Postoperative serum mir-28-5p level has predictive value for the prognosis after endovascular abdominal aortic aneurysm repair.

BACKGROUND: We explored the clinical significance of miR-28-5p pre- and post-endovascular abdominal aortic aneurysm repair (EVAR) in abdominal aortic aneurysm (AAA) patients. METHODS: Subjects included AAA patients receiving EVAR and non-AAA people without statistical differences from AAA patient in comorbidities/Framingham risk score. Fasting elbow venous blood (4 mL) was collected in the morning of the day of EVAR surgery and in the morning of 3 months post-EVAR. Pre-/post-EVAR serum miR-28-5p expression, AAA maximum diameter alterations, CD3+/CD4+/CD8+/TC/TG pre-/post-EVAR, and the correlations between miR-28-5p and AAA maximum diameter were investigated. Prediction of miR-28-5p on post-EVAR mortality, prognosis, and independent factors of post-EVAR death were analyzed using receiver operating characteristic curve (ROC)/Kaplan-Meier curve/univariable and multivariable Cox regression. According to the cut-off value of ROC curve for postoperative miR-28-5p was the cut-off value, and the patients were classified into the miR-28-5p high- and low-expression groups. The survival or death of both groups were compared after 48-month follow-up. RESULTS: Serum miR-28-5p levels in AAA patients dropped post-EVAR. AAA patients showed notable differences in CD3+/CD4+/CD8+/TC/TG levels pre-/post-EVAR. The miR-28-5p low-expression group exhibited higher CD3+/CD4+ and lower CD8+/TC/TG levels. We observed a positive correlation between post-EVAR miR-28-5p and AAA maximum diameter and between the pre-/post-EVAR miR-28-5p fold change and the AAA maximum diameter change. Postoperative miR-28-5p demonstrated good predictive value for postoperative death. Hypertension, Framingham risk score, TC, TG, and miR-28-5p were independent influencing factors of post-EVAR death. CONCLUSION: EVAR decreased serum miR-28-5p expression in AAA patients. Post-operative miR-28-5p level and pre-/post-operative fold change level are positively-correlated with AAA diameter.

Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Apoe-/- Mice.

AIM: Abdominal aortic aneurysm (AAA) is a lethal and multifactorial disease. To prevent a rupture and dissection of enlarged AAA, prophylactic surgery and stenting are currently available. There are, however, no medical therapies preventing these complications of AAA. Statin is one of the candidates, but its efficacy on AAA formation/progression remains controversial. We have previously demonstrated that nanoparticles (NPs) incorporating pitavastatin (Pitava-NPs)-clinical trials using these nanoparticles have been already conducted-suppressed progression of atherosclerosis in apolipoprotein E-deficient ( Apoe-/-) mice. Therefore, we have tested a hypothesis that monocytes/macrophages-targeting delivery of pitavastatin prevents the progression of AAA. METHODS: Angiotensin II was intraperitoneally injected by osmotic mini-pumps to induce AAA formation in Apoe-/- mice. NPs consisting of poly(lactic-co-glycolic acid) were used for in vivo delivery of pitavastatin to monocytes/macrophages. RESULTS: Intravenously administered Pitava-NPs (containing 0.012 mg/kg/week pitavastatin) inhibited AAA formation accompanied with reduction of macrophage accumulation and monocyte chemoattractant protein-1 (MCP-1) expression. Ex vivo molecular imaging revealed that Pitava-NPs not only reduced macrophage accumulation but also attenuated matrix metalloproteinase activity in the abdominal aorta, which was underpinned by attenuated elastin degradation. CONCLUSION: These results suggest that Pitava-NPs inhibit AAA formation associated with reduced macrophage accumulation and MCP-1 expression. This clinically feasible nanomedicine could be an innovative therapeutic strategy that prevents devastating complications of AAA.

The elevated expression of TLR4 and MMP9 in human abdominal aortic aneurysm tissues and its implication.

