Patients with moderate to severe sleep apnea who have significantly higher serum levels of inflammatory markers that serve as precursors to coronary artery disease, as well as lesions associated with silent brain infarction, have an elevated risk of stroke, according to a group of Japanese medical researchers.
The results appear in the second issue for March 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
Kenji Minoguchi, M.D., Ph.D., of Showa University School of Medicine in Tokyo, and nine associates studied silent brain infarction, brain tissue death from lack of blood supply, in 50 male patients with obstructive sleep apnea (OSA). The researchers also examined the effects of three months of treatment with nasal continuous positive airway pressure (nCPAP) on serum inflammatory marker levels in 24 male patients who had moderate to severe OSA.
According to the authors, the occurrence of stroke in patients with OSA is likely preceded by subclinical cerebrovascular disease, or silent brain infarction, which is detectable with brain magnetic resonance imaging (MRI). The lesions identified as silent brain infarction were either wedge-shaped or round and showed up in brain white matter on MRI scans.
"The percentage of silent brain infarction in patients with moderate to severe OSA at 25 percent was higher than that for obese control subjects at 6.7 percent, or even patients with mild OSA who had 7.7 percent," said Dr. Minoguchi.
The investigators noted that cardiovascular disease is commonly characterized by ongoing inflammatory responses that can enhance platelet activation and increase the prevalence of silent brain infarction.
Platelets are small, colorless, irregular blood cells that promote blood clotting. Two important proteins called soluble C40 ligand and soluble P-selectin are markers of platelet activation and appear to forecast future cerebrovascular events.
The researchers found that use of nCPAP, a treatment designed to reduce the number of episodes of breathing stoppage associated with sleep apnea, significantly lowered serum levels of C-reactive protein and the levels of the two platelet-activating proteins, all associated with cerebrovascular disease.
"As a result, nCPAP may be an important treatment intervention for decreasing the cerebrovascular risk in this susceptible population of obstructive sleep apnea patients," said Dr. Minoguchi.
In an editorial on this research in the same issue of the journal, Brian J. Murray, M.D., of Sunnybrook Health Sciences Center and the University of Toronto, Canada, wrote:
"The article by Drs. Minoguchi and colleagues provides further important observations on the association between stroke and obstructive sleep apnea, with significant public health implications. The authors, using brain magnetic resonance imaging, demonstrate that patients with obstructive sleep apnea have a higher incidence of so-called silent brain infarction (i.e., those devoid of obvious clinical symptoms leading to self-detection or identification by physician examination). The well-designed and executed study excluded patients with known risk-factor co-morbidities, thereby establishing the relationship between brain infarcts and obstructive sleep apnea itself. The significance of this finding pertains not only to stroke pathophysiology, but to dementia as well."