ATVB in Focus: Aortic Aneurysms

Surrogate Markers of Abdominal Aortic Aneurysm ProgressionSignificance

Anders Wanhainen, Kevin Mani, Jonathan Golledge
https://doi.org/10.1161/ATVBAHA.115.306538
Arteriosclerosis, Thrombosis, and Vascular Biology. 2016;36:236-244
Originally published December 29, 2015

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Abstract

The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice.

Introduction

The natural course of most abdominal aortic aneurysms (AAA) is to gradually expand and in some cases eventually rupture. There is currently no recognized specific pharmacological treatment to reduce growth or rupture risk of an AAA.1 Standard of care for patients with small AAAs (<55 mm) is limited to surveillance with open or endovascular surgical repair considered for large (>55 mm), rapidly growing (>10 mm/y) or symptomatic AAAs.2 Because most AAAs are asymptomatic, ultrasound-based screening programs targeting risk groups (commonly men aged ≥65 years) have been established in some countries.3 Such programs, along with the growing use of abdominal imaging for other problems, have led to an increase in the identification of patients with small AAAs. Predicting the progression of small AAAs is, therefore, a key management priority.

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Please see http://atvb.ahajournals.org/site/misc/ATVB_in_Focus.xhtml for all articles published in this series.

Maximum AAA diameter has traditionally been used as the main marker of disease progression although there are concerns about the reproducibility of readings and the sensitivity to detect true disease progression. Aneurysm volume has been suggested as a more sensitive anatomical marker for monitoring expansion, and biomechanical analyses have been proposed for identifying weak areas prone to rupture. Recently, functional and molecular imagings and circulating biomarkers have also been proposed as potential means to monitor the progression of AAA pathobiology. This review focuses on the current evidence on the value of different surrogate markers of AAA progression.

Morphological Markers

AAA Diameter

The most commonly used surrogate marker of rupture risk is the maximal AAA diameter. Because of its ease of use, safety, wide availability, and low cost, ultrasound is the most commonly used imaging modality for large-scale screening and monitoring of small AAAs. Although ultrasound is an excellent technique for this purpose, an intra- and interobserver variabilities (2 SDs) in the range of 2 to 7 mm and 2 to 10 mm, respectively,4,5 represent an important limitation that may have significant impact on clinical decision making. Modern computed tomography (CT) and magnetic resonance imaging (MRI) with advanced image processing methods, such as multiplanar reformation, are perceived to have higher accuracy and reproducibility, with a reported intra- and interobserver variability of <2 mm.6 Although CT or MRI is frequently the preferred imaging modalities for monitoring growth rates in small clinical trials, they are less suitable for mass screening and large-scale trials. Similar reproducibility for ultrasound and CT has been reported in some but not in all studies when a standardized protocol is used.7,8 One of the challenging aspects to assessing maximum AAA diameter is the variety of methods that can potentially be used and the lack of reporting of the exact techniques used in individual studies. Variations may occur in the plane of acquisition (eg, coronal or sagittal), the axis of measurement (eg, axial or orthogonal), the position of the measuring calipers (eg, inner to inner or outer to outer), the relationship with the cardiac cycle (systole versus diastole), and the selected region of the AAA.9 It has been suggested that diameters measured perpendicular to the aorta centerline (orthogonal), rather than within the axial plane, are more representative of the true AAA diameter.4,6 With ultrasound, measurements within the anteroposterior, rather than the transverse plane, have been reported to be more reproducible.4

There is no current consensus on how to place the calipers when measuring the diameter with ultrasound. Methods used include the outer-to-outer method, where calipers are placed on the outer layer of the aortic wall; the inner-to-inner method, where calipers are placed on the inner layer of the aortic wall; and the leading edge-to-leading edge method, where calipers are placed on the outer layer of the anterior wall and the inner layer of the posterior wall (Figure 1). Much of the reported variation in ultrasound measured AAA diameter is likely because of the variation in caliper placement.5,10 The UK Small Aneurysm Trial11 is based on the measurement of AAA diameter on the outer-to-outer method, and this method has been adopted into the current UK intervention criteria.12 The inner-to-inner method was used in the Multicentre Aneurysm Screening Study,13 and consequently it is used in the current UK National Health Service AAA screening programme.14 The leading edge-to-leading edge method is used in the current Swedish AAA screening programme.15 Studies comparing these methods show there is a significant difference in diameters measured with the different methods, which has an impact on the reported prevalence rates of AAA.5,10 In a Swedish AAA screening study, the difference in mean diameter was 4 mm between inner-to-inner and outer-to-outer, which resulted in an astonishing 77% difference in AAA prevalence (ie, 1.3% compared with 2.3%).5

Figure 1.
Figure 1.

Schematic of different methods to place the calipers when measuring the anteroposterior abdominal aortic diameter with ultrasound. Because of a better ultrasound reflection and lower variability, the anteroposterior diameter is preferable to the transverse diameter.

A systematic review of 15 studies reported considerable variation in small AAA growth rates (mean, −0.3 to +4.0 mm/y).15 The variation could not be explained by differences in initial AAA diameter alone.16 The authors suggested that methodological issues, such as differences in imaging modalities, variation in the plane of measurement, and cursor positioning, likely explained the large heterogeneity. Frequently, important methodological aspects were not reported. Furthermore, growth rates were estimated in a variety of different ways using (last−first diameter)/time, linear regression, or more complex techniques such as multilevel modeling, which has been shown to affect the growth estimation.17

Grondal et al reported that AAA diameter measurement by ultrasound was influenced by the pulse wave propagation, with an average maximal diameter difference of 1.9 mm between diastole and systole.7 Thus, ECG-gated imaging may further increase precision by reducing the effects of hemodynamic variations and has been used in clinical trials.8,18

A rapid increase in AAA diameter (>10 mm/y) is claimed to be a risk factor for rupture19 and is generally accepted as an indication for repair.2 The average annual growth rate for AAAs is ≈5% to 10% of the initial diameter; however, there is considerable heterogeneity in growth rates reported across studies.20 Furthermore, large individual variability in growth patterns exist, with most AAAs remaining static for periods of time followed by expansion (staccato growth), some growing at a continuous linear rate, and others having long periods of stability.21,22 In a study by Vega de Céniga et al,22 only 15 (11.5%) of 195 patients with 4 to 4.9 cm AAAs followed with 6 monthly CT scans over a mean of 50 months showed a continuous growth pattern. Although individual patient factors may partially explain the observed irregular expansion patterns, measurement error and variation of assessment techniques are likely an important contributor to this heterogeneity. Some authors claim that management decisions should not be based on the presumption that observed growth rates of AAAs can be extrapolated to predict future growth rates,23 and that rapid increase in AAA diameter should not be an indication for elective AAA repair.21

Despite its limitation, AAA diameter remains the most widely used and important marker of disease progression. The methods used to measure AAA diameter should be standardized and reported to minimize measurement error and increase generalizability.

