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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.)

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.)

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.)

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: 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.)

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.)

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.)

Objective: Current guidelines recommend administration of unfractionated heparin (UFH) and measurement of activated clotting time (ACT) during endovascular procedures. The aim of this study was to compare ACT and anti-activated factor X (anti-Xa) measurements for monitoring of UFH therapy during an aortic endograft procedure and to assess the association of peak ACT and peak anti-Xa activity with periprocedural bleeding., Methods: We retrospectively studied 104 patients with aortic aneurysm undergoing endovascular procedures with repeated coagulation measurements. After a UFH bolus, further UFH doses were given according to ACT (target range, ≥250 seconds) in clinical routine, and in parallel to each ACT (Hemochron; Accriva Diagnostics, Newport Beach, Calif) measurement, we determined anti-Xa activity (HemosIL Liquid anti-Xa; Instrumentation Laboratory, Bedford, Mass). UFH redosing was solely based on the ACT measurements. We defined periprocedural bleeding as a drop in hemoglobin level ≥3 g/dL or red blood cell transfusion within 24 hours., Results: After the initial UFH bolus (median, 67 IU/kg body weight), ACT and anti-Xa measurements showed a weak correlation (r s , 0.46; P < .001). Median ACT was 233 seconds (range, 127-374 seconds; interquartile range [IQR], 204-257 seconds); median anti-Xa activity was 1.0 IU/mL (range, 0.5-2.0 IU/mL; IQR, 0.9-1.2 IU/mL). Only 31% of the patients had an ACT value ≥250 seconds, whereas all patients had an anti-Xa activity ≥0.5 IU/mL. Accordingly, ACT triggered redosing of UFH frequently. Consequently, we saw a median total UFH use of 90 IU/kg during the procedure, a median peak ACT of 255 seconds (IQR, 234-273 seconds), and a median peak anti-Xa activity of 1.2 IU/mL (IQR, 1.0-1.4 IU/mL). Periprocedural bleeding occurred in 40 (38%) patients. Peak ACT ≥250 seconds was not associated with bleeding (odds ratio, 1.05; 95% confidence interval, 0.41-2.70; P = .952), whereas peak anti-Xa activity ≥1.2 IU/mL was independently associated with bleeding (odds ratio, 4.95; 95% confidence interval, 1.82-13.48; P = .002). Moreover, no periprocedural thromboembolic event occurred., Conclusions: In this retrospective study of patients with aortic aneurysm undergoing an endovascular procedure, ACT and anti-Xa measurements showed poor correlation; only increased peak anti-Xa activity was independently associated with periprocedural bleeding, not increased ACT. Our findings also suggest that monitoring of UFH therapy with anti-Xa during aortic endograft procedures may reduce total UFH use. We further speculate that this approach could reduce periprocedural bleeding., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Immune inflammation appears to play a role in aortic aneurysm (AA) pathology. Toll-like receptor 4 (TLR4) has been proved to involve in immune inflammatory diseases. However, the relationship between serum TLR4 and AA is still unclear., Methods: The study included 282 AA patients and 287 controls. The clinical test related information was collected in medical records. The levels of serum TLR4 were measured by enzyme-linked immunosorbent assay., Results: Serum TLR4 levels were significantly higher in case groups and could be influenced by age, smoking, hypertension, diabetes and hyperlipidemia. Serum TLR4 was positively correlated with circulating CRP, Hcy, D-dimer, Fg and Cys-c in AA patients, even after adjusting the possible influencing factors. The optimal cut-off value of TLR4 was 13.64 ng/ml for discriminating AA, and the screening accuracy was higher for those who were males (sensitivity of 63.5% and specificity of 68.6%), smokers (sensitivity of 63.5% and specificity of 82.7%) and hyperlipidemia (sensitivity of 59.1% and specificity of 81.2%). Multiple logistic analyses showed that serum TLR4 was significantly correlated with AA risk (OR = 1.119, 95% CI = 1.077-1.162, p < 0.001) and subjects with high TLR4 levels (>13.64 ng/ml) were more likely to have AA (OR = 4.225, 95% CI = 2.477-7.206, p < 0.001)., Conclusions: Serum TLR4 was closely related to AA and associated with some AA-related circulating markers. Serum TLR4 could be a novel and promising biomarker with important diagnostic and predictive value in the identification of aortic aneurysmal diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: D-dimer shows high sensitivity but low specificity for the diagnosis of acute aortic dissection (AAD). Previous reports indicated that negative D-dimer patients have shorter dissection length. However, whether patients with negative D-dimer results have a good prognosis is unknown. This study aimed to elucidate the clinical characteristics and implications of a negative D-dimer result on AAD diagnosis., Methods: The study group comprised 126 patients (71 males, 55 females; mean age, 69 ± 11 years) with AAD admitted to our hospital between April 2009 and March 2015. Blood samples on presentation were used for D-dimer measurement. Clinical characteristics and outcomes were assessed., Results: Nine (7.1%) and 117 (92.9%) exhibited negative and positive D-dimer results, respectively. The negative group showed a significantly lower extension score and a higher platelet count than the positive group. Multivariate analysis demonstrated that platelet count (odds ratio, 1.31 (1.09-1.58), p = 0.003) and extension score (odds ratio, 0.56 (0.33-0.96), p = 0.03) were significantly related to a negative result. Notably, 44% of patients in the negative group had type A dissection and 33% underwent an emergency operation due to cardiac tamponade., Conclusion: We found that high platelet count and low extension score were independent factors related to a negative D-dimer result. Even if the length of the dissection is short, an emergency operation is necessary in some patients with a negative D-dimer result. Physicians should recognize that a negative D-dimer result alone cannot exclude patients with fatal AAD conditions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The blotchy mouse caused by mutations of ATP7A develops low blood copper and aortic aneurysm and rupture. Although the aortic pathologies are believed primarily due to congenital copper deficiencies in connective tissue, perinatal copper supplementation does not produce significant therapeutic effects, hinting additional mechanisms in the symptom development, such as an independent effect of the ATP7A mutations during adulthood., Methods: We investigated if bone marrow from blotchy mice contributes to these symptoms. For these experiments, bone marrow from blotchy mice (blotchy marrow group) and healthy littermate controls (control marrow group) was used to reconstitute recipient mice (irradiated male low-density lipoprotein receptor -/- mice), which were then infused with angiotensin II (1,000 ng/kg/min) for 4 weeks., Results: By using Mann-Whitney U test, our results showed that there was no significant difference in the copper concentrations in plasma and hematopoietic cells between these 2 groups. And plasma level of triglycerides was significantly reduced in blotchy marrow group compared with that in control marrow group (P < 0.05), whereas there were no significant differences in cholesterol and phospholipids between these 2 groups. Furthermore, a bead-based multiplex immunoassay showed that macrophage inflammatory protein (MIP)-1β, monocyte chemotactic protein (MCP)-1, MCP-3, MCP-5, tissue inhibitor of metalloproteinases (TIMP)-1, and vascular endothelial growth factor (VEGF)-A production was