Tina Binesh Marvasti, Presenter: Nothing to Disclose

Navneet Singh MD, Abstract Co-Author: Nothing to Disclose

Mariam Afshin, Abstract Co-Author: Nothing to Disclose

Tishan Maraj, Abstract Co-Author: Nothing to Disclose

Pascal N. Tyrrell PhD, Abstract Co-Author: Nothing to Disclose

Alan Rowland Moody MD, Abstract Co-Author: Nothing to Disclose

Intraplaque hemorrhage (IPH) -a component of late-stage atherosclerotic plaque- is a source of free hemoglobin (Hb) that binds the haptoglobin (Hp) protein and forms a complex cleared by tissue macrophages. There are three Hp genotypes: Hp1-1, Hp2-2 and Hp1-2. The Hb-Hp2-2 complex has a lower binding affinity for macrophages, resulting in retention of vascular Hb and oxidative burden. Studies have shown a higher risk of CV events in Hp2-2 individuals. We hypothesized that Hp2-2 patients’ failure to clear Hb results in a greater prevalence and progression of MRI depicted IPH (MRIPH). We aimed to identify a biomarker (Hp) for routine testing of individuals at risk of IPH.

Patients with non-surgical carotid artery disease (30-95% stenosis) underwent 3T carotid MRI (Philips Achieva) of both carotids annually from 2010 to 2014. MRIPH uses a T1weighted inversion recovery fat suppressed 3D Fast Field Echo sequence in the coronal plane to detect IPH which appears of high signal due to methemoglobin. IPH was defined as a signal intensity 1.5x the adjacent sternocleidomastoid muscle. IPH volume was quantified using VesselMass software. Hp genotypes were identified using an established PCR protocol. Descriptive statistics and mixed effects model longitudinal regression analyses were performed.

The study cohort consisted of 80 patients (mean age, 72.8 years; range 52-100) with 160 carotid images. Patients homozygote for the Hp2 allele had a significantly higher prevalence of IPH at baseline (BL) compared to those carrying an Hp1allele (57%vs.34%, OR=2.52, 95%CI=1.23–5.144, p=0.01). IPH volume at BL did not differ significantly between the two groups (0.27vs.0.23 mL respectively, p=0.836). Longitudinal analysis of 18 IPH positive carotids with two years follow up data indicated a significant progression of IPH volume over time in Hp2 homozygote patients (β=0.12, SE=0.04, p<0.01) and regression of IPH volume in patients carrying an Hp1 allele (β=-0.09, SE=0.03, p=0.01).

Patients homozygote for the Hp2 allele had a significantly higher prevalence of carotid BL-IPH at which worsened over a two year follow up period. 

Detection of pre-symptomatic vascular disease allows for prevention of CV events. Hp genotype is a biomarker of high risk vascular disease (IPH) that when detected using simple genotyping methods can identify at-risk populations for more targeted imaging investigations.

Binesh Marvasti, T, Singh, N, Afshin, M, Maraj, T, Tyrrell, P, Moody, A, Haptoglobin 2-2 Genotype is Associated with Presence and Progression of MRI Depicted Carotid Intraplaque Hemorrhage .  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14018601.html