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Vascular Medicine
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© The Author(s) 2016
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DOI: 10.1177/1358863X15624025
vmj.sagepub.com
Introduction
Computed tomography (CT) scans are universally used for
the preoperative evaluation of the abdominal aortic aneu-
rysm (AAA) patient. Typically, aneurysm morphology is
carefully assessed and other anecdotal findings, such as a
pathologic mass, visceral organ abnormality, or prior surgi-
cal changes, are noted. The skeletal muscle area of the
abdomen, however, is not measured, although the ability to
do so is readily available.
Studies have shown reduced psoas muscle mass to be a
strong predictor of mortality in patients following open
aneurysm repair, as well as in those with critical limb
ischemia (CLI).1,2 However, to date, there are no data avail-
able on patients treated with endovascular aneurysm repair
(EVAR) who have sarcopenia. The purpose of this study
was to provide an estimate of long-term mortality risk for
EVAR patients with and without sarcopenia.
Methods
Patients and database
Following approval from the Greenville Health System’s
Institutional Review Board, we retrospectively reviewed
200 patients, from a prospective database, who underwent
elective EVAR repair between February 1999 and December
2007 by the vascular surgery service. This time interval
enabled access to imaging, demographic, and long-term
follow-up data. The study population represented approxi-
mately 50% of the AAA patients treated during that time
interval. Patients who underwent open aneurysm repair, had
no follow-up after treatment, or whose abdominal CT scan
was not available were excluded from this study. This study
only included Instructions for Use (IFU) patients; no snor-
kel, chimney, or fenestrated procedures were performed.
The CT scan used for muscle mass measurements was
performed just prior to the EVAR or on the first postopera-
tive visit (within 1 month). Measurements were made at the
mid-body of the third lumbar vertebral body (L3). Selection
of the proper axial slice was facilitated by cross-referencing
the axial image with the CT scout image. The muscle area
was determined by manually segmenting the muscle groups
(abdominal wall, paraspinal, psoas) utilizing a freeform
markup tool. Measurements were obtained on an AGFA©
PACS workstation and were performed by a single observer
Impact of sarcopenia on long-term mortality
following endovascular aneurysm repair
Allyson L Hale, Kayla Twomey, Joseph A Ewing,
Eugene M Langan III, David L Cull and Bruce H Gray
Abstract
Sarcopenia, also known as a reduction of skeletal muscle mass, is a patient-specific risk factor for vascular and cancer
patients. However, there are no data on abdominal aortic aneurysm (AAA) patients treated with endovascular
aneurysm repair (EVAR) who have sarcopenia. To determine the impact of sarcopenia on mortality following EVAR, we
retrospectively reviewed 200 patients treated with EVAR by estimating muscle mass on abdominal computed tomography
(CT) scans. Mortality was analyzed according to its presence (n=25) or absence (n=175). Sarcopenia was more common
in women than men (32.0% vs 9.7%; p=0.005). Patients with sarcopenia had an increased risk of mortality compared to
those without (76% vs 48%; p=0.016). Of note, the overall mortality rate was 51% with a median follow up of 8.4 years
(interquartile range, 5.3–11.7). In conclusion, the presence of sarcopenia on a CT scan is an important predictor of long-
term mortality in patients treated for AAA with EVAR. Pending further study, these data suggest that sarcopenia may aid
in pre-procedural long-term survival assessment of patients undergoing EVAR.
Keywords
abdominal aortic aneurysm, endovascular aneurysm repair, mortality, sarcopenia
Department of Surgery, Vascular Medicine Division, Greenville Health
System, Greenville, SC, USA
Corresponding author:
Bruce H Gray, Vascular Health Alliance, 200 Patewood Drive, Suite
C300, Greenville, SC 29615, USA.
Email: BGray@ghs.org
624025VMJ0010.1177/1358863X15624025Vascular MedicineHale et al.
research-article2016
Article
at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from
2	 Vascular Medicine
(KT). The summation of these muscle groups represented
the total skeletal muscle area (cm2) used for establishing the
presence or absence of sarcopenia. Sarcopenia was defined
as having a skeletal muscle area <114.0 cm2 (men) or <89.8
cm2 (women); this definition was originally derived from
data in donor liver transplantation patients and later used to
assess sarcopenia in CLI patients.2,3 Sarcopenia is not yet a
well-defined entity; as such, we performed a quartile analy-
sis on the distribution of muscle mass in EVAR patients to
evaluate the definition of sarcopenia used in the literature.
Data collection and statistical analysis
Data collection included patient demographics and comor-
bidities, including: age, sex, race, diabetes (DM), smok-
ing status, coronary artery disease (CAD), hypertension
(HTN), obesity, chronic obstructive pulmonary disease
(COPD), and AAA diameter (cm). The presence of CAD
was defined as having an abnormal electrocardiogram,
prior myocardial infarction, prior coronary bypass, or
prior percutaneous coronary intervention. Hypertension
was defined as having a resting blood pressure greater
than 140/90 mmHg or requiring antihypertensive medica-
tions. Obesity was defined as having a body mass index
(BMI) greater than 30.0. COPD was defined as having a
history of pulmonary obstructive disease or required use
of home oxygen secondary to lung disease. Data were
analyzed according to the last available follow-up visit.
Social security death index data were helpful in determin-
ing the date of death, which was the primary endpoint.
Follow up was defined as the date of the procedure to the
last date of observation.
Baseline descriptive statistics were used to determine the
study population, followed by bivariate analysis to determine
the differences in patient demographics. The differences in
continuous variables were analyzed using parametric t-tests
and the differences in discrete variables were analyzed with
chi-squared or, in the case of small sample sizes (n<5),
Fisher’s exact tests. Differences in Kaplan–Meier survival
curves were analyzed using a log-rank test. Statistically sig-
nificant covariates in the bivariate analyses were incorpo-
rated into a multivariate logistic regression. Resulting odds
ratios and 95% confidence intervals were calculated for each
covariate in the multivariate analysis. Data analysis was
performed using R statistical software (version 3.1.3; R
Foundation for Statistical Computing, Vienna, Austria).
Results
Patient characteristics and analysis
The original abdominal CT scans on 200 patients withAAA
who subsequently underwent EVAR by the vascular sur-
gery service at Greenville Health System were analyzed.
