Uric acid is closely linked to vascular nitric oxide activity - Evidence for mechanism of association with cardiovascular disease

Objectives The study was undertaken to determine whether the mechanism of a ssociation of elevated serum uric acid level (SUA) with cardiovascular dise ase (CVD) is secondary to a common link with vascular nitric oxide (NO) act ivity. Background Epidemiologic studies demonstrate an association of elevated SUA with CVD. The mechanism of this association is unknown, but both may be li nked via an impairment in vascular NO activity. To examine this, we determi ned the relationship of SUA to vascular NO activity and to CVD risk. We the n determined the effect of enhancing vascular NO activity on SUA. Methods In part 1, individuals with various degrees of CVD (n=458) were sur veyed and underwent measurement of flow-mediated brachial artery vasodilati on (FMV), a measure of vascular NO activity. In part 2, we performed an ana lysis of data pooled from six separate clinical trials of a medical food de signed to enhance vascular NO activity in individuals with CVD (n=217 subje cts representing 253 treatment periods) to determine the effect on SUA. Results In part 1, of all risk factors tested, SUA was second only to age i n correlation with FMV, accounting for 7% (p<0.0001) of the variability in FMV. Both SUA and FMV were related to the degree of disease risk (p<0.0001 and p=0.00025 by analysis of variance, respectively). By multivariate analy sis, SUA did not continue to contribute significantly to the determination of FMV. In part 2, enhancement of FMV (5.8 +/-4 to 8.6 +/-5, p<0.0001) was associated with a decrease in SUA (5.5<plus/minus>1.5 to 5.0 +/-1.5, p<0.00 01). There was no placebo effect on FMV or SUA. Conclusions These results suggest that the association of elevated SUA with CVD may be a consequence of an impairment of vascular NO activity. This ma y be owing to an ability of NO to modulate uric acid production through its influence on xanthine oxidase activity. (J Am Coll Cardiol 2001; 38:1950-8 ) (C) 2001 by the American College of Cardiology.