This prospective cohort study of middle-aged and older adults shows that among participants without hypertension at baseline, sleep-disordered breathing at baseline was positively associated with incidence of hypertension during follow-up; however, this relationship was attenuated and no longer statistically significant after adjustment for BMI. Although not statistically significant, the BMI-adjusted association between a baseline AHI greater than 30 and future hypertension (OR, 1.51; 95% CI, 0.93–2.47) does not exclude the possibility of a modest association of a magnitude consistent with risk estimates from our earlier cross-sectional analysis (2
The results of the key models need to be interpreted within the context of possible mechanisms by which sleep-disordered breathing might cause hypertension. Without adjustment for BMI, there is a clear dose–response relationship between AHI and risk for hypertension (see ). With adjustment for BMI, the dose–response relationship is flattened, and risk estimates are no longer statistically significant. The attenuation of this relationship after adjustment for baseline BMI may indicate that the association between sleep-disordered breathing and hypertension risk is confounded by obesity. Alternatively, this change in the estimated effect with adjustment for BMI is consistent with an underlying causal mechanism in which sleep-disordered breathing raises blood pressure by increasing BMI.
After adjustment for BMI, these results, showing at most a small effect of sleep-disordered breathing on the risk of developing future hypertension, are consistent with previous reports of cross-sectional investigations. Our earlier cross-sectional analysis of SHHS data revealed that participants with an AHI of 30 per hour or greater were more likely to have hypertension than those with an AHI below 1.5 per hour (OR, 1.37; 95% CI, 1.03–1.83; P
for trend = 0.005) even after adjustment for BMI (2
). The current analysis of risk for incident hypertension reveals an estimated BMI-adjusted association of similar magnitude, but the estimate has a wider CI. The greater degree of imprecision partly reflects the smaller number of participants in the longitudinal analysis, which was limited to the 2,470 subjects without baseline hypertension and with available follow-up data. The earlier cross-sectional analysis included 6,132 participants. In the longitudinal analysis, we did not observe an effect modification by age, while the cross-sectional association between sleep-disordered breathing and hypertension, adjusted for BMI, was limited to participants below 60 years of age (17
Our results do not confirm the relationship of sleep-disordered breathing to risk for incident hypertension observed in a previous cohort study of sleep-disordered breathing and hypertension incidence by Peppard and coworkers (9
). In that study, an AHI of 15 per hour or greater was associated with an OR of 3.15 (95% CI, 1.26–7.84) after adjustment for demographic factors and BMI. The relatively wide confidence intervals in the Peppard study reflect the relatively small numbers of subjects with an AHI of 5 to 14.9 (n = 96) or with an AHI 15 or greater (n = 37) in comparison with the SHHS. We repeated our analysis using the same AHI categories as Peppard and colleagues, and subjects with an AHI of 15 per hour or greater had an OR for incident hypertension of 1.07 (95% CI, 0.62–1.85). Although the 95% CIs around the estimated overall OR for SHHS overlap with those of Peppard and colleagues, the upper bound of the 95% CI observed in our study is below the estimate of 3.15 for subjects with an AHI 15 or greater in the Wisconsin study (9
). The Wisconsin study participants (9
) were on average 14 years younger and 1.5 kg/m2
more obese than participants in the SHHS; however, stratified analyses of our data did not reveal significant BMI-adjusted associations among the younger or more obese subjects in our sample. The Wisconsin cohort was recruited from among state employees in one geographical location; by contrast, our study included a diverse population, with all participants in established cohort studies. The differences in study findings might reflect the differing age ranges of the populations, the greater heterogeneity of the SHHS population, the different time of day of blood pressure measurements, or selection factors related to recruitment of the SHHS cohort from existing epidemiologic cohort studies. For example, participants in ongoing cardiovascular disease studies may have increased awareness of cardiovascular health issues and may have modified behaviors that affect risk for hypertension in association with sleep apnea.
