Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease

TLDR

Pulmonary hypertension prevalence, development mechanisms, and prognostic impact in adults with sickle cell disease are largely unknown. The study highlights the need for therapeutic trials in sickle cell patients with pulmonary hypertension. Pulmonary hypertension was defined as tricuspid regurgitant jet velocity ≥ 2.5 m/s and assessed by Doppler echocardiography in 195 patients over a mean 18‑month follow‑up. Pulmonary hypertension occurred in 32 % of patients and was independently associated with a history of cardiovascular or renal disease, higher systolic blood pressure, elevated LDH, alkaline phosphatase, and lower transferrin; a TR velocity ≥ 2.5 m/s predicted a ten‑fold higher mortality risk and remained significant after adjustment.

Abstract

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.