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\begin{document}

\title{Variants of the Aortic Arch in Adult General Population and their
Association with Thoracic Aortic Aneurysm Disease}



\author[1]{Sameh Yousef}%
\author[2]{saket singh}%
\author[2]{Abedalrazaq AlKukhun}%
\author[2]{Bilal Alturkmani}%
\author[2]{Makoto Mori}%
\author[3]{Julia Chen}%
\author[1]{Clancy Mullan}%
\author[1]{Cornell Brooks}%
\author[2]{Roland Assi}%
\author[2]{Peter Gruber}%
\author[2]{Isabel Cortopassi}%
\author[2]{Arnar Geirsson}%
\author[1]{Prashanth Vallabhajosyula}%
\affil[1]{Yale School of Medicine}%
\affil[2]{Yale University School of Medicine}%
\affil[3]{Yale-New Haven Hospital}%


\vspace{-1em}



  
  \date{June 11, 2024}


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\selectlanguage{english}
\begin{abstract}
Background. Query a single institution computed tomography (CT) database
to assess the prevalence of aortic arch anomalies in general adult
population and their potential association with thoracic aortopathies.
Methods. CT chest scan reports of patients aged 50-85 years old
performed for any indication at a single health system between 2013 and
2016 were included in the analysis. Characteristics of patients with and
without aortic arch anomalies were compared by t-test and Fisher exact
tests. Logistic regression analysis was performed to assess for
independent risk factors of thoracic aortic aneurysm. Results. Of 21,336
CT scans, 603 (2.8\%) described arch anomalies. Bovine arch (n=354,
58.7\%) was the most common diagnosis. Patients with arch anomalies were
more likely to be female (p\textless{}0.001),
non-Caucasian(p\textless{}0.001), and hypertensive (p\textless{}0.001).
Prevalence of thoracic aortic aneurysm in arch anomalies group was
10.8\% (n=65) compared to 4.1\% (n=844) in the non-arch anomaly cohort
(p\textless{}0.001). The highest prevalence of thoracic aneurysm was
associated with right-sided arch combined with aberrant left subclavian
configuration (33\%), followed by bovine arch (13\%), and aberrant right
subclavian artery (8.2\%). On binary logistic regression, arch anomaly
(OR=2.85 {[}2.16-3.75{]}), aortic valve pathology (OR 2.93
{[}2.31-3.73{]}), male sex (OR 2.38 {[}2.01-2.80{]}), and hypertension
(OR 1.47 {[}1.25-1.73{]}) were significantly associated with increased
risk of thoracic aneurysm disease. Conclusions. Reported prevalence of
aortic arch anomalies by CT imaging in the older adult population is
\textasciitilde{}3\%, with high association of thoracic aortic aneurysm
(OR=2.85) incidence in this subgroup. This may warrant a more tailored
surveillance strategy for aneurysm disease in this subpopulation.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Aortic arch anomalies constitute a broad spectrum of congenital variants
of the development of the aortic arch and great vessels. During
embryology, bilateral ventral and dorsal aortae are connected by arches,
most of them regress except for the 3\textsuperscript{rd} arch that
gives rise to the carotid arteries, the 4\textsuperscript{th} arch that
gives rise to the adult arch, and the 6\textsuperscript{th} arch that
gives rise to the ductus arteriosus \textsuperscript{1}. Due to this
complex developmental process, variations or anomalies of the arch and
its branches may occur \textsuperscript{2}. Anomalies of the origin of
arch vessels include common origin of the left common carotid and the
brachiocephalic arteries (bovine arch) \textsuperscript{3}, aberrant
origin of the right and left subclavian arteries from the descending
aorta that sometimes originate from a localized dilatation called
Kommerell's diverticulum \textsuperscript{4,5}\textbf{,} and aberrant
origin of the left vertebral artery from the arch itself rather than
originating from the left subclavian artery \textsuperscript{6}.
Anomalies of the laterality and position of the arch includes double
arch, right sided arch, circumflex arch, cervical arch, interrupted
arch, and pseudocoarctation \textsuperscript{7,8}. Some variants are
reported to be very common in the general population, with example
bovine arch reported to have a prevalence of \textasciitilde{}20\%,
while other variants such as double and cervical arch patterns are
rare\textsuperscript{2}. It has been reported that arch anomalies are
associated with increased incidence of congenital heart
disease\textsuperscript{9} and also thoracic aortopathies
\textsuperscript{10}, although large population studies on arch
anomalies are lacking. We assessed our institutional CT scan database to
better understand the prevalence of arch anomalies in the older adult
population age\emph{\textgreater{}} 50 years, and its possible
association with the thoracic aortic aneurysm disease.