significantly reduced in the plasma of blotchy marrow group compared with that in control marrow group (P < 0.05). More important, although angiotensin II infusion increased maximal external aortic diameters in thoracic and abdominal segments, there was no significant difference in the aortic diameters between these 2 groups. Furthermore, aortic ruptures, including transmural breaks of the elastic laminae in the abdominal segment and lethal rupture in the thoracic segment, were observed in blotchy marrow group but not in control marrow group; however, there was no significant difference in the incidence of aortic ruptures between these 2 groups (P = 0.10; Fisher's exact test)., Conclusions: Overall, our study indicated that the effect of bone marrow from blotchy mice during adulthood is dispensable in the regulation of blood copper, plasma cholesterol and phospholipids levels, and aortic pathologies, but contributes to a reduction of MIP-1β, MCP-1, MCP-3, MCP-5, TIMP-1, and VEGF-A production and triglycerides concentration in plasma. Our study also hints that bone marrow transplantation cannot serve as an independent treatment option., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Acute aortic dissection (AD) represents a diagnostic conundrum. Validated algorithms are particularly needed to identify patients where AD could be ruled out without aortic imaging. We evaluated the diagnostic accuracy of a strategy combining the aortic dissection detection (ADD) risk score with D-dimer, a sensitive biomarker of AD., Methods: Patients from two clinical centers with suspected AD were prospectively enrolled in a registry, from January 2008 to March 2013. The ADD risk score was calculated by retrospective blinded chart review. For D-dimer, a cutoff of 500 ng/ml was applied., Results: AD was diagnosed in 233 of 1035 (22.5%) patients. The ADD risk score was 0 in 322 (31.1%), 1 in 508 (49.1%) and >1 in 205 (19.8%) patients. The sensitivity and the failure rate of D-dimer were 100% and 0% in patients with ADD score 0, versus 97.5% (95% CI 91.4-99.6%) and 4.2% (95% CI 0.7-12.5%) in patients with ADD risk score >1. In patients with ADD risk score ≤ 1, the sensitivity and the failure rate of D-dimer were 98.7% (95% CI 95.3-99.8%) and 0.8% (95% CI 0.1-2.6%). The diagnostic efficiency of D-dimer in patients with ADD risk score 0 and ≤ 1 was 8.9% (95% CI 7.2-10.7%) and 23.6% (95% CI 21.1-26.2%) respectively., Conclusions: In a large cohort of patients with suspected AD, the presence of ADD risk score 0 or ≤ 1 combined with a negative D-dimer accurately and efficiently ruled out AD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Percutaneous endovascular aneurysm repair (PEVAR) can be performed with high technical success rates and low morbidity rates. Several peer-reviewed papers regarding PEVAR have routinely combined heparin reversal with protamine before sheath removal. The risks of protamine reversal are well documented and include cardiovascular collapse and anaphylaxis. The aim of this study is to review outcomes of patients who underwent PEVAR without heparin reversal., Methods: All patients who underwent percutaneous femoral artery closure after PEVAR between 2009-2012 without heparin reversal were reviewed. Only patients who underwent placement of large-bore (12- to 24-French) sheaths were included. Patient demographics, comorbidities, operative details, and complications were reported., Results: One hundred thirty-one common femoral arteries were repaired using the Preclose technique in 76 patients. Fifty-five patients underwent bilateral repair and 21 underwent unilateral repair. The mean age was 73.9±9.1 years. The mean heparin dose administered was 79±25.4 U/kg. The mean patient body mass index was 27.5±4.8 kg/m2. Ultrasound-guided arterial puncture was performed in all patients. Average operative times were 196.5±103.3 min, and the mean estimated blood loss was 277.6 mL. Four femoral arteries (3%) required open surgical repair after failed hemostasis with ProGlide closure (Abbott Vascular, Abbott Park, IL). Two patients required deployment of a third ProGlide device with successful closure. Two patients had small (<3 cm) groin hematomas that had resolved at the time of the postoperative computed tomography scan. No pseudoaneurysms or arteriovenous fistulas developed in our patient cohort. No early or late thrombotic complications were noted. One patient (1.3%) with a ruptured aneurysm died 48 hours after endovascular repair unrelated to femoral closure., Conclusions: PEVAR may be performed with low patient morbidity after therapeutic heparinization without heparin reversal. Femoral artery repair after the removal of large-diameter sheaths using the Preclose technique can be performed in this setting with minimal rates of early and late bleeding or thrombosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Biomarkers for monitoring progression and prognosis of thoracic aneurysm are of great interest. Homocysteine (Hcy) induces elastolysis in arterial media and may directly affect fibrillin-1 or collagen whereas lipoprotein (Lp) (a) inhibits elastolysis by reducing activation of matrix metallopeptidase-9., Methods: We studied 31 consecutive patients with acute aortic dissection (AAD) admitted for emergency surgery (group I, 60 ± 13 years old, 25 men), 30 consecutive patients with chronic aneurysms of the ascending aorta (group II, 67 ± 12 years old, 24 men) and 20 healthy controls (group III, 58 ± 15 years old, 14 men). We evaluated Hcy, folate, B12, Lp(a) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism at baseline., Results: Hcy, folate and B12 differed significantly among the 3 studied groups (P=0.016, P=0.004 and P=0.001, respectively). The levels of Hcy and B12 were significantly higher in group I compared to both groups II and III (P=0.05 and P=0.002, P<0.001 and P=0.017, respectively) and without significant differences between groups II and III (P=0.083 and P=0.124). Folate was significantly lower in group I compared to both groups II and III (P=0.001 and P=0.006, respectively) and without marked difference between groups II and III (P=0.409). No significant difference was found in serum levels of Lp (a) (P=0.074) or among the frequency of MTHFR C677T genotypes., Conclusions: Patients with AAD present with higher Hcy and lower folate compared to both chronic aneurysms and controls., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to assess the vitamin D status in patients with occlusive or aneurysmatic arterial disease in relation to clinical cardiovascular risk profiles and markers of atherosclerotic disease., Methods: We included 490 patients with symptomatic peripheral arterial disease (PAD, n = 254) or aortic aneurysm (n = 236). Cardiovascular risk factors and comorbidities carotid intima-media thickness (CIMT), ankle-brachial index (ABI), serum high-sensitive C-reactive protein (hs-CRP) and vitamin D were assessed. Patients were categorised into severely (≤25 nmol l(-1)) or moderately (26-50 nmol l(-1)) vitamin D deficient, vitamin D insufficient (51-75 nmol l(-1)) or vitamin D sufficient (>75 nmol l(-1))., Results: Overall, 45% of patients suffered from moderate or severe vitamin D deficiency. The prevalence of vitamin D deficiency was similar in patients with PAD and those with an aortic aneurysm. Low levels of vitamin D were associated with congestive heart failure and cerebrovascular disease. Adjusting for clinical cardiovascular risk factors, multivariable regression analyses showed that low vitamin D status was associated with higher CIMT (P = 0.001), lower ABI (P < 0.001) and higher hs-CRP (P = 0.022)., Conclusions: The current study shows a strong association between low vitamin D status and arterial disease, independent of traditional cardiovascular risk factors and irrespective of the type of vascular disease, that is, occlusive or aneurysmatic disease., (Copyright © 2012. Published by Elsevier Ltd.)

