Eur J Vasc Endovasc Surg (2017) -, 1e8

Higher 30 Day Mortality in Patients with Familial Abdominal Aortic

Aneurysm after EVAR
a,b,c a,d
K.M. van de Luijtgaarden , F. Bastos Gonçalves , S.E. Hoeks b, J.D. Blankensteijn e, D. Böckler f, R.J. Stolker b,
H.J.M. Verhagen a,*
a
Department of Vascular Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
b
Department of Anesthesiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
c
Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands
d
Department of Angiology and Vascular Surgery, Hospital de Santa Marta, CHLC & NOVA Medical School, Lisbon, Portugal
e
Department of Vascular Surgery, VU University Medical Centre, Amsterdam, The Netherlands
f
Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany

WHAT THIS PAPER ADDS

Familial abdominal aortic aneurysm (AAA) has been associated with more complications after endovascular
aneurysm repair (EVAR), but data from large patient cohorts are currently lacking. This study shows that patients
with a positive family history for aneurysms have a higher 30 day mortality after EVAR, using data from a large
worldwide registry. Also, higher long-term aneurysm related mortality and more complications after EVAR in
familial AAA patients are identified, underlining that patients with familial forms of AAA are at higher risk for
EVAR and warrant extra vigilance.

Objectives: To determine the influence of a positive family history for aneurysms on clinical success and mortality
after endovascular aneurysm repair (EVAR).
Methods: From 2009 to 2011, 1262 patients with abdominal aortic aneurysms (AAA) treated by EVAR were
enrolled in a prospective, industry sponsored clinical registry ENGAGE. Patients were classified into familial and
sporadic AAA patients according to baseline clinical reports. Clinical characteristics, aneurysm morphology, and
follow-up were registered. The primary endpoint was clinical success after EVAR, a composite of technical success
and freedom from the following complications: AAA increase >5 mm, type I and III endoleak, rupture,
conversion, secondary procedures, migration, and occlusion. Secondary endpoints were the individual
components of clinical success, 30 day mortality, and aneurysm related and all cause mortality.
Results: Of the 1262 AAA patients (89.5% male and mean age 73.1 years), 86 patients (6.8%) reported a positive
family history and were classified as familial AAA. Duration of follow-up was 4.4
1.7 years. Patients with familial
AAA were more often female (18.6% vs. 9.9%, p ¼ .012). No difference was observed in aneurysm morphology.
There was no significant difference in clinical success between patients with familial and sporadic AAA (72.1% vs.
79.3%, p¼.116). Familial AAA patients had a higher 30 day mortality after EVAR (4.7% vs. 1.0%, adjusted HR 5.7,
1.8e17.9, p ¼ .003) as well as aneurysm related mortality (5.8% vs. 1.3%, adjusted HR 5.4, 1.9e14.9, p ¼ .001),
while no difference was observed in all cause mortality (19.8% vs. 24.3%, adjusted HR 0.8, 0.5e1.4, p ¼ .501).
Conclusions: The current study shows a higher 30 day mortality after EVAR in familial AAA patients. Future
studies should determine the role of family history in AAA treatment, suitability for endovascular or open repair,
and on adaptation of post-operative surveillance. For the time being, patients with familial forms of AAA should
be considered at higher risk for EVAR and warrant extra vigilance.
Ó 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Article history: Received 9 December 2016, Accepted 24 April 2017, Available online XXX
Keywords: Abdominal aortic aneurysm, Familial abdominal aortic aneurysm, Post-operative mortality

* Corresponding author. Erasmus University Medical Centre, Department
of Vascular Surgery, Suite H-810, PO Box 2040, 3000 CA Rotterdam, The
Netherlands
E-mail address: h.verhagen@erasmusmc.nl (H.J.M. Verhagen).
1078-5884/Ó 2017 European Society for Vascular Surgery. Published by
Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejvs.2017.04.018
INTRODUCTION
Approximately 20% of patients with abdominal aortic
aneurysm (AAA) have a positive family history for aortic
aneurysms, which suggests a genetic susceptibility for
aneurysm formation in these families.1e3 It is unknown if
this familial predisposition has clinical consequences, or if it
has any influence on the results after endovascular aneu-
rysm repair (EVAR). Patients with familial AAA might behave

