ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression

Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size >5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative proteomic analysis of plasma proteins was per, formed in AAA patients at different stages of evolution [small AAA (aortic size=3-5cm) vs large AAA] using iTRAQ labelling, high, throughput nano-LC-MS/MS and a novel multi-layered statistical, model. Among the proteins identified, ApoA-I was decreased in patients with large AAA compared to those with small AAA. These results were validated by ELISA on plasma samples from small (n=90) and large AAA (n=26) patients (150 +/- 3 vs 133 +/- 5 mg/dl, respectively, p<0.001). ApoA-I levels strongly correlated with HDL-Cholesterol (HDL-C) concentration (r=0.9, p<0.001) and showed a negative correlation with aortic size (r=-0.4, p<0.01) and thrombus volume (r=-0.3, p<0.01), which remained significant after adjusting for traditional risk factors. In a prospective study, HDL-C independently predicted aneurysmal growth rate in multiple linear regression analysis (n=122, p=0.008) and was inversely associated with need for surgical repair (Adjusted hazard ratio: 0.18, 95% confidence interval: 0.04-0.74, p=0.018). In a nation-wide Danish registry, we found lower mean HDL-C concentration in large AM patients (n=6,560) compared with patients with aorto-iliac occlusive disease (n=23,496) (0.89 +/- 2.99 vs 1.59 +/- 5.74 mmol/l, p<0.001). Finally, reduced mean aortic AAA diameter was observed in AngII-infused mice treated with ApoA-I mimetic peptide compared with saline-injected controls. In conclusion, ApoA-I/HDL-C systemic levels are negatively associated with AAA evolution. Therapies targeting HDL functionality could halt AAA formation.