Serum Apelin in children and adolescents with sickle cell disease: relation to cardiopulmonary complications
Ehab Fahmy Abdelhady Ragab;
Abstract
SUMMARY
S
ickle cell disease (SCD) is one of the most common severe monogenic disorders in the world. Vascular dysfunction is the end result, due to complex and multifactorial interactions that ultimately manifest as the clinical phenotypes of SCD. Cardiovascular involvement represents a leading cause of mortality and morbidity in SCD. Pulmonary hypertension is a serious complication in patients with hemolytic anemias. It represents one element of the systemic vasculopathy seen in some patients with SCD (systemic hypertension, renal failure and priapism) and is linked to hemolytic rate, iron overload and cholestatic hepatic dysfunction.
The peptide apelin and the apelin receptor (APLNR) are present in the heart, the systemic and pulmonary vasculature, and the expression of apelin and APLNR is regulated by hypoxia inducible factor -1α and bone morphogenetic protein receptor-2. Furthermore, the apelin-APLNR system is involved in normal vascular development and regulation of apoptosis and has been shown to be involved in regulation of NO-dependent vasodilatation and to improve cardiac contractility. Therefore, we determined the levels apelin in young SCD patients and assess their relation to markers of hemolysis, iron overload and cardiopulmonary complications.
This study included 40 SCD patients (25 males and 15 females with a male-to-female ratio 1.7:1) recruited from the regular attendants of the Pediatric Hematology Clinic, Pediatric Hospital, Ain Shams University. Patients were compared with 40 age- and sex-matched healthy subjects (24 males and 16 females) enrolled as controls. The median age of SCD patients was 9.5 years (range: 2.5-18 years) while that of controls was 9.3 years (range: 2.5-16 years). All included patients were subjected to detailed medical history and thorough clinical examination with special emphasis on anthropometric measures, disease duration, evidence of renal, hepatic or cardiac disease, history of sickling crisis or splenectomy, transfusion history and chelation/ hydroxyurea therapy. Apelin levels were measured by enzyme linked immunosorbent assay (ELISA). All patients were in steady state.
In the current work, cardiopulmonary complications were found in 35% of patients (20% of them had pulmonary hypertension risk). Apelin levels were significantly lower in SCD patients compared with control group. Analysis of apelin in relation to the clinical characteristics of patients with SCD revealed that patients with cardiopulmonary complications whether those at risk of pulmonary hypertension or patients with heart disease had significantly lower apelin levels than those without.
SCD patients treated with hydroxyurea had higher apelin levels than untreated patients. Although patients receiving chelation therapy had higher levels of apelin compared with untreated patients, the difference did not reach a significant level. No association between apelin and other variables including sex, splenctomy or sickling crisis.
Correlation studies revealed significant negative correlations between serum apelin and age, disease duration, LDH, total and indirect bilirubin as well as serum ferritin.
As regards the relations between apelin and echocardiographic parameters among patients with SCD, significant negative correlations were found between this marker and end systolic diameter, tricuspid regurgitant jet velocity, right ventricle systolic pressure, pulmonary vascular resistance, tissue Doppler imaging S wave while apelin was positively correlated to end diastolic diameter indexed to body surface area, end systolic diameter indexed to body surface area, ejection fraction Simpson and right ventricle end diastolic diameter indexed to body surface area.
Multiple regression linear analysis showed that disease duration, LDH, indirect bilirubin, serum ferritin, EF Simpson, TRV and RVSP were independently related to apelin levels in SCD patients.
ROC curve analysis revealed that apelin cutoff value 1650 ng/L could significantly detect the presence of cardiopulmonary complications among SCD patients with 90.9% sensitivity and specificity of 72.4% while the cutoff value 2000 ng/L could significantly detect the presence of pulmonary hypertension among SCD patients with 100% sensitivity and specificity of 76.5%.
Logistic regression analysis showed that disease duration, LDH, serum ferritin and apelin levels are independently related to the risk of elevated TRV among SCD patients.
