This observational retrospective study based on a large sample cohort analyzed the association of admission WBCc in AAD patients with short- and long-term clinical outcomes. Our results indicated that a high-WBCc on admission in patients with AAD was associated with poor short- and long-term clinical outcomes. After adjustment using a multivariate Cox analysis, the WBCc is an independent predictor to short-term (30-days and 90-days) and long-term (1-year) mortality. AUC analysis indicated that the WBCc had a better performance than SIRS score in predicting short- and long-term mortality in patients with AAD. Moreover, a subgroup analysis showed that high-WBCc on admission carried an excess risk of 30-days mortality in patients who were younger than 69 years of age or had a history of respiratory disease.
AAD is an acutely presenting, serve disease with high mortality . Identification of risk factors for prognosis is of great value for risk stratification in AAD patients, but simple and effective biomarker is still lack. Inflammation is involved in medial degradation of aortic artery, arterial wall remodeling, which contributed to aortic wall weakness and rupture[15, 16]. In recent decades, studies showed that several indicators of the inflammatory reaction including CRP level, D-dimer level and PLTc were associated with clinical outcomes in acute aortic syndrome(AAS). The WBCc is a sensitive and non-specific inflammation biomarker and its elevation also has been observed in AAD patients in previous studies[11, 12, 20, 21]. However, the results of further studies on the association between the WBCc and prognosis of patients with AAD were inconsistent. A French study with a Western cohort showed that there was no association between the admission WBCc and in-hospital mortality in both type A and type B AAD patients(OR = 2.80, 95%CI: 0.80-12.58, P = 0.12), but its sample size was relatively small(n = 94). Recently, two studies from China[11, 12] respectively found that, in patients with type A or B AAD, the admission WBCc could predict in-hospital death, but failed to long-term outcomes. The differences in genetic background, type of AD and sample size may partially explain the inconsistency of results.
In the present study, approximately a quarter of AAD patients showed an elevated WBCc on admission. These patients had higher PLT, HCT, Hb, BUN and Glucose, and had more CHF, higher SAPS II and SIRS scores. Our results revealed that the WBCc is an independent predictor to short-term (30-days and 90-days) mortality, which confirmed previous findings from the two Chinese studies. Moreover, a novel finding is that the admission WBCc but also can predict long-term (1-year) mortality. Although the result of the multivariate Cox analysis of 5-years mortality did not reach statistical significance, since the 5-years mortality rate was significantly higher in high-WBCc AAD patients, univariate Cox regression analysis showed that WBCc was associated with 5-years mortality and sample size of high-WBCc patients with AAD was relatively small (n = 80), we could not easily conclude that there is no association between 5-years mortality and admission WBCc. The results from subgroup analysis and AUC analysis also proved an excellent performance of the WBCc in predicting short- and long-term mortality in AAD patients. Compared with other classic severity scores, the WBCc showed a better performance than SIRS score. The White blood cell (WBC) is an inflammatory reactant in the early stage of AAD. It has been proved that it can activate endothelial damage, procoagulant effects and microvascular damage, resulting in release of pro-inflammatory cytokines that contribute to a profound degradation of collagen and the extracellular matrix (ECM) related to smooth muscle cell (SMC) depletion, elastic fiber fragmentation and atherosclerosis underling aortic wall irreversible remodeling and weakness, which promote the progression of AAD. In addition, clinical studies showed that an increased WBCc on admission was related to some serious postoperative complications, such as sepsis, hemorrhage, delirium, stroke and myocardial infarction, and might be one of the reasons for the poor prognosis and death[22–25]. Perhaps, these explain why the high-WBCc are associated with poor clinical short- and long-term outcomes in patients with AAD.
In the subgroup analysis, there was no interaction in most strata, which proved the reliability of the WBCc on admission predicting short- and long-term mortality in patients with AAD. We also found that AAD patients who were younger than 69 years of age or had a history of respiratory disease with an elevated WBCc had an excess risk of 30-days mortality. Firstly, increasing age as an independent risk factor in 30-days mortality in AAD patients was showed in several research[12, 26]. They explained that the great number of pre-existing comorbidities in the elderly patients increased the mortality rate. In our study, younger patients with an increased WBCc had an excess risk of 30-days mortality and it may be because younger patients have fewer underlying diseases than the older, so that the impact of increased WBCc is magnified in this population. Secondly, respiratory disease can aggravate hypoxia and promote acidosis in patients with AAD, and these changes further decrease the patients’ cardiac contractility and vascular resistance, ultimately leading to circulatory shock and end-organ failure. Thus, it could be the main reason for higher risk of 30-days mortality in AAD patients who had a history of respiratory disease with an elevated WBCc. Our results indicated that more severe measures need to be taken in both of the above situations.
It is first time to reveal the potential value of the WBCc as a prognostic biomarker of both in short- and long-term mortality in AAD patients. Combined with previous studies, our results provide further evidence of the utility of this stable and convenient indicator predicting prognosis in AAD patients. In the future, additional researches are needed to further understand the role of different types of WBC or some of their components in the prognosis of AAD patients, which provide the possibility for the application of targeted intervention in the treatment of AAD.
There are several limitations need to be mentioned in the study. Firstly, this study is a single-center observation study, which may not be universally representative. However, the reliability of our results was strongly enhanced by large sample size from MIMIC-III database and most subgroups analysis having no interaction. Secondly, our study only analyzed the WBCc on admission. Observation of changes of the WBCc in different time periods may provide more valuable information for evaluating its prognostic value in AAD patients. Thirdly, more in-depth mechanism exploration should be conducted in the future.