Secondary Hypertension: Sleep Disturbances Including Sleep Apnea

Obstructive Sleep Apnea and Hypertension

Obstructive sleep apnea (OSA) and hypertension are common medical conditions which often coexist. Is there is a causal relationship between these two conditions? This question has been repeatedly raised in literature and has remained an area of interest for many years. The association between OSA and hypertension was initially reported by Tilkian et al in 1976 who demonstrated a substantial cyclical elevation in blood pressure with each apneic episode. Systemic hypertension was also noted in one-third of the patients with OSA.

In this chapter we will review the epidemiology of OSA and hypertension; mechanisms by which OSA leads to development and/or progression of hypertension; and the effect of treating OSA on hypertension.

Definition of Obstructive Sleep Apnea

OSA is defined by the occurrence of daytime sleepiness, loud snoring, witnessed breathing interruptions, or awakenings as a result of gasping or choking in the presence of at least five obstructive respiratory events (apneas, hypopneas, or respiratory effort–related arousals) per hour of sleep. The presence of 15 or more obstructive respiratory events per hour of sleep in the absence of sleep-related symptoms is also sufficient for the diagnosis of OSA because of a greater association of this severity of obstruction with important consequences such as increased cardiovascular disease risk.

Obstructive apneas or hypopneas occur when the upper airway dilator muscles fail to maintain the patency of the upper airway and airflow during sleep. Various factors that can increase the risk for developing OSA include altered facial structure, small upper airway lumen, poor upper airway muscle function, respiratory control instability, increased arousal response, small lung volumes, fluid retention, male sex, obesity, advancing age, genetic factors, menopause, and smoking.

Prevalence of Obstructive Sleep Apnea and Hypertension

Sleep apnea occurs in 3% to 7% of adult males and 2% to 5% of adult females in the general population. Peppard et al recently reported the prevalence of OSA of 26% among patients between 30 to 70 years of age. A population-based, age-stratified case control study done in Sweden assessed the prevalence of OSA in men. This study reported that the prevalence of OSA in primary hypertension was 35%. In the Wisconsin Sleep Cohort, the odds ratios for the presence of hypertension at 4-year follow-up was 2.89 with an apnea-hypopnea index (AHI) of 15 or more events per hour compared with those with an AHI of 0. This study demonstrated a dose-response relationship between the severity of OSA and presence of hypertension, independent of the confounding factors. The Sleep Heart Health Study showed similar findings with an increase in prevalence of hypertension with increasing AHI.

Rapid eye movement (REM) sleep is generally associated with a greater propensity for upper airway closure because of inhibition of muscle tone during this stage of sleep. As a result, the likelihood of OSA or worsening of OSA in REM sleep is increased. In addition, REM sleep is also associated with increased sympathetic activity which can contribute to a rise in blood pressure. The Wisconsin Sleep cohort reported a significant dose-relationships between REM AHI and prevalent hypertension. The higher relative odds of prevalent hypertension were most evident with REM AHI 15 or more. In individuals with a non-REM AHI 5 or less, a two-fold increase in REM AHI was associated with 24% higher odds ratio of hypertension. Longitudinal analysis also revealed a significant association between higher REM AHI and the development of hypertension ( p trend = 0.017).

A recent report with a 5-year follow-up from the Sleep Heart Health Study concluded that the association between hypertension and AHI was not significant after adjusting for body mass index (BMI). Similarly, the Vitoria Sleep Cohort also found no association between OSA and incidence of hypertension after adjustment for confounders. It is unclear why there are variations in the results of these studies but these could be accounted by differences in the populations sampled and techniques used to diagnose sleep apnea or AHI cutoff points may account for the variation related to the impact of OSA on prevalent and incident hypertension.

There is a striking association between drug-resistant hypertension and OSA. Prevalence of OSA in patients with drug-resistant hypertension has been reported to be approximately 64% to 83%. Pedrosa et al identified OSA as the most common secondary cause of hypertension in patients with drug-resistant hypertension ( Fig. 16.1 ).

Treatment of OSA with continuous positive airway pressure (CPAP) has been shown to lower blood pressure (BP) in this patient cohort. Similar impact of CPAP on BP was observed in a recent study including patients with resistant and nonresistant hypertension and OSA. These findings support the role of OSA in the pathogenesis of hypertension in these patients ( Fig. 16.2 ).