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Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study

Open ArchivePublished:April 20, 2021DOI:https://doi.org/10.1016/j.ejvs.2021.03.004

      Objective

      There are no recommendations for screening for thoracic aortic aneurysms (TAAs), even in patients with infrarenal abdominal aortic aneurysms (AAAs). The aims of this study were to determine the prevalence of TAAs in patients with AAAs and to analyse the risk factors for this association.

      Methods

      This was a multicentre prospective study. The Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study included 331 patients with infrarenal AAAs > 40 mm between September 2012 and May 2016. These patients were prospectively enrolled in three French academic hospitals.

      Results

      Patients were classified as having a normal, aneurysmal, or ectatic (non-normal, non-aneurysmal) thoracic aorta according to their maximum aortic diameter indexed by sex, age, and body surface area. Thoracic aortic ectasia (TAE) was defined as above or equal to the 90th percentile of normal aortic diameters according to gender and body surface area. Descending TAA was defined as ≥ 150% of the mean normal value, and ascending TAA as > 47 mm in men and 42 mm in women; 7.6% (n = 25) had either an ascending (seven cases; 2.2%) or descending aortic TAA (18 cases; 5.4%), and 54.6% (n = 181) had a TAE. Among the 25 patients with TAAs, five required surgery; two patients had TAAs related to penetrating aortic ulcers < 60 mm in diameter, and three had a TAA > 60 mm. In the multinomial regression analysis, atrial fibrillation (AF) (odds ratio [OR] 11.36, 95% confidence interval [CI] 2.18 – 59.13; p = .004) and mild aortic valvulopathy (OR 2.89, 1.04–8.05; p = .042) were independent factors associated with TAAs. Age (OR 1.06, CI 1.02 – 1.09; p = .003) and AF (OR 4.36, 1.21 – 15.61; p = .024) were independently associated with ectasia.

      Conclusion

      This study confirmed that TAAs coexisting with AAAs are not rare, and one fifth of these TAAs are treated surgically. Systematic screening by imaging the whole aorta in patients with AAAs is clinically relevant and should lead to an effective prevention policy.

      Graphical abstract

      Keywords

      Few retrospective studies in the literature address the question of the association between infrarenal abdominal aortic aneurysm and thoracic aortic aneurysm. To answer this question, the first prospective multicentre cohort with a new classification of thoracic aortic aneurysm based on gender, age, and body surface area that takes into account thoracic aortic ectasia as a distinct anatomical status was assembled. A prevalence of 7.6% was observed for thoracic aortic aneurysms in patients with asymptomatic abdominal aortic aneurysms > 40 mm, with a higher prevalence in women (13.6%) than men (7.1%).

      Introduction

      The Centers for Disease Control and Prevention (CDCP) have reported that thoracic and abdominal aortic aneurysms are the 15th leading cause of death in individuals aged > 55 years and the 19th leading cause of death overall.
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      These data have led to the introduction of AAA oriented screening for men between 65 and 75 years old and men or women over the age of 50 who have a family history of AAA in accordance with European and Haute Autorité de Santé (HAS) recommendations.
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      there is currently no recommendation to screen for descending TAAs, even in patients with AAAs. TAAs are estimated to be three to four times less frequent than AAAs, with an incidence, especially for the descending thoracic aorta, between 4 and 10.4 per 100 000 person years.
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      However, this incidence is probably an underestimation because of the absence of a screening policy.
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      the computed tomography (CT) scan remains the gold standard. Thus, TAA screening in general population would not be cost effective in healthcare policy.
      In the literature, the proportion of patients with an AAA associated with a TAA is between 10% and 28% in retrospective studies, depending on the descending TAA definition and on the population’s characteristics.
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      Moreover, TAAs are asymptomatic in > 95% of cases, meaning that most TAAs remain undetected unless discovered incidentally; thus, their true incidence is difficult to estimate.
      The Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study is a multicentre prospective study whose principal aim was to describe the prevalence of TAAs in patients presenting with an asymptomatic AAA. The secondary aims were to describe the demographic risk factors for this association.

