Javaheri Ali, Molina Maria, Zamani Payman, Rodrigues Amrith, Novak Eric, Chambers Susan, Stutman Patricia, Maslanek Wilhelmina, Williams Mary, Lilly Scott M, Heeger Peter, Sayegh Mohamed H, Chandraker Anil, Briscoe David M, Daly Kevin P, Starling Randall, Ikle David, Christie Jason, Rame J Eduardo, Goldberg Lee R, Billheimer Jeffrey, Rader Daniel J
Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Heart Lung Transplant. 2016 Nov;35(11):1295-1302. doi: 10.1016/j.healun.2016.06.022. Epub 2016 Jul 15.
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.
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.
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, R = 0.35).
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.
心脏移植术后血管病变(CAV)是心脏移植后死亡的主要原因。高密度脂蛋白(HDL)胆固醇流出能力(CEC)与冠状动脉疾病呈负相关。在两项独立研究中,我们检验了CEC降低与CAV患者死亡率和疾病进展相关的假设。
我们在一组CAV患者(n = 35)中检验了CEC与生存率之间的关系。为了确定CEC降低是否与CAV进展相关,我们利用器官移植临床试验05(CTOT05)研究的样本,通过血管内超声测量的最大内膜厚度(MIT)的平均变化来评估CEC与1年时CAV进展和状态之间的关联(n = 81)。
多变量Cox比例风险模型显示,每增加一个标准差的CEC水平,生存率提高(风险比0.26,95%置信区间0.11至0.63,p = 0.002)。发生CAV的患者在基线和移植后1年时CEC降低。我们观察到移植前CEC与MIT的平均变化之间存在显著关联,特别是在1年时发生CAV的患者中(β = -0.59,p = 0.02,R = 0.35)。
CEC降低与CAV患者的疾病进展和死亡率相关。这些发现提示了一个假设,即增加CEC的干预措施可能对心脏移植患者预防或治疗CAV有用。