Association of cardiovascular disease and urate levels with aortic aneurysm: a bilateral mendelian randomization study.

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 .

Preoperative clinical characteristics and risk assessment in Sun's modified classification of Stanford type A acute aortic dissection.

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.

Monocytes perturbation implicated in the association of stress hyperglycemia with postoperative poor prognosis in non-diabetic patients with Stanford type-A acute aortic dissection.

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.

Association of triglyceride-glucose index with the risk of incident aortic dissection and aneurysm: a large-scale prospective cohort study in UK Biobank.

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.

Effect of stress-induced hyperglycemia on long-term mortality in non-diabetic patients with acute type A aortic dissection: a retrospective analysis.

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.

Circulating biomarkers in acute aortic dissection versus acute myocardial infarction: a systematic review.

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.

Intestinal Fatty Acid-Binding Protein as a Potential Biomarker for Gastrointestinal Complications after Complex Endovascular Aortic Surgery.

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.

Analysis of differential metabolites in serum metabolomics of patients with aortic dissection.

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.

Systematic literature review and critical analysis of RDW in patients with aortic pathologies.

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.

Admission Hyperglycemia in Acute Type A Aortic Dissection Predicts for a Prolonged Duration of Mechanical Ventilation.

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.

U-shaped relationship between platelet-lymphocyte ratio and postoperative in-hospital mortality in patients with type A acute aortic dissection.

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.

Admission white blood cell count predicts post-discharge mortality in patients with acute aortic dissection: data from the MIMIC-III database.

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.

Differences in the clinical presentation, management, and in-hospital outcomes of acute aortic dissection in patients with and without end-stage renal disease.

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.

OPG/TRAIL ratio as a predictive biomarker of mortality in patients with type A acute aortic dissection.

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.

Letter to the Editor: Admission Values of Plasma Biomarkers Predict the Short-Term Outcomes in Acute Aortic Dissection.

Not applicable.

Low Serum-Free Testosterone Concentration in Chinese Male Patients with Uncomplicated Acute Type B Aortic Dissection.

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.

TLR4 rs1927914 polymorphism contributes to serum TLR4 levels in patients with aortic aneurysm.

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.

Non-O blood group is associated with lower risk of in-hospital mortality in non-surgically managed patients with type A aortic dissection.

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.