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Is uric acid related to heart disease?

 

Clinical bottom line

No overwhelming evidence exists to link uric acid levels to cardiovascular disease or mortality, except through links with other risk factors.


There have been suggestions that elevated uric acid levels are associated with increased heart disease, and death from heart disease. The problem is that elevated uric acid levels are found when people are overweight, and when they have other risk factors also associated with heart disease. Teasing out whether uric acid, per se, is an independent risk factor will be difficult. There are two good epidemiological studies that reach opposite conclusions.

References


BF Culleton et al. Serum uric acid and risk for cardiovascular disease and death: the Framingham heart study. Annals of Internal Medicine 1999 131: 7-13.


J Fang, MH Alderman. Serum uric acid and cardiovascular mortality. The NHANES 1 epidemiologic follow-up study, 1971-1992. JAMA 2000 283: 2404-2410.


Studies and results

The Framingham study collected data on 6,700 participants for a total of 117,000 person-years of follow up, with 617 cardiovascular disease events and 429 cardiovascular disease deaths after an initial uric acid measurement was made.

Analysis used the statistical significance of the trend for more deaths with higher initial serum uric acid. There was a significant trend when no covariates were included in their analysis, but inclusion of successive covariates, like blood pressure, cholesterol, smoking and comorbid conditions (all of which differed between the quintiles of uric acid level) eventually removed all statistical significance. Their conclusion was that uric acid was not associated with heart disease risk.

The First national Health and Nutritional Examination Survey (NHANES 1) was based on 5,900 subjects with serum uric acid measured at baseline. , with 1593 deaths, 731 of which were from cardiovascular causes. Using a quartile analysis, the age and race adjusted death rate was higher in the upper quartile of uric acid for men and women, and that an association between uric acid and cardiovascular mortality remained even after adjustment for eight covariables. Their conclusion was that uric acid was associated with heart disease risk.

Comment

What is a poor soul to think. Firstly, it is worth pointing out that there were differences in populations, with the Framingham study population being almost exclusively white, while the NHANES study represented the more heterogeneous US population, with about 12% of them black. The NHANES study also had a much higher overall rate of cardiovascular disease.

Both studies are good, they just reach opposite conclusions. No single observational study will settle this question. Perhaps the simple take-home message is that the usual healthy living lessons about weight control, good, diet and exercise will probably result in a lower uric acid level, and anyway are powerfully protective against heart disease.

Whether there are links with uric acid can be left to the academics for now.