High serum uric acid and low-grade inflammation are associated with smaller LDL and HDL particles

Elevated serum uric acid (UA) is associated with higher risk for cardiovascular disease (CVD). Smaller, denser low density lipoprotein (LDL) and high-density lipoprotein (HDL) particles are the potential risk factors for CVD, while the role and diagnostic value of inflammatory markers are firmly established. This current cross-sectional study investigates interrelationships between UA, high sensitivity C-reactive protein (hsCRP) and fibrinogen concentrations with LDL and HDL sizes in healthy middle-aged subjects. The outcomes-of-interest were smaller, denser LDL and HDL particles (LDL size ≤25.5 nm and HDL size ≤8.8 nm). Serum UA, hsCRP and plasma fibrinogen concentrations were measured by standard laboratory methods in a sample of 194 healthy volunteers (112 men and 82 women). LDL and HDL particle sizes were determined by gradient gel electrophoresis. The subjects in the highest UA tertile had significantly smaller LDL and HDL particle sizes (P < 0.05 and P < 0.01, respectively) and higher concentrations of fibrinogen and hsCRP (P < 0.05 and P < 0.01, respectively). Elevated UA (≥318 μmol/L) was a significant predictor of smaller, denser LDL and HDL particles (OR = 3.09; P < 0.01; n = 19 and OR = 4.40; P < 0.001; n = 23, respectively). The observed relationship with smaller HDL size persisted after adjustment for conventional cardiovascular risk factors. UA strongly correlated with both markers of inflammation. In addition, the higher hsCRP level correlated with smaller LDL size (P < 0.05), while fibrinogen concentration was inversely related to HDL size (P < 0.05). Multiple regression analysis revealed that HDL size and inflammatory markers remained independent determinants of UA concentration. In conclusion, higher serum UA and low-grade inflammation are closely linked to alterations in lipoprotein metabolism which may represent an early sign of atherosclerosis in asymptomatic subjects.