Current Hypertension Reports

, Volume 12, Issue 3, pp 189–195

Obstructive Sleep Apnea and Hypertension


    • Vascular Biology and Hypertension Program, Sleep/Wake Disorders CenterUniversity of Alabama at Birmingham

DOI: 10.1007/s11906-010-0112-8

Cite this article as:
Calhoun, D.A. Curr Hypertens Rep (2010) 12: 189. doi:10.1007/s11906-010-0112-8


Obstructive sleep apnea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is associated with an increased risk of prevalent hypertension, whereas prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure. However, these studies do indicate a wide variation in the blood pressure effects of CPAP, with some patients, on an individual basis, manifesting a large antihypertensive benefit. OSA is particularly common in patients with resistant hypertension. The reason for this high prevalence of OSA is not fully explained, but data from our laboratory suggest that it may be related to the high occurrence of hyperaldosteronism in patients with resistant hypertension. We hypothesize that aldosterone excess worsens OSA by promoting accumulation of fluid in the neck, which then contributes to increased upper airway resistance.


Sleep apneaHyperaldosteronismResistant hypertensionContinuous positive airway pressure


Obstructive sleep apnea (OSA) is characterized by repeated episodes of apnea and hypopnea secondary to complete or partial upper airway collapse during sleep. These apneic/hypopneic events are associated with significant reductions in blood oxygen saturation, increases in respiratory effort, and sleep disruption secondary to arousals. In addition to potentially causing significant daytime symptoms such as daytime sleepiness, untreated OSA is being increasingly recognized as an important contributing factor to long-term cardiovascular morbidity and mortality.

The association between OSA and hypertension is particularly strong. Moderate-severe OSA is positively related to the risk of having hypertension and the severity of hypertension. Ambulatory blood pressure studies and antihypertensive trials indicate that small changes in blood pressure levels, and in particular, nocturnal blood pressure, result in substantial changes in cardiovascular event rates. Accordingly, OSA, by inducing changes in daytime and nighttime blood pressure levels, would be expected to significantly impact cardiovascular outcomes. Recognizing this interaction, both globally and on an individual patient basis, may allow for better clinical management of the two disease processes, thereby facilitating reductions in overall cardiovascular risk.

Nocturnal Blood Pressure and Cardiovascular Risk

Absent or diminished nocturnal dipping of blood pressure is a strong, independent predictor of cardiovascular risk. The Ohasama study, one of earliest studies to relate nocturnal dipping of blood pressure to cardiovascular outcomes, demonstrated that on average, each 5% deficit in the normal decline in nocturnal blood pressure was associated with an approximately 20% greater risk in cardiovascular mortality [1]. Multiple subsequent studies have confirmed the outcome benefit of the normal decrease in blood pressure during sleep [24]. Common disease states that are associated with diminished or absence of nocturnal dipping of blood pressure include secondary causes of hypertension such as primary aldosteronism, chronic kidney disease, diabetes, older age, resistant hypertension, and OSA.

Separate from specific assessment of nocturnal dipping status, large, prospective studies using ambulatory blood pressure monitoring have demonstrated that nocturnal blood pressure levels are, in general, a better predictor of cardiovascular risk than daytime blood pressure levels. A particularly compelling example is the Dublin Outcome Study, during which 5292 untreated hypertensive patients who had both clinic and 24-hour ambulatory blood pressure measurements at baseline were prospectively followed for cardiovascular morbidity and mortality [5]. During a median follow-up period of approximately 8.5 years, 24-hour ambulatory blood pressure levels were superior to clinic blood pressure measurements in predicting cardiovascular mortality, and nighttime blood pressure was overall the best predictor of cardiovascular risk. In this study, a 10-mm Hg increase in mean nighttime systolic blood pressure was associated with a 21% increase in cardiovascular mortality. Other studies have confirmed nocturnal blood pressure to be a more potent predictor of cardiovascular risk than daytime blood pressure [6, 7].

Poorly controlled hypertension remains an important cause of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, stroke, and chronic kidney disease, worldwide. The above findings indicate that any disease process that contributes to higher blood pressure, and in particular, higher nocturnal blood pressure, will result in increased cardiovascular risk, and conversely, that even small reductions in blood pressure levels would be expected to reduce cardiovascular risk significantly. Benefit of even modest reduction in blood pressure has been demonstrated: data from observational studies and randomized trials indicate that a 2-mm Hg reduction in diastolic blood pressure on a population basis would result in a 17% decrease in the prevalence of hypertension, a 6% reduction in the risk of coronary heart disease, and a 15% reduction in the risk of stroke and transient ischemic attack [8]. A meta-analysis of randomized trials of antihypertensive medications indicated that a 10-mm Hg reduction in systolic blood pressure or a 5-mm Hg reduction in diastolic blood pressure reduces risk of coronary heart disease events by 22% and stroke by 41% [9].