Objectives: Customized aortic repair (CAR) is a new concept for endovascular aortic aneurysm repair in which a non-polymerised elastomer is injected to fill the aneurysm sac around a balloon catheter. Amongst other variables, the thrombogenicity of the elastomer should be tested, before further clinical experiments can take place. The aim of this human ex vivo study was to measure the thrombogenicity of the elastomer and to compare it to expanded polytetrafluoroethylene (ePTFE)., Design and Materials: In a validated ex vivo model, non-anticoagulated blood was drawn from the antecubital veins of 10 healthy donors with a 19-gauge needle. It was drawn through elastomer tubes and through ePTFE Gore-Tex vascular grafts, both 60 cm long and with an inner diameter of 3 mm., Methods: Fibrinopeptide A (FPA) and P-selectin expression was measured in blood samples, collected at the end of the grafts. After the experiments, the deposition of platelets and fibrin onto the grafts was visualised by scanning electron microscopy., Results: For these graft types, a progressive increase in FPA production was observed in time. No significant difference was observed between the elastomer and ePTFE grafts (p > 0.05). No increase in P-selectin expression, and thereby no platelet activation, was observed in the perfusate of either grafts (p > 0.05). By scanning electron microscopy, numerous platelet aggregates were observed on the ePTFE grafts, whereas just a few adhered platelets and no aggregates were observed in the elastomer grafts., Conclusions: The elastomer in its current formulation has a low thrombogenicity, comparable to ePTFE, making it an ideal substance for endovascular aneurysm sac filling. Further research should clarify the feasibility of CAR in vivo., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The role of inflammation in aortic dissection (AD) has not fully been investigated. We evaluated the potential relationships between interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP-9) and AD., Methods: Plasma concentrations of IL-6, TNF-α, MMP-9 and CRP were determined in 64 acute AD patients, 42 patients with chronic AD, 98 patients with hypertension alone, and 96 healthy subjects., Results: IL-6 concentrations were higher in acute AD than that in hypertension and healthy controls (10.98±2.38 vs. 3.79±1.56 and 3.32±1.60 pg/ml, P<0.05, respectively). Increased CRP concentrations were found in acute AD compared with chronic AD and hypertension as well as healthy subjects (13.48±3.74 vs. 4.12±2.99, 1.62±0.65 and 1.12±0.35 mg/l, P<0.001, respectively). Higher MMP-9 concentrations were detected in acute AD, chronic AD and hypertension compared with healthy controls (37.75±9.38, 55.78±6.41 and 31.03±7.94 vs. 21.24±7.28 ng/ml, P<0.05, P<0.001 and P<0.05, respectively), and in the dead compared to the survived (107.29±9.38 vs. 86.80±7.93 ng/ml, P<0.001) among acute AD patients. In acute AD, the time after onset had positive correlation with TNF-α (r=0.497, P=0.000), and negative correlation with CRP (r=-0.424, P=0.000). Plasma CRP levels decreased significantly when the onset time increased (P=0.013). Moreover, in the patients with acute AD who underwent surgery and stenting, plasma MMP-9 concentrations increased immediately after surgical treatment and stenting, and reached the peak values at 24h, then decreased at 1 week (P<0.001)., Conclusions: Our findings confirmed and extended previous studies that increased plasma inflammatory markers were significantly associated with AD., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: An abnormally elevated preoperative white blood cell count (WBC) has been associated with postoperative morbidity and mortality. However, it is unknown if a normal WBC is predictive of postoperative outcomes following vascular interventions. Thus, the objective of this study is to determine if a WBC within the normal range is predictive of outcomes following vascular interventions., Methods: The medical records of patients undergoing endovascular and open repair of carotid stenosis, aortic aneurysm, and peripheral arterial disease from 1999 to 2009 were retrospectively reviewed. Major adverse events (MAE) were defined as death, stroke, and myocardial infarction., Results: Of 1773 cases with normal preoperative WBC (3.5-10.5 K/μL), there were 804 [45.3%] endovascular and 969 [54.7%] open vascular surgeries. Patients with complications (55) or MAE (19) after endovascular intervention had higher preoperative WBC compared with patients without complications (WBC 7.7 ± 1.47 vs 7.1 ± 1.57, respectively, P = .002) or MAE (WBC 8.3 ± 1.26 vs 7.1 ± 0.06, respectively, P = .001). No difference was observed for patients who received open surgery. Patients undergoing endovascular intervention were 2.3, 4.8, and 22 times more likely to experience complications (P = .004), MAE (P = .003), or death (P = .036) when WBC exceeded 7.5 K/μL. Multivariate analysis showed that preoperative normal WBC was an independent predictor of complications, MAE, and death in patients after endovascular procedures but only for death in patients after open vascular procedures., Conclusions: This study demonstrates a strong linear correlation between an increasing preoperative WBC within the normal range and an increased risk for postoperative complications and death following endovascular interventions. The study also found a significant curvilinear U-shaped relation between a normal preoperative WBC and death in the open surgical cohort, with patients in the very low and very high normal WBC range at an increased risk of death., (Published by Mosby, Inc.)

