Gladwin Mark T, Sachdev Vandana, Jison Maria L, Shizukuda Yukitaka, Plehn Jonathan F, Minter Karin, Brown Bernice, Coles Wynona A, Nichols James S, Ernst Inez, Hunter Lori A, Blackwelder William C, Schechter Alan N, Rodgers Griffin P, Castro Oswaldo, Ognibene Frederick P
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Md 20892-1662, USA.
N Engl J Med. 2004 Feb 26;350(9):886-95. doi: 10.1056/NEJMoa035477.
The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown.
We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 195 consecutive patients (82 men and 113 women; mean [+/-SD] age, 36+/-12 years). Pulmonary hypertension was prospectively defined as a tricuspid regurgitant jet velocity of at least 2.5 m per second. Patients were followed for a mean of 18 months, and data were censored at the time of death or loss to follow-up.
Doppler-defined pulmonary hypertension occurred in 32 percent of patients. Multiple logistic-regression analysis, with the use of the dichotomous variable of a tricuspid regurgitant jet velocity of less than 2.5 m per second or 2.5 m per second or more, identified a self-reported history of cardiovascular or renal complications, increased systolic blood pressure, high lactate dehydrogenase levels (a marker of hemolysis), high levels of alkaline phosphatase, and low transferrin levels as significant independent correlates of pulmonary hypertension. The fetal hemoglobin level, white-cell count, and platelet count and the use of hydroxyurea therapy were unrelated to pulmonary hypertension. A tricuspid regurgitant jet velocity of at least 2.5 m per second, as compared with a velocity of less than 2.5 m per second, was strongly associated with an increased risk of death (rate ratio, 10.1; 95 percent confidence interval, 2.2 to 47.0; P<0.001) and remained so after adjustment for other possible risk factors in a proportional-hazards regression model.
Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Therapeutic trials targeting this population of patients are indicated.
镰状细胞病成年患者中肺动脉高压的患病率、其发生机制及其潜在的预后意义尚不清楚。
我们对195例连续患者（82例男性和113例女性；平均[±标准差]年龄为36±12岁）进行了肺动脉收缩压的多普勒超声心动图评估。肺动脉高压前瞻性地定义为三尖瓣反流喷射速度至少为每秒2.5米。患者平均随访18个月，数据在死亡或失访时进行截尾。
多普勒定义的肺动脉高压发生在32%的患者中。多因素logistic回归分析使用三尖瓣反流喷射速度小于每秒2.5米或每秒2.5米及以上的二分变量，确定自我报告的心血管或肾脏并发症病史、收缩压升高、高乳酸脱氢酶水平（溶血标志物）、高碱性磷酸酶水平和低转铁蛋白水平是肺动脉高压的显著独立相关因素。胎儿血红蛋白水平、白细胞计数、血小板计数以及羟基脲治疗的使用与肺动脉高压无关。与速度小于每秒2.5米相比，三尖瓣反流喷射速度至少为每秒2.5米与死亡风险增加密切相关（率比为10.1；95%置信区间为2.2至47.0；P<0.001），并且在比例风险回归模型中对其他可能的风险因素进行调整后仍然如此。
通过多普勒超声心动图诊断的肺动脉高压在镰状细胞病成年患者中很常见。它似乎是慢性溶血的并发症，对羟基脲治疗耐药，并具有很高的死亡风险。针对这类患者的治疗试验是必要的。
