- Email: [email protected]
Contemporary Characteristics and Outcomes of Young Patients (Under 50 Years) Undergoing Open Carotid Artery Surgery
Accepted Manuscript Contemporary Characteristics and Outcomes of Young Patients (under 50 years) Undergoing Open Carotid Artery Surgery Lauren M. Story, MS, Julie M. Duke, MD, Matthew R. Smeds, MD, Ahsan T. Ali, MD, Mohammed M. Moursi, MD, Lewis C. Lyons, MD, Guillermo A. Escobar, MD PII:
S0890-5096(16)31277-8
DOI:
10.1016/j.avsg.2017.01.017
Reference:
AVSG 3275
To appear in:
Annals of Vascular Surgery
Received Date: 13 December 2016 Revised Date:
10 January 2017
Accepted Date: 24 January 2017
Please cite this article as: Story LM, Duke JM, Smeds MR, Ali AT, Moursi MM, Lyons LC, Escobar GA, Contemporary Characteristics and Outcomes of Young Patients (under 50 years) Undergoing Open Carotid Artery Surgery, Annals of Vascular Surgery (2017), doi: 10.1016/j.avsg.2017.01.017. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Contemporary characteristics and outcomes of young patients (under 50 years) undergoing
2
open carotid artery surgery.
RI PT
3
4
Lauren M. Story MS, Julie M. Duke MD, Matthew R. Smeds MD, Ahsan T. Ali MD,
5
Mohammed M. Moursi MD, Lewis C. Lyons MD, and Guillermo A. Escobar MD
7
Corresponding Author:
8
Guillermo A. Escobar, MD
9
Assistant Professor of Surgery
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Section of Vascular Surgery,
11
University of Arkansas for Medical Sciences
12
4301 W Markham St. Little Rock, AR 72205.
13
Email: [email protected]
14
Phone: (501) 686-6176
15
Fax (501) 686-5328
16
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Disclosures
18
No author has a conflict of interest related to this research, and no external funding was obtained
19
to obtain or analyze this data.
21
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Abstract
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Stroke is the second leading cause of death worldwide, with 10% of neurological events
3
occurring in adults 18-49. The incidence in this age group has risen over the last two decades
4
(while falling in the aged), despite improved diagnostic capacity and greater ability to treat it
5
medically and surgically. We are unaware of any modern data regarding the risk factors and
6
outcomes after carotid artery surgery in this demographic. We sought to evaluate the
7
contemporary characteristics and outcomes of young adults undergoing carotid surgery.
8
Methods: Retrospective analysis of patients aged 18-49 years who underwent carotid surgery
9
from 2005-2015. We collected demographics, indications and outcomes; comparing them to
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previously published series.
11
Results: 16 patients with mean age of 46(41-49) years, and 44% were male. Most were
12
Caucasian (88%) and smokers (94%); consuming 1.3 packs/day with a mean pack-year history of
13
32(10-100). Average body mass index was 29. The majority (81%) were symptomatic prior to
14
surgery (69% of these were strokes). Complications after surgery were hyperperfusion (1) and
15
one deep vein thrombosis. Compared to young patients treated from 1973-1990s, we found
16
significantly more female patients (P<0.001), and more strokes (P<0.04) leading to the
17
procedure, while smoking remained the most prevalent risk factor.
18
Conclusion: Carotid artery surgery in young patients continues to be associated with
19
symptomatic stenosis and smoking; however, compared to 2-4 decades ago it may be more
20
common in young females, and following a stroke. This may be from an increased prevalence of
21
female smoking and improved neuro-imaging.
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Introduction: As of 2013, stroke is responsible for 1 out of every 20 deaths in the United States; with over 600,000 new events yearly. It is the fifth leading cause of death in the United States and the
4
second leading cause worldwide1. Even though the overall relative rate of stroke death declined
5
by 34% from 2003-2013, this decline was more significant in adults aged ≥65 years. Meanwhile,
6
in adults <50 years of age there has been an increase in hospitalizations due to ischemic stroke1.
7
Carotid disease is responsible for about 20% of all ischemic strokes, and these types of stroke
8
have a worse prognosis, and greater stroke recurrence rate2,3. Young adults are generally more
9
likely to survive a stroke; however, young survivors have a higher risk of mortality than same
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aged individuals in the general population. In addition, almost half are unable to return to work,
11
devastating their quality of life, family dynamics and hindering their economic potential.
12
Individuals aged 18-49 account for 10% of all neurological events, yet little research exists to
13
analyze their risk factors and long term outcomes after intervention 3.