Stratified analyses suggested that sleep-disordered breathing may predict future hypertension among women and less obese persons. These potentially significant associations should be interpreted cautiously, however, because they were not tests of a priori hypotheses and because the interactions between AHI and sex and AHI and obesity were not statistically significant. Nonetheless, the findings emphasize the need to further assess whether there are groups at greater risk for hypertension associated with sleep-disordered breathing. There was also a suggestion that sleep-disordered breathing may predict hypertension among persons with excessive daytime sleepiness.
) and human studies (19
) suggest sympathetic nervous system activation caused by hypoxemia (20
) and/or arousal from sleep (21
) as a potential mechanism linking sleep-disordered breathing and hypertension. Animal models of obstructive sleep apnea demonstrate acute increases in blood pressure during episodes of airway obstruction and arousal (22
). In a canine model, intermittent airway occlusion during nocturnal sleep led to increased nighttime and daytime blood pressure (24
). In this experiment, the increased blood pressure returned to baseline over several weeks after cessation of the intermittent airway occlusion. In patients with obstructive sleep apnea, nasal CPAP treatment has been shown to reduce blood pressure and plasma norepinephrine when measured as soon as 14 (25
) or 42 days (26
) after the initiation of treatment. A randomized clinical trial of nasal CPAP therapy in patients with obstructive sleep apnea syndrome revealed that this therapy reduced the ambulatory mean arterial pressure by 2.5 mm Hg (27
). Not all clinical trials of nasal CPAP treatment for sleep apnea have shown that this therapy reduces blood pressure (28
), and those that have revealed beneficial effects have involved patients with more severe degrees of obstructive sleep apnea and daytime sleepiness (28
). These studies of sleep apnea and hypertension appear to conflict with our observation that sleep-disordered breathing is not an independent predictor of hypertension. One possible explanation for this apparent conflict is that animal models and patients requiring CPAP treatment involve more severe degrees of sleep-disordered breathing than that detected in a general population cohort. Another possibility is that persons who are normotensive at baseline despite having sleep-disordered breathing may be relatively resistant to the development of hypertension. That is, sleep-disordered breathing may have a relatively rapid effect to raise blood pressure but relatively little impact on future hypertension risk after excluding persons who are normotensive despite sleep-disordered breathing at baseline.
Participants in the SHHS cohort were recruited from community-based samples, and consequently the distribution of sleep-disordered breathing in this sample is less severe than would be encountered in a clinical sample referred for evaluation of sleep-related symptoms. Thus, our findings cannot necessarily be extrapolated to clinic-based populations with a more severe range of disease. Also, because this cohort was assembled from existing cohort studies, one cannot exclude the possibility that other selection factors make this cohort different from the general population. Another potential limitation of our study is the approximately 5-year follow-up interval, a relatively short period for evaluation of incident hypertension. In addition, in this study as in others, there is a possibility of residual confounding by unmeasured covariates, such as salt intake or physical activity, which could differ between persons with and without sleep-disordered breathing. Finally, although the baseline and second follow-up examination blood pressures were measured with identical technique during early-evening home visits, the blood pressure measurements for most of the participants' first follow-up examination were measured at study clinic visits during the daytime, a setting more similar to a physician's office in which blood pressure would tend to be higher than during an early-evening home visit. Although this might increase the incidence of hypertension at the first follow-up examination compared with the second follow-up examination, this would be a nondifferential effect between subjects with and without sleep-disordered breathing. Our study, like most epidemiology studies with limitations in access to participants dictated by feasibility, did not include the measurement of blood pressure on multiple visits at the time of follow-up, such as clinicians are encouraged to use to when deciding whether to prescribe antihypertensive therapy (29
In summary, among 2,470 middle-aged and older men and women who were free of hypertension at baseline, sleep-disordered breathing measured at baseline was a not a significant independent predictor of incident hypertension after adjusting for BMI. Although our results do not exclude the possibility of a modest relationship between a baseline AHI greater than 30 and future hypertension, our results do not support the finding of a strong association between sleep-disordered breathing and future hypertension reported previously in another prospective cohort study.