Risk Factors for Death in 632 Patients with Sickle Cell Disease in the United States and United Kingdom

Background: The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial. Methods and Results: We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)>= 3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure >= 25 mm Hg was used. Among 572 subjects, 11.2% had TRV >= 3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values >= 160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV<3.0 m/sec. At 24 months the cumulative survival was 83% with TRV >= 3.0 m/sec and 98% with TRV, 3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1-30.1; p, 0.0001) for TRV >= 3.0 m/sec, 4.6 (1.8-11.3; p = 0.001) for NT-proBNP >= 160 pg/mL, and 14.9 (5.5-39.9; p<0.0001) for both TRV >= 3.0 m/sec and NT-proBNP >= 160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death. Conclusions: A TRV >= 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.