Screening for Abdominal Aortic Aneurysm During Transthoracic Echocardiography: A Systematic Review and Meta-analysis

Eur J Vasc Endovasc Surg (2018)

-,

1e17

REVIEW

Screening for Abdominal Aortic Aneurysm During Transthoracic Echocardiography: A Systematic Review and Meta-analysis Christos Argyriou a, George S. Georgiadis b,*, Nikolaos Kontopodis c, Arun D. Pherwani a, Joost A. Van Herwaarden d, Constantijn E.V.B. Hazenberg d, George A. Antoniou e a

Department of Vascular Surgery, Royal Stoke University Hospital, Stoke-on-Trent, UK Department of Vascular Surgery, “Democritus” University of Thrace, University General Hospital of Evros, Alexandroupolis, Greece c Vascular Surgery Unit, Department of Cardiothoracic and Vascular Surgery, University Hospital of Heraklion, University of Crete, Heraklion, Greece d Department of Vascular Surgery, University Medical Centre, Utrecht, The Netherlands e Department of Vascular and Endovascular Surgery, The Royal Oldham Hospital, Pennine Acute Hospitals NHS Trust, Manchester, UK b

WHAT THIS PAPER ADDS Patients undergoing transthoracic echocardiography (TTE) probably have a cardiovascular risk profile similar to that of patients with abdominal aortic aneurysm (AAA) and may represent a group with a higher prevalence of AAA. The feasibility of estimating the prevalence of AAA during screening with TTE was investigated by conducting a systematic review and meta-analysis. The data suggest that targeted screening in this population may be beneficial where population based screening programs are not available. Opportunistic screening may also be considered in the light of the declining incidence of AAA. Further research is required to investigate the clinical benefits of screening in this setting.

Background: Screening for abdominal aortic aneurysm (AAA) during transthoracic echocardiography (TTE) may be an effective targeted screening strategy. Objective: The aim was to assess the feasibility of AAA screening during TTE and to estimate the prevalence of AAA in patients undergoing TTE. Methods: Electronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies reporting on AAA screening during TTE. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used to calculate pooled prevalence estimates. Results: Twenty observational cohort studies were identified reporting a total of 43,341 participants (23,291 men and 20,050 women). Hypertension was reported in 41% (95% CI 38e43), hypercholesterolemia in 31% (95% CI 29e32), diabetes mellitus in 20% (95% CI 19e22), and tobacco use in 37% (95% CI 35e38). The aorta was visualised in 86% (95% CI 84e88) of the screened population. The pooled prevalence of AAA in the entire screened population was 0.033 (95% CI 0.024e0.044). The pooled prevalence of AAA in men was 0.046 (95% CI 0.032e0.065) and in women it was 0.014 (95% CI 0.008e0.022). The mean age of participants in whom an AAA was detected ranged across the studies from 66 to 85 years. The mean diameter of the aneurysm identified ranged across the studies from 35 mm to 45 mm. Clinical outcomes in participants with a detected AAA were poorly reported. Conclusions: Screening for AAA during TTE may identify a population group with a high risk of AAA in whom targeted screening may be beneficial. Further research is required to investigate the cost-effectiveness and clinical benefits of AAA screening in this setting. Ó 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. Article history: Received 31 July 2017, Accepted 3 January 2018, Available online XXX Keywords: Abdominal aortic aneurysm, Transthoracic echocardiography, Echocardiogram, Ultrasound, Screening

* Corresponding author. Alexandrou Papanastasiou 7 str., Alexandroupolis, 68131, Greece. E-mail addresses: [email protected]; [email protected] (George S. Georgiadis). 1078-5884/Ó 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.ejvs.2018.01.003

INTRODUCTION Abdominal aortic aneurysm (AAA) is a serious condition mainly encountered in the aging population of Western societies; it is associated with a significant morbidity and mortality in the event of rupture.1,2 The US Preventive

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Services Task Force recommends one time screening for AAA by ultrasonography in men 65e75 years who have ever smoked.3 The Society for Vascular Surgery (SVS) recommends one time ultrasound screening for all men at or older than 65 years and as early as 55 years if there is a family history of AAA, and one time ultrasound screening for all women at or older than 65 years with a family history of AAA or who have smoked.4 The European Society for Vascular Surgery (ESVS) guidelines, recommend population screening for older men, and for older women with a family history of AAA.5 The guideline recommendations are based on high level evidence from large scale population screening studies, including the Multicentre Aneurysm Screening Study MASS (UK),6 the West Australian Aneurysm Screening Study,7 the Chichester study (UK),2 and the Viborg Study (Denmark),8 which have demonstrated that screening for AAA decreases overall mortality. Furthermore, a pooled analysis of trial data found a significant reduction in aneurysm related and overall mortality in men after 3e5 years.9 The same meta-analysis found a significant increase in elective surgery for asymptomatic AAA resulting from population based screening and a significant decrease in emergency surgery for AAA.9 Abdominal ultrasonography is a non-invasive, highly sensitive, and cost-effective tool for AAA screening, with a reported visibility of 97.5e100% and diagnostic specificity close to 100%.10 Since there is emerging evidence to suggest that the incidence of AAA has decreased, mainly due to reduced smoking rates and modification of atherosclerotic risk factors,11 targeted AAA screening of high risk populations may be more cost-effective. The feasibility of AAA screening during transthoracic echocardiography (TTE) has been reported in several studies.12e16 Patients referred for echocardiography are thought to have cardiovascular risk factors which have been shown to be associated with AAA.14 Detection of AAA using TTE would involve few additional resources, as the same probe can be used to scan the aorta, which can be examined with the patient in the same position as for TEE. Considering that patients who undergo TTE have cardiovascular comorbidities, the prevalence of AAA in this group is speculated to be higher than that in the normal AAA screening population. The objective of the present review and meta-analysis was to assess the feasibility of AAA screening during TTE and to estimate AAA prevalence in patients undergoing TTE. MATERIALS AND METHODS Design The review conformed to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement standards.17 The objectives, selection criteria, outcome measures, and methods of analysis were specified in a study protocol, which was registered at the International Prospective Register of Systematic Reviews in Health and Social Care (CRD42017056286).18

Christos Argyriou et al.

