Sleep-related hypoxemia is a better indicator of atrial fibrillation (AF) risk than the commonly-used apnea-hypopnea index (AHI), new research suggests.
"Our findings suggest the importance of looking more at hypoxia when doing a sleep study and trying to stratify cardiovascular risk," co-investigator Catherine Heinzinger, DO, of the Cleveland Clinic, Ohio, told Medscape Medical News.
"There have been multiple studies showing that higher AHI, indicating more severe sleep apnea, is associated with atrial fibrillation. But pathologically, it makes a lot more sense that it would be the hypoxia or the gas exchange issues that are a result of sleep apnea that would be affecting the cardiovascular system," Heinzinger said.
The findings were presented at SLEEP 2022, the 36th annual meeting of the Associated Professional Sleep Societies.
Salient Driver?
Leveraging data from sleep studies conducted at the Cleveland Clinic, the researchers tested the hypothesis that sleep-disordered breathing and, in particular, sleep-related hypoxemia are associated with the development of AF after accounting for confounding factors.
Among 42,057 patients without AF at baseline,1947 (4.6%) developed AF over the next 5 years.
In a multivariate model, for each 10-unit increase in percent sleep time with oxygen saturation less than 90% (T90), incident AF increased by 6% (hazard ratio [HR], 1.06; 95% CI, 1.04-1.08).
Patients with the highest T90 (11.6%) had 28% greater risk for incident AF compared with reference patients with T90 of less than 0.1% (HR, 1.28; 95% CI, 1.11-1.47).
For every 10-unit decrease in minimum oxygen saturation (SaO2), the risk for AF increased by 9% (HR, 1.09; 95% CI, 1.03-1.15); and for every 10 unit decrease in mean SaO2, the risk for AF increased by 30% (HR, 1.3; 95% CI, 1.18-1.42).
In contrast, for each 10-unit increase in AHI, the risk for AF increased by only 2% (HR, 1.02; 95% CI, 1.00-1.03).
The fact the results were similar across all three hypoxemia measures, T90 and minimum and mean SaO2, shows "great internal consistency," Heinzinger said.
Though AHI also showed a positive relationship with AF, the magnitude of that association was significantly smaller than the magnitude of the association between the hypoxia measures and AF, she noted.
The findings suggest that sleep-related hypoxemia is the "salient driver" in the development of AF, said Heinzinger.
"We think that the mechanisms behind hypoxemia and atrial fibrillation are related to autonomic dysfunction; that is, surges of sympathetic activity and oxidative stress on tissues at the cellular level that cause changes in the cardiac substrate, like fibrosis, that then leads to arrhythmia, especially atrial fibrillation," she added.
'Compelling' Observation
Commenting on the findings for Medscape Medical News, Gregory M. Marcus, MD, University of California, San Francisco, noted that though obstructive sleep apnea is now a "well-established risk factor for the development of atrial fibrillation, we still do not understand how or why this occurs."
The finding in this new study that more severe hypoxemia contributes to risk for AF is "especially compelling" given that the AHI in the same cohort showed a far less significant relationship with future AF, said Marcus, who was not involved with the research.
However, he noted that because this was an observational study, "we need to be cautious before inferring causal relationships."
For example, there is now evidence that sleep disruption itself (such as with insomnia), even independent of obstructive sleep apnea, can predict the development of AF, Marcus said.
"Therefore, while this study provides valuable new insights warranting future assessments, it's possible the hypoxemia is simply a marker or epiphenomenon of some other causal process," he added.
The study was funded by the Cleveland Clinic Neurological Institute Center for Outcomes Research & Education Pilot Grant and the Neuroscience Transformative Research Resource Development Award. Heinzinger and Marcus have reported no relevant financial relationships.
SLEEP 2022: the 36th Annual Meeting of the Associated Professional Sleep Societies. Abstract 0745. To be presented June 8, 2022.
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