studies have raised the question about whether excessive urate lowering might have adverse consequences, and therefore some society gout guidelines have promulgated recommendations to be cautious with urate-lowering therapy, which may delay or negate optimal gout control. However, it is important to note that SU concentrations are strongly and positively associated with obesity and nutritional status.”
Data from the National Health and Nutrition Examination Survey (NHANES), between 1999 and 2006, was used to evaluate adult patients (≥ 20 years) using whole-body dual-energy x-ray absorptiometry (DXA) body composition scans as well as available SU concentrations. Body composition was assessed using body mass index (BMI), maximum lifetime BMI, waist circumference, and age-, sex-, and race-specific appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2) Z-Scores. Associations between SU and body composition were determined using logistic regression. Mortality was determined using NHANES Public Use Linked Mortality files from the National Center for Health Statistics (NCHS). SU and mortality were assessed before and after adjusting for differences in body composition via Cox regression.
Low SU concentrations were defined as <2.5 mg/dL in women and <3.5 mg/dL in men. Of the 13,979 patients evaluated, 50% were female, the mean age was 45.9 years, and the mean BMI was 28.3. Lower SU concentrations were associated with low lean mass (ALMI and ALMIFMI Z-Scores), an underweight BMI (defined as <18.5 kg/m2), and higher rates of weight loss.
More patients in the low SU group had lower ALMI Z-Scores (29%) when compared with the normal SU group (16%, p= 0.001). Additionally, low SU was associated with increased mortality before adjustments for body composition (HR (95% CI): 1.61 [1.14,2.28], p= 0.008). However, after adjusting for body composition and weight loss, results were non-significant (HR: 1.30 [0.92,1.85], p= 0.13).
Investigators were unable to characterize metabolic health more closely among participants exhibiting low circulating urate, which limited the study. Additionally, while NHANES is generally highly representative, the limited number of patients on urate lowering therapies hindered the ability to determine specific associations between low SU levels and outcomes for those currently treated with urate-lowering therapy. Long-term outcomes, such as dementia or cognitive decline, could not be examined. Future studies could be helpful, especially within older populations. The measure of historical weight loss used in this study was self-reported and did not include whether weight loss was intentional or unintentional, which may have been helpful. However, previous research suggests that weight loss in older adults is more likely to be unintentional.
“These observations suggest that the often-observed epidemiologic correlation between low SU and adverse health outcomes may be confounded,” investigators concluded. “Investigators should take care to consider confounding related to weight loss, sarcopenia, cachexia, frailty, and related conditions when interpreting associations between low SU levels and long-term outcomes in population-based studies.”
Baker JF, Weber DR, Neogi T, et al. Associations between low serum urate, body composition, and mortality [published online ahead of print, 2022 Aug 16]. Arthritis Rheumatol. 2022;10.1002/art.42301. doi:10.1002/art.42301