Eligibility criteria Observational cohort studies reporting on screening for AAA during TTE were considered. Studies that provided adequate information on methods and techniques of the screening test were included. Eligible studies should also provide information on the prevalence of newly detected AAA in the screened population. Participants of any age and gender who were screened for AAA during TTE performed for known or suspected cardiac disease were considered. Participants who were known to have an AAA and those with previous AAA repair were excluded. The primary outcome measure was the prevalence of newly detected AAA in the screened population. Baseline demographics and cardiovascular risk factors in the studied populations were recorded. Information sources and literature search strategy Studies were identified by searching electronic bibliographic databases and scanning reference lists of articles. The following electronic bibliographic sources were searched: PubMed/MEDLINE, SCOPUS, and the Cochrane Central Register of Controlled Trials (CENTRAL). Relevant terms to identify eligible reports were selected. The following MeSH terms and key words were used: “aortic aneurysm, abdominal”; “aortic aneurysm”; “screening”; “transthoracic echocardiography”; and “echocardiography”. Thesaurus headings, search operators, and limits in each of the above databases were adapted accordingly. The last search was run in May 2017. No language constraints were applied. Study selection and data management Eligibility assessment of identified studies was performed by two authors (C.A., N.K.). A data extraction sheet was developed, and it was pilot tested in randomly selected studies that met the inclusion criteria, and it was refined accordingly. One author (C.A.) extracted relevant information from selected studies. A second review author (N.K.) cross checked the data that were extracted from the studies. Study related information was collected: study design and year of publication; baseline demographics and clinical characteristics of the entire screened population and the group of participants in whom an AAA was detected; and outcome data, as outlined in the “Eligibility criteria” section. Risk of bias assessment The methodological quality of observational cohort studies was assessed with the NewcastleeOttawa scale (NOS).19 Using the tool, each study was judged on eight items, categorised into three groups: the selection of the study groups; the comparability of the groups; and the ascertainment of outcome of interest. Stars awarded for each quality item served as a quick visual assessment. Stars were awarded such that the highest quality studies were

Please cite this article in press as: Argyriou C, et al., Screening for Abdominal Aortic Aneurysm During Transthoracic Echocardiography: A Systematic Review and Meta-analysis, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.01.003

Screening for Abdominal Aortic Aneurysm

awarded up to nine stars. The quality assessment was performed independently by two authors (C.A., N.K.). Data synthesis Summary measures. Pooled variables were reported as the mean and 95% confidence interval (CI). Methods of analysis. Simple descriptive statistics were applied to calculate the pooled estimate of baseline demographics and clinical characteristics. The pooled prevalence of AAA in the entire study population was obtained by meta-analysing data from individual studies. The pooled proportion was calculated as the back transformation of the weighted mean of the transformed proportions. The fixed effect model was applied, unless significant heterogeneity was identified, in which case the random effects model proposed by DerSimonian and Laird was used. The unit of analysis was the individual participant undergoing screening for AAA. Assessment of heterogeneity. Inter-study heterogeneity was initially assessed visually using the forest plots. Furthermore, heterogeneity was examined with the combination of the Cochran’s Q (chi square test) test and the I2 statistic. A p values < .05 was considered significant for heterogeneity. Moreover, I2 values less than 50% were considered indicative of low heterogeneity, I2 values between 50% and 75% as indicative of moderate heterogeneity, and I2 values greater than 75% as indicative of significant heterogeneity. Assessment of reporting bias. Funnel plots were constructed and their symmetry was evaluated to visually assess publication bias, as long as a sufficient number of studies (more than 10) were available. Furthermore, the Egger’s regression intercept was calculated to formally assess reporting bias in the review. Sensitivity analysis. Heterogeneity and robustness of pooled proportions were explored by conducting sensitivity analyses. Specifically, sensitivity analyses were undertaken to assess the contribution of risk of bias. Subgroup analysis. The pooled estimate of AAA prevalence in males and females was calculated. Statistical software. The Comprehensive Meta-Analysis (CMA) software was used (Biostat, Englewood, NJ, USA). RESULTS Literature search results The search identified 1449 records of which 433 studies were duplicates and another 940 studies were irrelevant to the topic. Among the remaining 76 studies, 55 studies were excluded due to incomplete demographic and procedural data and one study because it enrolled a subset of patients of a larger study. Twenty studies12e16,20e34 met the inclusion criteria. The included articles were published between

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1995 and 2016, and reported on a total of 43,341 participants undergoing screening for AAA during TTE. The study flow diagram is presented in Fig. 1. The full text of the three studies20e22 that were published in non-English language could not be retrieved, so data to calculate the pooled prevalence estimate were obtained from the abstract. Patient demographics and comorbidities All data were derived from single or multicentre studies except for those of two studies that were part of national registries.23,24 In all studies, the indication for TTE was known or suspected cardiac disease except for two studies that did not report any information on their inclusion criteria.20,21 The included studies reported a total of 23,291 men (53.7%) and 20,050 women (46.3%). The screened population ranged across the studies from 84 to 13,166 participants. The mean age of the screened population ranged from 42 to 75 years. In the entire screened population, hypertension was present in 41% (95% CI 38e43), hypercholesterolemia in 31% (95% CI 29e32), diabetes mellitus in 20% (95% CI 19e22), and tobacco use in 37% (95% CI 35e38). The mean age of participants in whom an AAA was detected ranged across the studies from 66 to 85 years. In the same study group (participants found to have an AAA), hypertension was reported in 64% (95% CI 63e 66), hypercholesterolemia in 42% (40e43), diabetes mellitus in 20% (17e21), and tobacco use in 38% (95% CI 36e 39). All included studies defined an AAA as an aortic diameter
30 mm, except for the study of Eisenberg et al.,25 who considered a dilatation of the aorta to be present if its maximum diameter was
25 mm, the study of Bernard et al.,20 who recorded AAA > 35 mm, the study of Roshanali et al.,12 who recorded AAA diameter > 40 mm, and the study of Schwartz et al.,26 who defined AAA as aortic diameter > 33 mm. Baseline demographic and clinical characteristics of the study populations are presented in Tables 1 and 2. Screening technique Ultrasonographic images were acquired by experienced sonographers and recorded in a digital reporting system. No instructions on food or fluid intake were given prior to the examination. A routine examination was performed using the two dimensional mode with color Doppler. In all studies, after the TTE examination, images of the abdominal aorta were obtained in both longitudinal and transverse planes with the participant in the supine position. Four studies23,27e29 reported measurement of the maximum diameter of the abdominal aorta in the antero-posterior plane only. In most studies, the aortic diameter was measured from outer edge to outer edge,12e14,24,27,28,30,31 whereas the inner to inner diameter was obtained in three studies.25,26,32 In one study,12 the authors examined the suprarenal aorta only from the subcostal view. The abdominal aorta was visualised in 86% (95% CI 84e88) of the screened participants; technical limitations prevented visualisation of the aorta in the remaining participants.

