Serum Total IGF-I, Free IGF-I, and IGFBP-1 Levels in an Elderly Population

Relation to Cardiovascular Risk Factors and Disease

From the Department of Internal Medicine III (J.A.M.J.L.J., H.A.P.P., S.W.J.L.) and the Department of Epidemiology and Biostatics (H.A.P.P., D.E.G.), Erasmus University, Rotterdam; and the Julius Center for Patient Oriented Research, Utrecht University (R.P.S., D.E.G.), the Netherlands.

Correspondence to J.A.M.J.L. Janssen, Department of Internal Medicine III, Room D438, University Hospital Dijkzigt, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.

Abstract—Recently, a method to measure free insulin-like growth factor-I (IGF-I) levels has been developed. Free IGF-I levels may have greater physiological and clinical relevance than total (bound and free) IGF-I. The associations between the circulating IGF-I/IGF binding protein (IGFBP) system and cardiovascular disorders was studied. In a cross-sectional study of 218 healthy persons (103 men, 115 women) aged 55 to 80 years, fasting serum (total and free) IGF-I and IGFBP-1 levels, lipid profile, insulin, and glucose were measured. In addition, blood pressure, body mass index (BMI), and waist-hip ratio (WHR) were measured. Ultrasonography of both carotid arteries was performed to investigate the presence of atherosclerotic lesions. A history of angina pectoris, the presence of a possible or definite myocardial infarction on the ECG, and plaques in the carotid arteries were used as indicators of presence of cardiovascular signs and symptoms. Free IGF-I was inversely related to serum triglycerides (P=.04, adjusted for age and sex). Mean free IGF-I levels in subjects without signs or symptoms of cardiovascular diseases were significantly higher than in those with at least one cardiovascular symptom or sign (P=.002, adjusted for age and sex). Free IGF-I levels were also higher in subjects who had no atherosclerotic plaques in the carotid arteries (P=.02, adjusted for age and sex) and who had never smoked (P=.02, adjusted for age and sex). IGFBP-1 showed an inverse relation with insulin, BMI, and WHR and a positive relation with HDL cholesterol. The associations between IGFBP-1 levels and HDL cholesterol, WHR, and BMI remained significant after adjustment for fasting insulin levels. High fasting serum free IGF-I levels are associated with a decreased presence of atherosclerotic plaques and coronary artery disease and lower serum triglycerides, whereas high fasting IGFBP-1 levels are associated with a more favorable cardiovascular risk profile. The findings suggest that the IGF-I/IGFBP system is related to cardiovascular risk factors and atherosclerosis.

Key Words: free IGF-I • IGFBP-1 • atherosclerosis • cardiovascular risk factors • elderly

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