Please cite this article in press as: van de Luijtgaarden KM, et al., Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR,
European Journal of Vascular and Endovascular Surgery (2017), http://dx.doi.org/10.1016/j.ejvs.2017.04.018
2 K.M. van de Luijtgaarden et al.
differently after stent graft implantation because of altered
aneurysm morphology or accelerated degeneration of the
aortic wall. Inherited aortic wall deficits may influence seal
and fixation of implanted stent grafts.
Recently, the present study group reported that patients
with a positive family history (i.e. familial AAA patients)
developed significantly more aneurysm related complica-
tions after EVAR compared with patients with a sporadic
AAA (35% vs. 19% at 3.5 years of follow-up, respectively).4
This was the first study addressing this issue and has now
been supported by a study from Ryer et al.5 However, as
these are single centre studies, and the results require
verification using larger EVAR patient cohorts.
The aim of the current study was to evaluate clinical
success of endovascular repair for patients with and
without a positive family history of AAA from a large
worldwide EVAR registry.
METHODS
The study population was derived from consecutive pa-
tients enrolled in the Endurant Stent Graft Natural Selection
Global Post-market Registry (ENGAGE). The ENGAGE study
was initiated to evaluate the real life performance of the
Endurant Stent Graft System (Medtronic Vascular, Santa
Rosa, CA, USA) and is registered at http://clinicaltrials.gov
(NCT00870051). From March 2009 to April 2011, eligible
patients from 79 high volume sites in 30 countries
throughout the world were enrolled. Information on study
design, data collection, monitoring, and statistical methods
has been published previously.6
Classification of familial AAA
Patients were classified into familial and sporadic AAA
based on responses to the baseline questionnaires. The
specific question asked in the questionnaire was: “Family
history of aneurysms? Yes or No. If yes, specify .. ” All
patients with a positive family history for aneurysms were
subsequently classified as familial AAA, whereas patients
who reported a negative family history for aneurysms were
classified as sporadic AAA.
Clinical characteristics
Study data were recorded by each participating site prior to
surgery and included demographic characteristics, baseline
symptoms, physical measurements, risk factors and comor-
bidities, and pre-operative risk assessment. Demographic
characteristics included gender and age. Baseline symptoms
included abdominal/back or other complaints or asymp-
tomatic. Physical examination included height, weight, and
blood pressure. Risk factors and comorbidities included to-
bacco use, hypertension, hyperlipidaemia, history of diabetes
mellitus, cancer, alcoholism, cardiac diseases, myocardial
infarction, arrhythmia, angina pectoris, congestive heart
failure, coronary artery disease, cardiac revascularisation
(CABG of PTCA), valvular heart disease, chronic obstructive
pulmonary disease, renal insufficiency, carotid artery disease,
cerebrovascular disease, transient ischaemic attack, cerebral
Please cite this article in press as: van de Luijtgaarden KM, et al., Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR,
European Journal of Vascular and Endovascular Surgery (2017), http://dx.doi.org/10.1016/j.ejvs.2017.04.018
vascular accident, paraplegia, vascular disease, any thoracic
aneurysm, peripheral arterial disease, thromboembolic
event, bleeding disorder, liver disease, and gastrointestinal
complications. Furthermore, pre-operative risk assessment
was classified according to the American Society of Anes-
thesiologists Classification of health (ASA class-I-IV).7
Aneurysm morphology
Prior to surgery, all patients received computed tomography
angiography (CTA) imaging to determine eligibility for
endovascular repair. The aneurysm morphological charac-
teristics included maximum aneurysm diameter, proximal
and distal non-aneurysm aortic neck diameter, length of
non-aneurysmal aortic neck, distal diameter of non-