\textbf{Methods}

\textbf{Database and patient population} . Institutional electronic
medical record system was queried from years 2013-2016 to identify
patients with age [?] 50 and \(<\)85 years who received CT
chest imaging for either in inpatient, outpatient, or emergency
department encounters. We set the lower age limit of 50 years because
thoracic aortic aneurysm below this age is rare unless associated with
connective tissue disease, and the upper age limit was set as the
benefit of detection leading to intervention decreases at old age. After
excluding multiple scans obtained on the same patient during the study
period, there were 21,336 scans obtained on unique patients. In patients
with multiple scans, the scan with the earliest date was used for the
analysis. The Institutional Review Board approved this study. All CT
scan reports were screened for any comments on the aortic arch and great
vessels. Those reports were further reviewed for the description and
subcategorization of arch anomalies. Also, all CT scans were screened
for words and permutations related to thoracic aortic aneurysm (TAA)
(aneurysm, dilation, dilatation, ectasia, enlargement) and reports
containing such words were further reviewed for the site and the size of
the aneurysms. Aneurysms of the abdominal aorta were excluded. The site
of the thoracic aortic aneurysm was the site of the maximum diameter of
the aorta. Subjects with missing clinical or demographic data were
excluded.

\textbf{Validation sample} . Due to the concern that the aorta was not
accurately assessed on scans done without contrast and routine scans
done for non-thoracic pathology, a random sample of 200 scans was
generated and reviewed by two radiology trainee and a board certified
cardiothoracic radiologist with 10 years of experience in reading aorta
studies. All the 200 scans were non-contrast. The prevalence and the
type of the anomaly was documented, if found.

\textbf{Patient characteristics} . Indicated age, height, and weight
values were recorded at the time of the CT scan. Race was categorized
into Caucasian, African American, Asian, and other. Body surface area
was calculated using Mosteller equation.\textsuperscript{11} Smoking
history was dichotomized based on those with [?] 5 pack-year smoking
history indicating positive smoking history. Comorbidities (aortic valve
disease, hypertension, diabetes, dyslipidemia, congestive heart failure,
cocaine use, chronic kidney disease, myocardial infarction, chronic
obstructive pulmonary disease) were chosen as commonly evaluated
cardiovascular comorbidities and were defined using ICD-10 codes. To
define aortic dilatation and aneurysm; 4 cm cut-off value was used for
the root, ascending and the aortic arch, and 3 cm was used for the
descending thoracic aorta.

\textbf{Statistical analysis} \emph{.} Differences in the patient
characteristics were compared with two-tailed t-test for normally
distributed continuous variables and Fisher's exact test for categorical
variables. Multivariable logistic regression model was fitted to
identify independent risk factors of TAA. Age, sex, race, BSA, history
of hypertension, diabetes, dyslipidemia, smoking history, COPD, arch
anomalies and aortic valve diseases were included in the model. P value
of \textless{}0.05 and 95\% CI were used to define statistically
significant difference. Analysis was conducted using Microsoft excel
2019 and Prism 8.2 (GraphPad Software, San Diego, CA) for simple
analysis and SAS 9.4 (SAS Institute Inc, Cary, NC) for modelling.