S
ickle cell disease (SCD) is one of the most common severe monogenic disorders in the world. Vascular dysfunction is the end result, due to complex and multifactorial interactions that ultimately manifest as the clinical phenotypes of SCD. Cardiovascular involvement represents a leading cause of mortality and morbidity in SCD. Pulmonary hypertension is a serious complication in patients with hemolytic anemias. It represents one element of the systemic vasculopathy seen in some patients with SCD (systemic hypertension, renal failure and priapism) and is linked to hemolytic rate, iron overload and cholestatic hepatic dysfunction.
The peptide apelin and the apelin receptor (APLNR) are present in the heart, the systemic and pulmonary vasculature, and the expression of apelin and APLNR is regulated by hypoxia inducible factor -1α and bone morphogenetic protein receptor-2. Furthermore, the apelin-APLNR system is involved in normal vascular development and regulation of apoptosis and has been shown to be involved in regulation of NO-dependent vasodilatation and to improve cardiac contractility. Therefore, we determined the levels apelin in young SCD patients and assess their relation to markers of hemolysis, iron overload and cardiopulmonary complications.
This study included 40 SCD patients (25 males and 15 females with a male-to-female ratio 1.7:1) recruited from the regular attendants of the Pediatric Hematology Clinic, Pediatric Hospital, Ain Shams University. Patients were compared with 40 age- and sex-matched healthy subjects (24 males and 16 females) enrolled as controls. The median age of SCD patients was 9.5 years (range: 2.5-18 years) while that of controls was 9.3 years (range: 2.5-16 years). All included patients were subjected to detailed medical history and thorough clinical examination with special emphasis on anthropometric measures, disease duration, evidence of renal, hepatic or cardiac disease, history of sickling crisis or splenectomy, transfusion history and chelation/ hydroxyurea therapy. Apelin levels were measured by enzyme linked immunosorbent assay (ELISA). All patients were in steady state.
In the current work, cardiopulmonary complications were found in 35% of patients (20% of them had pulmonary hypertension risk). Apelin levels were significantly lower in SCD patients compared with control group. Analysis of apelin in relation to the clinical characteristics of patients with SCD revealed that patients with cardiopulmonary complications whether those at risk of pulmonary hypertension or patients with heart disease had significantly lower apelin levels than those without.
SCD patients treated with hydroxyurea had higher apelin levels than untreated patients. Although patients receiving chelation therapy had higher levels of apelin compared with untreated patients, the difference did not reach a significant level. No association between apelin and other variables including sex, splenctomy or sickling crisis.
Correlation studies revealed significant negative correlations between serum apelin and age, disease duration, LDH, total and indirect bilirubin as well as serum ferritin.
As regards the relations between apelin and echocardiographic parameters among patients with SCD, significant negative correlations were found between this marker and end systolic diameter, tricuspid regurgitant jet velocity, right ventricle systolic pressure, pulmonary vascular resistance, tissue Doppler imaging S wave while apelin was positively correlated to end diastolic diameter indexed to body surface area, end systolic diameter indexed to body surface area, ejection fraction Simpson and right ventricle end diastolic diameter indexed to body surface area.
Multiple regression linear analysis showed that disease duration, LDH, indirect bilirubin, serum ferritin, EF Simpson, TRV and RVSP were independently related to apelin levels in SCD patients.
ROC curve analysis revealed that apelin cutoff value 1650 ng/L could significantly detect the presence of cardiopulmonary complications among SCD patients with 90.9% sensitivity and specificity of 72.4% while the cutoff value 2000 ng/L could significantly detect the presence of pulmonary hypertension among SCD patients with 100% sensitivity and specificity of 76.5%.
Logistic regression analysis showed that disease duration, LDH, serum ferritin and apelin levels are independently related to the risk of elevated TRV among SCD patients.
Other data
| Title | Serum Apelin in children and adolescents with sickle cell disease: relation to cardiopulmonary complications | Other Titles | مستوى الأبيلين فى الأطفال والمراهقين المصابين بالأنيميا المنجلية وعلاقته بمضاعفات القلب والرئتين | Authors | Ehab Fahmy Abdelhady Ragab | Issue Date | 2015 |
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