Which is the most important factor in the relationship between cardiovascular events and obstructive sleep apnea: Blood pressure level, blood pressure variability or baroreflex sensitivity?

Dear Editor,

I read with great interest the article by Kuwabara et al1 The authors conducted a study to explore the association between nocturnal blood pressure (BP) parameters obtained by nocturnal BP monitoring and simultaneously examined polysomnography‐derived sleep parameters in 116 patients with obstructive sleep apnea (OSA). I would like to share my opinions about the study.

Obstructive sleep apnea is characterized by collapse of the pharyngeal airway during sleep, oxyhemoglobin desaturation, persistent inspiratory efforts against the occluded airway, excessive daytime drowsiness, followed by termination by arousal from sleep.

Obstructive sleep apnea is independently associated with cardiovascular disease (CVD), such as hypertension, acute coronary syndrome, stroke, cardiac arrhythmia, and heart failure. The main pathway is chronic intermittent hypoxia (CIH) and the most important pathophysiological consequence is elevated sympathetic activity (local and systematic). However, the inchoate cardiovascular changes that precede CIH‐induced hypertension are not completely understood.

Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA, and that OSA has been identified as the most common secondary contributing factor for the development and worsening of hypertension. In hypertensive patients, the risk of developing cardiovascular events and complications depends not only on the magnitude of the BP elevation, but also on the presence of associated cardiovascular risk factors, concomitant disease, and target organ damage.

The cardiovascular system exhibits significant circadian system, which is an important underlying mechanism that coordinates these rhythmic processes for the health. The nocturnal BP surge and disturbed circadian rhythms during sleep in OSA patients could be a strong trigger of cardiovascular events.2, 3 OSA could lead to an increase in not only the nocturnal BP level but also nocturnal BP variability, both of which may add to a high risk for cardiovascular events.4 However, dysregulation of homeostatic cardiovascular mechanisms and BP regulatory control when rhythms are disturbed have not been clearly understood.

It has been proposed that desaturation of oxygen during an apnea event is the trigger for BP fluctuation. BP fluctuations over time physiologically result from the complex interaction between environmental stimulation, the severity of OSA, different stages of sleep, and cardiovascular control mechanisms. In hypertension, BP variability increases with increasing BP levels, and evidence is available that its magnitude correlates closely with target organ damage and with the incidence of cardiovascular events, independent of absolute BP levels.

Recently studies indicate that besides BP, BP variability, and baroreflex sensitivity maybe important factors determining organ damage in hypertension. Thus, reduction in BP variability might represent a new strategy for the treatment of hypertension. Further study should be designed to pay more attention to the elevated BP variability, not only BP level in patients with OSA.

The renin‐angiotensin system (RAS) and inflammation may play a decisive role in hypertensive end‐organ damage including cardiac hypertrophy and vascular remodeling. It is the tissue RAS, rather the circulating RAS and inflammatory factors, that contributed to hypertensive cardiovascular hypertrophy. Statistically, cardiac hypertrophy was mainly determined by diastolic BP, BP variability, and the cardiac angiotensin‐converting enzyme gene expression, and aortic hypertrophy was mainly correlated with baroreflex sensitivity.

The differential oxygen decrease between eye movement (REM) sleep and non‐REM (NREM) sleep is likely due to the differentially occurring sleep breathing events in each sleep stage according to the severity of OSA. It is not known whether obstructive events during REM sleep have a different metabolic impact compared with those during NREM sleep. Many pathophysiological changes may be the result of certain events or the cause of further new sleep events.

Weight management, BP control, and smoking cessation may help prevent the development of CVD associated with OSA. Endurance training attenuates chemoreflex sensitization to CIH, which may partially explain the beneficial effects of exercise training in patients with cardiovascular disease. Continuos positive airway pressure can significantly decrease BP, especially if compliance to treatment is good.5

CONFLICT OF INTEREST

The authors have no conflict of interests to declare.