aneurysmal neck of iliac artery, angle between proximal
AAA neck and main axis, length from lowest renal artery to
aortic bifurcation, length of iliac artery from aortic bifur-
cation to the end of the seal zone, diameter of iliac aneu-
rysm, length of iliac aneurysm, iliac artery tortuosity (mild/
moderate/severe), iliac artery stenosis, and aortic mural
thrombus/calcification at the site of the proximal neck.
Clinical follow-up
The study follow-up was obtained according to standard
practice at each clinical site, with the exception of the
requirement for 30 day and 1 year imaging studies. Diag-
nostic images were analysed at both time points for tech-
nical outcomes and AAA changes or when additional
imaging was available. Follow-up was either based on
clinical follow-up (i.e. clinical success) or imaging studies
(i.e. in those endpoints where imaging is necessary such as
endoleak). Data obtained after 4 years of follow-up were
analysed in this study.
Endpoints
The primary endpoint of the study was clinical success at 4
years and was classified as recommended in the reporting
standards for EVAR.8 It was defined as a composite of
technical success (defined as successful delivery and
deployment of the Endurant stent graft in the planned
position without unintentional coverage of one or both
internal iliac arteries or visceral aortic branches and with
successful removal of the delivery system) and freedom
from the following complications through 4 years of follow-
up: AAA increase >5 mm, endoleak type I and III, aneurysm
rupture, conversion, secondary procedures, migration, and
occlusion (defined as 100% obstruction). Secondary end-
points were the individual components of clinical success,
30 day mortality (defined as all deaths within 30 days of
stent graft implant), aneurysm related mortality (defined as
all deaths within 30 days of stent graft implant plus all
aneurysm related deaths), and all cause mortality.
Data collection
Data on each patient were recorded on a web based elec-
tronic case report form (Viracity clinical Asset management,
Higher 30 Day Mortality in Patients
MERGE Healthcare, Chicago, IL, USA). Data were imported
by, or under supervision of, institutions’ principal in-
vestigators. Research analysts from Medtronic Bakken
Research Centre BV (Maastricht, the Netherlands) verified
the quality of the entered data during monitoring visits. The
institutional review boards from all participating centres
approved data collection and analysis, and informed con-
sent was obtained from all patients.
Statistical analysis
Qualified independent statisticians performed all statistical
analyses. Dichotomous data are described as counts and
percentages. Continuous variables are described as mean
(standard deviation) and were assessed for normality.
Bimodal, highly skewed, or markedly non-normal variables
were considered for non-parametric analyses, otherwise
parametric analyses were completed. Kaplan-Meier esti-
mates were calculated for aneurysm related, aneurysm
related without 30 day mortality, and all cause mortality
after EVAR. Estimates for familial and sporadic AAA were
compared using log-rank (Mantel-Cox) test of equality.
Multivariate Cox regression analyses were used to assess
the hazard ratio (HR), along with the 95% CI, for differences
between familial and sporadic AAA after EVAR. Variables
entered into the multivariate Cox regression model were
selected on the basis of significant univariate differences
between familial and sporadic AAA at baseline (i.e. age and
gender). Missing values were excluded from analysis. No
imputations were used on the data and only observed data
were analysed. The number non-missing for each variable
was present in the count for continuous variables or in the
sum of the counts of each category for categorical variables.
For all tests, a p value <.05 (two sided) was considered to
be statistically significant. All analyses were performed us-
ing SAS version 9.0 software for windows (SAS institute Inc.,
Cary, NC, USA).
RESULTS