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Christos Argyriou et al.

Records idenfied through database searching (PubMed/MEDLINE, SCOPUS, CENTRAL) (n=1449)

Screening

Idenficaon

4

Records screened (n=76)

Records excluded (n=1373) Duplicate publicaons (n=433) Other/irrelevant topic (n=940)

Eligibility

Full-text arcles assessed for eligibility (n=76)

Included

Records excluded, with reasons (n=56)

Studies included in meta-analysis (n=20)

Studies with incomplete procedural and demographic data (n=55) Studies with a subset populaon of a larger study (n=1)

Figure 1. Study flow diagram showing the number of studies that were screened, assessed for eligibility and included in/excluded from the systematic review (along with reasons for exclusion).

The average examination time for visualisation of the aorta during TTE was less than 5 min in most studies12,13,15,16,22,25,26,28,29,31e33; Spitell et al.30 reported an average examination time of 7.7 min. In the study of Aboyans et al.,23 imaging of the aorta lasted longer than three minutes in 3.6% of cases, whereas the average time to scan the abdominal aorta was 1 min and 44 s. Results of risk of bias assessment Risk of bias assessment was not undertaken in three studies,20e22 the full text of which could not be retrieved. One study scored seven stars,34 two studies scored six,12,22 nine studies scored five,14e16,26,28,30e33 and the remaining five studies scored four stars in the NOS.13,23,24,27,29 The results of the methodological quality assessment indicated in the NOS scores are presented in Table 3 and the rational for judgment for each NOS item in Table 4. Outcome synthesis An AAA was identified in 1039 participants undergoing screening. In the studies that reported separate prevalence data for males and females, there were 673 (66%) males and 196 (34%) females with a detected AAA. The mean diameter of the aneurysm identified in the screened population ranged across the studies from 35 mm to 45 mm.

The mean diameter of the aorta in the entire screened population ranged from 17 mm to 23 mm. In the study of Majeed et al.,24 24% of patients in whom an AAA was discovered had an aneurysm diameter > 50 mm and in the study of Schwartz et al.,26 the proportion was 23%. Spitell et al.30 reported that 31% of the patients in whom an AAA was detected during TTE had an aneurysm diameter > 45 mm; the corresponding proportion in the study of Roshanali et al.,12 who scanned the suprarenal aorta only, was 36%. The pooled prevalence of AAA in the entire screened population was 0.033 (95% CI 0.024e0.044) (Fig. 2A). Significant between study heterogeneity was identified (I2 ¼ 95%, p < .001). The likelihood of publication bias was low (p ¼ .530) (Fig. 2B). The pooled prevalence of AAA in males was 0.046 (95% CI 0.032e0.065) (Fig. 3A) with significant statistical heterogeneity among the studies (I2 ¼ 94%, p < .001). The likelihood of publication bias was low (p ¼ .629) (Fig. 3B). The pooled prevalence of AAA in females was 0.014 (95% CI 0.008e0.022) (Fig. 4A). The statistical heterogeneity among the studies was significant (I2 ¼ 87%, p < .001), whereas the likelihood of publication bias was low (p ¼ .414) (Fig. 4B). The analysis was repeated after excluding studies found to be of lower methodological quality (those achieving less

Please cite this article in press as: Argyriou C, et al., Screening for Abdominal Aortic Aneurysm During Transthoracic Echocardiography: A Systematic Review and Meta-analysis, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.01.003

Eisenberg25 1995

Gender (%) Participants with visualised abdominal aorta/overall number of participants 265/323 123M (46) 141F (54)

Schwartz26 1996

216/250

124M (49) 126F (51)

Spitell30 1997

200/209

107M (54) 93F (47)

Jaussi32 1999

297/298a

182M (60) 119F (40)

Seelig15 2000

13166

6953M (53) 6213F (47) NR

>30

Bernard20 2002 Giaconi21 2003 Bekkers14 2005

1106 165/181 742/796

822M (74) 284F (26) NR 386M (52) 356F (48)

>35 >30 >30

Rugierro22 2006

1103/1202

722M (60) 480F (40)

Roshanali12 2007

1175/1285

532M (41) 753F (59)

Gentile-Lorente31 2010

494/512

299M (61) 195F (39)

Author year

Mean age (SD or rangeb)

Inclusion criteria

57 (13e94) Known/suspected cardiac disease NR Known/suspected cardiac disease male > 55 years female > 65 years 71 (51e92) Known/suspected cardiac disease > 50 years HTN > 1year 59  17

Known/suspected cardiac disease

Known/suspected cardiac disease > 50 years NR NR 61 (45e79) NR 61 Known/suspected cardiac disease

67  11

Known/suspected cardiac disease > 40 years 42 (13e80) Known/suspected cardiac disease

65  12

Known/suspected cardiac disease

AAA definition/ diameter in mm

Comorbidities (%)

>25

CAD (7)

>33

>30

>30

>30 >40

>30

Measurement protocol

Mean aortic diameter in mm (SD or range)

Internal 17 (11e57) diameter NR NR Internal diameter in AP/ transverse planes 19 (14e52) Tobacco use (42) External Family history of AAA diameter in AP/ (7) transverse planes NR HTN (41) Smoking (47) Internal diameter DM (17) Hypercholesterolemia (35) CAD (24) NR AP/transverse NR planes NR NR NR

Mean examination time in minb (SD or range)

<5 <5

7.7 (1e20)

<5

5

NR NR NR NR 21 External diameter in AP/ transverse planes HTN (56) Smoking (17) NR 19  6 DM (11)

NR NR NR

19 (11e52) External diameter in AP/ transverse planes Suprarenal level 19  7 External CAD (34) HTN (71) Smoking (15) DM (26) diameter in AP/ Hypercholesterolemia transverse planes (65) PAD (31)

2.2 (1.1e4.1)

NR

Screening for Abdominal Aortic Aneurysm

34  9 s

< 3 min whole cohort; < 5 min in AAA Continued

5

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Table 1. Participant characteristics.