      Materials and methods

      Ethics and funding

      All patients included in this study were informed regarding the use of their data for clinical research, and written informed consent was obtained from all patients. This study was approved by a French national ethics committee. Inter-regional and institutional funding was received from the state through regional health agencies. The clinical trial registration for this study is NCT 01599533.

      Study design

      The ACTA study (Fig. 1) included three academic hospitals in southern France (Marseille, Nice, Toulouse) and began in 2012. The study recruited a prospective observational cohort of patients with degenerative asymptomatic infrarenal AAAs > 40 mm. The primary endpoint was the prevalence of TAAs associated with AAAs. The secondary endpoints were the analysis of demographic risk factors for TAAs and thoracic aortic ectasia (TAE). The number of patients to be included was calculated based on the primary endpoint. According to the hypothesis of 15% prevalence (based on 28.2% in the Larsson study
      • Larsson E.
      • Vishnevskaya L.
      • Kalin B.
      • Granath F.
      • Swedenborg J.
      • Hultgren R.
      High frequency of thoracic aneurysms in patients with abdominal aortic aneurysms.
      and the more selective criteria for descending TAA in this current study) and a precision of 5%, the number of patients to be enrolled was calculated as 196. It was decided to increase this number to improve the statistical power for secondary endpoints and to ensure the validity of the conclusions.
      Figure 1
      Figure 1Flowchart of the Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study. A total of 415 patients were screened for having an abdominal aortic aneurysm (AAA) > 40 mm and 344 were included. Frequencies are expressed with regard to the number of patients screened. Frequencies of NTA (normal thoracic aorta), TAE (thoracic aortic ectasia) and TAA (thoracic aortic aneurysm) phenotypes are expressed with regard to the number of patients analysed.
      All patients underwent follow up according to European standard healthcare practices.
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      • Boileau C.
      • Bossone E.
      • Bartolomeo R.D.
      • Eggebrecht H.
      • et al.
      2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC).

      Population

      All patients with an infrarenal AAA > 40 mm who were referred to a vascular surgery unit in three French academic hospitals between September 2012 and June 2016 were prospectively screened to be included in the study.
      Aortic rupture, aortic dissection, and thoraco-abdominal, mycotic, or inflammatory aneurysms were exclusion criteria. Patients with severe aortic valve disease (grade III or IV aortic stenosis or insufficiency)
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      • Brochet E.
      • Chauvel C.
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      • Cormier B.
      • et al.
      Update of the French Society of Cardiology recommendations on indications for Doppler echocardiography published in 1999.
      or a bicuspid aortic valve, patients with connective tissue diseases (including Marfan and related syndromes), and patients with a history of aortic surgery were excluded from the study. The ACTA study is a part of a larger research project (Supplementary Figure 1) involving biological marker analysis. Patients with acute cardiovascular events (e.g., stroke, myocardial infarction, pulmonary embolism, limb ischaemia) or health conditions influencing the interpretation of biological markers (e.g., cancer, infection) were excluded.

      Data collection

      Baseline data for each patient included clinical, biological, and radiological assessments. Patient data in each centre were evaluated by a multidisciplinary team (including a vascular surgeon, radiologist and cardiologist).
      Clinical and biological assessments were standardised. Epidemiological data (age, sex, body mass index [BMI], smoking habit, tobacco quantity); comorbidities (hypertension defined as systolic blood pressure > 140 mmHg or antihypertensive therapy, diabetes mellitus, hypercholesterolemia, moderate renal insufficiency defined as a creatinine clearance Modification of Diet in Renal Disease [MDRD] value between 30 and 60 mL/min/1.73 m2, chronic obstructive pulmonary disease [chronic bronchodilator treatment and/or airflow limitation measured by spirometry], atrial fibrillation, or mild aortic valvulopathy [defined as grade I or II aortic stenosis or insufficiency]); medical history (peripheral arterial aneurysm, peripheral artery disease surgery, family history of AAA/TAA), and AAA size were recorded. Fasting blood samples were collected at the initial visit, and the following biological parameters were analysed: creatine, C reactive protein, HbA1c, lipids (triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein), and thrombotic biomarkers (D dimers, fibrinogen, prothrombin time, partial thromboplastin time, and blood count).
      The radiological assessment included a CT scan of the whole aorta. The cardiological assessment included an electrocardiogram, a cardiac transthoracic Doppler ultrasound, and an abdominal Doppler ultrasound.

