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1.
Life Sci ; 240: 117069, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31751582

RESUMO

AIM: Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression. MAIN METHODS: This was a retrospective observational study that involved 181 patients with infra-renal AAA. They were divided into small and large AAA groups according to AAA diameter. 24 of them had repeated abdominal computed tomography angiography (CTA) scan and were divided into slow-growing and fast-growing AAA groups according to the median value of AAA growth rate. Baseline and follow-up plasma D-dimer level, maximum diameter of AAA, total infra-renal aortic volume and ILT volume were analyzed. KEY FINDINGS: Plasma D-dimer level was positively correlated with ILT volume (R = 0.382, P < 0.001) and maximum diameter of AAA (R = 0.442, P < 0.001). Increasing value of plasma D-dimer was positively associated with the accelerated growth rate of AAA (R = 0.720, P < 0.01). ILT volume showed positive correlation with maximum diameter (R = 0.859, P < 0.001) and growth rate of AAA (R = 0.490, P < 0.05). After adjusting the baseline ILT volume, the positive correlations remained to be statistically significant between plasma D-dimer level and AAA size (R = 0.200, P < 0.05), as well as increasing value of plasma D-dimer and growth rate of AAA (R = 0.642, P < 0.05). SIGNIFICANCE: Plasma D-dimer level reflected ILT burden in AAAs. Plasma D-dimer level and ILT volume were positively correlated with AAA size. Increasing value of plasma D-dimer and baseline ILT volume could be predictors of AAA progression.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose/complicações , Trombose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/sangue , Efeitos Psicossociais da Doença , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fumar/epidemiologia , Trombose/sangue , Tomografia Computadorizada por Raios X
2.
Biomed Pharmacother ; 118: 109229, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351425

RESUMO

Open surgical or percutaneous endovascular (EVAR) intervention is the only approved treatment for abdominal aortic aneurysm (AAA). Novel targeted therapy and companion diagnostic are needed. Our study aimed to investigate the expression of myeloid related protein 8/14 (MRP8/14) in AAA and explore whether MRP8/14 can be a biomarker and therapeutic target for AAA. The serum levels of MRP8/14 and inflammatory factors including TNF-α, IL-1ß, and IL-6 were increased in 20 human AAA patients compared to healthy people by ELISA assay. The mRNA and protein expressions of MRPs in AAA tissues of AAA patient were significantly elevated when compared with the levels in adjacent non-aneurysmal aortic segments in AAA patients. through PCR and western blot analysis. Correlation analysis and receiver operating characteristic (ROC) curve analysis confirmed that MRP8/14 was secreted into the serum and possessed the potential diagnostic value. Rat AAA models established by perfusion porcine pancreatic elastase and murine macrophage RAW264.7 cells were used to evaluate the mechanisms of MRP8/14 after treatment with antibodies. Similarly, MRP8, MRP14, and MRP8/14 were highly expressed in rat AAA model, while the administrations of antibodies of MRPs significantly reversed the improvement expressions of MRP8 and MRP14. In RAW264.7 cells, MRPs especially for MRP8/14 obviously increased the levels of MMP-2 and MMP-9. Under MRP8/14 stimulation, the antibodies of MRPs recovered the expressions of MMP-2 and MMP-9. Anti MRP8/14 antibody exhibited the strongest effect in the experiments. Our results indicated that MRP8/14 was associated with AAA presence and progression and could be considered as a biomarker for AAA diagnose. Anti MRP8/14 can be a potential therapeutic target for treatment of AAA.


Assuntos
Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/terapia , Complexo Antígeno L1 Leucocitário/metabolismo , Terapia de Alvo Molecular , Adulto , Animais , Aneurisma da Aorta Abdominal/sangue , Biomarcadores/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/sangue , Complexo Antígeno L1 Leucocitário/genética , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Pessoa de Meia-Idade , Modelos Biológicos , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Suínos
3.
Biomed Res Int ; 2019: 7976043, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205945