BACKGROUND: Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) have been investigated to play significant roles in the formation of abdominal aortic aneurysm (AAA). But the reports on the expression pattern of TLR4 and MMP9 in human AAA specimens were relatively scant. The aim of this study was to make a detailed analysis of TLR4 and MMP9 expression in situ and their association with clinical parameters involved in human AAA. METHODS: 40 AAA specimens were obtained from full-thickness aneurysmal tissues at the maximal dilation area during the open surgical repair, and 8 non-aneurysmal abdominal aortas from transplant donors served as controls. Expression of TLR4 and MMP9 protein was determined by immunohistochemistry. RESULTS: There were increased levels of TLR4 and MMP9 expression in human AAA tissues. Compared with macrophages or SMCs, lymphocytes showed a higher positive rate of TLR4 and MMP9 staining, and an elevated ratio of high MMP9 expression (all P < 0.05). There existed a significant association between TLR4 and MMP9 expression (r = 0.767, P < 0.001), and both TLR4 and MMP9 levels were statistically related to circulating CRP. Moreover, TLR4 expression in situ indicated a positive correlation with its serum level (r = 0.654, P = 0.006). Multiple analysis revealed that high TLR4 expression in situ was associated with the risk of large AAA (OR = 6.211, 95%CI = 1.226-31.480, P = 0.027), while high MMP9 expression was correlated to the presence of thrombus within AAA (OR = 5.494, 95%CI = 1.181-25.562, P = 0.030), separately compared with their low expression. CONCLUSIONS: This study confirmed the overexpression of TLR4 and MMP9 in human AAA tissues, and their close relationship implying in the pathogenesis of AAA. We further provided evidence that TLR4 had a potential effect on AAA size and MMP9 could influence the occurrence of thrombus within AAA.

Decreased transfusion requirements with use of acute normovolemic hemodilution in open aortic aneurysm repair.

OBJECTIVE: Acute normovolemic hemodilution (ANH) is an operative blood conservation technique involving the removal and storage of patient blood after the induction of anesthesia, with maintenance of normovolemia by crystalloid and/or colloid replacement. Developed and used predominately in cardiac surgery, ANH has been applied to the vascular surgery population. However, data regarding the effects on transfusion requirements in this population are limited. The objective of the present study was to compare the transfusion requirements and coagulopathy for patients who had undergone open abdominal aortic aneurysm repair (oAAAR) using ANH to those for patients who had received only product replacements, as clinically indicated. METHODS: We performed a retrospective review of patients who had undergone elective oAAAR at a quaternary aortic referral center from 2017 to 2019. Those eligible for ANH, with no active cardiac ischemia, no valvular disease, normal left ventricular and right ventricular function, chronic kidney disease stage <3, hematocrit >38%, and a normal coagulation profile were included in the present study. Patient demographics and characteristics and operative variables, including aneurysm extent, clamp site, visceral and renal ischemia time, operative time, and transfusion requirements, were collected. Postoperative morbidity, mortality, and length of stay were analyzed. The patients with and without ANH were matched and compared. Continuous measures were analyzed using Wilcoxon rank sum tests and t tests. RESULTS: During the study period, 209 oAAARs had been performed. Of the 209 patients, 76 had met the inclusion criteria. Of these 76 patients, 27 had undergone ANH and 49 had not. The patients with ANH had required fewer PRBC transfusions intraoperatively (median, 0 U; interquartile range [IQR], 0-1 U; median, 1 U; IQR, 0-2 U; P = .02), at 24 hours (median, 0 U; IQR, 0-1 U; vs median, 1 U; IQR, 0-2 U; P = .008), at 48 hours (median, 0 U; IQR, 0-1 U; vs median, 1 U; IQR, 0-2; P = .007), and throughout the admission (median, 0 U; IQR, 0-1 U; vs median, 2 U; IQR, 0-2 U; P = .011). No difference was found in the number of intraoperative platelet or cryoprecipitate transfusions. At 48 hours, the ANH group had had significantly greater platelet counts (142 ± 35.8 × 103/µL vs 124 ± 37.6 × 103/µL; P = .044), lower partial thromboplastin time, and lower international normalized ratio. No difference in myocardial infarction, return to the operating room, or mortality (one death overall). The ANH patients had a shorter length of stay (7.0 ± 2.7 vs 8.8 ± 4.8 days; P = .041). CONCLUSIONS: The use of ANH during oAAAR resulted in fewer intraoperative and postoperative PRBC transfusions with improved coagulation parameters and a shorter hospital length of stay.