A total of 1266 patients were initially enrolled in the study.
Three patients were subsequently excluded because of
emergency procedure caused by rupture (n ¼ 1), received
open repair (n ¼ 1), and missing informed consent (n ¼ 1).
One patient did not answer the question regarding family
history and was therefore also excluded. Therefore, the final
study population consisted of 1262 patients. The mean age
was 73.1 (8.1) years and 89.5% were male. A total of 86
patients (6.8%) reported a positive family history and were
classified as familial AAA, whereas 1176 patients (93.2%)
were classified as sporadic AAA. The clinical characteristics
of familial and sporadic AAA patients are presented in
Table 1. Compared with sporadic AAA, patients with familial
AAA were more often female (18.6% vs. 9.9%; p ¼ .012),
were younger (71.6 years vs. 73.2 years; p ¼ .047), had a
higher systolic blood pressure (142 mmHg vs. 136 mmHg;
p ¼ .007), had less prior history of cancer (10.6% vs. 21.2%;
p ¼ .020), and had less renal insufficiency (8.1% vs. 16.1%;
p ¼ .049).
Please cite this article in press as: van de Luijtgaarden KM, et al., Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR,
European Journal of Vascular and Endovascular Surgery (2017), http://dx.doi.org/10.1016/j.ejvs.2017.04.018
3
Aneurysm morphology
The majority of the aneurysm morphological characteristics
were similar between both groups, as presented in Table 2.
Minor differences were observed for aneurysm diameter
(58 mm vs. 61 mm; p ¼ .037) and right iliac stenosis (5.4%
vs. 8.6%, p ¼ .038). No differences were observed for
proximal neck angulation and iliac tortuosity.
Clinical success
Duration of follow-up was 4.4
1.7 years. There was no
statistically significant difference in clinical success between
familial and sporadic AAA patients (72.1% vs. 79.3%; p ¼
.116, Table 3) through follow-up. Technical success was
reached for 98.8% in familial AAA and 99.0% in sporadic
AAA (p ¼ .855). Patients with familial AAA suffered from
more stent graft occlusion (8.2% vs. 3.8%; p ¼ .048), but
this difference became insignificant after correction for age
and gender in multivariate analysis (adjusted HR 2.1, 95% CI
1.0e4.8, p ¼ .065). No differences between the groups
were observed for AAA diameter increase >5 mm, sec-
ondary procedures, type I or III endoleak, aneurysm
rupture, conversion to open repair, and stent graft migra-
tion, as presented in Table 3.
Mortality
There was a significant difference in 30 day mortality be-
tween patients with familial and sporadic AAA (4.7% vs.
1.0%, adjusted HR 5.7, 95% CI 1.8e17.9, p ¼ .003, Table 4).
Four deaths occurred in the familial AAA group, two pa-
tients had a history of a chronic pulmonary disease and died
because of complications from hospital acquired pneu-
monia. One patient had a concomitant thoracic aortic
aneurysm which ruptured several days after stent graft
implantation for an abdominal aortic aneurysm. One pa-
tient was readmitted 3 days after stent graft implantation
and was diagnosed with gastric perforation. The patient
died because of multiple organ failure several days later.
There was also a significant difference in aneurysm related
mortality (5.8% vs. 1.3%, adjusted HR 5.4, 95% CI 1.9e14.9,
p ¼ .001, Fig. 1). This was mostly explained by the higher 30
day mortality, as no difference was observed when
excluding 30 day mortality from aneurysm related mortality
(Fig. S1, supplementary data). No significant difference was
observed for all cause mortality (19.8% vs. 24.3%, adjusted
HR 0.8, 95% CI 0.5e1.4, p ¼ .501, Fig. 2). A list of the causes
of aneurysm related mortality is provided in Table S1
(supplementary data).
Additional analyses
Additional gender specific analyses showed that male fa-
milial AAA patients had more stent graft occlusion
compared with male sporadic AAA patients (10.1% vs. 3.6%,
p ¼ .007, Table S2) and that female familial AAA patients
had less technical success compared with male familial AAA
patients (93.8% vs. 100%, p ¼ .035, Table S3). No other
gender related differences were observed.
4 K.M. van de Luijtgaarden et al.