RESUMO

Background: In recent years, a rapid increase in studies focusing on the role of oxidative stress in the pathogenesis of an abdominal aortic aneurysm (AAA) has been observed. Oxidative modifications of proteins are infrequently evaluated in reference to AAA. Objectives: The intensity of oxidative protein modifications, presented as advanced oxidation protein products (AOPP) and carbonylated proteins (C=O), in AAA patients qualified for surgery was estimated. The effect of surgical techniques and intraoperative and postoperative treatment on AOPP and C=O levels was evaluated. Patients: The EVAR group, consisting of 30 patients, was classified for endovascular aneurysm repair, whereas 28 patients were classified for conventional open repair (OR). Methods: AOPP and C=O were measured using a colorimetric assay kit. Results: A significantly lower AOPP level obtained 2-4 days after EVAR surgery in comparison with the value found before surgery was noted. In the case of OR postoperative treatment, a tendency of AOPP level to increase was observed. The tendency of C=O to decrease after surgery in the EVAR group was indicated. However, the C=O level tended to increase after OR surgery and reached a significantly higher value 5-7 days after surgery compared with the value obtained before surgery. Conclusions: Based on our results, it may be concluded that AAA as well as surgical technique contribute to the formation of AOPP and C=O. The analysis of changes in AOPP and C=O values obtained after surgery revealed a significant effect of a patient's condition before surgery as well as the choice of surgery technique on the values of the studied parameters revealed during postoperative treatment.


Assuntos
Produtos da Oxidação Avançada de Proteínas/sangue , Aneurisma da Aorta Abdominal , Procedimentos Endovasculares , Estresse Oxidativo , Carbonilação Proteica , Idoso , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório
4.
Heart Vessels ; 34(12): 2031-2039, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31144100

RESUMO

This study is a prospective evaluation of the effectiveness of cardiac rehabilitation (CR) in terms of clinical outcomes for small abdominal aortic aneurysms (AAA) that were previously reported in a retrospective cohort study. We conducted a prospective non-randomized trial on patients with small AAA (N = 40; mean age 75.0 ± 6.6 years). Patients were enrolled into one of two groups, rehabilitation (CR) or non-rehabilitation (non-CR) group. Only CR group participated in a supervised-CR program including bicycle ergometer for 150 days. The AAA expansion rate and the risk of AAA repair were compared between two groups. We also researched the relationship between AAA expansion rate and body composition, blood IL-6 and TGFß1 levels. The CR (N = 15) and non-CR groups (N = 25) were comparable in terms their baseline data. The CR group had a significantly smaller change in the maximal AAA size (- 1.3 ± 2.4 mm/years) compared to the non-CR group (2.0 ± 3.6 mm/years) (p < 0.01). The IL-6, and TGFß1 levels were unrelated to the changes in AAA size. There was mild positive correlation between the change in systolic blood pressure from rest to exercise and the AAA expansion rate (p = 0.06). The risk of AAA repair after 12 months was lower in the CR group compared to the non-CR group (0% vs. 28%, respectively). CR in patients with small AAA significantly suppressed AAA expansion and resulted in a lowered risk of AAA repair.Clinical trial Trial name: The study of the profitability and protective effect of cardiac rehabilitation on abdominal aortic aneurysm. Number: UMIN000028237. UTL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R0000323.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/reabilitação , Reabilitação Cardíaca/métodos , Idoso , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico , Biomarcadores/sangue , Citocinas/sangue , Progressão da Doença , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Projetos Piloto , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
5.
FEBS Open Bio ; 9(6): 1137-1143, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31001930

RESUMO

Abdominal arterial aneurysm (AAA) shares many features with autoimmune diseases and appears to be a T-cell-mediated process. In addition, certain epigenetic changes, including DNA methylation, are associated with AAA. In this study, we investigated epigenetic modifications in regulatory T cells (Tregs) from AAA patients. We used flow cytometry to sort FOXP3+ CD4+ CD25+ Tregs from the peripheral blood of AAA patients and from healthy controls (HC), and then detected DNA methylation and histone modifications by ELISA. The DNA methylation rate of Tregs was significantly higher in AAA patients than in the HC group (0.159 ± 0.08% vs 0.098 ± 0.03%, P < 0.05), while the acetylation rates of H3 and H3K9 histones were lower in the AAA than in the HC group. We also examined the expression of mRNA encoding enzymes that catalyze making and removing epigenetic modifications by real-time PCR: we found that mRNA levels of DNA methyltransferase (DNMT) 1 and DNMT3A were higher in the AAA than in the HC group, mRNA levels of methyl-CpG-binding domain protein (MBD) 2 and MBD4 were higher in the AAA than in the HC group (MBD2: 6.21 ± 2.57 vs 3.04 ± 1.45; MBD4: 7.76 ± 3.48 vs 4.97 ± 3.10; both P < 0.05), and mRNA levels of histone deacetylase (HDAC) 1 and HDAC5 were significantly up-regulated in the AAA compared with the HC group (HDAC1: 2.17 ± 1.18 vs 1.51 ± 0.99; HDAC5: 1.35 ± 0.49 vs 0.94 ± 0.76; both P < 0.05). Together, our results reveal that rates of DNA methylation and histone modifications of Tregs are significantly altered in AAA patients.


