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Low-Plasma Insulin-Like Growth Factor-I Levels Are Associated with Impaired Endothelium-Dependent Vasodilatation in a Cohort of Untreated, Hypertensive Caucasian Subjects

Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy

Address all correspondence and requests for reprints to: Francesco Perticone, M.D., Department of Experimental and Clinical Medicine, Policlinico Mater Domini-Viale Europa, Campus Germaneto, 88100 Catanzaro, Italy. E-mail: perticone{at}unicz.it.

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.