Ali Javaheri1, Maria Molina2, Payman Zamani2, Amrith Rodrigues2, Eric Novak3, Susan Chambers2, Patricia Stutman2, Wilhelmina Maslanek2, Mary Williams2, Scott M Lilly4, Peter Heeger5, Mohamed H Sayegh6, Anil Chandraker7, David M Briscoe8, Kevin P Daly8, Randall Starling9, David Ikle10, Jason Christie2, J Eduardo Rame2, Lee R Goldberg2, Jeffrey Billheimer2, Daniel J Rader2. 1. Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: ali.javaheri@wustl.edu. 2. Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 3. Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri, USA. 4. Division of Cardiology, Ohio State University, Columbus, Ohio, USA. 5. Icahn School of Medicine at Mount Sinai, New York, New York. 6. Brigham & Women׳s Hospital, Harvard University, Boston, Massachusetts, USA; Department of Medicine and Immunology, American University of Beirut, Beirut, Lebanon. 7. Brigham & Women׳s Hospital, Harvard University, Boston, Massachusetts, USA. 8. Children's Hospital Boston, Boston, Massachusetts, USA. 9. Cleveland Clinic, Cleveland, Ohio, USA. 10. Department of Biostatistics, Rho Federal Systems Division, Rho, Inc., Chapel Hill, North Carolina, USA.
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.
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.
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