14
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While carotid endarterectomy has been well studied for the management of carotid disease in older patients, there is a paucity of recent data regarding the modern outcomes of
16
young patients undergoing carotid surgery. Our review of the literature revealed that there is no
17
data published on young patients undergoing carotid surgery since the 1990’s4-8; while, stroke
18
demographics and risk factors have significantly changed in the last 2-3 decades. Most notably,
19
obesity has risen in developed countries to a prevalence of one third of the population in the
20
United States, while smoking prevalence in adults has fallen from >42%% in 1965 to about 17%
21
in 20149. Despite this, the overall incidence of stroke has remained stable since the 1990’s, but
22
the incidence of “first” strokes has increased by 68%10. Other relevant factors in that have
23
changed significantly in the last 2 decades include: technological advances in neurological
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imaging, risk modification approaches and improved surgical outcomes overall. We therefore
2
sought to compare contemporary indications, risk factors and outcomes of young (<50 years)
3
patients undergoing carotid artery surgery in our institution, to available data on.
4
Methods:
5
We obtained an Institutional Review Board approval to perform a retrospective search
6
exclusively of patients from the age of 18-50 who underwent carotid surgery from 2005-2015 at
7
the University of Arkansas for Medical Sciences. No consent was obtained, due to the
8
retrospective nature of the analysis, and no planned change in their treatment plan. These data
9
were obtained from a prospectively managed hospital database. In this review we included
10
patient demographics, clinical presentation, clinical history, surgical approach, and surgical
11
outcomes. We defined symptomatic carotid stenosis as any stenosis >50% found on an
12
ultrasound, computed tomography angiography (CTA) or magnetic resonance imaging (MRI)
13
associated with a new, ipsilateral stroke or TIA. Stroke was always defined as a neurologist-
14
documented event and/or radiographic evidence of cerebral injury using computed tomography
15
or magnetic resonance imaging on the same side as the carotid stenosis, regardless of the clinical
16
recovery. TIA was defined as a patient-reported or clinician-witnessed motor or verbal deficit or
17
a patient-reported amaurosis fugax; and/or documented ophthalmologic evidence of retinal
18
ischemia ipsilateral to a carotid stenosis. Clinical manifestations that are not ipsilateral to a
19
significant carotid stenosis were classified as “asymptomatic carotid stenosis”, and dizziness was
20
not considered as a symptom for carotid disease. Hypercholesterolemia was considered as any
21
patient taking a cholesterol-lowering medication, or with a total cholesterol >180mg/dL.
22 23
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Fisher’s exact test was done on the pooled data collected from the historically published series, compared to the current study, and after pooled analysis using GraphPad Prism v.6.07
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software (La Jolla, CA USA). Variables that were not reported in the historically published series
2
did not undergo statistical analysis.
3
Results:
4
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We identified 16 patients <50 years old that underwent carotid endarterectomy at the University of Arkansas for Medical Sciences for the study period of 2005-2015, and collected
6
data from 5 historical series4-8, which report the demographics and outcomes of young patients
7
undergoing carotid surgery over 20 years ago. All of our patients were evaluated by a carotid
8
duplex, and all symptomatic patients underwent a combination of either a CT, MRI, or both.
9
Three symptomatic patients underwent a cerebral angiogram, one to treat an acute stroke and two
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to evaluate discordant findings from a CTA and a carotid duplex. Asymptomatic patients only
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underwent a carotid duplex.
The average age of our patients was 46 years with a range of 41-49 years which was
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similar to the previously reported series (table 1). There were less males (44%) than females in
14
our series which was statistically different from the average gender distribution of historic series
15
(Average historically was 64%, P=0.01. There was an overwhelming majority of active smokers
16
amongst our patient population (94%) which was consistent with the previous series (average
17
91% P=NS). We found an average of 32 pack-years, with a range of 10-100, and a mean of 1.3
18
packs per day. Sixty-nine percent of patients were hypertensive (consistent with previous series),
19
controlled on an average of 1.4 medications, although some patients were non-compliant (not
20
taking what was prescribed at the time of diagnosis) with their medication regimen at the time of
21
presentation. Hypercholesterolemia was found in 61% of patients. Mean total cholesterol was
22
195mg/dL (n=10), only one cholesterol level was >240 mg/dL. Body mass index (BMI) was
23
documented in 12/16 patients and the average was just below obesity at 29.
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Table 2 demonstrates the indications for surgery in our patients, and those reported previously. Thirteen of our 16 patients (81%) had a neurological event prior to diagnosis, while
3
the remaining three were diagnosed asymptomatic (one female). Over half (9 of 16 - 69%) of our
4
entire population suffered a stroke and two patients (15%) had an episode of isolated amaurosis
5
without any other neurological deficit. Compared to historic series, more symptomatic patients in
6
our series were diagnosed with stroke (P<0.04 – Figure 1). Eighty-one percent of patients had a
7
carotid stenosis >70%, with 31% of patients presenting with >90% stenosis. Only three patients
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had a stenosis of 50-70%. Four (25%) patients had bilateral carotid disease.
