Low-plasma insulin-like growth factor-I levels are associated with impaired endothelium-dependent vasodilatation in a cohort of untreated, hypertensive Caucasian subjects

CONTEXT: Accumulating evidence suggests that IGF-I has protective vascular effects, supporting the possibility that IGF-I deficiency may contribute to atherosclerosis. However, the relationship between plasma IGF-I levels and endothelium-dependent vasodilatation is still unsettled. OBJECTIVE: We designed this present study to test the hypothesis that low-plasma IGF-I levels are associated with reduced endothelial function independently classical cardiovascular risk factors. SETTING: Outpatients were included in the study. PATIENTS: A total of 100 never-treated hypertensive Caucasian subjects participating in the CAtanzaro MEtabolic RIsk factors Study was recruited. INTERVENTIONS: Subjects underwent forearm blood flow (FBF) evaluation by strain-gauge plethysmography in response to increasing doses of acetylcholine (ACh) (Sigma, Milan, Italy) and sodium nitroprusside (Malesci, Florence, Italy). Insulin sensitivity was estimated by the homeostasis model assessment index. RESULTS: Plasma IGF-I levels were significantly correlated with age (r = -0.300; P = 0.001), high-density lipoprotein serum cholesterol (r = 0.211; P = 0.017), homeostasis model assessment index (r = -0.355; P <0.0001), systolic blood pressure (r = -0.174; P = 0.042), glomerular filtration rate (r = 0.228; P = 0.011), and ACh-stimulated FBF (r = 0.565; P <0.0001). In a stepwise forward multivariate regression analysis, the strongest predictors of ACh-stimulated FBF response were plasma IGF-I levels, accounting for 31.9% of its variation. CONCLUSIONS: These results demonstrate, for the first time, that low-plasma IGF-I levels are highly associated with reduced endothelial function, an early step in atherogenesis process.