It is well-established that blood viscosity plays a significant role in the determination of the health of the individual. It has been reported that many cardiovascular diseases are associated with blood viscosity. In this paper, the dynamic behaviors of aortic aneurysm subject to physiological blood flow with normal and high viscosities are presented. Fluid-structure interaction (FSI) method was used in the computational simulation. The influence of blood viscosity on flow dynamics within the aneurysm sac, aneurismal diameter, cross sectional shape, wall axial displacement and wall shear stress (WSS) was studied in detail. This investigation uncovered the correlations between blood viscosity and the dynamic behaviors of aortic aneurysm, which have rarely been found in existing literatures. We believe that these findings may provide important implications for individualized endovascular treatment for patient with aortic aneurysm., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: We have previously shown that the angiotensin-converting enzyme (ACE) inhibitor perindopril reduced aortic diameter by 3-7mm in Marfan syndrome (MFS) patients. Excessive signalling by the transforming growth factor-beta (TGF-beta) has been implicated in the development of aortic dilatation. We hypothesised that reduction in aortic diameter would correlate with reduction in plasma TGF-beta and matrix metalloproteinase (MMP) levels., Methods: 17 MFS patients (aged 33+/-5 (mean+/-SD)) on standard beta-blocker therapy were randomised to also receive perindopril (n=10) or placebo (n=7) for 24 weeks in a double blind study. Aortic root diameters were assessed at four sites via transthoracic echocardiography. Venous blood samples were analysed for latent and active TGF-beta, MMP-2 and MMP-3 levels., Results: Perindopril significantly reduced aortic root diameters relative to placebo in both end-systole and end-diastole (by 1.2-3mm/m(2), p<0.001). In addition, compared to placebo perindopril significantly reduced latent TGF-beta levels by 14.0+/-4.5ng/ml (p=0.01), active TGF-beta levels by 4+/-1ng/ml (p=0.02), MMP-2 levels by 22+/-6ng/ml (p<0.001), and MMP-3 levels by 5+/-1ng/ml (p<0.001). There were moderately strong correlations between the pre/post intervention change in aortic diameters and the change in both latent (r=0.49-0.76, p=0.001-0.04) and active TGF-beta (r=0.59-0.73, p=0.002-0.02), MMP-2 (r=0.63-0.75, p=0.001-0.007), and MMP-3 plasma levels (r=0.81-0.83, p<0.0001)., Conclusions: Plasma TGF-beta, MMP-2 and MMP-3 should be further explored in longitudinal trials as potential prognostic indicators of progression of aortic dilatation and response to therapy in MFS.

