Date Published: February 5, 2019
Publisher: Public Library of Science
Author(s): Carolina López-Cano, Ferran Rius, Enric Sánchez, Anna Michela Gaeta, Àngels Betriu, Elvira Fernández, Andree Yeramian, Marta Hernández, Marta Bueno, Liliana Gutiérrez-Carrasquilla, Mireia Dalmases, Albert Lecube, Tatsuo Shimosawa.
Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous disease.
There is considerable evidence that obesity is a causal factor for sleep-disordered breathing (SDB) with more than 50% of patients having a body mass index (BMI) greater than 30 Kg/m2 [1, 2]. Sleep apnea-hypopnea syndrome (SAHS), the most common type of SDB, has been well established as an independent risk factor for some components of the metabolic syndrome, such as hypertension and glucose abnormalities, along with other cardiovascular risk factors [3, 4]. In this regard, early signs of atherosclerosis, such as an increase in carotid intima-media thickness (cIMT), have been reported in patients with SAHS without other cardiovascular diseases . In fact, observational studies have shown that patients with SAHS have an increased risk of death, especially from stroke and myocardial infarction [6, 7]. However, the correction of nocturnal chronic intermittent hypoxia (CIH) using continuous positive airway pressure (CPAP) has not been associated with a decreased risk of cardiovascular outcomes or death for patients with SAHS [8, 9]. These data increase the need for studies that describe better all mechanisms by which intermittent hypoxia damages the endothelial wall.
The main clinical features and metabolic data of the study population are presented in Table 1. A total of 40 patients (72.7%) were diagnosed with some degree of SAHS: 14 (35.0%) with mild, 6 (15.0%) with moderate and 20 (50.0%) with severe SAHS. In addition to a higher daytime sleepiness, subjects with SAHS were older and presented a higher prevalence of type 2 diabetes than patients without SAHS.
To the best of our knowledge, this is the first study to establish a relationship between repetitive nocturnal upper airway obstructions and adventitial VV density, one of the earlier steps in the development of atheromatous disease. We also provide evidence that the CT90% correlates with VV density in the univariate analysis. However, this late characterization of the severity of nocturnal hypoxemia disappears as an independent variable of the onset of atheromatous disease in the multivariate regression analysis.