Download Risk factors for breast cancer related lymphedema

REVIEW ARTICLE
Risk factors for breast cancer related lymphedema
Avaliação dos fatores de risco no linfedema pós-tratamento de câncer de mama
Laura Ferreira de Rezende1, Alessandra Vilanova Reis Rocha2, Caroline Silvestre Gomes2
Abstract
The main late complication after the surgery of breast cancer is the development of lymphedema, a chronic, progressive, usually incurable disease.
The increase in the volume of the limb can disfigure the body image and develop the physical and psychological morbidity of the patient, promoting
significant damage to the functions. This study was developed through a systematic review from the randomized crosschecking of the keywords
“lymphedema”, “lymphatic compensation”, “lymphatic system”, “axillary dissection”, “risk factors” and “breast cancer”. Eighteen articles were selected,
between 1979 and 2009, in which radiotherapy, axillary radiation, infection, axillary dissection followed by radiotherapy, obesity, number of removed and
impaired lymph nodes and aggressiveness of surgery were found as main risk factors for the development of lymphedema. The way of compensation
after the lymphatic axillary dissection, as the lympho-lymphatic anastomoses, may be hindered by scar formation, seroma after surgery, radiotherapy
and inappropriate exercises for the shoulder rehabilitation in breast cancer.
Keywords: Lymphedema; lymphatic system; lymph node excision; risk factors; breast neoplasms.
Resumo
A principal complicação tardia no pós-operatório de câncer de mama é o desenvolvimento do linfedema, uma doença crônica, progressiva,
geralmente incurável. O aumento do volume do membro pode desfigurar a imagem corporal, assim como aumentar a morbidade física e psicológica
da paciente, além de promover significativo prejuízo para as funções. O presente estudo foi desenvolvido por meio de uma revisão sistemática a
partir do cruzamento aleatório das palavras-chave: “linfedema”, “compensações linfáticas”, “sistema linfático”, “dissecção axilar”, “fatores de risco” e
“câncer de mama”. Foram selecionados 18 artigos entre os anos de 1979 e 2009, nos quais foram encontrados como principais fatores de risco para o
desenvolvimento do linfedema a radioterapia, radioterapia axilar, infecção, dissecção axilar seguida de radioterapia, obesidade, número de linfonodos
retirados e comprometidos e agressividade da cirurgia. As formas de compensação linfática após a dissecção axilar, como as anastomoses linfolinfáticas, podem ser prejudicadas pela formação cicatricial, seroma pós-operatório, radioterapia e exercícios inadequados para reabilitação de ombro
no câncer de mama.
Palavras-chave: Linfedema; sistema linfático; excisão de linfonodo; fatores de risco; neoplasias da mama.
Introduction
According to the International Society of Lymphology
(ISL)1, lymphedema is a clinical manifestation of insufficiency of the lymphatic system that results in a disorder of
lymph transport. It may affect the face, chest, neck, limbs
and pelvis and it is common in postoperative periods and
radiotherapy for oncologic treatment. Besides that, there
are: primary lymphedema due to lymphatic vascular malformations and secondary lymphedema, resulting from episodes of erysipelas or deep vein thrombosis, chronic vein
insufficiency, trauma and ulcerations.
Lymphedema is the postoperative complication of
higher morbidity in breast cancer, as its adverse effects affect directly the patients’ quality of life. Although the incidence is decreasing due to early diagnosis and progress in
therapeutic strategies - especially the sentinel lymph node
biopsy - this entity remains a significant challenge for the
patients and for the multidisciplinary team treating them2.
Despite those advances, the increase in breast cancer incidence and patients’ survival will inevitably increase the incidence of lymphedema3.
The estimates of incidence and prevalence of breast
cancer-related lymphedema vary significantly in literature
PhD; Physical Therapist; Professor of the Physical Therapy graduation course at Centro Universitário das Faculdades Associadas de Ensino (FAE), São João da Boa Vista (SP), Brazil.
Physical Therapy student at Centro Universitário das Faculdades Associadas de Ensino (FAE), São João da Boa Vista (SP), Brazil.
No conflicts of interest declared concerning the publication of this article.
Received on: 18.01.10, Accepted on: 8.12.10
J Vasc Bras. 2010;9(4):233-238.