AAA Volume

AAA volume has been reported to be a more sensitive and accurate predictor of AAA progression and to have excellent reproducibility (coefficients of variation of <3%).24 Changes in aneurysm morphology do not always result in maximum diameter changes, and volume measurements take this into account. Moreover, measuring volume overcomes variation introduced by measuring in different planes and axes.25 In a study by Parr et al,24 almost half of the patients with volumetric growth greater than the reader variability (ie, outside the 95% limits of agreements and therefore considered true growth) did not have corresponding diameter increases. Kontopodis et al26 reported that volumetric growth of 34 small AAAs was a better predictor of requirement for surgical repair than AAA diameter growth. Currently, there is, however, no defined threshold volumes at which surgical repair should be recommended.25

AAA volume can be measured with a variety of techniques, including CT, MRI, and ultrasound. Noncontrast CT has been reported to be comparable with contrast-enhanced CT for aortic volume analysis.27 Recent studies on 3-dimensional (3D) ultrasound report reproducibility similar to CT although this remains to be validated in other cohorts.28 There has been considerable progress in segmentation software, allowing a rapid semiautomatic or even completely automatic calculation of accurate volumes.6

Surveillance after endovascular aortic repair by CT or ultrasound is recommended by current guidelines.2 Continued sac expansion is suggestive of an endoleak and an important risk factor for secondary aneurysm rupture. Several studies have suggested that aortic volume is a much more sensitive indicator than aortic diameter for sac expansion after endovascular aortic repair.29–31 It has been suggested that a 2% increase in aortic volume is indicative of an endoleak after endovascular aortic repair.32 More widespread examination of the accuracy of AAA volume measurements in diagnosing endoleak is required. Currently, because most patients are followed with standard ultrasound, it would not be possible to introduce this method of diagnosing endoleak into clinical practice.

AAA Thrombus

Most AAAs have large quantities of intraluminal thrombus (ILT), which can be measured by imaging (Figure 2). The volume of ILT may influence biomechanical properties, which may affect the risk of rupture. Furthermore, cellular and metabolic activity within the thrombus could have secondary effects to weaken the adjacent aortic wall.24 Parr et al33 studied a group of 39 patients who underwent repeat CT imaging and reported an association between larger ILT volume and greater AAA growth, independent of initial aortic diameter. In addition, high ILT volume predicted an increase rate of cardiovascular events in a group of 98 patients.33 In a large population-based cohort study from Viborg, Denmark, 416 men with screening-detected AAAs were followed up for mean of 1.8 years with ultrasound. After adjusting for potential confounders (AAA diameter, smoking, blood pressure, and diabetes), a weak but significant correlation (correlation coefficient, 0.14) was found between the initial relative ILT cross-sectional area and the AAA growth rate.34 In a recent study from the Netherlands, an unorganized loose ILT, characterized by high thrombus signal intensity on T1-weighted MRI, was associated with higher AAA growth rates, and the authors suggested that MR thrombus characterization was a promising technique to identify fast growing aneurysms.35

Figure 2.
Figure 2.

Computed tomographic imaging showing (A) no, (B) eccentric, and (C) extensive luminal thrombus*.

Biomechanical Imaging

AAA rupture is thought to occur at sites where aortic wall stress surpasses the aortic wall strength. Aneurysm wall strength and wall stress are affected by various factors, including wall thickness, presence of thrombus, aneurysm geometry, blood pressure, and flow dynamics within the aorta. Morphological assessment of the aorta together with knowledge of blood pressure and flow dynamics may, therefore, offer a better tool for predicting AAA progression and rupture than simple diameter or volume measurements.

Finite element analysis has been used for the biomechanical evaluation of AAAs. This technique involves acquisition of morphological 3D imaging often with CT or MRI, vessel reconstruction, and segmentation, followed by finite element computation using dedicated software. Recently, the feasibility of wall stress analysis using 3D ultrasound was reported,36 which would be beneficial considering that ultrasound is the routine method for small AAA follow-up. The estimates of peak wall stress (PWS) can be highly complicated requiring detailed processing and advanced understanding of fluid mechanics. Recently, software has been developed to enable more user-friendly PWS estimation and also calculation of a peak wall rupture index (PWRI). Areas with increased PWS and PWRI can be identified (Figure 3).

Figure 3.
Figure 3.

Finite element analysis of an aortic aneurysm. Image courtesy of Roy Joy at Department of Vascular Surgery, Karolinska University Hospital/Karolinska Institutet, Stockholm, Sweden.

To facilitate clinical applicability of finite element analysis, efforts have been made to translate the biomechanical calculations such as PWRI, to clinically tangible data through identification of a PWRI-equivalent diameter of the AAA.37 Several retrospective studies indicate that finite element analysis can identify areas with increased risk of aneurysm expansion and rupture.38–40 A study of 30 asymptomatic, 15 symptomatic, and 15 ruptured AAA suggested that PWRI was the parameter that best distinguished between asymptomatic and symptomatic AAAs.40 The same group reported that regions of the AAA with increased PWRI had increased histopathological degeneration on examination of aortic wall specimens obtained at surgical repair.41 The findings suggest a potential means of linking biomechanical imaging to the molecular pathology of AAA.41 A recent meta-analysis reported that PWS was significantly greater in a series of 144 patients with ruptured or symptomatic AAAs than 204 individuals with asymptomatic AAAs.42

A serious limitation of current biomechanical imaging measurements is that none has been prospectively validated against the main outcome they are supposed to predict (ie, AAA rupture). It remains to be established whether the measurement of PWS or PWRI in surveillance programs will improve management of small AAAs. Because most small AAAs are currently monitored by standard ultrasound, this would require a significant change in practice.