      Definitions of the anatomy of the thoracic aorta and patient classification

      Patients were classified according to the anatomical status of their thoracic aorta as normal (NTA), ectatic (TAE), or aneurysmal (TAA), in reference to the maximum thoracic diameter (Fig. 2).
      Figure 2
      Figure 2New definitions for normal (NTA), ectatic (TAE) and aneurysmal (TAA) thoracic aortas according to the aortic segments, age, sex and body surface area (BSA) in m2. Data from Rogers et al.
      • Rogers I.S.
      • Massaro J.M.
      • Truong Q.A.
      • Mahabadi A.A.
      • Kriegel M.F.
      • Fox C.S.
      • et al.
      Distribution, determinants, and normal reference values of thoracic and abdominal aortic diameters by computed tomography (from the Framingham Heart Study).
      .

      Normal thoracic aorta

      The definition of NTA was based on the recent nomogram published by Rogers et al., who defined the mean diameter of each thoracic aortic segment depending on each person’s sex, age and body surface area (BSA: Boyd’s Formula = 0.0003207 × [Weight] 0.7285–0.0188 × log [Weight] × [Height] 0.3).
      • Rogers I.S.
      • Massaro J.M.
      • Truong Q.A.
      • Mahabadi A.A.
      • Kriegel M.F.
      • Fox C.S.
      • et al.
      Distribution, determinants, and normal reference values of thoracic and abdominal aortic diameters by computed tomography (from the Framingham Heart Study).
      For ascending aorta (AA) and descending aorta (DA), NTA was defined as measuring ≤ the 90th percentile.

      Thoracic aortic aneurysm

      For the DA, TAA was defined as ≥ 150% of the mean normal value as recommended in guidelines,
      • Hiratzka L.F.
      • Bakris G.L.
      • Beckman J.A.
      • Bersin R.M.
      • Carr V.F.
      • Casey Jr., D.E.
      • et al.
      2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.
      considering age, sex, and BSA, based on Rogers’s nomogram.
      • Rogers I.S.
      • Massaro J.M.
      • Truong Q.A.
      • Mahabadi A.A.
      • Kriegel M.F.
      • Fox C.S.
      • et al.
      Distribution, determinants, and normal reference values of thoracic and abdominal aortic diameters by computed tomography (from the Framingham Heart Study).
      For the AA, international guidelines recommended biannual monitoring of the AA when its diameter is > 45 mm.
      • Hiratzka L.F.
      • Bakris G.L.
      • Beckman J.A.
      • Bersin R.M.
      • Carr V.F.
      • Casey Jr., D.E.
      • et al.
      2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.
      Based on Rogers’s nomogram, cut off values for ascending TAA (> 150% of the mean) would have been over this recommended threshold (> 55 – 57.5 mm for men, > 50 – 52.7 mm for women), and consequently relevant only for elective surgery decision but not for the ascending TAA monitoring in clinical practice. Thus, the cut off values considering only sex were as previously published by Wanhainen et al. in a population of 70 year olds: AA > 47 mm for men, and AA > 42 mm for women.
      • Wanhainen A.
      • Themudo R.
      • Ahlstrom H.
      • Lind L.
      • Johansson L.
      Thoracic and abdominal aortic dimension in 70-year-old men and women – a population-based whole-body magnetic resonance imaging (MRI) study.

      Thoracic aortic ectasia

      TAE was defined as a non-normal and non-aneurysmal aorta, namely any aortic diameter ranging between the upper limit of NTA and the lower limit of TAA.
      This new classification was compared taking into account age, sex, and BSA with the classification based on sex specific criteria used by Larsson et al. to define TAA of the DA (> 33 mm for women, and > 37 mm for men).
      • Larsson E.
      • Vishnevskaya L.
      • Kalin B.
      • Granath F.
      • Swedenborg J.
      • Hultgren R.
      High frequency of thoracic aneurysms in patients with abdominal aortic aneurysms.
      A penetrating aortic ulcer (PAU) was defined as ulceration of an atheromatous plaque that extends deeply through the intima and into the aortic media.

