It is estimated that 1% to 5% of children in the United States have obstructive sleep apnea (OSA).1 Although the chronic cardiovascular (CV) effects of OSA in adults are well-established, researchers have yet to elucidate such effects in pediatric patients. To that end, a recent review published in CHEST explored the available evidence pertaining to pathways that influence CV risk in this population.1
In a retrospective study reviewed, of 446 children who were referred to a hypertension clinic, 52% with severe OSA demonstrated stage 2 hypertension.2 Several other studies have reported higher systolic and diastolic blood pressure in children with OSA. In addition, as higher body mass indices (BMI) have been noted in children with OSA compared with children without OSA, multiple studies aimed to differentiate the effect of OSA vs BMI and found that each is independently linked to adverse CV events.1
Other findings showed that treatment with adenotonsillectomy or continuous positive airway pressure (CPAP) was associated with blood pressure reduction in children with OSA, suggesting a causal relationship between high blood pressure and OSA that should be further investigated in this population.1 Various studies have also reported links between endothelial dysfunction and OSA in children, and adenotonsillectomy led to improved endothelial function in children with OSA and no family history of hypertension.3
There is robust evidence regarding the multifaceted, likely bidirectional, relationship between inflammatory processes and OSA in children. This includes research revealing “systemic inflammation that is quantified by circulating cytokines, acute phase reactants and inflammatory cells…. [and] evidence of tissue or organ-specific inflammation that mediates some of the phenotypic characteristics observed in children with OSA,” as well as evidence indicating a role of inflammation in OSA pathogenesis, the review authors wrote.1 For example, several studies of children with OSA demonstrated a correlation between circulating cytokines and/or inflammatory cells and endothelial dysfunction, and findings show increased acute phase reactants such as C-reactive protein in these patients.
OSA may also induce insulin resistance and thus increase the risk for atherosclerosis and other markers of CV disease risk. A large pediatric study found an independent, positive association between sleep fragmentation and insulin resistance in children age 5 to 12 years.4
Circadian alterations represent another potential pathway by which OSA may influence CV risk. One study showed changes in the diurnal rhythmicity of cytokines in children age 6 to 13 years with OSA; their tumor necrosis factor-a, interleukin-6, and interleukin-8 levels were higher in the morning compared with healthy controls, who had higher levels in the evening.5 “This reversal of diurnal rhythmicity occurred in addition to overall higher cytokine levels in children with OSA compared to controls,” according to the review.1 These preliminary results “may suggest that the loss of a normal diurnal rhythm of inflammation in OSA could be a mechanism of sustained inflammatory response throughout a 24-h period.”
Overall, the literature supports the hypothesis that CV and inflammatory processes in children with OSA are similar to those seen in adults with OSA, the review concluded. “Further research is needed to determine the causal relationship between OSA and the presence of cardiovascular risk factors as well as the reversibility of these processes with adequate treatment.”1
Pulmonology Advisor interviewed the following clinicians to learn more about CV risk in children with OSA: Ricky Mohon, MD, FAAP, FACP, medical director of sleep medicine and program director of pediatric pulmonology at the Breathing Institute at Children’s Hospital Colorado in Aurora; Ilya Khaytin, MD, PhD, attending physician in pulmonary and sleep medicine at Lurie Children’s Hospital of Chicago and assistant professor of pediatric critical care at Northwestern University Feinberg School of Medicine in Illinois; Gigi Chawla, MD, MHA, pediatrician, hospitalist, and chief of general pediatrics at Children’s Minnesota in Minneapolis; and Christopher Stille, MD, MPH/MSPH, pediatrician and chair of the Child Health Clinic at Children’s Hospital Colorado in Aurora.
Pulmonology Advisor: What is known thus far about CV risk in pediatric patients with OSA, and what are the proposed underlying mechanisms?
Dr Mohon: The full CV risk in pediatric patients with OSA is not well-described at this time and is still an area that needs additional research. We do know that chronic hypoxemia related to OSA can lead to pulmonary hypertension and ultimately cor pulmonale with right heart failure. Underlying mechanisms include increased sympathetic tone related to the recurrent hypoxemia that occurs secondary to the obstructed breathing. Physicians should be aware that sleep-related breathing disorders such as OSA can lead to cognitive impairments and possibly worsen other medical conditions including CV disease, hypertension, diabetes, and metabolic syndrome.
Dr Khaytin: Over the last few decades, it became clear that not only is OSA a common pediatric disease, but also affects multiple aspects of children’s health. OSA has complex interactions with the development of CV, metabolic, and neuropsychiatric problems. OSA causes hypoxemia with consequent reoxygenation after the obstruction is relieved, hypercapnia, negative intrathoracic pressure, and recurrent arousals from sleep. These direct effects of OSA are proposed to cause activation of the sympathetic nervous system, inflammation, and renin-angiotensin systems, collectively resulting in increased systemic and pulmonary blood pressure with cardiac remodeling and endothelial dysfunction.
The effect of OSA on the autonomic nervous system seems to be the most detrimental. Obstructive apneas cause arousals with activation of the sympathetic nervous system, resulting in repetitive changes in systemic and pulmonary arterial pressure.. The increased inspiratory effort with an obstructed breath causes an increase in negative intrathoracic pressure, with effects on venous return.