Overall demographic information is presented in Table 1.
There were 175 men and 25 women in the study. Mean age
at the time of treatment was 74 ± 7.5 years. The overall
mortality rate was 51%, with a median follow up of 8.4
years (interquartile range, 5.3–11.7) and median time to
death of 5.4 years (interquartile range, 3.0–8.4). Five major
postoperative complications were noted: two ruptures, one
graft migration, one graft infection, and one acute aneu-
rysm expansion.
The mean skeletal muscle area for all patients was 138.2
± 27.9 cm2. The majority of the EVAR sarcopenia patients
were in the lowest quartile of total muscle mass. The break-
down of the quartile analysis on skeletal muscle mass is
described in Table 2.
From the 200 AAA patients, 25 had sarcopenia and 175
did not. Demographic differences between patients with
sarcopenia and without are also described in Table 1.
Patients with sarcopenia tended to be older (77.9 vs 73.0
years; p=0.002), female (32% vs 9.7%; p=0.005), and have
a slightly larger aneurysm at the time of repair (5.87 cm vs
5.53 cm; p=0.080). Furthermore, patients with sarcopenia
had a significantly higher mortality rate during follow-up
than those without (76% vs 48%; p=0.016) (Figure 1).
Figure 1 shows the Kaplan–Meier life table analysis sur-
vival probabilities. The survival curves start to separate
between years 3 and 4, with a statistical difference that
strengthens over time (log-rank test, p=0.016).
When comparing living with deceased patients, three
important statistical demographic differences were seen
in those who died: increased age at time of EVAR (75.9
vs 71.2 years; p<0.001), presence of hypertension (92.2%
vs 81.4%; p=0.040), and presence of sarcopenia (18.5% vs
6.19%; p=0.016) (Table 1). Logistic regression analysis
was used to compare these three significant variables; sex
was also included in the analysis, as it was strongly associ-
ated with sarcopenia (Table 3). The odds ratios and 95%
confidence intervals shown in Table 3 demonstrate the sig-
nificance of sarcopenia (OR 3.17, 95% CI 1.20–9.54),
hypertension (OR 2.73, 95% CI 1.17–7.11), and advanced
age (76–85 years) (OR 0.97, 95% CI 1.04–3.58) on mortal-
ity following EVAR. Sex did not play a significant role in
mortality, nor did it act as a confounding factor with the
other three variables.
Discussion
These data confirm sarcopenia as an independent predictor
of long-term mortality in patients treated for AAA with
EVAR. Although risk prediction models for elective aneu-
rysm repair have been created, they primarily center on
30-day mortality, as opposed to long-term mortality (i.e.
Glasgow aneurysm score, Leiden Score, Hardman Index).4–6
However, in 2013, the Vascular Surgical Group of New
England (VSGNE) did identify four major and four minor
risk factors for assessing long-term survival (5 years) fol-
lowing AAA repair.7 Their major risk criteria included:
unstable angina or recent myocardial infarction, age >80
years, oxygen-dependent COPD, and estimated glomerular
filtration rate <30 ml/min/1.73 m2. The minor risk criteria
included: age 75–79 years, prior myocardial infarction, sta-
ble angina, and not taking aspirin or statins. Based on these
criteria, patients were evaluated and stratified as ‘low risk’
(no major risk factors, 1–2 minor risk factors), ‘medium
risk’ (1 major, 1–3 minor), or ‘high risk’ (1–2 major, >3
minor). The VSGNE ‘high risk’ group showed a mortality
rate of 43% at 5 years; this compares favorably to our group
of EVAR patients with sarcopenia who had a 5-year
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Hale et al.	 3
mortality rate of 40%. These data suggest that preoperative
risk assessment of long-term survival could potentially be
simplified to measuring sarcopenia. Complex risk predic-
tion models tend to lose calibration over time, so the sim-
pler the model, the less recalibration is needed.8
In our study, patients with sarcopenia had a signifi-
cantly higher long-term mortality rate during follow up
than those without (76% vs 48%; p=0.016). However,
noticeable separation between the two survival curves in
Figure 1 is not seen until year 4, with the gap continuing to
increase over time. As future studies on other patient popu-
lations are conducted, longer follow-up (5+ years) may be
necessary to accurately assess the long-term impact sarco-
penia has on patient outcomes, specifically mortality. The
measurement technique and cutoff values we used to
determine and define sarcopenia were previously utilized
in a study that evaluated mortality in patients with CLI.2
The cutoff values for skeletal muscle mass (<114.0 cm2 for
men and <89.8 cm2 for women) represent patients below
the fifth percentile of the standard value in healthy adults.3
We believe this is representative of our AAA population,
Table 1.  Patient characteristics.