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Endarterectomy with patch angioplasty was utilized in 75% (12) of the cases, while eversion endarterectomy was done in the remaining 25% (4). Shunts were used in 6 patients (all
11
of which were symptomatic), and heparin and protamine were administered in all cases. The
12
average time to surgery from time of diagnosis was 29 days with a range of 4-85 days. There
13
were 2 complications detected in our patients (Table 3), one case of hyperperfusion syndrome
14
with complete resolution of symptoms. The other was a post-operative deep vein thrombosis
15
(DVT) identified in the left popliteal vein, which prolonged the hospital stay. There were no new
16
strokes or cranial nerve injuries. The average hospital stay was 2.6 days (median 1 day).
17
Discussion:
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While one recently published series described “young” patients as those under the age of
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70 (literally calling them “youngsters”)11, we wanted to evaluate the outcomes of patients under
20
the age of 50 requiring carotid surgery to better understand the indications for, and the outcomes
21
after surgery. We found in our series that carotid endarterectomy most commonly follows a
22
stroke rather than a TIA or amaurosis, accompanied by a very high grade carotid stenosis (>70%
23
stenosis in 81%). This advanced atherosclerotic disease was most commonly seen in Caucasian
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patients, and unlike traditional cardiovascular disease risk for this age group, was less common
2
in males (44% vs. 64%). The most prevalent risk factors were smoking, obesity, hypertension
3
and hypercholesterolemia.
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Smoking is a well-established risk factor for stroke as a whole, especially in those who start smoking very young, but its epidemiology has changed over time. The prevalence of
6
smoking in American teenagers was as high as 36% in 1997, but despite a steady decline until
7
2003 it remains at just under 20%9. The percentage of adults who smoke in Arkansas is
8
significantly higher, currently averaging 25% (2016)12; which was paradoxically only measured
9
to be 10% in 201013. Mounting research strongly suggests that starting to smoke early may be
10
critical to stroke development, as smoking increases the risk in a dose-dependent fashion14; so
11
teens who smoke into adulthood are especially at risk. Ninety four percent of our patients were
12
smokers, averaging almost one and a half packs per day and over 30 pack-years, despite being
13
alive just over 40 years. Our prevalence was consistent with the findings reported by others two
14
decades ago (Table 1), although smoking intensity was not included in those manuscripts. Martin
15
et al4 from Dallas, Texas also found a high prevalence of smoking (92%), symptomatic stenosis
16
(92%) and a similar average age at presentation (43 years). However, the majority of their
17
symptomatic patients presented with TIA (75%) compared to our group where 69% presented
18
with stroke. Ballotta et al. (Padua, Italy) had the highest incidence of stroke within the published
19
series of symptomatic patients at 44%, yet this remains lower than our series5.
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The likelihood of stroke being the indication for surgery versus TIA in our series was
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significantly higher when compared to the older series. Over half (56%) of our patients had their
22
surgery following a stroke; higher than the Cleveland Clinic series (11%)6, Mignoli et al. (11%)7
23
and the Martin et al. series (23%)4, averaging 25% in these historical series. Our overall higher
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identification of “stroke” may simply be due to the higher sensitivity to detect strokes using
2
modern imaging modalities, as opposed to what was available/used 20-30 years ago. However,
3
because the series from Padua Italy (also published in the 1990’s) had a similar rate of stroke,
4
our collective patients’ disease may have greater virulence, or simply that our patients had longer
5
progression before diagnosis. The Cleveland Clinic series6 suggests this is unlikely as they had
6
the lowest stroke rate, yet included patients aged up to 50 and had a slightly higher average age
7
(47 years vs. 46 years in our series). The latter series also had a high number of patients that also
8
underwent cardiac surgical procedures, so the carotids they treated may have incidentally found
9
during the routine screening before cardiac surgery that was characteristic of that time period15.
10
Meanwhile, this alternate hypothesis may be supported in the case of the Mignoli series where
11
they did not include patients over 45; yet also had found a stroke in 11%. These conclusions are
12
tempered by the relatively low numbers in all published series in young patients.
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We found a significantly lower incidence in males (47%) in our series, which is not what
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is typically found in other atherosclerotic diseases where female gender is typically considered
15
protective (>70% of acute cardiac events occur in males)16. However, this difference in
16
distribution was striking as it has inverted the ratio of men:women, when compared to the series
17
studying patients operated on 20-30 years ago. The prevalence of males in these series was
18
consistently the majority of the patients; 61% (Cleveland), 63% (Mignoli), 58% (Martin), 74%
19
(Ballotta) and 63% (Rockman) with a mean of 64%. Recent epidemiological data mirrors our
20
findings, showing that the incidence of new strokes in men is 46%16, consistent with our
21
hypothesis. This difference may be explained by the gradual rise to equivalence of the
22
prevalence of smoking in women born after the 1970’s in our series, compared to the women
23
born in the 1930’s and 1940’s from the previous series.
