Elevated plasma MMP1 and MMP9 are associated with abdominal aortic aneurysm rupture.

BACKGROUND: The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) formation is well established. However the changes in plasma MMP levels with AAA rupture have not been reported. The aim of this study was to determine circulating levels of MMPs in non-ruptured and ruptured AAA immediately prior to open repair. METHODS: Concentrations of MMPs and their endogenous tissue inhibitors (TIMPs) were quantified using ELISA in pre-operative plasma samples from non-ruptured and ruptured AAA. RESULTS: MMP1 and MMP9 were elevated in the plasma of ruptured AAA versus non-ruptured AAA. A four-fold elevation in pre-operative plasma MMP9 was associated with non-survival at 30 days from rupture surgery compared with those surviving for greater than 30 days. CONCLUSION: In conclusion, these findings support the role of MMPs in AAA pathogenesis. Elevation of MMP9 was associated with ruptured aneurysm related 30-day mortality and may represent a survival indicator in this group.     

Indicators of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysms

PURPOSE: Chlamydia Pneumoniae has been shown to be associated with atherosclerosis, myocardial infarction, and abdominal aortic aneurysms (AAAs). The possible association between AAA expansion and C pneumoniae infection was therefore assessed. METHODS: Blood samples were taken from patients with an AAA that was considered for surgical repair after having been diagnosed by means of the Chichester aneurysm screening program (UK) as having an initially infrarenal aortic diameter of 3.0 to 5.9 cm. The patients were examined prospectively for as long as 11.5 years (mean, 4.1 years) with ultrasound scanning. Of 110 patients considered for surgery, 90 men and 10 women had blood samples taken. Their IgG and IgA antibodies against C pneumoniae were measured by means of a microimmunofluorescence test. Unpaired t tests, multiple linear regression analyses, and logistic regression analyses were used for statistical analysis. RESULTS: A total of 44% (95% CI, 31%-55%) of the men with an AAA had an IgA titer of 64 or more, an IgG titer of 128 or more, or both, compared with 10% of the women with an AAA (OR = 7.2; 95% CI, 1.05-160.8). A titer of IgG of 128 or more was significantly associated with higher expansion (5.3 vs 2.6 mm per year), even after adjustment for initial AAA size and age. A significant positive correlation between both IgA and IgG titers and mean annual expansion was observed (r = 0.28; 95% CI, 0.05-0.49; and r = 0.45; 95% CI, 0.24-0.62, respectively), persisting after adjusting for initial AAA size and age. An IgG titer of 128 or more was present significantly more often in cases with an expansion greater than 1 cm annually (adjusted OR = 12.6; 95% CI, 1.37-293). CONCLUSION: A high proportion of men with an AAA has signs of infection with C pneumoniae. The progression of their AAAs was positively correlated with the presence of indicators of C pneumoniae infection.     

Surgery for abdominal aortic aneurysms associated with malignancy

(Received for publication on June 20, 1997; accepted on Jan. 6, 1998)     

Inflammatory plasma biomarkers of abdominal aortic aneurysms

Aim-Background

Osteopontin (OPN) and osteoprotegerin (OPG) have been implicated in the development and progression of atherosclerosis. We studied the correlation of these two molecules with abdominal aortic aneurysm (AAA) in terms of its development and extent, and present our preliminary results.

Methods

Osteopontin and osteoprotegerin serum values in 74 patients with AAA were compared with the corresponding values of 20 patients (control group) who had similar characteristics and no AAA. All aneurysms were classified as Types A-E, according to their anatomical extent as seen on CT imaging (EUROSTAR criteria).

Results

Our results showed that osteopontin values were higher in patients with any type of aneurysm (OPN: 3661.64 ± 1126.49ng/ml) compared to the control group (OPN: 1418.30 ± 962.68ng/ml; p = 0.017, Types A-B: p = 0.03, Types C-E: p = 0.01). Osteopontin and osteoprotegerin values did not differ among aneurysms of different extent. Osteoprotegerin values of patients with any type of aneurysm (OPG: 354.28 ± 212.1ng/ml) and of controls (OPG: 364.87 ± 159.85ng/ml) showed no significant difference.