Background and Aim: The breakdown of mucosal barrier function due to intestinal hypo-perfusion is the earliest dysfunction of ischaemic colitis. Severe colon ischaemia after aortic reconstruction is associated with mortality rates up to 90%. Therefore, early detection and treatment of patients with extensive ischaemic colitis is of crucial importance. In experimental studies, both D-lactate and bacterial endotoxin have been reported as markers of intestinal mucosal barrier impairment. However, evidence of their value in clinical practice is lacking. The aim of this pilot prospective cohort study was to assess the association between ischaemia of the colon (assessed histologically) and plasma levels of D-lactate and endotoxin in patients undergoing open aortic reconstruction., Patients and Methods: Twelve consecutive patients underwent surgery between February and April 2003. Six patients underwent emergency surgery and six patients elective aortic surgery. D-Lactate and endotoxin levels were measured in blood samples collected according to a standardised protocol. For histological examination biopsies were obtained by sigmoidoscopy on days 4-6 after surgery, or earlier if indicated clinically., Results: As early as 2 h postoperatively, elevated plasma levels of d-lactate were measured in patients with histologically proven ischaemic colitis. The peak of D-lactate elevation was on postoperative days 1 and 2. Concentration of plasma endotoxin was not significantly different in patients with or without ischaemic colitis., Conclusion: Our data suggest that plasma D-lactate levels are a useful marker for early detection of ischaemic colitis secondary to aortic surgery.