Table 1. Clinical characteristics of patients with familial and sporadic AAA.

Variablea Familial AAA Sporadic AAA p value
n ¼ 86 n ¼ 1176
Gender .012
Female 18.6% (16/86) 9.9% (117/1,176)
Male 81.4% (70/86) 90.1% (1059/1,176)
Age, years 71.6
8.3 73.2
8.1 .047
Baseline symptoms
None 82.6% (71/86) 83.9% (987/1,176) .739
Abdominal pain 11.8% (10/86) 10.6% (125/1,176) .772
Back pain 5.9% (5/86) 5.2% (62/1,176) .829
Other symptoms 1.2% (1/86) 2.5% (30/1,176) .422
Physical measurements
Height, cm 174.3
9.8 172.7
8.1 .088
Weight, kg 82.3
15.8 81.1
15.3 .760
Systolic blood pressure, mmHg, mean 142.2
21.0 135.9
18.7 .007
Diastolic blood pressure, mmHg, mean 79.5
12.7 78.2
11.2 .340
Risk factors and comorbidities
Tobacco use 48.8% (41/84) 49.3% (567/1,149) .924
Hypertension 77.6% (66/85) 75.3% (874/1,161) .625
Hyperlipidaemia 64.6% (53/82) 60.3% (668/1,108) .437
Diabetes 16.3% (14/86) 19.2% (223/1,159) .500
Cancer 10.6% (9/85) 21.2% (245/1,157) .020
Alcoholism 4.7% (4/85) 3.1% (36/1,144) .435
Cardiac disease 55.8% (48/86) 53.6% (630/1,176) .687
MI 34.5% (29/84) 26.0% (293/1,125) .090
Arrhythmia 17.6% (15/85) 16.0% (184/1,149) .693
Angina 12.9% (11/85) 15.9% (183/1,150) .467
Congestive heart failure 1.2% (1/86) 6.1% (70/1,144) .057
Coronary artery disease 30.5% (25/82) 35.1% (399/1,137) .398
Cardiac revascularisation (CABG or PTCA) 32.1% (27/84) 26.9% (312/1,161) .295
Valvular heart disease 5.8% (5/86) 6.2% (71/1,150) .893
COPD 22.1% (19/86) 25.7% (297/1,156) .460
Renal insufficiency 8.1% (7/86) 16.1% (188/1,166) .049
Carotid artery disease 13.9% (10/72) 10.7% (105/983) .399
Cerebrovascular disease 16.3% (14/86) 12.5% (147/1,176) .311
Transient ischaemic attack 4.8% (4/84) 4.9% (57/1,165) .957
Cerebral vascular accident 8.2% (7/85) 5.1% (60/1,170) .219
Paraplegia 0.0% (0/85) 0.3% (3/1,170) .640
Vascular disease 37.2% (32/86) 30.5% (359/1,176) .196
Any thoracic aneurysm 3.6% (3/83) 1.8% (20/1,125) .237
Peripheral vascular disease 20.9% (18/86) 18.3% (212/1,159) .543
Thromboembolic event 6.0% (5/84) 3.1% (36/1,153) .162
Bleeding disorder 3.5% (3/86) 1.7% (20/1,176) .232
Liver disease 3.5% (3/86) 2.2% (26/1,176) .445
GI complications 27.9% (24/86) 19.2% (226/1,176) .051
ASA classification .111
Class I 3.5% (3/86) 6.2% (73/1176)
Class II 51.2% (44/86) 41.2% (484/1,176)
Class III 40.7% (35/86) 41.6% (489/1,176)
Class IV 4.7% (4/86) 11.1% (130/1,176)
AAA ¼ abdominal aortic aneurysm; ASA ¼ American Society of Anesthesiologists; MI ¼ myocardial infarction; COPD ¼ chronic obstructive
pulmonary disease; CABG ¼ coronary artery bypass surgery; PTCA ¼ percutaneous transluminal coronary angioplasty;
GI ¼ gastrointestinal.
a
Continuous data are presented as the mean
standard deviation and categorical data as percentages (denominator differs in case of
missing values).

