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.