All Sarcopenia Mortality
  Yes No p-value Deceased Living p-value
n 200 25 175 103 97  
Age, years, mean (SD) 74 (7.5) 77.9 (7.5) 73.0 (7.4) 0.002 75.9 (7.2) 71.2 (7.1) <0.001
Race, n (%) 0.873 0.878
 White 188 (94) 24 (96.0) 164 (93.7) 97 (94.2) 91 (93.8)  
  African American 11 (5.5) 1 (4.0) 10 (5.7) 6 (5.83) 5 (5.15)  
 Other 1 (0.5) 0 (0) 1 (0.57) 0 (0) 1 (1.03)  
Sex, n (%) 0.005 0.789
 Male 175 (87.5) 17 (68.0) 158 (90.3) 89 (86.4) 86 (88.7)  
 Female 25 (12.5) 8 (32.0) 17 (9.7) 14 (13.6) 11 (11.3)  
Smoking status, n (%) 0.815 0.162
 Former 109 (54.5) 15 (60.0) 94 (53.7) 62 (60.2) 47 (48.5)  
 Never 33 (16.5) 4 (16.0) 29 (16.6) 17 (16.5) 16 (16.5)  
 Current 58 (29) 6 (24.0) 52 (29.7) 24 (23.3) 34 (35.0)  
ESRD, n (%) 0.267 0.107
  Renal insufficiency 30 (15) 4 (16.0) 26 (14.9) 19 (18.5) 11 (11.3)  
 No 168 (84) 1(4.0) 1 (0.57) 82 (79.6) 86 (88.7)  
 Yes 2 (1) 20 (80.0) 148 (54.6) 2 (1.9) 0 (0)  
DM, n (%) 42 (21.0) 5 (20.0) 37 (21.1) 1.000 25 (24.3) 17 (17.5) 0.319
CAD, n (%) 123 (61.5) 17 (68.0) 106 (60.6) 0.621 68 (66.0) 55 (56.7) 0.163
HTN, n (%) 174 (87) 22 (88.0) 152 (86.9) 1.000 95 (92.2) 79 (81.4) 0.040
Hyperlipid, n (%) 120 (60) 12 (48.0) 108 (61.7) 0.275 59 (57.3) 61 (62.9) 0.507
Obese, n (%) 33 (16.5) 2 (8.0) 31 (17.7) 0.349 16 (15.5) 17 (17.5) 0.850
COPD, n (%) 52 (26) 11 (44.0) 41 (23.4) 0.051 32 (31.1) 20 (20.6) 0.128
Dementia, n (%) 8 (4) 1 (4.0) 7 (4.0) 1.000 4 (3.88) 4 (4.12) 1.000
Sarcopenia, n (%) 25 (12.5) 19 (18.5) 6 (6.19) 0.016
 Men 17 (9.7) 17 (68.0) 0 (0) 13 (12.6) 4 (4.12) 0.049
 Women 8 (32.0) 8 (32.0) 0 (0) 6 (5.83) 2 (2.06) 0.378
Total skeletal area,
cm2 mean (SD)
138.2 (27.9) 96.2 (14.0) 144.2 (24.0) <0.001 133.6 (27.1) 143.0 (28.2) 0.017
AAA diameter, cm,
mean (SD)
5.76 (0.91) 5.87 (1.13) 5.53 (0.87) 0.080 5.65 (1.04) 5.50 (0.73) 0.233
Mortality 103 (51.5) 19 (76.0) 84 (48.0) 0.016 103 (100.0)  
Time till death, years
(median)
5.43 4.94 5.66 0.532 5.91  
ESRD, end-stage renal disease; DM, diabetes mellitus; CAD, coronary artery disease; HTN, hypertension; COPD, chronic obstructive pulmonary
disease;AAA, abdominal aortic aneurysm.
Table 2. Total skeletal muscle area.
Size cm2 Died, n (%)
Total area
  Mean ± SD 138.2 ± 27.9  
Quartiles, men
 Q1, n=44 < 124.3 28 (63.6)
 Q2, n=44 124.4–140.1 24 (54.5)
 Q3, n=43 140.2–159.6 19 (43.2)
 Q4, n=44 >159.7 18 (40.9)
Quartiles, women
 Q1, n=7 < 86.7 5 (71.4)
 Q2, n=6 86.8–101.8 3 (50.0)
 Q3, n=6 101.9–118.7 3 (50.0)
 Q4, n=6 >118.8 3 (50.0)
Quartiles, combined
 Q1, n=51 mixeda 33 (64.7)
 Q2, n=50 mixed 27 (54.0)
 Q3, n=49 mixed 22 (44.9)
 Q4, n=50 mixed 21 (42.0)
aMixed by sex differences.
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4	 Vascular Medicine
as our 5-year survival rate in those without sarcopenia was
78.3%, compared to 77.5% in their CLI patients without
sarcopenia (Figure 1). The sarcopenic CLI population had
a lower 5-year survival rate (23.5%) than our AAA sarco-
penic population (40%). Sarcopenia is a consistent marker
of reduced survival, particularly in patients with CLI.
A similar measurement technique was used by Lee et al.
in a study that evaluated 262 patients who underwent open
AAA repair.9 They measured psoas muscle area on CT at
the L4 vertebra, as opposed to L3 in our study. At the 2.3-
year mean follow-up, 55 (21%) of their patients had died.
As psoas muscle area decreased, mortality increased; this
relationship was logarithmic and non-linear. Lee et al. used
the word ‘frailty’ to describe this patient-centered charac-
teristic and suggested that the measurement of psoas
muscle volume was an excellent predictor of mortality. Our
study builds upon these data by measuring more muscle
groups to define a threshold of low muscle mass. By defin-
ing sarcopenia to be a natural aspect of aging that involves
the reduction of skeletal muscle tissue, mass, and function,
we feel this is a more specific term than frailty.
A BMI greater than 30 has been shown to increase AAA
mortality risk. Using the National Surgical Quality
Improvement Program database (NSQIP), Giles et al.
showed a twofold increase in mortality in the morbidly
obese compared to the non-obese.10 We analyzed total mus-
cle area in quartiles and saw no relationship to mortality as
long as patients were ‘above the threshold’ for sarcopenia
(Table 2). With that said, the morbidly obese patient may
also be sarcopenic, as BMI is not equivalent to muscle mass
and should be measured and analyzed separately.11
In our study, women with AAA were more likely than
men to have sarcopenia (32.0% versus 9.7%; p=0.005). The
literature suggests that sex does not play a significant role
in long-term survival following aneurysm repair; however,
sarcopenia was not assessed in these studies.12,13 Although,
in our study, the number of women was low (n=25), sarco-
penia may be helpful in assessing risk based on sex. Further
investigation using a larger population of women would
strengthen, or refute, the association.
Lim et al. provided a contemporary study to the EVAR 2
Trial by evaluating high-risk EVAR patients.14,15 Using a
Figure 1.  Survival curves of patients with and without sarcopenia who underwent EVAR.
Table 3.  Logistic regression results comparing all significant
demographic variables in patients (living vs deceased)
undergoing EVAR.
Odds ratio 95% Confidence interval
(Intercept) 0.31 (0.12, 0.72)
Age 76–85 0.97 (1.04, 3.58)
Hypertension 2.73 (1.17, 7.11)
Sarcopenia 3.17 (1.20, 9.54)
Sex 0.97 (0.38, 2.44)
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Hale et al.	 5
backward stepwise logistic regression analysis, they identi-
fied five prognostic indicators for post-EVAR death; these
included: age, chronic kidney disease stages 4 and 5, con-
gestive heart failure, home oxygen use, and current cancer
therapy. Mortality at 4 years in their trial was 35%, in the
EVAR 2 it was 36%, and in our sarcopenic patients it was
28% (Figure 1).
