IGF system and peripheral arterial disease: relationship with disease severity and inflammatory status of the affected limb.

OBJECTIVES: IGF-1 and its binding proteins are involved in the pathogenesis of atherosclerosis. We designed this study to unravel the relationship of the IGF system with peripheral arterial disease (PAD). DESIGN: Case-control, cross-sectional study. MEASUREMENTS: Serum levels of IGF-1, IGFBP-3 and acid labile subunit (ALS) were measured in 96 PAD patients and 89 controls. In 28 patients who underwent peripheral angiography, C-reactive protein (CRP), IGF-1, IGFBP-3 and ALS were measured in blood from femoral vein of the affected limb and aorta. RESULTS: Compared to controls, PAD patients showed lower levels of IGFBP-3 (3569 +/- 115 vs. 3106 +/- 107 microg/l, P < 0.01), and ALS (12.2 +/- 0.5 vs. 8.3 +/- 0.5 mg/l, P < 0.01). In PAD, concentrations of IGFBP-3 and ALS were significantly lower in patients with ankle/brachial index less than median than in those with a less severe PAD. In the affected limb, CRP venous-arterial difference correlated negatively with that of IGF-1 (rho = -0.57, P < 0.01), and positively with that of IGFBP-3 (rho = 0.63, P < 0.01). At multivariate analysis, a high transfemoral gradient of CRP was independently associated with a low transfemoral gradient of IGF-1 (beta coefficient = -0.48, P < 0.01), and a high transfemoral gradient of IGFBP-3 (beta coefficient = 0.22, P < 0.05). CONCLUSIONS: This study is the first to demonstrate that the systemic levels of IGF axis components are associated with the presence and severity of PAD, and that the inflammatory status of the ischaemic limb affects the transfemoral concentrations of IGF-1 and IGFBP-3. Due to the importance of IGF axis in modulating atherosclerotic plaque progression, our data may contribute to a better understanding of PAD pathophysiology.