The Role of Obesity and Obstructive Sleep Apnea in the Pathogenesis and Treatment of Resistant Hypertension

The incidence of resistant hypertension, obesity, and obstructive sleep apnea (OSA), three highly prevalent conditions in the United States, is rising. Approximately one in three adults in the US has hypertension, and a significant proportion of these individuals have hypertension that is difficult to treat, or resistant. Obesity and OSA are well-established risk factors for resistant hypertension, a condition that portends significant cardiovascular risk. Awareness of the various mechanisms by which obesity and OSA impact systemic blood pressure is essential to better understand how best to effectively care for patients with resistant hypertension. In this review, we discuss the clinical and pathophysiologic associations between obesity, OSA, and resistant hypertension. Furthermore, we will explore the effect of continuous positive airway pressure therapy (CPAP) and other therapeutic interventions on blood pressure control in patients with resistant hypertension. Key Points Obesity, obstructive sleep apnea, and resistant hypertension are highly prevalent conditions, with increasing overall incidence [1-3]. Both obesity and obstructive sleep apnea are independent risk factors for the development of resistant hypertension. OSA is characterized by a physiologic cascade of collapse of the upper airway, which can lead to intermittent hypoxia, hypercapnia, significant negative intra-thoracic pressure, and increased SNS output. Intermittent hypoxia leads to activation of the endothelin system [17, 18, 19.], which can lead to the development of resistant hypertension. Intermittent hypoxia can lead to the over activation of the SNS, which can also contribute to the development of resistant hypertension [20, 21]. OSA leads to state of elevated adrenergic tone, which in turn may contribute to resistant hypertension [25-27]. OSA patients have a higher incidence of "non-dipping" of nocturnal systolic blood pressure, a marker of increased adrenergic tone. This potentially represents a risk factor for hypertensive end organ disease [31, 32]. The prevalence of OSA is significantly higher in patients predisposed to fluid accumulation: including kidney disease, heart failure and resistant hypertension [33]. Interventions (such as the daytime use of compression stocking) which reduce daytime lower extremity fluid accumulation can significantly reduce the severity of OSA, particularly in patients with comorbid resistant hypertension [35, 36]. CPAP therapy can significantly reduce blood pressure in patients with comorbid hypertension and OSA. The treatment effect is most pronounced in those with resistant hypertension and OSA [16.., 38-42].