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Published on: May 11, 2015
Systemic endothelial dysfunction in children with idiopathic pulmonary arterial hypertension correlates with disease
Debbie Friedman1, Jacqueline Szmuszkovicz, Miklos Rabai
1Children's Heart Center, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ 07112, USA. defriedman@barnabashealth.org
Insights
Systemic endothelial dysfunction is present in children with idiopathic pulmonary arterial hypertension (IPAH) and indicates disease severity. This finding suggests IPAH is a global vasculopathy, not limited to the lungs.
Area of Science:
- Cardiology
- Pediatric Cardiology
- Vascular Biology
- Pulmonary Hypertension Research
Background:
- Idiopathic pulmonary arterial hypertension (IPAH) is a severe condition characterized by pulmonary vascular remodeling and right heart failure.
- While pulmonary endothelial function is studied, IPAH's systemic vascular impact, especially in children, remains unexplored.
- This study investigates systemic endothelial function in pediatric IPAH, hypothesizing it correlates with disease severity.
Purpose of the Study:
- To assess systemic endothelial function in children diagnosed with idiopathic pulmonary arterial hypertension (IPAH).
- To determine the correlation between systemic endothelial function and clinical/echocardiographic markers of IPAH severity in pediatric patients.
- To evaluate if IPAH represents a systemic vasculopathy in children.
Main Methods:
- A prospective, cross-sectional study involving 13 children with IPAH and 13 age-matched controls.
- Brachial artery flow-mediated dilation (FMD), an endothelial-dependent measure, was used to assess systemic endothelial function.
- FMD measurements were compared between IPAH patients and controls and correlated with clinical and echocardiographic severity indices.
Main Results:
- Children with IPAH exhibited significantly reduced FMD compared to healthy controls (5.1% vs. 9.7%, p < 0.0001).
- In IPAH patients, FMD showed a direct correlation with cardiac index (R(2) = 0.34, p = 0.035).
- FMD inversely correlated with tricuspid regurgitation velocity (R(2) = 0.57, p = 0.019) and right ventricular myocardial performance index (R(2) = 0.44, p = 0.028), indicating poorer function with lower FMD.
Conclusions:
- The study confirms systemic endothelial dysfunction in pediatric IPAH, strongly associated with disease severity.
- These findings support the concept of IPAH as a global vasculopathy affecting both pulmonary and systemic vasculature.
- Further research into shared endothelial dysfunction mechanisms may offer new therapeutic targets for IPAH.
Background:
Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease manifested by progressive pulmonary vascular remodeling, compromised pulmonary blood flow and right heart failure. Most studies have explored how pulmonary endothelial function modulates disease pathogenesis. We hypothesize that IPAH is a progressive panvasculopathy, affecting both pulmonary and systemic vascular beds, and that systemic endothelial dysfunction correlates with disease severity. Recent studies have demonstrated systemic endothelial dysfunction in adults with pulmonary hypertension; however, adults often have additional comorbidities affecting endothelial function. Systemic endothelial function has not been explored in children with IPAH.
Methods:
In this single-center, prospective, cross-sectional study we examined brachial artery flow-mediated dilation (FMD), a nitric oxide-mediated, endothelial-dependent response, in children with IPAH and matched controls. FMD measurements were compared with clinical and echocardiographic measures of IPAH severity.
Results:
Thirteen patients and 13 controls were studied, ranging in age from 6 to 20 years. FMD was decreased in IPAH subjects compared with controls (5.1 ± 2.1% vs 9.7 ± 2.0%; p < 0.0001). In IPAH subjects, FMD correlated directly with cardiac index (R(2) = 0.34, p = 0.035), and inversely with tricuspid regurgitation velocity (R(2) = 0.57, p = 0.019) and right ventricular myocardial performance index (R(2) = 0.44, p = 0.028).
Conclusions:
The presence of systemic endothelial dysfunction in children with IPAH and its strong association with IPAH severity demonstrate that IPAH is a global vasculopathy. Although morbidity in IPAH is typically associated with pulmonary vascular disease, systemic vascular changes may also relate to disease pathogenesis and progression. Further study into shared mechanisms of systemic and pulmonary endothelial dysfunction may contribute to future therapies for IPAH.
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