By Barbara A. Phillips, MD, MSPH

Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington

Dr. Phillips serves on the speakers bureau for PotomaCME.

SYNOPSIS: Obstructive sleep apnea is associated with coronary artery calcification in non-obese individuals, but the effect is largely attenuated by body mass index.

SOURCE: Luyster FS, et al. Relation of obstructive sleep apnea to coronary artery calcium in non-obese versus obese men and women aged 45-75 years. Am J Cardiol 2014;114:1690-1694.

This report results from a secondary analysis of the Pittsburgh-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. For this analysis, the investigators used the baseline data on a subset (n = 252) of participants who had computed tomography and home sleep testing within 24 months of each other and whose weight was fairly constant. The final group was largely white (56%), male (61%), and the mean age was 61 years. Most of these participants (76%) had significant coronary artery calcification (CAC) and 37% had sleep apnea, as it was defined in this study. The main finding of the study was that the odds ratio for the presence of CAC was 2.33 (1.01-5.38) for participants with sleep apnea, compared to those without (P < 0.05) after adjustment for age, gender, race and ethnicity, smoking status, diabetes, hypertension, and dyslipidemia. However, after adjustment for body mass index (BMI), the relationship was no longer statistically significant. Furthermore, there was no association between severity of sleep-disordered breathing and CAC in those whose BMIs were over 30 kg/m2.

COMMENTARY

This study adds to the growing body of evidence that suggests a link between obstructive sleep apnea and coronary artery disease (CAD). However, based on these data alone, one might conclude that the relationship is mediated by obesity, which is common to both conditions. I suspect that this lackluster finding is largely due to the definition of sleep apnea that was used here, which was based on flow signals from portable studies. Measures of apnea and hypopnea (used to calculate the apnea plus hypopnea index [AHI]) that are based on measures of flow alone are not particularly reproducible, predictive, or reliable; interscorer reliability and predictive value are greatly improved by the use of some measure of oxygen desaturation (either 3% or 4%) to define respiratory events.1-3 Indeed, relationships between AHI and CAC have been demonstrated to be quite robust when based on definitions of sleep apnea in which the criteria for apnea and/or hypopnea include some measure of oxygen desaturation.4,5 Data are accumulating that the degree and duration of oxygen desaturation appear to be the primary predictors of most adverse outcomes, including even cancer, in patients with sleep-disordered breathing.6 We simply don’t have that data in the current study.

More compelling evidence that sleep apnea is associated with CAD comes from studies in which sleep apnea had been treated and markers or predictors of CAD are improved. One such trial was a randomized trial on the effects of 4 months of continuous positive airway pressure therapy on early markers of atherosclerosis, which demonstrated decreases in intima-media thickness, C-reactive protein, and catecholamines, strongly suggesting that sleep apnea is an independent risk factor for atherosclerosis.7

In conclusion, it appears that sleep apnea is a risk factor for CAD, but the effect is confounded by obesity and likely related to oxygen desaturation.

REFERENCES

1. Lin CL, et al. Comparison of the indices of oxyhemoglobin saturation by pulse oximetry in obstructive sleep apnea hypopnea syndrome. Chest 2009;135:86-93.

2. Redline S, et al. The scoring of respiratory events in sleep: Reliability and validity. J Clin Sleep Med 2007;3:169-200.

3. Whitney CW1, et al. Reliability of scoring respiratory disturbance indices and sleep staging. Sleep 1998;21:749-757.

4. Arik B, et al. Advanced age and apnea-hypopnea index predict subclinical atherosclerosis in patients with obstructive sleep apnea syndrome. Multidiscip Respir Med 2013;8:9.

5. Jung HH, et al. Sleep apnea, coronary artery disease, and antioxidant status in hemodialysis patients. Am J Kidney Dis 2005;45:875-882.

6. Campos-Rodriguez F1, et al; Spanish Sleep Network. Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort. Am J Respir Crit Care Med 2013;187:99-105.

7. Drager LF, et al. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 2007;176:706-712.