BALTIMORE-- Snoring, the most common symptom of sleep apnea, has been linked to hypertension in several studies--but these generally have included only small numbers of subjects. Furthermore, only some of these studies have shown an independent association between snoring and hypertension; in others, the association appeared to be secondary to age, sex, or obesity. Thus, the relationship between sleep-disordered breathing (SDB) and hypertension has remained unclear.

However, a recent large, cross-sectional study indicates that sleep apnea is independently associated with systemic hypertension in middle-aged and older persons.[1] Even stronger evidence of a link was obtained in a new prospective study.[2]

The cross-sectional study is part of the Sleep Heart Health Study (SHHS), sponsored by the National Heart, Lung, and Blood Institute. SHHS is a multicenter examination of the cardiovascular consequences of sleep apnea in participants recruited from ongoing population-based cohort studies. The team conducting this study was led by F. Javier Nieto, MD, PhD, an associate professor in the department of epidemiology at Johns Hopkins School of Hygiene and Public Health in Baltimore. They analyzed data on more than 6,000 participants, thereby conducting the largest cross-sectional study to date of the association between SDB and hypertension in apparently healthy middle-aged and older adults.

The prospective study was performed by Paul E. Peppard, PhD, and colleagues from the department of preventive medicine at the University of Wisconsin School of Medicine in Madison. They followed 709 subjects from the Wisconsin Sleep Cohort Study, a population-based, longitudinal study of the natural history of SDB in adults.

A DIRECT CORRELATION

Nieto et al assessed participants' breathing at home using a portable polysomnography monitor. During the home visit, blood pressure and anthropometric measurements were obtained. In addition, participants answered a self-administered questionnaire on snoring history, sleep apnea awareness and treatment, and sleepiness. Hypertension was defined as a blood pressure of 140/90 mm Hg or higher. The presence of SDB was assessed objectively using the apnea-hypopnea index (AHI), which is the average number of apneic or hypopneic episodes per hour of sleep; the arousal index, which is the average number of arousals per hour of sleep; and the percentage of sleep time during which oxygen saturation is below 90%. Self-reports of snoring were considered to be only indirect evidence of SDB.

As Figure 1 demonstrates, the likelihood of hypertension rose as the AHI increased. Compared with subjects who had an AHI below 1.5, those with an AHI of 30 or more had a 37% increase in the risk of hypertension. The likelihood of hypertension was also directly associated with the amount of sleep time during which oxygen saturation was below 90%.

Not surprisingly, these objective measurements of SDB were strongly associated with body habitus. However, even after the data were reanalyzed to control for body mass index, neck circumference, waist-to-hip ratio, alcohol use, and smoking status, the association held between SDB and hypertension. The association was also independent of sex, age, or ethnicity.

In contrast, subjects' self-reports of snoring showed little or no association with hypertension. This finding could explain the inconsistent results in previous studies that used snoring as a surrogate for SDB, Nieto et al noted. These investigators found only a weak link between the arousal index and SDB; but, they suggested, this may be due to the fact that subjects often move about when they are aroused during sleep; thus, subjects with frequent arousals may be more likely to have unreliable polysomnographic data.

PROSPECTIVE EVIDENCE

Additional support for a link between SDB and hypertension comes from the study by Peppard et al. These researchers were able to prospectively follow 525 participants for four years and an additional 184 subjects for eight years. All subjects underwent overnight polysomnography at baseline, and the AHI was used to identify SDB. The subjects were later reexamined to determine how many had hypertension at follow-up. Thus, this study differs from the one by Nieto et al in that it was designed to determine not only which participants had hypertension at baseline, but also which ones developed hypertension later on.

As Figure 2 illustrates, Peppard et al found that the baseline AHI was a strong predictor of hypertension at follow-up. The risk of hypertension at follow-up was almost three times higher in those with a baseline AHI of 15 or more than in those with an AHI of 0.

As in the other study, there was a strong association between the baseline AHI and body habitus. However, the link between SDB and hypertension remained significant even after the analysis was controlled for body mass index, neck and waist circumference, alcohol use, smoking status, age, and sex.

Sleep apnea has been reported to occur in about 30% of hypertensive subjects. Treatment of apnea often improves blood pressure control and inadequate management of apnea has been shown to increase cardiovascular mortality. But whether SDB contributes to the onset of hypertension is still unclear. Although researchers in both studies controlled for body mass index and other anthropometric measurements, it is possible that obesity is the underlying cause of both disorders and that the association between them is only coincidental.

Nieto et al acknowledged that their study does not prove a causal connection between SDB and hypertension. However, the researchers believe that their results support such a hypothesis, and they offered several explanations for how this may occur:

• Intermittent negative intrathoracic pressures during apneic episodes may lead to hemodynamic disturbances.
• Recurrent episodes of hypoxemia and hypercapnia result in increased sympathetic activity and abnormal activation of arterial chemoreceptors.
• Repeated arousals during sleep may also increase sympathetic activity.

The study by Peppard et al provides stronger evidence for a causal link, given that it found a dose-response relationship between SDB at baseline and the presence of hypertension at follow-up. In addition, these investigators were unable to find any evidence of a threshold AHI value--a level below which SDB was not associated with hypertension.

Peppard et al suggested that the connection between SDB, obesity, and hypertension may be even more complex than is often thought, because there is evidence that SDB can lead to obesity, just as obesity can lead to SDB. By better understanding the interplay among these three variables, researchers may be able to develop more effective methods for preventing and treating them.

--Margaret A. Inman

References
1. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. JAMA. 2000:283:1829-1836.
2. 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.