Background: Acute Stanford type A aortic dissection is associated with substantial perioperative morbidity and mortality. A sepsis-like state may lead to antithrombin (AT) III consumption and deficiency. The impact of preoperative AT III activity on outcome in patients undergoing emergency surgery is yet unknown., Methods: We measured preoperative AT III activity in 99 consecutive patients undergoing emergency aortic surgery for Stanford type A aortic dissection during a 4-year period in a retrospective study. Cardiovascular co-morbidities, risk factors and surgical data were recorded and patients were followed for 30-day mortality, and occurrence of multiple organ failure (MOF)., Results: During the first 30 days, 15 patients (15%) died, and 8 patients (8%) had MOF. Median AT III levels (IQR) in 30-day non-survivors versus survivors were 64% (52-72) versus 90% (75-97) (p<0.001), and in patients with versus without MOF were 66% (52.3-77.3) versus 88% (72-96) (p=0.018), respectively. Adjusted odds ratios for 30-day mortality and MOF for AT III activity (per % increments) were 0.92 (p=0.007), and 0.96 (p=0.012), respectively, indicating a significant inverse relationship between AT III activity and outcome., Conclusion: There is a strong inverse association between preoperative AT III activity and adverse outcome in patients undergoing surgical repair of acute Stanford type A aortic dissection. Larger studies are necessary to determine a cut-off value for AT III and to assess whether patients with low AT III levels benefit targeted therapeutic interventions.

Study Objective: Laboratory testing plays a minor role in the assessment of aortic dissection. Its main value is in the exclusion of other diseases. Following an incidental observation, we systematically investigated the relationship between elevated d-dimer levels and acute aortic dissection., Design: We prospectively tested d-dimer levels in patients with suspected acute aortic dissection (10 patients). In addition, we investigated 14 patients who had received a confirmed diagnosis of thoracic aortic dissection during the previous 5 years, in whom d-dimer testing had been performed for differential diagnosis. Thirty-five patients with acute chest pain of other origin served as a control group., Setting: Tertiary referral hospital., Patients: Twelve patients had type A dissection (Stanford classification), and 12 patients had type B., Measurements and Results: A d-dimer analysis was performed (Tina-quant assay; Roche Diagnostics; Mannheim, Germany) [normal limit of the assay, 0.5 micro g/mL]. The result of the d-dimer test was positive (ie, > 0.5 micro g/mL) in all patients (sensitivity of the test, 100%) with a mean value of 9.4 micro g/mL and a range of 0.63 to 54.7 micro g/mL. The degree of the elevation was correlated to the delay from the onset of symptoms to laboratory testing (mean, 12.6 h; range, 1 to 120 h) and showed a trend to the extent of the dissection, but not to the outcome (14 patients could be discharged; 10 patients died)., Conclusions: Based on our observation, we suggest that testing for d-dimer should be part of the initial assessment of patients with chest pain, especially if aortic dissection is suspected. A negative test result makes the presence of the disease unlikely.

The purpose of this study was to correlate the preoperative level of antioxidant defenses, measured by the plasma total antioxidant capacity (TAC), to the degree of postoperative systemic inflammatory response, measured by the severity of pulmonary injury following elective aortic surgery. Twenty-four patients had TAC measured preoperatively and 24 hr postoperatively. Chest radiography and arterial blood gases were obtained preoperatively and serially during the first 24 hr after surgery. Using objective radiologic criteria and blood gas analysis, the degree of pulmonary edema and pulmonary dysfunction were quantified. All patients showed evidence of pulmonary dysfunction in the first 24 hr following surgery. Fifteen of the 24 patients showed radiographic evidence of noncardiogenic pulmonary edema in the immediate postoperative period. In this group, the TAC was lower than in those without pulmonary edema immediately following surgery (p = 0.03). Preoperative TAC was associated with the degree of pulmonary edema in the postoperative period (r = -0.372, p = 0.067). These results suggest that preoperative antioxidant supplementation may favorably impact the severity of systemic inflammatory response following ischemia and reperfusion injury.

