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Quarterly Journal of Medicine


Clinical Articles, Lead Article

Hyperuricaemia an independent marker of CV risk

Gout and serum uric acid are independently associated with total and cardiovascular mortality, and these risks increase with rising uric acid concentrations, according to a study1 published recently in the Quarterly Journal of Medicine.

Mortality risks of gout and serum uric acid were determined for 15,773 participants, aged 20 years or older, in the Third National Health and Nutrition Examination Survey (NHANES) by linking baseline information collected during 1988–1994 with mortality data up to 2006. Multivariable Cox proportional hazards regression determined adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each exposure and all analyses were conducted in 2011 and 2012.

Professor Austin Stack (Univesity of Limerick, Ireland)

Professor Austin Stack (Univesity of Limerick, Ireland)

Compared with subjects without a history of gout, the multivariable HR for subjects with gout were 1.42 (CI 1.12–1.82) for total and 1.58 (CI 1.13–2.19) for cardiovascular mortality. Adjusted HRs per 59.5 mmol/l (1 mg/dl) increase in uric acid were 1.16 (CI 1.10–1.22) for total and cardiovascular mortality and this pattern was consistent across disease categories. In the conjoint analysis, the adjusted HRs for mortality in the highest two uric acid quartiles were 1.64 (CI 1.08–2.51) and 1.77 (CI 1.23–2.55), respectively, for subjects with gout, and were 1.09 (CI 0.87–1.37) and 1.37 (CI (1.11–1.70), respectively, for subjects without gout, compared with those without gout in the lowest quartile. A similar pattern emerged for cardiovascular mortality.

Lead author Professor Austin Stack (Univesity of Limerick, Ireland), speaking to BJC Arrhythmia Watch, said: “This study demonstrates that gout and elevated uric acid levels are independently associated with total and cardiovascular mortality in the general population. The risks were greatest for subjects with gout and the highest uric acid concentrations.”

“While, there is debate as to whether uric acid and gout can be truly considered risk factors (as no studies to date have demonstrated a reduction in cardiovascular event rates following treatment), it is abundantly clear that adults with hyperuricaemia and gout are more likely to have co-existing diabetes, hypertension, hyperlipidaemia, obesity, and physical inactivity, all of which are strongly associated with cardiovascular disease and death. Thus even if uric acid is considered a risk marker, screening for hyperuricaemia should lead to increased detection of high-risk individuals amenable to treatment,” he added.

“We do advocate the necessity for randomised controlled clinical trials to evaluate whether effective treatment of hyperuricaemia and gout results in fewer cardiovascular events and ultimately lower death risk. While we wait for these, we would suggest that individuals with hyperuricaemia be considered at high-risk for cardiovascular disease and death and that these undergo detailed cardiovascular risk assessment with appropriate intervention,” Professor Stack concluded.


Spiked rods of monosodium urate crystals under polarized light from a synovial fluid sample. © Bobjgalindo


1. Stack AG, Hanley A, Casserly, LF, et al. Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality. Q J Med 2013;106:647–58.

Published on: November 20, 2013

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