Small dense LDL-cholesterol relative to LDL-cholesterol is a strong independent determinant of hypoadiponectinemia in metabolic syndrome.

BACKGROUND Small dense low-density lipoprotein (sd-LDL) is an atherogenic lipoprotein closely associated with an increased risk of cardiovascular diseases. However, a precise analysis of the actual amount of sd-LDL-cholesterol (sd-LDL-C) in patients with metabolic syndrome (MS) has not been performed. METHODS AND RESULTS Among 214 patients enrolled in the present study, 101 patients (47%) met the Japanese MS criteria. The serum levels of sd-LDL-C determined with a dual detection HPLC system were higher in MS than non-MS patients, while total cholesterol and low-density lipoprotein-cholesterol (LDL-C) were similar between MS and non-MS patients. Compared with the sd-LDL-C and LDL-C level, the ratio sd-LDL-C/LDL-C was more closely correlated with various parameters associated with MS. A multivariate regression analysis revealed that the ratio sd-LDL-C/LDL-C is the strongest independent determinant of hypoadiponectinemia. Furthermore, weight reduction therapy through diet and exercise rapidly decreased LDL-C but slowly decreased sd-LDL-C. At 12 months after the therapy, weight reduction led to a significant decrease in the ratio sd-LDL-C/LDL-C in tandem with increasing adiponectin levels. CONCLUSIONS These findings demonstrate that the ratio sd-LDL-C/LDL-C is tightly connected with hypoadiponectinemia and provides a useful clinical indicator for MS. The results also suggest that the elevation of this ratio can be modulated by long-term lifestyle changes.