Abstract 42: Haptoglobin Genotype as a Marker of Vascular Intraplaque Hemorrhage
Background: Intraplaque hemorrhage (IPH), a component of late stage atherosclerosis, is a critical factor in plaque destabilization leading to stroke and myocardial infarction. Magnetic resonance imaging (MRI) is able to identify IPH and allows for identification of high risk patients. Currently however, no routinely available tests are conducted to identify individuals at risk of IPH.
IPH is a rich source of free hemoglobin (Hb), a potent oxidant. The plasma protein haptoglobin (Hp) binds Hb forming a Hb-Hp complex, that can be engulfed by tissue macrophages.The reduction in oxidative stress decreases vascular inflammation. In humans, the Hp gene has three different genotypes: Hp1-1, Hp2-2 and Hp1-2. The Hb-Hp2-2 complex has a lower binding affinity to macrophages, resulting in higher oxidative burden. Numerous studies have demonstrated a higher risk of cardiovascular events in Hp2-2 individuals. We therefore hypothesized that patients of a Hp2-2 genotype have a greater risk of MR-IPH.
Methods: From 2010 to 2014, patients with non-surgical carotid artery disease (30-95% stenosis) underwent 3T carotid MRI that included a MR-IPH sequence. A radiologist with 25 years of expertise in MR-IPH imaging determined the presence of MR-IPH using widely accepted methods. Patients’ charts were blindly reviewed for demographics and medical history. Patients were genotyped for Hp1/2 using an established PCR genotyping method. Statistical association analysis was performed using logistic regression.
Results and Conclusions: Out of the 80 recruited patients (mean age, 72.8 years; range 52-100), those with Hp2-2 genotype vs. Hp1-1/Hp1-2 had a prevalence of MR-IPH of 65% compared to 41%(p=0.09). Non-diabetics (HbA1c <6.5%) with Hp2-2 genotype had an increased risk of IPH compared to non-diabetics with Hp1-1/Hp 1-2 genotype (OR=3, 95% CI 1.04-8.73, p=0.03). Males were also at an increased risk of IPH (OR=4.05, 95% CI 1.53-10.70, p=0.004) and the majority (71%) of males with IPH were of the Hp2-2 genotype. In conclusion, non-diabetic Hp2-2 male patients with history of vascular disease are the population with the highest risk of developing IPH and they can be identified using simple haptoglobin genotype testing.
Author Disclosures: T. Binesh Marvasti: None. N. Singh: None. P. Tyrrell: None. B. Wong: None. D. Cole: None. A. Moody: None.
- © 2014 by American Heart Association, Inc.