SNOWMASS, COLO. — Individuals with obstructive sleep apnea exhibit a striking alteration in the typical day-night pattern of sudden cardiac death, underscoring the sleep disorder's potency as a risk factor for nocturnal cardiovascular events, Dr. Bernard J. Gersh said.
It's well established that the peak hours of sudden cardiac death (SCD) in the general population are 6 a.m. until noon, and that the fewest such deaths happen from midnight to 6 a.m. However, this diurnal pattern is reversed in people with obstructive sleep apnea (OSA), Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn., noted at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.
He cited a study by his colleagues, Dr. Apoor S. Gami and coworkers at the clinic, who reviewed the death certificates and medical records of 112 Minnesotans who underwent polysomnography and later died suddenly from cardiac causes. SCD occurred between midnight and 6 a.m. in 46% of the 78 people with OSA, compared with 21% of those who didn't fulfill criteria for OSA. Persons with OSA had a 2.6-fold greater risk of SCD between midnight and 6 a.m. than in the other 18 hours of the day.
By comparison, a large meta-analysis of studies examining the morning excess of SCD in the general population showed that only 16% of SCDs occurred between midnight and 6 a.m. (Am. J. Cardiol. 1997;79:1512–6). And that 16% figure is surely an overestimate, since it included some individuals with undiagnosed OSA, Dr. Gersh noted at the conference, which was cosponsored by the American College of Cardiology.
In the Minnesota study, severity of OSA correlated directly with the relative risk of SCD occurring from midnight to 6 a.m. Individuals with an apnea-hypopnea index of 40 or more were 40% more likely to experience SCD between midnight and 6 a.m. than were those with mild to moderate OSA as reflected in an apnea-hypopnea index of 5–39 (N. Engl. J. Med. 2005;352:1206–14).
Dr. Gersh observed that OSA is associated with numerous pathophysiologic changes that provide potential mechanisms promoting arrhythmias and SCD during sleep. These include nocturnal hypoxemia, hypercapnia, a tremendous increase in sympathetic nerve activity, hypertensive surges, endothelial dysfunction, vascular oxidative stress, inflammation, hypercoagulability, and markedly elevated left ventricular wall stress.
In contrast, normal individuals experience decreased sympathetic activity during sleep. Their risk not only of SCD but also of onset of acute MI is at a nadir during the 6-hour period beginning at midnight. The peak in the incidence of these events from 6 a.m. until noon is believed to be related to increased coagulability and sympathetic drive.
Dr. Gersh noted that in a separate study by Dr. Gami and coworkers—presented last fall at the American Heart Association annual meeting—they reported that onset of acute MI in individuals with OSA followed the same pattern of increased incidence during the hours of sleep as did SCD. Onset of MI occurred between midnight and 6 a.m. in 32% of individuals known to have OSA and just 5% of those without OSA.