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Our high prevalence of obesity is a trend that is concordant with a recent publication
1
from Silva et al. who evaluated 65 young (39-55 years of age) patients with carotid stenosis (did
3
not evaluate outcomes or treatment) 17. They found in their population (Brazil) that obesity was
4
significantly more prevalent than in older patients with carotid disease. However, their average
5
BMI was 27, while our series found an average BMI of 29 (12 patients had this data available),
6
with two thirds of these being obese (BMI >30). BMI was not reported in any of the historical
7
series.
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In conclusion, we find that compared to young patients treated prior to the 1990’s,
9
smoking continues to be a very consistent risk factor in young patients undergoing carotid
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surgery. This was despite the overall decrease in stroke and smoking rates in the United States
11
seen in the last 20 years (although our state maintains a very high smoking rate in adults). The
12
majority of young carotid stenosis patients still have surgery for symptomatic carotid disease, but
13
it was less likely to be to treat TIA or amaurosis. The latter may simply be due to better
14
diagnostic accuracy and liberal use of advanced imaging like MRI and CT in symptomatic
15
patients, while higher regional virulence may also play a role. We also found a significantly
16
higher proportion of young women having surgery when compared to previous series. Young
17
patients have low rates of perioperative complications after carotid surgery despite their high-
18
grade symptomatic stenosis. Long-term outcomes studies are warranted to determine the
19
consequences and longevity of these repairs, as well as to determine the fate of these patients in
20
this and other vascular beds. We should also remain determined to stop teen smoking, and
21
proactively screen young patients with known risk factors to avoid the devastating consequences
22
of carotid disease.
23
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References
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1. Writing Group M, Mozaffarian D, Benjamin EJ, et al. Executive Summary: Heart Disease and Stroke Statistics--2016 Update: A Report From the American Heart Association. Circulation 2016;133:447-54. 2. Ballotta E, Angelini A, Mazzalai F, Piatto G, Toniato A, Baracchini C. Carotid endarterectomy for symptomatic low-grade carotid stenosis. J Vasc Surg 2014;59:25-31. 3. Varona JF, Bermejo F, Guerra JM, Molina JA. Long-term prognosis of ischemic stroke in young adults. Study of 272 cases. J Neurol 2004;251:1507-14. 4. Martin GH, Allen RC, Noel BL, et al. Carotid endarterectomy in patients less than 50 years old. J Vasc Surg 1997;26:447-54; discussion 54-5. 5. Ballotta E, Da Giau G, Renon L. Early and late outcomes of young patients after carotid endarterectomy. Surgery 1999;125:581-6. 6. Levy PJ, Olin JW, Piedmonte MR, Young JR, Hertzer NR. Carotid endarterectomy in adults 50 years of age and younger: a retrospective comparative study. J Vasc Surg 1997;25:326-31. 7. Mingoli A, Sapienza P, Feldhaus RJ, et al. Carotid endarterectomy in young adults: is it a worthwhile procedure? J Vasc Surg 1997;25:464-70. 8. Rockman CB, Svahn JK, Willis DJ, et al. Carotid endarterectomy in patients 55 years of age and younger. Ann Vasc Surg 2001;15:557-62. 9. Trends in Current Cigarette Smoking Among High School Students and Adults, United States, 1965–2014. 2016. (Accessed 9-10-2016, 2016, at http://www.cdc.gov/tobacco/data_statistics/tables/trends/cig_smoking/.) 10. Hankey GJ. Stroke. Lancet 2016. 11. De Rango P, Simonte G, Farchioni L, et al. Safety of Carotid Revascularization in Symptomatic Patients with less than 70 Years. Ann Vasc Surg 2016;32:73-82. 12. 2016 County Health Rankings - Arkansas. 2016. (Accessed 12-30-2016, 2016, at http://www.countyhealthrankings.org/.) 13. Institute RWJFatUoWpH. 2010 County Health Rankings - Arkansas. 2010 ed2010. 14. Shah RS, Cole JW. Smoking and stroke: the more you smoke the more you stroke. Expert Rev Cardiovasc Ther 2010;8:917-32. 15. Kiernan TJ, Taqueti V, Crevensten G, Yan BP, Slovut DP, Jaff MR. Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting--a case control study. Vasc Med 2009;14:233-7. 16. Roger VL, Go AS, Lloyd-Jones DM, et al. Executive summary: heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 2012;125:188-97. 17. Silva ES, Giglio PN, Waisberg DR, Filho RG, Casella IB, Puech-Leao P. Obesity is a risk factor for significant carotid atherosclerosis in patients aged 39 to 55 years. Angiology 2014;65:602-6.
