Background
Optimal medical therapy (OMT) is the recommended treatment for patients presenting with uncomplicated type B aortic dissection (uTBAD). Although OMT is associated with excellent short-term prognosis, the long-term therapeutic effectiveness with OMT alone is unsatisfactory [
1‐
3]. Emerging evidence has demonstrated favorable outcomes when thoracic endovascular aortic repair (TEVAR) is used to treat uTBAD, as it can promote aortic remodeling and prevent aortic dissection progression [
4,
5]. Thus, it is essential to select those patients with uTBAD who would benefit from early endovascular therapy.
Multiple radiographic predictors of late aortic events have been identified, such as a large aortic diameter and patent or partially thrombosed false lumen [
6]. However, few studies have focused on laboratory biomarkers that predict late aortic events. Inflammation is involved in several diseases, including chronic heart failure, cardiovascular diseases and aortic dissection (AD) [
7,
8]. A high degree of inflammation predicts poor outcomes in AD [
9].
Recently, the systemic immune-inflammation index (SII) was developed to account for the inflammatory and immune statuses of patients. A high SII is related to poor outcomes in patients with cardiovascular disease [
10,
11]. For example, a high SII can predict the severity of stable coronary artery and ischemic stroke [
12,
13]. However, few studies have examined the usefulness of SII in patients with acute uTBAD undergoing OMT. In this study, we aimed to determine the predictive role of SII in patients with acute uTBAD undergoing OMT.
Discussion
There were three main findings of this study. First, among patients with acute uTBAD managed with OMT, there were significant rates of follow-up mortality and need for intervention. Second, a high SII was associated with an increased risk of mortality during the follow-up period. Third, multivariable cox analyses showed that a large MAD, diabetes and high SII were independent risk factors for composite outcomes. Our findings showed that SII can predict the follow-up outcomes in patients with acute uTBAD undergoing OMT. Therefore, SII could be considered a useful and relatively simple tool for stratification of the risk of poor outcomes and for facilitating management decisions.
Aortic dissection is a life-threatening disease caused by a tear in the intimal layer of the aorta, leading to separation between the intimal and medial layers of the aortic wall and false lumen formation [
16]. It is reported that mechanical stretch-induced endoplasmic reticulum stress promotes smooth muscle cell apoptosis, inflammation, and degeneration, providing insight into thoracic aortic aneurysm/dissection formation and progression [
17]. Antihypertensive therapy is the preferred medical treatment for AD, and timely endovascular therapy with a stent graft may be indicated for patients who have or may be at risk for complications [
14]. Therefore, it is essential to identify patients who are at increased risk of future aortic events to determine the optimal candidates for prophylactic endografts. Previous investigations into the radiographic risk factors of poor outcomes in AD patients have focused on two characteristics of TBAD anatomy: aortic diameter and false lumen. Multiple studies have identified that an aortic diameter > 40 mm at the time of presentation is a risk factor for subsequent poor outcomes [
18‐
20], which is similar to our results.
TBAD is associated with inflammation, and a high degree of inflammation predicts poor outcomes in AD [
9]. Although certain inflammatory factors are related to a poor prognosis in AD, these markers alone may not be particularly useful. Thus, a multi-biomarker strategy that combines biomarkers across the pathobiological axes of inflammation may provide incrementally useful prognostic information for predicting aortic related adverse events. PET/CT can assess inflammation in blood vessels and a high uptake [
18] F-FDG on PET/CT is demonstrated to correlate with an increased risk of AD rupture and progression [
9]. However, it is time-consuming, inconvenient and expensive. Moreover, some hospitals are not equipped with PET equipment. These factors limit the use of PET in patients with AD. Inflammatory markers based on laboratory tests, such as routine blood count, are cheap, convenient, and suitable for clinical practice, especially for long-term regular follow-up of patients, instead of PET-CT.
Recently, SII (calculated as total peripheral platelets count (P) × neutrophil-to-lymphocyte ratio) was developed as a novel index to evaluate the inflammatory and immune status of patients. A high SII was related to poor outcome in patient with cardiovascular disease [
10], [
11]. For example, a high SII can predict the severity of stable coronary artery and even predict ischemic stroke in the future [
12,
13]. Platelets, neutrophils and lymphocytes play important roles in the inflammatory state of AD. During this process, platelets activate the coagulation systems, thereby consuming clotting factors and producing a hypercoagulable state [
21]. In addition, platelets are associated with neutrophil activation and promote lymphocyte migration into peripheral lymph nodes [
22‐
24]. Neutrophils are important regulators of inflammatory responses and can secrete serine proteases, cathepsins and reactive oxygen intermediates, leading to endothelial cell damage, platelet aggregation and a hypercoagulable state [
24]. Neutrophils are related to endothelial damage, hypercoagulability, and platelet aggregation [
25]. Increased numbers of neutrophils are present in the vessel wall of patients with AD compared to the normal aortic vascular tissue [
26]. Lymphocytes play an important role in producing cytokines and provoking cytotoxic cell death [
27]. T lymphocytes can induce apoptosis in aortic vascular smooth muscle and stimulate the synthesis of matrix metalloproteinases [
28]. Excessive apoptosis promotes aortic inflammation and degeneration [
17].
Our results identified an association between high SII and increased long-term failure of OMT in patients with acute uTBAD. After blood pressure and heart rate regulation and symptomatic relief, the pre-discharge SII was lower than the admission SII, which may be a result of reduced inflammation severity. In addition, the pre-discharge SII was significantly higher in the high SII group than the low SII group. Therefore, the use of SII may be more useful than using individual cell counts, providing a more objective and comprehensive indicator of the inflammatory-immune state. In addition, we explored the associations of the C-reactive protein level and N/L ratio with composite outcomes, which demonstrated negative results.
Based on our results, SII is a useful, simple, and cost-effective tool for pre-OMT risk classification, especially for resource-poor areas. Patients with a high SII may benefit from more aggressive surveillance and treatment. TEVAR is highly effective in remodelling the aorta in the acute and subacute phases because of the compliant, elastic nature of a dissection flap, which is easily reapproximated to the outer aortic wall by the endograft. Hence, patients with acute uTBAD and a high SII may require pre-emptive TEVAR, given their significantly increased risk of poor outcomes during follow-up. Recently, statins were identified to have anti-inflammatory properties in cardiovascular disease. Therefore, they may also be used in patients with TBAD and a high SII to decrease inflammation and potentially improve outcomes. Of note, regular CT is essential for patients with acute uTBAD undergoing OMT, particularly those with a high SII, to promptly identify disease progression, such as rTAAD.
This study had limitations inherent to a retrospective analysis. First, the sample size was small and we did not explore the pathophysiological mechanisms. Second, this study is applicable to patients with acute uTBAD managed with conservative treatment, and the value of this index in other periods should be further explored. Third, complete blood count was not performed routinely during follow up, and some of the patients did not undergo imaging after OMT. The dynamic changes in SII were not analysed. In addition, because of the lack of an external cohort, external validation could not be provided. Further well-designed prospective clinical trials are needed to assess the predictive value of SII among patients with uTBAD.
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