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

Abstract

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. 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. Outpatients were included in the study. A total of 100 never-treated hypertensive Caucasian subjects participating in the CAtanzaro MEtabolic RIsk factors Study was recruited. 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. 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. 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.