The effects of ezetimibe and orlistat, alone or in combination, on high-density lipoprotein (HDL) subclasses and HDL-associated enzyme activities in overweight and obese patients with hyperlipidaemia.
BACKGROUND
High-density lipoprotein (HDL) includes discrete subfractions. HDL exhibits anti-atherogenic properties, which have been partly linked to the activity of HDL-associated enzymes, such as the lipoprotein associated phospholipase A(2) (HDL-LpPLA(2)) and paraoxonase-1 (PON1).


OBJECTIVE
We assessed in an open-label randomised study the effect of orlistat and ezetimibe, alone or in combination, on plasma HDL subclasses and HDL-associated enzyme activities in overweight and obese subjects (body mass index > 28 kg/m(2)) with hypercholesterolemia [total cholesterol > 200 mg/100 ml (5.2 mmol/l)].


METHODS
Eighty-six people were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, three times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months. HDL subfractions were determined using a polyacrylamide gel-tube electrophoresis method.


RESULTS
Levels of HDL cholesterol (HDL-C) and apolipoprotein AI did not change significantly in any group. In group O the cholesterol concentration of HDL-2 subclass increased significantly, while the cholesterol of HDL-3 subclass decreased significantly. In groups E and OE HDL-2 subclass did not significantly change, while the cholesterol concentration of HDL-3 subclass decreased significantly. We observed a non-significant decrease in the HDL-LpPLA(2) and PON1 activity in all groups. However, the ratios of both enzyme activities to low-density lipoprotein cholesterol (LDL-C) levels (an index of atherogenicity) significantly increased in all groups.


CONCLUSIONS
Although HDL-C levels did not change after treatment with orlistat and ezetimibe, alone or in combination, there were alterations of the HDL-2 and HDL-3 subclasses. The activity of HDL-LpPLA(2) and PON1 per mg LDL-C increased significantly in all groups.
Nakou
E S
ES
University of Ioannina, Medical School, Department of Internal Medicine, 45 110 Ioannina, Greece. egepi@cc.uoi.gr
Filippatos
T D
TD
Kiortsis
D N
DN
Derdemezis
C S
CS
Tselepis
A D
AD
Mikhailidis
D P
DP
Elisaf
M S
MS
D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000378:metabolism; D001384:Azetidines / Q000627:therapeutic use*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D018752:Diet, Fat-Restricted; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000201:enzymology / Q000628:therapy*; D007783:Lactones / Q000627:therapeutic use*; D016014:Linear Models; D053439:Lipoproteins, HDL2 / Q000097:blood; D053440:Lipoproteins, HDL3 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000201:enzymology / Q000628:therapy*; D000077403:Orlistat; D054467:Phospholipases A2 / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D019440:Anti-Obesity Agents; D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D007783:Lactones; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D000077403:Orlistat; D054467:Phospholipases A2; D043303:Aryldialkylphosphatase; D000069438:Ezetimibe