These outcome data highlight the importance of even small changes in blood pressure, and in particular changes in nocturnal blood pressure, in contributing to significant changes in cardiovascular risk. Accordingly, disease processes such as OSA that raise blood pressure, particularly at night, contribute importantly to increased cardiovascular morbidity and mortality.

OSA and Prevalence of Hypertension

OSA and hypertension commonly coexist. Approximately 50% of patients with OSA are hypertensive, and an estimated 30%–40% of hypertensive patients have OSA [1012]. Cross-sectional studies have been consistent in demonstrating that moderate-severe OSA (apnea-hypopnea index [AHI] > 15 events/h) is significantly associated with risk of having arterial hypertension [12]. These studies have generally shown a liner relationship between AHI and prevalence and severity of hypertension (ie, the more severe the OSA, the higher the risk of having hypertension of increasing severity).

In a series of cross-sectional analyses, Grunstein et al. [13, 14] reported that a high AHI is associated with an increased likelihood of having hypertension even after correcting for confounding variables such as age and obesity. Also using an observational design, Lavie et al. [15] performed overnight polysomnographic evaluations on 2677 adult subjects suspected of having OSA based on symptoms. Evening and morning blood pressures were also measured in these participants. In this analysis, both the prevalence and severity of hypertension increased with increasing severity of OSA. Overall, an increasing AHI was associated with higher systolic and diastolic blood pressure levels independent of age, body mass index (BMI), and gender. An increase of one event per hour in the AHI was associated with a 1% higher risk of having hypertension. A similar linear relationship between severity of OSA and prevalence of hypertension was also observed in the Wisconsin Sleep Cohort Study, which found that an AHI of 15 (compared with 0) increased the likelihood of having hypertension by 80% [16]. Overall, risk of being hypertensive increased in a dose-dependent fashion in relation to increasing severity of OSA. In this study, the 24-hour ambulatory blood pressure levels were higher in persons with more severe OSA [17]. The relationship was linear, with increasing severity of AHI being associated with progressively higher ambulatory blood pressure levels.

Population-based studies that include a broad cross-section of subjects, not only those suspected of having OSA, confirm a strong correlation between OSA and risk of being hypertensive. Bixler et al. [18], in an evaluation of 1741 adult subjects, reported that that having moderate-severe OSA (AHI ≥ 15 compared with 0) was significantly associated with risk of prevalent hypertension. Interestingly, the strength of the association decreased with increasing age, such that the relationship between OSA and hypertension was less pronounced in older subjects. In a very large population-based evaluation of 2148 subjects, an AHI ≥ 15 more than doubled the risk of having hypertension after adjusting for confounders such as BMI, neck circumference, and alcohol use [19]. In this study, it was further reported that an increase in the AHI of five events per hour increased the risk of having hypertension by 1.25%. In the Sleep Heart Health Study, which included 6123 subjects over 40 years of age, an AHI ≥ 30 compared with less than 1.5 was associated with an increased the risk of having hypertension of almost 40% [20]. These observational studies are consistent in demonstrating that moderate-severe OSA positively relates to both the prevalence and severity of hypertension.

OSA and Risk of Incident Hypertension

Two longitudinal studies have prospectively assessed the relationship between OSA severity and risk of developing hypertension in initially normotensive cohorts. In the Wisconsin Sleep Cohort Study, Peppard et al. [21] followed 709 normotensive subjects for 4 years after evaluation by overnight polysomnography [22]. Subjects with moderate-severe OSA (AHI ≥ 15 events/h) had a more than threefold increase in the risk of developing hypertension during the observation period compared to participants without OSA. In contrast, investigators from the Sleep Heart Health Study, in their analysis of 2470 middle-aged subjects who at baseline did not have hypertension, found that after 5 years of follow-up and after adjusting for BMI, there was not a significantly increased risk of incident hypertension [23]. Among subjects with severe OSA (AHI > 30 events/h), there was a trend toward increased risk of hypertension, but even that association failed to reach statistical significance. These disparate results from the Wisconsin Sleep Cohort Study and the Sleep Heart Health Study may be related to methodologic differences between the two studies, including differences in cohort size and diversity and use of attended in-laboratory versus at-home unattended polysomnography [24]. A particularly important distinction is that participants in the Wisconsin Sleep Cohort Study were, on average, considerably younger than participants in the Sleep Heart Health Study (47 vs 60 years, respectively). One can speculate that the younger cohort may have been more susceptible to the potential hypertensive effects of untreated OSA. Although these methodologic differences may be relevant to the observed difference in outcomes, additional prospective studies are needed to reconcile the positive results of the Wisconsin Sleep Cohort Study with the negative results of the Sleep Heart Health Study.

Effect of Continuous Positive Airway Pressure on Blood Pressure

If OSA contributes to the development and/or progression of hypertension, than effective treatment of OSA with positive air way pressure should lower blood pressure. Many continuous positive airway pressure (CPAP) studies of various designs have reported such antihypertensive benefit, with some studies reporting large reductions in blood pressure, particularly in hypertensive cohorts. However, many other studies have reported little or no benefit of CPAP on blood pressure levels. The lack of a consistent treatment effect may be related to a number of variables, including differences in study design, type and size of cohorts, degree of CPAP adherence, duration of treatment, and accuracy of blood pressure assessment [25]. Overall, the most scientifically rigorous studies (ie, randomized trials with a control group) suggest a modest but significant effect on blood pressure. This is particularly true of studies using 24-hour ambulatory blood pressure monitoring. These studies indicate a wide variation in the blood pressure response, with some very large reductions in blood pressure on an individual patient basis. The individuals more likely to benefit include patients with severe OSA and those most adherent with CPAP use.

Recently, four meta-analyses of randomized, controlled CPAP trials have been published (Table 1). Bazzano et al. [26] included in their analysis 16 randomized clinical trials published between 1980 and 2006, with a total of 818 participants, that compared CPAP to control, had a minimum treatment duration of 2 weeks, and reported blood pressure changes during the intervention or control period. Mean net change in systolic blood pressure for those treated with CPAP compared with control was −2.46 mm Hg; mean net change in diastolic blood pressure was −1.83 mm Hg; and mean net change in mean arterial pressure was −2.22 mm Hg. All of these changes were statistically significant. When differences in daytime and nighttime blood pressure levels were assessed separately in subgroup analyses, only the reduction in nighttime blood pressure achieved statistical significance. Although the authors concluded that their analysis did provide evidence that effective CPAP treatment reduces blood pressure in patients with OSA, the mean treatment effect was modest at best.
Table 1

Summary of meta-analyses of randomized controlled CPAP trials


Number of trials/patients

BP end point

Minimum CPAP duration


Alajmi et al. [27]



4 wk

SBP: −1.38 mm Hg (not significant)

DBP: −1.52 mm Hg (not significant)

More benefit in more severe OSA; trend for better SBP reduction with better CPAP adherence

Bazzano et al. [26]



2 wk

SBP: −2.46 mm Hg

DBP: −1.83 mm Hg

More benefit in patients with higher baseline BP, higher BMI, and more severe OSA

Haentjens et al. [29]



1 wk

24-h SBP: −1.64 mm Hg

24-h DBP: −1.48 mm Hg

More benefit in more severe OSA and with better CPAP adherence

Mo and He [28]



4 wk

24-h SBP: −0.95 mm Hg (not significant)

24-h DBP: −1.78 mm Hg

BMI body mass index, BP blood pressure, CPAP continuous positive airway pressure, DBP diastolic blood pressure, OSA obstructive sleep apnea, SBP systolic blood pressure

Alajmi et al. [27] performed a comprehensive literature search up to July 2006 to identify 10 randomized, controlled trials that included an appropriate control group and reported systolic and diastolic blood pressure before and after CPAP or control. The analysis included data from 587 subjects. Overall, the effects of CPAP were modest and not significant. CPAP compared with control reduced systolic blood pressure by 1.38 mm Hg and diastolic blood pressure by 1.53 mm Hg, with neither effect being statistically significant. Reductions in blood pressure tended to larger in patients with severe OSA (AHI > 30 events/h), and there was a trend for systolic blood pressure reduction to be associated with CPAP adherence.

Mo and He [28] included in their analysis randomized, controlled trials published between 2000 to 2006 in both English and Chinese. Study inclusion criteria included treatment duration of at least 4 weeks and measurement of 24-hour ambulatory blood pressure before and after CPAP or control (non-CPAP). Seven studies with 471 participants were included. Overall, CPAP reduced 24-hour systolic blood pressure by 0.95 mm Hg, 24-hour diastolic blood pressure by 1.78 mm Hg, and 24-hour mean blood pressure by 1.25 mm Hg, with only the change in 24-hour diastolic blood pressure being statistically significant.

Haentjens et al. [29] also included in their analysis only studies that had used 24-hour ambulatory blood pressure assessments. This included 572 patients from 12 randomized, placebo-controlled trials. CPAP treatment compared with placebo reduced 24-hour systolic blood pressure by 1.64 mm Hg and 24-hour diastolic blood pressure by 1.48 mm Hg. In a prespecified meta-regression analysis, greater CPAP treatment-related reduction in 24-hour mean blood pressure was observed in subjects with more severe OSA and in those most adherent with use of CPAP.

These meta-analyses of randomized, controlled trials demonstrate a consistent but modest antihypertensive effect of CPAP. This overall small treatment effect raises the question of why use of CPAP does not lower blood pressure more effectively. It must be emphasized that even small reductions in blood pressure result in substantial reductions in cardiovascular risk such that the overall modest antihypertensive effects observed with CPAP would be expected to significantly reduce cardiovascular events. However, given the strong evidence linking OSA to hypertension, it remains unclear why CPAP trials have not demonstrated larger antihypertensive benefit [30]. One reason may be related to duration of treatment effect. Most clinical trials have limited the intervention period to 12 weeks or less [29]. Given that OSA has likely been present for many years before being diagnosed, a longer treatment period may be needed to effectively reverse OSA-related increases in blood pressure. Alternatively, it is possible that the vascular changes induced by untreated OSA may be fixed and, therefore, cannot be reversed. If so, CPAP may be better at preventing than treating hypertension. A second issue may be related to CPAP adherence. Even in clinical trials, CPAP adherence has averaged less than 4–5 h a night, which would leave most individuals untreated for a large proportion of their normal sleep period [29]. With better adherence, better antihypertensive benefit might be seen. This possibility is suggested by studies showing that blood pressure benefit is enhanced in the patients most adherent with CPAP.

Mechanisms of OSA-Induced Hypertension

Proposed mechanisms by which OSA contributes to the development of hypertension are shown in Fig. 1. OSA-induced increases in sympathetic activation are well described and likely represent the most important effect by which OSA raises blood pressure. This effect is not limited to the period of apnea/hypopnea, but instead manifests as a sustained increase in sympathetic activation, including during the daytime when affected patients are awake [31]. Heightened sympathetic activity would be expected to increase blood pressure through increases in vascular resistance, cardiac output, and possibly, renin-angiotensin-aldosterone system activity. Effective treatment of the OSA with CPAP suppresses the sympathetic activation [32].
Fig. 1

Pathophysiologic mechanisms involved in the etiology of obstructive sleep apnea (OSA)—induced hypertension. RAAS—renin-angiotensin-aldosterone system

Other pathophysiologic features of OSA that likely contribute to increased risk of developing hypertension include a proinflammatory effect, increased oxidative stress, and increased vascular stiffness. Small mechanistic CPAP intervention trials suggest that each of these effects can be reduced with effective CPAP use, often quite rapidly [3337].

OSA and Resistant Hypertension

OSA is particularly common in patients with resistant hypertension. In a prospective evaluation of 41 patients with resistant hypertension, Logan et al. [38] found that 96% of the men and 65% of the women had significant OSA based on an AHI ≥ 10 events per hour. In an assessment of 71 consecutive subjects referred to the University of Alabama at Birmingham for resistant hypertension, we found that 90% of the men and 77% of the women had OSA based on an AHI greater than five events per hour [39]. Other studies indicate that as OSA severity increases there is an increasing need for additional blood pressure medications; and the more severe a patient’s OSA, the less likely his or her blood pressure is controlled with pharmacologic therapy [40•, 4143]. A prospective but uncontrolled trial of CPAP treatment demonstrated that CPAP use can have substantial antihypertensive benefit in patients with resistant hypertension. Logan et al. [44] reported that CPAP use after 2 months follow-up in 11 patients with resistant hypertension lowered nighttime systolic blood pressure by 14.4 ± 4.4 mm Hg and diastolic blood pressure by 7.8 ± 3.0 mm Hg.

The extraordinarily high prevalence of OSA in patients with resistant hypertension is not fully explained. Data from our laboratory suggest that OSA is linked to the high occurrence of hyperaldosteronism in patients with resistant hypertension. In an evaluation of 114 patients with resistant hypertension, we found that patients at high risk of having OSA based on their responses to the Berlin Questionnaire had significantly greater 24-hour urinary excretion of aldosterone and were almost twice as likely be diagnosed with primary aldosteronism compared with control subjects with resistant hypertension but at low risk of having OSA [39]. In a subsequent study, we reported that plasma aldosterone levels in patients with resistant hypertension are positively correlated with severity of OSA as indexed by AHI and hypoxic index [40•].

We hypothesize that hyperaldosteronism worsens OSA secondary to aldosterone-induced fluid retention, some of which is localized to the neck, leading to parapharyngeal edema, which then increases upper airway resistance. Such an increase in upper airway resistance attributable to increases in intravascular fluid expansion has been reported in healthy volunteers subjected to acute lower-body positive pressure [45]. Decreases in airway resistance and associated improvements in severity of OSA are observed in patients acutely diuresed for exacerbation of congestive heart failure [46]. We hypothesize that the same effect is occurring in patients with resistant hypertension but on a chronic basis (ie, persistent intravascular fluid retention worsens OSA through increased upper airway resistance due to increased parapharyngeal edema).

We recently published findings consistent with this hypothesis showing that aldosterone blockade with use of spironolactone reduces the severity of OSA in patients with resistant hypertension [47]. In this study, 12 patients with resistant hypertension and moderate-severe OSA (AHI > 15 events/h) were treated with spironolactone, 50 mg daily, in addition to their normal antihypertensive regimen, which included a thiazide diuretic in all patients. A full-night polysomnogram was done at baseline, and then repeated 8 weeks after beginning treatment with spironolactone. Spironolactone use was associated with an almost 50% reduction in severity of OSA based on improvement in the total AHI and significant reductions in AHI during supine sleeping and during rapid eye movement sleep, when OSA tends to be most severe (Fig. 2). These results are provocative in suggesting that aldosterone blockade may improve the severity of OSA in patients with resistant hypertension and are important in providing support for the hypothesized role of aldosterone excess in worsening OSA. The study is limited by not having a control group, such that a chance effect or an effect that might have been achieved with any other antihypertensive agent cannot be excluded. A controlled, randomized comparison of spironolactone with another type of antihypertensive is needed to fully test this effect.
Fig. 2

Effects of 8 weeks of treatment with spironolactone on apnea-hypopnea index (AHI), hypoxic index (HI), supine AHI, and rapid eye movement sleep (REM) AHI at 8 weeks compared with baseline in patients with resistant hypertension. (From Gaddam et al. [47]; with permission)

An alternative explanation for the high prevalence of OSA and resistant hypertension is that untreated OSA stimulates aldosterone release. Some experimental data suggest that intermittent hypoxia, such as occurs with OSA, stimulates the renin-angiotensin-aldosterone system [48], but data in human studies have been inconsistent. In a recent clinical evaluation, the first night of CPAP use did not lower plasma renin activity or plasma aldosterone levels in normotensive patients undergoing CPAP titration [49]. These findings argue against untreated OSA contributing to aldosterone excess, at least in normotensive patients. Studies of chronic CPAP use are needed in hypertensive patients, and in particular, patients with resistant hypertension, to determine if untreated OSA plays a role in stimulating aldosterone release in patients more likely to develop hyperaldosteronism.


Observational studies suggest that untreated OSA contributes importantly to the risk of developing hypertension. Treatment of OSA with CPAP is associated with consistent but generally modest reductions in blood pressure. The individual patient response to CPAP, however, can be large, such that use of CPAP should be encouraged in all hypertensive patients with OSA, particularly if the OSA is moderate or severe (>15 events/h). Patients with more severe OSA and most adherent with CPAP use are most likely to have a favorable antihypertensive effect. Resistant hypertension and OSA commonly coexist. Emerging data link the high prevalence of OSA in patients with resistant hypertension to hyperaldosteronism, including recent findings that aldosterone blockade with spironolactone reduces the severity of OSA in patients with resistant hypertension. If confirmed, this observation would support the use of aldosterone antagonists as a potential adjunct to CPAP therapy in patients with hyperaldosteronism and/or resistant hypertension.


No potential conflict of interest relevant to this article was reported.

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