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Objectives: The study aimed to investigate the interaction of intraoperative stress hyperglycemia with monocyte functions and their impact on major adverse events (MAEs) in acute aortic dissection (AAD) patients who underwent open repair surgery., Methods: A total of 321 adults who underwent open surgery for AAD at two tertiary medical centers in China were enrolled in the study. The primary endpoint was defined as the incidence and characteristics of perioperative stress hyperglycemia. The secondary endpoints included the incidence of postoperative MAEs, postoperative monocyte counts and inflammatory cytokine expression. Multi-logistic, linear regression and receiver operating characteristic (ROC) curve analyses were used to establish relationships between intraoperative time-weighted average glucose (TWAG), day-one postoperative monocyte counts, serum inflammatory cytokines and postoperative outcomes. In addition, in vitro experiments were conducted to evaluate changes in the inflammatory features of monocytes under high glucose conditions., Results: Intraoperative hyperglycemia, as indicated by a TWAG level over 142 mg/dL, was associated with elevated postoperative monocyte counts and inflammatory cytokines, which correlated with extended intensive care unit (ICU) stays and worsened outcomes. In vitro, high glucose treatment induced mitochondrial impairment in monocytes, increased the release of inflammatory cytokines and the proportion of classical monocytes from AAD patients., Conclusions: Intraoperative stress hyperglycemia, in combination with day-one postoperative monocyte counts, were clinically significant for predicting adverse outcomes in AAD patients undergoing open repair surgery. Elevated glucose concentrations shaped the inflammatory features of monocytes in AAD by impairing mitochondrial functions., (© 2024. The Author(s).)

Objectives: This study aims to retrospectively analyze the clinical features of Stanford type A acute aortic dissection (TAAAD) based on Sun's modified classification, and to investigate whether the Sun's modified classification can be used to assess the risk of preoperative rupture., Methods: Clinical data was collected between January 2018 and June 2019. Data included patient demographics, history of disease, type of dissection according to the Sun's modified classification, time of onset, biochemical tests, and preoperative rupture., Results: A total of 387 patients with TAAAD who met the inclusion criteria of Sun's modified classification were included. There were more complex types, with 75, 151 and 140 patients in the type A1C, A2C and A3C groups, respectively. The age of the entire group of patients was 51.46 ± 12.65 years and 283 (73.1%) were male. The time from onset to the emergency room was 25.37 ± 30.78 h. There were a few cases of TAAAD combined with stroke, pericardial effusion, pleural effusion, and lower extremity and organ ischemia in the complex type group. The white blood cell count (WBC), neutrophil count (NEC) and blood amylase differed significantly between the groups. Three independent risk factors for preoperative rupture were identified: neutrophil count, blood potassium ion level, and platelet count. Binary logistic regression analysis showed that the Sun's modified classification could not be used to assess the risk of preoperative rupture in TAAAD., Conclusion: TAAAD was classified as the complex type in most patients. WBC, NEC and blood amylase were significantly different between the groups. NEC and serum potassium ion level were independent risk factors for preoperative rupture of TAAAD, while platelet count was its protective factor. More samples are needed to determine whether Sun's modified classification can be used to evaluate the risk of preoperative rupture., (© 2024. The Author(s).)

The aim of this study is to investigate the potential causal relationships between coronary artery disease (CAD), myocardial infarction (MI), urate levels, and aortic aneurysm (AA), abdominal aortic aneurysm (AAA), thoracic aortic aneurysm(TAA), aortic dissection (AD) in individuals of European ancestry. To examine the potential causal relationships between CAD, MI, and urate levels with AA, AAA, TAA, AD, respectively, we performed a two-sample Mendelian randomization (MR) analysis. Genetic instruments that reached genome-wide significance (p < 5 × 10 - 8) for risk factors were obtained from genome-wide association studies(GWASs) conducted on individuals of European origin. On the other hand, genetic instruments of AA, AAA, TAA or AD were chosen from the FinnGen cohort. The primary analysis employed the inverse-variance weighted MR method, while sensitivity analyses were conducted using MR-Egger, weighted median MR, MR pleiotropy residual sum and outlier, and Phenoscanner searching. In addition, we performed the MR-Egger intercept analysis to identify potential pleiotropy and utilized Cochran's Q statistics to evaluate heterogeneity. Additionally, we conducted bidirectional Mendelian randomization experiments to mitigate the potential influence of reverse causation. According to the results of our study, there were statistically significant higher risks for AA in relation to CAD/MI(odds ratio (OR) with 95% confidence interval (CI): 1.309 (1.150-1.490), and 1.255 (1.147-1.373). Similarly, there were statistically significant higher risks for AAA in relation to CAD and MI (OR with 95% CI: 1.383 (1.189-1.609), and 1.352 (1.178-1.552). The sensitivity analysis demonstrated that the causative effects of CAD/MI, and AA /AAA, were robust. A positive causal link was observed between CAD/MI, and AA/AAA. Nevertheless, no causal link was found between CAD, MI, urate levels, and TAA ., (© 2024. The Author(s).)

Background: This study aimed to investigate the association between intestinal fatty acid-binding protein (I-FABP), acute gastrointestinal injury (AGI) grade, and gastrointestinal (GI) complications after fenestrated or branched endovascular aortic aneurysm repair., Methods: A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal, or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for I-FABP with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the AGI grade every day during postoperative intensive care., Results: Higher concentrations of I-FABP at 24 hr and 48 hr correlated to higher AGI grade on postoperative days 1, 2, and 3 (P = 0.032 and P = 0.048, P = 0.040 and P = 0.018, and P = 0.012 and P = 0.016, respectively). Patients who developed a GI complication within 90 days postoperatively had a higher overall AGI grade than those who did not develop a GI complication (P < 0.001), as well as higher concentrations of I-FABP at 48 hrs (P = 0.019). Patients developing GI dysfunction (AGI grade ≥2) had a higher frequency of complications (P = 0.009) and longer length of stay in the intensive care unit (P = 0.008)., Conclusions: In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma I-FABP concentrations and postoperative GI dysfunction, evaluated using the AGI grade, were associated with GI complications, indicating that these measures may be useful in the postoperative management of these patients., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Acute Type A Aortic Dissection (AAAD) is one of the most life-threatening diseases, often associated with transient hyperglycemia induced by acute physiological stress. The impact of stress-induced hyperglycemia on the prognosis of ST-segment elevation myocardial infarction has been reported. However, the relationship between stress-induced hyperglycemia and the prognosis of AAAD patients remains uncertain., Methods: The clinical data of 456 patients with acute type A aortic dissection were retrospectively reviewed. Patients were divided into two groups based on their admission blood glucose. Cox model regression analysis was performed to assess the relationship between stress-induced hyperglycemia and the 30-day and 1-year mortality rates of these patients., Results: Among the 456 patients, 149 cases (32.7%) had AAAD combined with stress-induced hyperglycemia (SIH). The results of the multifactor regression analysis of the Cox model indicated that hyperglycemia (RR = 1.505, 95% CI: 1.046-2.165, p  = 0.028), aortic coarctation involving renal arteries (RR = 3.330, 95% CI: 2.237-4.957, p  < 0.001), aortic coarctation involving superior mesenteric arteries (RR = 1.611, 95% CI: 1.056-2.455, p  = 0.027), and aortic coarctation involving iliac arteries (RR = 2.034, 95% CI: 1.364-3.035, p  = 0.001) were independent influences on 1-year postoperative mortality in AAAD patients., Conclusion: The current findings indicate that stress-induced hyperglycemia measured on admission is strongly associated with 1-year mortality in patients with AAAD. Furthermore, stress-induced hyperglycemia may be related to the severity of the condition in patients with AAAD.

Background: Triglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated., Methods: This study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI., Results: Over a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08-1.35), 1.21 (95% CI 1.08-1.35), and 1.30 (95% CI 1.16-1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20-1.52)., Conclusions: TyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA., (© 2024. The Author(s).)

