Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke.
BACKGROUND
Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.


OBJECTIVE
The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke.


METHODS
A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study.


METHODS
A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study.


RESULTS
Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease.


CONCLUSIONS
Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.
Kaplan
Robert C
RC
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA, and Department of Medicine, Lady Davis Research Institute of Jewish General Hospital, Montreal, Quebec, Canada. rkaplan@aecom.yu.edu
McGinn
Aileen P
AP
Pollak
Michael N
MN
Kuller
Lewis H
LH
Strickler
Howard D
HD
Rohan
Tom E
TE
Cappola
Anne R
AR
Xue
XiaoNan
X
Psaty
Bruce M
BM
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*
D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I