Elderly patients (>80 years) are more frequently being
treated with EVAR than open repair since the perioperative
risk is lower.16,17 Our data showed that patients >76 years of
age were at an approximately twofold risk for mortality
(Table 3). However, when we modeled multiple variations
of age, no arrangement of age with sarcopenia was found to
significantly impact mortality. This conclusion appears to
confound logic, as both age and sarcopenia were deter-
mined to be independent risk factors (Table 3). However,
this unexpected outcome is likely due to the combination of
our small study population (only 12.5% of patients had sar-
copenia) and the low age difference (4.9 years) between
those with sarcopenia and without. A larger study would
likely resolve this Type II error and provide an effect strong
enough to reach statistical significance.
In this study, the median follow up until death or the end
of the study was 8.4 years, with an interquartile range of
5.3–11.7 years. Our short-term mortality rate (3.5% at >6
months), as well as our 5-year mortality rate (20.5%), were
comparable to the EVAR population reported in the EVAR
1 Trial (4.1% at 6 months, 20.8% at 4 years).18 To our
knowledge, this paper represents the longest follow up, in
terms of mortality, on AAA patients undergoing EVAR in
the literature (Table 4).
Limitations
This study has all the inherent limitations of a retrospective
study performed from a prospective database. The entire
AAA population was not studied as most open AAA
patients fall out of follow-up and do not frequently require
CT scans at follow-up. However, considering we were
focusing on the long-term mortality and not perioperative
events, those who returned for their annual office visits
comprised the study population.
Lost to follow up can be a significant limitation in any
retrospective study. We had previously reported on sur-
vival in EVAR patients who participated in a clinical trial
(mandated follow up) as compared to those treated outside
of a trial (real-world follow-up). The long-term mortality
(5 years) was remarkably consistent between these two
patient populations, with a mortality rate of 36–39%.19
This compares quite favorably to our overall study popula-
tion where we noted a 40% mortality rate at 5 years. This
suggests that a sensitivity analysis on those lost to follow-
up is unnecessary.
Women and minorities are underrepresented in this
study population, which makes the data less generalizable.
We did not measure the use of aspirin or statins in our
patients, which may alter long-term outcomes. Lastly,
acquiring archived CT scan images performed prior to 2004
was challenging; this represented a major limitation to
evaluating all EVAR patients in this study.
Conclusion
The presence of sarcopenia on a CT scan is an important,
patient-specific, risk factor for long-term mortality in AAA
patients treated with EVAR. Pending further study, these data
suggest that sarcopenia may aid in the pre-procedural long-
term survival assessment of patients undergoing EVAR.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
References
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30-day mortality, morbidity, and failure to rescue after elec-
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and comorbidities. J Vasc Surg 2015; 61: 324–331.
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prognostic factor for overall survival in patients with critical
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Table 4.  Patient deaths according to time since EVAR.
All patients Sarcopenia No sarcopenia
  (n=200) (n=25) (n=175)
Mortality
All, n (%) 103 (51.5) 19 (76.0) 84 (48.0)
Time since procedure
  0–6 months 7 (3.5) 0 (0) 7 (4.0)
 6 months
– 5 years
41 (20.5) 10 (40.0) 31 (17.7)
  5–10 years 39 (19.5) 5 (20.0) 34 (19.4)
  10 years 16 (8.0) 4 (16.0) 12 (6.9)
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6	 Vascular Medicine
for future risk models. Eur J Cardiothorac Surg 2013; 43:
1146–1152.
	 9.	Lee JS, He K, Harbaugh CM, et al. Michigan Analytic
Morphomics Group (MAMG). Frailty, core muscle size, and
mortality in patients undergoing open abdominal aortic aneu-
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	10.	Giles KA, Wyers MC, Pomposelli FB, et al. The impact of
body mass index on perioperative outcomes of open and
endovascular abdominal aortic aneurysm repair from the
National Surgical Quality Improvement Program, 2005–
2007. J Vasc Surg 2010; 52: 1471–1477.
	11.	Wannamethee SG, Atkins JL. Muscle loss and obesity: The
health implications of sarcopenia and sarcopenic obesity.
Proc Nutr Soc 2015; 27: 1–8.
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tion, comorbidities, and age but not female gender predict
survival after endovascular repair of abdominal aortic aneu-
rysm. J Vasc Surg 2015; 61: 853–861.
	14.	 Lim S, Halandras PM, Park T, et al. Outcomes of endovascu-
lar abdominal aortic aneurysm repair in high-risk patients.
J Vasc Surg 2015; 61: 862–868.
	15.	United Kingdom EVAR Trial Investigators,Greenhalgh
RM, Brown LC, Powell JT, et al. Endovascular repair of
aortic aneurysm in patients physically ineligible for open
repair. N Engl J Med 2010; 362: 1872–1880.
	16.	Schwarze ML, Shen Y, Hemmerich J, et al. Age-related
trends in utilization and outcome of open and endovascular
repair for abdominal aortic aneurysm in the United States,
2001–2006. J Vasc Surg 2009; 50: 722–729.
	17.	 Schermerhorn ML, Buck DB, O’Malley AJ, et al. Long-term
outcomes of abdominal aortic aneurysm in the Medicare
population. N Engl J Med 2015; 373: 328–338.
	18.	United Kingdom EVAR Trial Investigators,Greenhalgh
RM, Brown LC, Powell JT, et al. Endovascular versus open
repair of abdominal aortic aneurysm. N Engl J Med 2010;
362: 1863–1871.