1
2
234
J Vasc Bras 2010, Vol. 9, Nº 4
due to lack of standardization of criteria and methodological limitations of studies, along with variation of population sampling and duration of postoperative follow-up4,5.
Studies have reported several evaluation methods, including patients’ self-reported symptoms (for example,
limb heaviness, pain, swelling and loss of function), objective measurements (using a variety of tools and protocols) and a combination of patients’ reports and objective
measurements6,7.
The prevalence of lymphedema after breast cancer surgery varies significantly because there are no clear and uniform standards of evaluation. It is believed that this value
varies from 24 to 49% after mastectomy, 4 to 28% after tumor resection with axillary dissection8, and 34% after surgery and radiotherapy9.
The pathogenesis of post-mastectomy lymphedema
has yet to be completely understood. A literature review
shows there are as many theories as there are authors on the
subject. As to the pathophysiology, lymphedema is characterized by a significant reduction in lymph transport, a
mechanism necessary for the absorption of blood filtrate
that accumulates in the insterstitial space1.
Lymphedema is a chronic, progressive and often incurable disease. The swelling of the limbs may disfigure
the patient’s body image, as well as increase the patient’s
physical and psychological morbidity, besides resulting in
significant functional disability9. Although there are satisfactory treatments available, the lack of knowledge about
prevention and cure makes the professionals involved in a
continuing search for better results10.
Lymphedema may be defined as an abnormal accumulation of protein in the insterstitial space, with edema and
chronic inflammation of the extremity11. It is the result of a
functional overload of the lymphatic system, where lymph
volume exceeds its transport capacity by lymphatic capillaries and collectors12,13. The presence of proteins in the interstitial space triggers local fibrosis formation, impairing
lymphatic circulation and contributing to the severity of
the disease14. Besides, axillary lymph node dissection will
impair lymph transport capacity15.
Methods
A systematic review was carried out, with the objective
of evaluating the risk factors for the development of lymphedema in breast cancer postoperative period.
We searched for papers published in the past 30
years that were indexed in Lilacs and Medline databases.
The keywords used in the research were: “lymphedema”,
Lymphedema risk factors and breast cancer PO - Rezende LF et al.
“lymphatic compensation”, “lymphatic system”, “axillary
dissection”, “axillary lymphadenectomy”, “lymph nodes”,
“risk factors”, “lymphatic drainage”, “breast cancer”, and
“lymphoscintigraphy”.
We selected all papers whose objectives were related to:
risk factors for lymphedema, incidence and onset of lymphedema, progression of lymphedema and lymphatic compensation after axillary dissection.
Results
Information presented in Table 1 is the result of the
bibliographical survey on risk factors in postoperative
breast cancer patients with and without lymphedema, aiming to determine the impact on lymphatic compensations
in this period. Twenty-one papers were selected. The risk
factors reported in the papers are presented in Table 1,
while in Table 2 this relation is presented in numbers. Table
3 demonstrates the authors’ justification on how risk factors make lymphatic compensation more difficult and lead
to lymphedema.
Discussion
About 140 million people worldwide have lymphedema: 20 million in the breast cancer postoperative period,
which represents 98% of the upper limb lymphedemas33.
There are many factors associated with the risk of lymphedema development, and their interference in the lymphatic system compensation after axillary dissection may
provide options of prevention and/or cure.
This paper aimed to relate the risk factors considered
to trigger the development of lymphedema with a possible
explanation for the physiological organization of the lymphatic system facing each one of them. Knowledge of the
factors and mechanisms involved in the development of
lymphedema in the breast cancer postoperative period is
essential for the prevention and cure of this disease.
Surgical aggressiveness is a risk factor for lymphedema10,17-19,24, which may explain the higher incidence in the
mastectomy postoperative period in comparison with conservative surgery: 24 to 49% after mastectomy 4 to 28% after
tumor resection with axillary dissection9. One of the explanations would be that patients subjected to mastectomy usually
have more advanced disease and need more aggressive axillary lymph node dissection due to tumor involvement. After
the operation, weight gain may also be a risk factor28.
Axillary lymph node dissection is a well-known risk
factor for lymphedema10,16,18,21. Once axillary lymph nodes
Lymphedema risk factors and breast cancer PO - Rezende LF et al.
