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. Author manuscript; available in PMC: 2015 Jan 9.
Published in final edited form as: J Vasc Surg. 2014 Sep;60(3):639–644. doi: 10.1016/j.jvs.2014.03.237

Preoperative symptom type influences the 30-day perioperative outcomes of carotid endarterectomy and carotid stenting in the Society for Vascular Surgery Vascular Registry

Patrick J Geraghty a, Thomas E Brothers b, David L Gillespie c, Gilbert R Upchurch d, Michael C Stoner e, Flora S Siami f, Christopher T Kenwood f, Philip P Goodney g
PMCID: PMC4287967  NIHMSID: NIHMS652335  PMID: 25154963

Abstract

Objective

The objective of this study was to determine the effect of presenting symptom types on 30-day periprocedural outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in contemporary vascular practice.

Methods

Retrospective review was undertaken of the Society for Vascular Surgery Vascular Registry database subjects who underwent CEA or CAS from 2004 to 2011. Patients were grouped by discrete 12-month preprocedural ipsilateral symptom type: stroke, transient ischemic attack (TIA), transient monocular blindness (TMB), or asymptomatic (ASX). Risk-adjusted odds ratios (ORs) were used to compare the likelihood of the 30-day outcomes of death, stroke, and myocardial infarction (MI) and the composite outcomes of death + stroke and death + stroke + MI.

Results

Symptom type significantly influences risk-adjusted 30-day outcomes for carotid intervention. Presentation with stroke predicted the poorest outcomes (death + stroke + MI composite: OR, 1.3; 95% confidence interval [CI], 0.83–2.03 vs TIA; OR, 2.56; 95% CI, 1.18–5.57 vs TMB; OR, 2.12; 95% CI, 1.46–3.08 vs ASX), followed by TIA (death + stroke + MI composite: OR, 1.97; 95% CI, 0.91–4.25 vs TMB; OR, 1.63; 95% CI, 1.14–2.33 vs ASX). For both CAS and CEA patients, presentation with stroke or TIA predicted a higher risk of periprocedural stroke than in ASX patients. Presentation with stroke predicted higher 30-day risk of death with CAS but not with CEA. MI rates were not affected by presenting symptom type. The 30-day outcomes for the TMB and ASX patient groups were equivalent in both treatment arms.

Conclusions

Presenting symptom type significantly affects the 30-day outcomes of both CAS and CEA in contemporary vascular surgical practice. Presentation with stroke and TIA predicts higher rates of periprocedural complications, whereas TMB presentation predicts a periprocedural risk profile similar to that of ASX disease.


In addition to prior completed ipsilateral stroke, hemispheric transient ischemic attack (TIA) ipsilateral to significant carotid bifurcation stenosis has long been known to predict subsequent ipsilateral stroke and excess cardiovascular mortality.1,2 In similar fashion, transient monocular blindness (TMB, also known as amaurosis fugax) associated with carotid bifurcation stenosis foretells an elevated risk of subsequent stroke, although less than that described for TIA.3

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) firmly established the benefit of carotid endarterectomy (CEA) for symptomatic moderate to severe carotid stenoses.4,5 NASCET also added to our knowledge of the natural history of symptomatic carotid disease; analysis of the medical treatment arm of NASCET demonstrated a higher 2-year risk of stroke for patients presenting with hemispheric TIA (43.5% ± 6.7%) in comparison to TMB (16.6% ± 5.6%).6 Separate examination of surgical results from NASCET showed that procedural stroke outcomes were poorer for patients presenting with hemispheric TIA rather than TMB,7 confirming the findings of earlier investigators.8

Yet even as NASCET and the Asymptomatic Carotid Atherosclerosis Study9 established the primacy of CEA for stroke reduction in symptomatic and asymptomatic lesions, early experiences with angioplasty and stent placement for carotid disease were being reported.10,11 During the next decade, carotid artery stenting (CAS) was compared with CEA in randomized trials ranging from the Stenting and Angioplasty with Protection in Patients with High Risk for Endarterectomy (SAPPHIRE) study to the more recent and better powered Carotid Revascularization Endarterectomy vs Stenting Trial (CREST).12,13 Both trials enrolled asymptomatic and symptomatic patients, and their publication has provided further insight into the comparative benefits of CAS and CEA. However, neither study examined the relationship of presenting symptom type (stroke, TIA, or TMB) to procedural outcomes.