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Mean age (SD or rangeb)

AAA definition/ diameter in mm

Comorbidities (%)

Measurement protocol

Mean aortic diameter in mm (SD or range)

Mean examination time in minb (SD or range)

>30 or Infra/ suprarenal ratio > 1.5 >30

CAD (34) HTN (66) Smoking (64) DM (29) Hypercholesterolemia (64) PAD (13) HTN (46) Smoking (38) DM (24) Hypercholesterolemia (24) PAD (31) HTN (51) Smoking (73) DM (24) Hypercholesterolemia (44) PAD (7) HTN (63) Smoking (57) DM (18) CAD (32)

External diameter in AP plane

18  5

NR

NR

19 (5e95)

47 sec (36e58)

External diameter in AP plane

17 (9e45)

3 (1e10)

External diameter

23  0.5

4.4  0.9

External diameter

NR

NR

Dupont27 2010

Gender (%) Participants with visualised abdominal aorta/overall number of participants 217 189M (87) 28F (13)

Oh33 2010

4939/6267

2365M (48) 2574F (52) 61 (12e98) Known/suspected cardiac disease

Cueff28 2012

180/193

150M (77) 43F (23)

65 (27e98) Known/suspected cardiac disease

>30

Navas13 2012

84/90

43M (48) 47F (52)

72  10

>30

Majeed24 2014

10403

5625M (54) 4778F (46) 70  11

Author year

Inclusion criteria

64 (56e73) Known/suspected cardiac disease

Known/suspected cardiac disease > 55 years Known/suspected cardiac disease > 50 years Known/suspected cardiac disease > 65 years

>30

NR

NR 1 min 44 s  HTN (68) Smoking (33) AP plane 1 min 30 s DM (23) Hypercholesterolemia (53) PAD (9) CAD (27) Lee29 2015 920/1300 677M (74) 243F (26) 64  10 Known/suspected >30 HTN (59) Smoking (41) AP plane 19  5 2 cardiac disease DM (48) PAD (2) NR NR NR Kato34 2015 7619 3992M (52) 3627F (48) 66 (IQR Known/suspected >30 or 50% HTN (55) DM (29) Hypercholesterolemia 15e83) cardiac disease increased (28) CAD (31) diameter compared with normal aorta Matsumura16 2016 1818/1912 897M (49) 921F (51) 67  16 Known/suspected >30 NR AP/transverse 17  6 31 (13e53) s cardiac disease planes Abbreviations: AAA ¼ abdominal aortic aneurysm; AP ¼ antero-posterior; CAD ¼ coronary artery disease; DM ¼ diabetes mellitus; F ¼ female; HTN ¼ hypertension; IQR ¼ interquartile range; M ¼ male; NR ¼ not reported; PAD ¼ peripheral arterial disease; SD ¼ standard deviation. a Overall 301 patients 3 excluded because of previous AAA surgery. b Unless stated otherwise. Aboyans23 2014

1338/1404

779M (58) 559F (42)

75  7

>30

Christos Argyriou et al.

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Table 1-continued

Gender (%) AAA prevalence Mean age in males/females (SD or range) (%)

Mean AAA diameter in mm (SD or rangea)

Comorbidities

Significant associations Follow up

Eisenberg25 1995

Number of participants with AAA (prevalence %) 7 (2.6)

M (4.8) F (0.7)

66 (37e80)

6M (86) 1F (14)

33 (25e67)

CAD (43)

Male gender Older age

Schwartz26 1996

13 (6)

M (5.6) F (4.7)

NR

7M (54) 6F (46)

(33e66)

NR

NR

Spitell30 1997

13 (6.5)

M (8.4) F (4.3)

73 (54e88)

9M (69) 4F (31)

39 (30e52)

NR

Jaussi32 1999

17 (5.7)

M (8.2) F (1.6)

67  8

15M (88) 2F (12)

41  9

Current smoker (77) Family history (15) HTN (82) Hypercholesterolemia (63) PAD (29) smoking (88) CAD (65)

Seelig15 2000

108 (0.8)

M (1.34) F (0.24) 74 (59e90)

93M (86) 15F (14)

38 (30e68)

Bernard20 2002 Giaconi21 2003 Bekkers14 2005

11 (1) 7 (3.8) 42 (5.7)

NR NR M (8.5) F (2.5)

NR NR 72  9

NR NR 33M (79) 9F (21)

NR NR 39 (30e74)

Rugierro22 2006

62 (5.6)

M (8.4) F (1.7)

72  9

55M (89) 7M (11)

NR

Roshanali12 2007 Gentile-Lorente31 2010

47 (4) 25 (5.1)

M (4.5) F (3.6) M (7.3) F (1.5)

67 (53e80) 71  8

23M (49) 24 F (51) 45 (40e52) NR 22M (88) 3F (12) 40  12 (30e69) HTN (60) DM (49) hypercholesterolemia (72) PAD (100)

Author year

HTN (82) DM (13) hypercholesterolemia (24) CAD (60) Smoking (78) NR NR HTN (57) DM (13) hypercholesterolemia (24)

NR

Male gender Older age HTN Smoking (associated with diameter > 20 mm) NR

NR NR Male gender Older age Dilated ascending aorta Lower EF Higher LV dimensions Higher mass index Age Gender HTN Smoking NR Age DM Femoral murmur

1 pt lost 6 pts alive after at least 6 months 1 pt refused surgery 1 pt increased diameter > 3.5 cm In 23% > 50 mm In 23% 40e50 mm In 54% 33e40 mm In 31% > 45 mm

Screening for Abdominal Aortic Aneurysm

8 AAAs were repaired after 1 year

17 pts underwent repair after a mean interval of 14 months (range 0.2e49) NR NR In 24% > 60 mm In 7% 40e50 mm In 69% 30 e40 mm

NR

In 36% > 45 mm NR

Continued

7

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Table 2. Characteristics of participants with abdominal aortic aneurysm.

