Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival in heart
transplant recipients (HTR) accounting for almost 30% of deaths after 5 years. Early
non-invasive detection remains a major challenge due the insensitivity and invasiveness
of current diagnostic tests. Small vessel disease and endothelial dysfunction are key
players in the pathophysiology of CAV. We hypothesize that in HTR there is an
impairment of endothelial cellular repair and changes in arterial elasticity, especially in
small arteries, resulting in a reduction of small artery elasticity (SAE), an increase in the
number of circulating endothelial cells (CEC), and increased CEC activation. In
addition, these changes are significant in HTR who develop CAV.
Methods: Ninety-seven HTR and 22 normal controls were included in this study. SAE
was measured from the radial artery. CEC (CD146+ cells) were enumerated and
assessed for activation based on VCAM expression. Continuous variables were
analyzed using t-test and dichotomous variables using Chi-square. Logistic regression
using stepwise selection was performed to evaluate determinants of CEC, CEC
activation, and SAE.
Results: The median age was 61years(range, 18-76). The mean duration of transplant
was 5.4 ± 5.3 year. 77 % were male and 57% had CAV. HT was associated with
significantly lower SAE (p<0.0001) and increased CEC activation (p=0.0004) when
compared to healthy controls. We also found that CAV was significantly associated
with SAE and CEC (p = 0.04 and 0.01, respectively). On stepwise regression,
hypertension treatment and duration of transplant were associated with CAV.
Conclusion: Heart transplant is characterized by endothelial activation and dysfunction
as evidenced by a reduction in SAE and increased CEC activation. Prospective studies
to evaluate these markers as predictors of risk are needed for further evaluation.
University of Minnesota Master of Science thesis. January 2011. Major: Clinical Research. Advisors: Daniel Duprez, Jay Cohn, John Connett. 1 computer file (PDF); viii, 38 pages.
Colvin, Monica Mechele.
Markers of Endothelial Function in Heart Transplant Recipients and Associations with Cardiac Allograft Vasculopathy.
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