The Society for Vascular Surgery Vascular Registry (SVS-VR) carotid module collected demographic, procedural, and outcomes data from contributing centers for CEA and CAS from 2004 through 2011. By the nature of registry design, patients entered into the SVS-VR are unmatched, yet risk-adjusted data from this “real-world” experience provide valuable insight into current vascular surgical outcomes.14 Using the SVS-VR, we sought to determine the effect of presenting symptom type on early outcomes of CEA and CAS in contemporary vascular practice.

METHODS

The derivation of 30-day periprocedural outcomes data from the SVS-VR, inclusive of procedural and predischarge data, has previously been reported.14 All registry patients who underwent CEA or CAS with available 30-day outcomes reporting were identified. For clarity of comparison, carotid procedures undertaken for atherosclerotic, radiation-induced, or restenotic lesions of the carotid bifurcation and internal carotid artery were included, but procedures undertaken for trauma, dissection, or unspecified causes were excluded. Procedures undertaken only on the common carotid or external carotid arteries were excluded. CEA and CAS patients were grouped by discrete preprocedural ipsilateral symptom type occurring within the 12 months before intervention: stroke, TIA, TMB, or asymptomatic (ASX). Patients reporting more than one symptom (eg, TIA and stroke) were excluded from analysis. Risk-adjusted odds ratios (ORs) were used to compare the likelihood of the 30-day outcomes of death, stroke, and myocardial infarction (MI) and the composite outcomes of death + stroke and death + stroke + MI.

Statistical methods

Descriptive statistical comparisons were conducted with χ2 tests for categorical variables and analysis of variance for continuous variables. Descriptive statistics are listed as mean ± standard deviation for continuous variables and percentage (frequency) for categorical variables. Outcomes analyses comparing across symptom groups were conducted in subsets of the cohort with the Fisher exact test for discrete/categorical data. Adjusted ORs found through multivariable logistic regression were used to compare the selected outcomes measures between the symptom-defined groups. Adjusted ORs for the multiple symptom group comparisons were adjusted for significant baseline factors that were retained after applying backwards elimination methods. Differences in multiple symptom group comparisons were considered significant if P < .0083 (using a Bonferroni correction factor of 6). All other differences were considered significant if P < .05. All statistical analyses were performed by New England Research Institute (NERI, Watertown, Mass) with SAS Statistical Software (Cary, NC).

All data entered into the SVS-VR are fully compliant with the Health Insurance Portability and Accountability Act regulations and are auditable. All data reports and analyses performed include only de-identified and aggregated data. NERI maintains the online database, and funding for the administration and database management of the Vascular Registry has been provided by the Society for Vascular Surgery.

RESULTS

A total of 5758 CEA procedures and 2882 CAS procedures from the SVS-VR met the specified inclusion criteria. Demographics and medical history for the exclusive presenting symptom groups (Table I) reflect the heterogeneity of these unmatched registry populations. The CAS treatment group contains higher percentages of interventions for restenosis and postradiation changes than the CEA group does (Table II), consistent with this technique’s ability to avoid the surgical challenges associated with the hostile or previously operated on neck. Unadjusted event rates for CAS and CEA procedures, delineated by presenting symptom type, are displayed in Table III. Although certain unadjusted event rates in Table III are compelling (such as the 11.6% periprocedural incidence of the composite death + stroke + MI in patients presenting with stroke who were treated with CAS), the unmatched nature of the enrolled CAS and CEA patient populations invalidates comparisons between the endovascular and surgical treatment groups.

Table I.

