Severe Sleep Apnea Linked to Resistant Hypertension

Fran Lowry

October 02, 2014

Severe obstructive sleep apnea may interfere with blood pressure (BP)–lowering treatment in patients at high cardiovascular disease risk or with established cardiovascular disease, results of a multicenter clinical trial suggest.

Doctors should consider that severe obstructive sleep apnea (OSA) may be the reason why they cannot get their hypertensive patients to respond to optimal antihypertensive treatment, lead author, Harneet Walia, MD, from the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, told Medscape Medical News.

"We found an association between severe untreated obstructive sleep apnea and resistant elevated BP, despite the use of antihypertensive medications in patients who have cardiovascular risk or cardiovascular disease," Dr Walia said.

"If someone has high BP and it is resistant to antihypertensive medication, this should be one of the warning signs telling the physician to screen that patient for severe obstructive sleep apnea," she said.

Dr. Harneet Walia

Their findings were published in the September issue of the Journal of Clinical Sleep Medicine.

HeartBEAT Trial

Dr Walia and her team analyzed data from the baseline examination of the patients participating in the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) multicenter randomized controlled trial.

The goal of the HeartBEAT trial is to compare conservative medical therapy, supplemental nocturnal oxygen therapy, and positive airway pressure therapy on cardiovascular biomarkers in OSA. Participating sites are Brigham and Women's Hospital, Case Medical Center, Johns Hopkins Medical Center, and Veterans Affairs Boston Healthcare System.

Their analysis included 284 HeartBEAT participants (mean age, 63 years [range, 56 - 70 years]).

Of these patients, 23.6% had severe OSA, as defined by a score on the apnea hypopnea index (AHI) of 30 or greater; 61.6% (175 patients) had controlled BP, 28.5% (81 patients) had uncontrolled elevated BP (≥130/80 mm Hg), and 9.9% (28 patients) had resistant elevated BP. Blood pressure values were obtained from ambulatory BP monitoring.

Among patients receiving an intensive antihypertensive regimen, resistant elevated BP was more prevalent in those with severe obstructive sleep apnea (58.3%) than in those with moderate obstructive sleep apnea (28.6%) (P = .01).

Patients with severe obstructive sleep apnea had a 4-fold higher odds of resistant elevated BP despite receiving an aggressive antihypertensive mediation regimen, even after consideration of well-recognized hypertension risk factors, including age, sex, race, body mass index, smoking, diabetes mellitus, and cardiovascular disease (adjusted odds ratio, 4.1; 95% confidence interval [CI], 1.7 - 10.2).

CPAP Plus Spironolactone?

In an accompanying Commentary in the same issue, Susan M. Harding, MD, from the University of Alabama, Birmingham, discusses some of the mechanisms that may drive this relationship and suggests it may be bidirectional.

Of note is the fact that in this cohort, none of the 28 participants with elevated blood pressure despite intensive antihypertensive treatment was receiving an aldosterone blocker, she writes.

"Our laboratory has noted a correlation between plasma aldosterone levels and OSA severity in resistant HTN [hypertension] patients. We also observed that spironolactone reduced OSA severity in these patients, despite remaining on a thiazide diuretic," Dr Harding writes. "Aldosterone excess mediates chronic fluid retention, so our data support the hypothesis that aldosterone-mediated chronic fluid retention could impact (worsen) OSA severity."

Further, their group found that increased dietary sodium correlated with sleep apnea severity in patients with resistant hypertension and hyperaldosteronism, she added. "Although this finding needs to be verified in a randomized controlled trial, we postulate that the aldosterone-induced worsening of OSA may be mediated through increased fluid retention in the surrounding soft tissues of the upper airway."

Other researchers have also found a "significant spontaneous fluid shift" from the legs to the neck during sleep in patients with drug-resistant hypertension, she points out, which may partly explain the more severe sleep apnea in those with resistant hypertension, she notes.

Previous work has shown that 12 weeks of CPAP therapy can result in a "mild" reduction of 3.1 mm Hg in the mean 24-hour BP in patients with resistant hypertension, and an AHI or more than 15/hour, change that can reduce cardiovascular risk, she concludes.

"Since spironolactone has the potential to improve BP control and AHI in patients with resistant HTN, spironolactone should be considered, along with CPAP therapy, in these patients," Dr Harding concludes. "Future research will define the best management strategies for OSA patients with resistant hypertension; hopefully it will not take another 30 years."

Aggressive Management

Commenting on this study for Medscape Medical News, Mary Ann Bauman, MD, medical director for Women's Health and Community Relations, INTEGRIS Health, Oklahoma City, Oklahoma, said the study raises an interesting question about patients with cardiovascular disease and severe OSA.

"These patients were taken from cardiologists' practices, and presumably the cardiologists were being very aggressive with their antihypertensive management. The criteria for BP control, 130 over 80, is very strict but is considered appropriate for patients with cardiovascular disease," Dr Bauman said.

She added that she would like to see more evidence that treating severe OSA would indeed make a difference in patients with significant cardiovascular disease.

Also, Dr Bauman observed, from her standpoint as a primary care physician, treating sleep apnea is often problematic.

"It is often very difficult to get patients to continue treatment for sleep apnea. Some patients like those CPAP [continuous positive airway pressure] machines, but many patients hate them. They feel like they are choking when they use them, the machines make it uncomfortable to sleep with a partner, those kinds of things," she added. "So I think we do want to know if treating sleep apnea really helps with BP control."

"If we have convincing data that treating severe obstructive sleep apnea actually does result in improved BP control, and as a result, improved cardiovascular disease risk, it may be an incentive to get patients off of their intensive antihypertensive regimens where they are taking 3 meds. They may be willing to give CPAP a try and persevere with it."

Also commenting on the findings, Shirin Shafazand, MD, from the Division of Pulmonary Critical Care and Sleep Medicine, University of Miami, Miller School of Medicine, Florida, noted that the study adds to the existing body of literature that suggests a significant association between obstructive sleep apnea and hypertension.

Dr Shafazand points out that the study was not able to compare patients with severe OSA to those with mild or no OSA and that it did not evaluate the effect of CPAP therapy, the gold standard of therapy for obstructive sleep apnea, on BP.

She cited a recent study (JAMA. 2013;310:2407-2415) suggesting that among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with controls resulted in a decrease in 24-hour mean and diastolic BP and an improvement in the nocturnal BP pattern.

"The mean improvement in 24 hour BP measurements was around 3 mmHg," she told Medscape Medical News. "This is in keeping with several other studies looking at BP and OSA treatment. The cumulative literature to date appears to support the authors conclusions that for patients, especially those at high CV [cardiovascular] risk, with resistant hypertension on 3 or more medications, diagnosing and treating severe OSA likely has a beneficial impact on BP control."

The study was supported by the National Institutes of Health National Heart Lung Blood Institute. Dr Walia, Dr Bauman, Dr Harding, and Dr Shafazand have disclosed no relevant financial relationships.

J Clin Sleep Med. 2014;10:835-843. Abstract Editorial


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