Introduction: This systematic review aimed to discuss the current knowledge of possibly useful circulatory biomarkers (other than D-dimers) in the diagnosis of patients with an acute aortic dissection (AAD), to distinguish these patients from patients with Acute Myocardial Infarction (AMI)., Evidence Acquisition: This study followed the PRISMA guidelines. The databases PubMed, EMBASE and Scopus were systematically searched from inception to May 2023. Studies were included if they presented measurements of biomarker(s) in the blood/plasma/serum samples from adult patients with AAD versus AMI. Articles were excluded if aortic dissection was subacute or chronic (>14 days), if they lack a control group (AMI), or if they were animal studies, revisions, or editorials. The main outcome was the identification of biomarkers that exhibited diagnostic potential to differentiate patients with AAD versus AMI., Evidence Synthesis: The research query resulted in 1342 articles after the removal of duplicates, from which seven were included in the systematic review. The biomarkers identified included general blood assessment, metabolomics, products of the degradation of fibrin, extracellular matrix markers and an ischemia-associated molecule. Most studies lack diagnostic validity such as sensitivity and specificity. In six studies, the concentration of a total of six biomarkers showed significative differences between AAD and AMI group., Conclusions: A great heterogeneity of molecules has been studied as putative diagnostic markers of AAD versus AMI. Studies of better quality are needed, presenting the diagnostic validity of the molecules under analysis and the putative synergic diagnostic value of the molecules identified so far.

Diseases of the aorta, such as aortic aneurysm, dissection, and rupture, account for a large proportion of acute clinical emergencies. The red blood cell distribution width (RDW), which directly reflects anisocytosis (i.e., the heterogeneity of erythrocyte volumes), has emerged as a promising biomarker for many cardiovascular pathologies. Thus, we aimed to explore the implication of RDW in aortic pathologies. We searched Scopus and PubMed using the keywords "RDW" OR "red blood cell distribution width" AND "aortic aneurysm" OR "aortic dilatation" OR "aortic dissection" for identifying studies in which RDW values were measured in patients with these aortic diseases. Ten observational studies were finally included. In all studies, RDW value was increased in patients with aortic diseases. In the four studies in which sufficient RDW data were available for pooling, the weighted mean difference (WMD) of RDW in patients with or without complicated aortic pathologies was 0.575 (95 %CI, 0.254-0.896). RDW may be a valuable diagnostic and prognostic biomarker in patients with aortic pathologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pathogenesis and diagnostic biomarkers of aortic dissection (AD) can be categorized through the analysis of differential metabolites in serum. Analysis of differential metabolites in serum provides new methods for exploring the early diagnosis and treatment of aortic dissection., Objectives: This study examined affected metabolic pathways to assess the diagnostic value of metabolomics biomarkers in clients with AD., Method: The serum from 30 patients with AD and 30 healthy people was collected. The most diagnostic metabolite markers were determined using metabolomic analysis and related metabolic pathways were explored., Results: In total, 71 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism and four different metabolites considered of most diagnostic value including N2-gamma-glutamylglutamine, PC(phocholines) (20:4(5Z,8Z,11Z,14Z)/15:0), propionyl carnitine, and taurine. These four predictive metabolic biomarkers accurately classified AD patient and healthy control (HC) samples with an area under the curve (AUC) of 0.9875. Based on the value of the four different metabolites, a formula was created to calculate the risk of aortic dissection. Risk score = (N2-gamma-glutamylglutamine × -0.684) + (PC (20:4(5Z,8Z,11Z,14Z)/15:0) × 0.427) + (propionyl carnitine × 0.523) + (taurine × -1.242). An additional metabolic pathways model related to aortic dissection was explored., Conclusion: Metabolomics can assist in investigating the metabolic disorders associated with AD and facilitate a more in-depth search for potential metabolic biomarkers., (© 2024. The Author(s).)

Previous studies have demonstrated that admission hyperglycemia is a predictor of mortality and poor prognosis in patients with cardiovascular diseases, such as acute myocardial infarction. However, the prognostic value of admission hyperglycemia in patients with acute type A aortic dissection (AAAD) has never been explored. To clarify the association between hyperglycemia and in-hospital outcomes, we retrospectively analyzed 734 patients with AAAD. The interest endpoints were in-hospital mortality rate, the duration of intensive care unit and hospital stays, the occurrence of prolonged mechanical ventilation (PMV), and other complications. All patients were divided into the normal blood glucose group (≤ 140 mg/dL) and hyperglycemia group (> 140 mg/dL), to compare the in-hospital outcomes rate in the two groups. There were 531 (72.3%) patients with normal blood glucose levels and 203 (27.7%) patients with hyperglycemia. The in-hospital mortality rate was 21.1%, and no statistically significant differences were found between the two groups (20.3% versus 23.2%, P = 0.403). PMV is the most frequent postoperative complication, the incidence of which was significantly higher in the hyperglycemia group than in the normal blood glucose group (59.6% versus 50.8%, P = 0.040). The logistic regression analysis revealed that hyperglycemia (odds ratio (OR): 1.492; 95% CI: 1.014 to 2.197; P = 0.042) was an independent risk factor for PMV after adjusting for confounding factors. Age (OR: 1.021; 95% CI: 1.006-1.037; P = 0.007) and body mass index (OR: 1.101; 95% CI: 1.051-1.153; P < 0.001) were also associated with PMV. In conclusion, our study showed for the first time that a strong correlation between admission hyperglycemia and increased postoperative PMV in patients with AAAD, but not with in-hospital mortality rate.

Background: The platelet-lymphocyte ratio (PLR), a novel inflammatory marker, is generally associated with increased in-hospital mortality risk. We aimed to investigate the association between PLR and postoperative in-hospital mortality risk in patients with type A acute aortic dissection (AAAD)., Methods: Patients (n = 270) who underwent emergency surgery for AAAD at Xiangya Hospital of Central South University between January 2014 and May 2019 were divided into three PLR-based tertiles. We used multiple regression analyses to evaluate the independent effect of PLR on in-hospital mortality, and smooth curve fitting and a segmented regression model with adjustment of confounding factors to analyze the threshold effect between PLR and in-hospital mortality risk., Results: The overall postoperative in-hospital mortality was 13.33%. After adjusting for confounders, in-hospital mortality risk in the medium PLR tertile was the lowest (Odds ratio [OR] = 0.20, 95% confidence interval [CI] = 0.06-0.66). We observed a U-shaped relationship between PLR and in-hospital mortality risk after smoothing spline fitting was applied. When PLR < 108, the in-hospital mortality risk increased by 10% per unit decrease in PLR (OR = 0.90, P = 0.001). When the PLR was between 108 and 188, the mortality risk was the lowest (OR = 1.02, P = 0.288). When PLR > 188, the in-hospital mortality risk increased by 6% per unit increase in PLR (OR = 1.06, P = 0.045)., Conclusions: There was a U-shaped relationship between PLR and in-hospital mortality in patients with AAAD, with an optimal PLR range for the lowest in-hospital mortality risk of 108-188. PLR may be a useful preoperative prognostic tool for predicting in-hospital mortality risk in patients with AAAD and can ensure risk stratification and early treatment initiation., (© 2021. The Author(s).)

