Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age.
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) > or = 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 < or = -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 < or = -2 to -1. Our results support a role of the IGF/IGFBP-3 axis in the pathogenesis of atherosclerosis.
Colao
A
A
Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University, Naples, Italy. colao@unina.it
Spiezia
S
S
Di Somma
C
C
Pivonello
R
R
Marzullo
P
P
Rota
F
F
Musella
T
T
Auriemma
R S
RS
De Martino
M C
MC
Lombardi
G
G
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood*; D002339:Carotid Arteries / Q000033:anatomy & histology; D006706:Homeostasis; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D011237:Predictive Value of Tests; D012016:Reference Values; D017539:Tunica Intima / Q000033:anatomy & histology
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D008055:Lipids; D007334:Insulin-Like Growth Factor I