Reduced blood oxygen levels, largely attributed to airway obstruction, emerge as a major factor
Summary Rationale : Obstructive sleep apnea (OSA) is characterized by frequent reductions in ventilation, leading to oxygen desaturations and/or awakenings. Objectives : In this study, the association of hypoxic load with incident cardiovascular disease (CVD) was examined and compared with that of “ventilatory load” and “excitation load.” Finally, we evaluated the extent to which ventilatory load, visceral obesity, and pulmonary function explain variations in hypoxic load. Methods : Hypoxic, ventilatory, and arousal loads were measured from baseline polysomnograms in the Multi-Ethnic Study of Atherosclerosis (MESA) and Osteoporotic Fractures in Men (MrOS) studies. Ventilatory load was defined as the event-specific area under the ventilation signal (normalized mean, area below mean), and awakening load was defined as the normalized cumulative duration of all awakenings. Adjusted hazard ratios (aHRs) for incident CVD and mortality were calculated. Exploratory analyzes quantified the contributions of ventilatory load, baseline SpO2, visceral obesity, and spirometry parameters to hypoxic load. Measurements and main results : Hypoxic and ventilatory loads were significantly associated with incident CVD (aHR per 1SD increase in hypoxic load: MESA, 1.45 [1.14, 1.84]; MrOS, 1.13 [1 .02, 1.26]; ventilatory load: MESA, 1.38 [1.11, 1.72]; MrOS, 1.12 [1.01, 1.25]), while the excitation load did not. Similar associations with mortality were also observed. Finally, 78% of the variation in hypoxic load was explained by ventilatory load, while other factors only explained <2% of the variation. Conclusion : Hypoxic and ventilatory burden predicted CVD morbidity and mortality in two population-based studies. Hypoxic load is minimally affected by measures of adiposity and captures the risk attributable to the ventilatory load of OSA rather than the tendency toward desaturation. |
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Researchers have found that people with obstructive sleep apnea have an increased cardiovascular risk due to reduced blood oxygen levels, which is largely explained by interrupted breathing. Obstructive sleep apnea has long been associated with an increased risk of cardiovascular problems, including heart attacks, strokes and death, but the findings of this study, partially supported by the National Institutes of Health and published in the American Journal of Respiratory and Critical Care Medicine , shows the mechanism primarily responsible for the link.
"These findings will help better characterize high-risk clinical forms of obstructive sleep apnea," said Ali Azarbarzin, Ph.D., study author and director of the Sleep Apnea Health Outcomes Research Group at the Brigham and Women’s Hospital and Harvard Medical School, Boston. “We believe that including a higher-risk version of obstructive sleep apnea in a randomized clinical trial would demonstrate that treating sleep apnea could help prevent future cardiovascular outcomes.”
Researchers reviewed data from more than 4,500 middle-aged and older adults participating in the Men’s Osteoporotic Fracture Study (MrOS) and the Multi-Ethnic Study of Atherosclerosis (MESA), and sought to identify characteristics of obstructive sleep apnea. which could explain why some people were more likely than others to develop cardiovascular disease or related death.
Physiological features of obstructive sleep apnea evaluated included hypoxic loading , which is a reduction in blood oxygen levels during sleep; ventilatory load , which are interruptions in breathing due to airway obstruction; and nighttime awakenings , which are when a person wakes up suddenly due to interrupted breathing and which can cause their blood pressure or heart rate to increase.
While the severity of sleep apnea is defined by how many times the airway is blocked during an hour of sleep, this study sought to better characterize the underlying mechanisms of obstructive sleep apnea and identify those that strongly predict increased cardiovascular risk.
Through MrOS, 2,627 men, with an average age of 76, were followed for about nine to 12 years. MESA included data from 1,973 men and women, with an average age of 67, who were followed for about seven years. During this time, participants completed health screenings and sleep assessments and shared information about their health. Approximately 110 participants in MESA and 382 in MrOS experienced a primary cardiovascular event.
For every measure of observed reduction in blood oxygen levels, or hypoxic load , a person in MESA had a 45% increased associated risk of having a primary cardiovascular event. In MrOS, the observed increased risk was 13%.
Airway obstruction, measured by complete or partial closure of the airway, accounted for 38% of the risks observed in MESA and 12% in MrOS.
Similar results were also observed for predicting premature death based on hypoxic and ventilatory burden .
Sudden awakenings were not associated with cardiovascular outcomes in MESA, but were linked to cardiovascular disease-related deaths in MrOS.
Furthermore, the researchers found that a high hypoxic burden was mainly due to severe airway obstruction and not to other factors, such as abdominal obesity or reduced lung function.
“That’s something that makes this metric specific to sleep apnea,” said Gonzalo Labarca, MD, an author of the study and an instructor of medicine at Brigham and Women’s Hospital and Harvard Medical School. “The connections are less explained by obesity or another factor.”
The authors noted that the findings have the potential to change the way sleep apnea is evaluated, but need to be validated through future studies.
"Understanding these mechanisms could change how sleep apnea clinical trials are designed and what is measured in clinical practice," said Marishka K. Brown, Ph.D., director of the National Center for Disorders Research. of Sleep at the National Heart, Lung Center. and the Blood Institute (NHLBI), part of the NIH.
Previous studies have estimated that nearly up to 425 million adults worldwide and about 54 million in the United States have obstructive sleep apnea and are therefore at increased risk of cardiovascular disease, the leading cause of death in the United States. world.
This study was supported in part by NHLBI and the National Center for Advancing Translational Sciences, the National Institute on Aging, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Reference : Labarca G, Vena D, Hu W, et al. Sleep apnea physiological burdens and cardiovascular morbidity and mortality. Am J Respir Crit Care Med. 2023; doi: 10.1164/rccm.202209-1808O