Sex hormones in men with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAAs) primarily affect elderly men. The effect of sex on aneurysm development has been associated with the effects of sex hormones through mechanisms that are not fully understood. The present study examined the association between the levels of sex hormones and the occurrence of AAAs in elderly men. METHODS: A prospective case-control study was conducted of 452 men aged 65 years participating in screening for AAAs from 2013 to 2019. Of the 452 men, 230 had an AAA and 222 an aortic diameter of <30 mm (control group). Questionnaires and blood samples were collected and stored consecutively. The serum levels of total testosterone, estradiol, progesterone, luteinizing hormone, and sex hormone-binding globulin were analyzed using electrochemiluminescent immunoassays. Multivariable logistic regression analysis was used to assess the association between sex hormones and AAA. RESULTS: The median aneurysm diameter was 33 mm. Men with AAA had greater estradiol (93 pmol/L vs 84 pmol/L; P =.003) and progesterone (0.41 nmol/L vs 0.17 nmol/L; P < .001) levels compared with the controls. The testosterone levels were lower in the AAA group than in the control group (13 nmol/L vs 14 nmol/L; P = .026). AAA was associated with detectable levels of progesterone (odds ratio [OR], 6.69; 95% confidence interval [CI], 3.86-11.47), smoking (OR, 5.26; 95% CI, 3.12-8.85), coronary heart disease (OR, 4.06; 95% CI, 1.92-8.58), and a body mass index >25 kg/m2 (OR, 2.26; 95% CI, 1.34-3.82). CONCLUSIONS: The observed higher estradiol and progesterone levels in men with an AAA suggest an effect of sex hormones on aneurysm development. The association between progesterone levels and the aortic diameter stresses the importance of focusing on the potential effect of this unconsidered female sex hormone on aneurysm formation.

An iron oxide nanoworm hybrid on an interdigitated microelectrode silica surface to detect abdominal aortic aneurysms.

An abdominal aortic aneurysm (AAA) is abnormal swelling in the abdominal aorta and a prevalent life-threatening disease. This research introduces a new interdigitated microelectrode (IDME)-sensing surface modified by iron oxide nanoworms (IONWs) for detecting the AAA biomarker insulin-like growth factor-1 (IGF1). A sandwich pattern was formulated with the IGF1 aptamer and IGFBP1 (IGF binding protein-1) on the IONW-constructed IDME hybrid to identify IGF1. The surface morphology of the IONWs revealed a uniform distribution of worm-like structures (80-100 nm) as confirmed by FESEM and FETEM analyses. Further, the presence of the major elements, Fe and O, was confirmed by EDX and XPS studies. The crystal planes that appeared in the IONW reflect cubic magnetite. IONW-modified IDME attained a limit of detection for IGF1 of 1 fM (3σ) with an aptamer-IGF1-IGFBP1 sandwich. This sandwich with IGFBP1 enhanced the current level at all concentrations of IGF1 and displayed linearity in the range 1 fM to 100 pM with a determination coefficient of R2 = 0.9373 [y = 3.38221x - 4.79]. Control experiments with complementary aptamer sequences, IGF2 and IGFBP3 did not show notable signal changes, indicating the specific detection of IGF1. This IONW constructed electrode helps to achieve the detection of low amounts of IGF1 and diagnose AAA at the stage prior to rupture.

Vitamin K2 Dependent Matrix Gla Protein Relating to Abdominal Aortic Aneurysm and Overall Mortality: A Combined Case Control and Cohort Study.

