Central sleep apnea indicates autonomic dysfunction in asymptomatic carotid stenosis: a potential marker of cerebrovascular and cardiovascular risk

Abstract

Study objectives: Arteriosclerosis related stenosis in the carotid bulb causes autonomic imbalance, likely due to carotid chemoreceptor and baroreceptor dysfunction. The latter are associated with increased cerebrovascular and cardiovascular mortality. Chemoreceptor and baroreceptor dysfunction is also involved in the origin of central sleep apnea syndrome (CSA) in different clinical entities. We hypothesized that CSA is associated with stenosis of the internal carotid artery (ICA). The mechanism of this association is an autonomic imbalance induced by stenosis-mediated chemoreceptor and baroreceptor dysfunction.

Design: Cross-sectional prospective study.

Setting: University-based tertiary referral sleep clinic and research center.

Patients: Fifty-nine patients with various degrees of asymptomatic extracranial ICA (elCA) (n = 49) and intracranial ICA (ilCA) stenosis (n = 10) were investigated.

Interventions: Polysomnography to detect CSA and analysis of spontaneous heart rate variability (HRV) to detect autonomic imbalance.

Measurements and results: CSA occurred in 39% of the patients with elCA stenosis but was absent in patients with ilCA stenosis. CSA was present in patients with severe elCA stenosis of > or = 70% on one side. Independent predictors for CSA were severity of stenosis, asymmetric distribution of stenosis between both elCA and autonomic imbalance, namely a decrease of parasympathetic tone. The specific constellation of HRV-parameters indicated increased chemoreceptor sensitivity and impaired baroreflex sensitivity.

Conclusions: CSA indicates autonomic dysfunction in patients with asymptomatic elCA stenosis. Detection of CSA may help to identify asymptomatic patients with an increased risk of cerebrovascular or cardiovascular events who particularly benefit from carotid revascularization.

Figure 1

Hypothetic mechanisms for the development of CSA and autonomic dysfunction in eICA stenosis.

Figure 2

Relationship between the severity of eICA arteriosclerosis/stenosis and CSA. Circles reflect individual patients.

Figure 3

Scheme of the proposed chemoreflex and baroreflex dysfunction in eICA stenosis. The eICA stenosis induces carotid body ischemia that leads to increased peripheral chemoreflex sensitivity which induces sympathetic overactivity (chemoreflex–broken lines). In parallel, stenosis mediated reduced stretch sensitivity of the carotid arterial baroreceptors decreases baroreflex sensitivity (baroreflex–continuous line) resulting in a loss of parasympathetic tone (baroreflex–continuous lines). The decreased baroreflex sensitivity also reduces the tonic baroreflex mediated inhibition of the sympathetic tone and the chemoreflex in the solitary tract nucleus. Consequently, the decreased baroreflex potentiates chemoreflex sensitivity at the brainstem level in addition to the increased stenosis mediated peripheral chemoreflex sensitivity. The increased peripheral and central chemoreflex sensitivity induces respiratory instability (CSA).