Haptoglobin polymorphism in relation to coronary plaque characteristics on radiofrequency intravascular ultrasound and near-infrared spectroscopy in patients with coronary artery disease

Background Conflicting results exist regarding the association between a common Haptoglobin (Hp) polymorphism and risk of coronary artery disease. We investigated the association of three functionally different anti-oxidant and anti-inflammatory Hp phenotypes (Hp1-1, Hp2-1, Hp2-2) with invasively measured degree and composition of coronary atherosclerosis as determined by intravascular ultrasound (-virtual histology) (IVUS(-VH)) as well as near-infrared spectroscopy (NIRS). Methods Non-culprit coronary artery segments of 581 patients with acute coronary syndrome (ACS) or stable angina pectoris were imaged with IVUS(-VH). In 203 patients, the segments were also imaged with NIRS. Pre-procedural blood samples were drawn for Hp phenotyping. Degree (segment plaque volume, segment plaque burden (PB); presence of lesions with PB≥70%) and composition (segment fractions of fibrous, fibro-fatty, dense calcium, and necrotic core tissue; presence of IVUS-VH derived thin-cap fibroatheroma lesions) of coronary atherosclerosis were measured. Results No differences were present between the three Hp phenotypes with regard to degree and composition of coronary atherosclerosis in the full cohort. However, ACS patients with a Hp2-1 or Hp2-2 phenotype had a higher segment PB percentage (β[95% CI]: 3.88[0.31–7.44], p=0.033), increased prevalence of lesions with PB≥70% (OR[95% CI]: 3.61[1.06–12.30], p=0.040), and a tendency towards a higher segment plaque volume (β[95% CI]: 1.29[−0.04–2.62], p=0.056) in multivariable analyses. Conclusions Although in the full cohort no associations could be demonstrated between Hp phenotypes and plaque characteristics, a significant association was present between phenotypes resulting from a genotype containing a Hp2 allele (Hp2-1 or Hp2-2) and a higher degree of atherosclerosis in patients with ACS.