J Vasc Bras 2010, Vol. 9, Nº 4
235
Table 1 – Risk factors related to lymphedema development in breast cancer postoperative period
Publication
Herd-Smith et al.16
Soran et al.2
Type of study
Cross-sectional
Case-control
Sample
1.278 patients in breast cancer PO
104 in control group without lymphedema and 52
women with lymphedema
511 women with unilateral breast cancer, ≤ 75 years
old.
40 women divided into 2 groups: with and without
lymphedema.
462 women with lymphedema in breast cancer PO
Hayes et al.17
Prospective
Aboul-Enein et al.15
Case-control
Bergmann et al.8
Cross-sectional
Pain et al.18
Johansson et al.19
Prospective
Case-control
70 patients in breast cancer PO
103 patients in breast cancer PO with lymphedema of
the upper limb, but without recurrence. Lymphedema
developed three months after surgery at minimum
Ozaslan e Kuru20
Prospective
Erickson et al.21
Purushotham et al.22
Literature review
Prospective
Meeske et al.23
Cross-sectional
240 patients in radical mastectomy PO with complete
axillary dissection – minimum 18 months of PO
Axillary lymph node dissection and axillary RT
212 patients in breast cancer PO with axillary lymph
node dissection
494 patients in breast cancer PO
Rett e Lopes24
Literature review
-
Park et al.25
Nielsen et al.26
Ellis27
Prospective
Systematic review
Literature review
450 patients in breast cancer PO
-
Petrek et al.28
Cohort
Rezende et al.10
Literature review
923 patients in breast cancer PO with axillary lymph
node dissection
-
Pain et al.29
Bergmann et al.30
Prospective
Literature review
18 patients in breast cancer PO
-
Freitas Jr et al.31
Guedes Neto et al.32
Retrospective
Retrospective
109 patients in breast cancer PO
142 patients with post-mastectomy lymphedema
Risk factors
Axillary lymph node dissection, RT
Infection, BMI and level of activities performed with
the hands
Aging, surgery aggressiveness dissection of 20 or
more lymph nodes, adjuvant therapy and RT
Upper limb infection, axillary RT, obesity, reduced
movements of the shoulder
Axillary lymph node dissection
Extension and type of surgery, size of the tumor,
number of lymph nodes removed and involved,
postoperative seroma, infection, dehiscence,
phlebitis, cellulites, erysipela in the upper limb and
axillary RT
Number of lymph nodes removed (univariate
analysis), axillary RT and BMI
Age at diagnosis, history of hypertension, obesity, 10
or more lymph nodes removed, sentinel lymph node
Axillary dissection followed by RT; scar dehiscence,
nervous lesions, venous alterations, infections,
inflammation and upper limb seroma; positive
lymph nodes, obesity, alteration in movement range,
surgical technique
Advanced disease, mastectomy, axillary RT, BMI > 25.
Lymphatic system insufficiency by trauma, diseases
or genetic factors
Infection and trauma in the upper limb, weight gain
after surgery
Dissection and axillary RT, obesity, surgical extent
and infection, age, number of lymph nodes involved
Axillary dissection, RT in drainage system and
obesity.
Age and obesity
Lymphangitis, functional limitations of the arm and
basis disease recurrence.
PO: postoperative; BMI: body mass index; RT: radiotherapy.
are removed, the main lymphatic collectors of the region
have no path to continue the lymphatic drainage. The absence of lymph nodes causes an obstruction of the lymphatic system, leading to functional overload of the upper
limb lymphatic system, where the lymph volume exceeds
transport capacity by the lymphatic collectors and lymph
absorption the capillaries24.
A risk factor of great importance in the literature is the
number of removed and involved lymph nodes10,19,20,24,25.
Table 2 – Risk factor with major influence on lymphedema development
according to the selected papers
Risk factor
Papers (n)
Obesity
10
Axillary lymph node dissection
8
Radiotherapy
7
Infection in the arm
6
Surgical aggressiveness
4
236
J Vasc Bras 2010, Vol. 9, Nº 4
Lymphedema risk factors and breast cancer PO - Rezende LF et al.
