Inflammatory mediators after endovascular aortic aneurysm repair

doi:10.1016/j.cyto.2014.07.256

Cytokine

Volume 70, Issue 2, December 2014, Pages 151-155

https://doi.org/10.1016/j.cyto.2014.07.256 Get rights and content

Highlights

•
SuPAR, IL-6 and ET-1 increased and IgM anti-PC decreased after elective EVAR.
•
Our results indicate on-going inflammatory activation in AAA patients after EVAR.
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The level of IL-6 was associated with aneurysm sac size after EVAR.

Abstract

Objective

To evaluate patterns of inflammatory mediators before and after elective endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA).

Materials and methods

Inflammatory mediators including soluble urokinase plasminogen activator (suPAR), endothelin (ET)-1, tumour necrosis factor (TNF)-α, interleukin (IL)-6, CD40 ligand (CD40L) and IgM antibodies against phosphorylcholine (IgM anti-PC), were evaluated before and after elective EVAR in 21 patients. Five patients undergoing open AAA repair (OR) were evaluated for comparison.

Results

SuPAR (p < 0.001), ET-1 (p = 0.003) and IL-6 (p = 0.02) increased whereas IgM anti-PC decreased (p < 0.001) after EVAR. Both suPAR (p = 0.04) and IL-6 (p = 0.03) increased in the five patients with unchanged/expanded aneurysm sac after EAR, whereas only suPAR increased (p = 0.04) and IL-6 remained unchanged (p = 0.2) among the 16 patients with shrinking aneurysm sac. No difference was noted between patients undergoing EVAR and OR regarding levels or changes of studied markers.

Conclusions

These changes in plasma biomarker profile are compatible with on-going inflammatory activation in AAA patients after EVAR. The potential role of IL-6 as a plasma biomarker for treatment failure in surveillance programs after EVAR needs to be further evaluated.

Introduction

Abdominal aortic aneurysm (AAA) mainly affects males and is a common and potentially life threatening condition due to the risk for aneurysm rupture [1]. The pathophysiologic mechanisms involved in the development and growth of AAA are multifactorial; previous studies have shown associations with inflammatory activity, changes in coagulation, endothelial dysfunction as well as with the classical risk factors of atherosclerosis [2], [3], [4], [5].

Patients with large AAAs can undergo either open (OR) or endovascular (EVAR) aneurysm repair to prevent rupture. The long-term effects of EVAR on systemic inflammatory mediators remain poorly understood. The retention of a biologically active mural thrombus and aneurysm sac following EVAR may be a source of inflammatory mediators, which may influence postoperative protection against aneurysm sac expansion and rupture and overall cardiovascular morbidity [6]. It may also lead to clinical failure, and increase the risk of reintervention [6]. Postoperative levels of inflammatory mediators may also be useful markers of cardiovascular disease activity.

The inflammatory activity in AAA is reflected in increased values of several different inflammatory mediators [2]. One of these is glycosylphosphatidylinositol phospholipase D (GPI-PLD), which is an enzyme that cleaves the GPI anchor of the urokinase plasminogen activator receptor (uPAR), forming a free suPAR. SuPAR is involved in tissue remodelling [7], [8] and is a marker of low-grade inflammation associated with risk of developing cardiovascular disease [9]. Endothelin (ET)-1 is a potent vasoconstrictor regulating release of vasoactive substances and stimulating muscle cell mitogenesis [10], [11]. It has a putative role in the pathogenesis of atherosclerosis and might also be associated with aneurysm growth [12]. Tumour necrosis factor (TNF)-α [13], [14] and interleukin (IL)-6 [15], [16], [17], [18] are pro-inflammatory cytokines in the acute phase inflammatory response, and involved in both atherogenesis and AAA development [19]. CD40L is a key mediator in B-cell activation and is also increased in cells involved in the atherosclerotic process [20], [21]. IgM anti-PC, on the other hand, are natural antibodies against oxidised low-density lipoprotein (oxLDL), an important mediator in the development of atherosclerosis and atherogenesis [22]. Low levels of IgM anti-PC are associated with an increased risk of atherosclerotic cardiovascular disease [23], [24], [25], but the marker has not yet been evaluated in patients with AAA.

The main aims of this study where to evaluate potential relationships between levels of suPAR, ET-1, TNF-α, IL-6, CD40L, IgM anti-PC and aneurysm sac size change after elective EVAR for AAA. A small group of patients undergoing open surgery for AAA was studied for comparison.

Section snippets

Patients

We studied AAA patients included in a scientific follow-up program at the Vascular Centre, Malmö University Hospital [26]. Among 57/206 study patients undergoing elective AAA repair between 2003 and 2010, 26 consented to a postoperative follow-up blood sample and were included in the present study in which pre- and postoperative laboratory analyses and repeated computed tomography (CT) scans were evaluated. Among EVAR patients (n = 21), 14 underwent standard EVAR and seven underwent fenestrated

Patient characteristics

Twenty-six patients (23 [89%] men) with a median age of 74 (IQR 69–78) years were included in this study. Twenty-three (88%) were smokers and 20 (77%) suffered from hypertension. At a preoperative CT scan, 12 (46%) patients had medium sized AAA, whereas nine patients had large aneurysms. Five patients had small AAAs and were operated because of either rapid growth or symptomatic AAA (Table 1).

