Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome.
BACKGROUND
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a macrophage-synthesized lipase that is primarily bound to small electronegative low-density lipoproteins (LDLs). Lipoprotein-associated phospholipase A2 oxidatively modifies LDL and generates the proinflammatory byproducts oxidized fatty acids (ox-FAs) and lysophosphatidylcholine. Fenofibrate reduces Lp-PLA2 mass; however, it remains unknown whether the anti-inflammatory effects of fenofibrate are related to changes in LDL subclasses.


METHODS
This was a randomized, double-blind, controlled clinical trial designed to investigate the effects of 3-month treatment with fenofibrate (160 mg/d) on Lp-PLA2 mass, LDL subclasses, and ox-FAs among 55 hypertriglyceridemic (> or = 1.7 and < 6.78 mmol/L) subjects with the metabolic syndrome.


RESULTS
Fenofibrate treatment lowered fasting Lp-PLA2 mass by 13.2% (-19.0 to -7.7) versus placebo (2.3% [-5.0 to 4.1], P = .0002) and total ox-FA by 15.5% (-34.2 to +1.4) versus an 11.5% increase with placebo (P = .0013). In age-, sex-, and treatment-adjusted models, changes in Lp-PLA2 mass were associated with reductions in chemical LDL cholesterol (r = 0.59, P < .01) and measured total LDL particles (LDL-Ps) (r = 0.64, P < .01) and small LDL-Ps (r = 0.57, P < .01). In models that included small LDL, effects of fenofibrate on Lp-PLA2 mass were attenuated (P = .125), but not in models that included LDL cholesterol (P < .0001) and LDL-Ps (P = .005). Changes in Lp-PLA2 mass were not significantly associated with changes in ox-FA or inflammatory markers.


CONCLUSIONS
Among hypertriglyceridemic subjects with the metabolic syndrome, fenofibrate therapy reduced Lp-PLA2 mass, and these changes were associated with fewer small LDL-Ps.
Rosenson
Robert S
RS
Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48106-0636, USA. rrosenso@umich.edu
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood* / Q000187:drug effects; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects
D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D008244:Lysophosphatidylcholines; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D011345:Fenofibrate