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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

Department of Epidemiology and Population Health (R.C.K., A.P.M., H.D.S., T.E.R., X.X.), Albert Einstein College of Medicine, Bronx, New York 10461; Cancer Prevention Research Unit, Departments of Medicine and Oncology (M.N.P.), Lady Davis Research Institute of Jewish General Hospital and McGill University, Montreal, Quebec, Canada H3T 1E2; Department of Medicine and Epidemiology (L.H.K.), University of Pittsburgh, Pittsburgh, Pennsylvania 15261; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine (A.R.C.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; and Departments of Epidemiology, Medicine and Health Services, Cardiovascular Health Research Unit (B.M.P.), University of Washington, Seattle, Washington 98101

Address all correspondence and requests for reprints to: Robert C. Kaplan, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 1306C, Bronx, New York 10461. E-mail: rkaplan{at}aecom.yu.edu.

Context: 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.

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

Main Outcome Measures: 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.

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, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.

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