Assuntos
Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/genética , Epigênese Genética/genética , Linfócitos T Reguladores/fisiologia , Acetilação , Idoso , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Endodesoxirribonucleases/genética , Feminino , Histona Desacetilase 1/genética , Histona Desacetilases/genética , Histonas/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Regulação para Cima/genética
6.
Biochimie ; 162: 1-7, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30922869

RESUMO

OBJECTIVES: The potential implication of micro-RNAs (miRs) in the negative association between diabetes and abdominal aortic aneurysm (AAA) has so far never been addressed. The aim of this study was to compare miR expression between diabetic and non-diabetic patients with AAA. METHODS: Ten diabetic patients were prospectively included and compared to 10 age- and sex-matched non-diabetic patients with infrarenal AAA. A profiling analysis of 752 human miRs was performed from peripheral blood mononuclear cells (PBMCs) using miRCURY LNA Universal RT microRNA PCR (Exiqon- Qiagen®). miR that showed significant differential expression (P < 0.05) were selected and further analyzed in the entire cohort in sera, plasma and aneurysmal aortic tissues. RESULTS: Four miRs were significantly differentially expressed in PBMCs of diabetic patients compared to non-diabetics: 3 were upregulated (miR-144-3p, 20a-5p and 188-3p) and 1 downregulated (miR-548k). miR-144-3p and miR-548k were also increased in aneurysmal tissue and miR-20a-5p was increased in serum. The expression of miR-20a-5p in PBMCs was correlated with fructosamine concentration (r = 0.62, p = 0.006). CONCLUSIONS: Even if further studies are required to determine their direct role in AAA, these miRs could represent interesting new targets.


Assuntos
Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/metabolismo , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , MicroRNAs/metabolismo , Idoso , Aneurisma da Aorta Abdominal/sangue , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade
7.
Ann Vasc Surg ; 58: 270-275, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30769065

RESUMO

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a useful predictor of cardiovascular risk and adverse outcomes. According to previous studies, an NLR >5 has the highest sensitivity and specificity for postoperative morbidity and mortality in cardiovascular disease. This study aims to evaluate the NLR in cases of infrarenal unruptured abdominal aortic aneurysm (uAAA) and ruptured abdominal aortic aneurysm (rAAA) and to assess the role of NLR as a prognostic marker of 30-day mortality in patients with uAAA and rAAA who underwent surgical repair. METHODS: This retrospective cohort study examined 255 consecutive patients with intact or ruptured infrarenal AAA who underwent elective or urgent open repair surgery within our clinic in a 10-year period. Differences in prevalence were assessed using chi-squared calculations and values greater than 5 and a P-value less than 0.05 were considered significant. The averages were compared using the ANOVA parameter test when the Bartlett P-value was greater than 0.05. RESULTS: The average NLR appeared to be significantly higher in the group of patients with rAAA (9.3 vs. 3.39, respectively P < 0001). Furthermore, NLR > 5 occurred in 77.6% of patients with rAAA but only 32.5% in patients with uAAA (odds ratio 5.085; 95% confidence interval [CI]: 3.0025-8.6145; P < 0000.1). In terms of the postoperative prognosis in patients with uAAA, mortality after 30 days postoperatively was considerably higher at 16.6% in patients with NLR >5 compared with 6% for patients with NLR < 5 (RR: 2.77; 95% CI: 1.020-7.55; P < 0.045). In the case of rAAA, mortality after 30 days was higher in patients with NLR >5 (61.44%) than those with NLR < 5 (45.83%). There was no relationship between NLR and length of hospital stay or between NLR and the maximum diameter of the AAA. There was also no difference in the NLR between genders or age groups. CONCLUSIONS: The main findings of this study were the poor outcomes in terms of 30-day mortality for the patients presenting NLR values greater than 5 undergoing open surgical repair in both categories: infrarenal uAAA and rAAA. We also show that NLR is significantly higher among patients with rAAA and that an NLR >5 indicates a 5 times greater possibility of AAA being ruptured. We can use this easily determinable, broadly available, and inexpensive marker to identify high-risk patients, individually, or integrated into a risk-stratification system for patients diagnosed with AAA. This would help in the therapeutic management of AAA, including the avoidance of open surgery when there are prohibitive risks, instead opting for an endovascular approach.


