CLINICAL STUDY: ENDOTHELIAL FUNCTION
Uric acid is closely linked to vascular nitric oxide activity
Evidence for mechanism of association with cardiovascular disease
Andrew J. Maxwell, MD, FACC*,a and
Kristen A. Bruinsma, MSa
a Division of Research and Development, Cooke Pharma, Inc., Belmont, California, USA
Manuscript received February 9, 2001;
revised manuscript received July 31, 2001,
accepted August 22, 2001.
* Reprint requests and correspondence: Dr. Andrew J. Maxwell, Pediatric Cardiology, Stanford University, 6167 Jarvis Avenue, #244, Newark, California 94560-1210 USA
amaxwell{at}ntgr8.com
OBJECTIVES
The study was undertaken to determine whether the mechanism of association of elevated serum uric acid level (SUA) with cardiovascular disease (CVD) is secondary to a common link with vascular nitric oxide (NO) activity.
BACKGROUND
Epidemiologic studies demonstrate an association of elevated SUA with CVD. The mechanism of this association is unknown, but both may be linked via an impairment in vascular NO activity. To examine this, we determined the relationship of SUA to vascular NO activity and to CVD risk. We then determined the effect of enhancing vascular NO activity on SUA.
METHODS
In part 1, individuals with various degrees of CVD (n = 458) were surveyed and underwent measurement of flow-mediated brachial artery vasodilation (FMV), a measure of vascular NO activity. In part 2, we performed an analysis of data pooled from six separate clinical trials of a medical food designed to enhance vascular NO activity in individuals with CVD (n = 217 subjects 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 in 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 analysis, 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 ± 1.5 to 5.0 ± 1.5, p < 0.0001). 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 may be owing to an ability of NO to modulate uric acid production through its influence on xanthine oxidase activity.
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Abbreviations and Acronyms
| | ANOVA | = analysis of variance | | BMI | = body mass index | | CAD | = coronary artery disease | | CVD | = cardiovascular disease | | FMV | = flow-mediated vasodilation | | HDL | = high-density lipoprotein | | LDL | = low-density lipoprotein | | NO | = nitric oxide | | PAD | = peripheral arterial disease | | SUA | = serum uric acid level |
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