      Radiological analysis

      A 64 multidetector CT scan (GE Medical Systems) was performed. For all patients, a three phase CT scan was performed with bolus tracking and then a portal phase. All CT scans were analysed by a cardiovascular imaging specialised radiologist on dedicated three dimensional imaging software (Osirix®, Pixmeao, Geneva, Switzerland). Diameter measurements were performed on the perpendicular axis according to the centreline using a semi-automated centreline algorithm. The thoracic aortic analysis was not blinded to the presence of AAA. Maximum aortic diameters were measured at different levels: AA, arch, DA, visceral segment of the aorta and abdominal aorta.
      The volume of the whole thoracic aorta was measured by semi-automatic segmentation using Osirix®.
      To assess the interobserver variability of the aortic diameter and volume measurements a random sample of 50 patients was analysed by a second radiologist.
      The interobserver intraclass correlation coefficient for aortic diameter measurements was greater than 0.97, with an average difference of 0.5 mm between readers across the measurements. No difference in patient classification was found.
      The interobserver intraclass correlation coefficient for aortic volumes measurements was greater than 0.86.
      Cardiac transthoracic echography analysis was performed to evaluate left ventricular systolic function, aortic valve function and maximum aortic diameters at the sinus of Valsalva, at the sinotubular junction and at the AA in the parasternal long axis view.

      Statistical analysis

      All analyses were performed using the Statistical Package for Social Sciences software, version 20 (SPSS, IBM Corporation, USA). Means and standard deviations are used to describe continuous variables; categorical variables are presented as numbers and frequencies.

      Primary endpoints: study prevalence

      According to the thoracic status, three groups were described: patients with TAA, patients with NTA and patients with TAE. Their prevalence values are presented as numbers and percentage.

      Secondary endpoints: risk factors associated with thoracic aortic disease

      A comparative analysis of these three groups of patients (NTA, TAE and TAA) was conducted.
      A univariable analysis was performed first using Fisher’s exact or χ2 tests for categorical variables. For continuous variables, normality was assessed by the Kolmogorov-Smirnov test. Analysis of variance or Kruskal–Wallis test were used to compare variables with a normal and non-normal distribution respectively.
      A multivariable analysis was performed using a multinomial logistic regression. The group of patients with an NTA was used as a reference. All variables with p < .20 in the univariable analysis were included in the multivariable analysis.
      All statistical tests were two tailed, and p < .050 was considered statistically significant.

      Results

      Description of the population

      A total of 415 patients were screened for having an AAA > 40 mm, and 344 were included. The thoracic aorta was not assessed in 13 patients, and these patients were excluded from the study (Fig. 1). In total, 331 patients were analysed.
      The demographic data are presented in Table 1.
      Table 1Baseline characteristics. Epidemiological and clinical data of the Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study population of 331 patients with a >40 mm infrarenal abdominal aortic aneurysm
      VariablesPatients (n = 331)
      Epidemiology
       Age – y72.3 ± 7.8
       Female22 (6.6)
       BMI – kg/m226.7 ± 3.8
      Smoking behaviour
      Never45 (13.6)
      Past181 (54.7)
      Current105 (31.7)
      Past or current286 (86.4)
      Heart
       Atrial fibrillation28 (8.5)
       Myocardial infarction78 (23.6)
      Mild aortic valvulopathy112 (33.8)
      Aortic insufficiency102 (30.8)
      Aortic stenosis10 (3.0)
      Vascular
       Peripheral arterial aneurysms85 (25.7)
       Peripheral artery disease surgery53 (16.0)
       Stroke40 (12.1)
      Others
       Hypertension252 (76.1)
       Diabetes mellitus54 (16.3)
       Hypercholesterolemia236 (71.3)
       Moderate renal insufficiency92 (27.9)
       COPD52 (15.7)
      Heredity
       Family history of AAAs28 (8.5)
       Family history of TAAs1 (0.3)
       Hereditary atherosclerosis57 (17.2)
      Abdominal aorta
       Infrarenal aortic mean diameter – mm52.9 ± 9.2
      Data are presented as n (%) or mean ± standard deviation. BMI = body mass index; COPD = chronic obstructive pulmonary disease; AAA = abdominal aortic aneurysm; TAA = thoracic aortic aneurysm.