Background: Inflammation underlies both the pathogenesis and prognosis in patients with acute aortic dissection (AAD). This study aimed to assess the association of ICU admission of white blood cell count (WBCc) with post-discharge mortality in these patients., Methods: Clinical data were extracted from the MIMIC-III V1.4 database. After adjusted to covariables, Cox regression analysis and Kaplan-Meier survival curve were performed to determine the relationship between WBCc on admission and post-discharge mortality (30-day, 90-day, 1-year and 5-year) in AAD patients. Subgroup analysis and receiver operating characteristic (ROC) curve analysis were used to test the performance of WBCc in predicting mortality in AAD patients., Results: A total of 325 eligible patients were divided into 2 groups: normal-WBCc group (≤ 11 k/uL) and high-WBCc group (> 11 K/uL). In univariate Cox regression analysis, high WBCc was significant risk predictor of 30-day, 90-day, 1-year and 5-year mortality [hazard ratio (HR), 95% CI, P 2.58 1.36-4.91 0.004; 3.16 1.76-5.70 0.000; 2.74 1.57-4.79 0.000; 2.10 1.23-3.54 0.006]. After adjusting for age and other risks, high WBCc remained a significant predictor of 30-day, 90-day and 1-year mortality in AAD patients (HR, 95% CI, P 1.994 1.058-3.76 0.033; 2.118 1.175-3.819 0.013; 2.37 1.343-4.181 0.003). The area under ROC curve of WBCc for predicting 30-day, 90-day, 1-year and 5-year mortality were 0.69, 0.70, 0.66 and 0.61, respectively. The results from subgroups analysis showed that there was no interaction in most strata and patients who were younger than 69 years of age or had history of respiratory disease with an elevated WBCc had an excess risk of 30-day mortality (HR, 95% CI, P 3.18 1.41-7.14 0.005; 3.84 1.05-14.13 0.043)., Conclusions: Higher than normal WBCc on admission may predict post-discharge mortality in patients with AAD., (© 2021. The Author(s).)

Objective: Although aortic dissection occurs predominantly in men, its association with androgens is unknown. The aim of this study was to evaluate the androgen levels in Chinese male patients with uncomplicated, acute type B aortic dissection., Study Design: Cross-sectional study., Materials and Methods: A total of 192 age-matched male patients with uncomplicated, acute type B aortic dissection or essential hypertension were recruited between 2016 and 2018. The demographic and clinical data were analyzed., Results: Male patients with uncomplicated, acute type B aortic dissection had lower serum total testosterone and free testosterone than male patients with essential hypertension (7.6 ± 3.7 nmol/L vs. 10.9 ± 3.8 nmol/L, P < 0.001; 36.0 ± 19.8 pmol/L vs. 56.4 ± 19.2 pmol/L, P < 0.001). Lower free testosterone level was significantly associated with uncomplicated, acute type B aortic dissection (univariate odds ratio 0.948, P < 0.001; multivariate odds ratio = 0.966, P = 0.002). No statistical difference was observed for free testosterone between younger patient groups (aged < 51 years; aged 51-60 years) and older patient groups (aged 61-70 years; aged >70 years) with uncomplicated, acute type B aortic dissection (33.7 ± 19.8 pmol/L vs. 38.5 ± 19.8 pmol/L, P = 0.239)., Conclusions: Lower free testosterone was independently associated with uncomplicated, acute type B aortic dissection in the Chinese male population with hypertension. Additional studies are needed to clarify whether earlier onset in Chinese patients with aortic dissection is associated with androgen deficiency., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Few studies have evaluated the clinical presentation, management, and outcomes of patients with end-stage renal disease (ESRD) presenting with acute aortic dissection (AAD) in real-world clinical practice. Thus, this study investigated the clinical characteristics, management, and outcomes of AAD patients with ESRD., Methods: A total of 217 patients were included. We evaluated the differences in the clinical features, management, and in-hospital outcomes of patients with and without a history of ESRD presenting with AAD., Results: A history of ESRD was present in 71 of 217 patients. Patients with ESRD had atypical clinical manifestations (p < 0.001) and were more likely to be managed medically compared with patients without ESRD (p = 0.002). Hypertension and type B aortic dissection were significantly more common among patients with ESRD. Moreover, patients with ESRD had lower leucocyte and platelet counts than patients without ESRD in laboratory findings (p < 0.001). However, hospitalization days and in-hospital mortality were similar between the two groups (p > 0.05). Multivariate analysis identified Type A aortic dissection as an independent predictor of in-hospital mortality among patients without ESRD (OR, 13.68; 95% CI, 1.92 to 98.90; P = 0.006)., Conclusions: This study highlights differences in the clinical characteristics, management, and outcomes of AAD patients with ESRD. These patients usually have atypical symptoms and more comorbid conditions and are managed more conservatively. However, these patients have no in-hospital survival disadvantage over those without ESRD. Further studies are needed to better understand and optimize care for patients with ESRD presenting with AAD.

Following hospital discharge, patients with type A acute aortic dissection (TA-AAD) may present an increase in mortality risk. However, little is known about specific biomarkers associated with post-discharge survival, and there is a paucity of prognostic markers associated with TA-AAD. Here, we identify nine candidate proteins specific for patietns with TA-AAD in a cross-sectional dataset by unbiased protein screening and in-depth bioinformatic analyses. In addition, we explore their association with short-term and long-term mortality in a derivation cohort of patients with TA-AAD, including an internal (n = 300) and external (n = 236) dataset. An elevated osteoprotegerin (OPG)/tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) ratio was the strongest predictor of overall, 30-day, post-30-day mortality in both datasets and was confirmed to be a strong predictor of mortality in an independent validation cohort (n = 400). Based on OPG/TRAIL ratio-guided risk stratification, patients at high risk (>33) had a higher 1-year mortality (55.6% vs. 4.3%; 68.2% vs. 2.6%) than patients at low risk (<4) in both cohorts. In Conclusion, we show that an elevated OPG/TRAIL ratio is associated with a significant increase in short-term and long-term mortality in patients with TA-AAD.

Toll-like receptor 4 (TLR4) is a crucial regulator of inflammatory reactions and vascular remodeling. Elevated TLR4 expression has been proved to be correlated with an increased risk of aortic aneurysm (AA). This study aimed to explore the influence of TLR4 gene polymorphisms on TLR4 expression levels and its probable functional significance in AA disease. A total of 294 AA patients and 285 controls were enrolled in the study and serum TLR4 levels were detected by ELISA. All the participants were genotyped for two tag-SNPs in TLR4 (rs1927914 in the promoter region and rs11536889 in the 3'-untranslated region) using the KASP method. Relative luciferase activity was measured by the dual-luciferase reporter assay system. The rs1927914 TC, TC/CC genotypes and C allele showed associations with increased serum TLR4 levels in the total population and AA patients (all P<0.05). Further stratified analysis demonstrated that AA subjects with TC or TC/CC genotype of rs1927914 had significantly higher serum levels of TLR4 than those with TT genotype in male, age>60y, hypertension, diabetes, TAA type and size>5.0 cm subgroups (all P<0.05). In binary logistic analysis, rs1927914 TC genotype and dominant model presented significant associations with high TLR4 levels (OR = 1.579 and 1.431, P = 0.020 and 0.049, respectively) after adjusting age, hypertension and diabetes. However, rs11536889 polymorphism had no significant influence on serum TLR4 levels. Regarding rs1927914, luciferase activity of the C allele construct was significantly increased in comparison with the T allele construct (0.589 ± 0.004 vs. 0.340 ± 0.014, P<0.001). Our results provided evidence that rs1927914 polymorphism contributed to serum TLR4 levels, possibly by influencing promoter activity of TLR4, and could be a novel genetic factor in the formation of AA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The association between different ABO blood groups and mortality of aortic dissection (AD) remains controversial. This study aimed to examine whether different ABO blood groups affect the prognosis of AD., Methods: Demographic and clinical data were collected from 877 patients diagnosed with AD from 2015 to 2019 in the First Affiliated Hospital of Shantou University Medical College. The association between in-hospital mortality of AD patients and ABO blood group was analyzed using Cox proportional hazards regression models., Results: This retrograde cohort study demonstrated that for 877 patients, male gender, non-O blood group, Stanford type B AD (TBAD), higher presenting systolic and diastolic blood pressure, and being a recipient of aortic arch replacement surgery (surgery) or endovascular stent-graft implantation (stent-graft) were associated with decreased in-hospital mortality of AD. In Cox proportional hazards models, non-O blood group was associated with lower risk of early mortality regardless of adjustment (HR = 0.668, 95% confidence interval [CI] 0.473-0.944 before adjustment, HR = 0.662, 95% CI 0.468-0.935 after adjustment for age and sex, and HR = 0.641, 95% CI 0.453-0.906 after adjustment for AD types, SBP and surgery). Further analyses revealed that for patients diagnosed with type A AD (TAAD), non-O blood group renders a significant 34.3% decrease in the risk of in-hospital mortality compared with blood group O. Specifically, this difference in mortality risk was found among TAAD patients who did not undergo surgery (HR = 0.579, 95% CI 0.377-0.889), rather than those who did. There was no significant difference in early mortality for patients with TBAD, whether or not stent-grafts were implanted., Conclusions: Non-O blood type decreases the risk of in-hospital mortality, especially for TAAD, in AD patients without surgical intervention. More attention must be paid to blood type O TAAD patients without surgical interventions, and early surgical intervention may be an effective means to decrease in-hospital mortality of TAAD.