Conclusions

Serum osteopontin may be a potential independent biomarker for AAA development, although it is not associated with the extent of the aneurysm. Serum osteoprotegerin seems to be of less prognostic value. The role of their levels concerning treatment of AAA remains questionable and needs further research.     

Circulating biomarkers are not associated with endoleaks after endovascular repair of abdominal aortic aneurysms

Objective

Endoleak is a common complication of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) but can be detected only through prolonged follow-up with repeated aortic imaging. This study examined the potential for circulating matrix metalloproteinase 9 (MMP9), osteoprotegerin (OPG), D-dimer, homocysteine (HCY), and C-reactive protein (CRP) to act as diagnostic markers for endoleak in AAA patients undergoing elective EVAR.

Systemic dilation diathesis in patients with abdominal aortic aneurysms: a role for matrix metalloproteinase-9?

INTRODUCTION: Accumulating evidence suggests that patients with abdominal aortic aneurysm (AAA) suffer from a systemic dilating condition affecting all arteries. Matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), appear to be involved in aneurysm formation, as evidenced by increased aortic tissue MMP activity and plasma MMP levels in patients with AAA. Hypothesizing that an imbalance in plasma MMP/TIMP level might be associated with a systemic dilation diathesis, we studied mechanical vessel wall properties of non-affected arteries of patients with either AAA or aorto-iliac obstructive lesions in association with plasma MMP-9 and TIMP-1 levels. METHODS: Twenty-two patients with AAA and 12 with aorto-iliac occlusive disease (AOD) were included. Diastolic diameter (d) and distension (Deltad) were measured at the level of the common carotid artery (CCA) and suprarenal aorta (SA) using ultrasonography. Distensibility (DC) and compliance (CC) were calculated from d, Deltad and brachial pulse pressure. Plasma MMP-9 and TIMP-1 were determined with specific immunoassays. RESULTS: The average (+/-SD) age was 72.3+/-5.6 and 65.0+/-8.2 years for the AAA and AOD patients, respectively, (P=0.005). CCA diameter was 9.1+/-1.3mm in AAA patients and AOD 7.8+/-1.4mm in AOD patients, P=0.009. This difference persisted after correction for age. Plasma MMP-9 and TIMP-1 did not differ significantly between AAA and AOD patients. In the total 34 patients, the MMP-9/TIMP-1 ratio was correlated inversely with distensibility (r=-0.74, P=0.002) and to compliance (r=-0.58, P=0.024) of the suprarenal aorta. CONCLUSIONS: The CCA diameter was larger in AAA patients compared to AOD patients. MMP-9/TIMP-1 ratio was associated with decreased distensibility and compliance of the suprarenal aorta. These data support the idea that AAA patients exhibit a systemic dilation diathesis, which might be attributable to MMP/TIMP imbalances.     

Functional matrix metalloproteinase-9 polymorphism (C-1562T) associated with abdominal aortic aneurysm

PURPOSE: Matrix metalloproteinase-9 (MMP-9) is a potent endopeptidase with activity against both collagens and elastin. Expression of MMP-9 is elevated in vascular disease, and in particular within aneurysm tissues. This study tested the hypothesis that the functionally more active T allele of the MMP9 C-1562T polymorphism may be overrepresented in patients with abdominal aortic aneurysm (AAA) compared with control subjects and patients with atherosclerotic peripheral vascular disease (PVD). METHODS: Seven hundred eighty-nine unrelated persons (AAA, n = 414; control subjects, n = 203; PVD, n = 172) were genotyped for the common C-1562T functional promoter polymorphism of the MMP9 gene. RESULTS: Genotypes containing the T allele of this polymorphism were significantly more common in patients with AAA compared with both control subjects and patients with PVD (adjusted odds ratio, 2.41 and 2.94, respectively). The greatest shift between groups was observed in male patients, with a difference of 20.6% in CT/TT genotypes. and 12.1% in T allele frequency between patients with AAA compared with patients with PVD. CONCLUSIONS: This study provides further evidence to support the role of MMP-9 in the pathogenesis of AAA, and indicates that the MMP9 C-1562T functional polymorphism may represent a genetic component contributing to susceptibility to this vascular disease.     