      Prevalence of TAAs and aortic phenotypes in the AAA population

      Of the 331 patients with AAAs > 40 mm, 54.6% (181/331) had TAE, and 7.6% (25/331) had TAAs. Of the 25 patients with TAAs, seven (2.1%) had an ascending TAA, and 18 (5.4%) had a descending TAA (Table 2). Thoracic PAUs were diagnosed in 2.4% (8/331) of patients. Of the 181 TAEs, three were only on the AA; 162, on the DA; and 16, on both the ascending and the descending thoracic aorta.
      Table 2Repartition of the status of thoracic aorta according to the aortic segments in the Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study population of 331 patients
      Patients with a normal thoracic aorta are indicated in green (n = 125; 37.8%). Patients with at least one thoracic aortic segment with an ectasia and without any thoracic aortic aneurysm are indicated in yellow (n = 181; 54.7%). Patients with at least one aneurysmal thoracic aortic segment are indicated in orange (n = 25; 7.6%).
      Ascending aortaDescending Aorta
      NormalEctasiaAneurysmTotal
      Normal125 (37.8)162 (48.9)16 (4.8)303 (91.5)
      Ectasia3 (0.9)16 (4.8)2 (0.6)21 (6.1)
      Aneurysm0 (0.0)7 (2.1)0 (0)7 (2.1)
      Total128 (38.7)185 (55.9)18 (5.4)331 (100)
      Data are presented as n (%).
      Patients with a normal thoracic aorta are indicated in green (n = 125; 37.8%). Patients with at least one thoracic aortic segment with an ectasia and without any thoracic aortic aneurysm are indicated in yellow (n = 181; 54.7%). Patients with at least one aneurysmal thoracic aortic segment are indicated in orange (n = 25; 7.6%).
      On the AA, TAA in women (n = 2) measured 44.5 mm (44.0 – 45.0) (median [min – max]) and in men 48.0 mm (48.0 – 52.0) (n = 5). On the DA, TAA in women (n = 2) measured 56.0 mm (54.0 – 58.0) and in men 50.8 mm (44.0 – 71) (n = 16).
      Whole thoracic aortic volumes were significantly different in the three thoracic aortic status groups (p < .001; mean NTA volume: 235.2 mL ± 36.3, mean TAE volume: 286.5 mL ± 56.5, mean TAA volume: 413.6 mL ± 113.2).
      Among the 25 patients with TAAs, five were treated within an average of 20.6 ± 11.8 months. Two patients presented with a PAU, and three presented with a TAA > 60 mm in diameter. Locations of these TAAs were on the descending thoracic aorta in four cases and on the AA in one case. All these patients treated for TAA did not meet the indications for AAA treatment (abdominal aortic diameter < 55 mm).
      The rates of TAE and TAAs were 63.6% (14/22) and 18.2% (4/22) respectively in women, compared with 47.2% (146/309) and 7.1% (22/309) respectively in men (Table 3).
      Table 3Univariable analysis of the epidemiological and clinical data for thoracic status of the 331 patients with a >40 mm abdominal aortic aneurysm participating in the Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study
      NTA (n = 125)TAE (n = 181)TAA (n = 25)p
      Epidemiology
       Age – y69.8 ± 7.673.6 ± 7.475.4 ± 8.6<.001
       Female4 (3.2)14 (7.7)4 (16.0).040
       BMI – kg/m227.1 ± 3.926.5 ± 3.626.4 ± 4.8.41
      Smoking behaviour.16
      Never11 (8.8)29 (16.0)5 (20)
      Past71 (56.8)100 (55.2)10 (40)
      Current43 (34.4)52 (28.8)10 (40)
       Tobacco quantity – pack-year39.2 ± 27.240.5 ± 32.141.5 ± 35.1.90
      Heart
       Atrial fibrillation3 (2.4)20 (11.0)5 (20.0).001
       Mild Aortic valvulopathy29 (23.2)70 (38.7)13 (52.0).001
      Vascular
       Peripheral arterial aneurysm31 (24.8)48 (26.5)6 (24).93
       Peripheral artery disease surgery26 (20.8)24 (13.3)3 (12).16
      Other
       Hypertension94 (75.2)141 (77.9)17 (68.0).49
       Diabetes Mellitus26 (20.8)24 (13.3)4 (16.0).20
       Hypercholesterolemia91 (72.8)126 (69.6)18 (72.0).73
       Moderate renal insufficiency26 (21.0)56 (30.9)13 (52.0).060
       COPD18 (14.4)31 (17.1)4 (16.0).84
      Heredity
       Family history of AAA12 (9.6)15 (8.3)1 (4.0).75
      Abdominal aortic aneurysm diameter
       Abdominal aortic aneurysm diameter – mm52.4 ± 8.253.2 ± 9.554.1 ± 10.1.56
      Data are presented as n (%) or mean ± standard deviation. NTA = normal thoracic aorta; TAE = thoracic aortic ectasia; TAA = thoracic aortic aneurysm; COPD = chronic obstructive pulmonary disease.