Functional and Molecular Imagings

AAA surveillance programmes are currently based on morphological assessment; however, the traditional imaging modalities cannot assess the pathological process that is ongoing in a degenerative aneurysm. The potential role of functional imaging is to differentiate aneurysms with pathological properties that indicate more aggressive disease or to monitor the response to medical interventions. Functional imaging involves the use of tracers to assess cellular activity or aortic wall cell composition, combined with morphological imaging such as CT or MR to visualize the AAA.

Positron Emission Tomography

The functional imaging that is currently most used in clinical practice is positron emission tomography fused with CT imaging (PET/CT). 18-fluorodeoxyglucose or FDG-PET is often used in oncological staging or assessment of autoimmune rheumatologic disease, as increased glucose metabolism indicates the presence of inflammation or cell proliferation. FDG-PET/CT imaging is used for diagnosis of mycotic aneurysms, aortic graft infections, and sometimes for evaluation of symptomatic aneurysms.43–45 Increased FDG-uptake has been reported in symptomatic AAAs.46 In an analysis of 12 asymptomatic AAAs with FDG-PET/CT imaging, no aneurysm wall–specific uptake could be identified in any patient.47 Thus, currently, the role of FDG-PET/CT in evaluation asymptomatic small AAAs is unclear. It is possible that the use of other radionucleotide markers, such as those representative of angiogenesis, maybe more useful.48

MRI and Functional Imaging

Functional imaging with MRI has the benefit that it combines morphological and mechanical imaging of the aorta with the assessment of aortic wall composition and cellular activity. In addition, MRI does not involve ionizing radiation, which may be an issue because most patients with asymptomatic small AAAs require repeat imaging. Functional MRI imaging of phagocytic activity of macrophages has been reported in humans, using superparamagnetic iron oxide as the MR contrast agent. These particles have been used in imaging of macrophage activity in atherosclerosis.49,50 There are initial reports that suggest uptake of iron oxide in the aortic wall is representative of macrophage activity.51 One study, which included 29 patients, reported iron oxide uptake to be associated with a threefold increased expansion rate.51 These promising results remain to be validated. The inherent properties of iron oxide as a contrast agent for MRI may affect the clinical applicability of these results because results are highly dependent on imaging technique and protocol. Recently, PET-MR was introduced and may offer increased possibilities in imaging of cardiovascular disease.52

Circulating Markers

Circulating markers representative of the pathological processes occurring within AAA could be valuable for many reasons. First, they could be used in clinical trials investigating novel drug therapies for AAA to determine the likely success of therapies under investigation. Second, blood markers could be used to identify patients who are at high risk of AAA rupture requiring early surgical intervention or those at low risk of AAA rupture in whom AAA surveillance could be continued. Third, they could be used to identify patients who are at risk of complications after AAA repair, eg, to detect continued perfusion of the AAA (endoleak) after endovascular repair.

Current Research to Identify Circulating Markers of AAA Progression

A large number of circulating markers have been associated with AAA presence and size. These include markers related to thrombus remodeling (eg, D-dimer), the extracellular matrix (eg, aminoterminal propeptide of type III procollagen), proteolytic enzymes (eg, matrix metalloproteinase-9), lipids (eg, high-density lipoprotein), and inflammation (eg, interleukin-6).53,54

In contrast, there have been fewer studies investigating circulating markers associated with AAA progression. Studies of this type are difficult to design and carry out for many reasons. First, during surveillance of patients, there are frequently losses to follow-up because of patients undergoing AAA repair or serious complications.17 Second, monitoring AAA growth is not straightforward because of the complexity of measuring AAA diameter accurately outlined above.23,24

Currently, no circulating markers have been accepted to be sufficiently valuable to be introduced into clinical practice.

Circulating Markers Associated With AAA Growth

Tables 1 and 2 illustrate some of the marker investigated for the association with small AAA growth.55–70 Of the marker examined, only 2, namely D-dimer and plasmin–antiplasmin complex, have been associated with AAA growth after adjusting for initial AAA diameter in at least 2 distinct studies (Table 1).55–57 In the largest of these studies, in which 299 patients with small AAAs were included, it was reported that the use of plasma D-dimer plus initial aortic diameter enable the identification of groups of patients with AAA growth as disparate as 0.4 and 2.5 mm/y.56 Other markers investigated have been examined in single cohorts only, or findings have been inconsistent across studies (eg, C-reactive protein and matrix metalloproteinase-9; Tables 1 and 2).

View this table:
Table 1.

Examples of Circulating Biomarkers Assessed for Associated With Small AAA Growth in At Least 2 Studies

View this table:
Table 2.

Examples of Circulating Biomarkers Assessed for Associated With Small AAA Growth in Single Studies

Circulating Markers Associated With AAA Rupture

Few studies have investigated the association of circulating markers with subsequent AAA rupture. Studies investigating predictors of AAA rupture are difficult to perform and are subject to bias because they require large sample sizes, given that rupture of small AAAs is rare and most large AAAs undergo surgical repair. Currently, no circulating biomarkers have been convincingly shown to predict AAA rupture. Satta et al64 reported the assessment of 18 patients whose AAA subsequently ruptured were compared with 55 patients whose AAA remained intact during follow-up. The investigators reported that serum concentrations of the collagen turnover marker procollagen-IIIN-terminal propeptide were significantly higher in patients who later developed AAA rupture although it was not stated whether this association was independent of initial AAA diameter.

