How Do You Rate Urate?

Abstract & Commentary

Synopsis: Elevated serum uric acid is a marker for cardiovascular mortality.

Source: Niskanen LK, et al. Arch Intern Med. 2004;164:1546-1551.

Analyzing data from the Kuopio Ischaemic Heart Disease Risk Factor Study, Niskanen and colleagues looked for associations between serum uric acid (SUA) and risk factors for cardiovascular and all-cause mortality. The Kuopio study was a prospective, population-based inquiry that followed 2682 Finnish men who were 42, 48, 54, and 60 years old at baseline between 1984 and 1989. Follow-up (mean, 11.9 years) was through 1998. The current study excluded men with cardiovascular disease (except hypertension), cancer, or diabetes mellitus and men with missing SUA levels, leaving 1423 subjects. During follow-up, there were 157 deaths (55 from cardiovascular disease [CVD]). Age, smoking, alcohol intake, low socioeconomic status, hypertension, and body mass index were all associated with CVD death in univariate analysis. Age, smoking, alcohol intake, low socioeconomic status, use of hypertensive medications, and waist circumference were all associated with all-cause mortality. SUA was associated with CVD death and showed a trend to all-cause mortality. There was a "dose-response" effect with age-adjusted proportional hazards analysis showing a 2.7-fold increase when comparing the lowest tertile with the upper two. Adjusting for factors related with gout or metabolic syndrome did not weaken the association.

Comment by Allan J. Wilke, MD

The strengths of this study are its prospective design, long follow-up, and the exclusion of significantly ill men.

Uric acid is a byproduct of purine. Hyperuricemia can result from increased purine intake, purine overproduction, increased purine breakdown, or impaired urate excretion by the kidneys. Such a variety of mechanisms makes it difficult to ascribe a causative role in CVD to SUA. A recent study of Korean men did not find that SUA is an independent risk factor for death from cancer, atherosclerotic CVD, or all causes,1 nor was this the case among community-dwelling elderly patients in the United States.2 However, among men and women with known coronary artery disease, SUA was an independent predictor of mortality.3 The National Health and Nutrition Examination Survey epidemiologic follow-up study also found SUA to be an independent risk for cardiovascular death.4 Is SUA an evildoer or an innocent bystander in CVD? This question is yet to be answered. More practically, does treatment of elevated SUA reduce CVD risk? Until recently, there was no evidence for that. This may be changing. The Losartan Intervention for End Point reduction in hypertension study showed that losartan was superior to atenolol in reducing CVD morbidity and mortality, and it reduced the increase in SUA better than atenolol, which appeared to account for 29% of the treatment effect.5

Assuming that you can extrapolate these findings from a group of middle-aged male Finns to your next patient with an elevated SUA, what are you going to do? At the very least, keeping a high index of suspicion for possible cardiovascular disease is in order.

Dr. Wilke, Associate Professor of Family Medicine, Medical College of Ohio, Toledo, OH, is Associate Editor of Internal Medicine Alert.


1. Jee SH, et al. Eur J Cardiovasc Prev Rehabil. 2004;11: 185-191.

2. Hu P, et al. J Am Geriatr Soc. 2001;49:1679-1684.

3. Bickel C, et al. Am J Cardiol. 2002;89:12-17.

4. Fang J, Alderman MH. JAMA. 2000;283:2404-2410.

5. Hoieggen A, et al. Kidney Int. 2004;65:1041-1049.