Stanford type B aortic dissection (TBAD) is a catastrophic vascular disease with high mortality and poor prognosis (1, 2) that is characterized by the blood passing through the first one-third of the external media in the aortic wall (3). The annual incidence of AD is estimated to be 2.6–3.6 per 100,000 adults worldwide (4–6). Most patients die within the first week, and ~25–50% of patients who survive the acute phase require surgery during the chronic phase (7, 8). The overall in-hospital mortality of TBAD was reported to be 13%. Despite the increase in the use of thoracic endovascular aortic repair (TEVAR) and the application of hybrid surgery, in-hospital mortality has not changed significantly in the past 20 years (9). Compared with medical therapy, TEVAR has proven to be more effective in improving aortic remodeling and long-term survival (10). However, neither TEVAR nor medical therapy can fully prevent aortic wall degeneration or disease progression. Approximately 35% of patients treated with TEVAR and 65% of patients receiving medical therapy develop late aortic events (LAEs) within 5 years (11, 12).

The occurrence of LAEs severely affects the prognosis of patients with TBAD (13, 14). In most studies, LAEs were defined as the development of aortic expansion (>55 mm), rapid dilatation of the dissected aorta (>10 mm per 10–12 mo), new dissection, malperfusion, rupture, or impending rupture and aortic-related death after patients were discharged following surgery or medical treatment (10, 15–19). Previous studies have demonstrated that several predictors could be used to identify TBAD patients at high risk for aortic expansion during follow-up and predict the individual risk of LAEs. Radiologic predictors included an initial maximum diameter of the aorta ≥40 mm (10, 15, 16, 20–23), a proximal descending thoracic aortic false lumen (FL) diameter ≥22 mm (24), a partially thrombosed FL (17, 25–28), a large entry tear >10 mm (10), a fusiform index ≥0.64 (29), and ulcer-like projections (30, 31). Clinical predictors included younger age (<60 years) (32, 33), heart rate ≥60/min (34), and Marfan syndrome (35). Laboratory findings involved fibrinogen-fibrin degradation product levels ≥20 mg/ml at admission (36) and peak C-reactive protein levels ≥9.61 mg/dl (37). Identification of these predictors might benefit patients through early TEVAR or closer follow-up and contribute to the development of individualized treatment strategies (14, 19, 38).

Obstructive sleep apnoea (OSA) is characterized by recurrent upper airway obstruction with interruption of airflow and persistence of inspiratory effort during sleep (39) and is one of the most common risk factors for cardiovascular diseases (40). The prevalence of OSA in TBAD is 66.2–81.7% (41–43), which is dramatically higher than the reported incidence of 9–38% in the general population (44, 45). The potential correlation between OSA and TBAD was first reported by Sampol et al. (46). An increasing number of studies have shown that OSA is an important cause of AD (42, 47–49).

However, few studies have evaluated the effects of OSA on vascular changes in TBAD patients. The aim of this study was to explore the effect of OSA on aortic morphological changes in TBAD patients and its relation to LAEs.

To our knowledge, this is the first study to find that TBAD patients with OSA have a higher risk of aortic dilatation and that some of the imaging differences are related to LAEs.

This case-control study included 143 TBAD patients, and the prevalence of OSA was as high as 64.3%. In 2003, Sampol et al. (46) first found a correlation between OSA and aortic dissection, and an increasing number of studies have shown that OSA is an independent risk factor for AD, especially for TBAD patients with moderate to severe OSA (47–49). Previous studies have indicated that OSA may lead to dilatation of the aorta, including the aortic root (52–55), thoracic aorta (56) and abdominal aorta (57); other studies have come to the opposite conclusion (58), and most of the OSA patients in these studies had no history of cardiovascular disease. However, the effect of OSA on vascular morphology changes in TBAD has rarely been reported. As seen in our results, the main change in the aorta for TBAD patients with OSA is aortic dilatation, which also includes enlargement of the FL. The mechanism of aortic dilatation and the development of TBAD induced by OSA has not been fully elucidated. The possible mechanism includes changes in intrathoracic pressure, meaning that the increase in pleural negative pressure can lead to mechanical stretch of the aorta (54, 55, 59–61), which further leads to the expansion of the aortic root, thoracic aorta and thoracic FL; patients with frequent intermittent hypoxia leading to oxidative stress and increases in sympathetic activity exhibit an increase in blood pressure due to the activation of the renin–angiotensin–aldosterone system (59, 60, 62). The state of chronic intermittent hypoxemia and the altered microenvironment in OSA patients, such as the increase in IL-6 levels and reduction in TGF-β levels, could damage the function of endothelial cells and promote a Th17/Treg imbalance, which leads to a reduction in the production of endothelium-dependent vasodilator substances and contributes to vascular dysfunction and stimulation of systemic inflammation (63–67).

Another important finding in our study showed that vascular changes in TBAD patients with OSA were related to the predictors of LAEs, which included an initial aortic diameter ≥40 mm, a FL diameter of the proximal descending thoracic aortic ≥22 mm, and a partially thrombosed FL. Previous studies have proven that the postdischarge mortality of patients with these factors will be substantially increased (10, 15, 20, 21, 23–25). An aortic diameter >40 mm and a FL diameter >22 mm have been suggested as high-risk features by SVS/STS research (50). Our results indicate that for patients with OSA, the risk of these imaging signs was several times higher than that of non-OSA patients. Univariate analysis revealed that the risk of aortic diameter dilation larger than 40 mm in OSA patients was ~4.6 times higher than that in non-OSA patients when we adjusted for age, sex, BMI, and hypertension in the multivariate analysis. In addition, age is an independent risk factor for aortic enlargement in TBAD patients, which suggests that the degree of aortic dilatation is more obvious in elderly TBAD patients with OSA.

