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. 2016 Nov;35(11):1295-1302.
doi: 10.1016/j.healun.2016.06.022. Epub 2016 Jul 15.

Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients

Ali Javaheri  1 , Maria Molina  2 , Payman Zamani  2 , Amrith Rodrigues  2 , Eric Novak  3 , Susan Chambers  2 , Patricia Stutman  2 , Wilhelmina Maslanek  2 , Mary Williams  2 , Scott M Lilly  4 , Peter Heeger  5 , Mohamed H Sayegh  6 , Anil Chandraker  7 , David M Briscoe  8 , Kevin P Daly  8 , Randall Starling  9 , David Ikle  10 , Jason Christie  2 , J Eduardo Rame  2 , Lee R Goldberg  2 , Jeffrey Billheimer  2 , Daniel J Rader  2
Affiliations

Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients

Ali Javaheri et al. J Heart Lung Transplant. 2016 Nov.

Abstract

Background: Cardiac allograft vasculopathy (CAV) is a major cause of mortality after cardiac transplantation. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is inversely associated with coronary artery disease. In 2 independent studies, we tested the hypothesis that reduced CEC is associated with mortality and disease progression in CAV.

Methods: We tested the relationship between CEC and survival in a cohort of patients with CAV (n = 35). To determine whether reduced CEC is associated with CAV progression, we utilized samples from the Clinical Trials in Organ Transplantation 05 (CTOT05) study to determine the association between CEC and CAV progression and status at 1 year (n = 81), as assessed by average change in maximal intimal thickness (MIT) on intravascular ultrasound.

Results: Multivariable Cox proportional hazard models demonstrated that higher levels of CEC were associated with improved survival (hazard ratio 0.26, 95% confidence interval 0.11 to 0.63) per standard deviation CEC, p = 0.002). Patients who developed CAV had reduced CEC at baseline and 1-year post-transplant. We observed a significant association between pre-transplant CEC and the average change in MIT, particularly among patients who developed CAV at 1 year (β = -0.59, p = 0.02, R2 = 0.35).

Conclusion: Reduced CEC is associated with disease progression and mortality in CAV patients. These findings suggest the hypothesis that interventions to increase CEC may be useful in cardiac transplant patients for prevention or treatment of CAV.

Keywords: cardiac allograft vasculopathy; cholesterol efflux capacity; high-density lipoprotein; survival; transplantation.

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Conflict of interest statement

statement The other authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Study design of the Penn transplant and CTOT05 cohorts. In the Penn angiographic cohort, 35 patients with CAV had CEC measured at time of the catheterization. We tested the relationship between CEC and survival. In the CTOT05, 81 subjects had samples available for CEC assays and paired IVUS assessment of CAV. We tested the relationship between CAV status and progression, as assessed by IVUS, and CEC.
Figure 2
Figure 2
CEC capacity is lower in patients with CAV who died compared to survivors with CAV. (A) CEC in patients with CAV who died compared with survivors. (B) Forest plot demonstrating hazardratio (HR) and upper and lower confidence limits (UCL and LCL, respectively) for CEC in a Cox survival analysis. (C) Scatterplot of CEC capacity versus cyclosporine dose with regression line and 95% confidence estimate around regression line.
Figure 3
Figure 3
CEC is significantly decreased before transplant in patients who met pre-specified intravascular ultrasound criteria for CAV versus those who did not. (A) CEC before transplant. (B) CEC at 1 year.
Figure 4
Figure 4
CEC is independently associated with CAV as measured by IVUS. Forest plot depicting odds ratio (OR) with upper and lower confidence limits (UCL and LCL, respectively) for CEC, HDL-C, LDL-C and diabetes in a logistic regression model for CAV.
Figure 5
Figure 5
CEC is associated with progressive changes on intravascular ultrasound in CAV patients. Change in maximal intimal thickness over 1 year (y-axis) is plotted against normalized cholesterol efflux capacity (x-axis) with regression line and 95% confidence interval.
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