Abstract
Introduction: The association of elevated plasma triglyceride concentrations, decreased HDL-cholesterol,
and dense LDL (dLDL) is referred to as the atherogenic lipoprotein phenotype. dLDL
particularly plays a role in the metabolic syndrome and type 2 diabetes and may be
one of the factors responsible for the increased risk for coronary artery disease
in these patients. The effect of fenofibrate and atorvastatin on the LDL subfraction
profile in patients with combined hyperlipidemia and a preponderance of dLDL was studied
in a sequential design.
Methods: Six male patients with combined hyperlipidemia and dLDL received 160 mg/die supra-bioavailable
fenofibrate. After a washout phase of 8 weeks all patients received 10 mg/die atorvastatin
for another 8 weeks. At baseline, after fenofibrate, and after atorvastatin treatment
LDL subfractions were analyzed by equilibrium density gradient ultracentrifugation,
Results: Treatment with atorvastatin and fenofibrate reduced serum cholesterol by 30 % and
21 % (p = 0.046) (p-values for differences between treatment groups), triglycerides
by 32 % and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol
by 3 % and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the
following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 %
and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028);
LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040 kg/L)
- 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6 (1.044 -
1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate reduced LDL
density significantly (p = 0.028 versus atorvastatin).
Conclusions: Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative effect)
whereas fenofibrate reduced predominantly dLDL and changed the LDL profile towards
medium dense LDL-particles (qualitative effect). Since medium dense LDL have a higher
affinity to the LDL-receptor fenofibrate may have a higher antiatherogenic potential
than assessed by the reduction of total LDL-cholesterol and triglycerides alone.
Key words
PPAR-alpha agonists - LDL-subfractions - atherogenic lipoprotein phenotype - triglycerides
- high density lipoproteins
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Dr. M. D. Karl Winkler
Department of Clinical Chemistry
School of Medicine
Albert-Ludwigs-University
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