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Figure Legends
1
2
Table 1: Patient demographics. (NR=Not reported)
4
Table 2: Indications for carotid surgery. (TIA = Transient Ischemic Attack, NR=Not reported).
5
*Levy et al. listed their frequency of carotid stenosis as >80%.
6
Table 3: Perioperative complications (NR=Not reported)
7
Figure 1: Bar graph demonstrating the indications for carotid surgery in symptomatic patients for
8
the current series, and in those treated before.
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S0890-5096(16)31277-8
DOI:
10.1016/j.avsg.2017.01.017
Reference:
AVSG 3275
To appear in:
Annals of Vascular Surgery
Received Date: 13 December 2016 Revised Date:
10 January 2017
Accepted Date: 24 January 2017
Please cite this article as: Story LM, Duke JM, Smeds MR, Ali AT, Moursi MM, Lyons LC, Escobar GA, Contemporary Characteristics and Outcomes of Young Patients (under 50 years) Undergoing Open Carotid Artery Surgery, Annals of Vascular Surgery (2017), doi: 10.1016/j.avsg.2017.01.017. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
1
Contemporary characteristics and outcomes of young patients (under 50 years) undergoing
2
open carotid artery surgery.
RI PT
3
4
Lauren M. Story MS, Julie M. Duke MD, Matthew R. Smeds MD, Ahsan T. Ali MD,
5
Mohammed M. Moursi MD, Lewis C. Lyons MD, and Guillermo A. Escobar MD
7
Corresponding Author:
8
Guillermo A. Escobar, MD
9
Assistant Professor of Surgery
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Section of Vascular Surgery,
11
University of Arkansas for Medical Sciences
12
4301 W Markham St. Little Rock, AR 72205.
13
Email: [email protected]
14
Phone: (501) 686-6176
15
Fax (501) 686-5328
16
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Disclosures
18
No author has a conflict of interest related to this research, and no external funding was obtained
19
to obtain or analyze this data.
21
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Abstract
2
Stroke is the second leading cause of death worldwide, with 10% of neurological events
3
occurring in adults 18-49. The incidence in this age group has risen over the last two decades
4
(while falling in the aged), despite improved diagnostic capacity and greater ability to treat it
5
medically and surgically. We are unaware of any modern data regarding the risk factors and
6
outcomes after carotid artery surgery in this demographic. We sought to evaluate the
7
contemporary characteristics and outcomes of young adults undergoing carotid surgery.
8
Methods: Retrospective analysis of patients aged 18-49 years who underwent carotid surgery
9
from 2005-2015. We collected demographics, indications and outcomes; comparing them to
M AN U
SC
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1
previously published series.
11
Results: 16 patients with mean age of 46(41-49) years, and 44% were male. Most were
12
Caucasian (88%) and smokers (94%); consuming 1.3 packs/day with a mean pack-year history of
13
32(10-100). Average body mass index was 29. The majority (81%) were symptomatic prior to
14
surgery (69% of these were strokes). Complications after surgery were hyperperfusion (1) and
15
one deep vein thrombosis. Compared to young patients treated from 1973-1990s, we found
16
significantly more female patients (P<0.001), and more strokes (P<0.04) leading to the
17
procedure, while smoking remained the most prevalent risk factor.
18
Conclusion: Carotid artery surgery in young patients continues to be associated with
19
symptomatic stenosis and smoking; however, compared to 2-4 decades ago it may be more
20
common in young females, and following a stroke. This may be from an increased prevalence of
21
female smoking and improved neuro-imaging.
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1
2
Introduction: As of 2013, stroke is responsible for 1 out of every 20 deaths in the United States; with over 600,000 new events yearly. It is the fifth leading cause of death in the United States and the
4
second leading cause worldwide1. Even though the overall relative rate of stroke death declined
5
by 34% from 2003-2013, this decline was more significant in adults aged ≥65 years. Meanwhile,
6
in adults <50 years of age there has been an increase in hospitalizations due to ischemic stroke1.
7
Carotid disease is responsible for about 20% of all ischemic strokes, and these types of stroke
8
have a worse prognosis, and greater stroke recurrence rate2,3. Young adults are generally more
9
likely to survive a stroke; however, young survivors have a higher risk of mortality than same
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3
aged individuals in the general population. In addition, almost half are unable to return to work,
11
devastating their quality of life, family dynamics and hindering their economic potential.
12
Individuals aged 18-49 account for 10% of all neurological events, yet little research exists to
13
analyze their risk factors and long term outcomes after intervention 3.
