Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment.
OBJECTIVE
We investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis.


BACKGROUND
BECAIT, the first double-blind, placebo-controlled, randomized, serial angiographic trial of a fibrate compound, demonstrated that progression of focal coronary atherosclerosis in young patients after infarction could be retarded by bezafibrate treatment.


METHODS
The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1, as well as on basal and postload glucose and insulin levels, were examined, and on-trial determinations were related to the angiographic outcome measurements.


RESULTS
Bezafibrate treatment resulted in a significant reduction of serum IGF-I levels, both at two and five years, and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter (r = 0.25, p < 0.05) and mean segment diameter (r = 0.29, p < 0.05). In contrast, none of the available indexes of insulin resistance (homeostasis model assessment estimate, basal and postload plasma insulin concentrations and serum IGFBP-1 levels) were related to the angiographic changes, nor were they significantly affected by bezafibrate treatment. Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease (CAD) progression was independent of baseline angiographic score, age, body mass index, serum lipoprotein and plasma fibrinogen concentrations and measures of glucose-insulin homeostasis.


CONCLUSIONS
IGF-I could be implicated in the progression of premature CAD, and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis.
Ruotolo
G
G
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, Sweden.
Båvenholm
P
P
Brismar
K
K
Eféndic
S
S
Ericsson
C G
CG
de Faire
U
U
Nilsson
J
J
Hamsten
A
A
D000328:Adult; D001629:Bezafibrate / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D018970:Insulin-Like Growth Factor Binding Protein 1; D008074:Lipoproteins; D007334:Insulin-Like Growth Factor I; D001629:Bezafibrate