Assuntos
Aneurisma da Aorta Abdominal/sangue , Ruptura Aórtica/sangue , Neutrófilos , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Ruptura Aórtica/cirurgia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Ann Vasc Surg ; 59: 84-90, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30802592

RESUMO

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cardiovascular (CV)-related disease that requires surgical treatment to prevent rupture. The elevation of arterial stiffness (AS) is an increasingly recognized independent determinant of CV morbidity and mortality and plays a special role in atherosclerosis. The importance of the surgical technique used for AAA repair in the long-term outcomes still needs to be clarified, and whether endovascular aortic repair (EVAR) or open surgical repair (OSR) confers high AS measurements and thus worse prognosis in terms of CV morbidity needs further investigation. METHODS: A prospective nonrandomized study that included consecutive patients requiring either EVAR or OSR for AAA disease between February 2015 and January 2016 was conducted. This study is registered on the National Institutes of Health website (ClinicalTrials.gov) and identified with NCT02642952. Several noninvasive measurements of AS and central aortic hemodynamics were obtained before surgery and in the first postoperative control (4-6 weeks), with change from baseline in heart rate-adjusted augmentation index (AIx@75) as main outcome. Likewise, inflammatory circulating biomarkers were also measured in the same time line. RESULTS: We included 44 patients, 25 in the EVAR group and 19 in the OSR group. Subjects who underwent EVAR were older and presented larger aneurysm diameter at baseline. There was a significant decrease in AIx@75 in the EVAR group after treatment (-4.1 ± 8.1%, P = 0.018), for a moderate effect size (d = 0.508), whereas the decreasing trend in the OSR group (-2.5 ± 6.7%, P = 0.127) was not statistically significant. No significant changes in carotid-radial pulse wave velocity (PWVCR) and central blood pressures were observed. The inflammatory markers increased after surgical repair, with significant changes in homocysteine in both EVAR (5.2 ± 6.9 µmol/L, P = 0.002) and OSR (1.8 ± 2.1 µmol/L, P = 0.002) groups. CONCLUSIONS: Our study suggests that both treatments confer better postoperative values of AS measured by AIx@75 and produces no changes in PWVCR, in the early term. Whether this situation is maintained during follow-up needs further investigation.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Mediadores da Inflamação/sangue , Rigidez Vascular , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Biomarcadores/sangue , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Estudos Prospectivos , Desenho de Prótese , Análise de Onda de Pulso , Fatores de Tempo , Resultado do Tratamento
9.
Ann Vasc Surg ; 57: 210-219, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30684630

RESUMO

BACKGROUND: In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture. METHODS: In this observational study, aneurysm tissue and blood of ruptured (n = 13) AAA patients were investigated versus nonruptured (n = 26) patients. Nondilated aortas (n = 5) from deceased patients and venous blood from healthy volunteers (n = 10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively. RESULTS: NGAL (in µg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P < 0.01) and 14 (range 12-22) in controls (P < 0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P = 0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs = 0.80, P < 0.01), MMP-9 (Rs = 0.56, P = 0.02), and caspase-3 (Rs = 0.75, P = 0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P = 0.34 and P = 0.95, respectively). CONCLUSIONS: This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.


