IGF-I and IGFBP2 in peripheral artery disease: results of a prospective study

Background and objectives. The search for novel risk factors of cardiovascular disease (CVD) has provided valuable clinical data concerning underlying mechanism of disease. Increasing evidence indicates a possible involvement of insulin-like growth factor-I (IGF-I) and its binding protein 2 (IGFBP-2) in the pathogenesis of CVD disorders. The aim of this study was to examine the relationship between levels of IGF-I and IGFBP-2 with all-cause and CVD mortality in a prospective study of patients with lower-extremity peripheral artery disease (PAD). Methods and material. Serum IGF-I and IGFBP-2 levels were obtained in 440 patients (257 males) with symptomatic PAD. Patients were followed for a median of 6.1 (IQ 5.1-7.2) years. The relationship between times to lethal outcome and baseline serum IGF-I and IFGBP-2 levels were examined by Cox proportional hazard analysis. The role of IFGBP-2 for prognosis of CVD death was assessed with c-statistic. Results. During follow-up 115 (26%) patients (48 females and 67 males) died, and 53 (12%) died from CVD-related causes. Cox regression analysis revealed that an increase of 100 mu g/l of baseline IFGBP-2 were significantly associated with an increased risk for CVD mortality [crude hazard ratio (HR) 1.14 (95% CI (1.05-1.23)), and adjusted HR 1.12 (95% CI (1.01-1.24))]. The receiver operating characteristic (ROC) analysis yielded area under curve of 0.61 (95% CI: 0.51-0.67, p = 0.022). However, the model including IFGBP-2 did not show a significant improvement in accuracy of CVD death prediction [the area under ROC curve 0.73 (0.66-0.80) vs. 0.75 (0.69-0.82), p = 0.696], and net reclassification improvement was 10.3% (p = 0.23). Conclusions. Increased IFGBP-2 concentration was significantly and independently associated with long-term CVD mortality in patients with lower-extremity PAD. However, risk prediction of CVD mortality did not improve by adding IFGBP-2 to a model containing conventional CVD risk factors.