Table 3 – How the risk factors make the compensation of local lymphatic harder and lead to lymphedema
Publication
Herd-Smith et al.16
Soran et al.2
Aboul-Enein et al.15
Bergmann et al.8
Pain et al.18
Johansson et al.19
Ozaslan e Kuru20
Purushotham et al.22
Meeske et al.23
Rett e Lopes24
Nielsen et al.26
Ellis27
Rezende et al.10
Pain et al.29
Bergmann et al.30
Freitas Jr et al.31
Influence of risk factors for lymphedema on lymphatic compensations in axillary dissection PO
RT would promote the formation of tissue fibrosis and consequent lymphatic vasoconstriction, deficit of lymph node filtration and
alteration in the immunological response
The formation of lymphatic anastomoses prevent lymphedema and, even without the manifestation of symptoms, most patients in
breast cancer PO have lymphatic dysfunction
The incidence of lymphedema is predetermined and a consequence of a failure in lymph-venous communication, which does not allow
an adequate lymph fluid drainage after axillary dissection
Due to lymphatic obstruction, compensation mechanisms develop to establish and maintain the lymphatic circulation in the affected
upper limb without lymphedema.
The longer the period of the lymphatic obstruction, the higher the risk of an unbalance in the system, thus causing lymphedema.
This balance may also be affected by other factors such as:
*“exhaustion” of compensation mechanism;
*lymph vessels fibrosis from de fourth decade of life on;
*local trauma;
*surgical lesion in the collectors;
*inflammation;
*excessive muscle effort;
*exposure to higher temperatures, atmospheric pressure and its changes
Axillary dissection alters the flow into the axillary vein and increases the risk of lymphedema.
Exercise may contribute to reduce the development of lymphedema because it activates lymphatic flow by contracting the skeletal
muscle, improves the range of movements, and stimulates the immunological system.
The obstruction of the lymphatic system is not the only mechanism of lymphedema physiopathology. The total blood flow and the size
of the vascular bed seem to have increased the lymphedema.
The tumoral involvement of lymph nodes requires greater axillary dissection, which would lead to a faster ability to develop collateral
lymph vessels, promoting an adequate lymphatic drainage after the dissection and consequent risk reduction.
Higher blood pressure enables lymphatic flow into the tissues.
Younger patients are more prone to develop lymphedema as a result of the aggressiveness of the tumor and treatment
Lymphedema results from a functional overload of the lymphatic system, since the lymph fluid exceeds the capacity of the collectors
and lymphatic capillaries.
Preventive guidelines are beneficial for preventing lymphedema.
Lymphatic system deficit may result from trauma, diseases or genetic factors
Lymphatic anastomoses are impaired by the healing process, postoperative seroma, RT and inadequate exercise for shoulder
rehabilitation in breast cancer PO period.
The restoration of the flow is benefited by the shoulder immobilization, manual lymphatic drainage and muscle contraction.
The risk may be predetermined by a reduction of the lymphatic flow in the contralateral limb
RT in the lymphatic drainage system promotes a reduction of lymph regeneration, fibrosis and surgical wound healing
A decrease in the blood and lymph flow is considered to be one of the conditions to lypogenesis and fat accumulation, besides
increasing the risk of complications in PO
The dissection of only the lymph system at the Nerg’s level I may increase the risk.
Obesity would increase the risk due to a possible difficulty in lymphatic reflow in patients with more fat tissue.
PO: postoperative; RT: radiotherapy.
However, Purushotham et al.22 suggest that lymph nodes’
involvement may prevent lymphedema because, as a consequence to axillary dissection, there is more time and ability
for collateral lymph vessels to develop, which may promote
an adequate drainage after this procedure and reduction of
lymphedema risk.
Another extensively discussed risk factor is axillary
radiotherapy8,10,16-21, a postoperative complementary treatment that causes destruction of lymph vessels resulting
from the fibrosis, which may lead to significant loss of the
lymph nodes’ filtration function and to an altered immunological response.
Obesity8,10,21,23,24 and body mass index2,18,20,24 are widely
discussed factors in literature. Meesk et al.23 suggest the hypothesis that arterial hypertension is a risk factor, for the
increase in blood flow would facilitate the lymphatic flow
into tissues.
Old age10,17,24 is also mentioned as a risk factor because
fibrosis of the lymphatic system occurs from the fourth
decade of life on. Therefore, it is expected that the longer
the period after lymphatic obstruction, the higher the risk
of lymphatic failure, which leads to the development of
lymphedema. Johansson et al.19 suggest that the tumor size
is a significant factor, since in young patients breast cancer
Lymphedema risk factors and breast cancer PO - Rezende LF et al.
and its treatment tend to be more aggressive and there is a
higher incidence of lymphedema.
