Differential effects of fenofibrate and extended-release niacin on high-density lipoprotein particle size distribution and cholesterol efflux capacity in dyslipidemic patients.
BACKGROUND
The effectiveness of therapies that raise high-density lipoprotein cholesterol (HDL-C) to lower cardiovascular disease risk is currently under debate, and further research into the relationship between HDL-C and function is required.


OBJECTIVE
o investigate whether 2 established HDL-C-raising therapies had differential effects on parameters of high-density lipoprotein (HDL) quality and function, such as HDL particle profile and cholesterol efflux capacity (CEC), in patients with dyslipidemia.


RESULTS
Sixty-six patients with dyslipidemia, 24 with low HDL-C levels (<40 mg/dL) and 42 with normal HDL-C levels (40-59 mg/dL), were treated for 6 weeks with fenofibrate (160 mg/d) or extended-release (ER) niacin (0.5 g/d for 3 weeks, then 1 g/d) with 4 weeks of washout between treatments. Lipoprotein particle size distribution was determined using nuclear magnetic resonance, and pathway-specific serum CECs were assessed in J774 macrophages, hepatoma, and Chinese hamster ovary-human adenosine triphosphate-binding cassette transporter G1 cells. Comparable increases in HDL-C and apolipoprotein A-I levels were seen with fenofibrate and ER niacin. There was a shift toward larger HDL, predominantly to medium-size HDL particles for fenofibrate (+209%) and to large HDL particles for ER niacin (+221%). Minor changes in serum CECs were observed with fenofibrate and ER niacin for all the efflux pathways measured. Small increases in plasma cholesteryl ester transfer protein and lecithin: cholesterol acyltransferase concentrations, and decreases in cholesteryl ester transfer protein activity were seen with both drugs.


CONCLUSIONS
Fenofibrate and ER niacin increased plasma HDL-C level similarly, but modulated HDL particle size distribution differently; however, these changes did not result in differential effects on serum CECs.
Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. Electronic address: guido.franceschini@unimi.it.
Guido
G
Franceschini
Elda
E
Favari
Laura
L
Calabresi
Sara
S
Simonelli
Alighiero
A
Bondioli
Maria Pia
MP
Adorni
Francesca
F
Zimetti
Monica
M
Gomaraschi
Karine
K
Coutant
Simona
S
Rossomanno
Eric J
EJ
Niesor
Franco
F
Bernini
Renee
R
Benghozi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D008076:Cholesterol, HDL / Q000097:blood / Q000737:chemistry* / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010316:Particle Size; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D012449:Safety; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D009525:Niacin; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011345:Fenofibrate
Cholesterol efflux capacity; Cholesteryl ester transfer protein; Fenofibrate; High-density lipoprotein cholesterol; Niacin