Background: Inflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 ( TLR4 ) is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of TLR4 and AAD is far from clear. The purpose of our study was to illustrate the relevance of TLR4 polymorphisms with the susceptibility to AAD., Methods: A total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of TLR4 polymorphisms (rs10759932 in the promoter and rs11536889 in the 3'-untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects' medical records, and serum TLR4 levels were collected from our previously published data., Results: We found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393, 95%CI = 0.164-0.939, P = 0.036; recessive model: OR = 0.439, 95%CI = 0.196-0.984, P = 0.045) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects (GC vs. GG: OR = 3.382, 95%CI = 1.051-10.885, P = 0.041; dominant model: OR = 3.043, 95%CI = 1.041-8.900, P = 0.042). In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD ( P interaction = 0.038, OR = 15.229) after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD ( P = 0.037), while AAD patients carrying CC genotype of rs10759932 showed lower serum TLR4 levels than TT genotype carriers ( P = 0.043)., Conclusions: Our findings provide evidence for the association between TLR4 polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of TLR4 in the pathophysiology of AAD., Competing Interests: The authors state that they have no competing interests., (Copyright © 2020 Tan Li et al.)

Background : Recently, considerable evidence pointed out monocyte to high-density lipoprotein ratio (MHR) is highly related to inflammatory related diseases. We aim to explore the level of MHR in acute aortic dissection (AAD) patients and determine whether MHR can be a novel diagnostic marker of AAD. Research design and methods : A total of 228 subjects including 128 AAD patients and 110 healthy control were enrolled. MHR levels and other serum samples were obtained at admission. Results : The baseline MHR levels were significantly higher in patients with AAD ( p  < 0.0001). A cutoff value of MHR >0.37 was associated with a sensitivity of 86.70% and a specificity of 93.60% for AAD. MHR levels were positively correlated with the time from symptom onset (R 2  = 0.0318, p  = 0.0003). Additionally, the area under the curve (AUC) was increased to 0.979 in patients whose time from onset of symptoms >24 h, with a sensitivity of 98.04% and a specificity of 93.64%. Multivariate logistic regression demonstrated that MHR levels, history of hypertension, and coronary artery disease (CHD) emerged as independent predictors of AAD. Expert Opinion: MHR has a high diagnostic value in AAD patients, especially in those whose time from onset of symptoms >24 h.

The concentrations of several diagnostic markers have been found to increase dramatically in critically ill patients with a severe disturbance of normal physiological homeostasis, without indication of the diseases they are normally associated with. To prevent false diagnoses and inappropriate treatments of critically ill patients, it is important that the markers aiding the selection of second-line treatments are evaluated in such patients and not only in the healthy population and patients with diseases the markers are associated with. The levels of trypsinogen isoenzymes, the trypsin inhibitor serine peptidase inhibitor Kazal type 1 (SPINK1), hCG and hCGβ, which are used as pancreatitis and cancer markers, were analyzed by immunoassays from serum samples of 17 adult patients who have undergone surgery of the ascending aorta during hypothermic circulatory arrest (HCA) with optional selective cerebral perfusion. Highly elevated levels of trypsinogen-1, -2 and -3, SPINK1 and hCGβ were observed in patients after HCA. This was accompanied by increased concentrations of S100β and NSE. In conclusion, this study highlights the importance of critically evaluating the markers used for aiding selection of second line of treatments in critically ill patients.

Background: Acute aortic dissection (AAD) is the most devastating aortic pathology, and the incidence is increasing worldwide. However, the occurrence and development of AAD are unpredictable. A thorough understanding of the serum metabolic landscape through metabolomic analysis may help identify new biomarkers for AAD and offers new insights into its prevention and evaluation., Methods: Nineteen patients with Stanford type A aortic dissection and 20 healthy individuals were enrolled in this study. We use global and targeted mass spectrometry-based metabolomics to investigate the serum metabolomics profiles, and the data were analyzed by principal component analysis and orthogonal partial least squares discriminant analysis., Results: Initial untargeted metabolomics analysis revealed significant changes of lipids and polar metabolites in patients with AAD. Alterations of the phosphatidylcholine metabolic pathway were further observed by targeted metabolomics. Trimethylamine N-oxide (TMAO) levels were obviously increased in patients with AAD compared with controls (P < 0.005), whereas the levels of carnitine (P < 0.005), choline, and betaine (P < 0.05) were decreased. Furthermore, TMAO levels were associated with disease severity in AAD and correlated positively with C-reactive protein levels (r = 0.537, P = 0.018), IL-6 levels (r = 0.546, P = 0.016), D-dimer levels (r = 0.694, P = 0.001), and maximum aortic diameter on admission (r = 0.748, P = 0.002)., Conclusions: Patients with AAD showed a predominant and consistent change of metabolites levels, especially the compounds in the phosphatidylcholine metabolic pathway. TMAO could potentially serve as a biomarker for the auxiliary diagnosis and evaluation of AAD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To evaluate the diagnostic accuracy and clinical utility of the acute aortic dissection detection risk score (ADD-RS) alone or with D-dimer as a screening test to exclude acute aortic syndrome., Methods: We conducted a systematic review and meta-analysis of studies examining the diagnostic accuracy of ADD-RS. We searched MEDLINE, Embase and Cochrane Controlled Register of Trials up to 12 December 2018., Results: We identified nine studies involving 26,598 patients for ADD-RS alone and 3421 patients with D-dimer. Overall, the methodological quality based on the Quality Assessment of Diagnostic Accuracy Studies 2 was moderate to high. Bivariate meta-analyses showed that the pooled sensitivities were 0.94 (95% confidence interval (CI) 0.90, 0.96) at the threshold of ADD-RS ≥1, 0.46 (95% CI, 0.34, 0.59) at ADD-RS ≥2, 1.00 (95% CI 0.99, 1.00) at ADD-RS ≥1 with D-dimer and 0.99 (95% CI 0.97, 1.00) at ADD-RS ≥2 with D-dimer. For the low prevalence population, failure rate and efficiency were 0.8% and 38.3% at ADD-RS ≥1, 0.03% and 14.5% at ADD-RS ≥1 with D-dimer, and 0.1% and 33.6% at ADD-RS ≥2 with D-dimer, respectively. For the high prevalence population, failure rate and efficiency were 3.8% and 33.3% at ADD-RS ≥1, 0.2% and 12.3% at ADD-RS ≥1 with D-dimer and 0.6% and 28.4% at ADD-RS ≥2 with D-dimer, respectively., Conclusions: ADD-RS alone or with D-dimer was a useful screening test with high sensitivity to exclude acute aortic syndrome. However, the optimal threshold of ADD-RS alone or with D-dimer may depend on the clinical setting.

