Obstructive Sleep Apnea and Hypertension
The relationship between obstructive sleep apnea (OSA) and hypertension (HTN) has been a point of interest for decades. The cascade of physiologic perturbations that occur as a result of repeated upper airway narrowing, outlined in previous entries on this website, has been the foundation for further study.
Early on, scores of papers described case series and cross-sectional reports linking OSA and HTN. While important, these studies were limited by potential confounding effects of comorbid variables, particularly obesity. Prevalence data from the Sleep Heart Health Study (SHHS), suggesting the association was limited by the inability to prove that OSA preceded the onset of HTN.1 The first study to accomplish this was the landmark prospective longitudinal Wisconsin Sleep Cohort.2 For the first time, persuasive evidence implicating OSA as a possible causal factor in hypertension was now available. Specifically, the presence of hypertension four years after initial assessment was found to be dependent upon the severity of OSA at baseline. It is worth mentioning that there were notable limitations to the study. For example, it did not specifically identify subjects free of HTN at baseline and there was no accounting of the 10% of patients at baseline and 17% at follow-up who were treated with antihypertensive medications.
While these two cohort studies found an association between OSA and HTN, the third and most recent longitudinal cohort study did not. The Vitoria Sleep Cohort out of Spain, comprised of a general population sample somewhat younger and thinner than the SHHS and the Wisconsin Sleep Cohort, failed to show a significant association between OSA and incident HTN, after adjustment for the usual confounders. Methodological differences between the studies may also help to explain the disparity in results.
Beyond these cohort studies, more instructive data comes from interventional trials, which ask the key question: Will treatment of OSA appreciably alter blood pressure (BP)?
Notably, nearly all interventional trials studying this question have utilized continuous positive airway pressure (CPAP) as the treatment of choice for OSA. While clearly the most effective treatment, nearly all such trials have been limited by issues related to compliance with CPAP. Nevertheless, the results have been important.
Several small, short-term interventional trials have shown CPAP to acutely reduce sympathetic drive and BP during sleep. What may be a more important question is whether nighttime CPAP therapy will impact daytime BP, where data have been less clear-cut. Numerous observational studies, often uncontrolled and from highly select populations, have suggested improvements in daytime BP control with the use of CPAP. Subsequent randomized, placebo-controlled studies, however, have yielded variable results, due in large part to variations in population sample and methodology, thus potentially limiting the generalizability of the studies.
With the largest randomized controlled trial published to date, Pepperell and colleagues from Oxford found a small but significant reduction in daytime BP in a normotensive cohort after four weeks of therapy, an effect which appeared to be driven primarily by those with more frequent oxyhemoglobin desaturation episodes.3 Becker et al carried out one of the longest trials (>60 days) and found fairly dramatic reductions in mean BP (9.9+/-11.4 mm Hg) in a small cohort with severe OSA (mean AHI > 60/hr), though the analysis was not an intention-to-treat and two-thirds of the sample was taking antihypertensive medications.4 Offering some insight into the mechanisms of the systemic effects of OSA, a randomized controlled trial (RCT) from Barbe et al. suggests that normotensive subjects with severe OSA but without demonstrable daytime sleepiness are immune to the BP reducing effects of CPAP.5 This finding was also suggested by a subsequent paper from the Oxford group which showed that those who were objectively sleepy had a more robust response to the BP lowering effects of CPAP than those who were not sleepy. Accounting for the dozen or so RCT's published (in both normotensive and hypertensive populations) a meta-analysis showed an approximate pooled 1.8 mmHg reduction in mean BP associated with the use of CPAP in those with OSA. This effect was weighted by a few studies with a large treatment effect, since more than half of these trials did not show a significant change in BP associated with CPAP.
Finally, an elegant and intriguing trial by Pepin and colleagues reminds us that drug therapy should probably be given first consideration when it comes to reducing BP in those with OSA and HTN.6 In a cross-over study of valsartan and CPAP, the drug treatment induced a fourfold higher decrease in mean 24-hour BP than CPAP. Interestingly, in the subset of patients who didn't respond to either single therapy, combining drug treatment with CPAP appeared to have a synergistic effect in reducing BP. Studies such as this should force us to re-think the care models of the OSA patient with HTN, which should incorporate varied approaches to treatment, accounting for patient preferences and phenotypic responses to treatment.
- Nieto FJ, Young TB, Lind BK, Shahar E, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study: Sleep Heart Health Study. JAMA 2000; 283:1829-36.
- Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342:1378-84.
- Pepperell JC, Ramdassingh-Dow S, Crosthwaite N. et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet 2002;359:204-10.
- Becker HF, Jerrentrup A, Ploch T, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003;107:68-73.
- Barbé F, Mayoralas LR, Duran J, et al. Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness. a randomized, controlled trial. Ann Intern Med 2001;134:1015-23.
- Pépin JL, Tamisier R, Barone-Rochette G, Launois SH, Lévy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med 2010;182:954-60.
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