Effect of CPAP on the Incidence of Hypertension and CV Events in Nonsleepy Patients With Sleep Apnea
Editor’s Note: This review is based on Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, et al. Effect of CPAP on the Incidence of HTN and CV Events in Nonsleepy Patients with OSA, an RCT. JAMA 2012;307:2161-8.
The link between obstructive sleep apnea (OSA) and systemic hypertension (HTN), two exceedingly common conditions that often co-exist, remains a point of emphasis in the care of medical patients. Early cross-sectional reports were limited by study design and potential confounding effects of comorbid variables, particularly obesity. Subsequent population-based studies, such as the Sleep Heart Health Study, demonstrated an association between OSA and HTN, but these prevalence data lacked longitudinal observation to implicate causality. This gap was partially filled by the Wisconsin Sleep Cohort, the first to provide persuasive evidence implicating OSA as a possible causal factor in hypertension. Specifically, the presence of hypertension four years after initial assessment was found to be dependent upon the severity of OSA at baseline. Post-hoc analysis excluding those with HTN or taking anti-hypertensives at baseline resulted in similar associations between OSA severity, based upon the apnea-hypopnea index (AHI) and hypertension at four year follow-up. Collectively, the data are compelling to implicate OSA in both acute increases in sleep-related blood pressure (BP) but also in sustained daytime hypertension as well.
CPAP treatment has been shown to acutely attenuate sympathetic drive and nocturnal BP in patients with OSA. Data regarding effects on daytime BP haven’t been as definitive. Systematic review of randomized, placebo-controlled studies have yielded variable results between studies, though pooled data suggests some blood pressure lowering effects of CPAP therapy.
An emerging point of interest is the potential role that sleep apnea-related symptoms, namely excessive daytime sleepiness (EDS), may have in mediating the BP-lowering response to CPAP. Importantly, although EDS is the most important symptom attributed to sleep apnea, it is not universally reported. A tool commonly used in the clinic setting to assess EDS is the Epworth scale. While probably not as specific as objective nap testing but far easier to use, the Epworth is a validated questionnaire where patients rate their chance of dozing in real-life situations. A score of 11 or more indicates EDS, while 10 or less is considered to represent the absence of sleepiness.
Two small, short-term randomized trials showed that in OSA patients without EDS, CPAP therapy had no impact on daytime BP measurements. One paper studied mostly normotensive patients; the other was comprised of hypertensive patients. Why sleepiness would modify the cardiovascular response to CPAP isn’t known. Intermediary pathways are yet to be identified. Conceivably, the mechanism may relate in part to compliance with therapy, since less symptomatic patients may wear CPAP less, resulting in a lower “dose” of therapy than more symptomatic patients.
The current paper by Barbe et al., describes a multicenter randomized trial of CPAP therapy in non-sleepy OSA patients (ESS 10 or less), where the primary outcome was a composite endpoint of incident hypertension or a myriad of cardiovascular events typical of large CV trials. At baseline, patients had moderate to severe OSA, with an AHI of at least 20. Randomization was to CPAP or no active intervention (beyond dietary counseling and sleep hygiene advice).
Seven-hundred-twenty-three patients were randomized and followed for a median of four years. The primary outcome incidence density was not significantly different between the groups (9.2/100 person-years in the CPAP group vs. 11.02/100 person years in the control group). Disease severity (the AHI and the duration with saturations < 90%) did not appear to affect the primary outcome. However, post-hoc analysis suggested that a) the incidence of the primary outcome was less in those who used CPAP > four hours per night and b) those with worse oxygenation and less CPAP usage may have had higher events.
The study raises important questions, some of which remain unanswered. First, we need to acknowledge the possibility that the trial was underpowered to detect a true difference. The authors utilized an expected event rate derived from a large observational (non-randomized) study of CV outcomes in patients with OSA, some of whom did not use CPAP. In that study, the event rate with CPAP treatment was nearly four times lower than the event rate encountered in the current study. Other methodological limitations include BP measurement, in this case spot checks in a clinic, which is vulnerable to bias.
Notwithstanding methodological shortcomings, the issue of whether OSA patients without symptoms, particularly EDS, should or should not be treated continues to be raised. Based on this and other studies, one might conclude that there appears to be little rationale to recommend CPAP therapy for OSA patients without evidence of sleep-related symptoms, particularly EDS, for the primary purpose of reducing the risk of CV events. However, until larger trials more definitively address the question, clinical judgment will continue to guide practice.
- Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, et al. Effect of CPAP on the Incidence of HTN and CV Events in Nonsleepy Patients with OSA, an RCT. JAMA 2012;307:2161-8.
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