Review articleCardiovascular variability characteristics in obstructive sleep apnea
Introduction
Obstructive sleep apnea (OSA) has been linked to cardiovascular morbidity and mortality in several epidemiological and clinical studies Kales et al., 1984, Young et al., 1997, Hung et al., 1990, Dyken et al., 1996, Bliwise et al., 1988, He et al., 1988. A recent prospective study by Peppard et al. (2000) have shown a dose–response association between sleep-disordered breathing at baseline and the presence of de novo hypertension 4 years later that was independent of confounding factors. These findings strongly indicate that OSA may play a causal role in development of hypertension. The mechanisms underlying the link between OSA and cardiovascular disease are not completely established. However, there is increasing evidence that autonomic mechanisms are implicated. Our understanding of pathophysiology in sleep apnea has been recently advanced by applications of measurements of heart-rate variability and of direct intraneural measurements of sympathetic traffic to muscle blood vessels.
We will review, first, autonomic function during sleep in patients with OSA. Second, we will describe abnormalities in autonomic cardiovascular regulation in wakefulness in patients with OSA. Last, we will discuss the potential mechanisms underlying altered cardiovascular variability in patients with sleep apnea.
Section snippets
Sympathetic and hemodynamic responses to obstructive sleep apnea
Responses to sleep in normal individuals should to be taken into account when evaluating the responses to sleep in OSA. Normal sleep is associated with distinct alterations in blood pressure and heart rate. These alterations are dependent upon sleep stage and appear to be mediated primarily by changes in autonomic circulatory control (Somers et al., 1992). During non-REM sleep, there is a reduction in heart rate, blood pressure and sympathetic nerve traffic. This overall inhibition of the
Autonomic function in wakefulness in patients with sleep apnea
Several studies have shown that patients with sleep apnea have very high levels of sympathetic activity even during wakefulness when breathing patterns are normal and no evidence of hypoxia or hypercapnia is apparent (Fig. 1) Carlson et al., 1993, Somers et al., 1995, Narkiewicz et al., 1998a. This is true whether these patients are newly diagnosed, never treated sleep apneic patients on no medications, or whether they are on antihypertensive therapy.
Time and frequency measures of
Mechanisms underlying altered cardiovascular variability in patients with sleep apnea
Possible mechanisms underlying the derangement in neural control in sleep apnea include abnormalities in chemoreflex function. The arterial chemoreceptors may exert important influences on neural circulatory control even during normoxia (Trzebski, 1992). Elimination of the influences of arterial chemoreceptors using 100% oxygen in a double-blind study showed that in patients with OSA, suppression of the chemoreflexes slowed heart rate and decreased MSNA (Fig. 4) (Narkiewicz et al., 1998b).
Conclusions
Abnormalities in cardiovascular variability are evident in sleep apnea even in the absence of overt cardiovascular disease, and may be linked to the severity of OSA. These abnormalities in cardiovascular variability may precede, and conceivably predispose to, subsequent clinically significant cardiac and vascular dysfunction in OSA patients.
Acknowledgments
Dr. Narkiewicz was a recipient of a Fogarty Fellowship (NIH 3F05 TW05200) and a Perkins Memorial Award from the American Physiological Society. Dr. Somers is an Established Investigator of the American Heart Association and is also supported by NIH HL 61560, HL 65176 and M01-RR00585. The authors also acknowledge the support of NIH FIRCA RO3 TWO 1148, and are grateful to their colleagues who contributed to the studies described in this review.
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