Future Progress in Identifying Circulating Markers of AAA Progression

Table 3 illustrates some advantages and disadvantages of techniques in current use or under investigation for predicting AAA progression. Given the potential ease of measuring blood markers in clinical trials and clinical practice, there is continued interest in such tools. Further work is, however, needed to identify groups of markers, which are reflective of the pathological processes present in AAA and which can be used as surrogate markers in clinical trials and clinical practice. Many proteomics and metabolomics studies have been performed in an attempt to screen for markers; however, currently, these techniques have many limitations, such as the difficulty in detecting less abundant proteins within blood samples and problems in processing high numbers of samples reproducibly.71 Recently, many investigators have reported circulating micro-RNAs associated with AAA presence, such as miR-155, miR-191-3p, miR-455-3p, miR-1281, and miR-411.72–74 Theoretical micro-RNAs have advantages over other circulating nucleic acids as markers in diagnostic tests because of their stability in blood samples. There have also been studies using lipidomics.75 Techniques to screen large numbers of circulating micro-RNAs and lipids are better developed than for proteins, and therefore it is possible that these fields of investigation maybe more fruitful in identifying effective markers. Ultimately, any markers identified by these screening techniques will need to be tested in large numbers of patients from different populations to assess their value in different situation such as determining the response to treatment or predicting which AAAs should receive early or delayed intervention.

View this table:
Table 3.

Theoretical Advantages and Disadvantages of Imaging and Circulating Biomarkers as Surrogate Markers of AAA Progression

Conclusions

AAA diameter remains the most widely used and important marker of AAA progression although it has many limitations. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers have potential to be adopted in practice in the future.

Disclosures

None.

Footnotes

  • Nonstandard Abbreviations and Acronyms
    FDG
    18-fluorodeoxyglucose
    AAA
    abdominal aortic aneurysm
    CT
    computed tomography
    ILT
    intraluminal thrombus
    MRI
    magnetic resonance imaging
    PET
    positron emission tomography
    PWS
    peak wall stress
    PWRI
    peak wall rupture index

  • Received October 30, 2015.
  • Accepted December 14, 2015.

