PH linked to increased risk of sleep disorders, brain structure changes
However, sleep disorders do not increase risk for PH, study finds
Pulmonary hypertension (PH) is associated with an increased risk for sleep disorders, including obstructive sleep apnea, and structural brain changes at the genetic level, according to a recent study.
These findings may help “develop new guidelines for the clinical management, personalized diagnosis, and treatment of PH, sleep disorder diseases, and their associated neurological comorbidities [coexisting disorders],” researchers wrote.
The study, “Triangular Causality Among Pulmonary Hypertension, Sleep Disorders, and Brain Structure at the Genetic Level: A Mendelian Randomization Study Focused on the Lung-Brain Axis,” was published in Nature and Science of Sleep.
PH is a progressive disease characterized by unusually high blood pressure in the pulmonary arteries, the blood vessels that supply the lungs. This restricts blood flow to the lungs and causes more strain on the heart which needs to work harder to pump blood.
Sleep disturbances common in PH
People living with PH may experience systemic (body-wide) complications, including sleep disorders and chronic kidney disease. The most common sleep disturbance is obstructive sleep apnea (OSA), which is when breathing is interrupted due to airway blockage, with impacts on sleep quality and daytime function.
However, existing research shows the prevalence of PH in patients with OSA varies significantly, with few studies investigating the prevalence of OSA in PH patients, the researchers noted.
To learn more about the relationship between PH and sleep disorders, researchers in China conducted a genetic-level study, based on genome-wide association study data. This type of approach looks at genetic variations to find genes associated with specific diseases.
For that, they analyzed data from four international studies, which included several sites across the U.S., France, Germany, the Netherlands, Italy, and the U.K. Then, identified gene variants were analyzed for their potential relationship with PH and sleep disorders, using a method called Mendelian randomization, which assesses the association between factors such as lifestyle habits or biomarkers and specific health outcomes.
Overall, a total of 11,744 individuals of European ancestry were included, and 2,085 of them had a PH diagnosis. The researchers identified 24 genetic variants, in 18 genes, strongly associated with PH. Further analysis demonstrated these genes were enriched in biological pathways related to calcium-mediated signaling and ion protein channels, “both of which are strongly linked to the physiological mechanisms of PH.”
PH increases risk for sleep disorders by 1.8%
Results showed PH significantly increased the risk for sleep disorders by 1.8%, including OSA by 2.2%. On the contrary, no evidence was found to suggest having sleep disorders may increase the risk for PH.
A total of 153 genetic variants, linked to 15 brain structures, were identified. Results indicated PH could be a risk factor for changes in total brain structure and white matter, which is composed of nerve cell extensions. However, no specific changes in any brain region increased the risk for PH.
Although initial findings indicated changes in brain surface area could be a risk factor for developing OSA, this effect was not confirmed in a further analysis.
Still, changes in the amygdala, which is a brain region involved in processing memory and emotional responses, were associated with a lower risk of developing sleep disorders by 0.4%, and OSA by 0.3%.
“This study identifies significant causal links between PH, sleep disorders, and structural brain changes, establishing a triangular cyclic relationship that supports the lung-brain axis concept,” the researchers wrote. The lung-brain axis refers to the connections between neurological and respiratory functions.
The scientists also noted the potential relationships were obtained using a computational model, so applying “these results to clinical practice, extensive trials and observational clinical studies [is] necessary to ensure a robust and conclusive framework.”
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