Assuntos
Aorta Abdominal/química , Aneurisma da Aorta Abdominal/sangue , Ruptura Aórtica/sangue , Lipocalina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/patologia , Ruptura Aórtica/patologia , Apoptose , Biomarcadores/sangue , Caspase 3/análise , Dilatação Patológica , Progressão da Doença , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Retrospectivos , Tirosina/análogos & derivados , Tirosina/análise , Regulação para Cima , Remodelação Vascular
11.
Eur J Clin Invest ; 49(3): e13055, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30475403

RESUMO

BACKGROUND: Major surgery comes with a high risk for postoperative inflammatory complications. Preoperative risk scores predict mortality risk but fail to identify patients at risk for complications following cardiovascular surgery. We therefore assessed the value of preoperative red cell distribution width (RDW) as a predictor for pneumonia and sepsis after cardiovascular surgery and studied the relation of RDW with hematopoietic tissue activity. METHODS: RDW is an easily accessible, yet seldomly used parameter from routine haematology measurements. RDW was extracted from the Utrecht Patient Orientated Database (UPOD) for preoperative measurements in patients undergoing open abdominal aortic anuerysm repair (AAA)(N = 136) or coronary artery bypass grafting (CABG)(N = 2193). The cohorts were stratified in tertiles to assess effects over the different groups. Generalized Linear Models were used to determine associations between RDW and postoperative inflammatory complications. Hematopoietic tissue activity was scored using fluor-18-(18F)-deoxyglucose positron emission tomography and associated with RDW using linear regression models. RESULTS: In total, 43(31.6%) and 73 patients (3.3%) suffered from inflammatory complications after AAA-repair or CABG, respectively; the majority being pneumonia in both cohorts. Postoperative inflammatory outcome incidence increased from 19.6% in the lowest to 48.9% in the highest RDW tertile with a corresponding risk ratio (RR) of 2.35 ([95%CI:1.08-5.14] P = 0.032) in AAA patients. In the CABG cohort, the incidence of postoperative inflammatory outcomes increased from 1.8% to 5.3% with an adjusted RR of 1.95 ([95%CI:1.02-3.75] P = 0.044) for the highest RDW tertile compared with the lowest RDW tertile. FDG-PET scans showed associations of RDW with tissue activity in the spleen (B = 0.517 [P = 0.001]) and the lumbar bone marrow (B = 0.480 [P = 0.004]). CONCLUSION: Elevated RDW associates with increased risk for postoperative inflammatory complications and hematopoietic tissue activity. RDW likely reflects chronic low-grade inflammation and should be considered to identify patients at risk for postoperative inflammatory complications following cardiovascular surgery.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ponte de Artéria Coronária/efeitos adversos , Pneumonia/diagnóstico , Sepse/diagnóstico , Idoso , Aneurisma da Aorta Abdominal/sangue , Biomarcadores/metabolismo , Índices de Eritrócitos/fisiologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos
12.
Ann Vasc Surg ; 56: 202-208, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30500639

RESUMO

BACKGROUND: We investigated the potential association between perioperative fibrinogen levels and outcome in patients undergoing elective endovascular abdominal aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). METHODS: Consecutive patients with an intact AAA undergoing elective EVAR with a specific bifurcated endograft (Endurant, Medtronic) were recruited between December 2012 and October 2016. Preoperative and 24-hr postoperative fibrinogen levels were recorded, and potential associations with outcome were tested. Primary outcome measures included endoleaks, lower limb ischemic complications, including endograft limb occlusion, and aneurysm-related reinterventions. RESULTS: Ninety-four patients (91 male, mean age 71.8 ± 8.0 years) with an intact AAA were enrolled in the study. The technical success was 98% (2 failures: 1 type Ia endoleak on completion angiography, 1 lower limb ischemia immediately postoperatively requiring femoral endarterectomy). There was 1 death during the first 30 days due to myocardial infarction (1%). Another patient died 15 months after the procedure from cardiac causes. During the existing follow-up (mean 14.8 ± 14.3 months), 14 patients (15%) developed an endoleak (4, type Ia endoleak and 10, type II endoleak), 6 patients (6.3%) had lower limb ischemia/endograft limb occlusion, and 10 patients (10.6%) required reintervention. Compared with the preoperative values, no significant change occurred with regard to the fibrinogen levels 24 hr after procedure (mean preoperative fibrinogen 360 ± 101 mg/dl vs 24-hr postoperative fibrinogen 349 ± 105 mg/dl, P = 0.1). Neither preoperative nor 24-hr postoperative fibrinogen levels were significantly associated with the development of endoleaks, lower limb ischemia, or reinterventions. However, the difference in fibrinogen levels (baseline to 24 hr after procedure) was significantly higher in patients with endoleaks (median -65 mg/dl vs. 15 mg/dl, P = 0.04). CONCLUSIONS: Perioperative fibrinogen levels may play a role in predicting midterm outcomes in patients undergoing elective EVAR and appears to be associated, directly or indirectly, with the development of endoleaks. Further studies are needed to investigate these findings and explore future therapeutic implications.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Fibrinogênio/análise , Idoso , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Biomarcadores/sangue , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Procedimentos Cirúrgicos Eletivos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
13.
Vasc Endovascular Surg ; 53(1): 5-11, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30021492