References

  1. 1.↵
    1. Golledge J,
    2. Norman PE
    . Current status of medical management for abdominal aortic aneurysm. Atherosclerosis. 2011;217:57–63. doi: 10.1016/j.atherosclerosis.2011.03.006.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Moll FL,
    2. Powell JT,
    3. Fraedrich G,
    4. Verzini F,
    5. Haulon S,
    6. Waltham M,
    7. van Herwaarden JA,
    8. Holt PJ,
    9. van Keulen JW,
    10. Rantner B,
    11. Schlösser FJ,
    12. Setacci F,
    13. Ricco JB
    ; European Society for Vascular Surgery. Management of abdominal aortic aneurysms clinical practice guidelines of the European society for vascular surgery. Eur J Vasc Endovasc Surg. 2011;41(suppl 1):S1–S58. doi: 10.1016/j.ejvs.2010.09.011.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. The International AAA Screening Group,
    2. Björck M,
    3. Bown MJ,
    4. Choke E,
    5. Earnshaw J,
    6. Flørenes T,
    7. Glover M,
    8. Kay M,
    9. Laukontaus S,
    10. Lees T,
    11. Lindholt J,
    12. Powell JT,
    13. van Rij A,
    14. Svensjö S,
    15. Wanhainen A
    . International update on screening for abdominal aortic aneurysms: issues and opportunities. Eur J Vasc Endovasc Surg. 2015;49:113–115.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Beales L,
    2. Wolstenhulme S,
    3. Evans JA,
    4. West R,
    5. Scott DJ
    . Reproducibility of ultrasound measurement of the abdominal aorta. Br J Surg. 2011;98:1517–1525. doi: 10.1002/bjs.7628.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Gürtelschmid M,
    2. Björck M,
    3. Wanhainen A
    . Comparison of three ultrasound methods of measuring the diameter of the abdominal aorta. Br J Surg. 2014;101:633–636. doi: 10.1002/bjs.9463.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Kauffmann C,
    2. Tang A,
    3. Therasse E,
    4. Giroux MF,
    5. Elkouri S,
    6. Melanson P,
    7. Melanson B,
    8. Oliva VL,
    9. Soulez G
    . Measurements and detection of abdominal aortic aneurysm growth: Accuracy and reproducibility of a segmentation software. Eur J Radiol. 2012;81:1688–1694. doi: 10.1016/j.ejrad.2011.04.044.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Grøndal N,
    2. Bramsen MB,
    3. Thomsen MD,
    4. Rasmussen CB,
    5. Lindholt JS
    . The cardiac cycle is a major contributor to variability in size measurements of abdominal aortic aneurysms by ultrasound. Eur J Vasc Endovasc Surg. 2012;43:30–33. doi: 10.1016/j.ejvs.2011.09.025.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Bredahl K,
    2. Eldrup N,
    3. Meyer C,
    4. Eiberg JE,
    5. Sillesen H
    . Reproducibility of ECG-gated ultrasound diameter assessment of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2013;45:235–240. doi: 10.1016/j.ejvs.2012.12.010.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Long A,
    2. Rouet L,
    3. Lindholt JS,
    4. Allaire E
    . Measuring the maximum diameter of native abdominal aortic aneurysms: review and critical analysis. Eur J Vasc Endovasc Surg. 2012;43:515–524. doi: 10.1016/j.ejvs.2012.01.018.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Hartshorne TC,
    2. McCollum CN,
    3. Earnshaw JJ,
    4. Morris J,
    5. Nasim A
    . Ultrasound measurement of aortic diameter in a national screening programme. Eur J Vasc Endovasc Surg. 2011;42:195–199. doi: 10.1016/j.ejvs.2011.02.030.
    OpenUrlCrossRefPubMed
  11. 11.↵
    The UK Small Aneurysm Trial: design, methods and progress. The UK Small Aneurysm Trial participants. Eur J Vasc Endovasc Surg. 1995; 9:42–48.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Powell JT,
    2. Brown LC,
    3. Forbes JF,
    4. Fowkes FG,
    5. Greenhalgh RM,
    6. Ruckley CV,
    7. Thompson SG
    . Final 12-year follow-up of surgery versus surveillance in the UK Small Aneurysm Trial. Br J Surg. 2007;94:702–708. doi: 10.1002/bjs.5778.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Ashton HA,
    2. Buxton MJ,
    3. Day NE,
    4. Kim LG,
    5. Marteau TM,
    6. Scott RA,
    7. Thompson SG,
    8. Walker NM
    ; Multicentre Aneurysm Screening Study Group. The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial. Lancet. 2002;360:1531–1539.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Davis M,
    2. Harris M,
    3. Earnshaw JJ
    . Implementation of the National Health Service Abdominal Aortic Aneurysm Screening Program in England. J Vasc Surg. 2013;57:1440–1445. doi: 10.1016/j.jvs.2012.10.114.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Svensjö S,
    2. Björck M,
    3. Gürtelschmid M,
    4. Djavani Gidlund K,
    5. Hellberg A,
    6. Wanhainen A
    . Low prevalence of abdominal aortic aneurysm among 65-year-old Swedish men indicates a change in the epidemiology of the disease. Circulation. 2011;124:1118–1123. doi: 10.1161/CIRCULATIONAHA.111.030379.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Thompson SG,
    2. Brown LC,
    3. Sweeting MJ,
    4. Bown MJ,
    5. Kim LG,
    6. Glover MJ,
    7. Buxton MJ,
    8. Powell JT
    . Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic aneurysms: implications for surveillance intervals and their cost-effectiveness. Health Technol Assess. 2013;17:1–118. doi: 10.3310/hta17410.
    OpenUrlPubMed
  17. 17.↵
    1. Brady AR,
    2. Thompson SG,
    3. Fowkes FG,
    4. Greenhalgh RM,
    5. Powell JT
    ; UK Small Aneurysm Trial Participants. Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance. Circulation. 2004;110:16–21. doi: 10.1161/01.CIR.0000133279.07468.9F.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Sillesen H,
    2. Eldrup N,
    3. Hultgren R,
    4. Lindeman J,
    5. Bredahl K,
    6. Thompson M,
    7. Wanhainen A,
    8. Wingren U,
    9. Swedenborg J
    ; AORTA Trial Investigators. Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm. Br J Surg. 2015;102:894–901. doi: 10.1002/bjs.9824.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Thompson AR,
    2. Cooper JA,
    3. Ashton HA,
    4. Hafez H
    . Growth rates of small abdominal aortic aneurysms correlate with clinical events. Br J Surg. 2010;97:37–44. doi: 10.1002/bjs.6779.
    OpenUrlPubMed
  20. 20.↵
    1. Bown MJ,
    2. Sweeting MJ,
    3. Brown LC,
    4. Powell JT,
    5. Thompson SG
    , the RESCAN Collaborators. Surveillance intervals for small abdominal aortic aneurysms: a meta-analysis. JAMA. 2013;309:806–813.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Sharp MA,