Purpose: This study was performed to evaluate the effects of a residual dissection on coagulation, fibrinolysis, and platelet function after surgical treatment of acute type A aortic dissection., Methods: Between 1987 and 1995, 48 consecutive patients underwent emergency surgery for acute type A aortic dissection. Thirty-five of 41 survivors were followed-up for periods ranging from 6 to 112 months (median, 30.3 months). These survivors were classified into three groups by computed tomographic scanning and angiography. Fifteen patients had no residual dissection (group I). Of the 20 patients who had residual dissection, nine had an enlarged aorta greater than 45 mm in maximal diameter (group II), and 11 had an aorta less than 45 mm in maximal diameter (group III). For all patients, blood samples were collected for coagulation, fibrinolysis, and platelet function studies on the same day that the computed tomographic scanning had been performed., Results: beta-thromboglobulin, thrombin-antithrombin III complex, D-dimer, and alpha 2 plasmin inhibitor-plasmin complex concentrations were significantly higher in group II than in the other two groups. Strong correlations between the maximal diameter of the dissected aorta and beta-thromboglobulin, thrombin-antithrombin III complex, D-dimer, and plasmin inhibitor-plasmin complex concentrations were evident. In contrast, correlations between the length of the dissected aorta and coagulation/fibrinolysis measurements were weak., Conclusions: Our findings suggest that the coagulopathy worsened in proportion to the degree of dilatation of the dissected aorta.

The immune response associated with an inflammatory abdominal aortic aneurysm was studied by determining the phenotypes of lymphocytes in the peripheral blood, the aortic aneurysm wall, and the perianeurysmal tissue. Increased numbers of activated T cells were found in all three areas. After aneurysm repair, peripheral blood analysis demonstrated normalization of the T-cell subsets. These data suggest that inflammatory abdominal aortic aneurysm is associated with a measurable immune response in peripheral blood with elevation of the same subset of inflammatory cells (CD4) as detected in abdominal aortic aneurysm tissue, and the immune response regresses after aneurysm repair.

We analyzed the short-term and long-term outcome of 42 patients with distal type aortic dissection. Twenty-eight patients underwent intensive medical therapy within two weeks after the onset of pain (acute dissection). The remaining 14 patients had chronic dissection. The goals of medical treatment were to control blood pressure and to attain a negative C-reactive protein test result. Hospital survival rate in the patients with acute dissection was 96% (27/28). In-hospital complications included changes in mental status, renal dysfunction, bradycardia, orthostatic hypotension, and liver dysfunction, all of which were managed medically. Three of these patients underwent surgical therapy in the chronic phase and were discharged uneventfully. Fifteen (62.5%) of the 24 medically treated patients were discharged with negative C-reactive protein tests. Spontaneous resolution of a dissection was demonstrated by radiological examinations in 8 cases. Five-year survival rates in 24 medically treated patients was 93%. Hospital survival rate in the patients with chronic dissection was 100% (14/14). The rigorous control of blood pressure in the acute phase, and subsequent meticulous evaluation of the dissection by radiological tests and C-reactive protein test provides acceptable short-term and long-term outcomes of patients with acute distal dissection without the need for emergency surgical intervention.

The complexity of infrarenal aortic reconstruction increases when bypass grafts to revascularize associated renal and visceral arteries are needed. Lesions in these vessels, however, are usually limited to their aortic orifices and therefore are amenable to retroperitoneal transaortic endarterectomy. A combined infrarenal aortic reconstruction and transaortic endarterectomy of the renal/visceral vessels was used in 18 (16%) of 120 patients undergoing elective infrarenal aortic reconstruction over a 2-year-period. Transaortic endarterectomy was performed primarily for renal preservation in 11 patients with bilateral, high-grade renal artery stenoses and abnormal renal function (serum creatinine greater than or equal to 1.9 mg/dl). In seven patients transaortic endarterectomy was performed as a secondary procedure during the course of complex reconstruction of aneurysmal or occlusive aortic disease. Mean serum creatinine, which was elevated preoperatively in 14 (78%) patients (3.3 mg/dl), decreased significantly after the operation (2.0 mg/dl, p less than 0.01). A single death occurred in the 18 patients undergoing transaortic endarterectomy. Renal function preservation can be achieved by renal revascularization in patients with bilateral renal artery stenoses and decreased renal function. The retroperitoneal approach to aortic reconstruction and the use of transaortic endarterectomy allows correction of most renal/visceral vessel involvement in complex aortic revascularization procedures.