Sedentary lifestyle17 and reduced shoulder range of motion 8,24 have been listed as probable risk factors, for exercises may contribute to the recovery from breast cancer treatment by re-opening lymph vessels, activating the lymphatic
flow by skeletal muscle contraction, improving range of
motion, and stimulating the immune system.
Infection is also a risk factor2,8,10,18,19,21,24,27,28. Episodes
of phlebitis19, cellulitis and erysipelas of the upper limbs19,21
are frequently discussed as resulting in lymphatic obstruction. Postoperative seroma and scar maturation may be risk
factors18,24 because lymphatic anastomoses are impaired by
scar tissue formation related to the seroma itself27.
Conclusions
Currently, studies on lymphedema found in the literature show a satisfactory knowledge about treatment and
follow-up of patients with this disease. However, many questions remain to be discussed on the etiopathogenesis of this
disease. Health care professionals should use the knowledge
of well-defined risk factors as tools to inform and instruct
patients. Orienting patients about risk factors that have already been established is essential. Many factors have been
discussed in literature, but there is still the need for further
studies to explain the role of each of those factors on the formation of lymphatic anastomoses, on lymphatic compensations and on the subsequent incidence of lymphedema.
References
1.
2.
International Society of Limphology. The diagnosis and treatment of peripheral lymphedema. Consensus document of the
International Society of Lymphology. Lymphology. 2003;36:84-91.
Soran A, D’angelo G, Begovic M, et al. Breast cancer-related lymphedema – what are the significant predictors and how they affect
the severity of lymphdema? Breast J. 2006;12:536-43.
3.
Szuba A, Shin WS, Strauss W, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema.
J Nucl Med. 2003;44:43-57.
4.
Petrek JA, Heelan MC. Incidence of breast carcinoma-related
lymphedema. Cancer. 1998;83(12 Suppl American):2776-81.
5.
McCredie MR, Dite GS, Porter L, et al. Prevalence of self-reported arm morbidity following treatment for breast cancer in the
Australian Breast Cancer Family Study. Breast. 2001;10:515-22.
6.
7.
Duff M, Hill AD, McGreal G, Walsh S, McDermott EW, O’Higgins
NJ. Prospective evaluation of the morbidity of axillary clearance for
breast cancer. Br J Surg. 2001;88:114-7.
Kwan W, Jackson J, Weir LM, Dingee C, McGregor G, Olivotto
IA. Chronic arm morbidity after curative breast cancer
J Vasc Bras 2010, Vol. 9, Nº 4
237
treatment: prevalence and impact on quality of life. J Clin Oncol.
2002;20:4242-8.
8.
Bergmann A, Mattos IE, Koifman RJ. Diagnótico do linfedema:
análise dos métodos empregados na avaliação do membro superior após linfadenectomia axilar para tratamento do câncer de
mama. Rev Bras Cancerol. 2004;50:311-20.
9.
Warren AG, Brorson H, Borud LJ, Slavin SA. Lymphedema: a comprehensive review. Ann Plast Surg. 2007;59:464-72.
10. Rezende LF, Pedras FV, Ramos CD, Gurgel MSC. Avaliação das
compensações linfáticas no pós-operatório de câncer de mama
com dissecção axilar através da linfocintilografia. J Vasc Bras.
2008;7:370-5.
11. Brennan MJ, DePompolo RW, Garden FH. Focused review: postmastectomy lymphedema. Arch Phys Med Rehabil. 1996,77(3
Suppl):S74-80.
12. Bernas MJ, Witte CL, Witte MH; International Society of
Lymphology Executive Committee. The diagnosis and treatment
of peripheral lymphedema: draft revision of the 1995 Consensus
Document of the International Society of Lymphology Executive
Committee for discussion at the September 3-7, 2001, XVIII
International Congress of Lymphology in Genoa, Italy. Lymphology.
2001;34:84-91.
13. Camargo M, Marx A. Reabilitação física no câncer de mama. São
Paulo: Roca; 2000.
14. Burt J, White G. Lymphedema. In: Burt J, White G. Lymphedema: a
breast cancer patient’s guide to prevention and healing. New York:
Hunter House Publishers; 1999; p. 2-23.
15. Aboul-Enein A, Eshmawy I, Arafa S, Abboud A. The role of lymphovenous communication in the development of postmastectomy lymphedema. Surgery. 1984;95:562-6.