	19.	Jones WB, Taylor SM, Kalbaugh CA, et al. Lost to follow-
up: A potential under-appreciated limitation of endovascular
aneurysm repair. J Vasc Surg 2007; 46: 434–441.
at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from

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Vasc Med-2016-Hale-1358863X15624025

  • 1. Vascular Medicine 1­–6 © The Author(s) 2016 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1358863X15624025 vmj.sagepub.com Introduction Computed tomography (CT) scans are universally used for the preoperative evaluation of the abdominal aortic aneu- rysm (AAA) patient. Typically, aneurysm morphology is carefully assessed and other anecdotal findings, such as a pathologic mass, visceral organ abnormality, or prior surgi- cal changes, are noted. The skeletal muscle area of the abdomen, however, is not measured, although the ability to do so is readily available. Studies have shown reduced psoas muscle mass to be a strong predictor of mortality in patients following open aneurysm repair, as well as in those with critical limb ischemia (CLI).1,2 However, to date, there are no data avail- able on patients treated with endovascular aneurysm repair (EVAR) who have sarcopenia. The purpose of this study was to provide an estimate of long-term mortality risk for EVAR patients with and without sarcopenia. Methods Patients and database Following approval from the Greenville Health System’s Institutional Review Board, we retrospectively reviewed 200 patients, from a prospective database, who underwent elective EVAR repair between February 1999 and December 2007 by the vascular surgery service. This time interval enabled access to imaging, demographic, and long-term follow-up data. The study population represented approxi- mately 50% of the AAA patients treated during that time interval. Patients who underwent open aneurysm repair, had no follow-up after treatment, or whose abdominal CT scan was not available were excluded from this study. This study only included Instructions for Use (IFU) patients; no snor- kel, chimney, or fenestrated procedures were performed. The CT scan used for muscle mass measurements was performed just prior to the EVAR or on the first postopera- tive visit (within 1 month). Measurements were made at the mid-body of the third lumbar vertebral body (L3). Selection of the proper axial slice was facilitated by cross-referencing the axial image with the CT scout image. The muscle area was determined by manually segmenting the muscle groups (abdominal wall, paraspinal, psoas) utilizing a freeform markup tool. Measurements were obtained on an AGFA© PACS workstation and were performed by a single observer Impact of sarcopenia on long-term mortality following endovascular aneurysm repair Allyson L Hale, Kayla Twomey, Joseph A Ewing, Eugene M Langan III, David L Cull and Bruce H Gray Abstract Sarcopenia, also known as a reduction of skeletal muscle mass, is a patient-specific risk factor for vascular and cancer patients. However, there are no data on abdominal aortic aneurysm (AAA) patients treated with endovascular aneurysm repair (EVAR) who have sarcopenia. To determine the impact of sarcopenia on mortality following EVAR, we retrospectively reviewed 200 patients treated with EVAR by estimating muscle mass on abdominal computed tomography (CT) scans. Mortality was analyzed according to its presence (n=25) or absence (n=175). Sarcopenia was more common in women than men (32.0% vs 9.7%; p=0.005). Patients with sarcopenia had an increased risk of mortality compared to those without (76% vs 48%; p=0.016). Of note, the overall mortality rate was 51% with a median follow up of 8.4 years (interquartile range, 5.3–11.7). In conclusion, the presence of sarcopenia on a CT scan is an important predictor of long- term mortality in patients treated for AAA with EVAR. Pending further study, these data suggest that sarcopenia may aid in pre-procedural long-term survival assessment of patients undergoing EVAR. Keywords abdominal aortic aneurysm, endovascular aneurysm repair, mortality, sarcopenia Department of Surgery, Vascular Medicine Division, Greenville Health System, Greenville, SC, USA Corresponding author: Bruce H Gray, Vascular Health Alliance, 200 Patewood Drive, Suite C300, Greenville, SC 29615, USA. Email: BGray@ghs.org 624025VMJ0010.1177/1358863X15624025Vascular MedicineHale et al. research-article2016 Article at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from
  • 2. 2 Vascular Medicine (KT). The summation of these muscle groups represented the total skeletal muscle area (cm2) used for establishing the presence or absence of sarcopenia. Sarcopenia was defined as having a skeletal muscle area <114.0 cm2 (men) or <89.8 cm2 (women); this definition was originally derived from data in donor liver transplantation patients and later used to assess sarcopenia in CLI patients.2,3 Sarcopenia is not yet a well-defined entity; as such, we performed a quartile analy- sis on the distribution of muscle mass in EVAR patients to evaluate the definition of sarcopenia used in the literature. Data collection and statistical analysis Data collection included patient demographics and comor- bidities, including: age, sex, race, diabetes (DM), smok- ing status, coronary artery disease (CAD), hypertension (HTN), obesity, chronic obstructive pulmonary disease (COPD), and AAA diameter (cm). The presence of CAD was defined as having an abnormal electrocardiogram, prior myocardial infarction, prior coronary bypass, or prior percutaneous coronary intervention. Hypertension was defined as having a resting blood pressure greater than 140/90 mmHg or requiring antihypertensive medica- tions. Obesity was defined as having a body mass index (BMI) greater than 30.0. COPD was defined as having a history of pulmonary obstructive disease or required use of home oxygen secondary to lung disease. Data were analyzed according to the last available follow-up visit. Social security death index data were helpful in determin- ing the date of death, which was the primary endpoint. Follow up was defined as the date of the procedure to the last date of observation. Baseline descriptive statistics were used to determine the study population, followed by bivariate analysis to determine the differences in patient demographics. The