Treating Sleep-Disordered Breathing in Hypertensive Patients Yields Real Impacts on Patient-Reported Outcomes

By Harneet K. Walia, MD

Sleep-disordered breathing (SDB) is highly prevalent in neurological populations and is often accompanied by worsening of a variety of patient-reported outcomes (PROs), including excessive daytime sleepiness, depressive symptoms and fatigue. These symptoms have been observed to demonstrate striking yet complex interrelationships in SDB and hypertension — observations that loom large in light of the high prevalence (estimated from 50 to 85 percent1,2) of SDB in patients with hypertension and resistant hypertension.

These symptoms also contribute significantly to SDB’s considerable impact on quality of life, which is a key emphasis of recent quality measures developed by the American Academy of Sleep Medicine (AASM) to guide management of obstructive sleep apnea.3 And since individuals with hypertension appear to have lower quality of life than those without hypertension,4 coexisting hypertension is germane to quality-of-life considerations as well.

Given the strong association between SDB and hypertension, particularly resistant hypertension, there is a need for greater understanding of PROs in individuals suffering from both conditions. Moreover, patients with and without concomitant hypertension could demonstrate varying subjective changes in response to SDB treatment, the first line of which is usually pressure stenting with continuous positive airway pressure (PAP).

Novel study of PROs after SDB therapy in the setting of hypertension

To explore these issues, Cleveland Clinic researchers retrospectively examined PROs collected from patients with both SDB and hypertension. We postulated that treatment of SDB with PAP would be associated with improvement in PRO measures ranging from sleepiness to depressive symptoms to fatigue, and we aimed to determine any effect modifiers of these relationships.

Electronic medical record (EMR) data were extracted for all adults with outpatient visits in Cleveland Clinic’s Sleep Disorders Center from February 2008 to July 2013 who had a confirmed hypertension diagnosis and self-reported use of PAP therapy.

Our study leveraged the Knowledge Program©, a system pioneered by Cleveland Clinic’s Neurological Institute to electronically collect disease-based PROs in the patient’s EMR at the point of care to make the measures immediately available to providers to inform clinical care. PROs collected in the Sleep Disorders Center include:

• Epworth Sleepiness Scale (ESS) score
• Patient Health Questionnaire-9 (PHQ-9) score for depression
• Fatigue Severity Scale (FSS) score
• Self-reported number of days per week and hours per night of PAP use

Of the 1,000 patients with hypertension and SDB reporting use of PAP who had pre- and post-PAP PRO data, 894 (89 percent) had complete visit data over the course of the study. Among these patients, 130 (15 percent) had resistant hypertension. Compared with patients with nonresistant hypertension, those with resistant hypertension were significantly older, had a higher mean body mass index (BMI), and were significantly more likely to have diabetes and cardiac disease.

Key findings: PRO improvements across the board

Notably, there was no difference in PRO outcomes between the resistant and nonresistant hypertension groups.

In models fully adjusted for age, sex, race, BMI, median income by zip code, and cardiac and diabetes history, statistically significant improvements (P < .001) were observed during the year following PAP therapy initiation in each of the following:

• ESS score (–2.09; 95% CI, –2.37 to –1.82)
• PHQ-9 score (–1.91; 95% CI, –2.25 to –1.56)
• FSS score (–4.06; 95% CI, –4.89 to –3.22)

These improvements were observed in the sample overall and were not dependent on resistant hypertension status.

Notable subanalysis findings

Various subanalyses revealed notable additional findings, including the following:

• Among the 147 patients objectively determined to be adherent to PAP therapy, improvements in all PRO measures (ESS, PHQ-9 and FSS) were more pronounced than in the overall sample.
• Greater improvements in all PROs were observed after PAP therapy in Caucasians compared with African Americans and other races.
• Younger patients had worse scores than older patients on all three PROs at baseline (P < .01), but the statistical interaction of the effect of PAP therapy and age relative to PROs was statistically significant for ESS (P = .04) and PHQ-9 (P = .0003) scores, demonstrating greater improvement in younger versus older patients.

Potential implications call for prospective study

This observational study, recently published in the Journal of Clinical Sleep Medicine,5 provides novel longitudinal documentation of improvement in daytime sleepiness, depressive symptoms and fatigue in patients with SDB and hypertension treated with PAP in a real-world setting. We are aware of no prior study evaluating changes in sleep-related functional outcomes of PAP therapy in a strictly hypertensive cohort containing a sizable sample of patients with resistant hypertension.

As expected, the reported effects were somewhat more robust in patients with the best PAP adherence, and both this and the overall findings provide support for untreated SDB as a potential etiology for the reduced quality of life reported in hypertensive patients.4

While this work has implications for population health and aligns with the AASM’s call for tracking outcomes in SDB care paths,3 these findings should be built upon in prospective randomized studies of PROs in response to PAP in patients with SDB and hypertension — ideally with a comparative group of normotensive patients. Future studies should aim to confirm our findings of similar PRO response in resistant and nonresistant hypertension as well as enhanced response in Caucasians and younger patients, with an eye toward informing SDB treatment guidelines.

References

1. Torres G, Sanchez-de-la-Torre M, Barbe F. Relationship between OSA and hypertension. Chest. 2015;148:824-832.
2. Pedrosa RP, Drager LF, Gonzaga CC, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58:811-817.
3. Aurora RN, Collop NA, Jacobowitz O, et al. Quality measures for the care of adult patients with obstructive sleep apnea. J Clin Sleep Med. 2015;11:357-383.
4. Trevisol DJ, Moreira LB, Kerkhoff A, et al. Health-related quality of life and hypertension: a systematic review and meta-analysis of observational studies. J Hypertens. 2011;29:179-188.
5. Walia HK, Griffith SD, Thompson NR, et al. Impact of sleep-disordered breathing treatment on patient reported outcomes in a clinic-based cohort of hypertensive patients. J Clin Sleep Med. 2016;12:1357-1364.

Dr. Walia is a staff physician in Cleveland Clinic’s Sleep Disorders Center and Assistant Professor of Family Medicine in Cleveland Clinic Lerner College of Medicine.