OBJECTIVE: Inactivation of matrix Gla protein (MGP), using vitamin K antagonists or vitamin K deficiency results in increased vascular calcification, which has been associated with increased risk of symptomatic or ruptured abdominal aortic aneurysm (AAA). Insufficient activation of MGP leads to increased levels of undercarboxylated forms of MGP, measured as a dephosphorylated, undercarboxylated MGP (dp-ucMGP) in plasma. This study aimed to investigate whether the level of inactivated MGP influenced the risk of having an AAA, the risk of AAA progression, and overall mortality. METHODS: This combined case control and cohort study was based on data from the randomised, clinically controlled Viborg Vascular (VIVA) screening trial. Cases (n = 487) with an AAA and controls (n = 189) with neither peripheral artery disease nor AAA, had their plasma quantified for dp-ucMGP. Plasma levels were compared with the presence of an AAA, AAA growth rate, need for repair, and overall mortality. dp-ucMGP was divided into tertiles in regression analyses. RESULTS: The plasma levels of dp-ucMGP were higher for AAA cases compared with controls (median of 517 pmol/L vs. 495 pmol/L, p = .036). Adjusted analyses regarding dp-ucMGP being predictive of AAA, AAA growth rate, and need for repair all failed to show correlation. Overall mortality for AAA cases exhibited a significant association for the third tertile of dp-ucMGP with a hazard ratio of 2.55 (95% CI 1.29 - 5.05) compared with the first tertile. Overall mortality for controls was not correlated with dp-ucMGP plasma levels. CONCLUSION: dp-ucMGP did not correlate with the risk of having an AAA, AAA growth rate, or risk of surgery. For people with an AAA, dp-ucMGP was correlated with an increased mortality risk for the highest tertile of dp-ucMGP. This could suggest a role for prophylactic measures with vitamin K2 supplements to people at risk of AAA.

Low glucose and serum levels cause an increased inflammatory factor in 3T3-L1 cell through Akt, MAPKs and NF-кB activation.

Abdominal aortic aneurysm (AAA) involves the degradation of vascular fibres, and dilation and rupture of the abdominal aorta. Hypoperfusion in the vascular walls due to stenosis of the vasa vasorum is reportedly a cause of AAA onset and involves the induction of adventitial ectopic adipocytes. Recent studies have reported that ectopic adipocytes are associated with AAA rupture in both human and hypoperfusion-induced animal models, highlighting the pathological importance of hypoperfusion and adipocytes in AAA. However, the relationship between hypoperfusion and AAA remains unknown. In this study, we investigated the changes in inflammation-related factors in adipocytes at low glucose and serum levels. Low glucose and serum levels enhanced the production of AAA-related factors in 3T3-L1 cells. Low glucose and serum levels increased the activation of protein kinase B (also known as Akt), extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, and nuclear factor (NF) кB at the protein level. The inflammatory factors and related signalling pathways were markedly decreased following the return of the cells to normal culture conditions. These data suggest that low glucose and serum levels increase the levels of inflammatory factors through the activation of Akt, mitogen activated protein kinase, and NF-κB signalling pathways.

Neutrophil-to-Lymphocyte Ratio Associated With Adverse Events After Endovascular Aneurysm Repair (EVAR).

BACKGROUND: The blood neutrophil-to-lymphocyte ratio (NLR) is a surrogate biomarker of systemic inflammation with important prognostic significance in multiple disease processes, including cardiovascular diseases. It is inexpensive, widely available, and may be related to the outcomes of patients after surgery. We aimed to investigate the possible association of NLR with the outcomes of patients following endovascular aneurysm repair (EVAR). METHODS: This single-center, retrospective study of a prospectively maintained database evaluated 777 patients with a diagnosed abdominal aortic aneurysm (AAA) who underwent EVAR and were longitudinally followed between 2001 and 2017. NLR was defined as the ratio of absolute neutrophil count to absolute lymphocyte count. The mortality and reinterventions were used to evaluate outcomes using the appropriate univariate models, and the effect of clinical variables on NLR was further investigated using multivariate modelling. RESULTS: The median NLR for all patients was 3 IQR [2.2 - 4.6]. A cut-off point of 3.6 was uncovered in a training set of 388 patients using the maximally ranked statistic method. Patients with NLR < 3.6 had significantly improved mortality rates (P< 0.0001) in the training set, and results were internally validated in a testing set of 389 patients (P = 0.042). Multivariate analysis revealed that high NLR (HR 1.4 95% CI [1.0 - 2.0]; P< 0.05) remained an independent predictor of mortality in a multivariate analysis controlling for characteristics such as comorbidities, age, and maximal aortic diameter. 5-year mortality and 30-day, 1-year and 5-year reinterventions were all higher in the high NLR group. CONCLUSION: High NLR was significantly associated with higher rates of death at 5 years as well as higher rates of reinterventions at 30 days, 1 year and 5 years. We also suggest that an internally validated cut-off point of NLR >3.6 may be clinically important to help segregate patients into high and low NLR categories. It remains unclear whether NLR is directly linked to adverse events post-EVAR or whether it is a surrogate for an inflammatory state that predisposes patients to higher risk of death or reinterventions.

