Insulin Growth Factor 1 and Cardiac Allograft Vasculopathy

Abstract

Purpose Cardiac Allograft Vasculopathy (CAV) is major comorbidity after heart transplantation (OHT) with no definitive therapy besides re-transplantation. Its pathophysiology is not well defined and non-invasive markers of early disease are lacking. Low Insulin Growth Factor 1 (IGF1) and high Insulin Growth Factor Binding protein 3(IGFBP3) have been implicated in the development of atherosclerosis and native coronary artery disease (CAD). The purpose of this study is to evaluate the role of IGF1 and IGFBP3 in CAV. Methods and Materials The Intermountain Heart Collaborative Study Registry was queried for stored blood samples for heart transplant recipients (1995-2010). IGF1 and IGFBP3 plasma levels were done by ELISA and measured at baseline before the diagnosis of CAV in the CAV group and at similar time points after transplantation in the control group (±2 years) which was matched by gender and age. Demographic, clinical and laboratory data were collected at the time of the sample collections. CAV was defined CAV1-3 per International Society for Heart and Lung Transplantation. A non-parametric analysis for comparing the IGF1 and IGFBP3 for the CAV and non-CAV matched patients was done. Results 41 matched CAV and control pairs were analyzed. Average age was 53 ±12 years, 83% were male, and 96% were Caucasian. There was no difference in IGF1 and IGFBP3 serum levels between the two groups at baseline (see Table). Conclusions Although low serum IGF1 is a risk factor of development of CAD, this association was not found in patients with CAV post-transplant. This observation likely reflects differences in pathophysiology between the two diseases as immunologic process plays a major role in the CAV compare to native atherosclerosis. Larger studies are needed to further explore the role of IGF1 in CAV. CAV(n=41) Control (n=41) P value DM % 7.8 (9.8 0.69 HTN % 48.8 36.6 0.37 Average IGF1 (ng/ml)±std 116.66 ±55.73 105±39.02 0.61 Average IGFBP3 (ng/ml))±std 1670.14 ±513.28 1623.75 ±1026.93 0.82 DM: Diabetes Mellitus, HTN: Hypertension, std: standard deviation