Horseshoe and pelvic kidneys associated with abdominal aortic aneurysms

The preoperative recognition of the existence of horseshoe or pelvic kidney with abdominal aortic aneurysm would greatly facilitate the proper operative care of these patients. Preoperative intravenous pyelography should be done routinely in all patients with abdominal aortic aneurysms. The diagnosis of an associated horseshoe or pelvic kidney can usually be established by this simple test if it is properly interpreted. If these anomalies are demonstrated or suspected, an aortogram should be performed to establish the status of the arterial supply to the kidneys. Some of the anomalous blood supply to the kidneys may not be apparent even after the aortogram. If the aneurysm can be resected without compromising the blood supply to the isthmus, this should be done and the aortic graft tunneled behind the isthmus [4]. However, if the isthmus has a large blood supply from the aneurysm and if division of this blood supply renders the isthmus ischemic, then the isthmus should be excised. In patients with pelvic kidney, to reduce ischemia to the kidney, aortic clamping time should be reduced to a minimum by completely freeing the aneurysm and dividing all the related lumbar arteries prior to aortic clamping.     

Plasma endothelin levels in patients with abdominal aortic aneurysms.

OBJECTIVES: endothelin 1,2 plays a significant role in the process of atherogenesis and vascular wall injury. The aim of this study was to assess whether plasma endothelin 1,2 levels were elevated in patients with large or symptomatic abdominal aortic aneurysms (AAAs). DESIGN: a prospective open study. MATERIALS AND METHODS: plasma endothelin 1,2 levels were measured in 65 consecutive patients with infrarenal aortic aneurysms and compared with the levels in 44 healthy volunteer controls. The data for abdominal aneurysm patients was analysed in four subgroups: (i) small aneurysms (<5 cm), (ii) large aneurysms (>/=5 cm), (iii) asymptomatic aneurysms and (iv) symptomatic aneurysms. Comparisons were made between endothelin 1,2 levels in aneurysm patients and controls and between the different aneurysm subgroups. RESULTS: a highly significant difference (p<0.0001) was found between aneurysm patients and controls. Patients with large aneurysms had significantly higher levels than patients with small aneurysms (p<0.01). There was no statistical difference in endothelin 1,2 levels between symptomatic and asymptomatic patients; however, the highest levels were found in large, symptomatic aneurysms and the lowest in small, asymptomatic aneurysms. CONCLUSIONS: plasma endothelin 1,2 is an endogenous marker of aneurysm diameter. Further studies are required to determine whether it relates to the rate of growth of aneurysms.     

Surgical treatment of abdominal aortic aneurysms associated with horseshoe kidney

Abdominal aortic aneurysm surgery associated with a horseshoe kidney (HSK) is a serious technical challenge for the surgeon. We reviewed our experience with 127 patients electively operated on between 1990 and 2004 for abdominal aortic aneurysm. Pre- and perioperative medical, surgical, and radiologic data were retrospectively reviewed. Preoperative diagnosis was achieved with computed tomography with or without angiography or with additional conventional aortography.Seven patients were recognized to have had a HSK, with a mean age of 67.29 +/- 2.43 years. Preoperative serum creatinine levels were similar in patients with or without HSK (1.0 +/- 0.08 vs 0.9 +/- 0.12 mg/dL; not significant). In five of the patients with HSK, reimplantation of the anomalous renal artery was necessary. In all 127 patients, hospital mortality consisted of 5 patients, none of whom had an HSK. Dealing with HSK seemed to increase aortic clamp times (30.43 +/- 3.55 vs 27.04 +/- 3.92 minutes; p < .05) slightly. Patients with or without HSK were given similar amounts of intravenous fluid replacement (2,214.2 +/- 441.3 vs 1,923.3 +/- 433.6 mL/patient; not significant) and allogeneic blood transfusion (0.71 +/- 0.49 vs 0.9 +/- 0.4 U/patient; not significant) and had a similar intensive care unit stay.Abdominal aortic aneurysms associated with HSK have been managed without division of the isthmic tissue. The left retroperitoneal approach provided adequate exposure for all patients with HSK.     