Challenges of applying circulating biomarkers for abdominal aortic aneurysm progression.

As a prevalent potentially life-threatening condition, abdominal aortic aneurysm (AAA) presents increasing risk of rupture as its diameter grows. However, rapid progression and rupture may occasionally occur in smaller AAAs. Earlier surgery for patients with high risk of disease progression may improve the outcome. Therefore, more precise indicators for invasive treatment in addition to diameter and abdominal symptoms are demanded. This systematic review aimed to identify potential circulating biomarkers that may predict growth rate of AAA. Cochrane and PubMed library were searched (until August 2020) for researches which reported circulating biomarkers associated with AAA expansion, and 25 papers were included. Twenty-eight identified biomarkers were further classified into five categories (inflammation and oxidative stress, matrix degradation, hematology and lipid metabolism, thrombosis and fibrinolysis, and others), and discussed further with their correlation and regression analysis results. Larger prospective trials are required to establish and evaluate prognostic models with highest values with these markers.

The potential role of plasma fibroblast growth factor 21 as a diagnostic biomarker for abdominal aortic aneurysm presence and development.

AIMS: Fibroblast growth factor 21 (FGF21) has been identified as the master hormonal regulator of energy balance, its elevation is observed in a series of metabolic and cardiovascular diseases. Studies have implicated the role of FGF21 signaling in the pathogenesis of abdominal aortic aneurysm (AAA). We will investigate the association of FGF21 and AAA development. MATERIALS AND METHODS: In this study, we assayed plasma levels of FGF21 in 82 patients with AAA and 44 control subjects, then analyzed their relationship with clinical, biochemical and histological phenotypes. The expression of ß-klotho, an essential co-receptor of FGF21, was assessed with IHC staining and RT-qPCR. Machine learning models incorporate a combination of FGF21 and clinical data were utilized in the prediction of AAA occurrence. KEY FINDINGS: FGF21 was statistically higher in patients with AAA (781 pg/ml [533, 1213]) than in control subjects (567 pg/ml [324, 939]). After adjustment for age and BMI, we found a positive association of FGF21 levels with AAA diameters, hypertension rate and hsCRP, and a negative correlation between FGF21 levels and HDL-c. Furthermore, the protein levels of ß-klotho in abdominal aorta of AAA were found significantly lower than in control group indicating the presence of FGF21 resistance. Combining FGF21 levels with four clinical characteristics significantly improved the stratification of AAA and control groups with an AUC of 0.778. SIGNIFICANCE: Combining detection of plasma FGF21 and clinical characteristics may be reliable for identifying the presence of AAA. The role of FGF21 as a therapeutic target of AAA warrants further investigation.

Abdominal aortic aneurysm and virus infection: A potential causative role for cytomegalovirus infection?

An abdominal aortic aneurysm (AAA) is a multifactorial disease with a variety of genetic and environmental risk factors, but the exact mechanism of AAA formation and progression is still not well understood. The present study investigated the frequency of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and papillomavirus types 6 and 11 (HPV6 and HPV11), their impact on clinical manifestations of cardiovascular diseases, and their possible association with inflammation in patients with AAA and healthy volunteers. Genotyping of CMV UL75, EBV LMP-1, and HPV6, and HPV11 E6 was performed by polymerase chain reaction (PCR), while the viral DNA loads were measured by quantitative real-time PCR. Cytokine levels were determined by enzyme-linked immunosorbent assays. The CMV UL75 was detected more frequently in the blood of patients with AAA than in the blood of healthy volunteers (32.7% vs. 6.3%, p < .0001). Neither EBV LMP-1 nor HPV6 E6 was found in blood and aortic wall biopsies, while the HPV11 E6 was detected in 36.4% of AAA walls. The CMV infection in patients with AAA was associated with an increased risk of hypertension and coronary artery disease (OR, 9.057; 95% CI, 1.141-71.862; p = .037; and OR, 2.575; 95% CI, 1.002-6.615; p = .049, respectively). Additionally, CMV-infected patients with AAA had higher tumor necrosis factor-α levels compared with noninfected subjects (p = .017). Our findings suggest that CMV infection can stimulate local inflammation in the aorta but is not a direct cause of most abdominal aortic aneurysms.

