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Targeting uric acid

The conference’s keynote lecture, delivered by Professor Austin Stack (University Hospital, Limerick, Ireland), homed in on the idea that serum uric acid directly contributes to increased cardiovascular disease. This was shown in his team’s work published in 2013,1 which used retrospective data to identify a direct correlation between raised serum uric acid concentrations and increased risk of developing cardiovascular disease.

This, therefore, begs two questions:

  • Firstly, does uric acid directly cause vascular endothelial damage, contributing to acute renal dysfunction – thereby increasing the risk of cardiovascular disease?
  • Secondly, does uric acid increase the risk of hypertension, chronic kidney disease and diabetes mellitus – which, in turn, increases the risk of cardiovascular problems?
Professor Austin Stack (University Hospital, Limerick, Ireland)

Professor Austin Stack (University Hospital, Limerick, Ireland)

An increase in serum uric acid is thought to result in a proportional fall in nitric oxide levels by decreasing its production. Certainly, animal studies artificially inducing hyperuricaemia have resulted in endothelial damage, and this is separate to the damage caused by reactive oxygen species (ROS) produced by xanthine oxidase.2

In humans, there have been several studies to suggest that in those with major cardiovascular co-morbidities such as hypertension, type 2 diabetes and chronic kidney disease, higher levels of serum uric acid have also been found. This previously was thought to be a result of renovascular damage and nephrosclerosis,3 but more recent studies have shown hyperuricaemia to be a predictor of onset. This risk of comorbidity has been seen to be significantly higher in the higher quartiles of uric acid concentration, suggesting a further direct correlation.

What then can be done? Is there a role for xanthine oxidase inhibitors such as allopurinol? Certainly, evidence from a study looking at adolescent hypertension suggested that taking allopurinol for only four weeks was enough to significantly reduce blood pressure in two thirds of the participants.4 Despite the encouraging results, this small study had many limitations. Further studies in humans have suggested that allopurinol use slows deterioration in renal function, and that contributes to a reduced risk of cardiovascular events.5 Professor Stack highlighted though that no large randomised control trials have yet demonstrated the beneficial effects of allopurinol in reducing cardiovascular risk, and perhaps it is time for us to focus on uric acid – a forgotten risk factor.

References

1. Stack AG, Hanley A, Casserly LF et al. Independent and conjoint associations with gout and hyperuricaemia with total and cardiovascular mortality. Q J Med 2013;106:647–58. http://dx.doi.org/10.1093/qjmed/hct083

2. Khosla UM, Zharikov S, Finch JL et al. Hyperuricaemic induces endothelial dysfunction. Kidney Int 2005;67:1739–742. http://dx.doi.org/10.1111/j.1523-1755.2005.00273.x

3. Messerli FH, Frohlich ED, Dreslinski GR et al. Serum uric acid in essential hypertension: an indicator of renal vascular involvement. Ann Intern Med 1980; 93:817–21.

4. Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: A randomized trial. JAMA 2008;300:924–32. http://dx.doi.org/10.1001/jama.300.8.924

5. Goicoechea M, García de Vinuesa S, Verdalles U et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. CJASN 2010;5:1388–93. http://dx.doi.org/10.2215/CJN.01580210

Published on: February 21, 2017

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