1.
Effect of rosuvastatin monotherapy or in combination with fenofibrate or ω-3 fatty acids on lipoprotein subfraction profile in patients with mixed dyslipidaemia and metabolic syndrome.
Agouridis, AP, Kostapanos, MS, Tsimihodimos, V, Kostara, C, Mikhailidis, DP, Bairaktari, ET, Tselepis, AD, Elisaf, MS
International journal of clinical practice. 2012;(9):843-53
Abstract
BACKGROUND Raised triglycerides (TG), decreased high-density lipoprotein cholesterol (HDL-C) levels and a predominance of small dense low density lipoproteins (sdLDL) are characteristics of the metabolic syndrome (MetS). OBJECTIVE To compare the effect of high-dose rosuvastatin monotherapy with moderate dosing combined with fenofibrate or ω-3 fatty acids on the lipoprotein subfraction profile in patients with mixed dyslipidaemia and MetS. METHODS We previously randomised patients with low-density lipoprotein cholesterol (LDL-C) > 160 and TG > 200 mg/dl to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or ω-3 fatty acids 2 g/day (Rω group, n = 30). In the present study, only patients with MetS were included (24, 23 and 24 in the R, RF and Rω groups respectively). At baseline and after 12 weeks of treatment, the lipoprotein subfraction profile was determined by polyacrylamide 3% gel electrophoresis. RESULTS The mean LDL size was significantly increased in all groups. This change was more prominent with RF than with other treatments in parallel with its greater hypotriglyceridemic capacity (p < 0.05 compared with R and Rω). A decrease in insulin resistance by RF was also noted. Only RF significantly raised HDL-C levels (by 7.7%, p < 0.05) by increasing the cholesterol of small HDL particles. The cholesterol of larger HDL subclasses was significantly increased by R and Rω. CONCLUSIONS All regimens increased mean LDL size; RF was the most effective. A differential effect of treatments was noted on the HDL subfraction profile.
2.
Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome.
Chan, DC, Watts, GF, Ooi, EM, Ji, J, Johnson, AG, Barrett, PH
Arteriosclerosis, thrombosis, and vascular biology. 2008;(10):1831-7
-
-
Free full text
-
Abstract
OBJECTIVE The metabolic syndrome (MetS) is characterized by insulin resistance and dyslipidemia that may accelerate atherosclerosis. Disturbed apolipoprotein (apo) C-III metabolism may account for dyslipidemia in these subjects. Atorvastatin and fenofibrate decrease plasma apoC-III, but the underlying mechanisms are not fully understood. METHODS AND RESULTS The effects of atorvastatin (40 mg/d) and fenofibrate (200 mg/d) on the kinetics of very-low density lipoprotein (VLDL)-apoC-III were investigated in a crossover trial of 11 MetS men. VLDL-apoC-III kinetics were studied, after intravenous d(3)-leucine administration using gas chromatography-mass spectrometry and compartmental modeling. Compared with placebo, both atorvastatin and fenofibrate significantly decreased (P<0.001) plasma concentrations of triglyceride, apoB, apoB-48, and total apoC-III. Atorvastatin, not fenofibrate, significantly decreased plasma apoA-V concentrations (P<0.05). Both agents significantly increased the fractional catabolic rate (+32% and +30%, respectively) and reduced the production rate of VLDL-apoC-III (-20% and -24%, respectively), accounting for a significant reduction in VLDL-apoC-III concentrations (-41% and -39%, respectively). Total plasma apoC-III production rates were not significantly altered by the 2 agents. Neither treatment altered insulin resistance and body weight. CONCLUSIONS Both atorvastatin and fenofibrate have dual regulatory effects on VLDL-apoC-III kinetics in MetS; reduced production and increased fractional catabolism of VLDL-apoC-III may explain the triglyceride-lowering effect of these agents.
3.
Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia.
Koh, KK, Han, SH, Quon, MJ, Yeal Ahn, J, Shin, EK
Diabetes care. 2005;(6):1419-24
Abstract
OBJECTIVE Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 +/- 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 +/- 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 +/- 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 +/- 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients.