Correspondence

Sleep-Disordered Breathing and Hypertension

N Engl J Med 2000; 343:966-967September 28, 2000

Article

To the Editor:

The article by Peppard et al. (May 11 issue)1 provides interesting epidemiologic data that suggest a causal role of sleep-disordered breathing in hypertension. If the breathing disorder is symptomatic (e.g., obstructive sleep apnea), the standard treatment is nasal continuous positive airway pressure. If a causal relation exists, then treatment with continuous positive airway pressure should reduce blood pressure in patients with hypertension and obstructive sleep apnea.

We studied the effect of nasal continuous positive airway pressure on blood pressure in 17 hypertensive patients (15 men and 2 women; mean [±SD] age, 53±6 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 33.5±5.5) and in 7 normotensive patients (all men; age, 50±10 years; body-mass index, 35.1 ± 11.4) with moderate-to-severe obstructive sleep apnea (apnea–hypopnea index, 60±19 and 53±28 events per hour, respectively). Before and after the use of continuous positive airway pressure, 24-hour blood pressure was recorded noninvasively at 15-minute intervals (oscillometric blood pressure measurement). After four to six months of treatment with continuous positive airway pressure, the mean 24-hour systolic and diastolic pressure had decreased significantly in the hypertensive group, whereas there was no significant change in the normotensive group (Table 1Table 1Mean (±SD) 24-Hour Blood Pressure in 17 Hypertensive and 7 Normotensive Patients with Obstructive Sleep Apnea Who Were Treated with Nasal Continuous Positive Airway Pressure (CPAP).).

These data provide additional evidence of a causal link between obstructive sleep apnea and hypertension. We therefore suggest that hypertension in patients with obstructive sleep apnea be classified as secondary hypertension.

Wulf Pankow, M.D.
Achim Lies, M.D.
Friedrich W. Lohmann, M.D.
Krankenhaus Neukölln, D-12351 Berlin, Germany

1 References

1. 1

   Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342:1378-1384
   Full Text | Web of Science | Medline

To the Editor:

The conclusions reached by Peppard et al. with regard to the association between obstructive sleep apnea and hypertension are incorrect. What they have established, as have other researchers, is that an index of apnea and 4 percent oxyhemoglobin desaturation is associated with systemic hypertension. Peppard et al. do not prove that there is any association between the apnea–hypopnea index and hypertension, though logic would suggest that there is. This is not an issue of semantics, but one of critical importance for the clinical management of sleep disorders.

The authors' definition of hypopnea, with the requirement of 4 percent desaturation, is much too restrictive. There is ample evidence that desaturation is not required to cause arousal, and arousals are the predominant link to blood-pressure elevations that are associated with the termination of apnea.1

The study by Peppard et al. cannot address the important issue of the increasing number of patients seen in sleep-disorder clinics who have extreme daytime sleepiness, fragmented sleep, and nonapneic sleep-disordered breathing, often with minimal desaturation. It is important to show conclusively that such patients do or do not have an increased risk of hypertension.

Robert Joseph Thomas, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215

1 References

1. 1

   Ringler J, Basner RC, Shannon R, et al. Hypoxemia alone does not explain blood pressure elevations after obstructive apneas. J Appl Physiol 1990;69:2143-2148
   Web of Science | Medline

To the Editor:

Peppard et al. suggest that sleep-disordered breathing is a risk factor for hypertension. Although their analysis was adjusted for several potential confounding factors, such as age and body-mass index, no data are provided on the potential confounding effect of the antihypertensive medication that was used. At base line, 10 percent of all the study participants were receiving antihypertensive treatment, and the proportion was 17 percent at follow-up. In addition, the proportion of patients who were receiving antihypertensive treatment at base line was highest in the group with the highest base-line apnea–hypopnea index.

Although this finding can be interpreted as supporting the authors' main conclusion, an effect of antihypertensive drugs on the breathing pattern itself during sleep should be considered. Some antihypertensive drugs may affect the breathing pattern during sleep.

Frederieke M. Brouwers, M.D.
Jacques W.M. Lenders, M.D., Ph.D.
University Medical Center St. Radboud, 6500 HB Nijmegen, the Netherlands

Author/Editor Response

The authors reply:

To the Editor: Dr. Pankow and colleagues provide data from a lengthy intervention trial demonstrating reduced blood pressure in patients with hypertension and sleep apnea who were treated with continuous positive airway pressure. Since elevated blood pressure resulting from sleep-disordered breathing may not be entirely reversible — perhaps because of long-term cardiovascular structural changes — intervention trials alone may not be sufficient to establish the full role of sleep-disordered breathing in hypertension. Prospective observational data and the results of intervention trials, together, provide evidence of an important causal role of sleep-disordered breathing in hypertension.

Dr. Thomas suggests that the apnea–hypopnea index we used may not adequately measure the aspects of sleep-disordered breathing that are most germane to the development of hypertension. We agree that our use of a conservative definition of sleep-disordered breathing may have resulted in underestimates of the degree of association between sleep-disordered breathing and hypertension. However, we have examined alternative definitions of sleep-disordered breathing as predictors of daytime hypertension, including varying degrees of oxygen desaturation and sleep fragmentation. None of these alternatives were substantially better predictors of hypertension than the definition we used. Thomas's assertion that “arousals are the predominant link to blood-pressure elevations” is not corroborated by a recent epidemiologic study1 or a study of acute blood-pressure responses to events in sleep-disordered breathing.2

Drs. Brouwers and Lenders suggest that antihypertensive medications may cause unstable breathing during sleep and that this could lead to a spurious relation between hypertension and sleep-disordered breathing. To address this possibility, we reanalyzed our data with the use of an “incidence cohort” approach. Of the study participants described in our article, those classified as hypertensive at base line (i.e., those who were using antihypertensive medications or whose blood pressure was 140/90 mm Hg or higher) were excluded. We analyzed the data on the remaining, normotensive study participants at four years of follow-up for the development of hypertension. The odds ratios for hypertension according to the base-line apnea–hypopnea index in this group (Table 1Table 1Adjusted Odds Ratios for Hypertension at the Four-Year Follow-up among Participants in the Wisconsin Sleep Cohort Study Who Were Classified as Normotensive at Base Line, According to the Apnea–Hypopnea Index at Base Line.) were similar to those reported in our article. In this analysis, the use of antihypertensive medication could not confound the association between sleep-disordered breathing and hypertension because, by definition, the normotensive study participants were not using antihypertensive agents when sleep-disordered breathing was quantified at base line.

Paul E. Peppard, Ph.D.
Terry Young, Ph.D.
University of Wisconsin–Madison, Madison, WI 53705

2 References

1. 1

   Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study: Sleep Heart Health Study. JAMA 2000;283:1829-1836
   CrossRef | Web of Science | Medline

2. 2

   Morgan BJ, Dempsey JA, Pegelow DF, et al. Blood pressure perturbations caused by subclinical sleep-disordered breathing. Sleep 1998;21:737-746
   Web of Science | Medline

Citing Articles (14)

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   Markku Partinen, Christer Hublin. 2011. Epidemiology of Sleep Disorders. , 694-715.
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   S. Ma, S.W. Mifflin, J.T. Cunningham, D.A. Morilak. (2008) Chronic intermittent hypoxia sensitizes acute hypothalamic–pituitary–adrenal stress reactivity and Fos induction in the rat locus coeruleus in response to subsequent immobilization stress. Neuroscience 154:4, 1639-1647
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   Aynur Okcay, Virend K. Somers, Sean M. Caples. (2008) Obstructive Sleep Apnea and Hypertension. The Journal of Clinical Hypertension 10:7, 549-555
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   Sean M. Caples, Virend K. Somers. (2007) Sleep, Blood Pressure Regulation, and Hypertension. Sleep Medicine Clinics 2:1, 77-86
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   R. Wolk, V. K. Somers. (2006) Obesity-related cardiovascular disease: implications of obstructive sleep apnea. Diabetes, Obesity and Metabolism 8:3, 250-260
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   Lalita Khaodhiar, Karen C McCowen, George L Blackburn. 2006. Risk Assessment and Treatment Standards of Obesity and Overweight in Relation to Cardiovascular Disease. , 225-256.
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   Ching-Chi Lin, Wen-Yeh Hsieh, Chon-Shin Chou, Shwu-Fang Liaw. (2006) Cardiopulmonary exercise testing in obstructive sleep apnea syndrome. Respiratory Physiology & Neurobiology 150:1, 27-34
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   Nadeem Akhtar, Christian Guilleminault. (2005) Obstructive sleep apnea syndrome in the elderly. Aging Health 1:2, 285-302
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   Ching-Chi Lin, Ching-Kai Lin, Kun-Ming Wu, Chon-Shin Chou. (2004) Effect of Treatment by Nasal CPAP onCardiopulmonary Exercise Test in ObstructiveSleep Apnea Syndrome. Lung 182:4, 199-212
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    Raj N. Kalaria, Louise Spoors, Elizabeth A. Laude, Celia J. Emery, Denise Thwaites-Bee, John Fairlie, Arthur E. Oakley, David H. Barer, Gwenda R. Barer. (2004) Hypoxia of sleep apnoea: cardiopulmonary and cerebral changes after intermittent hypoxia in rats. Respiratory Physiology & Neurobiology 140:1, 53-62
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    Robert Wolk, Virend K Somers. (2003) Cardiovascular consequences of obstructive sleep apnea. Clinics in Chest Medicine 24:2, 195-205
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    Kenneth R. Casey, Michael J. Lefor. (2002) Management of the hospitalized patient with sleep disordered breathing. Current Opinion in Pulmonary Medicine 8:6, 511-515
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    Sevag Bananian, Stuart G. Lehrman, George P. Maguire. (2002) Cardiovascular Consequences of Sleep-related Breathing Disorders. Heart Disease 4:5, 296-305
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    Donald S. Silverberg, Arie Oksenberg. (2001) Are sleep-related breathing disorders important contributing factors to the production of essential hypertension?. Current Hypertension Reports 3:3, 209-215
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