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Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age

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Abstract

To investigate the relationships between the GH-IGF-I axis and the atherosclerotic profile, we designed this open, observational, prospective study. Peak GH after GHRH+arginine (ARG) test, serum IGF-I and IGF binding protein-3 (IGFBP-3), lipid profile, homeostasis model assessment (HOMA) index and intima-media thickness (IMT) at common carotid arteries were measured in 174 healthy individuals (92 women, 82 men, aged 18–80 yr). Exclusion criteria for this study were: 1) body mass index (BMI) ≥30 kg/m2; 2) personal history of cardiovascular diseases; 3) previous or current treatments of diabetes or hypertension; 4) previous corticosteroids treatment for longer than 2 weeks or estrogens for longer than 3 months; 5) smoking of more than 15 cigarettes/day and alcohol abuse. Subjects were divided according to age in decade groups from <20 to >70 yr. BMI increased with age, as did systolic and diastolic blood pressures, although they remained in the normal range. The GH peak after GHRH+ARG test was significantly higher in the subjects aged <20 yr than in all the other groups (p<0.01), but was similar in the remaining groups. An inverse correlation was found between the IGF-I z-score and total/HDL-cholesterol ratio (p=0.02) and mean IMT (p=0.0009); IGFBP-3 z-score and mean IMT (p=0.043); IGF: IGFBP-3 molar ratio and total/HDL-cholesterol ratio (p<0.0001) and mean IMT (p<0.0001). Atherosclerotic plaques were found in 7 out of 12 subjects (53.8%) with a z-IGF-I score from ≤−2 to −1, in 4 out of 63 (6.3%) with a z-IGF-I score from −0.99 to 0.1 out of 66 (1.5%) with a z-IGF-I score from 0.1 to 1 and none of the 33 subjects with an IGF-I z-score >1 (p=0.006). At multi-step regression analysis, age was the best predictor of HDL-cholesterol levels and mean IMT, IGF-I level was the best predictor of total cholesterol and total/HDL-cholesterol ratio, the IGF-I/IGFBP-3 molar ratio was the best predictor of triglycerides levels. The z-scores of IGF-I and IGFBP-3 were the second best predictors of mean IMT after age. In conclusion, IGF-I and IGFBP-3 were negatively correlated with common cardiovascular risk factors, studied as total/HDL-cholesterol ratio, and/or early atherosclerosis, studied as IMT at common carotid arteries. The prevalence of atherosclerotic plaques, though not hemodinamically significant, was higher in the subjects having a z-score of IGF-I of ≤−2 to −1. Our results support a role of the IGF/IGFBP-3 axis in the pathogenesis of atherosclerosis.

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Authors and Affiliations

  1. Department of Molecular and Clinical Endocrinology and Oncology, “Federico II” University of Naples, Via S. Pansini 5, 80131, Naples, Italy

    A. Colao MD, PhD, C. Di Somma, R. Pivonello, P. Marzullo, F. Rota, T. Musella, R. S. Auriemma, M. C. De Martino & G. Lombardi

  2. Emergency Unit, “S. Maria degli Incurabili” Hospital of Naples, Naples, Italy

    S. Spiezia

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  1. A. Colao MD, PhD
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  2. S. Spiezia
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  3. C. Di Somma
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  4. R. Pivonello
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  5. P. Marzullo
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  6. F. Rota
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  7. T. Musella
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  10. G. Lombardi
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Correspondence to A. Colao MD, PhD.

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Colao, A., Spiezia, S., Di Somma, C. et al. Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age. J Endocrinol Invest 28, 440–448 (2005). https://doi.org/10.1007/BF03347225

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