Old Disease, New Tricks: A Novel Approach to Understanding Gout

The implication of these findings is that TRAF1 may be a possible therapeutic target for inflammasome-driven diseases like gout.²

Michael Pillinger, MD

Endothelial & Vascular Dysfunction in Gout

The second speaker in the session was Michael Pillinger, MD, professor of medicine and of biochemistry and molecular pharmacology, NYU Grossman School of Medicine, New York. He discussed how gout treatment may or may not affect endothelial and vascular dysfunction.

To begin his presentation, Dr. Pillinger explained that there are four elements to gout as we know it:

1. Hyperuricemia;
2. MSU crystal formation and deposition;
3. Disease flares; and
4. Tophi.

However, this conceptual framework ignores the effects that gout may have on the vasculature, and indeed, Dr. Pillinger says this should serve as a fifth element of how we understand the disease.

In terms of the effects that gout has on the vasculature, it is notable that patients with gout have higher rates of cardiovascular disease (CVD) than the general population. Rates of CVD are more similar to those seen in patients with rheumatoid arthritis and psoriatic arthritis. Dr. Pillinger referenced work that shows how hyperuricemia is associated with hypertension, systemic inflammation and CVD via endothelial dysfunction and abnormal vascular remodeling. In fact, there is evidence that soluble urate inhibits endothelial cell production of nitric oxide (NO).³ This is an important observation because NO mediates endothelium-dependent relaxation, inhibits platelet aggregation, prevents platelet adhesion to endothelial surfaces and induces disaggregation of platelets.

Given these findings, Dr. Pillinger described a study (in which he was a co-author) that sought to assess if gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) could improve arterial function and reduce inflammation in patients. In this study, 38 patients with untreated gout received colchicine (in a dose of 0.6 mg twice daily or once daily based on ability to tolerate the medication) and an XOI (allopurinol or febuxostat) that was titrated to ACR guideline-defined serum urate target. Treatment was initiated during periods in between gout flares, and the start of treatment with colchicine and XOI were staggered to allow for assessment of a potential independent effect of colchicine alone.

Dr. Pillinger and colleagues used brachial artery flow-mediated dilation to measure endothelium-dependent arterial responsiveness and nitrate-mediated dilation to measure endothelium-independent arterial responsiveness. This team also used high-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) to evaluate systemic inflammation.