Department of Medicine, Division of Cardiology, University of California at San Francisco, San Francisco, California, USA.
J Heart Lung Transplant. 2009 Oct;28(10):1081-6. doi: 10.1016/j.healun.2009.06.005.
Endothelial and leukocytes-derived microparticles (EMPs and LMPs, respectively) are increased in patients with pulmonary hypertension (PH). We hypothesized that the levels of circulating EMPs and LMPs could predict outcome in these patients.
Patients undergoing right heart catheterization for untreated pre-capillary PH were eligible for the study. Baseline hemodynamics and biologic and clinical parameters were measured at the time of enrollment. Measurements of CD62e(+), CD144(+) and CD31(+)/CD41(-) EMPs and CD45(+) LMPs were performed using flow cytometry in venous platelet-free plasma samples. After inclusion, patients were treated at the discretion of the physician and prospectively followed for 12 months. The primary end-point was the combined occurrence of death and re-admission for right heart failure (RHF) or worsening of RHF symptoms.
Seven of 21 patients (mean age 54.1 +/- 3.5 years, 62% female) experienced the primary end-point during the study period. These patients had higher baseline levels of CD62e(+) EMPs, LMPs and hsCRP (high sensitivity C-reactive protein) compared to patients without events (p < 0.05), whereas no difference was observed for other microparticles and functional and hemodynamics parameters. Receiver operating curve analysis showed that baseline CD62e(+) EMPs levels of >353 events/microl predicted clinical complications. Kaplan-Meier analysis revealed that patients with baseline CD62e(+) EMPs above this cut-off value had a significantly worse prognosis compared with those subjects who had levels below this cut-off (p = 0.02, log-rank statistics).
Elevated levels of circulating CD62e(+) EMPs but not LMPs in PH patients prior to treatment are associated with adverse clinical events. Assessment of CD62e(+) EMPs levels may represent a new tool for stratification of PH patients.
内皮细胞和白细胞衍生的微颗粒(分别为 EMP 和 LMP)在肺动脉高压(PH)患者中增加。我们假设循环 EMP 和 LMP 的水平可以预测这些患者的预后。
患有未经治疗的毛细血管前 PH 的接受右心导管检查的患者有资格参加研究。在入组时测量基线血流动力学和生物学及临床参数。使用流式细胞术测量静脉无血小板血浆样本中 CD62e(+)、CD144(+)和 CD31(+)/CD41(-)EMP 和 CD45(+)LMP。纳入后,根据医生的判断对患者进行治疗,并前瞻性随访 12 个月。主要终点是死亡和因右心衰竭(RHF)或 RHF 症状恶化而再次入院的复合发生。
21 名患者中有 7 名(平均年龄 54.1 +/- 3.5 岁,62%为女性)在研究期间发生了主要终点事件。与无事件患者相比,这些患者的基线 CD62e(+)EMP、LMP 和 hsCRP(高敏 C 反应蛋白)水平更高(p < 0.05),而其他微颗粒和功能及血流动力学参数无差异。接受者操作特征曲线分析显示,基线 CD62e(+)EMP 水平 >353 事件/微升可预测临床并发症。Kaplan-Meier 分析显示,基线 CD62e(+)EMP 值高于该截值的患者与低于该截值的患者相比预后明显较差(p = 0.02,对数秩统计)。
在接受治疗之前,PH 患者循环中 CD62e(+)EMP 的水平升高而不是 LMP 与不良临床事件相关。评估 CD62e(+)EMP 水平可能是 PH 患者分层的新工具。