      Demographic risk factors associated with the thoracic status

      Patients without thoracic aortic disease were compared with patients with TAAs and to patients with TAE, through univariable and multivariable analyses (Table 3).
      In the univariable analysis, TAAs and TAE were statistically associated with older age, female gender, atrial fibrillation (AF) and mild aortic valvulopathy.
      In the multivariable analysis, the presence of AF (p = .001) and mild aortic valvulopathy (p < .001) were independent factors associated with TAAs. Age (p = .006) and AF (p = .023) were independent factors associated with ectasia (Table 4).
      Table 4Multivariable analysis of risk factors for thoracic status in the 331 patients with a > 40 mm abdominal aortic aneurysm in the Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study. The patients with normal thoracic aorta was set as the reference group to express the OR (odds ratio) and 95% CI (confidence interval) of different variables for the TAE (thoracic aortic ectasia) and TAA (thoracic aortic aneurysm) classes
      VariableTAETAA
      OR (95% CI)pOR (95% CI)p
      Age – y1.057 (1.019–1.097).0041.063 (0.987–1.146).11
      Female1.308 (0.309–5.540).7154.221 (0.636–28.019).14
      Smoking behaviour
      The “Smoking behaviour” variable has three states: “never”, “past”, and “current”. “Never” was set as the reference to express the OR of “past” and “current” in the TAE and TAA groups.
       Never
       Past0.810 (0.338–1.942).6370.774 (0.148–4.038).76
       Current1.060 (0.410–2.741).9043.320 (0.579–19.026).18
      Atrial fibrillation4.208 (1.165–15.605).02811.359 (2.183–59.132).004
      Mild aortic valvulopathy1.527 (0.880–2.649).1332.892 (1.039–8.046).042
      Peripheral artery disease surgery0.621 (0.326–1.183).1480.536 (0.137–2.097).37
      Diabetes mellitus0.657 (0.338–1.257).2141.246 (0.354–4.378).73
      Moderate renal insufficiency1.368 (0.737–2.540).3211.921 (0.640–5.761).24
      Independent risk factors are depicted with p < .05.
      The “Smoking behaviour” variable has three states: “never”, “past”, and “current”. “Never” was set as the reference to express the OR of “past” and “current” in the TAE and TAA groups.

      Biological risk factors associated with thoracic status

      Standard metabolic parameters (cholesterolaemia, glycaemia, lipoprotein A) and thrombotic biomarkers were not different between the NTA, TAE, and TAA groups (Table 3).

      Comparison of TAA prevalence with “former” and “newer” classifications

      Former classification

      Sex specific criteria, published by Wanhainen et al., were used to define a TAA.
      • Wanhainen A.
      • Themudo R.
      • Ahlstrom H.
      • Lind L.
      • Johansson L.
      Thoracic and abdominal aortic dimension in 70-year-old men and women – a population-based whole-body magnetic resonance imaging (MRI) study.
      These criteria do not take into account age or BSA: AA > 42 mm and DA > 33 mm for women; and AA > 47 mm and DA > 37 mm for men, respectively.
      The TAA prevalence was 25.9% (86/331), with values of 24.3% (75/309) and 50% (11/22) in men and women, respectively.