    2. Collin J
    . A myth exposed: fast growth in diameter does not justify precocious abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg. 2003;25:408–411. doi: 10.1053/ejvs.2002.1850.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Vega de Céniga M,
    2. Gómez R,
    3. Estallo L,
    4. de la Fuente N,
    5. Viviens B,
    6. Barba A
    . Analysis of expansion patterns in 4–4.9 cm abdominal aortic aneurysms. Ann Vasc Surg. 2008;22:37–44.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Kurvers H,
    2. Veith FJ,
    3. Lipsitz EC,
    4. Ohki T,
    5. Gargiulo NJ,
    6. Cayne NS,
    7. Suggs WD,
    8. Timaran CH,
    9. Kwon GY,
    10. Rhee SJ,
    11. Santiago C
    . Discontinuous, staccato growth of abdominal aortic aneurysms. J Am Coll Surg. 2004;199:709–715. doi: 10.1016/j.jamcollsurg.2004.07.031.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Parr A,
    2. Jayaratne C,
    3. Buttner P,
    4. Golledge J
    . Comparison of volume and diameter measurement in assessing small abdominal aortic aneurysm expansion examined using computed tomographic angiography. Eur J Radiol. 2011;79:42–47. doi: 10.1016/j.ejrad.2009.12.018.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Kitagawa A,
    2. Mastracci TM,
    3. von Allmen R,
    4. Powell JT
    . The role of diameter versus volume as the best prognostic measurement of abdominal aortic aneurysms. J Vasc Surg. 2013;58:258–265. doi: 10.1016/j.jvs.2013.05.001.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Kontopodis N,
    2. Metaxa E,
    3. Papaharilaou Y,
    4. Georgakarakos E,
    5. Tsetis D,
    6. Ioannou CV
    . Value of volume measurements in evaluating abdominal aortic aneurysms growth rate and need for surgical treatment. Eur J Radiol. 2014;83:1051–1056. doi: 10.1016/j.ejrad.2014.03.018.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Nambi P,
    2. Sengupta R,
    3. Krajcer Z,
    4. Muthupillai R,
    5. Strickman N,
    6. Cheong BY
    . Non-contrast computed tomography is comparable to contrast-enhanced computed tomography for aortic volume analysis after endovascular abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg. 2011;41:460–466. doi: 10.1016/j.ejvs.2010.11.027.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Arsicot M,
    2. Lathelize H,
    3. Martinez R,
    4. Marchand E,
    5. Picquet J,
    6. Enon B
    . Follow-up of aortic stent grafts: comparison of the volumetric analysis of the aneurysm sac by ultrasound and CT. Ann Vasc Surg. 2014;28:1618–1628. doi: 10.1016/j.avsg.2014.03.034.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Wever JJ,
    2. Blankensteijn JD,
    3. Th M Mali WP,
    4. Eikelboom BC
    . Maximal aneurysm diameter follow-up is inadequate after endovascular abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg. 2000;20:177–182. doi: 10.1053/ejvs.1999.1051.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Kritpracha B,
    2. Beebe HG,
    3. Comerota AJ
    . Aortic diameter is an insensitive measurement of early aneurysm expansion after endografting. J Endovasc Ther. 2004;11:184–190. doi: 10.1583/03-976.1.
    OpenUrlAbstract/FREE Full Text
  31. 31.↵
    1. van Keulen JW,
    2. van Prehn J,
    3. Prokop M,
    4. Moll FL,
    5. van Herwaarden JA
    . Potential value of aneurysm sac volume measurements in addition to diameter measurements after endovascular aneurysm repair. J Endovasc Ther. 2009;16:506–513. doi: 10.1583/09-2690.1.
    OpenUrlAbstract/FREE Full Text
  32. 32.↵
    1. Bley TA,
    2. Chase PJ,
    3. Reeder SB,
    4. François CJ,
    5. Shinki K,
    6. Tefera G,
    7. Ranallo FN,
    8. Grist TM,
    9. Pozniak M
    . Endovascular abdominal aortic aneurysm repair: nonenhanced volumetric CT for follow-up. Radiology. 2009;253:253–262. doi: 10.1148/radiol.2531082093.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Parr A,
    2. McCann M,
    3. Bradshaw B,
    4. Shahzad A,
    5. Buttner P,
    6. Golledge J
    . Thrombus volume is associated with cardiovascular events and aneurysm growth in patients who have abdominal aortic aneurysms. J Vasc Surg. 2011;53:28–35. doi: 10.1016/j.jvs.2010.08.013.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Behr-Rasmussen C,
    2. Grøndal N,
    3. Bramsen MB,
    4. Thomsen MD,
    5. Lindholt JS
    . Mural thrombus and the progression of abdominal aortic aneurysms: a large population-based prospective cohort study. Eur J Vasc Endovasc Surg. 2014;48:301–307. doi: 10.1016/j.ejvs.2014.05.014.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Nguyen VL,
    2. Leiner T,
    3. Hellenthal FA,
    4. Backes WH,
    5. Wishaupt MC,
    6. van der Geest RJ,
    7. Heeneman S,
    8. Kooi ME,
    9. Schurink GW
    . Abdominal aortic aneurysms with high thrombus signal intensity on magnetic resonance imaging are associated with high growth rate. Eur J Vasc Endovasc Surg. 2014;48:676–684. doi: 10.1016/j.ejvs.2014.04.025.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Kok AM,
    2. Nguyen VL,
    3. Speelman L,
    4. Brands PJ,
    5. Schurink GW,
    6. van de Vosse FN,
    7. Lopata RG
    . Feasibility of wall stress analysis of abdominal aortic aneurysms using three-dimensional ultrasound. J Vasc Surg. 2015;61:1175–1184. doi: 10.1016/j.jvs.2014.12.043.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Gasser TC,
    2. Nchimi A,
    3. Swedenborg J,
    4. Roy J,
    5. Sakalihasan N,
    6. Böckler D,
    7. Hyhlik-Dürr A
    . A novel strategy to translate the biomechanical rupture risk of abdominal aortic aneurysms to their equivalent diameter risk: method and retrospective validation. Eur J Vasc Endovasc Surg. 2014;47:288–295. doi: 10.1016/j.ejvs.2013.12.018.
    OpenUrlCrossRefPubMed
  38. 38.↵
    1. Gasser TC,
    2. Auer M,
    3. Labruto F,
    4. Swedenborg J,
    5. Roy J
    . Biomechanical rupture risk assessment of abdominal aortic aneurysms: model complexity versus predictability of finite element simulations. Eur J Vasc Endovasc Surg. 2010;40:176–185. doi: 10.1016/j.ejvs.2010.04.003.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Boyd AJ,
    2. Kuhn DC,
    3. Lozowy RJ,
    4. Kulbisky GP
    . Low wall shear stress predominates at sites of abdominal aortic aneurysm rupture. J Vasc Surg. 2015. doi: 10.1016/j.jvs.2015.01.040.
  40. 40.↵
    1. Erhart P,