14
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10
While carotid endarterectomy has been well studied for the management of carotid disease in older patients, there is a paucity of recent data regarding the modern outcomes of
16
young patients undergoing carotid surgery. Our review of the literature revealed that there is no
17
data published on young patients undergoing carotid surgery since the 1990’s4-8; while, stroke
18
demographics and risk factors have significantly changed in the last 2-3 decades. Most notably,
19
obesity has risen in developed countries to a prevalence of one third of the population in the
20
United States, while smoking prevalence in adults has fallen from >42%% in 1965 to about 17%
21
in 20149. Despite this, the overall incidence of stroke has remained stable since the 1990’s, but
22
the incidence of “first” strokes has increased by 68%10. Other relevant factors in that have
23
changed significantly in the last 2 decades include: technological advances in neurological
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ACCEPTED MANUSCRIPT 4
imaging, risk modification approaches and improved surgical outcomes overall. We therefore
2
sought to compare contemporary indications, risk factors and outcomes of young (<50 years)
3
patients undergoing carotid artery surgery in our institution, to available data on.
4
Methods:
5
We obtained an Institutional Review Board approval to perform a retrospective search
6
exclusively of patients from the age of 18-50 who underwent carotid surgery from 2005-2015 at
7
the University of Arkansas for Medical Sciences. No consent was obtained, due to the
8
retrospective nature of the analysis, and no planned change in their treatment plan. These data
9
were obtained from a prospectively managed hospital database. In this review we included
10
patient demographics, clinical presentation, clinical history, surgical approach, and surgical
11
outcomes. We defined symptomatic carotid stenosis as any stenosis >50% found on an
12
ultrasound, computed tomography angiography (CTA) or magnetic resonance imaging (MRI)
13
associated with a new, ipsilateral stroke or TIA. Stroke was always defined as a neurologist-
14
documented event and/or radiographic evidence of cerebral injury using computed tomography
15
or magnetic resonance imaging on the same side as the carotid stenosis, regardless of the clinical
16
recovery. TIA was defined as a patient-reported or clinician-witnessed motor or verbal deficit or
17
a patient-reported amaurosis fugax; and/or documented ophthalmologic evidence of retinal
18
ischemia ipsilateral to a carotid stenosis. Clinical manifestations that are not ipsilateral to a
19
significant carotid stenosis were classified as “asymptomatic carotid stenosis”, and dizziness was
20
not considered as a symptom for carotid disease. Hypercholesterolemia was considered as any
21
patient taking a cholesterol-lowering medication, or with a total cholesterol >180mg/dL.
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Fisher’s exact test was done on the pooled data collected from the historically published series, compared to the current study, and after pooled analysis using GraphPad Prism v.6.07
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software (La Jolla, CA USA). Variables that were not reported in the historically published series
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did not undergo statistical analysis.
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Results:
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We identified 16 patients <50 years old that underwent carotid endarterectomy at the University of Arkansas for Medical Sciences for the study period of 2005-2015, and collected
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data from 5 historical series4-8, which report the demographics and outcomes of young patients
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undergoing carotid surgery over 20 years ago. All of our patients were evaluated by a carotid
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duplex, and all symptomatic patients underwent a combination of either a CT, MRI, or both.
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Three symptomatic patients underwent a cerebral angiogram, one to treat an acute stroke and two
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to evaluate discordant findings from a CTA and a carotid duplex. Asymptomatic patients only
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underwent a carotid duplex.
The average age of our patients was 46 years with a range of 41-49 years which was
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similar to the previously reported series (table 1). There were less males (44%) than females in
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our series which was statistically different from the average gender distribution of historic series
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(Average historically was 64%, P=0.01. There was an overwhelming majority of active smokers
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amongst our patient population (94%) which was consistent with the previous series (average
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91% P=NS). We found an average of 32 pack-years, with a range of 10-100, and a mean of 1.3
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packs per day. Sixty-nine percent of patients were hypertensive (consistent with previous series),
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controlled on an average of 1.4 medications, although some patients were non-compliant (not
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taking what was prescribed at the time of diagnosis) with their medication regimen at the time of
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presentation. Hypercholesterolemia was found in 61% of patients. Mean total cholesterol was
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195mg/dL (n=10), only one cholesterol level was >240 mg/dL. Body mass index (BMI) was
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documented in 12/16 patients and the average was just below obesity at 29.
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Table 2 demonstrates the indications for surgery in our patients, and those reported previously. Thirteen of our 16 patients (81%) had a neurological event prior to diagnosis, while
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the remaining three were diagnosed asymptomatic (one female). Over half (9 of 16 - 69%) of our
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entire population suffered a stroke and two patients (15%) had an episode of isolated amaurosis
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without any other neurological deficit. Compared to historic series, more symptomatic patients in
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our series were diagnosed with stroke (P<0.04 – Figure 1). Eighty-one percent of patients had a
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carotid stenosis >70%, with 31% of patients presenting with >90% stenosis. Only three patients
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had a stenosis of 50-70%. Four (25%) patients had bilateral carotid disease.
