Background/Purpose: There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in Communities (ARIC).

Methods: ARIC is a prospective population-based cohort recruited in 1987-1989 from 4 US communities, consisting of 4 visits over 9 years. Participants were included in this analysis if they answered the gout query and were free of gout at baseline. Incident gout was defined as self-reported onset after baseline. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model (age as time scale), we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, eGFR, BMI, and alcohol intake) and clinical factors (coronary heart disease, CHF, diabetes, hypertension, diuretic use, and serum urate level).

Results: A total of 10,791 ARIC participants met the study criteria. The study population was 43% male, 21% African American and the mean age at cohort entry was 54 years (SD=5.7). The mean hemoglobin level was 13.9 g/dL (SD=1.37); for men 14.9 g/dL (SD=1.1) and for women 13.1 g/dL (SD=1.1). At baseline, 1,084 (10%) participants were classified as having anemia; 66% of the participants with anemia were women. There were 271 cases of incident gout. The results are presented in the table. Patients with anemia had a 2-fold increased risk of developing gout (HR=2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR=1.73, 95% CI: 1.24, 2.41) and after additionally adjusting for serum urate level (HR=1.83, 95% CI: 1.30, 2.57). There was no evidence of effect measure modification by race (p=0.83) or kidney function (p-value=0.29) and limited support for an interaction by sex (p=0.06). Among female participants, the HR of incident gout by baseline anemia status was 2.38 (95% CI: 1.47, 3.84) compared to 1.43 (95% CI: 0.88, 2.30) for male participants.

Table: HR of incident gout by baseline anemia in ARIC
Model	HR (95% CI)
Unadjusted	2.01 (1.46, 2.76)*
Sex and race adjusted	1.52 (1.10, 2.12)*
Sex, race and eGFR adjusted	1.54 (1.11, 2.14)*
Adjusted for confounders1	1.64 (1.18, 2.28)*
Additionally adjusted for clinical factors2	1.73 (1.24, 2.41)*
Additionally adjusted for serum urate	1.83 (1.30, 2.57)**
1 Confounders: Sex, race, categorical eGFR, BMI and alcohol intake. 2 Clinical factors: Baseline hypertension, diuretic use, CHD, and CHF. * p< 0.05 ** p<0.001

Conclusion: We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately 2-fold increased risk of gout independent of kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anemia-and-the-onset-of-gout-in-a-population-based-cohort-of-adults-atherosclerosis-risk-in-communities-study/