differences in continuous variables were analyzed using parametric t-tests and the differences in discrete variables were analyzed with chi-squared or, in the case of small sample sizes (n<5), Fisher’s exact tests. Differences in Kaplan–Meier survival curves were analyzed using a log-rank test. Statistically sig- nificant covariates in the bivariate analyses were incorpo- rated into a multivariate logistic regression. Resulting odds ratios and 95% confidence intervals were calculated for each covariate in the multivariate analysis. Data analysis was performed using R statistical software (version 3.1.3; R Foundation for Statistical Computing, Vienna, Austria). Results Patient characteristics and analysis The original abdominal CT scans on 200 patients withAAA who subsequently underwent EVAR by the vascular sur- gery service at Greenville Health System were analyzed. Overall demographic information is presented in Table 1. There were 175 men and 25 women in the study. Mean age at the time of treatment was 74 ± 7.5 years. The overall mortality rate was 51%, with a median follow up of 8.4 years (interquartile range, 5.3–11.7) and median time to death of 5.4 years (interquartile range, 3.0–8.4). Five major postoperative complications were noted: two ruptures, one graft migration, one graft infection, and one acute aneu- rysm expansion. The mean skeletal muscle area for all patients was 138.2 ± 27.9 cm2. The majority of the EVAR sarcopenia patients were in the lowest quartile of total muscle mass. The break- down of the quartile analysis on skeletal muscle mass is described in Table 2. From the 200 AAA patients, 25 had sarcopenia and 175 did not. Demographic differences between patients with sarcopenia and without are also described in Table 1. Patients with sarcopenia tended to be older (77.9 vs 73.0 years; p=0.002), female (32% vs 9.7%; p=0.005), and have a slightly larger aneurysm at the time of repair (5.87 cm vs 5.53 cm; p=0.080). Furthermore, patients with sarcopenia had a significantly higher mortality rate during follow-up than those without (76% vs 48%; p=0.016) (Figure 1). Figure 1 shows the Kaplan–Meier life table analysis sur- vival probabilities. The survival curves start to separate between years 3 and 4, with a statistical difference that strengthens over time (log-rank test, p=0.016). When comparing living with deceased patients, three important statistical demographic differences were seen in those who died: increased age at time of EVAR (75.9 vs 71.2 years; p<0.001), presence of hypertension (92.2% vs 81.4%; p=0.040), and presence of sarcopenia (18.5% vs 6.19%; p=0.016) (Table 1). Logistic regression analysis was used to compare these three significant variables; sex was also included in the analysis, as it was strongly associ- ated with sarcopenia (Table 3). The odds ratios and 95% confidence intervals shown in Table 3 demonstrate the sig- nificance of sarcopenia (OR 3.17, 95% CI 1.20–9.54), hypertension (OR 2.73, 95% CI 1.17–7.11), and advanced age (76–85 years) (OR 0.97, 95% CI 1.04–3.58) on mortal- ity following EVAR. Sex did not play a significant role in mortality, nor did it act as a confounding factor with the other three variables. Discussion These data confirm sarcopenia as an independent predictor of long-term mortality in patients treated for AAA with EVAR. Although risk prediction models for elective aneu- rysm repair have been created, they primarily center on 30-day mortality, as opposed to long-term mortality (i.e. Glasgow aneurysm score, Leiden Score, Hardman Index).4–6 However, in 2013, the Vascular Surgical Group of New England (VSGNE) did identify four major and four minor risk factors for assessing long-term survival (5 years) fol- lowing AAA repair.7 Their major risk criteria included: unstable angina or recent myocardial infarction, age >80 years, oxygen-dependent COPD, and estimated glomerular filtration rate <30 ml/min/1.73 m2. The minor risk criteria included: age 75–79 years, prior myocardial infarction, sta- ble angina, and not taking aspirin or statins. Based on these criteria, patients were evaluated and stratified as ‘low risk’ (no major risk factors, 1–2 minor risk factors), ‘medium risk’ (1 major, 1–3 minor), or ‘high risk’ (1–2 major, >3 minor). The VSGNE ‘high risk’ group showed a mortality rate of 43% at 5 years; this compares favorably to our group of EVAR patients with sarcopenia who had a 5-year at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from
  • 3. Hale et al. 3 mortality rate of 40%. These data suggest that preoperative risk assessment of long-term survival could potentially be simplified to measuring sarcopenia. Complex risk predic- tion models tend to lose calibration over time, so the sim- pler the model, the less recalibration is needed.8 In our study, patients with sarcopenia had a signifi- cantly higher long-term mortality rate during follow up than those without (76% vs 48%; p=0.016). However, noticeable separation between the two survival curves in Figure 1 is not seen until year 4, with the gap continuing to increase over time. As future studies on other patient popu- lations are conducted, longer follow-up (5+ years) may be necessary to accurately assess the long-term impact sarco- penia has on patient outcomes, specifically mortality. The measurement technique and cutoff values we used to determine and define sarcopenia were previously utilized in a study that evaluated mortality in patients with CLI.2 The cutoff values for skeletal muscle mass (<114.0 cm2 for men and <89.8 cm2 for women) represent patients below the fifth percentile of the standard value in healthy adults.3 We believe this is representative of our AAA population, Table 1.  