High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms

ObjectiveIdentifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA.MethodsPlasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair.ResultsA significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = −0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair.ConclusionsHigh levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.     

Endovascular therapy of spontaneous aortocaval fistulae associated with abdominal aortic aneurysms

We report a case of an abdominal aortic aneurysm (AAA) associated with an aortocaval fistula managed with endovascular techniques. The patient had a known AAA, and on the latest computed follow-up tomographic scan, evidence of fistulization between the aorta and the vena cava was suggested, which was later corroborated by standard contrast angiography. His comorbidities precluded an open repair, and this prompted consideration for an endovascular intervention. Successful exclusion of the AAA was performed, with no evidence of endoleaks or persistence of the fistula. The endovascular approach provides an efficacious alternative to traditional methods for repair of an aortocaval fistula, which is especially important in elderly patients with several comorbidities.     

Unusual aspects of aortovenous fistulas associated with ruptured abdominal aortic aneurysms

Three unusual cases of an abdominal aortic aneurysm spontaneously rupturing into the retroperitoneum and an adherent posterior vein are reported. No patient demonstrated signs or symptoms of an aortovenous fistula before surgery. Emergent surgery prevented extensive preoperative diagnostic testing. The three abdominal aortic aneurysms were very large and averaged 13 cm in diameter. One fistula involved an inflammatory aneurysm, which is the fifth such case reported. The aortic fistulas were to the inferior vena cava (158 other cases reported in the English-language literature), a left renal vein (16 other cases reported), and an iliac vein (7 other cases reported). Routine use of the cell-saver, oversewing of the fistula from within the aneurysm, and a heightened awareness that this unusual complication is more common in the presence of a very large, ruptured abdominal aortic aneurysm should improve survival.     

Factors associated with abdominal compartment syndrome complicating endovascular repair of ruptured abdominal aortic aneurysms

BACKGROUND: Endovascular treatment of ruptured abdominal aortic aneurysms (r-AAAs) has the potential to offer improved outcomes. As our experience with endovascular repair of r-AAA evolved, we recognized that the development of abdominal compartment syndrome (ACS) led to an increase in morbidity and mortality. We therefore reviewed our experience to identify risk factors associated with the development of ACS. METHODS: From January 2002 to December 2004, 30 patients underwent emergent endovascular repair of r-AAA by using commercially available stent grafts. All patients who developed ACS underwent emergent laparotomy. Physiological and clinical parameters were analyzed between patients with and without ACS after endovascular r-AAA repair. RESULTS: Over the past 3 years, 30 patients underwent endovascular r-AAA repair, and 6 (20%) patients developed ACS. Patients with ACS had a higher incidence of the need for aortic occlusion balloon (67% vs 12%; P = .01), a markedly longer activated partial thromboplastin time (128 +/- 84 seconds vs 49 +/- 31 seconds; P = .01), a greater need for blood transfusion (8 +/- 2.5 units vs 1.8 +/- 1.7 units; P = .08), and a higher incidence of conversion to aortouni-iliac devices because of ongoing hemodynamic instability and an inability to expeditiously cannulate the contralateral gate (67% vs 8%) when compared with patients without ACS. The mortality was significantly higher in the patients with ACS (67%; 4 of 6) compared with patients without ACS (13%; 3 of 24; P = .01). CONCLUSIONS: ACS is a potential complication of endovascular repair of r-AAA and negatively affects survival. Factors associated with the development of ACS include (1) use of an aortic occlusion balloon, (2) coagulopathy, (3) massive transfusion requirements, and (4) conversion of bifurcated stent grafts into aortouni-iliac devices. We recommend that, after endovascular repair of r-AAA, these patients undergo vigilant monitoring for the development of ACS.     