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Gender (%) AAA prevalence Mean age in males/females (SD or range) (%)

Mean AAA diameter in mm (SD or rangea)

Comorbidities

Dupont27 2010

Number of participants with AAA (prevalence %) 15 (6.9)

M (7.9)

15M (100)

35  9

Oh33 2010

27 (0.5)

M (0.97) F (0.16) 67 (37e79)

23M (85) 4F (15)

43 (30e95)

Cueff28 2012

9 (4.6)

M (4.6) F (4.6)

85  3

7M (78) 2F (22)

35 (30e45)

Navas13 2012 Majeed24 2014

5 (5.9) 366 (3.5)

NR M (4.8) F (2)

NR 78  8

NR (34e51) 269M (74) 97F (26) 39 (IQR 32e48)

Aboyans23 2014

50 (3.7)

M (5.4) F (1.4)

76  8

42M (84) 8 F (16)

Smoking Carotid disease CAD Large femoral or popliteal pulse Male gender Age > 60 years HTN Smoking Hypercholesterolemia HTN (67) smoking (78) NR DM (33) hypercholesterolemia (56) PAD (33) NR NR NR Older age Male gender LV end diastolic dimension Interventricular septum thickness LV posterior wall thickness Left atrial diameter Posterior wall diameter HTN (66) smoking (50) Gender Smoking DM (22) hypercholesterolemia Family history (60) PAD (4) CAD (34) LV end diastolic diameter LV end systolic diameter Ascending aorta diameter

Author year

67 (58e75)

36  7

HTN (60) Smoking (100) DM (40) hypercholesterolemia (60) PAD (40) HTN (66) smoking (67) DM (15) hypercholesterolemia (7) PAD (37)

Significant associations Follow up

In 4 pts (2%) popliteal aneurysm 2 pts referred for surgery 7 pts underwent AAA repair after 9 months

66% 30e35 mm 11% 36e40 mm 22% > 40 mm NR In 24% > 50 mm 27 pts (7.3%) had AAA repair

54% 30e34 mm 22% 35e39 mm 14% 40e44 mm 2% 45 e49 mm 8% > 50 mm Christos Argyriou et al.

Please cite this article in press as: Argyriou C, et al., Screening for Abdominal Aortic Aneurysm During Transthoracic Echocardiography: A Systematic Review and Meta-analysis, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.01.003

Table 2-continued

30% underwent repair during 1eyear follow up Abbreviations: AAA ¼ abdominal aortic aneurysm; CAD ¼ coronary artery disease; DM ¼ diabetes mellitus; EF ejection fraction; F female; HTN ¼ hypertension; IQR interquartile range; LV left ventricular; M male; NR ¼ not reported; PAD ¼ peripheral arterial disease; pt patient; SD standard deviation. a Unless stated otherwise.

NR

77  9 M (3.9) F (1.3) Matsumura16 2016 47 (2.6)

NR 136 (1.78) Kato34 2015

NR

22 (2.4) Lee29 2015

M (2.8) F (1.2)

69  6

19M (86) 3 F (14)

43  12

HTN (85) smoking (77) Age DM (39) PAD (8) Smoking PAD Aortic root diameter NR NR NR Gender Age CAD HTN 35M (74) 12 F (26) 44  11 (30e90) Smoking (72) HTN (70) Age CAD (55) Aortic root size

NR

Screening for Abdominal Aortic Aneurysm

9 Table 3. NewcastleeOttawa assessment scale. Author year Selection Comparability Outcome Eisenberg25 1995 3 0 3 Schawrtz26 1996 2 0 3 Spitell30 1997 2 0 3 2 0 3 Jaussi32 1999 Seelig15 2000 2 0 3 Bernard20 2002a e e e Giaconi21 2003a e e e Bekkers14 2005 2 0 3 Rugierro22 2006a e e e Roshanali12 2007 3 0 3 Gentille-Lorente31 2010 2 0 3 Dupont27 2010 1 0 3 Oh33 2010 2 0 3 2 0 3 Cueff28 2012 Navas13 2012 1 0 3 Majeed24 2014 1 0 3 Aboyans23 2014 1 0 3 Lee29 2015 1 0 3 Kato34 2015 3 1 3 Matsumura16 2016 2 0 3 a Studies published in non-English language and full text could not be retrieved.

than five stars on the NOS) and the non-English language studies the full text of which could not be retrieved. The pooled estimate of the overall prevalence was 0.030 (95% CI 0.020e0.046) (test for heterogeneity: I2 ¼ 96%, p < .001). The pooled prevalence in males was 0.046 (95% CI 0.028e0.076) (test for heterogeneity: I2 ¼ 95%, p < .001) and that in females was 0.015 (95% CI 0.007e0.029) (test for heterogeneity: I2 ¼ 89%, p < .001). DISCUSSION A systematic review of the literature was undertaken and data were collated from 20 observational studies investigating the feasibility and prevalence of AAA screening during TTE. It was found that visualisation of the abdominal aorta during TTE was possible in 86% of the total screened population, which is in accordance with data from population screening trials.2,6e8 Analysis of a total of 43,341 participants undergoing screening for AAA during TTE found a pooled prevalence of 3.3%. The pooled AAA prevalence in the male population was 4.6%, and the prevalence in females was 1.4%. Aneurysm prevalence ranged from 0.5% to 6.9% across the studies included in this review. While these figures may be similar to those reported in large population based screening trials, such as the Multicentre Aneurysm Screening Study MASS (UK),6 the West Australian Aneurysm Screening Study,7 the Chichester study (UK),2 and the Viborg Study (Denmark),8 in which prevalence rates range from 4% to 7.2%,2 they probably indicate a higher prevalence than contemporary epidemiological data on AAA. A decrease in the incidence of AAA has been recorded in Western countries, and contemporary data suggest that the prevalence of AAA is 1e2% compared with previously reported figures of 4e5%.35 Norman et al.36 found that in Australia, the age