Patient characteristics. All Sarcopenia Mortality   Yes No p-value Deceased Living p-value n 200 25 175 103 97   Age, years, mean (SD) 74 (7.5) 77.9 (7.5) 73.0 (7.4) 0.002 75.9 (7.2) 71.2 (7.1) <0.001 Race, n (%) 0.873 0.878  White 188 (94) 24 (96.0) 164 (93.7) 97 (94.2) 91 (93.8)     African American 11 (5.5) 1 (4.0) 10 (5.7) 6 (5.83) 5 (5.15)    Other 1 (0.5) 0 (0) 1 (0.57) 0 (0) 1 (1.03)   Sex, n (%) 0.005 0.789  Male 175 (87.5) 17 (68.0) 158 (90.3) 89 (86.4) 86 (88.7)    Female 25 (12.5) 8 (32.0) 17 (9.7) 14 (13.6) 11 (11.3)   Smoking status, n (%) 0.815 0.162  Former 109 (54.5) 15 (60.0) 94 (53.7) 62 (60.2) 47 (48.5)    Never 33 (16.5) 4 (16.0) 29 (16.6) 17 (16.5) 16 (16.5)    Current 58 (29) 6 (24.0) 52 (29.7) 24 (23.3) 34 (35.0)   ESRD, n (%) 0.267 0.107   Renal insufficiency 30 (15) 4 (16.0) 26 (14.9) 19 (18.5) 11 (11.3)    No 168 (84) 1(4.0) 1 (0.57) 82 (79.6) 86 (88.7)    Yes 2 (1) 20 (80.0) 148 (54.6) 2 (1.9) 0 (0)   DM, n (%) 42 (21.0) 5 (20.0) 37 (21.1) 1.000 25 (24.3) 17 (17.5) 0.319 CAD, n (%) 123 (61.5) 17 (68.0) 106 (60.6) 0.621 68 (66.0) 55 (56.7) 0.163 HTN, n (%) 174 (87) 22 (88.0) 152 (86.9) 1.000 95 (92.2) 79 (81.4) 0.040 Hyperlipid, n (%) 120 (60) 12 (48.0) 108 (61.7) 0.275 59 (57.3) 61 (62.9) 0.507 Obese, n (%) 33 (16.5) 2 (8.0) 31 (17.7) 0.349 16 (15.5) 17 (17.5) 0.850 COPD, n (%) 52 (26) 11 (44.0) 41 (23.4) 0.051 32 (31.1) 20 (20.6) 0.128 Dementia, n (%) 8 (4) 1 (4.0) 7 (4.0) 1.000 4 (3.88) 4 (4.12) 1.000 Sarcopenia, n (%) 25 (12.5) 19 (18.5) 6 (6.19) 0.016  Men 17 (9.7) 17 (68.0) 0 (0) 13 (12.6) 4 (4.12) 0.049  Women 8 (32.0) 8 (32.0) 0 (0) 6 (5.83) 2 (2.06) 0.378 Total skeletal area, cm2 mean (SD) 138.2 (27.9) 96.2 (14.0) 144.2 (24.0) <0.001 133.6 (27.1) 143.0 (28.2) 0.017 AAA diameter, cm, mean (SD) 5.76 (0.91) 5.87 (1.13) 5.53 (0.87) 0.080 5.65 (1.04) 5.50 (0.73) 0.233 Mortality 103 (51.5) 19 (76.0) 84 (48.0) 0.016 103 (100.0)   Time till death, years (median) 5.43 4.94 5.66 0.532 5.91   ESRD, end-stage renal disease; DM, diabetes mellitus; CAD, coronary artery disease; HTN, hypertension; COPD, chronic obstructive pulmonary disease;AAA, abdominal aortic aneurysm. Table 2. Total skeletal muscle area. Size cm2 Died, n (%) Total area   Mean ± SD 138.2 ± 27.9   Quartiles, men  Q1, n=44 < 124.3 28 (63.6)  Q2, n=44 124.4–140.1 24 (54.5)  Q3, n=43 140.2–159.6 19 (43.2)  Q4, n=44 >159.7 18 (40.9) Quartiles, women  Q1, n=7 < 86.7 5 (71.4)  Q2, n=6 86.8–101.8 3 (50.0)  Q3, n=6 101.9–118.7 3 (50.0)  Q4, n=6 >118.8 3 (50.0) Quartiles, combined  Q1, n=51 mixeda 33 (64.7)  Q2, n=50 mixed 27 (54.0)  Q3, n=49 mixed 22 (44.9)  Q4, n=50 mixed 21 (42.0) aMixed by sex differences. at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from
  • 4. 4 Vascular Medicine as our 5-year survival rate in those without sarcopenia was 78.3%, compared to 77.5% in their CLI patients without sarcopenia (Figure 1). The sarcopenic CLI population had a lower 5-year survival rate (23.5%) than our AAA sarco- penic population (40%). Sarcopenia is a consistent marker of reduced survival, particularly in patients with CLI. A similar measurement technique was used by Lee et al. in a study that evaluated 262 patients who underwent open AAA repair.9 They measured psoas muscle area on CT at the L4 vertebra, as opposed to L3 in our study. At the 2.3- year mean follow-up, 55 (21%) of their patients had died. As psoas muscle area decreased, mortality increased; this relationship was logarithmic and non-linear. Lee et al. used the word ‘frailty’ to describe this patient-centered charac- teristic and suggested that the measurement of psoas muscle volume was an excellent predictor of mortality. Our study builds upon these data by measuring more muscle groups to define a threshold of low muscle mass. By defin- ing sarcopenia to be a natural aspect of aging that involves the reduction of skeletal muscle tissue, mass, and function, we feel this is a more specific term than frailty. A BMI greater than 30 has been shown to increase AAA mortality risk. Using the National Surgical Quality Improvement Program database (NSQIP), Giles et al. showed a twofold increase in mortality in the morbidly obese compared to the non-obese.10 We analyzed total mus- cle area in quartiles and saw no relationship to mortality as long as patients were ‘above the threshold’ for sarcopenia (Table 2). With that said, the morbidly obese patient may also be sarcopenic, as BMI is not equivalent to muscle mass and should be measured and analyzed separately.11 In our study, women with AAA were more likely than men to have sarcopenia (32.0% versus 9.7%; p=0.005). The literature suggests that sex does not play a significant role in long-term survival following aneurysm repair; however, sarcopenia was not assessed in these studies.12,13 Although, in our study, the number of women was low (n=25), sarco- penia may be helpful in assessing risk based on sex. Further investigation using a larger population of women would strengthen, or refute, the association. Lim et al. provided a contemporary study to the EVAR 2 Trial by evaluating high-risk EVAR patients.14,15 Using a Figure 1.  Survival curves of patients with and without sarcopenia who underwent EVAR. Table 3.  Logistic regression results comparing all significant demographic variables in patients (living vs deceased) undergoing EVAR. Odds ratio 95% Confidence interval (Intercept) 0.31 (0.12, 0.72) Age 76–85 0.97 (1.04, 3.58) Hypertension 2.73 (1.17, 7.11) Sarcopenia 3.17 (1.20, 9.54) Sex 0.97 (0.38, 2.44) at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from
  • 5. Hale et al. 5 backward stepwise logistic regression analysis, they identi- fied five prognostic indicators for post-EVAR death; these included: age, chronic kidney disease stages 4 and 5, con- gestive heart failure, home oxygen use, and current cancer therapy. Mortality at 4 years in their trial was 35%, in the EVAR 2 it was 36%, and in our sarcopenic patients it was 28% (Figure 1). Elderly patients (>80 years) are more frequently being treated with EVAR than open repair since the perioperative risk is lower.16,17 Our data showed that patients >76 years of age were at an approximately twofold risk for mortality (Table 3). However, when we modeled multiple variations of age, no arrangement of age with sarcopenia was found to significantly impact mortality. This conclusion appears to confound logic, as both age and sarcopenia were deter- mined to be independent risk factors (Table 3). However, this unexpected outcome is likely due to the combination of our small study population (only 12.5% of patients had sar- copenia) and the low age difference (4.9 years) between those with sarcopenia and without. A larger study would likely resolve this Type II error and provide an effect strong enough to reach statistical significance. In this study, the median follow up until death or the end of the study was 8.4 years, with an interquartile range of 5.3–11.7 years. Our