RESUMO

INTRODUCTION:: The predictive value of the platelet to lymphocyte ratio (PLR) has been demonstrated in several cardiovascular diseases. The aim of this study was to investigate the interest of the preoperative PLR as a predictor of 30-day postoperative outcome in patients with abdominal aortic aneurysm (AAA) undergoing open or endovascular surgical repair. MATERIAL AND METHODS:: Two hundred twenty-four consecutive patients with infrarenal AAA were retrospectively included and divided into 4 quartiles according to the value of the preoperative PLR: PLR < 91.5 (group I), 91.5 < PLR < 120.8 (group II), 120.8 < PLR < 163.3 (group III), and PLR > 163.3 (group IV). RESULTS:: The AAA diameter was similar among the groups (54.9 mm vs 58.6, 57.5, and 58.7 mm; P = .4655). The proportion of symptomatic AAA and the procedural characteristics did not differ. Patients from group I and IV had significantly higher rates of all-cause postoperative complications compared to group II and III (55.4% and 64.3% vs 39.3% and 46.4%, respectively; P = .0478). The all-cause mortality tended to be higher in group I and IV (7.1% and 8.9% vs 0% and 3.6%, respectively; P = .1305). CONCLUSION:: Extreme values of PLR are associated with a higher risk of complications following AAA surgical repair, suggesting its interest as a biomarker to evaluate the surgical risk.


Assuntos
Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/cirurgia , Plaquetas , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Linfócitos , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Implante de Prótese Vascular/mortalidade , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Angiology ; 70(2): 130-140, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29945457

RESUMO

Animal and human laboratory studies suggest that the pathogenesis of abdominal aortic aneurysms (AAAs) involves inflammation and degradation and remodeling of the extracellular matrix. This study prospectively assessed the association between biomarkers for these mechanisms and the presence of AAA during 24 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) study. The ARIC prospectively identified clinically diagnosed AAAs in 15 792 men and women from baseline in 1987 to 1989 to 2011 using hospital discharge codes and death records. Additional asymptomatic AAAs were detected by an abdominal ultrasound scan in 2011 to 2013. Matrix metalloproteinase (MMP)-3, MMP-9, interleukin 6 (IL-6), N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin were measured in blood samples collected between 1987 and 1992 in participants with AAA (544 clinically diagnosed AAAs and 72 ultrasound-detected AAAs) and a random sample of 723 participants selected from baseline and matched with AAAs by age, race and sex. Higher concentrations of MMP-9 and IL-6 were associated with future risk of clinically diagnosed AAA (hazard ratios [95% confidence intervals]: 1.55 [1.22-1.97] and 1.87 [1.48-2.35], respectively, comparing highest versus lowest tertiles) after multivariable adjustment ( P for trend < .001). Matrix metalloproteinase-9 was also associated with ultrasound-detected AAA. In conclusion, blood concentrations of MMP-9 and IL-6 measured in middle age predicted the risk of AAA during 24 years of follow-up.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Aterosclerose/sangue , Biomarcadores/sangue , Matriz Extracelular , Inflamação/sangue , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/sangue , Aterosclerose/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco
15.
Rev Cardiovasc Med ; 20(4): 201-208, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31912711