Biomolecular assembly on interdigitated electrode nanosensor for selective detection of insulin-like growth factor-1.

This research is focussed to quantify IGF1 by electroanalytical analysis on InterDigitated electrode surface and characterized by the microscopic observations. For the detection, antibody and aptamer were used to analyze the level of IGF1. The sandwich pattern (aptamer-IGF1-antibody) was designed on the chemically modified IDE surface and reached the limit of detection to 10 fM with 100 folds enhancement in the sensitivity. Different control experiments (absence of IGF1, binding with IGF2 and with non-complementary aptamer) were failed to show the current changes, discriminated the specific detection. A good detection strategy is to complement the currently following imaging systems for AAA.

Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy.

Endogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.

Sensitive determination of NT-proBNP for diagnosing abdominal aortic aneurysms incidence on interdigitated electrode sensor.

Abdominal aortic aneurysm (AAA) is a vascular disease found to have progressive growth in the area of aorta. Rupturing of aorta causes excessive bleeding that leads to health-related issues, which can be fatal sometimes. Therefore, it becomes important to make early diagnosis of AAA and its condition and start immediate treatment. Blood-based biomarker helps to diagnose AAA and to monitor the condition after AAA surgery. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a hormone produced in the heart in small quantities and increased when the heart needs to work harder. NT-proBNP was proved to be strongly linked with AAA incidence. Moreover, quantifying the level of NT-proBNP helps to determine the risk factors on cardiovascular system after the surgery. This work is quantifying the NT-proBNP on interdigitated electrode sensor by using NT-proBNP binding aptamer. The detection limit of NT-proBNP was calculated as 1 pg/mL on a linear regression curve [y = 0.2148x + 0.8849; R² = 0.9049]. The linear range with dose-dependent analysis was from 0.01 until 100 ng/mL. Moreover, the control experiment with complementary aptamer sequence did not show the current signal, specifying the detection of NT-proBNP. This research benefits to identify the heart condition of patient after the removal of AAA.

The Effect of Transfusion of Two Units of Fresh Frozen Plasma on the Perioperative Fibrinogen Levels and the Outcome of Patients Undergoing Elective Endovascular Repair for Abdominal Aortic Aneurysm.

BACKGROUND: We aimed to investigate whether the transfusion of 2 units of fresh frozen plasma (FFP) immediately post aneurysm exclusion has any effect on the perioperative fibrinogen levels and the outcome of patients undergoing elective endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). METHODS: Consecutive infrarenal AAA patients undergoing elective EVAR with the bifurcated Endurant-II stent-graft (Medtronic) were recruited from 2 vascular units. The first unit has a routine policy of administering 2 units of FFP immediately upon aneurysm exclusion (FFP group), whereas the second unit has no such policy (control group). Serum fibrinogen levels were measured on admission and 24 hr post-EVAR and the perioperative change in fibrinogen (Δfib) was calculated (24-hr postoperative minus preoperative fibrinogen). The 2 groups were compared with regards to the perioperative fibrinogen levels (preoperative, 24-hr postoperative, and Δfib) and the outcome (endoleaks, reinterventions, major adverse cardiovascular events, death) during follow up. RESULTS: A total of 70 patients (41 in the FFP group, 29 controls) were examined. There were 68 men, the mean age was 70 ± 7 years and the maximum AAA diameter was 63.3 ± 13.8 mm. During the follow up (34 ± 19 months), a total of 6 endoleaks were recorded (2 type Ia, 2 type Ib and 1 type II). Mean preoperative fibrinogen, 24-hr postoperative fibrinogen and Δfib was 391.1 ± 92.8 mg/dL, 367.7 ± 97.8 mg/dL and -23.5 ± 51.02 mg/dL, respectively. There was a trend for the fibrinogen to fall 24 hr postprocedure, but this was not statistically significant (P = 0.07). There was a weak negative association between Δfib and endoleaks (P = 0.007, r = -0.29). Compared to controls, the FFP group had a higher 24-hr postoperative fibrinogen (401.8 ± 112.9 mg/dL vs. 319.3 ± 34.9 mg/dL, P < 0.0001) and a lower Δfib (-3.00 ± 56.01 mg/dL vs. -52.48 ± 21.15 mg/dL, P < 0.0001). No significant difference was observed between the 2 groups with regards to endoleaks, reinterventions, major adverse cardiovascular events, or deaths. CONCLUSIONS: Transfusion of 2 units of FFP postaneurysm exclusion prevents a significant drop in plasma fibrinogen 24 hr post-EVAR, but the impact on clinical outcome has yet to be defined.

