Haptoglobin phenotype correlates with development of cardiac transplant vasculopathy

Cameron G. Densem, Julie Wassel, Ann Cooper, Nizar Yonan, Nicholas H. Brooks, Brian Keevil

    Research output: Contribution to journalArticlepeer-review


    Objectives: The purpose of this study was to investigate the association between haptoglobin phenotypic variation and development of cardiac transplant vasculopathy. Background: The development of coronary vasculopathy determines long-term survival after cardiac transplantation. Serum haptoglobin levels are associated with non-transplant atherosclerosis. In addition to free hemoglobin binding, haptoglobin influences free radical formation, prostaglandin synthesis and angiogenesis. Three phenotypes of haptoglobin exist in humans, which have both quantitative and qualitative differences. Methods: Coronary disease was diagnosed at post-transplant routine surveillance angiography. Hemoglobin (10%) was added to recipient plasma to form a haptoglobin-hemoglobin complex. Sample aliquots were applied to acid hemoglobin plates and electrophoretically separated. Phenotypes were recognized by comparing the electrophoretic pattern with that of established standards. Haptoglobin concentrations were measured using an immunoturbidimetric technique with polyethylene glycol (PEG)-enhanced precipitation. Results: Ninety-three patients were independently studied. Phenotype 1-1 was found in 20.4%, 2-1 in 41.9% and 2-2 in 37.6%. Haptoglobin levels were highest in 1-1 recipients (2.1 ± 0.58 g/liter) compared with 1.78 ± 0.88 g/liter and 1.3 ± 0.81 g/liter in 2-1 and 2-2 individuals, respectively (p = 0.001). Haptoglobin phenotype was significantly related to the development of vasculopathy; recipients with a 2-1 phenotype were more likely to develop angiographic disease (p = 0.0084). No differences were found among the 3 groups according to univariate analysis. Multivariate analysis identified 3 risk factors for vasculopathy development: age of donor (hazard ratio 1.056 [95% confidence interval 1.02 to 1.094], p = 0.0023); pre-transplant recipient body mass index (hazard ratio 1.116 [95% confidence interval 1.015 to 1.23], p = 0.024), and haptoglobin phenotype (hazard ratio 2.725 [95% confidence interval 1.031 to 7.19], p = 0.012). Conclusions Haptoglobin, through phenotype-dependent mechanisms, correlates with the development of coronary vasculopathy. This finding furthers our understanding of the disease, opens up new areas of research, and may lead to novel therapies.
    Original languageEnglish
    Pages (from-to)43-49
    Number of pages6
    JournalJournal of Heart and Lung Transplantation
    Issue number1
    Publication statusPublished - Jan 2004


    • Adult
    • Coronary Angiography
    • blood: Coronary Disease
    • Female
    • analysis: Haptoglobins
    • Heart Transplantation
    • Humans
    • Male
    • Middle Aged
    • Phenotype
    • Polymorphism, Genetic
    • blood: Postoperative Complications
    • Prognosis
    • Research Support, Non-U.S. Gov't
    • Time Factors


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