The presence of gout is associated with cardiometabolic comorbidities, independent of serum urate (SU) levels, suggesting the involvement of separate SU-independent mechanisms, including inflammation driven by crystal deposition, nonpurine dietary factors, and proinflammatory genotype, according to results of a case-control study published in Rheumatology (Oxford).

Researchers sought to determine the association between gout, comorbidities and SU, and whether the association between gout and comorbidities was independent of SU levels. They performed 2 separate analyses using  UK Biobank data, with 1 of the analyses excluding participants with gout to examine the link between comorbidities and SU, and the other including participants with gout as the index condition to study the association between gout and comorbidities. Levels of SU were measured at the baseline visit. Self-reported physician-diagnosed conditions were used to define gout and all comorbidities except chronic kidney disease (CKD), which was defined using an estimated glomerular filtration rate cutoff. All participants who received urate-lowering therapy (ULT) were also classified as having gout.

Data from 10,265 patients with gout (11% women; mean participant age, 59.92±7.00 years; mean body mass index, 30.61±5.02; mean SU, 6.67±1.78 mg/dL) and 458,781 control participants were included in the analysis to examine the association between gout and comorbidities.


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The prevalence of self-reported physician-diagnosed comorbidities in patients with gout, included hypertension (57.20%); hypercholesterolemia (27.56%); diabetes mellitus (DM; 12.47%); ischemic heart disease (IHD; 13.49%); congestive cardiac failure (CCF; 0.60%); and CKD stage 3b or higher (3.96%). Researchers observed that gout was independently associated with hypertension, DM, hypercholesterolemia, IHD, CCF, and CKD, observed on a multivariate analysis model that included SU levels.

In a post hoc sensitivity analysis in which the researchers examined the association between gout and comorbidities after excluding patients with gout receiving ULT, hypertension, IHD, DM, CCF, and hypercholesterolemia were all linked to gout on univariate and adjusted analyses, even after adjustment for SU levels. On the other hand, the positive association between gout and increasing CKD grades, became negative after adjusting for SU levels.

Study limitations included the self-reporting of gout status and prescription data; the fact that participants were not required to fulfil the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria; and the classification of SU levels based on single measurement.

Researchers concluded, “This is a novel finding and further research is required to ascertain and better understand the underlying mechanisms so that they can be addressed. Translational research in this field will help reduce the burden of cardiovascular comorbidities in gout.”

Reference

Sandoval-Plata G, Nakafero G, Chakravorty M, Morgan K, Abhishek A. Association between serum urate, gout and comorbidities: a case-control study using data from the UK Biobank. Rheumatology (Oxford). Published online December 13, 2020. doi:10.1093/rheumatology/keaa773