DISCUSSION one study from Ryer et al. reports on the influence of family
The most important finding of this study was that patients history on post-operative mortality after EVAR,5 with no
with a positive family history have a higher 30 day mortality increased 30 day mortality in their population. The current
compared with patients with a negative family history. Only study is based on a much larger patient cohort, however,

Please cite this article in press as: van de Luijtgaarden KM, et al., Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR,
European Journal of Vascular and Endovascular Surgery (2017), http://dx.doi.org/10.1016/j.ejvs.2017.04.018
Higher 30 Day Mortality in Patients 5

Table 2. Aneurysm morphology of patients with familial and sporadic AAA.

Variablea Familial AAA Sporadic AAA p value
n ¼ 86 n ¼ 1176
Maximum aneurysm diameter, mm 58.0
10.1 (86) 60.5
11.7 (1,160) .037
Proximal non-aneurysm aortic neck diameter, mm 23.5
3.3 (86) 23.7
3.5 (1,171) .795
Distal non-aneurysm aortic neck diameter, mm 24.9
4.5 (85) 24.9
4.0 (1,160) .794
Length of non-aneurysmal aortic neck, mm 28.7
13.0 (85) 26.9
12.3 (1,165) .215
Distal diameter of non-aneurysm neck of right iliac, mm 14.5
4.0 (75) 14.1
3.5 (1,031) .459
Distal diameter of non-aneurysm neck of left iliac, mm 13.8
3.6 (77) 13.8
3.5 (1,030) .964
Angle between proximal AAA neck & main axis, degrees 26.8
24.7 (84) 30.6
23.7 (1,142) .095
Length from lowest renal artery to aortic bifurcation, mm 122.2
19.1 (85) 120.3
19.3 (1,168) .323
Length of right iliac from aortic bifurcation to end of seal zone, mm 58.7
27.0 (79) 57.5
24.3 (1,051) .673
Length of left iliac from aortic bifurcation to end of seal zone, mm 59.0
27.0 (76) 58.8
24.7 (1,039) .351
Diameter of right iliac aneurysm, mm 35.2
18.3 (11) 29.8
13.1 (167) .190
Diameter of left iliac aneurysm, mm 26.7
8.8 (8) 29.8
13.1 (153) .864
Length of right iliac aneurysm, mm 46.7
23.9 (12) 42.6
20.7 (147) .426
Length of left iliac aneurysm, mm 32.5
14.3 (9) 43.4
22.8 (131) .180
Right iliac tortuosity .072
Mild 61.6% (53/86) 49.5% (579/1,169)
Moderate 33.7% (29/86) 41.4% (484/1,169)
Severe 4.7% (4/86) 9.1% (106/1,169)
Left iliac tortuosity .177
Mild 55.8% (48/86) 46.7% (545/1,167)
Moderate 37.2% (32/86) 41.3% (482/1,167)
Severe 7.0% (6/86) 12.0% (140/1,167)
Right iliac stenosis 5.4%
15.0 (86) 8.6%
17.3 (1,157) .038
Left iliac stenosis 7.7%
18.5 (86) 9.5%
18.0 (1,155) .075
Aortic mural thrombus/calcification at the proximal neck 6.9%
11.3 (86) 10.6%
17.7 (1,156) .104
AAA ¼ abdominal aortic aneurysm.
a
Continuous data are presented as the mean
standard deviation (number of patients available for analysis) and categorical data as
percentage (number of patients available for analysis).

Table 3. Clinical success through 4 years of follow-up.

Variablea Familial AAA Sporadic AAA p value
n ¼ 86 n ¼ 1144
Clinical success 72.1% (62/86) 79.3% (907/1,144) .116
Technical success 98.8% (85/86) 99.0% (1133/1,144) .855
AAA increase >5 mm 15.7% (23/83) 10.4% (115/1,106) .136
Endoleak type I and III 2.4% (2/85) 1.8% (20/1,126) .701
Aneurysm rupture 1.2% (1/86) 0.9% (10/1,144) .784
Conversion 1.2% (1/86) 1.0% (12/1,144) .921
Secondary procedures 16.3% (14/86) 10.9% (25/1,144) .131
Migration 1.2% (1/85) 0.4% (4/1,126) .255
Occlusion 8.2% (7/85) 3.8% (43/1,126) .048
AAA ¼ abdominal aortic aneurysm.
a
The number of patients available for analysis is presented in brackets.

emphasising the need to determine the underlying cause of unclear. The cause of this phenomenon appears unrelated
this discrepancy in 30 day mortality. to EVAR implantation as technical success was similar in
The reason familial AAA patients have worse outcome both groups. In the familial AAA group, four post-operative
after EVAR compared with sporadic AAA patients remains deaths were observed. Although the complications seemed

Table 4. Cox regression analyses.

