Raichlin Eugenia, McConnell Joseph P, Bae Jang-Ho, Kremers Walter K, Lerman Amir, Frantz Robert P
William J. Von Liebig Transplant Center, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Transplantation. 2008 Apr 15;85(7):963-8. doi: 10.1097/TP.0b013e3181684319.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor for coronary artery disease (CAD) in nontransplant patients. We evaluated the association between Lp-PLA2, cardiac allograft vasculopathy (CAV) assessed by 3D intravascular ultrasound, and incidence of cardiac adverse events in heart transplant recipients.
Fasting blood samples were obtained and stored from a cross-section of 112 cardiac transplant recipients attending the Mayo cardiac transplant clinic in 2000 to 2001, mean of 4.7 years after transplant. Lp-PLA2 was measured in plasma aliquots using an enzyme-linked immunoassay. Fifty-six of these patients subsequently underwent two 3D intravascular ultrasound studies in 2004 to 2006 12 months apart. Cardiovascular (CV) events included percutaneous coronary intervention, coronary artery bypass grafting (CABG), reduction in left ventricular ejection fraction (LVEF) < or =45% secondary to CAV and CV death.
High Lp-PLA2 level was associated with increase in plaque volume (r=0.43, P=0.0026) and percent plaque volume (r=0.45, P=0.0004). The association remained significant after adjusting for clinical and lipid variables. During follow-up of 5.1+/-1.6 years, 24 CV adverse events occurred in 15 of 112 (13%) heart transplant patients. Lp-PLA2 level>236 ng/mL (higher tertile) identified a subgroup of patients having a 2.4-fold increase of relative risk for combined endpoint of CV events (percutaneous coronary intervention, CABG, LVEF<45%, and CV death; 95% CI 1.16-5.19, P=0.012) compared with patients with Lp-PLA2< or =236 ng/mL.
Lp-PLA2 is independently associated with progression of CAV and predicts a higher incidence of CV events and CV death in transplant patients. This finding supports the concept that systemic inflammation is an important mediator of CAV. Lp-PLA2 may be a useful marker for risk of CAV and a therapeutic target in posttransplant patients.
脂蛋白相关磷脂酶A2（Lp-PLA2）是非移植患者冠状动脉疾病（CAD）的一个危险因素。我们评估了Lp-PLA2、通过三维血管内超声评估的心脏移植血管病变（CAV）与心脏移植受者心脏不良事件发生率之间的关联。
采集了2000年至2001年在梅奥心脏移植诊所就诊的112名心脏移植受者的空腹血样并储存，移植后平均4.7年。使用酶联免疫测定法在血浆等分试样中测量Lp-PLA2。其中56名患者随后在2004年至2006年期间相隔12个月接受了两次三维血管内超声检查。心血管（CV）事件包括经皮冠状动脉介入治疗、冠状动脉旁路移植术（CABG）、因CAV导致左心室射血分数（LVEF）降低至≤45%以及CV死亡。
高Lp-PLA2水平与斑块体积增加（r=0.43，P=0.0026）和斑块体积百分比增加（r=0.45，P=0.0004）相关。在调整临床和脂质变量后，这种关联仍然显著。在5.1±1.6年的随访期间，112名心脏移植患者中的15名（13%）发生了24起CV不良事件。与Lp-PLA2≤236 ng/mL的患者相比，Lp-PLA2水平>236 ng/mL（较高三分位数）的患者亚组发生CV事件联合终点（经皮冠状动脉介入治疗、CABG、LVEF<45%和CV死亡）的相对风险增加2.4倍（95%CI 1.16 - 5.19，P=0.012）。
Lp-PLA2与CAV的进展独立相关，并预测移植患者中CV事件和CV死亡的发生率更高。这一发现支持了全身炎症是CAV重要介质的概念。Lp-PLA2可能是CAV风险的有用标志物以及移植后患者的治疗靶点。
