Death by Gout?

Humans are the only mammals that are able to experience hyperuricemia. Increases in uric acid are likely due to mutations over time in the enzyme uricase. The increase in uric acid may not all be bad. It may be evolutionarily protective leading to increased BP, increased NaCl retention, increased insulin resistance, and central adiposity, which may enhance survival in leaner times. High uric acid levels may also be neuroprotective as an antioxidant. So evolutionarily, there may be an advantage to have higher uric acid levels.

However, life has changed and most developed countries are not in “leaner times.” Hyperuricemia is a clear risk factor for gout. It is also a risk factor for urolithiasis and a risk marker (maybe a risk factor) for CV and renal disease.

The initial Framingham data found hyperuricemia to be a risk for CV disease. However, when other risk factors (smoking, diabetes etc) were controlled, hyperuricemia was not found to be an independent risk factor. Subsequent meta-analytic data shows that hyperuricemia can increase the risk for stroke incidence & associated mortality, atrial fibrillation, ischemic cardiovascular mortality, incident heart failure, and it is a marker of poor prognosis for patients with heart failure and recent MI. In long-term follow-up studies, hyperuricemia has been found to be predictive of incipient hypertension, metabolic syndrome, and type 2 diabetes.

The question remains, is uric acid a risk marker or a risk factor for CV disease? The answer would lie within research that shows lowering uric acid levels improves cardiovascular mortality.

Observed cardiovascular benefits of lowering uric acid include: reductions in blood pressure in hypertensive patients with hyperuricemia and improved survival in patients with heart failure including those with gout. The mechanisms underpinning the potential clinical benefits of urate lowering therapy (ULT) are not fully understood but may include a reduction in oxidative stress, improved endothelial function, and reduced levels of inflammation. Interestingly, ULT has been shown to reduce C-reactive protein levels in patients with asymptomatic hyperuricemia and in those with gout.

These initial findings highlight the need for further research on the benefits of ULT in diseases other than gout.

More reports from EULAR 2015