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NewcastleeOttawa scale item

Rational for judgment Eisenberg25

Representativeness of the exposed cohort

Selection of the nonexposed cohort Ascertainment of exposure Demonstration that outcome of interest was not present at start of study

Comparability of cohorts on the basis of the design or analysis Assessment of outcome Was follow-up long enough for outcomes to occur Adequacy of follow-up of cohorts

10

Schwartz26

Spittell30

The exposed The exposed cohort was cohort was somewhat somewhat representative representative of the average of the average population in population in the community the community There was no comparative group

GentilleLorente31 The exposed cohort was somewhat representative of the average population in the community

The exposed cohort was a selected population group

Jaussi32

Seelig15

Bekkers14

Roshanali12

The exposed cohort was somewhat representative of the average population in the community

The exposed cohort was a selected population group

The exposed cohort was somewhat representative of the average population in the community

The exposed cohort was somewhat representative of the average population in the community

No. Outcome of interest was present at the start of study

Yes. Outcome of interest was not present at the start of study

No. Outcome of interest was present at the start of study

Yes. Outcome of interest was not present at the start of study

The presence of AAA was ascertained by using record linkage Yes. Outcome of interest was not present at the start of study

No. Outcome of interest was present at the start of study

Yes. Outcome of interest was not present at the start of study

No information whether known AAAs were included at the start of the study

NA

The outcomes were assessed using record linkage The follow up was adequate to assess outcomes

NA

Rational for judgment Dupont27 Oh33 The exposed The exposed cohort was cohort was a somewhat selected representative population of the average group population in the community

Cueff28 The exposed cohort was a selected population group

Navas13 The exposed cohort was a selected population group

Majeed24 The exposed cohort was a selected population group

Aboyans23 The exposed cohort was a selected population group

Lee29 The exposed cohort was a selected population group

Matsumura16 The exposed cohort was somewhat representative of the average population in the community

Kato34 The exposed cohort was somewhat representative of the average population in the community

Christos Argyriou et al.

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Table 4. The rationale for judgment for each NewcastleeOttawa scale item.

The presence of AAA was ascertained by using record linkage Yes. Outcome of No information No information interest was not whether known whether known present at the AAAs were AAAs were start of study included at the included at the start of the start of the study study NA

The comparative group was drawn from the same community No information whether known AAAs were included at the start of the study

No. Outcome of interest was present at the start of study

No. Outcome of interest was present at the start of study

No. Outcome of interest was present at the start of study

No. Outcome of interest was present at the start of study

Yes. Outcome of interest was not present at the start of study

The cohorts were different in terms of baseline characteristics but were comparable in terms of analysis and design

Screening for Abdominal Aortic Aneurysm

The outcomes were assessed using record linkage The follow up was adequate to assess outcomes NA NA, not applicable; AAA, abdominal aortic aneurysm.

11

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There was no comparative group

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Christos Argyriou et al.

Figure 2. (A) Forest plot for the overall prevalence of AAA in the entire screened population. (B) Funnel plot for the overall prevalence of AAA (p ¼ .530).

standardised mortality rate related to AAA has fallen by an average of 6% per year for men and 2.9% for women since 1999. Based on these results, the authors suggested a “true” fall in the incidence of AAA during this time interval. Additionally, Sandiford et al.,37 who investigated trends in the incidence of AAA and associated mortality in New Zealand, recorded a decrease in standardised AAA related mortality rates of 53% for men and 34.1% for women during a period spanning from 1991 to 2007. They also found that new AAA related admissions and hospital death rates have declined sharply since 2000, and overall survival appears to be improving, largely due to the decreasing disease incidence. Furthermore, Svensjö et al.38 reported an AAA prevalence in 65 year old men of 1.7% in a screening study conducted in a Swedish population, which according to the authors is “the lowest reported in a predominantly white

population to date”. Another report investigating trends in AAA epidemiology in England, Wales, and Scotland found that AAA related mortality decreased more than twofold in subjects < 75 years and by 25% in those > 75 years over a period from 1997 to 2009, which suggests that the age at which clinically relevant aneurysms present has increased and that, currently, the AAA incidence in men in England, Wales, and Scotland is declining rapidly.39,40 The decline in AAA incidence in Western countries has been consistently reported by several authors, who have highlighted potential implications for the cost-effectiveness of current population based AAA screening programs.11,36e38 Considering that the target condition is becoming less common, the prevalence of AAA could ultimately fall to a point where screening the general population may not be cost-effective. Therefore, targeting screening to specific populations where the AAA

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Screening for Abdominal Aortic Aneurysm

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Figure 3. (A) Forest plot for the prevalence of AAA in males. (B) Funnel plot for the prevalence of AAA in males (p ¼ .629).

prevalence is expected to be higher may become a more attractive and widely adopted strategy. There is abundant evidence correlating atherosclerotic risk factors with increased AAA prevalence.41e44 This correlation has made authors speculate that the decreasing incidence of AAA may have resulted from increased awareness and modification of atherosclerotic risk factors.39 Smoking has been found to be one of the main risk factors for AAA formation and expansion, and there is compelling evidence to suggest a causal relationship between a reduction in AAA incidence and reducing smoking rates.11 Moreover, a global epidemiology study indicated that reduced AAA related mortality rates are not universal and, despite being profound in countries such as the UK and the United States, it may have remained stable or even increased in other countries such as Hungary and Romania.41 An important finding of this study is the positive linear and statistically significant relationship between AAA related mortality and global trends in systolic blood

pressure, cholesterol, and smoking prevalence in both male and female populations.41 A recent meta-analysis reported a significantly higher incidence of AAA among patients with coronary artery disease (CAD) than the general population (OR 2.38).42 The pooled prevalence of AAA among men with CAD was 9.5%, while it was found to be even higher among participants undergoing coronary artery bypass surgery or those with three vessel disease, in whom a prevalence of up to 11.4% was reported. Another meta-analysis of a total of 13,388 patients with CAD reported similar results.43 Interestingly, significant associations between smoking, hypertension, and concomitant carotid disease and AAA have been found among patients with CAD.43 In accordance with this finding, a contemporary study found increasing prevalence of AAA with increasing severity of CAD.44 The authors of this study found an AAA prevalence of 2.5% in patients undergoing coronary angiography in whom no significant lesion was detected, whereas the corresponding figures for patients

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Christos Argyriou et al.