      Newer classification taking into account age, sex, and body surface area for the descending aorta

      The TAA prevalence was 7.6%, with values of 6.7% (21/309) and 18.2% (4/22) in men and women, respectively.
      The repartition of the BSA indexed diameter of the DA was different between the three groups (Supplementary Figure 2A). A ROC curve determined 22 mm/m2 as reliable cut off value to define descending TAAs in this population (Supplementary Figure 2B) with a sensitivity and a specificity of 88.9% and 98.6% respectively.

      Discussion

      This prospective study revealed a TAA prevalence of 7.6% in patients with an asymptomatic infrarenal AAA > 40 mm in diameter, which was mainly localised in the DA.
      In the literature, the prevalence and incidence of TAAs in patients with AAAs is unclear because of the lack of both prospective data and a clear definition for these TAAs, especially those in the DA.
      • Schlosser F.J.
      • Mojibian H.
      • Verhagen H.J.
      • Moll F.L.
      • Muhs B.E.
      Open thoracic or thoracoabdominal aortic aneurysm repair after previous abdominal aortic aneurysm surgery.
      Consequently, there are currently no standard prevention programs with recommendations for imaging of the thoracic aorta in patients with AAAs.
      In public healthcare, there are two clinical challenges: (1) the diagnosis of a synchronous thoracic aortic disease (TAE or TAAs or PAUs) in the presence of a degenerative infrarenal AAA and (2) the reliable monitoring of patients at risk of a thoracic aortic event (rupture/dissection) to guide cost effective secondary prevention in an ageing population. In fact, the secondary prevention policy is actually based on “hinge points” according to various sizes for AA and DA.
      • Chau K.H.
      • Elefteriades J.A.
      Natural history of thoracic aortic aneurysms: size matters, plus moving beyond size.
      To address the usefulness of systematic thoracic aortic disease screening in the AAA population, a new classification of thoracic aortic status was proposed based on diameter according to location in either the ascending or the descending aorta, and demographic characteristics (age, gender, BSA). Previous studies defined TAAs as a non-normal aorta without considering aortic dilatation due to ageing and cardiovascular risk factors in the elderly population. Wanhainen et al. suggested a dividing line between an NTA and a TAA according to sex adjusted diameter.
      • Wanhainen A.
      • Themudo R.
      • Ahlstrom H.
      • Lind L.
      • Johansson L.
      Thoracic and abdominal aortic dimension in 70-year-old men and women – a population-based whole-body magnetic resonance imaging (MRI) study.
      Regarding these results, Larsson et al., in a retrospective study, reported a 24% prevalence of concomitant TAAs in AAA patients.
      • Larsson E.
      • Vishnevskaya L.
      • Kalin B.
      • Granath F.
      • Swedenborg J.
      • Hultgren R.
      High frequency of thoracic aneurysms in patients with abdominal aortic aneurysms.
      Without taking into account age and BSA and using the same definition as Wanhainen et al. for descending TAA, the TAA prevalence would have been overestimated as 25.9%, which is in the same range as that found by Larsson et al.
      • Larsson E.
      • Vishnevskaya L.
      • Kalin B.
      • Granath F.
      • Swedenborg J.
      • Hultgren R.
      High frequency of thoracic aneurysms in patients with abdominal aortic aneurysms.
      More recently, in another retrospective study, Chaer et al. found AAAs to be associated with synchronous TAAs in 10.8% of cases.
      • Chaer R.A.
      • Vasoncelos R.
      • Marone L.K.
      • Al-Khoury G.
      • Rhee R.Y.
      • Cho J.S.
      • et al.
      Synchronous and metachronous thoracic aneurysms in patients with abdominal aortic aneurysms.
      The prevalence of synchronous TAAs was closer to that found in the investigation, even though their study defined a TAA as a reported diameter of > 30 mm, which may have overestimated the prevalence of TAAs.
      In the study, an attempt was made to identify a higher risk population through a more discriminating definition of descending TAA. Among the TAA group, 20% required surgery in the short or midterm. These results highlight the importance of a clinically relevant definition of TAAs associated with AAAs in this elderly population in order to limit surveillance to patients at higher risk of an aortic event. While this value must be refined with larger cohorts, the data suggest a BSA indexed diameter of the DA of 22 mm/m2 as a reliable cut off value to define descending TAA in this population.