\textbf{Results}

In this cohort of 21,336 unique patients aged 50-85 years who underwent
CT including the chest (49.3\% (n=10,508) were CT scans with intravenous
contrast and 2.5\% (n=540) were EKG-gated) for any clinical indication,
arch anomalies were reported in 2.8\% (n=603 patients). Bovine arch was
the most common variant (n=354, 58.7\% of all anomalies), followed by
aberrant right subclavian artery (n=147, 24.4\%), aberrant left
vertebral artery (n=95, 15.8\% ), aberrant left subclavian artery
combined with right sided arch (n=12, 2\%), double arch (n=1, 0.2\%),
pseudocoarctation (n=1, 0.2\%) (Figure 1). Aberrant left subclavian
artery arising from Kommerell's diverticulum was noted in 5 patients and
aberrant right subclavian artery arising from Kommerell's diverticulum
was reported in 3 patients. On bivariate analysis, patients with arch
anomalies were more likely to be females (p\textless{}0.001),
non-Caucasian (p\textless{}0.001), hypertensive (p\textless{}0.001),
diabetic (p=0.012), had hyperlipidemia (p=0.037), and with significantly
higher prevalence of aortic valve disease (p\textless{}0.001) and TAA
(p\textless{}0.001). Patients with arch anomalies less commonly had
history of smoking and COPD (Table1).

The prevalence of TAA disease was different according to the type of
arch anomaly (Figure 3). Subjects with aberrant left subclavian artery
combined with right sided arch had the highest prevalence of TAA (33\%
versus 4.4\%; 4 out of 12 patients; P\textless{}0.001), followed by
bovine arch (13\% versus 4.4\%,; 46 out of 354 patients with bovine
aortic arch; P\textless{}0.001), and aberrant right subclavian artery
(8\% versus 4.4\%; 12 out of 147 patients with aberrant right subclavian
artery; P\textless{}0.001). Aberrant left vertebral artery was not
associated with increased prevalence of TAA (3\% versus 4.4\%; 3 out of
95 patients with aberrant left vertebral artery; P=0.99). The regional
distribution of TAA was not different between the arch anomaly group and
the no anomaly group. TAA in both groups were more likely to affect the
ascending aorta \textgreater{} descending aorta \textgreater{} aortic
root \textgreater{} aortic arch (Figure 2). The aortic diameter in the
respective region was also not different between the 2 groups. In the
region of the root: mean aortic diameter was 4.2 \selectlanguage{ngerman}± 0.3 cm versus 4.3 ±
0.4 cm, P=0.68; in the ascending aorta: 4.3 ± 0.3 cm versus 4.3 ± 0.4
cm, P=0.92; in the arch: 4.6 ± 0.5 cm versus 4.6 ± 0.7 cm, P=0.96; and
in the descending aorta: 3.6 ± 0.6 cm versus 3.7 ± 0.8 cm, P=0.60. In
the validation sample, 49 cases were previously known to have TAA and
were excluded from the analysis. In the remaining 151 scans, 32 patients
were found to have bovine arch (prevalence=21\%). Type 1 arch was
present in 28 cases and type 2 was present in 4 cases. Also, the
aberrant left vertebral artery was encountered in 10 patients (6.6\%).
Other anomalies were not encountered in the validation sample.

To define independent risk factors for TAA and dilatations, a
multivariable logistic regression analysis was performed. The model
included patient's age, male sex, Caucasian race, BSA, smoking,
hypertension, hyperlipidemia, COPD, aortic valve disease, and arch
anomalies. Age (OR = 1.04 CI{[}1.03-1.05{]}), male sex (OR = 2.38
{[}2.01-2.80{]}), BSA (OR = 1.45 {[}1.13-1.86{]}), hypertension (OR =
1.47{[}1.25-1.73{]}), aortic valve disease (OR = 2.93 {[}2.31-3.73{]}),
and arch anomalies (OR = 2.85 {[}2.16-3.75{]}) were independent risk
factors for TAA (Figure 4).