Background: Evidence regarding the characteristics and prognosis in acute type A aortic dissection (AAD) patients with negative D-dimer result is limited. We aimed to investigate the characteristics and prognosis in AAD patients with negative D-dimer result., Methods and Results: 370 AAD patients within 24 h of symptom onset were enrolled in a hospital in China from January 2014 to December 2018. Nine (2.43%) and 361 (97.57%) exhibited negative and positive D-dimer results, respectively. The average age of nine negative D-dimer result participants was 47.67 ± 10.95 years old, and about seven (77.78%) of them were male. The negative group showed a significantly lower blood pressure, white blood cell, hemoglobin, activated partial thromboplastin, ejection fraction and symptom with pain than the positive group. Multivariate analysis showed white blood cell (×10 9 /L) (P = 0.008; odds ratio, 0.566) and symptom with pain (P < 0.001; odds ratio, 0.013) were significantly related to a negative result. The result of the fully-adjusted model showed negative D-dimer result was negatively associated with in-hospital mortality compared with positive group in AAD patients after adjusting confounders (OR = 0.34, 95%CI 0.01 to 10.82)., Conclusions: Negative D-dimer result is strongly influenced by white blood cell and symptom with pain. Negative D-dimer result was negatively associated with in-hospital mortality compared with positive group in AAD patients., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Acute aortic dissection (AAD) is an acute life-threatening cardiovascular disease, which is frequently complicated with oxygenation impairment (OI). We aim to investigate predictors of the development of OI in the patients with AAD., Methods: We retrospectively collected clinical data of AAD in hypertensive patients from July 2012 to March 2020. The patients included in this study were divided into OI (+) group (oxygenation index≤200) and OI (-) group (oxygenation index> 200). Both groups were compared according to demographic and clinical characteristics, and laboratory findings. Characteristics of hypertension in the patients with AAD were described. Predictors for the development of OI were assessed. And cutoff values were determined by receiver operating characteristics (ROC) curve., Results: A total of 208 patients were included in this study and the incidence of OI was 32.2%. In OI (+) group, patients had significantly higher peak body temperature (37.85 ± 0.60 vs 37.64 ± 0.44 °C, P = .005), higher levels of CRP (42.70 ± 28.27 vs 13.90 ± 18.70 mg/L, P = .000) and procalcitonin (1.07 ± 3.92 vs 0.31 ± 0.77μg/L, P = .027), and lower levels of albumin (34.21 ± 5.65 vs 37.73 ± 4.70 g/L, P = .000). Spearman's rank correlation test showed that the minimum oxygenation index was positively correlated with albumin, and was negatively correlated with the peak body temperature, serum CRP, procalcitonin, BNP and troponin. The stepwise multiple linear regression analysis showed that the peak body temperature, serum CRP and albumin were independently associated with development of OI. An optimal cutoff value for CRP for predicting OI was ≥9.20 mg/L, with a sensitivity of 91.0% and a specificity of 61.0%., Conclusions: The peak body temperature, serum CRP and albumin were independent predictors of OI development in the patients with AAD. The serum CRP on admission≥9.20 mg/L might be a valuable and reliable indicator in predicting the development of OI.

Acute aortic dissection (AAD) is an emergent vascular disease. Currently, its diagnosis depends on clinical and radiological investigations but lacking of serum biomarkers. In this study, we aimed to identify potential serum biomarkers for AAD using label-free proteomics approach. A total of 90 serum samples were collected from three groups: patients with acute aortic dissection (AAD, n = 30), patients with acute myocardial infarction (AMI, n = 30), and healthy controls ( n = 30), and the first four samples from each group were selected for label-free proteomics analysis. Using label-free approach, a total of 22 differentially expressed proteins were identified in the serum samples of the AAD group, of which 15 were upregulated and 7 were downregulated as compared to the AMI and healthy control groups. The most prominent increased protein was vinculin, which was selected to validate in total samples. The level of vinculin was significantly elevated in AAD patients (15.8 ng/ml, IQR: 9.3-19.9 ng/ml) than that in AMI patients (8.6 ng/ml, IQR:5.3-11.4 ng/ml) and healthy volunteers (5.3 ng/ml, IQR:2.8-7.6 ng/ml), P < 0.0001. Furthermore, the concentration of vinculin both increased in type A and B dissection. At the early stage of AAD, vinculin maintained a high level to 48 hours compared with that of AMI. Our study demonstrated that vinculin may play a role in the early diagnosis of AAD., Competing Interests: There are no conflicts of interest., (Copyright © 2020 He-Qing Wang et al.)

Since aortic aneurysms (AAs) are mostly asymptomatic, but they have a high mortality rate upon rupture, their detection and progression evaluation are clinically important issues. To discover diagnostic biomarkers for AA, we performed proteome analysis of aortic media from patients with thoracic atherosclerotic AA (TAAA), comparing protein levels between the aneurysm and normal tissue areas. After hierarchical clustering analysis of the proteome analysis data, tissue samples were classified into three groups, regardless of morphological features. This classification was shown to reflect disease progression stage identified by pathological examination. This proteomics-based staging system enabled us to identify more significantly altered proteins than the morphological classification system. In subsequent data analysis, Niemann-Pick disease type C2 protein (NPC2) and insulin-like growth factor-binding protein 7 (IGFBP7) were selected as novel biomarker candidates for AA and were compared with the previously reported biomarker, thrombospondin 1 (THBS1). Blood concentrations of NPC2 and IGFBP7 were significantly increased, while THBS1 levels were decreased in TAAA and abdominal atherosclerotic AA patients. Receiver operating characteristic analysis of AA patients and healthy controls showed that NPC2 and IGFBP7 have higher specificity and sensitivity than THBS1. Thus, NPC2 and IGFBP7 are promising biomarkers for the detection and progression evaluation of AA.

Objectives. To evaluate the distribution and impact of ABO blood groups on postoperative outcomes in patients undergoing surgery for acute type A aortic dissection (ATAAD). Design . A total of 1144 surgical ATAAD patients from eight Nordic centres constituting the Nordic consortium for acute type A aortic dissection (NORCAAD) were analysed. Blood group O patients were compared to non-O subjects. The relative frequency of blood groups was assessed with t-distribution, modified for weighted proportions. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality. Cox regression analyses were performed for assessing independent predictors of late mortality. Results. There was no significant difference in the proportions of blood group O between the study populations in the NORCAAD registry and the background population (40.6 (95% CI 37.7-43.4)% vs 39.0 (95% CI 39.0-39.0)%). ABO blood group was not associated with any significant change in risk of 30-day or late mortality, with the exception of blood group A being an independent predictor of late mortality. Prevalence of postoperative complications was similar between the ABO blood groups. Conclusions. In this large cohort of Nordic ATAAD patients, there were no associations between ABO blood group and surgical incidence or outcomes, including postoperative complications and survival.

Background: The purpose of the study was to examine the association between white blood cell count (WBCc) on admission and early outcome in patients with the acute Stanford type A aortic dissection (TAAD)., Methods: From January 2012 to December 2018, we retrospectively evaluated a series of 331 consecutive patients underwent surgery for TAAD in Tongji Hospital. The patients were divided into 2 groups based on the WBCc, i.e. the normal WBCc group (WBCc≤11 × 10 9 /L) and leukocytosis group (WBCc> 11 × 10 9 /L). The perioperative data were compared between the 2 groups. The in-hospital mortality and the compositive adverse event including multi-organ dysfunction syndrome, postoperative stroke, tracheotomy, and re-exploration for stopping bleeding were set as end points. Cox regression were used to assess the potential risk factors., Results: The in-hospital mortality was nearly 3 time higher in the leukocytosis group than in the normal WBCc group (20.9% vs.8.1%, P = 0.001), and 15.1% overall. For the circulatory arrest, there was significant higher mortality in patients with leukocytosis than normal WBCc group (26.1%vs.8.9%, P = 0.001). After adjustment for confounding factors, the leukocytosis was found to be a strong independent predictor of in-hospital mortality (odds ratio = 3.10; 95% confidence interval 1.38 to 6.97, P = 0.006). The leukocytosis was also a risk factor of adverse events (odds ratio = 1.80; 95% confidence interval 1.07 to 3.04, P = 0.027)., Conclusions: The WBCc within 24 h of admission for TAAD is a strong and independent predictor of in-hospital mortality as well as short-term clinical events. The results of this study have important clinical implications for risk-stratifying patients with TAAD.