short-term mortality rate (3.5% at >6 months), as well as our 5-year mortality rate (20.5%), were comparable to the EVAR population reported in the EVAR 1 Trial (4.1% at 6 months, 20.8% at 4 years).18 To our knowledge, this paper represents the longest follow up, in terms of mortality, on AAA patients undergoing EVAR in the literature (Table 4). Limitations This study has all the inherent limitations of a retrospective study performed from a prospective database. The entire AAA population was not studied as most open AAA patients fall out of follow-up and do not frequently require CT scans at follow-up. However, considering we were focusing on the long-term mortality and not perioperative events, those who returned for their annual office visits comprised the study population. Lost to follow up can be a significant limitation in any retrospective study. We had previously reported on sur- vival in EVAR patients who participated in a clinical trial (mandated follow up) as compared to those treated outside of a trial (real-world follow-up). The long-term mortality (5 years) was remarkably consistent between these two patient populations, with a mortality rate of 36–39%.19 This compares quite favorably to our overall study popula- tion where we noted a 40% mortality rate at 5 years. This suggests that a sensitivity analysis on those lost to follow- up is unnecessary. Women and minorities are underrepresented in this study population, which makes the data less generalizable. We did not measure the use of aspirin or statins in our patients, which may alter long-term outcomes. Lastly, acquiring archived CT scan images performed prior to 2004 was challenging; this represented a major limitation to evaluating all EVAR patients in this study. Conclusion The presence of sarcopenia on a CT scan is an important, patient-specific, risk factor for long-term mortality in AAA patients treated with EVAR. Pending further study, these data suggest that sarcopenia may aid in the pre-procedural long- term survival assessment of patients undergoing EVAR. Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. References 1. Arya S, Kim SI, Duwayri Y, et al. Frailty increases the risk of 30-day mortality, morbidity, and failure to rescue after elec- tive abdominal aortic aneurysm repair independent of age and comorbidities. J Vasc Surg 2015; 61: 324–331. 2. Matsubara Y, Matsumoto Aoyagi Y, et al. Sarcopenia is a prognostic factor for overall survival in patients with critical limb ischemia. J Vasc Surg 2015; 61: 945–950. 3. Masuda T, Shirabe K, Ikegami T, et al. Sarcopenia is a prognostic factor in living donor liver transplantation. Liver Transpl 2014; 20: 401–407. 4. Hardman DT, Fisher CM, Patel MI, et al. Ruptured abdomi- nal aortic aneurysms: Who should be offered surgery? J Vasc Surg 1996; 23: 123–129. 5. Steyerberg EW, Kievit J, de Mol Van Otterloo JC, et al. Perioperative mortality of elective abdominal aortic aneu- rysm surgery. A clinical prediction rule based on literature and individual patient data. Arch Intern Med 1995; 155: 1998–2004. 6. Baas AF, Janssen KJ, Prinssen M, et al. The Glasgow Aneurysm Score as a tool to predict 30-day and 2-year mortality in the patients from the Dutch Randomized Endovascular Aneurysm Management trial. J Vasc Surg 2008; 47: 277–281. 7. DeMartino RR, Goodney PP, Nolan BW, et al. Optimal selec- tion of patients for elective abdominal aortic aneurysm repair based on life expectancy. J Vasc Surg 2013; 58: 589–595. 8. Hickey GL, Grant SW, Murphy GJ, et al. Dynamic trends in cardiac surgery: Why the logistic EuroSCORE is no longer suitable for contemporary cardiac surgery and implications Table 4.  Patient deaths according to time since EVAR. All patients Sarcopenia No sarcopenia   (n=200) (n=25) (n=175) Mortality All, n (%) 103 (51.5) 19 (76.0) 84 (48.0) Time since procedure   0–6 months 7 (3.5) 0 (0) 7 (4.0)  6 months – 5 years 41 (20.5) 10 (40.0) 31 (17.7)   5–10 years 39 (19.5) 5 (20.0) 34 (19.4)   10 years 16 (8.0) 4 (16.0) 12 (6.9) at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from
  • 6. 6 Vascular Medicine for future risk models. Eur J Cardiothorac Surg 2013; 43: 1146–1152. 9. Lee JS, He K, Harbaugh CM, et al. Michigan Analytic Morphomics Group (MAMG). Frailty, core muscle size, and mortality in patients undergoing open abdominal aortic aneu- rysm repair. J Vasc Surg 2011; 53: 912–917. 10. Giles KA, Wyers MC, Pomposelli FB, et al. The impact of body mass index on perioperative outcomes of open and endovascular abdominal aortic aneurysm repair from the National Surgical Quality Improvement Program, 2005– 2007. J Vasc Surg 2010; 52: 1471–1477. 11. Wannamethee SG, Atkins JL. Muscle loss and obesity: The health implications of sarcopenia and sarcopenic obesity. Proc Nutr Soc 2015; 27: 1–8. 12. Chung C, Tadros R, Torres M, et al. Evolution of gender- related differences in outcomes from two decades of endo- vascular aneurysm repair. J Vasc Surg 2015; 61: 843–852. 13. Gloviczki P, Huang Y, Oderich GS, et al. Clinical presenta- tion, comorbidities, and age but not female gender predict survival after endovascular repair of abdominal aortic aneu- rysm. J Vasc Surg 2015; 61: 853–861. 14. Lim S, Halandras PM, Park T, et al. Outcomes of endovascu- lar abdominal aortic aneurysm repair in high-risk patients. J Vasc Surg 2015; 61: 862–868. 15. United Kingdom EVAR Trial Investigators,Greenhalgh RM, Brown LC, Powell JT, et al. Endovascular repair of aortic aneurysm in patients physically ineligible for open repair. N Engl J Med 2010; 362: 1872–1880. 16. Schwarze ML, Shen Y, Hemmerich J, et al. Age-related trends in utilization and outcome of open and endovascular repair for abdominal aortic aneurysm in the United States, 2001–2006. J Vasc Surg 2009; 50: 722–729. 17. Schermerhorn ML, Buck DB, O’Malley AJ, et al. Long-term outcomes of abdominal aortic aneurysm in the Medicare population. N Engl J Med 2015; 373: 328–338. 18. United Kingdom EVAR Trial Investigators,Greenhalgh RM, Brown LC, Powell JT, et al. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med 2010; 362: 1863–1871. 19. Jones WB, Taylor SM, Kalbaugh CA, et al. Lost to follow- up: A potential under-appreciated limitation of endovascular aneurysm repair. J Vasc Surg 2007; 46: 434–441. at HIGH POINT UNIV on April 23, 2016vmj.sagepub.comDownloaded from