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Endarterectomy with patch angioplasty was utilized in 75% (12) of the cases, while eversion endarterectomy was done in the remaining 25% (4). Shunts were used in 6 patients (all
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of which were symptomatic), and heparin and protamine were administered in all cases. The
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average time to surgery from time of diagnosis was 29 days with a range of 4-85 days. There
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were 2 complications detected in our patients (Table 3), one case of hyperperfusion syndrome
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with complete resolution of symptoms. The other was a post-operative deep vein thrombosis
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(DVT) identified in the left popliteal vein, which prolonged the hospital stay. There were no new
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strokes or cranial nerve injuries. The average hospital stay was 2.6 days (median 1 day).
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Discussion:
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While one recently published series described “young” patients as those under the age of
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70 (literally calling them “youngsters”)11, we wanted to evaluate the outcomes of patients under
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the age of 50 requiring carotid surgery to better understand the indications for, and the outcomes
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after surgery. We found in our series that carotid endarterectomy most commonly follows a
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stroke rather than a TIA or amaurosis, accompanied by a very high grade carotid stenosis (>70%
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stenosis in 81%). This advanced atherosclerotic disease was most commonly seen in Caucasian
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patients, and unlike traditional cardiovascular disease risk for this age group, was less common
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in males (44% vs. 64%). The most prevalent risk factors were smoking, obesity, hypertension
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and hypercholesterolemia.
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Smoking is a well-established risk factor for stroke as a whole, especially in those who start smoking very young, but its epidemiology has changed over time. The prevalence of
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smoking in American teenagers was as high as 36% in 1997, but despite a steady decline until
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2003 it remains at just under 20%9. The percentage of adults who smoke in Arkansas is
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significantly higher, currently averaging 25% (2016)12; which was paradoxically only measured
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to be 10% in 201013. Mounting research strongly suggests that starting to smoke early may be
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critical to stroke development, as smoking increases the risk in a dose-dependent fashion14; so
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teens who smoke into adulthood are especially at risk. Ninety four percent of our patients were
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smokers, averaging almost one and a half packs per day and over 30 pack-years, despite being
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alive just over 40 years. Our prevalence was consistent with the findings reported by others two
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decades ago (Table 1), although smoking intensity was not included in those manuscripts. Martin
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et al4 from Dallas, Texas also found a high prevalence of smoking (92%), symptomatic stenosis
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(92%) and a similar average age at presentation (43 years). However, the majority of their
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symptomatic patients presented with TIA (75%) compared to our group where 69% presented
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with stroke. Ballotta et al. (Padua, Italy) had the highest incidence of stroke within the published
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series of symptomatic patients at 44%, yet this remains lower than our series5.
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The likelihood of stroke being the indication for surgery versus TIA in our series was
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significantly higher when compared to the older series. Over half (56%) of our patients had their
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surgery following a stroke; higher than the Cleveland Clinic series (11%)6, Mignoli et al. (11%)7
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and the Martin et al. series (23%)4, averaging 25% in these historical series. Our overall higher
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identification of “stroke” may simply be due to the higher sensitivity to detect strokes using
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modern imaging modalities, as opposed to what was available/used 20-30 years ago. However,
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because the series from Padua Italy (also published in the 1990’s) had a similar rate of stroke,
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our collective patients’ disease may have greater virulence, or simply that our patients had longer
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progression before diagnosis. The Cleveland Clinic series6 suggests this is unlikely as they had
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the lowest stroke rate, yet included patients aged up to 50 and had a slightly higher average age
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(47 years vs. 46 years in our series). The latter series also had a high number of patients that also
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underwent cardiac surgical procedures, so the carotids they treated may have incidentally found
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during the routine screening before cardiac surgery that was characteristic of that time period15.
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Meanwhile, this alternate hypothesis may be supported in the case of the Mignoli series where
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they did not include patients over 45; yet also had found a stroke in 11%. These conclusions are
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tempered by the relatively low numbers in all published series in young patients.
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is typically found in other atherosclerotic diseases where female gender is typically considered
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protective (>70% of acute cardiac events occur in males)16. However, this difference in
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distribution was striking as it has inverted the ratio of men:women, when compared to the series
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studying patients operated on 20-30 years ago. The prevalence of males in these series was
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consistently the majority of the patients; 61% (Cleveland), 63% (Mignoli), 58% (Martin), 74%
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(Ballotta) and 63% (Rockman) with a mean of 64%. Recent epidemiological data mirrors our
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findings, showing that the incidence of new strokes in men is 46%16, consistent with our
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hypothesis. This difference may be explained by the gradual rise to equivalence of the
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prevalence of smoking in women born after the 1970’s in our series, compared to the women
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born in the 1930’s and 1940’s from the previous series.
