When Is CPAP an Antihypertensive in Sleep Apnea Patients?

The data demonstrating an association between sleep disordered breathing (SDB) and hypertension continue to accrue. Several population-based¹ and clinic-based,² longitudinal³ and cross-sectional,⁴ prospective³ and retrospective studies demonstrate increased incidence and prevalence of hypertension in patients with sleep apnea.⁵ However, the studies on effect of SDB therapy on hypertension have been far from conclusive. Some therapeutic trials reveal minimal or no effect⁶ while others reveal amelioration in most or all subjects with obstructive sleep apnea (OSA) after continuous positive airway pressure (CPAP) therapy.⁷ One study revealed decrease in blood pressure not only with therapeutic CPAP, but also with placebo (CPAP administered at ineffective pressure).⁸ Another study showed improvement in hypertension with CPAP use only in sleep apnea patients who have daytime sleepiness.⁹ Thus, whether, and in which subgroup of OSA patients, CPAP decreases blood pressure is still unclear.

In this issue of the Journal, Dernaika et al.¹⁰ report on the effect of CPAP therapy in OSA patients with hypertension. The authors found that the OSA patients with blood pressure resistant to antihypertensive medications had a significant decrease in blood pressure after CPAP therapy for approximately 1 year, permitting a de-escalation of antihypertensive medication therapy in this group. In contrast, in the group of OSA patients in whom blood pressure was controlled with antihypertensives, CPAP did not produce a further drop in the blood pressure. Multivariate regression revealed that hypertension severity at baseline (OR 5.4, 95% CI 2.3–8.9) and diuretic therapy (OR 3.2, 95% CI 1.8–6.1) predicted a 10% or greater decrease in mean arterial pressure at 12 months.

These findings lend further credence to the association between sleep apnea and hypertension and suggest an ameliorative effect of CPAP in patients with severe hypertension. The current work also suggests that studies evaluating change in blood pressure in sleep apnea patients should have at least a 6-month follow up to demonstrate an effect. But what explains the apparent dichotomy between the ameliorative effect seen in patients with resistant hypertension, but not in those with controlled hypertension? Hypertension has several etiologies, only some of which are clearly understood. SDB can worsen hypertension through several diverse pathways.¹¹ The apneas/ hypopneas and associated hypoxemia contribute to increased sympathetic activity, alter rennin-angiotensin pathway, impede xanthine oxidoreductase production, and cause endothelial dysfunction.¹² Endothelial dysfunction, in turn, leads to a cascade of events which promote hypertension and atherosclerosis. Antihypertensive medications modify several of these pathways and restore endothelial integrity. In some cases, SDB may possibly either overwhelm these salutary effects or act through a different mechanism not amenable to the effects of the antihypertensives. CPAP therapy improves endothelial function,¹³ decreases the abnormally increased levels of circulating apoptotic endothelial cells,¹⁴ attenuates free radical production from neutrophils and monocytes,¹⁵ reduces the levels of C-reactive protein (CRP), a marker of vascular inflammation,¹⁶ increases vasodilator levels,¹⁷ and mediates a decline in vasoconstrictor levels¹⁸ in patients with sleep apnea. It is conceivable that complex pathways, yet to be clearly elucidated, mediate some of the cardiovascular effects of sleep apnea and cause resistant hypertension; and CPAP therapy alleviates these effects through a mechanism distinct from the medications.

Despite advancing our knowledge of the role of CPAP in ameliorating resistant hypertension in OSA patient, the current work expectedly suffers from inherent drawbacks of the retrospective trials. Confounding factors such as physical activity and dietary habits were not evaluated. Furthermore, no data were provided to clarify the mechanistic pathways linking SDB to resistant hypertension. Also, although CPAP lowers BP, whether this translated into decreased risk of cardiovascular events independent of any increased physical activity and/ or weight loss after CPAP therapy is not known. Finally, the patient population in this study, as in most Veterans Affairs hospitals, was overwhelmingly male.

The findings from this study leave a few unanswered questions. The authors did not find the baseline apnea hypopnea index or CPAP compliance hours to be predictors of decrease in mean arterial pressure. It is possible that baseline hypoxemia rather than the severity of disease in terms of apnea hypopnea index may be a better predictor of improvement in hypertension. Indeed, nocturnal oxygen desaturation has been associated with hypertension¹⁹ and the severity of nocturnal hypoxemia correlates with daytime urinary norepinephrine levels in sleep apnea patients.²⁰ CPAP usage hours may not have been a predictor because of the fairly similar average use in all subjects. It is possible that even in patients with resistant hypertension, lower CPAP use may have produced less robust decrease in blood pressure.

However, despite the limitations of this study, it demonstrates that sleep apnea confers additive cardiovascular burden and CPAP can ameliorate this burden. Further prospective studies with substantive sample sizes and designed to control for various confounders will facilitate firmly establishing this link and provide a clear evidence of the effect of CPAP on blood pressure in patients with sleep apnea. In view of this and similar studies, it is imperative from the clinical perspective that diagnostic testing be conducted to evaluate SDB in patients with resistant hypertension, and treating the former, if present.

DISCLOSURE STATEMENT

The authors have indicated no financial conflicts of interest.