Type of mortality Familial AAA Sporadic AAA Adjusted HR 95% CI p value
n¼86 n¼1144
30 day mortality 4.7% (4/86) 1.0% (12/1,144)5.7 1.8e17.9 .003
Aneurysm related mortality at 4 years 5.8% (5/86) 1.3% (15/1,144)5.4 1.9e14.9 .001
All cause mortality at 4 years 19.8% (17/86) 24.3% (278/1144)
0.8 0.5e1.4 .501
AAA, abdominal aortic aneurysm.
Cox regression analyses assessing the effect of familial AAA vs. sporadic AAA (i.e. no family history of aneurysm), adjusting for age and
gender as covariates.
Please cite this article in press as: van de Luijtgaarden KM, et al., Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR,
European Journal of Vascular and Endovascular Surgery (2017), http://dx.doi.org/10.1016/j.ejvs.2017.04.018
6 K.M. van de Luijtgaarden et al.

Figure 1. Kaplan-Meier estimates for freedom from aneurysm related mortality.

unrelated, they may be explained by altered post-
implantation inflammatory reaction in familial AAA pa-
tients. Alternatively, one may hypothesize that familial AAA
patients have an, as yet unknown, inherited connective
tissue disorder leading to all kinds of diseases such as
aneurysm formation, pulmonary disease, and gastrointes-
tinal complications.9,10 For instance, both patients who died
because of pulmonary complications were known to have
pulmonary disease, which may have resulted in the post-
operative complication and eventually death. The

Figure 2. Kaplan-Meier estimates for freedom from all cause mortality.