RESUMO

Aortic aneurysms are mostly asymptomatic but have high rates of mortality when there is rupture or dissection. Matrix metalloproteinases is involved in the evolution of aortic aneurysms. Advanced glycation end products and its cell receptor RAGE (receptor for AGE) and sRAGE (soluble receptor of AGE) have been suggested to be involved in the pathogenesis of numerous diseases. This review addresses the role of AGE, RAGE and AGE-RAGE stress (AGE/sRAGE) in the pathogenesis of abdominal aortic aneurysm and thoracic aortic aneurysm in humans. AGERAGE interaction not only increases the generation of reactive oxygen species and inflammatory cytokines, but also activates NF-kB. There are increases in the levels of AGE in aortic tissue, skin and serum in patients with thoracic aortic aneurysm and abdominal aortic aneurysm. Levels of RAGE in tissue are elevated in abdominal aortic aneurysm. AGE-RAGE stress is elevated in patients with thoracic aortic aneurysm. The serum levels of cytokines and Matrix metalloproteinases are elevated in patients with thoracic aortic aneurysm and abdominal aortic aneurysm. The levels of AGE and AGE-RAGE stress correlate positively with cytokines and Matrix metalloproteinases, but the serum levels of sRAGE correlate negatively with cytokines and Matrix metalloproteinases. Cytokines levels are positively correlated with the levels of Matrix metalloproteinases in patients with thoracic aortic aneurysm. In conclusion, elevated levels of AGE, RAGE and AGE-RAGE stress, and reduced levels of sRAGE increase the levels of cytokines that in turn increase the production of Matrix metalloproteinases resulting in formation of aortic aneurysms. The data suggest that AGE-RAGE stress is involved in the pathogenesis of aortic aneurysms. Treatment options have also been discussed.


Assuntos
Aorta/metabolismo , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Torácica/sangue , Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/fisiopatologia , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Torácica/tratamento farmacológico , Aneurisma da Aorta Torácica/patologia , Aneurisma da Aorta Torácica/fisiopatologia , Citocinas/sangue , Dilatação Patológica , Humanos , Mediadores da Inflamação/sangue , Metaloproteinases da Matriz/sangue , Espécies Reativas de Oxigênio/sangue , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Transdução de Sinais , Remodelação Vascular
17.
Arterioscler Thromb Vasc Biol ; 38(11): 2750-2754, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30354236

RESUMO

Objective- The ability of HDL (high-density lipoprotein) to promote macrophage cholesterol efflux is considered the main HDL cardioprotective function. Abdominal aortic aneurysm (AAA) is usually characterized by cholesterol accumulation and macrophage infiltration in the aortic wall. Here, we aim to evaluate the composition of circulating HDL particles and their potential for promoting macrophage cholesterol efflux in AAA subjects. Approach and Results- First, we randomly selected AAA and control subjects from Spain. The AAA patients in the Spanish cohort showed lower plasma apoA-I levels concomitantly associated with low levels of plasma HDL cholesterol and the amount of preß-HDL particles. We determined macrophage cholesterol efflux to apoB-depleted plasma, which contains mature HDL, preß-HDL particles and HDL regulatory proteins. ApoB-depleted plasma from AAA patients displayed an impaired ability to promote macrophage cholesterol efflux. Next, we replicated the experiments with AAA and control subjects derived from Danish cohort. Danish AAA patients also showed lower apoA-I levels and a defective HDL-mediated macrophage cholesterol efflux. Conclusions- AAA patients show impaired HDL-facilitated cholesterol removal from macrophages, which could be mechanistically linked to AAA.


Assuntos
Aneurisma da Aorta Abdominal/sangue , HDL-Colesterol/sangue , Macrófagos/metabolismo , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Apolipoproteína A-I/sangue , Apolipoproteína B-100/sangue , Estudos de Casos e Controles , Dinamarca , Feminino , Lipoproteínas de Alta Densidade Pré-beta/sangue , Humanos , Masculino , Espanha
18.
Int Angiol ; 37(6): 444-450, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30350931

RESUMO

INTRODUCTION: The presence of an abdominal aortic aneurysm (AAA) is associated with increased thrombin formation, fibrin turnover and fibrinolysis. EVIDENCE ACQUISITION: The aim of this study was to review the relevant literature and summarize the evidence regarding the impact of endovascular repair on the circulating markers of coagulation and fibrinolysis postprocedure. EVIDENCE SYNTHESIS: The main findings are that the increased thrombin activation, and formation, as well as fibrinolysis, in patients with AAA is exacerbated after endovascular repair in the short-term and the mid-term, implying that this may be a period associated with an increased likelihood for adverse cardiovascular events. It is estimated that this prothrombotic state is normalized within a year of the endovascular procedure. Furthermore, elevated levels of specific markers of fibrinolysis are associated with the presence of an endoleak during the follow-up imaging and the clinical implications of these findings merit investigation. CONCLUSIONS: Further and larger studies are needed to explore the impact of these changes in coagulation and fibrinolysis on the outcome of endovascular repair in patients with AAA.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Coagulação Sanguínea , Implante de Prótese Vascular , Procedimentos Endovasculares , Fibrinólise , Trombina/metabolismo , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Biomarcadores/sangue , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
J Am Heart Assoc ; 7(19): e009866, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30371299

