Pulmonary hypertension as a risk factor for death in patients with sickle cell disease.
BACKGROUND
The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Md 20892-1662, USA. mgladwin@nih.gov
Mark T
MT
Gladwin
Vandana
V
Sachdev
Maria L
ML
Jison
Yukitaka
Y
Shizukuda
Jonathan F
JF
Plehn
Karin
K
Minter
Bernice
B
Brown
Wynona A
WA
Coles
James S
JS
Nichols
Inez
I
Ernst
Lori A
LA
Hunter
William C
WC
Blackwelder
Alan N
AN
Schechter
Griffin P
GP
Rodgers
Oswaldo
O
Castro
Frederick P
FP
Ognibene
D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D000986:Antisickling Agents / Q000627:therapeutic use; D001794:Blood Pressure; D002423:Cause of Death; D004351:Drug Resistance; D015150:Echocardiography, Doppler; D005260:Female; D006461:Hemolysis; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000145:classification / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D015995:Prevalence; D011651:Pulmonary Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D012307:Risk Factors; D015996:Survival Rate; D014262:Tricuspid Valve Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology; D016276:Ventricular Function
D000986:Antisickling Agents; D006918:Hydroxyurea