BackgroundTraditionally viewed as a disease of White men, global frequency and disability burden of female gout are rising disproportionately to male gout.1 Moreover, emerging US cohort data suggest gout and hyperuricemia impart larger burdens on Black adults than Whites.2 These racial disparities may be largely attributable to differences in non-genetic, mainly modifiable gout risk factors e.g., BMI, diet,3,4 and chronic kidney disease (CKD). However, national-level, general population data on racial differences in burden of gout, and potential mediators, are lacking.ObjectivesTo determine and quantify sex-specific mediators of racial disparities in gout prevalence among a nationally representative sample of US adults.MethodsUsing recent decadal data (2007-2016) on physician-diagnosed gout and hyperuricemia from the National Health and Nutrition Examination Survey, we compared contemporary sex- and race-specific prevalences and conducted sequential causal mediation analysis (adjusting for upstream mediators following causal pathways)5 to determine the proportion of the racial differences attributable to 7 potentially mediating social and clinical factors (see DAG in Figure 1): low education, poverty, body mass index (BMI), alcohol, poor quality diet (poor DASH adherence), diuretic use, and CKD (eGFR <60 mL/min, using the latest equations that do not include a coefficient for Black race6, per National Kidney Foundation and American Society of Nephrology recommendations.7)ResultsAge standardised prevalence of gout was 3.5% and 2.0% in Black and White women, respectively (age-adjusted OR =1.8 [95% CI: 1.3 to 2.5]), and 7.0% and 5.4% in Black and White men (age-adjusted OR =1.3 [1.0 to 1.6]). Most risk factors were more frequent/elevated in Blacks than Whites, except alcohol consumption, which was lower in Blacks (both sexes). BMI levels and poverty were higher in Black women, but similar between Black and White men.Largest mediating factor of excess gout cases among Black women was excess BMI, accounting for 56% of the racial difference (independent of education, poverty, diet, and alcohol), followed by CKD (24%), poverty (17%), and poor diet (12%) (see Table 1).Table 1.Indirect (mediation) effects of potential mediators, using sequential mediation analysis, for the association between Black race and odds of gout in US women and men.WOMENMENEffect Estimate (OR), 95% CIProportion Mediated, %Effect Estimate (OR), 95% CIProportion Mediated, %Indirect (Mediation) EffectEducation (high school or less)1.01 (0.98 to 1.03)2.4%1.01 (0.98 to 1.03)3.3%Poverty1.07 (1.04 to 1.10)16.9%1.00 (0.99 to 1.00)0.53%Alcohol consumption (# drinks/week, continuous)0.99 (0.96 to 1.01)-3.4%0.99 (0.98 to 1.00)-4.5%DASH diet score (continuous; higher scores = ↓ adherence)1.05 (0.96 to 1.01)12.0%1.05 (1.01 to 1.10)19.8%Body mass index (continuous)1.25 (1.14 to 1.37)55.9%1.03 (1.02 to 1.04)11.9%Diuretic use1.03 (1.01 to 1.05)7.6%1.04 (1.02 to 1.06)14.2%Chronic kidney disease1.10 (1.04 to 1.16)23.9%1.12 (1.08 to 1.17)45.6%Direct Effect0.94 (0.68 to 1.30)a−15.2%1.02 (0.83 to 1.26)b9.2%Total Effect1.49 (1.12 to 1.98)100%1.29 (1.05 to 1.57)100%DASH=Dietary Approaches to Stop Hypertension;ap=0.52,bp=0.83Among men, CKD was the largest mediator (46%), followed by poor diet (20%) and diuretic use (14%). BMI (12%) and poverty (0.5%) mediated smaller proportions of the racial difference among men compared to women. Mediators of racial differences in hyperuricemia closely agreed with gout results.ConclusionContrasting with historical views, gout is more frequent among Black adults in the US than their White counterparts, especially women (two-times greater in Black women vs. White). Culturally informed efforts to reduce these disparities should focus on excess adiposity, diet quality, and kidney disease while recognising the impact of poverty in female gout.