\textbf{Comment}

In this study, we examined our clinical CT scan database to define arch
anomalies, its variants, and the possible association with TAA. We found
the reported prevalence of arch anomalies on initial survey to be 2.8\%,
with bovine aortic arch being the most common anomaly (58.7\% of all
anomalies and 1.6\% in this population), and aberrant left subclavian
artery combined with right sided arch to have the highest association
with TAA (33\%, P\textless{}0.001) \textsuperscript{12-14}. The reported
prevalence of 2.8\% of arch anomalies was much lower than what we found
in the validation sample (21\% for bovine arch and 6.6\% for aberrant
left vertebral artery). The results of the validation sample correspond
to previously published reports on the prevalence of bovine arch
anomaly. \textsuperscript{2,16} This deviation from the literature in
the initial survey is due to under reporting in our clinical database,
as the CT scans included in this study were done for indications other
than aorta diseases (such as lung cancer screening, pulmonary diseases,
infection/ sepsis, trauma, pulmonary embolism, esophageal diseases) and
it is possible that the arch anatomy received less attention from the
reader since most of these cases were report by radiologists without
fellowship training in cardiovascular imaging. With this relatively high
prevalence of bovine arch, the clinical significance of it should be
considered. Morrehead et al reported 31.1\% prevalence of bovine arch,
including 14.9\% type I bovine arch, and 16.2\% type II bovine arch in
patients with thoracic aortic pathology.\textsuperscript{15} Dumfarth et
al reported bovine aortic arch to be the most common anomalous branch
pattern in patients with thoracic aortic disease, with a prevalence of
24.6\%. This was followed by isolated left vertebral artery in 6.3\% of
patients with thoracic aortic disease, and an aberrant right subclavian
artery in 1.8\%.\textsuperscript{18} Wanamaker et al., reported similar
finding with bovine arch being the most common association with aortic
dissection followed by isolated left vertebral
artery.\textsuperscript{10}

We also noticed that patients with arch anomalies had higher association
with aortic valve disease and hypertension. It is difficult to know if
one factor predisposes the occurrence of the other but we can
hypothesize that it is also possible that fewer /anomalous branching of
the aorta in this region leads to abnormal flow dynamics throughout the
aortic wall in this region putting it under abnormal hemodynamic stress
which when combined with other factors like hypertension or wall stress
caused by abnormal aortic valve geometry could result in an aggressive
phenotype leading to aortic dilatation and even dissection due to the
added/synergistic effect of multiple wall stressors.\textsuperscript{19}

Given the nearly 3 fold higher association with TAA in the arch anomaly
subgroup compared to subjects without arch anomalies in this cohort and
also from the forementioned reports, greater attention needs to be paid
to carefully look and document for bovine arch anatomy in patients
undergoing routine CT chest imaging, with follow-up over time for
development of TAA. To some extent, the argument for this is similar to
incidental diagnosis of bicuspid aortic valve congenital variant, which
occurs in \textasciitilde{}1-2\% of the general population. These
patients are carefully monitored over time for development of aortic
valvulopathy and ascending aortopathy, although majority of subjects
with bicuspid aortic valve will not need any surgical intervention.

The prevalence of other aortic arch variants noted in our study is in
accordance to that reported in the literature, which is
\textasciitilde{}1-2\% \textsuperscript{17}. Our study also shows
differential influence of the type of arch anomaly on the size of the
aorta. Right sided aortic arch combined with aberrant left subclavian
had the highest association with TAA (33\%), while aberrant left
vertebral artery was not associated with increased risk of TAA (3\%).

In this cohort, we also defined independent risk factors for TAA and
found significant association of arch anomaly with incidental aortic
aneurysm (OR 2.85). Other independent factors were: aortic valve disease
(OR=2.95), age, male sex, and increased BSA, while diabetes was found to
be protective (OR=0.75). Given the strong association of arch anomalies
with TAA in this study and also in the literature, and the fact that TAA
in this sub-population tends to dissect more often\textsuperscript{4,5},
we suggest further investigation for inclusion of aortic arch anomalies
in the guidelines for screening for TAA. Current guidelines for
screening and follow-up of patients with known thoracic aortic disease
does not take into consideration the presence of aortic arch anomalies
\textsuperscript{20, 21}.

\textbf{Limitations}

The study defined aortic arch anomalies in patients undergoing CT scan
chest for variety of indications at a single institution. Most of these
indications were for non-cardiac/vascular reasons. While this eliminates
investigator bias, we noticed that CT scans read by radiologists who are
not fellowship trained in cardiovascular imaging underreport the
presence of arch anomalies, particularly the ``bovine arch'' variant.
The study included all types of CT scans (contrast CT
scans=49.3\%(n=10,508) and EKG gated scans=2.5\%(n=540)) which allowed
for a larger sample size, but might have resulted into significantly
lower rates of the reported anomalies, which are known to be better
visualized using contrast studies. We used a size threshold for
diagnosing TAA (4 cm as cut-off value for defining the root, ascending
and arch dilatations/aneurysms and 3 cm for the descending aorta) as
aortic size continues to be the initial screening tool for TAA by most
radiologists and physicians who can further refer the patients for
appropriate consultation. Although, the impact of normalization to body
characteristics (age, sex, BSA) in this study is unknown and might
influence the prevalence of TAA. The study did not address the
prevalence of arch anomalies in patients with thoracic aortic dissection
as the number of dissection patients in this database was too low to
analyze (n=32).