Objective: Hyperglycaemia following branched endovascular repair (BEVAR) of extensive aortic aneurysms is associated with post-operative lower extremity weakness (LEW). Insulin administration to maintain euglycaemia appears to decrease LEW rates. The purpose of this study was to examine changes in insulin receptor content of neuron derived blood exosomes (NDEs) after BEVAR., Methods: Ten patients with a range of post-operative lower extremity neurological deficits after elective BEVAR were included in the study. Blood samples were collected pre-operatively, immediately after aneurysm repair, and on post-operative day 1. NDE insulin receptor substrate proteins were quantified by enzymevlinked immunosorbent assays., Results: NDE levels of phosopho-serine312-type 1 insulin receptor substrate ([P-Ser312-IRS1], an inhibitor of insulin signalling) increased sevenfold in the immediate post-operative period (from 7.90 ± 0.89 to 58.54 ± 6.77 pg/mL; p < .001), whereas those of pan-tyrosine-phospho insulin receptor substrate ([P-panTyr-IRS1], which facilitates insulin signalling), rose only 50% (from 0.41 ± 0.07 to 0.63 ± 0.10 pg/mL; p = .03). As a result, the mean ratio of P-Ser312-IRS1 to P-panTyr-IRS1, which reflects the level of insulin resistance, increased fivefold immediately post-operatively (from 22.31 ± 3.28 to 106.33 ± 11.83; p < .001) and returned to normal levels by the next day (18.72 ± 1.87)., Conclusion: BEVAR is associated with an acute state of insulin resistance within neuronal tissue. Further studies in a larger cohort of patients are needed to understand the potential interconnected processes of insulin resistance, hyperglycaemia, and spinal cord ischaemia after extensive endovascular aortic procedures., (Copyright © 2019 European Society for Vascular Surgery. All rights reserved.)

Compelling evidence has shown that microRNAs (miRs) are involved in the pathophysiology of BAV-associated aortopathy. The purpose of this study was to assess the biological role as well as the circulating expression of two miRs (miR-424-3p and miR-3688-3p) that have been previously identified as significantly dysregulated in thoracic aortic aneurysm specimens of BAV patients. Bioinformatic tools were used to predict miR gene targets followed by functional validation transfecting synthetic miR mimics and negative controls into human aortic smooth muscle cells (HASMCs). Levels of miRs and target genes were evaluated by qRT-PCR. The circulating miR expression profile analysis was assessed on plasma samples collected from a cohort of 72 patients with aortopathy including 39 BAV (33 males; 58 ± 13 years) and 33 TAV patients (26 males; 67 ± 9 years). Computational analysis revealed that SMAD7 and YAP1 were potential targets of miR-424-3p and miR-3688-3p, respectively. Transfection with mimics confirmed a significantly decreased gene expression of SMAD7 and YAP1 compared to mimic negative control (p = 0.04 and p = 0.0005, respectively) or blank control (p = 0.01 and p = 0.0007, respectively). Overexpression of miR-3688-3p also significantly upregulated pro-apoptotic caspase-3 gene expression compared to mimic negative control (p = 0.02) or blank control (p = 0.01). Furthermore, a significant down-regulation of the circulating miR-424-3p was observed in BAV compared to TAV patients (p = 0.001). In multiple linear regression analysis, the aortic valve morphology (β = - 0.29, p = 0.04) and the presence of aortic stenosis (β = - 0.28, p = 0.03) had a significant effect on the miR-424-3p expression. In conclusion, our study demonstrated that miR-424-3p and miR-3688-3p directly targeted SMAD7 and YAP1 in HASMCs, pivotal genes of the TGF-β and Hippo-signaling pathways. Circulating miR-424-3p was also found to be significantly decreased in BAV patients when compared to TAV patients, especially in patients with aortic stenosis. Further large studies of well-characterized BAV patient cohorts are needed to define the clinical significance of the miR-424-3p.

Acute aortic syndromes (AASs) are difficult to diagnose emergencies. Plasma soluble ST2 (sST2), a prognostic biomarker for heart failure, has been proposed as a diagnostic biomarker of AASs outperforming D-dimer, the current diagnostic standard. We performed a prospective diagnostic accuracy study of sST2 for AASs in the Emergency Department (ED). In 2017-2018, patients were enrolled if they had ≥1 red-flag symptoms (chest/abdominal/back pain, syncope, perfusion deficit) and a clinical suspicion of AAS. sST2 was detected with the Presage® assay. Adjudication was based on computed tomography angiography (CTA) or on diagnostic outcome inclusive of 30-day follow-up. 297 patients were enrolled, including 88 with AASs. The median age was 67 years. In 162 patients with CTA, the median sST2 level was 41.7 ng/mL (IQR 29.4-103.2) in AASs and 34.6 ng/mL (IQR 21.4-51.5) in alternative diagnoses (P = 0.005). In ROC analysis, the AUC of sST2 was 0.63, as compared to 0.82 of D-dimer (P < 0.001). Sensitivity and specificity values of sST2 associated with different cutoffs were: 95.5% and 10.8% (≥12 ng/mL), 84.1% and 29.7% (≥23.7 ng/mL), 35.2% and 85.1% (≥66.5 ng/mL). Results were similar in the full cohort. In conclusion, in patients from a European ED, plasma sST2 provided modest accuracy for diagnosis of AASs.

Objectives . The present study aimed to evaluate prognostic value of inflammatory markers for in-hospital mortality and renal complication in patients undergoing surgery for acute type A aortic dissection (ATAAD). Design . Serum concentration of C-reactive protein, leukocyte counts, procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6 and IL-8 were measured on the day of admission to the hospital (T0) and on 1st (T1), 2nd (T2), and 7th (T3) day after surgery. Results . 328 patients were included. There were significant differences between survivor group and non-survivor group in PCT, IL-2R, and IL-6 ( p  = .001, p  = .015, and p  = .005). There were significant differences between patients with different AKI stage in PCT and IL-2R ( p  = .001, p  < .001). The area under receiver operating characteristics (ROC) curve on 30-day death was 0.686 for PCT, 0.718 for IL-2R, 0.694 for IL-6 and 0.627 for IL-8. The area under ROC curve on stage III AKI was 0.852 for PCT, 0.749 for IL-2R, 0.626 for IL-8, and 0.636 for TNF-α. IL-2 > 1438 U/ml and IL-6 > 45.5 pg/ml were independently associated with 30-day mortality ( p  = .014 and p  < .001). The area under ROC curve was 0.849 on score 2 (using 1 point for PCT > 4.58 ng/ml, 1 point for IL-2R > 1438 U/ml, 1 point for APACHE II score >15.5, and 1 point for IL-6 > 45.5 pg/ml). Conclusions . PCT and cytokines may be considered as predictors for adverse renal outcomes and mortality in patients with ATAAD patients after surgery. They are earlier than traditional biomarkers and combination of these biomarkers will improve the accuracy.

