Relationships between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Intervention Study (DAIS).
BACKGROUND
The Diabetes Atherosclerosis Intervention Study showed that treatment with fenofibrate decreases progression of coronary atherosclerosis in subjects with type 2 diabetes. We determined whether on-treatment plasma lipid concentrations and LDL particle size contribute to the favorable effect of fenofibrate on the progression of coronary artery disease (CAD).


RESULTS
A total of 418 subjects with type 2 diabetes were randomly assigned to 200 mg micronized fenofibrate daily or placebo. The mean follow-up time was 39.6 months. LDL peak particle diameter (LDL size) was determined by polyacrylamide gradient gel electrophoresis from 405 subjects at baseline and at the end of the study. Progression of CAD was measured with quantitative coronary angiography. LDL size increased significantly more in the fenofibrate group than in the placebo group (0.98+/-1.04 versus 0.32+/-0.92 nm, P<0.001). In the combined group, small LDL size was significantly associated with progression of CAD measured as the increase of percentage diameter stenosis (r=-0.16, P=0.002) and decreases in minimum (r=-0.11, P=0.030) and mean (r=-0.10, P=0.045) lumen diameter. High on-treatment LDL cholesterol, apolipoprotein B, and triglyceride concentrations were also associated with the progression of CAD. In regression analyses, small LDL size added to the effect of LDL cholesterol and apolipoprotein B on the progression of CAD. Similar associations were observed in the fenofibrate group, whereas in the placebo group, lipoprotein variables were not significantly correlated with the progression of CAD.


CONCLUSIONS
Changes in LDL size and plasma lipid levels account for part of the antiatherogenic effect of fenofibrate in type 2 diabetes.
Vakkilainen
Juha
J
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Steiner
George
G
Ansquer
Jean-Claude
JC
Aubin
Francois
F
Rattier
Stephanie
S
Foucher
Christelle
C
Hamsten
Anders
A
Taskinen
Marja-Riitta
MR
D000328:Adult; D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010316:Particle Size
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011345:Fenofibrate