16. Herd-Smith A, Russo A, Muraca MG, Del Turco MR, Cardona G.
Prognostic factors for lymphedema after primary treatment of
breast carcinoma. Cancer. 2001;92:1783-7.
17. Hayes SC, Janda M, Cornish B, Battistutta D, Newman B.
Lymphedema after breast cancer: incidence, risk factors, and effect
on upper body function. J Clin Oncol. 2008,26:3536-42.
18. Pain SJ, Vowler S, Purushotham AD. Axillary vein abnormalities
contribute to development of lymphoedema after surgery for
breast cancer. Br J Surgery. 2005,92:311-15.
19. Johansson K, Ohlsson K, Ingvar C, Albertsson M, Ekdahl C. Factors
associated with the development of arm lymphedema following breast cancer treatment: a match pair case-control study.
Lymphology. 2002;35:59-71.
20. Ozaslan C, Kuru B. Lymphedema after treatment of breast cancer.
Am J Surg. 2004;187:69-72.
21. Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL. Arm edema
in breast cancer patients. J Natl Cancer Inst. 2001;93:96-111.
22. Purushotham AD, Bennett Britton TM, Klevesath MB, Chou P,
Agbaje OF, Duffy SW. Lymph node status and breast cancer-related lymphedema. Ann Surg. 2007;246:42-45.
23. Meeske KA, Sullivan-Halley J, Smith AW, McTiernan A,
Baumgartner KB, Harlan LC, et al. Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White
women. Breast Cancer Res Treat. 2009;113:383-91.
238
J Vasc Bras 2010, Vol. 9, Nº 4
24. Rett MT, Lopes MCA. Fatores de risco relacionados ao linfedema.
Rev Bras Mastologia. 2002;12:39-42.
25. Park JH, Lee WH, Chung HS. Incidence and risk factors of breast
cancer lymphoedema. J Clin Nurs. 2008;17:1450-59.
26. Nielsen I, Gordon S, Selby A. Breast cancer-related lymphoedema
risk reduction advice: a challenge for health professionals. Cancer
Treat Rev. 2008;34:621-8.
27. Ellis S. Structure and function of the lymphatic system: an overview. The Lymphoedema Supplement. Br J Community Nurs.
2006;11(4 Suppl):S4-S6.
28. Petrek JA, Senie RT, Peters M, Rosen PP. Lymphedema in a cohort
of breast carcinoma survivors 20 years after diagnosis. Cancer.
2001,92:1368-77.
29. Pain SJ, Purushotham AD, Barber RW, Ballinger JR, Solanki CK,
Mortimer PS, et al. Variation in lymphatic function may predispose
to development of breast cancer-related lymphoedema. Eur J Surg
Oncol. 2004,30:508-14.
30. Bergmann A, Mattos IE, Kofman RJ. Fatores de risco para linfedema
após câncer de mama: uma revisão da literatura. Fisioter pesqui.
2008,15:207-13.
Lymphedema risk factors and breast cancer PO - Rezende LF et al.
31. Freitas Jr R, Ribeiro LFJ, Taia L, Kajita D, Fernandes MV, Queiroz GS.
Linfedema em pacientes submetidos à mastectomia radical modificada. Rev Bras Ginecol Obstet. 2001;23:205-8.
32. Guedes Neto HJ, Kupsinskas Junior AJ, Stuart S, Barbosa EM,
Bacarat FF. Considerações sobre linfedema pós-mastectomia. Cir
Vasc Angiol. 1995;11:107-10.
33. Campisi C, Michelini S, Boccardo F. Guidelines of the Societá
Italiana di Linfangiologia. Lymphology. 2004;37:182-4.
Correspondence:
Laura Ferreira de Rezende Franco
Largo Engenheiro Paulo de Almeida Sandeville, 15 – Santo André
CEP 13870-000 – São João da Boa Vista (SP), Brazil
E-mail: [email protected]
Authors’ contribution:
Study conception and design: LFR
Data analysis and interpretation: LFR, AVRR and CSG
Data collection: LFR, AVRR and CSG
Writing: LFR, AVRR and CSG
Critical analysis: LFR
Final text approval *: LFR, AVRR and CSG
* All authors have read and approved the final version of the paper submitted
to the J Vasc Bras.