Background: The present study aimed to evaluate the value of admission serum uric acid (UA) level in predicting in-hospital risk of death in patients with acute type A aortic dissection (AAAD)., Methods: From January 2016 to June 2019, 186 consecutive patients with AAAD who underwent thoracic aortic surgery were retrospectively studied. Serum UA levels were measured on admission. Forward conditional logistic regression was performed to identify independent risk factors for in-hospital death. Receiver operating characteristic (ROC) analysis was performed to assess the most clinical useful level of serum UA for predicting postoperative in-hospital mortality., Results: Increased level of serum UA was found in non-survivors compared with those survived (446 ± 123 vs 371 ± 111 umol/L, p < 0.001). Age (OR = 1.063, 95% CI 1.016-1.112, p = 0.009), UA (OR = 1.006, 95% CI 1.002-1.010, p = 0.002), D-dimer (OR = 1.025, 95% CI 1.005-1.013, p = 0.012), operation time (OR = 1.009, 95% CI 1.005-1.013, p < 0.001) and extent of aortic replacement (OR = 0.412, 95% CI 0.220-0.768, p = 0.005) were identified as independent risk factors of in-hospital mortality in AAAD patients. The best cut-off value of admission serum UA in predicting in-hospital mortality was determined to be 415 umol/L. Subgroup analysis showed that in the subgroup of total arch replacement, UA was significantly associated with in-hospital death (OR = 1.010, 95% CI 1.005-1.015, p < 0.001), while in patients underwent ascending aorta replacement or hemiarch replacement, the relationship was no longer significant (OR = 1.001, 95% CI 0.996-1.006, p = 0.611)., Conclusions: Elevated serum UA level on admission is an independent predictor of in-hospital mortality in patients with AAAD.

Background: Acute aortic dissection (AAD) is a life-threatening disorder in vascular surgery with a high early mortality. Serum amyloid A (SAA) is a kind of acute-phase protein with a rapid diagnostic value in other diseases. However, the researches on the performance of SAA for the diagnosis of AAD is still lacking. This retrospective study aimed to evaluate the SAA levels and further explore its potential diagnostic role in AAD patients., Methods: SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) in 63 controls and 87 AAD patients. Laboratory examinations were also performed. And relative clinical information was collected from participants included in this study., Results: SAA levels were significantly higher in AAD patients than those in healthy controls. SAA levels were independently associated with the risk of AAD. There was a positive significant correlation between SAA and C reactive protein (R = 0.442, and P = 0.001). Based on receiver-operating characteristic (ROC) analysis, the area under the curve (AUC) of SAA for the diagnosis of AAD were 0.942 with optimal cut-off points of 0.427 mg/L. For in-hospital mortality, the AUC of SAA were 0.732 with optimal cut-off points of 0.500 mg/L. According to logistic regression analysis, higher SAA levels represent a higher risk of in-hospital mortality (OR = 1.25; 95%CI: 1.07-1.47; P = 0.005)., Conclusion: Our findings demonstrated that SAA levels were significantly enhanced in AAD. SAA was closely correlated with inflammatory parameters and coagulation-related parameters in AAD. Furthermore, SAA could be a potential bio-marker for identifying AAD in the early diagnosis. Finally, SAA > 5.0 mg/L are independently related to AAD in-hospital mortality.

Background: Acute aortic dissection (AD) is a lethal vascular disease, accounting for over 90% cases of acute aortic syndrome. Despite advances in understanding associated risk factors, the long-term prognosis for AD patients is still poor. Several prognostic biomarkers have been used for AD as per the IRAD, such as older age (>70 years), onset of chest pain and hypotension, but they are not effective in all patients. Instead, C-reactive protein (CRP) is a consistent inflammatory marker. CRP levels are abnormally increased in AD. However, the prognostic value of serum CRP level in AD remains unclear., Objective: To perform a systematic review and meta-analysis (registration no CRD42017056205) to evaluate whether CRP is a biomarker associated with in-hospital mortality in type-A AD., Methods: PubMed, Web of Science, CNKI, SciELO, and EMBASE were searched for papers published from January 2000 to October 2017 for studies on the prognostic role of CRP at admission in type-A AD patients. Outcome data were extracted and pooled hazard ratios (HRs) were calculated., Results: 18 (N = 2875 patients) studies met the inclusion criteria. Elevated CRP level was associated with a significantly increased risk of in-hospital mortality in patients with type-A AD (HR = 1.15, 95% CI: 1.06-1.25, p = 0.001). The pooled sensitivity of CRP in type-A AD patients was 77% (95% CI 69%-84%, p < 0.001), and the specificity was 72% (95% CI 66%-78%, p < 0.001)., Conclusion: Elevated CRP level is significantly associated with increased risks of in-hospital mortality in patients with type-A AD. CRP is a convenient prognostic factor in type-A AD patients.

The emerging evidence emphasizes red blood cell distribution width (RDW) as optimal prognostic biomarker for cardiovascular diseases. However, several clinical biases impede its clinical application. Recent recommendations suggest combining RDW with other biomarkers. Accordingly, we propose evaluating the well-recognized biomarkers of vascular aging ( i.e. , the leukocyte telomere length and telomerase activity , and reduced levels of endothelial progenitor cells [EPCs]) with RDW, for predicting the risk for vascular aging and onset and prognosis of age-related degenerative arterial diseases, such as sporadic ascending aorta aneurysm (AAA), characterized to have an increased incidence in old people. Consequently, in this study (and for the first time), we simultaneously investigated the relationship between RDW values, systemic inflammatory molecules, mean values of leukocyte telomere length, telomerase activity and EPCs, and the risk for vascular aging and AAA onset and prognosis. To achieve this aim, we selected 80 old and 80 young healthy subjects and 80 AAA cases. Appropriate methodologies were used for assessing blood parameters, aorta alterations, genotyping, impairment of the leukocyte telomere length, and telomerase activity. The main findings obtained demonstrated that increased RDW values along with the augmented blood levels of high-sensitive C-reactive protein and the reduced mean values of both leukocyte telomere length, telomerase activity, and EPCs are independently associated with the high risk for both vascular aging and AAA onset and prognosis. They might be used as the best predictor biomarker profile for vascular aging, and for both diagnosis and outcome of sporadic AAA.

Purpose: Platelets are crucial components of the coagulation processes, and low admission platelet count (PLC) is associated with adverse clinical outcomes in patients with Stanford type A acute aortic dissection (AAD)., Methods: A total of 130 consecutive patients undergoing Stanford type A AAD surgery in Beijing Anzhen Hospital were enrolled between January 2013 and July 2014. Preoperative clinical and laboratory data from patients were collected. Multiple regression analyses were used to determine the independent factors of low admission platelets., Results: Adjusted multiple regression analysis showed that age (β: -1.069, 95% confidence interval [CI]: -2.109, -0.029), sex (β: -29.973, 95% CI: -56.512, -3.433), tissue factor pathway inhibitor (TFPI; β: 0.197, 95% CI: 0.039, 0.354), fibrinogen degradation product (FDP) (β: -0.476, 95% CI: -0.879, -0.074), and attack time (β: 11.125, 95% CI: 7.963, 14.287) were significantly associated with admission PLC. Admission PLC increased with attack time up to the 3 days (β: 16.2, 95% CI: 12.1, 20.2)., Conclusions: We found that increasing age, male patients, patients with lower serum levels of TFPI and higher serum levels of FDP, and patients with a shorter attack time were significantly associated with lower PLC at admission. Moreover, the turning point of attack time is 3 days after the onset of dissection.

The prevalence and extent of immunoglobulin G4 (IgG4)-positive cell infiltration were investigated in 282 surgical samples of aortic wall and aortic valve. Tissue infiltration of IgG4-positive cells was observed in 24 (17.3%) of 139 aortic valve samples and 46 (32%) of 143 aortic wall samples, and the condition of IgG4-positive cell infiltration > 30/hpf together with IgG4/CD138 ratio > 40% was observed in 2 (1.4%) of aortic valve samples and 14 (9.8%) of aortic wall samples. Among 275 patients, preoperative serum IgG4 level was available in 48 patients (50 samples), and it was > 135 mg/dL in only one patient. Of these 48 patients with serum IgG4 measurement, 29 patients had aortic valve stenosis and 12 had aortic aneurysm. Compared with 23 aortic stenosis patients without tissue infiltration of IgG4-positive cells in the aortic valve, six patients with IgG4-positive cell infiltration had a more prevalent smoking history (26% versus 83%) and borderline significantly higher serum IgG4 (median, 24.5 mg/dL versus 55.5 mg/dL), although either preoperative peak pressure gradient between left ventriculum and aorta or aortic valve area did not differ significantly between groups. Compared with six aortic aneurysm patients without tissue infiltration of IgG4-positive cells in the aortic wall, six patients with IgG4-positive cell infiltration had borderline significantly higher serum IgG4 (median, 28.9 mg/dL versus 68.2 mg/dL). The current study showed that tissue IgG4-positive infiltration is not a rare occurrence in the aortic stenosis and aortic aneurysm. Clinical significance of tissue IgG4-postive cell infiltration in these patients requires further investigation.

