Abstract
Aims: The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and nitric oxide (NO) availability on this relationship. Methods: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. Results: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant number of subjects without, and with, severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelial function and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability. Conclusions: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability.
Highlights
A number of large epidemiologic studies have demonstrated the predictive value of serum uric acid (SUA) on the risk of cardiovascular (CV) disease and mortality, independently from common CV risk factors [1,2,3]
The microvascular data set of the Italian Society of Hypertension has already shown its ability to provide reliable information on the relationship of small resistance artery remodeling with levels of cardiovascular risk factor, endothelial function and nitric oxide (NO) availability in previous publications [18,20]
In 70 subjects recruited in Pisa, the acquisition of the remodeling parameters was followed by the assessment of endothelial function and NO availability, as previously reported and described in the supplementary material
Summary
A number of large epidemiologic studies have demonstrated the predictive value of serum uric acid (SUA) on the risk of cardiovascular (CV) disease and mortality, independently from common CV risk factors [1,2,3] Based on these findings, European Guidelines have included SUA among factors to be assessed for the CV risk stratification of patients with arterial hypertension [4]. We used the large microvascular data set from the Italian Society of Hypertension including microvascular, SUA and cardiovascular risk factor data from more than 100 subjects to assess: (i) whether SUA can provide additional information on the severity of resistance artery remodeling than that obtained from traditional scores used to define the patient’s cardiovascular risk, (ii) the predominant pattern of small vessel remodeling associated with different SUA levels, and (iii) whether the relationship between SUA and measures of resistance artery remodeling is mediated by endothelial dysfunction and reduced NO availability
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