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Our high prevalence of obesity is a trend that is concordant with a recent publication
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from Silva et al. who evaluated 65 young (39-55 years of age) patients with carotid stenosis (did
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not evaluate outcomes or treatment) 17. They found in their population (Brazil) that obesity was
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significantly more prevalent than in older patients with carotid disease. However, their average
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BMI was 27, while our series found an average BMI of 29 (12 patients had this data available),
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with two thirds of these being obese (BMI >30). BMI was not reported in any of the historical
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series.
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In conclusion, we find that compared to young patients treated prior to the 1990’s,
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smoking continues to be a very consistent risk factor in young patients undergoing carotid
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surgery. This was despite the overall decrease in stroke and smoking rates in the United States
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seen in the last 20 years (although our state maintains a very high smoking rate in adults). The
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majority of young carotid stenosis patients still have surgery for symptomatic carotid disease, but
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it was less likely to be to treat TIA or amaurosis. The latter may simply be due to better
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diagnostic accuracy and liberal use of advanced imaging like MRI and CT in symptomatic
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patients, while higher regional virulence may also play a role. We also found a significantly
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higher proportion of young women having surgery when compared to previous series. Young
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patients have low rates of perioperative complications after carotid surgery despite their high-
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grade symptomatic stenosis. Long-term outcomes studies are warranted to determine the
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consequences and longevity of these repairs, as well as to determine the fate of these patients in
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this and other vascular beds. We should also remain determined to stop teen smoking, and
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proactively screen young patients with known risk factors to avoid the devastating consequences
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of carotid disease.
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References
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1. Writing Group M, Mozaffarian D, Benjamin EJ, et al. Executive Summary: Heart Disease and Stroke Statistics--2016 Update: A Report From the American Heart Association. Circulation 2016;133:447-54. 2. Ballotta E, Angelini A, Mazzalai F, Piatto G, Toniato A, Baracchini C. Carotid endarterectomy for symptomatic low-grade carotid stenosis. J Vasc Surg 2014;59:25-31. 3. Varona JF, Bermejo F, Guerra JM, Molina JA. Long-term prognosis of ischemic stroke in young adults. Study of 272 cases. J Neurol 2004;251:1507-14. 4. Martin GH, Allen RC, Noel BL, et al. Carotid endarterectomy in patients less than 50 years old. J Vasc Surg 1997;26:447-54; discussion 54-5. 5. Ballotta E, Da Giau G, Renon L. Early and late outcomes of young patients after carotid endarterectomy. Surgery 1999;125:581-6. 6. Levy PJ, Olin JW, Piedmonte MR, Young JR, Hertzer NR. Carotid endarterectomy in adults 50 years of age and younger: a retrospective comparative study. J Vasc Surg 1997;25:326-31. 7. Mingoli A, Sapienza P, Feldhaus RJ, et al. Carotid endarterectomy in young adults: is it a worthwhile procedure? J Vasc Surg 1997;25:464-70. 8. Rockman CB, Svahn JK, Willis DJ, et al. Carotid endarterectomy in patients 55 years of age and younger. Ann Vasc Surg 2001;15:557-62. 9. Trends in Current Cigarette Smoking Among High School Students and Adults, United States, 1965–2014. 2016. (Accessed 9-10-2016, 2016, at http://www.cdc.gov/tobacco/data_statistics/tables/trends/cig_smoking/.) 10. Hankey GJ. Stroke. Lancet 2016. 11. De Rango P, Simonte G, Farchioni L, et al. Safety of Carotid Revascularization in Symptomatic Patients with less than 70 Years. Ann Vasc Surg 2016;32:73-82. 12. 2016 County Health Rankings - Arkansas. 2016. (Accessed 12-30-2016, 2016, at http://www.countyhealthrankings.org/.) 13. Institute RWJFatUoWpH. 2010 County Health Rankings - Arkansas. 2010 ed2010. 14. Shah RS, Cole JW. Smoking and stroke: the more you smoke the more you stroke. Expert Rev Cardiovasc Ther 2010;8:917-32. 15. Kiernan TJ, Taqueti V, Crevensten G, Yan BP, Slovut DP, Jaff MR. Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting--a case control study. Vasc Med 2009;14:233-7. 16. Roger VL, Go AS, Lloyd-Jones DM, et al. Executive summary: heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 2012;125:188-97. 17. Silva ES, Giglio PN, Waisberg DR, Filho RG, Casella IB, Puech-Leao P. Obesity is a risk factor for significant carotid atherosclerosis in patients aged 39 to 55 years. Angiology 2014;65:602-6.
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Figure Legends
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Table 1: Patient demographics. (NR=Not reported)
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Table 2: Indications for carotid surgery. (TIA = Transient Ischemic Attack, NR=Not reported).
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*Levy et al. listed their frequency of carotid stenosis as >80%.
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Table 3: Perioperative complications (NR=Not reported)
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Figure 1: Bar graph demonstrating the indications for carotid surgery in symptomatic patients for
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the current series, and in those treated before.
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