Obstructive sleep apnea (OSA) may increase the risks of death, heart disease, stroke, and kidney disease, as well as hasten kidney function decline, according to a study of more than 3 million U.S. veterans.
Compared with OSA-negative patients, untreated OSA was associated with an 86% higher mortality risk (adjusted hazard ratio 1.86, 95% CI 1.81 to 1.91), and treated OSA was associated with a 35% higher mortality risk (aHR 1.35, 95% CI 1.21 to 1.51), wrote Miklos Z. Molnar, MD, PhD, of the University of Tennessee Health Science Center in Memphis, and colleagues, in the journal Thorax.
Untreated OSA also was associated with a 3.5 times higher risk of incident coronary heart disease (aHR 3.54, 95% CI 3.40 to 3.69), and a 3.5 times higher risk of incident strokes (aHR 3.48, 95% CI 3.28 to 3.64), while treated OSA was associated with a threefold higher risk of incident CHD (aHR 3.06, 95% CI 2.62 to 3.56) and 3.5-fold higher risk of incident strokes (aHR 3.50, 95% CI 2.92 to 4.19). The risk of incident kidney disease also was significantly higher in untreated (aHR 2.27, 95% CI 2.19 to 2.36) and treated OSA (aHR 2.79, 95% CI 2.48 to 3.13). The median (IQR) of the estimated glomerular filtration rate (eGFR) slope was -0.41 (-2.01 to 0.99) mL/min/1.73 m2 in OSA-negative patients, -0.61 (-2.69 to 0.93) mL/min/1.73 m2 in untreated OSA positive patients, and -0.87 (-3.00 to 0.70) mL/min/1.73 m2 in treated OSA-positive patients.
"To our knowledge, this is the largest study to find substantial associations between a diagnosis of incident OSA and kidney function decline and incident decrease in eGFR," Molnar and colleagues wrote.
The researchers obtained data from the Racial and Cardiovascular Risk Anomalies in CKD study, which examines risk factors in patients with incident CKD among U.S. veterans, and identified diagnoses of incident OSA, CPAP, and polysomnography from the VA Inpatient and Outpatient Medical SAS data sets. Patients were included in the study if they had a baseline estimated glomerular filtration rate (eGFR) of greater than or equal to 60 mL/min/1.73 m2 and did not have a diagnosis of OSA at the first encounter of the inclusion period (Oct. 1, 2004 to Sept. 30, 2006). The final cohort comprised 3,079,514 patients. The mean age was 60.5 years at baseline. Ninety-three percent were male, 79% were white, 22% were patients with diabetes, and the mean baseline eGFR was 83.6 mL/min/1.73 m2.
Investigators defined incident OSA as a new ICD9-CM code for OSA during the inclusion period. Among the more than 3 million patients studied, 21,764 had incident diagnosis of OSA but without continuous positive airway pressure (CPAP) treatment, and 1,478 had incident diagnosis of OSA treated with CPAP. Comorbidities were defined as those diagnosed during the inclusion period.
The researchers defined five outcomes: all-cause mortality, incident CHD, incident ischemic stroke, incidence of CKD, and slopes of eGFR. They obtained data on all-cause mortality from the VA Vital Status Files. Incident CHD was defined as the composite outcome of a first occurrence of an ICD-9-CM or CPT code for acute myocardial infarction, coronary artery bypass grafting, or percutaneous angioplasty after Oct. 1, 2006. Incident stroke was defined as the first occurrence of ICD-9-CM or CPT code for ischemia after Oct. 1, 2006. Incident CKD was defined as two consecutive eGFR levels <60 mL/min/1.73 m2 separated by at least 90 days, and a greater than 25% decrease from baseline eGFR. Rapid deterioration of kidney function was defined as eGFR slopes of less than -5 mL/min/1.73 m2 per year.
In the adjusted logistic regression model, younger age, male gender, Caucasian race, unmarried status, higher BMI, and most of the comorbidities were associated with the diagnosis of incident OSA. Patients were followed for a median of 7.74 years or until July 26, 2013.
There were several limitations to the study, including that because it was an observational study, researchers could only report associations and not claim that OSA was the cause of worse clinical outcomes. In addition, models could only be adjusted for identified confounders for which the authors had available data, and the study was limited by the use of diagnostic codes to define OSA, CPAP treatment, and polysomnography.
The proportion of patients who received CPAP treatment was smaller than expected, they said, "which raises the possibility" that patients received CPAP treatment outside the VA health system, refused CPAP treatment, had mild/positional OSA, or received surgical or CPAP treatment after the follow-up period. Also, the study population consisted of mostly male U.S. veterans, and without information on cause of death, the researchers could not analyze associations with cause-specific mortality.
"Improvement of the diagnostics and early detection, as well as the effect of proper therapy for OSA on preventing clinical events [such as incident CHD, stroke and CKD] need to be tested in clinical trials," Molnar and colleagues wrote.
From the American Heart Association:
The work was supported by the National Institutes of Health, the U.S. Department of Veterans Affairs, and the Netherlands Organisation for Scientific Research.
The authors reported they had no conflicts of interest to disclose.
- Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner