CWRU receives NHLBI grant to study sleep apnea as possible cause of AF

Case Western Reserve UniversityNov 22 2011

NHLBI funding supports Case Western Reserve research on sleep disorders cause of irregular heart rhythms

Case Western Reserve University School of Medicine has received a $3.8 million grant from the National Heart, Lung, and Blood Institute (NHLBI) to study sleep apnea as a possible cause of atrial fibrillation (AF), the most commonly diagnosed type of arrhythmia, or irregular heart rhythm.

AF is characterized by an abnormally rapid heart rate that can inhibit blood flow, and raise the risk of stroke and heart failure. The five-year, NHLBI grant will enable researchers to study how sleep apnea, a treatable disorder in which breathing repeatedly stops and starts during sleep, produces functional and structural changes in the heart that may well contribute to the development of AF.

"The new research will characterize what aspects of sleep apnea lead to AF, honing in on the effects of sleep apnea-induced changes to the structure of the heart, including increases in blood pressure and reductions in oxygen levels," says the study's principal investigator, Reena Mehra MD, MS, associate professor of medicine in the Department of Medicine at Case Western Reserve University School of Medicine and a pulmonary, critical care and sleep medicine physician at University Hospitals Case Medical Center. "The data generated from the research will fuel the development of new approaches for prevention and treatment of AF, and, will help identify key factors for future clinical trials," she says.

More fully identifying AF risk factors and developing new treatments is instrumental to stemming the growing rate of AF, a condition that could afflict up to 16 million individuals by the year 2050, according to research projections.

The growing prevalence of AF is not fully explained by known risk factors, such as age, existing heart disease and family history, highlighting the need to more precisely identifying potential novel AF triggers, Dr. Mehra explains.

Because sleep disorders like sleep apnea are common among patients with heart disease, Dr. Mehra and her team believe that the repetitive episodes of breathing pauses during sleep may provide a potential basis for much of the unexplained risk factors underlying AF.

In prior research, she and her colleagues established a strong association between sleep apnea and AF, basing their findings on thousands of participants in large scale epidemiologic cohorts. The data, however, did not include information characterizing changes in heart structure, nor did it include temporally collected, detailed biochemical measures collected from blood and urine, which can indicate how inflammation and oxidative stress caused by sleep apnea may lead to AF.

The newly funded research aims to gather more specific data, obtained by examining images of the heart that detail its pumping function and the condition of its walls.

Sleep apnea results in intermittent lowering of oxygen levels, alteration of nervous system function and changes the pressures within the chest, resulting in immediate, direct changes in the heart. Some or all of these factors may increase AF propensity, Dr. Mehra explains. Sleep apnea may also result in longer-term changes in cardiac structure which can also increase AF risk, prior research has shown.

The basis of the new research will be a case control study of 150 individuals with paroxysmal AF (PAF), an occasional, irregular heart rhythm and early-stage risk factor for persistent AF, which occurs before changes in the heart's condition and function are present and also involves 150 individuals serving as matched controls. A subset of those with PAF who are identified to have sleep apnea will also undergo treatment for their sleep apnea.

In addition, the researchers seek to clarify the extent by which the frequency of stopped breathing, the type of sleep apnea and reduced oxygen supply are associated with PAF, independent of any structural abnormalities in the heart. Throughout their study, researchers will assess how changes in cardiac structure, inflammation, or autonomic nervous system dysfunction are involved in the relationship between sleep apnea and PAF, identifying if patterns of AF differ in patients with sleep apnea.

The research findings could identify key outcomes for clinical trials and ultimately bolster evidence for considering sleep apnea as a potential target for new strategies to reduce AF-related morbidity including stroke, heart failure and also death.