Update on Gout and Hyperuricemia

J. F. Baker; H. Ralph Schumacher

Disclosures

Int J Clin Pract. 2010;64(3):371-377. 

In This Article

Other Considerations

Cardiovascular Risk

Acute flares of gouty arthritis are associated with increases in inflammatory markers such as CRP.[42] Elevated CRP is an independent risk factor for cardiovascular disease.[43] A history of gouty arthritis appears also to be an independent risk factor for acute myocardial infarction, perhaps through this increase in systemic inflammation.[44] Large population based studies have shown that a diagnosis of gout is associated with increased cardiovascular and overall mortality independent of other risk factors.[45–47]

As previously mentioned, hyperuricemia is associated with a number of cardiovascular risk factors including obesity, hypertension and dyslipidemia. Studies suggest that uric acid has harmful cardiovascular effects independent of these associations.[48] SUA levels are associated with carotid atherosclerosis independent of hypertension and other risk factors.[49] Gout and hyperuricemia are independent risk factors for the development of acute myocardial infarction, stroke and peripheral arterial disease.[44,50,51] Emerging data also suggest that hyperuricemia is an independent predictor of cardiovascular morbidity and mortality.[48,51]

The effect of hyperuricemia on cardiovascular outcomes is likely to be the modest when compared with other risk factors. There have been no studies to suggest a benefit of uric acid-lowering therapy on cardiovascular outcomes in either asymptomatic hyperuricemia or hyperuricemic patients with gout.

Endothelial Dysfunction and Hypertension

Serum uric acid levels have been associated with endothelial dysfunction.[52] Induction of elevated uric acid levels in rats with a uricase inhibitor has been shown to decrease nitric oxide production by endothelial cells and increase blood pressure; a finding that was reversible with allopurinol.[53] Soluble uric acid activates the renin-angiotensin system and has been shown to have proinflammatory and proliferative effects on vascular smooth muscle cells.[54,55]

The association between hyperuricemia and hypertension is well known. Large epidemiological studies, including a subset of the Framingham Heart Study, have also revealed that hyperuricemia predicts incident hypertension.[54] Several small studies have demonstrated some improvement in blood pressure in patients treated with allopurinol.[56,57] It is not yet clear if hypertensive patients with gout will receive blood pressure reduction upon initiation of uric acid-lowering therapy.

Progression of Kidney Disease

Hyperuricemia has also been shown to predict the development of chronic kidney disease in a number of studies.[58] It is unclear from these studies if an elevated SUA has a causal role in the incidence and progression of renal disease or if it is simply a sensitive marker of nephron loss. In patients with stage 3–4 chronic kidney disease, hyperuricemia is also an independent risk factor for all-cause mortality.[59]

One uncontrolled study has suggested that withdrawal of chronic allopurinol therapy may result in worsening hypertension and accelerated loss of renal function.[60] A controlled clinical trial of allopurinol in 54 patients with hyperuricemia and mild-moderate chronic kidney disease resulted in decreased progression of disease at 12 months of therapy.[57] This evidence would support aggressive, goal-oriented treatment of hyperuricemia in patients with renal disease and gout.

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