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This version published online on January 30, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1631
A more recent version of this article appeared on April 1, 2007
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Submitted on July 27, 2006
Accepted on January 19, 2007

Association of total IGF-I, IGFBP-1 and IGFBP-3 levels with incident coronary events and ischemic stroke

Robert C Kaplan PhD*, Aileen P McGinn PhD, Michael N Pollak MD, Lewis H Kuller MD, DrPH, Howard D Strickler MD, MPH, Tom E Rohan MD, PhD, Anne R Cappola MD, ScM, XiaoNan Xue PhD, and Bruce M Psaty MD, PHD

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (RCK, APM, HDS, TER, XX); Cancer Prevention Research Unit, Departments of Medicine and Oncology, Lady Davis Research Institute of Jewish General Hospital and McGill University, Montreal, Quebec, Canada; (MNP); Department of Medicine and Epidemiology, University of Pittsburgh, Pittsburgh, PA (LHK); Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia (ARC); Departments of Epidemiology, Medicine and Health Services, Cardiovascular Health Research Unit, University of Washington, Seattle (BMP)

* To whom correspondence should be addressed. E-mail: rkaplan{at}aecom.yu.edu.

Context: Prior observational studies have demonstrated that the growth hormone/insulin like-growth factor (GH/IGF) axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.

Objective: To assess the association between levels of total IGF-I, IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke

Design and Participants: A case cohort analysis was conducted among adults >=65 years old in the Cardiovascular Health Study (CHS).

Main Outcome Measures: 534 coronary events (316 nonfatal MI's, 48 fatal MI's and 170 fatal CHD events), and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1,122 randomly-selected participants from CHS.

Results: Mean follow-up time (years) was 6.7 for coronary events, 5.6 for strokes and 9.3 for comparison subjects. Hazard ratios (HRs) [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 HR per standard deviation=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 CHD.

Conclusion: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, while low IGFBP-3 level was associated with increased risk of incident coronary events.
Key words: myocardial infarction • stroke • epidemiology • insulin-like growth factor






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