Phlebotomy decreases arterial stiffness and endothelial dysfunction in patients with hereditary hemochromatosis

Hereditary Hemochromatosis (HH) is a genetically determined disease of iron overload with excessive tissue storage, which can lead to tissue injury, fibrosis and organ failure. Recently, an increase of cardiovascular risk (CVR) has been reported in this group. Pulse wave velocity (PWV) is the simplest way to assess arterial stiffness (AS), and has predictive value for CVevents. PWV variation preand postinduced ischemia of brachial artery has been validated to evaluate endothelial dysfunction (ED). We previously reported a significant enhanced PWV and endothelial dysfunction in 30 HH patients compared with healthy controls. Patients with HH treated with repetitive phlebotomies (standard of care for these patients) show significantly longer survival rate (5-10 years) than untreated patients. We hypothesized that phlebotomy reduces iron overload and decreases the excessive storage of this metal in the arterial wall, reducing the vascular stiffness and therefore decreasing carotid-femoral PWV. To test this hypothesis we measured carotid-femoral PWV before and after phlebotomy in HH patients to assess AS and carotid-braquial PWV variation pre and post induced ischemia to assess ED. We compared these results against matching controls. PWV and PWV variation were assessed using Complior System (Artech-Medical, Francia). Carotid-femoral PWV was significantly increased in HH patients compared to control group (8.5 1.7 m/s vs 6.4 0.8 m/s, P<0.001, n1⁄422/30 patients/ group). Change in braquial PWVafter transient ischemiawas reduced in HH patients (0.3%) compared to controls (8.2%) (P<0.001). Phlebotomy significantly reduced carotid-femoral PWV (Post-phlebotomy: 6.5 0.8 m/s vs pre-plebotomy: 8.5 1.7 m/s, P<0.00001) back to control values (6.4 0.8 m/s). Change in braquial PWV was parcially rescued after phlebotomy (0.7 14% vs 2.4 8.7%). These results showed a significant reduction in AS and a partial rescue of ED in HH patients post-phlebotomy, suggesting that the arterial wall may represent a novel target in HH treatment endpoint organs. Our findings may support features research including more patients with HH and others iron overload disorders.