Metformin Prescription Associated with Reduced Abdominal Aortic Aneurysm Growth Rate and Reduced Chemokine Expression in a Swedish Cohort.

BACKGROUND: Recent reports suggest that the negative association between diabetes mellitus and abdominal aortic aneurysm (AAA) may be driven by metformin, the world's most common antidiabetic drug rather than diabetes per se. We sought to investigate the association among AAA growth rate, chemokine profile, and metformin prescription in a contemporary Swedish cohort. METHODS: Patients under surveillance for small AAA were identified at 4 Swedish vascular centers with active AAA screening programs. Annual AAA growth rate, medical history, and prescribed medications were recorded for linear regression analysis. In a subset of patients with AAA and control subjects without AAA or diabetes, plasma samples were available and analyzed for 40 inflammatory chemokines. RESULTS: A total of 526 patients were included for AAA growth analysis: 428 without type 2 diabetes mellitus (T2DM), 65 with T2DM and metformin prescription, and 33 with T2DM but without metformin prescription. Patients were included from 2005 to 2017 with mean follow-up of 3.2 (1.7) years and median annual AAA growth rate 1.6 mm, range -4.8 to 15.4 mm. Mean (standard deviation) annual AAA growth rates were 2.3 (2.2) mm in non-T2DM patients versus 1.1 (1.1) mm in patients with T2DM with metformin prescription and 1.6 (1.4) mm among those with T2DM without metformin prescription. With non-T2DM patients as reference in an unadjusted and 2 adjusted models, metformin prescription was significantly associated with reduced AAA growth rate (P < 0.001, P = 0.005, and P = 0.024, respectively), but not T2DM without metformin prescription (P = 0.137, P = 0.331, and P = 0.479, respectively). Among 240 patients with AAA (152 without T2DM, 51 with T2DM and metformin, and 37 with T2DM without metformin) and 59 without AAA or T2DM, metformin prescription was associated with reduced expression of chemokines representing all classes of leukocytes. CONCLUSIONS: Metformin prescription is associated with reduced AAA growth rate, possibly mediated by broad anti-inflammatory effects. A randomized controlled trial is needed to determine what role metformin may play in AAA disease, particularly in the absence of T2DM.

Perioperative cardiovascular complications rate and activity of coagulation and fibrinolysis among patients undergoing vascular surgery for peripheral artery disease and abdominal aortic aneurysm.

OBJECTIVES: To compare preoperative coagulation and fibrinolysis activity and incidence of perioperative complications between patients undergoing vascular procedures for peripheral artery disease and abdominal aortic aneurysm. METHODS: This is a substudy of a prospective observational cohort study (VISION; NCT00512109) in which we recruited patients aged ≥45 years, undergoing surgery for peripheral artery disease and abdominal aortic aneurysm. Blood samples were obtained 24 h preoperatively to measure platelet count, concentrations of coagulation coagulation (fibrinogen, factor VIII, von Willebrand factor:Ristocetin cofactor, antithrombin III), fibrinolysis (dimer D, plasmin-antiplasmin complexes, tissue plasminogen activator) markers and level of soluble CD40 ligand. Incidence of myocardial infarction, stroke, and death (composite endpoint) was assessed in 30-day follow-up. RESULTS: The study group included 131 patients at the mean age of 68.3 years among whom reason for surgery was peripheral artery disease in 77 patients (58.8%) and abdominal aortic aneurysm in 54 patients (41.2%). Peripheral artery disease group was characterized by higher platelet count (250.5 versus 209.5 (×103/µl), p = 0.001), concentrations of fibrinogen (5.4 versus 4.1 (g/l), p < 0.001), factor VIII (176.9 versus 141.9 (%), p < 0.001), von Willebrand factor:Ristocetin cofactor (188.9 versus 152.3 (%), p = 0.009), and soluble CD40 ligand (9016.0 versus 7936.6 (pg/ml), p = 0.005). The dimer D level was higher (808.0 versus 2590.5 (ng/ml), p < 0.001) in the abdominal aortic aneurysm group. Incidence of major cardiovascular events (death, myocardial infarction, stroke) within 30 days from surgery did not differ between the groups (39.0% versus 29.6%, p = 0.27). CONCLUSIONS: The study suggests higher activation of coagulation and relatively lower fibrinolytic activity in peripheral artery disease group compared to patients undergoing surgery for abdominal aortic aneurysm without a significant difference in cardiovascular outcomes.