Preoperative correlations between laboratory markers and AAA diameter

A significant inverse correlation (r = −0.41, p = 0.04) was found between preoperative level of suPAR and

Discussion

In the present study, levels of different inflammatory mediators, such as suPAR, ET-1 and IL-6 all increased after EVAR for AAA, whereas levels of the protective mediator IgM anti-PC decreased [23], [24], [25]. EVAR may elicit a postoperative systemic inflammatory response, referred to as post-implantation syndrome (PIS) featuring pyrexia, negative blood culture results, leucocytosis, increased C-reactive protein and/or coagulation disturbances [28]. The reported incidence of PIS after EVAR

Conflict of interest

No conflicts of interest exist for any of the authors.

Funding acknowledgement

This research received no specific Grant from any funding agency in the public, commercial, or not-for-profit sectors.

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A stable aneurysm sac after endovascular aneurysm repair as a predictor for mortality: An in-depth analysis
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Citation Excerpt :
Another potential explanation for the association between mortality and failure of aneurysm sac regression is the ongoing wall stress of the aneurysm sac. Multiple studies have been performed to identify biomarkers as predictors or the consequence of an AAA, which could be linked to wall stress.35-37 Others have shown that after EVAR, plasma matrix metalloproteinases become elevated and will remain elevated when a type II endoleak is present.38-40
The aim of the present study was to compare the long-term survival of patients with a stable aneurysm sac vs those with aneurysm sac regression after endovascular aneurysm repair (EVAR) and to identify the independent risk factors for aneurysm sac regression and mortality after EVAR.
We reviewed all the patients who had undergone EVAR from 2005 to 2018 with computed tomography angiography available at 1 year of follow-up. Aneurysm sac regression was defined as a diameter decrease of >10%. We used multivariable regression to identify the independent risk factors for sac regression. Kaplan-Meier analysis and Cox regression were performed to test the differences in 5-year mortality between a stable sac diameter and sac regression.
The inclusion criteria were met by 325 patients, with 185 in the sac regression group and 140 in the stable sac group. Multivariable logistic regression analysis showed that treatment of a ruptured aneurysm was an independent risk factor for aneurysm sac regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.96). Age (HR, 1.05; 95% CI, 1.01-1.09), ischemic heart disease (HR, 1.94; 95% CI, 1.13-3.31), neck thrombus (HR, 2.72; 95% CI, 1.07-6.95), and a type II endoleak (HR, 19.21; 95% CI, 7.32-50.40) were independent risk factors for a stable aneurysm sac diameter. Multivariable Cox regression showed a significantly increased risk of mortality for patients with a stable aneurysm sac after EVAR (odds ratio, 2.25; 95% CI, 1.36-3.72). No significant differences were found in cause of death between the two groups.
A stable aneurysm sac after EVAR was associated with increased mortality. Age, ischemic heart disease, neck thrombus, and a type II endoleak were independent risk factors for a stable aneurysm sac. However, a well-founded explanation for this finding is still lacking. Future research should focus on aggressive treatment of type II endoleaks and inflammatory processes as potential pathophysiologic mechanisms.
Factors associated with sac regression after F/BEVAR for complex abdominal and thoracoabdominal aneurysms
2022, Seminars in Vascular Surgery
Citation Excerpt :
The biological mechanisms that determine whether a nonexpansile sac will remain stable or regress are poorly understood. Studies have linked various inflammatory biomarkers and circulating matrix metalloproteins to aneurysm progression in general [16,17], and there is also some evidence that inflammation may play a role in sac remodeling post-EVAR [18,19]. Persistent inflammation in the aortic wall may preclude fibrosis and contraction, resulting in a failure to regress phenotype [20].
The behavior and remodeling of the residual aneurysm sac after endovascular repair is predictive of long-term outcomes. Although persistent growth is clearly a harbinger of complications, only recently has the relative advantage of sac regression over sac stability been recognized. There is a growing literature examining the prognostic implications of sac regression after standard infrarenal endovascular aortic repair, and various factors associated with increased likelihood of regression have been identified. However, there is a relative paucity of data on sac regression after more complex aneurysm repairs using fenestrated and/or branched technology. In this article, we aim to review sac regression and its importance as a whole, and specifically examine the role of regression after fenestrated and/or branched endovascular aortic repair for more extensive abdominal and thoracoabdominal aneurysms.
Influence of inflammatory activity of the mural thrombus in patients with abdominal aortic aneurysms with endoluminal repair
2018, Angiologia