\textbf{Conclusions}

This study investigated the reported prevalence of arch anomalies and
its variants in the adult general population (50 to 85 years of age)
undergoing CT chest imaging at a tertiary care center. Arch anomalies
were under-reported and the high association with TAA in this
subpopulation (OR 2.85) may warrant more methodological approach in
reviewing the arch pattern and also more periodic imaging surveillance
and patient counselling in patients with aortic arch anomalies.

\textbf{References}

\begin{enumerate}
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\end{enumerate}

\textbf{Legend to Figures}

\textbf{Figure 1.} Distribution of aortic arch anomaly variants is
shown.

\textbf{Figure 2.} Anatomic distribution of TAA in subjects with and
without arch anomalies is shown.

\textbf{Figure 3.} Percentage of subjects with concomitant TAA for each
arch anomaly variant is shown

\textbf{Figure 4.} Multivariable regression analysis of 21,336 subjects
was performed to assess for risk factors associated with incidental TAA.
Arch anomaly was significantly associated with TAA incidence (OR 2.85).

OR: odds ratio, CI: 95\% confidence interval, AV: aortic valve, COPD:
chronic obstructive pulmonary disease, BSA: body surface area.

\textbf{Table 1} . Characteristics of patients with and without arch
anomalies.\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Anomalies} n=603 (2.8\%)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{No anomalies} n=20733 (97.2\%)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
P\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Age (years)} \selectlanguage{ngerman}\textbf{± SD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Age (years)} \selectlanguage{ngerman}\textbf{± SD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
66 \selectlanguage{ngerman}\textbf{±} 9.2\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
66.6 \selectlanguage{ngerman}\textbf{±} 9.3\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.154\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Male sex}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Male sex}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
253 (42)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11722 (56.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{BSA (m\textsuperscript{2})}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{BSA (m\textsuperscript{2})}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.9 \selectlanguage{ngerman}\textbf{±} 0.3\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.89 \selectlanguage{ngerman}\textbf{±} 0.3\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.104\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Race}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Caucasian}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
449 (74.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
16643 (80.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{African American}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
84 (13.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2186 (10.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Asian}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (0.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
311 (1.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Other}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
67 (11.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1587 (7.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Smoking}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Smoking}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
233 (38.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8969 (43.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.024\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Hypertension}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Hypertension}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
405 (67.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12090 (58.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Hyperlipidemia}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Hyperlipidemia}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
285 (47.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8911 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.037\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Diabetes Mellitus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Diabetes Mellitus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
162 (26.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4651 (22.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.012\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{CHF}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{CHF}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
47 (7.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1757 (8.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.603\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Cocaine use}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Cocaine use}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
66 (0.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.267\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{CKD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{CKD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
35 (5.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1503 (7.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.201\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Previous MI}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Previous MI}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
41 (6.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1265 (6.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.490\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{AV disease}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{AV disease}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
41 (6.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
249 (1.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{MV disease}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{MV disease}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
25 (4.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
705 (3.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.306\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{COPD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{COPD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
80 (13.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3531 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.015\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Congenital anomalies}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Congenital anomalies}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
13 (2.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
265 (1.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.067\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{TAA}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{TAA}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
65 (10.8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
844 (4.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{TAD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{TAD}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
32 (0.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textgreater{}0.999\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

BSA=Body Surface Area, CHF=Congestive Heart Failure, CKD=Chronic Kidney
Disease, MI=Myocardial Infarction, AV=Aortic valve, MV=Mitral Valve,
COPD=Chronic Obstructive Pulmonary Disease, TAA=Thoracic Aortic Aneurysm
and TAD=Thoracic Aortic Dissection\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure1/Figure1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure2/Figure2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure3/Figure3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/figure4/figure4}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

