Pulmonary arterial hypertension and left‐sided heart disease in sickle cell disease: Clinical characteristics and association with soluble adhesion molecule expression

Pulmonary hypertension (PH), a risk factor for mortality in sickle cell disease (SCD), has pathologic features of both pulmonary arterial hypertension (PAH) and PH related to left‐sided heart disease (LHD) suggesting a link between these two entities. We hypothesized that both are characterized by endothelial dysfunction and increased adhesion molecule expression. SCD patients and normal volunteers underwent a screening questionnaire, echocardiogram, and blood donation for preparation of platelet‐poor plasma. PAH was defined as a tricuspid regurgitant jet (TRJ) velocity ≥2.5 m/sec and/or the presence of isolated right ventricular hypertrophy or decreased systolic function. LHD was defined as either left‐sided systolic/diastolic dysfunction or significant valvular disease. Plasma vascular cell adhesion molecule‐1 (VCAM‐1), intercellular adhesion molecule‐1 (ICAM‐1), P‐ and E‐selectin, nitric oxide (NOx), erythropoietin, and vascular endothelial growth factor (VEGF) levels were assayed by enzyme‐linked immunoassay. Forty‐three percent of sickle cell anemia (HbSS) and 28% of hemoglobin SC disease (HbSC) disease patients had PAH. Additionally, 10–15% of SCD patients had LHD. VCAM‐1 levels were significantly increased in HbSS patients compared with HbSC patients and normal volunteers. VCAM‐1 and P‐selectin levels correlated positively with TRJ velocity in HbSS patients (r = 0.45, P = 0.03, r = 0.2, P = 0.05, respectively). ICAM‐1, E‐selectin, NOx, erythropoietin, and VEGF levels were similar across subject groups. PH is common in SCD and, at times, due to LHD. Increased VCAM‐1 and P‐selectin expression was associated with TRJ elevation regardless of etiology suggesting a similar effect on endothelial gene expression and possibly providing a pathologic link between PAH and PH related to LHD in SCD. Am. J. Hematol. 2008. © 2008 Wiley‐Liss, Inc.