Los mecanismos fisiopatológicos que se encuentran implicados en el crecimiento de los aneurismas de aorta abdominal (AAA) son multifactoriales, como cambios inflamatorios, hemostáticos, disfunciones endoteliales y los clásicos factores de riesgo ateroscleróticos. La persistencia de un trombo mural biológicamente activo y del saco aneurismático, al igual que el posible desarrollo de endofugas tipo 2, puede ser el origen de la activación de mediadores inflamatorios, cuyas consecuencias se desconocen. Nuestro objetivo es definir un modelo predictivo de complicaciones después de la reparación endoluminal del aneurisma de aorta abdominal a corto y medio plazo a partir de variables clínicas, serológicas y anatómicas.
Se incluyeron 50 pacientes intervenidos de AAA ateroscleróticos asintomáticos entre enero 2016 y noviembre 2016, en el Servicio de Angiología y Cirugía Vascular del Hospital Clínico Universitario de Valladolid. Se recogieron datos clínicos (edad, sexo, factores de riesgo cardiovascular, comorbilidad y medicación), diámetro basal de los AAA, crecimiento aórtico a los 6 meses y concentraciones basales circulantes de proteína C reactiva, interleucina 2 (IL2), IL6 y homocisteína, en el preoperatorio, a los 7 días del postoperatorio y a los 6 meses. A los pacientes se les realizó una angioTAC en el postoperatorio inmediato y a los 6 meses.
Se observó un crecimiento medio del diámetro de los AAA con fuga de 6,18 mm, mientras que los AAA correctamente presurizados disminuyeron su diámetro medio en 4,69 mm, siendo esta diferencia estadísticamente significativa (p = 0,001). En relación con los cambios en el trombo del saco aneurismático, en los pacientes con AAA con fuga el trombo se incrementó en 7,74 mm de media, mientras que en los pacientes con AAA correctamente sellados y sin fugas se incrementó solo en 3,08 mm, siendo esta diferencia estadísticamente significativa (p = 0,027). Se estableció una correlación estadísticamente significativa entre la modificación del tamaño del aneurisma postEVAR y los niveles plasmáticos de PCR y homocisteína a los 7 días, y de la modificación del tamaño del trombo intraaórtico y los niveles plasmáticos de IL2 a los 7 días y a los 6 meses.
Los patrones de biomarcadores estudiados a corto y a medio plazo después de EVAR deben ser considerados como indicadores un proceso activo de inflamación que ejerce su influencia en la remodelación aórtica.
The pathophysiological mechanisms that are involved in the growth of abdominal aortic aneurysms (AAA) are multifactorial, and include inflammatory changes, as well as haemostatic and endothelial dysfunctions and, the classic atherosclerotic risk factors. The persistence of a biologically active mural thrombus and the aneurysmal sac, as well as the possible development of type 2 endoleaks, can be the origin of the activation of inflammatory mediators, the consequences of which are unknown. The aim of this study is to define a predictive model of complications after endoluminal repair of abdominal aortic aneurysm in the short and medium-term using clinical, serological, and anatomical variables.
A total of 50 hospital patients with asymptomatic atherosclerotic AAA were included in the study between January 2016 and November 2016, in the Angiology and Vascular Surgery Department of the Hospital Clínico Universitario de Valladolid. Clinical data were collected (age, gender, cardiovascular risk factors, comorbidity, medication), baseline AAA diameter, aortic growth at 6 months, as well as baseline C-reactive protein levels, interleukin-2 (IL2), IL6 and homocysteine, preoperatively, 7 days postoperatively, and 6 months later. The patients had an angioCT scan in the immediate postoperative period, and at 6 months.
A mean growth in diameter of 6.18 mm was observed in the AAA with a leak, while the correctly pressurised AAA showed a decrease of 4.69 mm in their mean diameter, with this difference being statistically significant (P = .001). As regards the changes in the thrombus of the aneurysmal sac, in patients with AAA with a leak the thrombus increased by a mean of 7.74 mm, while patients with AAA correctly sealed and without leakage only increased by 3.08 mm, with this difference being statistically significant (P = .027). A statistically significant relationship was observed between the change in the size of the post-EVAR aneurysm and the plasma levels of CRP and homocysteine at 7 days, and of the change in the size of the intra-aortic thrombus and the plasma levels of IL2 at 7 days and at 6 months.
The biomarker patterns studied in the short and medium term after EVAR should be considered as indicators of an active inflammation process that exerts its influence on aortic remodelling.
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View full text

Inflammatory mediators after endovascular aortic aneurysm repair

Highlights

Abstract

Objective

Materials and methods

Results

Conclusions

Introduction

Section snippets

Patients

Patient characteristics

Preoperative correlations between laboratory markers and AAA diameter

Discussion

Conflict of interest

Funding acknowledgement

Lancet

J Vasc Surg

Am J Pathol

Cytokine

J Vasc Surg

J Vasc Surg

Blood

Eur J Vasc Endovasc Surg

Int J Cardiol

Atherosclerosis

J Autoimmun

Eur J Vasc Endovasc Surg

Thromb Res

Resuscitation

Eur J Vasc Endovasc Surg

J Vasc Surg

Am J Pathol

J Vasc Surg

J Vasc Surg

Elevated circulating levels of inflammatory cytokines in patients with abdominal aortic aneurysm

Arterioscler, Thromb, Vasc Biol

Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms

Circulation