Systemic levels of cotinine and elastase, but not pulmonary function, are associated with the progression of small abdominal aortic aneurysms.

OBJECTIVE: to study whether smoking and impaired pulmonary function are associated with the expansion of abdominal aortic aneurysms (AAA). METHODS AND MATERIAL: seventy-nine men with small (3-5 cm), screen-detected AAA underwent a simple 5-step smoking history, measurement of the forced first second expiratory volume (FEV1), venepuncture and annual ultrasound scan for mean follow-up period of 3.5 years. RESULTS: all but one patient had a significantly reduced FEV1 (p<0.05, Mann-Whitney). The FEV1/expected FEV1 ratio (rFEV1) was not related to AAA expansion but was negatively correlated with P-elastase-alpha1-antitrypsin-complexes (P-Elastase). P-Elastase was positively correlated with smoking and S-cotinine. Smoking, S-cotinine, and P-elastase were positively correlated with the mean annual AAA expansion rate but not rFEV1. CONCLUSION: in general, patients with AAA have impaired pulmonary function. A simple five step smoking classification is as predictive of AAA-expansion as S-cotinine. Smoking may cause elastase secretion leading to pulmonary and aortic elastin degradation but the lack of association between AAA-expansion and rFEV1 suggest that other mechanisms are important.     

Activity of matrix metalloproteinase-2 and -9 in abdominal aortic aneurysms. Relation to size and rupture.

OBJECTIVES: to investigate the activity of matrix metalloproteinase (MMP)-2 and -9 in asymptomatic abdominal aortic aneurysms (aAAAs) and ruptured abdominal aortic aneurysms (rAAAs). DESIGN: cross-sectional study. MATERIALS AND METHODS: MMP-2 and MMP-9 activity was estimated in biopsies from the anterior wall of 60 AAAs using gelatin zymography. There were 20 medium-sized (diameter 5<7 cm) aAAAs, 20 large (>57 cm) aAAAs and 20 rAAAs. MMP activity was quantified using a laser densitometer and expressed as arbitrary units (au). RESULTS: mean (SEM) MMP-9 activity was significantly lower in large aAAAs (1190 au +/-247) than in rAAAs (2647 au +/-498, p<0.05). There was no difference in MMP-2 activity. CONCLUSION: High MMP-9 activity in the AAA wall is associated with rupture.     

Inflammatory abdominal aortic aneurysms

In a series of 517 operations for abdominal aortic aneurysm from 1971 to 1988 there were 45 cases (8.7%) with an inflammatory aneurysm with a typical thick glistening whitish fibrous layer. Almost two-third of the patients had rather severe chronic or acute progressive pain in the abdomen, the back or the flank. Unilateral (7) or bilateral (2) hydronephrosis due to ureteral compression occurred in 9 patients (20%). A diagnosis of inflammatory aneurysm was made preoperatively only in 10 patients. In 8 of the 9 patients with hydronephrosis ureterolysis was done, unilaterally (6) or bilaterally (2). After ureterolysis all had complete resolution of the hydronephrosis. Preoperative diagnostic methods are excretory urography, showing medial deviation, ultrasonography and CT-scanning of the abdominal aorta. All patients with an inflammatory aneurysm should undergo aortic replacement to prevent rupture and achieve pain relief. Ureterolysis in cases of hydronephrosis is strongly recommended and may be performed safely and with excellent results.     

Familial abdominal aortic aneurysms

The case histories of three brothers, the only siblings of one family, all of whom underwent surgery for the treatment of a previously asymptomatic ruptured abdominal aortic aneurysm, are recorded. The possibility of underlying constitutional and hereditary factors is discussed and the suggestion of a primary familial incidence of atheromatous, nondissecting aortic aneurysm is raised.