Figure 4. (A) Forest plot for the prevalence of AAA in females. (B) Funnel plot for the prevalence of AAA in females (p ¼ .414).

with one, two, and three vessel disease were 4.3%, 5.7%, and 14.4%, respectively.44 These data provide evidence to suggest that AAA is more common among patients with cardiac disease, which is the population typically undergoing TTE. Patients undergoing TTE for cardiac conditions may represent a population with a higher AAA prevalence than the general population undergoing AAA screening within the current screening programs. It could be argued that in case of an implemented national AAA screening program, opportunistic abdominal aortic imaging during TTE is probably of no value, since subjects with an AAA would have already been identified through abdominal ultrasound within the screening program. However, an important reflection of these results is that in view of the declining AAA incidence and the questionable cost-effectiveness of current national screening programs, opportunistic screening during TTE would be of value in detecting AAA in a high risk population. Another perspective of these findings is the consideration of

screening in countries where an AAA screening program is not available. In this setting, TTE would provide a means of screening for AAA in a population with an expected higher disease prevalence that would not be otherwise examined. The prevalence of AAA in women is well documented to be lower than in men. Therefore, the guideline on screening women is different and, according to the SVS recommendations, screening should be applied in “women at or older than 65 years with a family history of AAA or who have smoked”, while ESVS guidelines suggest that “population screening of older women for AAA does not reduce the incidence of aneurysm rupture”, and “population screening of older female smokers for AAA may require further investigation”.4,5 These recommendations are mainly based on the Chichester study that is the only large, population based randomised trial to examine the value of screening for AAA in women; it found an overall AAA prevalence in women of 1.3% and no survival benefit in this group undergoing screening.45 Considering that these data are

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Screening for Abdominal Aortic Aneurysm

outdated and that more recent research indicates even lower rates, currently estimated to be below 1%, the costeffectiveness of AAA screening in women is questionable. Indeed, Svensjö et al.46 in a study conducted in Sweden, recorded an AAA prevalence of 0.5% among women older than 70 years. Similarly, Ulug et al.47 in a recent metaanalysis recorded a pooled AAA prevalence of 0.74% among female participants. A contemporary study by Chabok et al.,48 which investigated the AAA prevalence in women in the UK, found an overall prevalence of 0.29% for individuals aged 66e85 years. Interestingly, the authors built up a model that included other variables such as history of stroke, hypertension, smoking, ankle brachial index, atrial fibrillation, and carotid stenosis, and identified a subgroup of female participants with an AAA prevalence of 1.57%.48 This figure is similar to that found in the metaanalysis here (1.4%), suggesting that female patients undergoing TTE for cardiac disease may have demographic characteristics and comorbidities similar to those included in the high risk model proposed by Chabok et al.48 The findings in the present study could therefore provide an evidence basis to recommend opportunistic screening for AAA in female patients during TTE. Of note, the 2014 European Society of Cardiology guidelines on aortic disease recommended opportunistic screening, defined as the use of ultrasound to detect AAA in situations where both the ultrasound machines and expertise are easily accessible, but where abdominal imaging is not specifically planned (class IIa level A recommendation for men and class IIb level C for women).49 Accordingly, this review summarises the available evidence suggesting that opportunistic screening where a formal population based AAA screening program is not available and AAA screening in female populations during TTE may be beneficial. Opportunistic screening may also be suggested in the light of the declining incidence of AAA and the questionable effectiveness of current screening protocols in the general population. The results of this study should be interpreted in the context of its limitations. The risk of bias in the included observational studies as assessed with the NOS was high, thus indicating the need for further research and possibly higher quality evidence. All studies included in this analysis were observational cohort studies; no randomised trials were identified investigating the effectiveness of AAA screening during TTE, as indicated by clinical parameters such as aneurysm related or all cause mortality. Additionally, no data on the cost-effectiveness of AAA screening during TTE are available. CONCLUSIONS Randomised clinical trials have demonstrated that population based screening for AAA reduces aneurysm related mortality. Contemporary epidemiological studies indicate that the incidence of AAA has decreased since those large population based screening trials were published. A high AAA prevalence was found among patients undergoing TTE

