Associations of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-2 and IGFBP-3 with ultrasound measures of atherosclerosis and plaque stability in an older adult population.
BACKGROUND
Circulating IGF-I is inversely associated with ischemic heart disease incidence. Whether this association relates to alterations in plaque growth or stability, and the role of IGF-II and the major binding proteins [IGF binding protein (IGFBP)-2 and -3], is unclear.


OBJECTIVE
Our objective was to test the hypothesis that circulating IGF-I is inversely, and IGF-II is positively, associated with subclinical atherosclerosis and plaque stability.


METHODS
This was a cross-sectional analysis based on 310 participants in the United Kingdom-based Boyd Orr cohort who were aged 63-82 yr. Cohort members from Aberdeen, Bristol, Dundee, Wisbech, and London were invited to clinics for fasted venepuncture and arterial ultrasound examination.


RESULTS
Arterial intima-media thickness, arterial plaque prevalence, and computerized assessment of plaque echogenicity (a measure of stability), undertaken using the gray scale median, were calculated.


RESULTS
In total, 269 of 310 (86.8%) participants had at least one carotid or femoral plaque. In models controlling for IGFBP-3, there was a 44% (95% confidence interval 12-64%) reduction in the odds of any plaque and a 28% lower (0-48%) odds of echolucent (unstable) plaques per sd increase in IGF-I. IGFBP-3 was positively associated with plaque instability (odds ratio: 1.38; 0.99-1.93). IGF-II was positively associated (0.05-mm increase per sd; 95% confidence interval 0.01-0.09), and IGFBP-2 was inversely associated, with carotid bifurcation intima-media thickness. Neither IGF-II nor IGFBP-2 was associated with plaque prevalence or echogenicity.


CONCLUSIONS
High-circulating IGF-I levels may promote arterial plaque stability. IGF-II and IGFBP-2 do not appear to play a role in plaque development or stability.
Martin
Richard M
RM
Department of Social Medicine, North Bristol, University of Bristol, Bristol BS8 2PR, United Kingdom. richard.martin@bristol.ac.uk
Gunnell
David
D
Whitley
Elise
E
Nicolaides
Andrew
A
Griffin
Maura
M
Georgiou
Niki
N
Davey Smith
George
G
Ebrahim
Shah
S
Holly
Jeff M P
JM
D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000000981:diagnostic imaging; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014463:Ultrasonography
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II