Effects of Exercise Training on Vascular Markers of Disease Progression in Patients with Small Abdominal Aortic Aneurysms.

BACKGROUND: Currently, no medical therapy is effective in limiting progression of small abdominal aortic aneurysms (AAA; ≤5.5 cm). Previously, we have demonstrated safety and efficacy of exercise training in patients with AAA. However, the impact of exercise training on vascular markers of AAA progression, such as lipid accumulation product and matrix metalloproteinase 9 (MMP-9, linked to destruction of aortic matrix), is unknown. The aim of this study was to assess the impact of exercise training on AAA diameter, lipid accumulation product, MMP-9, and other risk markers of vascular disease. METHODS: In this randomized trial, complete data of 96 patients (male: n = 87, female: n = 9; exercise training (exercise) n = 42, usual care n = 54) were studied. Changes in AAA diameter, exercise capacity, lipid accumulation product (men = [waist circumference 65] × fasting triglycerides; women = [waist circumference -58] × triglycerides) and MMP-9 were performed. RESULTS: The exercise group demonstrated a significant increase in maximal exercise time and estimated metabolic equivalent of tasks. Lipid accumulation product decreased in exercise and increased in usual care (P < .001 between groups); MMP-9 remained statistically unchanged in exercise, but increased significantly in usual care (P = .005; between groups P = .094). In both groups, there was a significant increase in transverse diameter, but no difference between groups; neither group assignment nor level of fitness correlated with AAA enlargement. No adverse clinical events occurred. CONCLUSIONS: This is the first study to demonstrate that in AAA, exercise beneficially modifies lipid accumulation product and MMP-9, both markers of vascular disease, without inducing aneurysmal growth beyond what is otherwise observed during usual care.

The Role of Serum Calprotectin as a New Marker in Abdominal Aortic Aneurysms - A Preliminary Report.

BACKGROUND: Abdominal Aortic Aneurysm (AAA) remains a surgical challenge. There are many recognizable markers associated with the formation of AAA. Previous experiments carried out on animal models have shown a correlation between serum calprotectin and the occurrence of AAA. OBJECTIVE: This study aimed to evaluate the level of calprotectin as a potential diagnostic biomarker in patients with diagnosed AAA. METHODS: The study group consisted of 75 patients aged 35-75 years assigned to two groups: a control group (n=43) of healthy subjects without AAA and a study group (n=32) of patients with a diagnosed AAA. The first calprotectin test was performed upon patient admission to the hospital, and the second control test was performed after three months. The concentration of calprotectin in plasma was determined using the Immunoenzymatic Method (ELISA) with the commercially available Assaypro Kit (AssayMax™ Human Calprotectin ELISA Kit), as well as the sandwich method with polyclonal antibodies to human calprotectin and peroxidase enzyme. RESULTS & DISCUSSION: Serum calprotectin levels in AAA patients were three times higher than in healthy subjects (p<0.05). A statistically significant twofold decrease in calprotectin concentration was observed after AAA surgery compared to the control group (p<0.05). CONCLUSION: Calprotectin levels can be an important marker in the detection of AAA. In conclusion, AAA patients showed a threefold increase in serum calprotectin level and a twofold decrease in this marker after AAA surgery.