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Circulation. 2002;106:939-944
Published online before print August 5, 2002, doi: 10.1161/01.CIR.0000027563.44593.CC
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(Circulation. 2002;106:939.)
© 2002 American Heart Association, Inc.


Clinical Investigation and Reports

Low Serum Insulin-Like Growth Factor I Is Associated With Increased Risk of Ischemic Heart Disease

A Population-Based Case-Control Study

Anders Juul, MD, PhD; Thomas Scheike, MSc; Michael Davidsen, MSc; Jesper Gyllenborg, MD; Torben Jørgensen, MD, PhD

From the Department of Growth and Reproduction, Rigshospitalet (A.J., J.G.); Department of Biostatistics, Panum Institute (T.S.); and Centre for Preventive Medicine, Medical Department M, and Glostrup County Hospital (M.D., T.J.), University of Copenhagen, Denmark.

Correspondence to Anders Juul, MD, PhD, Department of Growth and Reproduction, Rigshospitalet section 5064, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail ajuul{at}dadlnet.dk

Background— Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD).

Methods and Results— We conducted a nested case-control study within a large prospective study on cardiovascular epidemiology (DAN-MONICA). We measured IGF-I and IGFBP-3 in serum from 231 individuals who had a diagnosis of IHD 7.63 years after blood sampling and among 374 control subjects matched for age, sex, and calendar time. At baseline when all individuals were free of disease, subjects in the low IGF-I quartile had significantly higher risk of IHD during the 15-year follow-up period, with a relative risk (RR) of 1.94 (95% CI, 1.03 to 3.66) of IHD compared with the high IGF-I quartile group, when IGFBP-3, body mass index, smoking, menopause, diabetes, and use of antihypertensives were controlled for. Conversely, individuals in the high IGFBP-3 quartile group had an adjusted RR of 2.16 (95% CI, 1.18 to 3.95) of having IHD. Identification of a high-risk population with low IGF-I and high IGFBP-3 levels resulted in markedly higher risk of IHD (RR 4.07; 95% CI, 1.48 to 11.22) compared with the index group.

Conclusions— Individuals without IHD but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period. Our findings suggest that IGF-I may be involved in the pathogenesis of IHD.


Key Words: atherosclerosis • epidemiology • myocardial infarction • growth substances




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