    2. Hyhlik-Dürr A,
    3. Geisbüsch P,
    4. Kotelis D,
    5. Müller-Eschner M,
    6. Gasser TC,
    7. von Tengg-Kobligk H,
    8. Böckler D
    . Finite element analysis in asymptomatic, symptomatic, and ruptured abdominal aortic aneurysms: in search of new rupture risk predictors. Eur J Vasc Endovasc Surg. 2015;49:239–245. doi: 10.1016/j.ejvs.2014.11.010.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Erhart P,
    2. Grond-Ginsbach C,
    3. Hakimi M,
    4. Lasitschka F,
    5. Dihlmann S,
    6. Böckler D,
    7. Hyhlik-Dürr A
    . Finite element analysis of abdominal aortic aneurysms: predicted rupture risk correlates with aortic wall histology in individual patients. J Endovasc Ther. 2014;21:556–564. doi: 10.1583/14-4695.1.
    OpenUrlAbstract/FREE Full Text
  42. 42.↵
    1. Khosla S,
    2. Morris DR,
    3. Moxon JV,
    4. Walker PJ,
    5. Gasser TC,
    6. Golledge J
    . Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms. Br J Surg. 2014;101:1350–1357; discussion 1357. doi: 10.1002/bjs.9578.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Tegler G,
    2. Sörensen J,
    3. Björck M,
    4. Savitcheva I,
    5. Wanhainen A
    . Detection of aortic graft infection by 18-fluorodeoxyglucose positron emission tomography combined with computed tomography. J Vasc Surg. 2007;45:828–830. doi: 10.1016/j.jvs.2006.12.018.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Davison JM,
    2. Montilla-Soler JL,
    3. Broussard E,
    4. Wilson R,
    5. Cap A,
    6. Allen T
    . F-18 FDG PET-CT imaging of a mycotic aneurysm. Clin Nucl Med. 2005;30:483–487.
    OpenUrlCrossRefPubMed
  45. 45.↵
    1. Reeps C,
    2. Essler M,
    3. Pelisek J,
    4. Seidl S,
    5. Eckstein HH,
    6. Krause BJ
    . Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms. J Vasc Surg. 2008;48:417–23; discussion 424. doi: 10.1016/j.jvs.2008.03.059.
    OpenUrlCrossRefPubMed
  46. 46.↵
    1. Sakalihasan N,
    2. Van Damme H,
    3. Gomez P,
    4. Rigo P,
    5. Lapiere CM,
    6. Nusgens B,
    7. Limet R
    . Positron emission tomography (PET) evaluation of abdominal aortic aneurysm (AAA). Eur J Vasc Endovasc Surg. 2002;23:431–436. doi: 10.1053/ejvs.2002.1646.
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Tegler G,
    2. Ericson K,
    3. Sörensen J,
    4. Björck M,
    5. Wanhainen A
    . Inflammation in the walls of asymptomatic abdominal aortic aneurysms is not associated with increased metabolic activity detectable by 18-fluorodeoxglucose positron-emission tomography. J Vasc Surg. 2012;56:802–807. doi: 10.1016/j.jvs.2012.02.024.
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Tegler G,
    2. Estrada S,
    3. Hall H,
    4. Wanhainen A,
    5. Björck M,
    6. Sörensen J,
    7. Antoni G
    . Autoradiography screening of potential positron emission tomography tracers for asymptomatic abdominal aortic aneurysms. Ups J Med Sci. 2014;119:229–235. doi: 10.3109/03009734.2014.894157.
    OpenUrlCrossRefPubMed
  49. 49.↵
    1. Tang TY,
    2. Muller KH,
    3. Graves MJ,
    4. Li ZY,
    5. Walsh SR,
    6. Young V,
    7. Sadat U,
    8. Howarth SP,
    9. Gillard JH
    . Iron oxide particles for atheroma imaging. Arterioscler Thromb Vasc Biol. 2009;29:1001–1008. doi: 10.1161/ATVBAHA.108.165514.
    OpenUrlAbstract/FREE Full Text
  50. 50.↵
    1. Sadat U,
    2. Taviani V,
    3. Patterson AJ,
    4. Young VE,
    5. Graves MJ,
    6. Teng Z,
    7. Sadat U,
    8. Taviani V,
    9. Patterson AJ,
    10. Young VE,
    11. Graves MJ,
    12. Teng Z
    . Ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging of abdominal aortic aneurysms–a feasibility study. Eur J Vasc Endovasc Surg. 2011;41:167–174.
    OpenUrlCrossRefPubMed
  51. 51.↵
    1. Richards JM,
    2. Semple SI,
    3. MacGillivray TJ,
    4. Gray C,
    5. Langrish JP,
    6. Williams M,
    7. Dweck M,
    8. Wallace W,
    9. McKillop G,
    10. Chalmers RT,
    11. Garden OJ,
    12. Newby DE
    . Abdominal aortic aneurysm growth predicted by uptake of ultrasmall superparamagnetic particles of iron oxide: a pilot study. Circ Cardiovasc Imaging. 2011;4:274–281. doi: 10.1161/CIRCIMAGING.110.959866.
    OpenUrlAbstract/FREE Full Text
  52. 52.↵
    1. Naeger DM,
    2. Behr SC
    . PET/MR imaging: current and future applications for cardiovascular disease. Magn Reson Imaging Clin N Am. 2015;23:95–103. doi: 10.1016/j.mric.2014.09.006.
    OpenUrlCrossRefPubMed
  53. 53.↵
    1. Golledge J,
    2. Tsao PS,
    3. Dalman RL,
    4. Norman PE
    . Circulating markers of abdominal aortic aneurysm presence and progression. Circulation. 2008;118:2382–2392. doi: 10.1161/CIRCULATIONAHA.108.802074.
    OpenUrlFREE Full Text
  54. 54.↵
    1. Stather PW,
    2. Sidloff DA,
    3. Dattani N,
    4. Gokani VJ,
    5. Choke E,
    6. Sayers RD,
    7. Bown MJ
    . Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm. Br J Surg. 2014;101:1358–1372. doi: 10.1002/bjs.9593.
    OpenUrlCrossRefPubMed
  55. 55.↵
    1. Vega de Ceniga M,
    2. Esteban M,
    3. Barba A,
    4. Estallo L,
    5. Blanco-Colio LM,
    6. Martin-Ventura JL
    . Assessment of biomarkers and predictive model for short-term prospective abdominal aortic aneurysm growth-A pilot study. Ann Vasc Surg. 2014;28:1642–1648.
    OpenUrlCrossRefPubMed
  56. 56.↵
    1. Golledge J,
    2. Muller R,
    3. Clancy P,
    4. McCann M,
    5. Norman PE
    . Evaluation of the diagnostic and prognostic value of plasma D-dimer for abdominal aortic aneurysm. Eur Heart J. 2011;32:354–364. doi: 10.1093/eurheartj/ehq171.
    OpenUrlAbstract/FREE Full Text
  57. 57.↵
    1. Lindholt JS,
    2. Jørgensen B,
    3. Fasting H,
    4. Henneberg EW
    . Plasma levels of plasmin-antiplasmin-complexes are predictive for small abdominal aortic aneurysms expanding to operation-recommendable sizes. J Vasc Surg. 2001;34:611–615. doi: 10.1067/mva.2001.119040.
    OpenUrlCrossRefPubMed
  58. 58.↵
    1. De Haro J,
    2. Acin F,
    3. Bleda S,
    4. Varela C,
    5. Medina FJ,
    6. Esparza L
    . Prediction of asymptomatic abdominal aortic aneurysm expansion by means of rate of variation of C-reactive protein plasma levels. J Vasc Surg. 2012;56:45–52. doi: 10.1016/j.jvs.2012.01.003.
    OpenUrlCrossRefPubMed
  59. 59.↵
    1. Norman P,
    2. Spencer CA,
    3. Lawrence-Brown MM,
    4. Jamrozik K