Please cite this article in press as: van de Luijtgaarden KM, et al., Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR,
European Journal of Vascular and Endovascular Surgery (2017), http://dx.doi.org/10.1016/j.ejvs.2017.04.018
Higher 30 Day Mortality in Patients
ruptured thoracic aortic aneurysm in one patient may also
be related to some sort of unknown connective tissue dis-
order leading to multiple aneurysms. Lastly, the gastric
perforation (which led to the death of the patient) several
days after EVAR may be related to some sort of connective
tissue disorders, as described previously.10 The conclusion
from the present study is that increased 30 day mortality is
seen after EVAR in familial AAA patients, and the study
hypothesis is that this may be related to some sort of un-
known inherited connective tissue disorder, and should
initiate further research on familial AAA. The worse
outcome in familial AAA patients may also be associated
with the higher proportion of females in the familial AAA
population. Female patients are known to have higher peri-
operative mortality.11e13 Correction for gender did not
affect the results, however, as shown by additional gender
based analysis. In addition, overall results for females versus
males in more contemporary studies do not show this dif-
ference, possibly because of improved delivery systems.14
Higher aneurysm related mortality was also observed in
familial AAA patients, although this was mostly explained by
the higher 30 day mortality. This is in agreement with
previous findings by Brewster et al.,15 who concluded that
family history of aneurysmal disease was associated with a
trend towards a higher aneurysm related mortality over a
course of 12 years (OR 9.5). However, all cause mortality
was not different between groups, suggesting that if
adequate exclusion of the aneurysm is maintained, mor-
tality is not different for familial and sporadic AAA. This is
supported by a previous single centre study on familial AAA
and outcome after EVAR, in which no difference was
described in overall mortality after 3 years of follow-up.4
Although definite conclusions cannot be drawn from the
present study, the observed increased risk for familial AAA
patients regarding 30 day mortality after EVAR (HR 5.7)
should be noted and taken into account when treating fa-
milial AAA patients. Future studies should determine the
role of family history and suitability for EVAR. There is
currently insufficient data to support the preferential option
of open repair for familial AAA patients, as only the study of
Ryer et al. reports clinical outcome after open repair and
this showed no differences between familial and sporadic
AAA patients.5
The present study did not show a statistically significant
difference in clinical success through 4 years of follow-up, but
a 7% difference was identified between familial and sporadic
AAA patients suggesting a clinically relevant difference be-
tween groups. This 7% difference mainly resulted from more
stent graft occlusion, although it became insignificant in
multivariate analysis.The reason for this higher occlusion rate
remains to be elucidated, as no significant differences were
found in aneurysm morphology with regard to iliac di-
ameters, stenosis, or tortuosity. The 7% difference was
further based on higher rates of AAA diameter increase,
endoleak I and III, secondary procedures, and migration, but
none reached statistical significance. Therefore, these results
only partly support the previous findings that patients with
familial AAA have more complications after EVAR.4 In the
Please cite this article in press as: van de Luijtgaarden KM, et al., Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR,
European Journal of Vascular and Endovascular Surgery (2017), http://dx.doi.org/10.1016/j.ejvs.2017.04.018
7
previous study, aneurysm sac growth and secondary in-
terventions were the most important elements accounting
for the difference, and it was hypothesized that an intrinsic
weakness of the aortic wall results in more rapid progression
of aneurysm disease and contributes to the higher need for
secondary interventions in familial AAA patients.4 This was
supported by the study from Ryer et al., who described a
higher rate of endoleaks (24% vs. 12%, p ¼ .03) and sec-
ondary intervention following EVAR (21% vs. 12%, p ¼ .04) in
familial AAA patients.5 That no significant differences for
aneurysm growth and secondary procedures were identified
in the current study may result from use of self reported
family history to define familial AAA. A low degree of familial
AAA of only 7% was observed, whereas previous studies using
semi-structured questionnaires revealed a familial AAA
prevalence of approximately 20%.3,4 The outcomes of the
relevant studies so far do not preclude endovascular repair in
patients with familial AAA, but should create awareness that
these patients may react differently on endovascular repair
and may require additional interventions to maintain
adequate aneurysm exclusion.
Patients with familial AAA were younger and seemed to
have marginally higher systolic blood pressure and less
cancer. Several previous studies also showed that familial
AAA patients are generally younger,3,4,16 and although most
studies report variable results on hypertension in patients
with familial AAA,3,16e18 data on cancer prevalence in fa-
milial AAA are scarce. Overall, the current study supports
the view of previous observations that familial AAA patients
are more often female, tend to be younger, and seem to
have a lower atherosclerotic risk profile.
No major morphological differences were observed be-
tween familial and sporadic AAA in any registered param-
eters. Therefore, disparities between the groups cannot be
attributed to any morphological differences in the
commonly evaluated parameters. The results also preclude
conventional aneurysm morphology parameters as markers
to identify patients with familial AAA, which is also a rele-
vant finding of this study.
There are several limitations of this study that must be
noted. First, as reported previously, potential under classi-
fication of familial AAA patients is the greatest limitation of
the study and may have influenced results. Ideally, familial
AAA is being established based on a semi-structured
questionnaire. Nevertheless, the data presented in this
study represent the definition of familial AAA used in most
outpatient clinic settings. Second, the study has a relatively
short follow-up of 4 years. Longer- term follow-up may be
needed before definite conclusions can be drawn, as com-
plications related to loss of seal because of aortic wall
degeneration may only become apparent later. Third, no
systemic molecular screening was performed for aneurysm
related diseases such as Marfan, Loeys-Dietz, or the
vascular Ehlers-Danlos syndrome. However, these syn-
dromes are rarely a cause of AAA and are usually identified
at a far younger age. Therefore, it is thought that the po-
tential contribution of these syndromes would be exceed-
ingly small.
8 K.M. van de Luijtgaarden et al.
In conclusion, the current study shows a higher 30 day
mortality after EVAR in patients with familial AAA in the
ENGAGE registry and underlines the importance of family
history in aneurysm patients. The data also suggest that
more complications may develop over time in familial AAA
patients, although the data were not statistically significant.
More data are required to determine the role of family
history in AAA treatment, suitability for endovascular or
open repair, and on adaptation of post-operative surveil-
lance. For the time being, patients with familial forms of
AAA should be considered a higher risk when considering
EVAR, and warrant extra vigilance.
CONFLICT OF INTEREST
None.
FUNDING
KM van de Luijtgaarden and F Bastos Gonçalves are sup-
ported by an unrestricted grant from the “Lijf & Leven”
Foundation, Rotterdam, the Netherlands. The ENGAGE
Registry was funded by Medtronic Inc.
APPENDIX A. SUPPLEMENTARY DATA
Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.ejvs.2017.04.018.
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