Objectives: Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD., Methods: Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis., Results: A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender., Conclusions: The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene (FBN1), resulting in aortic aneurysm formation and dissections. Interestingly, variable aortopathy is observed even within MFS families with the same mutation. Thus, additional risk factors determine disease severity. Here, we describe a case of a 2-month-old Fbn1 C1039G/+ MFS mouse with extreme aortic dilatation and increased vascular inflammation, when compared to MFS siblings, which coincided with unilateral renal cystic disease. In addition, this mouse presented with increased serum levels of creatinine, angiotensin-converting enzyme, corticosterone, macrophage chemoattractant protein-1, and interleukin-6, which may have contributed to the vascular pathology. Possibly, cystic kidney disease is associated with aneurysm progression in MFS patients. Therefore, we propose that close monitoring of the presence of renal cysts in MFS patients, during regular vascular imaging of the whole aorta trajectory, may provide insight in the frequency of cystic kidney disease and its potential as a novel indicator of aneurysm progression in MFS patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Matrix metalloproteinase 9 (MMP9) and Toll-like receptor 4 (TLR4) play important roles in aortic pathophysiology. However, there is lacking research on serum TLR4 levels in acute aortic dissection (AAD) patients, and the performance of serum MMP9 and TLR4 for the diagnosis of AAD is still unknown. This study aimed to evaluate the serum levels of MMP9 and TLR4 in AAD patients, identify their associations with circulating C-reactive protein (CRP) and D-dimer, which are well-known classical biomarkers of AAD, and further explore the potential diagnostic role of MMP9 and TLR4 in AAD., Methods: Serum levels of MMP9 and TLR4 were measured by enzyme-linked immunosorbent assay (ELISA) in 88 AAD patients and 88 controls. The clinical test related information was collected from patients' electronic medical records., Results: Serum MMP9 and TLR4 levels were significantly higher in AAD patients than those in healthy controls in the general and stratified comparisons. Either serum MMP9 or TLR4 was independently associated with the risk of AAD (all p < 0.001). There was a positive significant association between serum MMP9 and TLR4 (r = 0.518, p < 0.001). Both MMP9 and TLR4 levels were statistically correlated with circulating CRP, but not D-dimer. Based on receiver-operating characteristic (ROC) analysis, the area under the curves (AUCs) of MMP9 and TLR4 alone for the diagnosis of AAD were 0.810 and 0.799 with optimal cut-off points of 379.47 ng/ml and 7.83 ng/ml, respectively. Moreover, a combination of serum MMP9 and TLR4 increased the AUC to 0.89 with a sensitivity of 60.2% and specificity of 94.3%., Conclusions: Serum MMP9 and TLR4 could be potential biomarkers for identifying AAD, while the combined diagnostic value was higher in safely ruling out AAD.

Complement-C1q/tumor necrosis factor-related protein-3 (CTRP3) is one kind of adipocytokines and has been reported to play key roles in many cardiovascular diseases by regulating inflammation. Inflammation was reported to be involved in the development of acute aortic dissection (AAD). The purpose of this study was to investigate whether serum levels of CTRP3 were associated with AAD. The serum was collected from 108 participants, including 60 patients with AAD and 32 patients with hypertension, as well as 16 healthy subjects. Serum levels of CTRP3, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay kits. Decreased serum levels of CTRP3 were found in AAD patients compared with hypertension and healthy subjects (35.89 ± 11.26 vs 52.60 ± 13.90 and 51.71 ± 18.64 ng/mL, p < 0.001, respectively). IL-6 and TNF-α levels were significantly higher in AAD patients than those in hypertension and healthy subjects (IL-6: 31.33 ± 15.18 vs 13.13 ± 8.63 and 9.40 ± 6.27 pg/mL, p < 0.001; TNF-α: 36.87 ± 11.16 vs 29.66 ± 5.12 and 22.93 ± 7.18 pg/mL, p < 0.001, respectively). In AAD, CTRP3 levels showed a negative correlation with IL-6 and TNF-α levels respectively (r = -0.508, p < 0.001; r = -0.393, p = 0.002, respectively). In conclusion, decreased levels of CTRP3 may be associated with the development of AAD., (Copyright © 2018. Published by Elsevier Inc.)

BACKGROUND The aim of this observational case-control study was to compare the levels of plasma resistin between patients with acute aortic dissection and matched controls, and to use propensity score matching (PSM) to reduce case selection bias and clinical confounders. MATERIAL AND METHODS With the use of PSM, this study included 43 pairs of patients with acute aortic dissection (type-A and type-B dissection) and matched controls. Plasma resistin levels and other laboratory parameters were compared between the two groups, including white blood cell (WBC) count, glucose, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-dimer. The correlations between resistin and other laboratory parameters were evaluated in patients with acute aortic dissection. RESULTS Following PSM adjustment for clinical variables, including age, sex, body mass index, smoking, alcohol drinking, hypertension, diabetes mellitus, coronary heart disease and stroke, plasma resistin levels were significantly increased in patients with acute aortic dissection when compared with controls (35.2±13.8 vs. 18.4±9.1 ng/ml) (p<0.001). WBC counts, and levels of glucose, hs-CRP, IL-6, TNF-α and D-dimer were also significantly increased in the patients with aortic dissection compared with the control group. After adjustment for these variables, the association between plasma resistin levels and acute aortic dissection remained significant (OR, 1.114; 95% CI, 1.036-1.224) (p<0.001). Plasma resistin levels was positively correlated with WBC count (r=0.368, p=0.015), hs-CRP (r=0.359, p=0.022), IL-6 (r=0.306, p=0.046) and TNF-α levels (r=0.315, p=0.040) in patients with acute aortic dissection. CONCLUSIONS Acute aortic dissection is associated with elevated levels of plasma resistin and other pro-inflammatory cytokines. Plasma resistin levels is positively associated with other pro-inflammatory cytokines in acute aortic dissection.

Background: Inflammation plays an important role in the initiation and progression of acute aortic dissection (AAD). New inflammatory indices derived from full cell blood count and its differential may be associated with increased risk. We evaluated platelet-lymphocyte (PLR), red cell distribution width (RDW) and RDW/PLT's (platelets) (RPR) in AAD., Methods: We studied 120 consecutive patients with AAD type I admitted for emergency surgery (group I), 121 consecutive patients with aortic aneurysms of the ascending aorta prior to elective repair (group II) and 121 controls (group III), age and sex matched., Results: PLR was significantly higher in group I vs both groups II and III (P < .001). There was an excellent correlation of PLR with neutrophil/lymphocyte ratio (NLR) in all three groups (P < .001 for all). After adjustment for hemoglobin, RDW did not differ but RPR remained significantly higher in group I compared to groups II and III (P < .001). The best cutoff value of PLR to predict dissection was 159 with 53% sensitivity and 86% specificity. No association between PLR, RDW, and RPR and mortality in group I was found., Conclusions: Indices derived from full cell blood count may provide diagnostic information in patients with AAD; whether these indices may contribute to prognosis assessment should be further investigated., (© 2018 Wiley Periodicals, Inc.)