RESUMO

Background There is no drug therapy for abdominal aortic aneurysm ( AAA ). FAME-2 (Fenofibrate in the Management of Abdominal Aortic Aneurysm 2) was a placebo-controlled randomized trial designed to assess whether administration of 145 mg of fenofibrate/d for 24 weeks favorably modified circulating markers of AAA. Methods and Results Patients with AAA s measuring 35 to 49 mm and no contraindication were randomized to fenofibrate or identical placebo. The primary outcome measures were the differences in serum osteopontin and kallistatin concentrations between groups. Secondary analyses compared changes in the circulating concentration of AAA -associated proteins, and AAA growth, between groups using multivariable linear mixed-effects modeling. A total of 140 patients were randomized to receive fenofibrate (n=70) or placebo (n=70). By the end of the study 3 (2.1%) patients were lost to follow-up and 18 (12.9%) patients had ceased trial medication. A total of 85% of randomized patients took ≥80% of allocated tablets and were deemed to have complied with the medication regimen. Patients' allocated fenofibrate had expected reductions in serum triglycerides and estimated glomerular filtration rate, and increases in serum homocysteine. No differences in serum osteopontin, kallistatin, or AAA growth were observed between groups. Conclusions Administering 145 mg/d of fenofibrate for 24 weeks did not significantly reduce serum concentrations of osteopontin and kallistatin concentrations, or rates of AAA growth in this trial. The findings do not support the likely benefit of fenofibrate as a treatment for patients with small AAA s. Clinical Trial Registration URL : www.anzctr.org.au . Unique identifier: ACTRN 12613001039774.


Assuntos
Aneurisma da Aorta Abdominal/tratamento farmacológico , Fenofibrato/administração & dosagem , Osteopontina/sangue , Serpinas/sangue , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Hipolipemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia
20.
BMC Cardiovasc Disord ; 18(1): 202, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373522

RESUMO

BACKGROUND: Matrix metalloproteinase-9 (MMP9) has been reported to play a key role in the pathogenesis of aortic aneurysm. However, few studies have assessed serum MMP9 levels in both abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). In this study, we investigated the serum levels of MMP9 in aortic aneurysm to evaluate its predictive and diagnostic efficacy for AAA and TAA, and explored the association of MMP9 with circulating laboratory markers. METHODS: A total of 296 subjects were enrolled, including 105 AAA patients, 79 TAA patients and 112 healthy controls. The levels of serum MMP9 were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to control group, both AAA and TAA patients had higher serum MMP9 levels in the overall comparison and subgroup analysis based on subjects aged<65 years, either male or female, hypertension, non-diabetes and non-hyperlipidemia (all P<0.05). Moreover, MMP9 levels were significantly higher in TAA group than those in AAA group in the total comparison, and this discrepancy was also found in the non-diabetes, non-hyperlipidemia and aortic diameter ≥ 5.5 cm subgroup analysis. Serum MMP9 levels were influenced by age and hypertension. There was a positive association of serum MMP9 with CRP (r = 0.33, P < 0.001) and Hcy (r = 0.199, P = 0.033). Multiple logistic analyses showed that serum MMP9 was an independent risk factor for AAA and TAA. Based on receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of MMP9 for predicting TAA was 0.83 with 70% sensitivity and 91% specificity, while the AUC of MMP9 to detect AAA was 0.69 and the sensitivity and specificity were 50% and 88%. CONCLUSIONS: Serum MMP9 was closely related to the existence of aortic aneurysms and could be a valuable marker for the discrimination of aortic aneurysm, especially for TAA.


Assuntos
Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Torácica/sangue , Metaloproteinase 9 da Matriz/sangue , Idoso , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/enzimologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/enzimologia , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
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