    . C-reactive protein levels and the expansion of screen-detected abdominal aortic aneurysms in men. Circulation. 2004;110:862–866. doi: 10.1161/01.CIR.0000138746.14425.00.
    OpenUrlAbstract/FREE Full Text
  60. 60.↵
    1. Lindholt JS,
    2. Erlandsen EJ,
    3. Henneberg EW
    . Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br J Surg. 2001;88:1472–1475. doi: 10.1046/j.0007-1323.2001.01911.x.
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Flondell-Sité D,
    2. Lindblad B,
    3. Kölbel T,
    4. Gottsäter A
    . Markers of proteolysis, fibrinolysis, and coagulation in relation to size and growth rate of abdominal aortic aneurysms. Vasc Endovascular Surg. 2010;44:262–268. doi: 10.1177/1538574410361971.
    OpenUrlAbstract/FREE Full Text
  62. 62.↵
    1. Speelman L,
    2. Hellenthal FA,
    3. Pulinx B,
    4. Bosboom EM,
    5. Breeuwer M,
    6. van Sambeek MR,
    7. van de Vosse FN,
    8. Jacobs MJ,
    9. Wodzig WK,
    10. Schurink GW
    . The influence of wall stress on AAA growth and biomarkers. Eur J Vasc Endovasc Surg. 2010;39:410–416. doi: 10.1016/j.ejvs.2009.12.021.
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Lindholt JS,
    2. Heickendorff L,
    3. Vammen S,
    4. Fasting H,
    5. Henneberg EW
    . Five-year results of elastin and collagen markers as predictive tools in the management of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2001;21:235–240. doi: 10.1053/ejvs.2001.1329.
    OpenUrlCrossRefPubMed
  64. 64.↵
    1. Satta J,
    2. Haukipuro K,
    3. Kairaluoma MI,
    4. Juvonen T
    . Aminoterminal propeptide of type III procollagen in the follow-up of patients with abdominal aortic aneurysms. J Vasc Surg. 1997;25:909–915.
    OpenUrlCrossRefPubMed
  65. 65.↵
    1. Lindholt JS,
    2. Jørgensen B,
    3. Shi GP,
    4. Henneberg EW
    . Relationships between activators and inhibitors of plasminogen, and the progression of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2003;25:546–551. doi: 10.1053/ejvs.2002.1872.
    OpenUrlCrossRefPubMed
  66. 66.↵
    1. Martinez-Pinna R,
    2. Ramos-Mozo P,
    3. Madrigal-Matute J,
    4. Blanco-Colio LM,
    5. Lopez JA,
    6. Calvo E,
    7. Camafeita E,
    8. Lindholt JS,
    9. Meilhac O,
    10. Delbosc S,
    11. Michel JB,
    12. Vega de Ceniga M,
    13. Egido J,
    14. Martin-Ventura JL
    . Identification of peroxiredoxin-1 as a novel biomarker of abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 2011;31:935–943. doi: 10.1161/ATVBAHA.110.214429.
    OpenUrlAbstract/FREE Full Text
  67. 67.↵
    1. Martín-Ventura JL,
    2. Lindholt JS,
    3. Moreno JA,
    4. Vega de Céniga M,
    5. Meilhac O,
    6. Michel JB,
    7. Egido J,
    8. Blanco-Colio LM
    . Soluble TWEAK plasma levels predict expansion of human abdominal aortic aneurysms. Atherosclerosis. 2011;214:486–489. doi: 10.1016/j.atherosclerosis.2010.11.009.
    OpenUrlCrossRefPubMed
  68. 68.↵
    1. Lindholt JS,
    2. Jørgensen B,
    3. Klitgaard NA,
    4. Henneberg EW
    . Systemic levels of cotinine and elastase, but not pulmonary function, are associated with the progression of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2003;26:418–422.
    OpenUrlCrossRefPubMed
  69. 69.↵
    1. Golledge J,
    2. Muller J,
    3. Shephard N,
    4. Clancy P,
    5. Smallwood L,
    6. Moran C,
    7. Dear AE,
    8. Palmer LJ,
    9. Norman PE
    . Association between osteopontin and human abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 2007;27:655–660. doi: 10.1161/01.ATV.0000255560.49503.4e.
    OpenUrlAbstract/FREE Full Text
  70. 70.↵
    1. Moran CS,
    2. McCann M,
    3. Karan M,
    4. Norman P,
    5. Ketheesan N,
    6. Golledge J
    . Association of osteoprotegerin with human abdominal aortic aneurysm progression. Circulation. 2005;111:3119–3125. doi: 10.1161/CIRCULATIONAHA.104.464727.
    OpenUrlAbstract/FREE Full Text
  71. 71.↵
    1. Moxon JV,
    2. Padula MP,
    3. Herbert BR,
    4. Golledge J
    . Challenges, current status and future perspectives of proteomics in improving understanding, diagnosis and treatment of vascular disease. Eur J Vasc Endovasc Surg. 2009;38:346–355. doi: 10.1016/j.ejvs.2009.05.008.
    OpenUrlCrossRefPubMed
  72. 72.↵
    1. Biros E,
    2. Moran CS,
    3. Wang Y,
    4. Walker PJ,
    5. Cardinal J,
    6. Golledge J
    . microRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155. Clin Sci (Lond). 2014;126:795–803. doi: 10.1042/CS20130599.
    OpenUrlCrossRefPubMed
  73. 73.↵
    1. Zhang W,
    2. Shang T,
    3. Huang C,
    4. Yu T,
    5. Liu C,
    6. Qiao T,
    7. Huang D,
    8. Liu Z,
    9. Liu C
    . Plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm. Clin Biochem. 2015;48:988–992. doi: 10.1016/j.clinbiochem.2015.04.016.
    OpenUrlCrossRefPubMed
  74. 74.↵
    1. Stather PW,
    2. Sylvius N,
    3. Sidloff DA,
    4. Dattani N,
    5. Verissimo A,
    6. Wild JB,
    7. Butt HZ,
    8. Choke E,
    9. Sayers RD,
    10. Bown MJ
    . Identification of microRNAs associated with abdominal aortic aneurysms and peripheral arterial disease. Br J Surg. 2015;102:755–766. doi: 10.1002/bjs.9802.
    OpenUrlCrossRefPubMed
  75. 75.↵
    1. Moxon JV,
    2. Liu D,
    3. Wong G,
    4. Weir JM,
    5. Behl-Gilhotra R,
    6. Bradshaw B,
    7. Kingwell BA,
    8. Meikle PJ,
    9. Golledge J
    . Comparison of the serum lipidome in patients with abdominal aortic aneurysm and peripheral artery disease. Circ Cardiovasc Genet. 2014;7:71–79. doi: 10.1161/CIRCGENETICS.113.000343.
    OpenUrlAbstract/FREE Full Text

Significance

Abdominal aortic aneurysm is a common and potentially lethal disease. Predicting the progression of small abdominal aortic aneurysm s is essential in clinical practice and research. Here, we review the current evidence on the value of different surrogate markers of abdominal aortic aneurysm progression, such as abdominal aortic aneurysm diameter and volume measurement, biomechanical analyses, functional and molecular imagings, and circulating biomarkers.

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  • Surrogate Markers of Abdominal Aortic Aneurysm ProgressionSignificance
    Anders Wanhainen, Kevin Mani and Jonathan Golledge
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2016;36:236-244, originally published December 29, 2015
    https://doi.org/10.1161/ATVBAHA.115.306538
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