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Failing Doctors, Failing Hearts
Abstract & Commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a consultant for Cephalon, and serves on the speakers bureaus for Resmed and Respironics.
Synopsis: Obstructive sleep apnea is associated with an increased risk of incident heart failure in community-dwelling middle-aged and older men, but not in women.
Source: Gottlieb DJ, et al. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure. The Sleep Heart Health Study. Circulation 2010 July 12; Epub ahead of print.
This report is from the well-established Sleep Heart Health Study (SHHS), now in its 15th year. For this report, the authors analyzed about 8.5 years of data from 4422 of the original cohort. All the participants included in this report had acceptable in-home polysomnograms (sleep studies) and were free of coronary heart disease or heart failure at baseline. As is true of most of the SHHS analyses, the apnea plus hypopnea indices (AHIs) were calculated based largely on oximetry (the criteria to score both apneas and hypopneas required at least a 4% fall in oxygen saturation). Coronary heart disease (CHD) was defined as the first occurrence of myocardial infarction, CHD death, or coronary revascularization procedure over the period of follow-up. Incident heart failure was simply defined as the first documentation of heart failure during this time. Because the people included in this report were part of a study designed to assess occurrence, risk, and outcomes of cardiac disease, the events reported are probably reasonably precise. The investigators also had extensive information about medications, lifestyle, and medical illness.
The median AHI was 2.7 in women and 6.2 in men. Not surprisingly, increasing severity of obstructive sleep apnea (OSA) was associated with male sex, higher BMI, higher systolic blood pressure, lower HDL cholesterol, and higher prevalence of hypertension and diabetes. Although 24% of men and 11% of women had OSA that most clinicians would choose to treat (AHI of at least 15) on the baseline research polysomnogram, only about 19% of those with an AHI of 15 or higher had a physician diagnosis of OSA when asked about this 5 years after the research polysomnogram. Only 79 survey respondents (2.1%) reported any kind of treatment for OSA.
With regard to heart failure, there was a strong association of AHI with incident heart failure in men but not in women, even after adjusting for age, race, smoking, and BMI. Further adjustment for many relevant covariates did not affect this finding much. The higher the AHI, the greater the risk of incident heart failure; each 10-unit increase in AHI corresponded to an increased hazard ratio for heart failure of 1.13 for men.
On the other hand, the association of AHI with CHD was not strong, and was not statistically significant after adjustment for confounders, although it was significant for men younger than 70 who had an AHI of 15 or higher.
There are several relevant points about this study. The first is that the risk of heart disease associated with OSA found in this analysis is weaker than that reported in several previous clinic-based studies, and may be negligible for women. Does that mean that we should stop telling patients that untreated sleep apnea is a risk factor for heart disease? I don't think so. Remember, this study comes from a population-based cohort; many of these individuals were presumably asymptomatic. There is some evidence that the association of sleep disordered breathing with hypertension and other cardiovascular disease is stronger in individuals who report daytime sleepiness (the cardinal symptom of OSA) than in those who do not.1 Patients who present with symptoms and have OSA on their sleep study are likely to be different (and at higher risk) than those who are asymptomatic and found incidentally on a population-based study. Randomized trials of CPAP efficacy might help to resolve this dilemma, but withholding CPAP therapy from sleepy patients with OSA over a long period of time is unethical because of the risk of driving accidents and the effectiveness of CPAP in relieving sleepiness. So, we are left with long-term observational trials of clinical populations. While patients who do not use CPAP are a poor control group, since they are also likely to be non-adherent in general, long-term observational studies comparing patients on CPAP therapy with untreated patients have consistently shown significantly increased cardiovascular mortality and morbidity in the untreated group.2 And we do have randomized controlled studies of CPAP on blood pressure, demonstrating modest but significant reductions in blood pressure, even in nonsleepy people.3 What I really wish these authors had done was to match the (very few) patients who were diagnosed with sleep apnea and who used CPAP with other members of the cohort with similar demographics and severity of illness to see if they fared better.
Another consideration is that the mean age of this cohort was 62; several studies have demonstrated that untreated OSA is more deadly in younger than in older people.4 It's possible that this older cohort, perhaps because of survivor bias, had already outlived the worst that OSA could do.
One question that arises from this paper is whether it's "worth it" to treat OSA in women. This particular study, which focused on CHD and heart failure, did not find convincing evidence that untreated OSA is a risk for these conditions in women, and the risk was not strong for people older than age 70. On the other hand, CHD and heart failure are not the only adverse outcomes of OSA to consider. OSA also increases the risk of car crash5 and hypertension, gender and age notwithstanding.
The finding of this study that surprised me most was the fact that only about 2% of these patients were treated for sleep apnea, although 24% of men and 11% of women met the diagnostic criteria (AHI of at least 15) at baseline. It's not clear where the ball is being dropped, but certainly some large part of this failure is lack of action on the part of physicians. This study adds convincing evidence that untreated OSA increases the risk of heart failure, a chronic and miserable condition, in middle-aged men. In this cohort, most of these prime candidates for CPAP treatment went untreated. We need to start taking sleep apnea to heart.
1. Kapur VK, et al; Sleep Heart Health Study Group. Sleep disordered breathing and hypertension: Does self-reported sleepiness modify the association? Sleep 2008;31:1127-1132.
2. Ryan S, et al. Systemic inflammation: A key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome? Thorax 2009;64:631-636.
3. Barbe F, et al; the Spanish Sleep and Breathing Group. Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea. Am J Respir Crit Care Med 2010;181:718-726.
4. Lavie P. Mortality in sleep apnoea syndrome: A review of the evidence. Eur Respir Rev 2007;16:203-210.
5. Tregear S, et al. Obstructive sleep apnea and risk of motor vehicle crash: Systematic review and meta-analysis. J Clin Sleep Med 2009;5:573-581.