Fibrin prepared from 15 pathologic thrombi was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the extent and pattern of fibrinolysis that occurs in vivo. Two groups of patients could be distinguished on the basis of the polypeptide chain composition of fibrin in their thrombi. Those patients who presented with acute vascular obstruction, either arterial or venous, showed a minimal degree of fibrin degradation, with a dominance of intact, undegraded crosslinked gamma-gamma dimers. On the other hand, patients with long-standing symptoms associated with chronic aortic aneurysms had thrombi containing extensively degraded fibrin. Thrombi in large aortic aneurysms were dissected into concentric layers that showed different degrees of fibrinolysis. The luminal surface consisted of fresh, red thrombus and contained undegraded crosslinked fibrin similar to that found in patients with acute occlusive disease. Deeper layers of the thrombus showed gamma-gamma chain degradation throughout, indicating that this portion was undergoing active thrombolysis. The findings demonstrate that the variability in the pathophysiologic balance between coagulation and fibrinolysis is reflected in vivo by the polypeptide chain composition of crosslinked fibrin in thrombi. The results support the hypothesis of a dynamic equilibrium between clotting and lysis, but indicate that the balance between these two processes may be distinctly different in separate areas of a single clot.

The correlation between mixed venous oxygen saturation (SvO2) and hemodynamic measurements was studied in 13 patients undergoing descending thoracic aortic aneurysm resection (DTAAR). A significant correlation (p less than 0.05) was found between cardiac index (CI) and SvO2 after the induction of anesthesia and at the end of surgery. However, no significant correlation could be found between SvO2 and CI during the most critical periods of the surgery that included the collapse of the left lung, the aortic clamping, and the aortic declamping. During DTAAR, continuous SvO2 monitoring is useful, but it cannot substitute for intermittent cardiac output and oxygen consumption (VO2) determinations.

The existence of inhibitors of plasminogen activator has been shown to play an important role in regulation of fibrinolysis and postoperative thrombosis. Platelets and endothelium are sources of plasminogen activator inhibitor (PAI). This study determines the contribution of platelet-released PAI to perioperative fibrinolytic shutdown. PAI levels were measured in 25 patients having aortic surgery. In nine patients the platelet-released PAI contribution was determined by in vitro activation of platelets with phorbol-myristate-acetate (PMA). Mean preoperative PAI levels (3.78 +/- 1.19 U/ml) were similar to controls (3.01 +/- 1.04 U/ml) (p greater than 0.05). Plasma PAI showed an operative increase to a maximum at 8 hours postoperatively and returning to preoperative values by the second postoperative day. In the nine patients who were subjected to studies with in vitro activation, the preoperative PAI level (4.0 +/- 0.9 U/ml) was elevated to 5.1 +/- 0.7 U/ml (p = 0.001) with PMA induction. Maximum stimulated release of platelet granule contents (platelet releasate) could account for an increase of only 1.0 U/ml compared with a postoperative increase of 2.3 U/ml. Postoperative mean peak plasma PAI (6.3 +/- 0.4 U/ml) could not be further elevated by induced release (6.3 +/- 0.4 U/ml) (p = 0.003). A statistically significant increase in PAI occurred in aortic surgery patients postoperatively. The platelet releasable pool of PAI contributed to the increase and was functionally exhausted postoperatively. Postoperative increases of PAI were twice that induced by platelet in vitro stimulation alone. The perioperative increase in PAI was partly due to platelet release.

Massive coagulopathy and bleeding continues to play a major role in the operative mortality and perioperative multi-system failure of patients requiring elective thoracoabdominal aneurysm repair. It was the purpose of this study to determine the coagulation defect that occurs with supraceliac aortic clamping and the effects of increasing aortic cross-clamp time (AXCT) on the coagulation system and its recovery. Through a standard thoracoabdominal incision, 16 mongrel dogs had their aortas cross-clamped simultaneously just above the diaphragm and at the aortic bifurcation. Animals were divided into four groups of four animals each; sham operation, 30 minute AXCT, 60 minute AXCT, and 90 minute AXCT. Central venous blood was sampled prior to aortic cross clamping (AXC), during AXC and 1 hour, 2 hours, 5 hours, 7 hours, 12 hours, and 24 hours after the clamp was removed. All samples were assayed for platelets, fibrinogen, fibrin split products, prothrombin time (PT) and partial thromboplastin time (PTT). Platelets and fibrinogen decreased as PT and PTT increased with increasing AXCT consistent with disseminated intravascular coagulation (DIC) (P less than .001). Fibrin split products were positive in the 90 minute AXCT group only. The drop in platelets was greater for increasing AXCT and continued to fall in the 30, 60 and 90 minute AXCT groups at 24 hours (p less than .001). Fibrinogen dropped to the lowest levels between two and twelve hours after AXC and returned to normal at twenty-four hours in the 60 and 90 minute AXCT groups (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)