15

compared with contemporary data from epidemiological studies investigating AAA prevalence in the general population. In view of the declining incidence of AAA and the questionable effectiveness of current screening protocols in the general population, opportunistic screening may be suggested. TTE could also be a valuable tool for opportunistic AAA screening where a population based screening program is not available. Further research is required to investigate the cost-effectiveness and clinical benefits of TEE for AAA screening in this setting. CONFLICT OF INTEREST None. FUNDING None. REFERENCES 1 Bickerstaff LK, Hollier LH, Van Peenen HJ, Melton LJ, Pairolero PC, Cherry KJ. Abdominal aortic aneurysms: the changing natural history. J Vasc Surg 1984;1:6e12. 2 Ashton HA, Gao L, Kim LG, Druce PS, Thompson SG, Scott RA. Fifteen-year follow-up of a randomized clinical trial of ultrasonographic screening for abdominal aortic aneurysms. Br J Surg 2007;94:696e701. 3 US Preventive Services Task Force. Screening for abdominal aortic aneurysm. Ann Intern Med 2005;142:198e202. 4 Chaikof EL, Brewster DC, Dalman RL, Makaroun MS, Illig KA, Sicard GA, et al. Society for Vascular Surgery. The care of patients with an abdominal aortic aneurysm: the Society for Vascular Surgery practice guidelines. J Vasc Surg 2009;50: S2e49. 5 Moll FL, Powell JT, Fradrich G, Verzini F, Haulon S, Waltham M, et al. Management of abdominal aortic aneurysms. Clinical practice guidelines of the European Society for Vascular Surgery. Eur J Vasc Endovasc Surg 2011;1:S1e58. 6 Ashton HA, Buxton MJ, Day NE, Kim LG, Marteau TM, Scott RA, et al. 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: 1531e9. 7 Norman PE, Jamrozik K, Lawrence-Brown MM, Le MT, Spencer CA, Tuohy RJ, et al. Population based randomised controlled trial on impact of screening on mortality from abdominal aortic aneurysm. BMJ 2004;329:1259. 8 Lindholt JS, Juul S, Fasting H, Henneberg EW. Preliminary ten year results from a randomised single centre mass screening trial for abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 2006;32:608e14. 9 Lindholt JS, Norman P. Screening for abdominal aortic aneurysm reduces overall mortality in men. A Meta-analysis of the mid- and long-term effects of screening for abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2008;36:167e71. 10 Lindholt JS, Vammen S, Juul S, Henneburg EW, Fasting H. The validity of ultrasonographic scanning as screening method for abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 1999;17: 472e5. 11 Lederle FA. The rise and fall of abdominal aortic aneurysm. Circulation 2011;124:1097e9.

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Christos Argyriou et al. 28 Cueff C, Keenan NG, Krapf L, Steg PG, Cimadevilla C, Ducrocq G, et al. Screening for abdominal aortic aneurysm in coronary care unit patients with acute myocardial infarction using portable transthoracic echocardiography. Eur Heart J Cardiovasc Imaging 2012;13:574e8. 29 Lee SH, Chang SA, Jang SY, Lee SC, Song YB, Park SW, et al. Screening for abdominal aortic aneurysm during transthoracic echocardiography in patients with significant coronary artery disease. Yonsei Med J 2015;56:38e44. 30 Spittell PC, Ehrsam JE, Anderson L, Seward JB. Screening for abdominal aortic aneurysm during transthoracic echocardiography in a hypertensive patient population. J Am Soc Echocardiogr 1997;10:722e7. 31 Gentille-Lorente DI, Salvadó-Usach T. Screening for abdominal aortic aneurysm by means of transthoracic echocardiography. Rev Esp Cardiol 2011;64:395e400. 32 Jaussi A, Fontana P, Mueller XM. Imaging of the abdominal aorta during examination of patients referred for transthoracic echocardiography. Schweiz Med Wochenschr 1999;129:71e6. 33 Oh SH, Chang SA, Jang SY, Park SJ, Choi JO, Lee SC, et al. Routine screening for abdominal aortic aneurysm during clinical transthoracic echocardiography in a Korean population. Echocardiography 2010;27:1182e7. 34 Kato T, Ishida S, Miyamoto S, Iura T, Ban Y, Fujikawa J, et al. A propensity score-matching analysis of transthoracic echocardiography and abdominal ultrasonography for the detection of abdominal aortic aneurysms. Clin Med Insights Cardio 2015;19:11e5. 35 National Abdominal Aortic Aneurysm Screening Programme. 2013/14 AAA Screening Data. Retrieved December 6, 2017, from http://aaa.screening.nhs.uk/2015-16datareports. 36 Norman PE, Spilsbury K, Semmens JB. Falling rates of hospitalization and mortality from abdominal aortic aneurysms in Australia. J Vasc Surg 2011;53:274e7. 37 Sandiford P, Mosquera D, Bramley D. Trends in incidence and mortality from abdominal aortic aneurysm in New Zealand. Br J Surg 2011;98:645e51. 38 Svensjö S, Björck M, Gürtelschmid M, Djavani Gidlund K, Hellberg A, 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;124:1118e23. 39 Anjum A, Powell JT. Is the incidence of abdominal aortic aneurysm declining in the 21st century? Mortality and hospital admissions for England & Wales and Scotland. Eur J Vasc Endovasc Surg 2012;43:161e6. 40 Choke E, Vijaynagar B, Thompson J, Nasim A, Bown MJ, Sayers RD. Changing epidemiology of abdominal aortic aneurysms in England and Wales: older and more benign? Circulation 2012;125:1617e25. 41 Sidloff D, Stather P, Dattani N, Bown M, Thompson J, Sayers R, et al. Aneurysm global epidemiology study: public health measures can further reduce abdominal aortic aneurysm mortality. Circulation 2014;129:747e53. 42 Hernesniemi JA, Vänni V, Hakala T. The prevalence of abdominal aortic aneurysm is consistently high among patients with coronary artery disease. J Vasc Surg 2015;62:232e40. 43 Elkalioubie A, Haulon S, Duhamel A, Rosa M, Rauch A, Staels B, et al. Meta-analysis of abdominal aortic aneurysm in patients with coronary artery disease. Am J Cardiol 2015;116:1451e6. 44 Durieux R, Van Damme H, Labropoulos N, Yazici A, Legrand V, Albert A, et al. High prevalence of abdominal aortic aneurysm

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Screening for Abdominal Aortic Aneurysm in patients with three-vessel coronary artery disease. Eur J Vasc Endovasc Surg 2014;45:273e8. 45 Scott RA, Bridgewater SG, Ashton HA. Randomized clinical trial of screening for abdominal aortic aneurysm in women. Br J Surg 2002;89:283e5. 46 Svensjö S, Björck M, Wanhainen A. Current prevalence of abdominal aortic aneurysm in 70-year-old women. Br J Surg 2013;100:367e72. 47 Ulug P, Powell JT, Sweeting MJ, Bown MJ, Thompson SG. SWAN Collaborative Group. Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women. Br J Surg 2016;103:1097e104.

17 48 Chabok M, Nicolaides A, Aslam M, Farahmandfar M, Humphries K, Kermani NZ, et al. Risk factors associated with increased prevalence of abdominal aortic aneurysm in women. Br J Surg 2016;103:1132e8. 49 Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2873e926.

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