      TAA screening by a whole aorta CT scan appears to be the more relevant recommendation for selecting higher aortic risk patients in the AAA population, as TAA and TAE patients cannot be distinguished according to epidemiological characteristics. In the study, TAAs were more common in women (18.2% vs. 7.1%), as was observed by Larsson et al.,
      • Larsson E.
      • Vishnevskaya L.
      • Kalin B.
      • Granath F.
      • Swedenborg J.
      • Hultgren R.
      High frequency of thoracic aneurysms in patients with abdominal aortic aneurysms.
      who found an association between AAAs and TAAs in 48% of women vs. 23% of men. AF and mild aortic valvulopathy were also independent risk factors associated with TAA compared with NTA cases. Several studies have detailed the positive relationship between AF
      • Shaikh A.Y.
      • Wang N.
      • Yin X.
      • Larson M.G.
      • Vasan R.S.
      • Hamburg N.M.
      • et al.
      Relations of arterial stiffness and brachial flow-mediated dilation with new-onset atrial fibrillation: the Framingham Heart Study.
      and hypertension, such as that between hypertension and aortic stiffness. In addition, aortic stiffness is probably involved in the pathogenesis and/or evolution of aortic dilatation and is an independent marker of the risk of aortic rupture.
      • Jue J.
      • Boodhwani M.
      • Beauchesne L.
      • Dennie C.
      • Nagpal S.
      • Chan K.L.
      • et al.
      Greater aortic stiffness and pulsatile arterial load are associated with larger thoracic aortic aneurysm size in women.
      In the study, the independent associations between AF, mild aortic valvulopathy and a dilated aorta may indicate a more severe aortic stiffness than expected by ageing alone.
      • Greenwood S.A.
      • Mangahis E.
      • Castle E.M.
      • Wang J.
      • Campbell J.
      • Deshpande R.
      • et al.
      Arterial stiffness is a predictor for acute kidney injury following coronary artery bypass graft surgery.
      • Al-Aly Z.
      • Zeringue A.
      • Fu J.
      • Rauchman M.I.
      • McDonald J.R.
      • El-Achkar T.M.
      • et al.
      Rate of kidney function decline associates with mortality.
      • Bahous S.A.
      • Stephan A.
      • Blacher J.
      • Safar M.
      Cardiovascular and renal outcome in recipients of kidney grafts from living donors: role of aortic stiffness.
      Finally, by differentiating TAA from TAE cases, the TAAs are assumed to be at more risk of an aortic event (rupture, dissection or surgery) based on their significant difference in whole thoracic aortic volume.
      The cost effectiveness of scheduling a follow up in the TAE subgroup should be evaluated in terms of advanced age, the expected evolution profile (3 mm/year in descending TAAs), and the known risk of other cardiovascular events in AAA patients.
      • Erbel R.
      • Aboyans V.
      • Boileau C.
      • Bossone E.
      • Bartolomeo R.D.
      • Eggebrecht H.
      • et al.
      2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC).

      Limitations

      This study has limitations that could affect the external validity of this study, including (1) recruitment of patients from centres in southern France, (2) selection of patients with asymptomatic infrarenal AAA > 40 mm, without indexed diameter introducing a severity bias for women, (3) exclusion criteria related to systemic inflammation (4) lack of ethnicity report, and (5) measurement of the maximum segmental aortic diameter on the perpendicular axis according to the centreline whereas Rogers et al. reported means of axial aortic diameters at specific prespecified locations.

      Conclusion

      This prospective ACTA study demonstrates that synchronous TAAs and AAAs are not rare, and one fifth of these TAAs are treated surgically. It appears that initial imaging of the whole aorta should be indicated in this population.

      Conflict of interest

      None.

      Funding

      This study was supported by a grant obtained from the French Ministry of Health that covered the cost of the study. The sponsor had no role in the study design.

      Acknowledgements

      We thank Séverine Sauriez for her excellent technical assistance.

      Appendix A. Supplementary data

      The following are the Supplementary data to this article:

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