Lipoprotein Subfractions Partly Mediate the Association Between Serum Uric Acid and Coronary Artery Disease

Background: Serum uric acid (SUA) has been established to be highly associated with coronary artery disease (CAD) susceptibility and lipid metabolism, but the underlying mechanisms are unclear. Recently, lipoprotein subfractions have been proposed to be more valuable in CAD risk evaluation. Hence, we sought to investigate whether the relationship between SUA and CAD is partly mediated by lipoprotein subfractions.

Methods: A total of 401 consecutive subjects undergoing coronary angiography were enrolled. The baseline clinical data including the SUA level and lipid profiles were collected. The lipoprotein subfractions were determined using the Lipoprint system.

Results: In the overall population, the upper SUA quintiles had significantly higher atherogenic lipid parameters and unbalanced lipoprotein subfractions especially higher small dense low-density lipoprotein-cholesterol (sdLDL-C) and lower large high-density lipoprotein-cholesterol (HDL-C) (p<0.05). The levels of SUA and lipoprotein subfractions were dramatically different between male and female. After adjusting for traditional risk factors including gender, multivariate linear regression analysis suggested that SUA was positively associated with sdLDL-C (β=0.113, p=0.013) but negatively related to large HDL-C level (β=-0.152, p=0.002). Given the significant association of the SUA level with lipoprotein subfractions and incident CAD (adjusted OR=1.312, 95% CI 1.069-1.609, p=0.009), we performed the mediation analyses and found that 8.7-10.5% of the effect of SUA on CAD susceptibility was mediated by the increased sdLDL-C or decreased large HDL-C level (p<0.05).

Conclusions: The SUA level was proved to be associated with lipoprotein subfractions including sdLDL-C (positive) and large HDL-C (negative), which partly mediated the association between SUA and CAD susceptibility.