In addition, we observed the effect of OSA on the size and thrombosis of the FL. Song et al. (24) revealed that patients with an FL diameter of the initial upper descending thoracic aorta ≥22 mm showed a higher rate of aortic adverse events such as aneurysmal dilation or aortic-related death. From the results, the risk of a proximal descending aortic FL larger than 22 mm was ~2.5 times higher in OSA patients than in non-OSA patients after adjusting for other relevant factors (model 2). This suggests that OSA is an important factor related to the prognosis of TBAD patients. Our study shows that OSA is an important factor leading to an increased risk of partial FL thrombosis. Wang et al. (41) came to the same conclusion. The results showed that the risk of FL thrombosis in patients with OSA is increased by ~2.5-fold and that the proportion of FL thrombosis increases with the severity of OSA. Patients with OSA are in a state of chronic intermittent hypoxemia, which may lead to endothelial cell damage and the release of inflammatory factors, causing hypercoagulability of blood. This process increases the chance of FL thrombosis and is accompanied by intrathoracic pressure fluctuations, which leads to changes in aortic transmural pressure and mechanical stretching of the aorta. Furthermore, it may interfere with thrombosis of the FL, and both processes eventually cause a higher probability of partial thrombosis.

We classified OSA according to its severity as mild, moderate and severe. As seen in our results, moderate OSA patients showed a higher OR than severe and mild OSA patients in the logistic regression analyses on an aortic diameter ≥40 mm. This may be due to the sampling error caused by the relatively small sample size after grouping or other unknown factors in moderate OSA. Most of the vascular morphology differences were reflected in the patients with moderate and severe OSA, including the aortic diameter at onset, the maximum diameter of the descending aorta, the diameter of the distal aortic arch, and the maximum diameter of the FL. Moderate to severe OSA has a significant effect on morphological changes in the aorta. Furthermore, TBAD patients with moderate to severe OSA may have a worse prognosis.

We also measured other vascular morphological parameters correlated with prognosis that were reported by previous studies, including the fusiform index (29), but there was no significant difference between OSA and non-OSA in TBAD patients. This is because the fusiform index was defined to express the dilatation degree of the descending aorta, which is a method used to describe the morphological changes in the aorta by local dilation. However, our study found that patients with OSA tend to present dilation of the whole aorta, which may explain why there was no significant difference in the degree of local expansion between OSA and non-OSA patients. We used the SVS/STS classification system to describe the extent of FL involvement. There was no significant difference between OSA and non-OSA, which shows that although OSA can lead to enlargement of the FL, it cannot lead to extension of the FL. The SVS/STS classification system also provides a way for us to further study the area of dissection involved.

From the blood gas analysis results, nearly half of the patients had a decrease in pO₂, of which 7 patients reached type I respiratory failure. We considered that this is an acute manifestation rather than a chronic progressive condition because when taking the patients' medical history, we found that almost all patients with decreased pO₂ complained of dyspnoea and sweating caused by pain, and when we rechecked the blood gas before discharge, it had returned to the normal range.

The strengths of our study include that this is the first study to explore the effect of OSA on vascular morphological changes in TBAD patients and the first to identify OSA as an independent risk factor related to LAEs. To comprehensively and systematically assess changes in the aorta, we included up to nine indicators, including not only aortic dilatation, FL status, and imaging signs with LAEs but also the dissection process-involved zones according to the SVS/STS classification system. We first found that the effect of OSA on the aorta was mainly manifested as aortic dilation rather than an increase in the involved zones. There are still some limitations to our study, which include the need for further investigations in animal experiments to reveal the molecular mechanism of the occurrence and development of TBAD caused by OSA. Further studies on the prognosis of TBAD patients with OSA are also needed.

TBAD patients with OSA, especially moderate to severe OSA, have vascular morphological changes in the different regions of the aorta that mainly manifest as aortic dilation. OSA was an independent risk factor for a maximum aortic diameter at onset ≥40 mm, an FL diameter in the proximal descending aorta ≥22 mm, and a partially thrombosed FL. The imaging differences related to LAEs suggest that OSA is an important factor that affects the prognosis of TBAD patients.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

The studies involving human participants were reviewed and approved by the Medical Research Ethics Committee of the First Hospital of China Medical University. The patients/participants provided their written informed consent to participate in this study.

JiawZ and SX first conceived this article, and designed the research method of this study. JiawZ was responsible for data analysis and writing the manuscript, collected the medical records, and imaging data as well as drafted the manuscript. ZZ and YY also collected the medical records and performed sleep monitoring. LW and HW drafted the discussion. LF and BZ gave the help of statistical analysis. WW and JianZ participated in the design of the study and analyzed sleep monitoring data. SX carried out critical revision and finalization of the manuscript. All authors approved the final manuscript.

This work was supported by the National Natural and Science Foundation of China (Grant Numbers: 81974049).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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