Demographics and medical history

Mutually exclusive symptom in last 12 months
P valuea
Stroke (n = 947) TIA (n = 1449) TMB (n = 508) ASX (n = 5736)
Age, years (range) 69.7 (29–94) 71.6 (18–98) 69.7 (47–94) 71.2 (39–95) <.0001
Gender, male (%) 61.1% (579/947) 59.8% (866/1449) 68.3% (347/508) 58.2% (3336/5736) <.0001
Race, white 87.9% (832/947) 92.8% (1344/1449) 92.7% (471/508) 93.7% (5374/5736) <.0001
Ethnicity, Hispanic 4.6% (44/947) 3.1% (45/1449) 2.8% (14/508) 3.2% (185/5736) .1100
Coronary artery disease 45.3% (429/947) 49.6% (718/1449) 47.8% (243/508) 54.4% (3121/5736) <.0001
MI 16.7% (158/947) 16.7% (242/1449) 16.9% (86/508) 19.2% (1104/5736) .0437
Valvular heart disease 6.1% (58/947) 7.5% (109/1449) 6.5% (33/508) 7.6% (438/5736) .3401
Cardiac arrhythmia 12.2% (116/947) 13.0% (188/1449) 12.8% (65/508) 14.0% (805/5736) .3684
Congestive heart failure 10.7% (101/947) 10.0% (145/1449) 9.6% (49/508) 10.0% (574/5736) .9184
Hypertension 84.6% (801/947) 83.8% (1214/1449) 76.4% (388/508) 84.7% (4861/5736) <.0001
Diabetes 36.3% (344/947) 32.2% (467/1449) 28.0% (142/508) 32.7% (1877/5736) .0118
Chronic obstructive pulmonary disease 18.0% (170/947) 19.3% (280/1449) 22.6% (115/508) 17.7% (1013/5736) .0285
Chronic renal failure 4.0% (38/947) 3.5% (50/1449) 2.0% (10/508) 3.3% (192/5736) .2294
Peripheral vascular disease 33.5% (317/947) 37.6% (545/1449) 36.0% (183/508) 43.9% (2520/5736) <.0001
Current or past smoker 59.6% (564/947) 58.5% (847/1449) 66.5% (338/508) 60.9% (3494/5736) .0120
Cancer 15.2% (144/947) 16.9% (245/1449) 19.1% (97/508) 14.2% (816/5736) .0037
Coagulopathy 1.5% (14/947) 1.4% (20/1449) 0.6% (3/508) 1.3% (72/5736) .5013
ASA grade
 ≤3 88.1% (834/947) 91.5% (1326/1449) 92.9% (472/508) 92.1% (5282/5736) .0004
 >3 11.9% (113/947) 8.5% (123/1449) 7.1% (36/508) 7.9% (454/5736)
New York Heart Association class
 ≤2 93.7% (887/947) 92.1% (1335/1449) 93.3% (474/508) 93.7% (5372/5736) .2147
 >2 6.3% (60/947) 7.9% (114/1449) 6.7% (34/508) 6.3% (364/5736)
Aspirin 79.3% (751/947) 84.9% (1230/1449) 82.9% (421/508) 84.9% (4872/5736) .0001
Clopidogrel 46.5% (440/947) 50.0% (725/1449) 51.0% (259/508) 39.0% (2235/5736) <.0001
Aspirin or clopidogrel 88.4% (837/947) 92.0% (1333/1449) 92.1% (468/508) 90.3% (5179/5736) .0146
Age ≥80 years 20.3% (192/947) 23.2% (336/1449) 18.3% (93/508) 19.5% (1117/5736) .0115
Embolic protection (CAS only) 95.8% (322/336) 97.0% (554/571) 97.9% (184/188) 98.0% (1751/1787) .0992

ASA, American Society of Anesthesiologists; ASX, asymptomatic; CAS, carotid artery stenting; MI, myocardial infarction; TIA, transient ischemic attack; TMB, transient monocular blindness.

a

P value for age was found by analysis of variance. All others found by χ2 tests.

Table II.

Distribution by exclusive presenting symptom type and etiology

Etiology Stroke, No. (%) TIA, No. (%) TMB, No. (%) ASX, No. (%) Total, No. (%)
CEA patients
 Atherosclerosis 604 862 313 3904 5683 (98.7)
 Radiation 0 1 2 3 6 (0.1)
 Restenosis 7 15 5 42 69 (1.2)
 Total 611 (10.6) 878 (15.3) 320 (5.5) 3949 (68.6) 5758 (100)
CAS patients
 Atherosclerosis 293 413 140 1202 2048 (71.1)
 Radiation 10 24 16 91 141 (5.9)
 Restenosis 33 134 32 494 693 (24.0)
 Total 336 (11.7) 571 (19.8) 188 (6.5) 1787 (62.0) 2882 (100)

ASX, Asymptomatic; CAS, carotid artery stenting; CEA, carotid endarterectomy; TIA, transient ischemic attack; TMB, transient monocular blindness.

Table III.

Unadjusted event rates by procedure and presenting symptom type

Thirty-day adverse event CAS patients
P valuea
Symptom in last 12 months (mutually exclusive)
Stroke ipsilateral (n = 336) TIA ipsilateral (n = 571) TMB ipsilateral (n = 188) ASX (n = 1787)
Death 6.3% (21/336) 1.1% (6/571) 0.5% (1/188) 1.3% (24/1787) <.0001
Stroke 8.6% (29/336) 7.9% (45/571) 3.2% (6/188) 3.2% (57/1787) <.0001
MI 1.2% (4/336) 1.2% (7/571) 1.6% (3/188) 1.1% (20/1787) .8652
Death + stroke + MI 11.6% (39/336) 9.6% (55/571) 4.8% (9/188) 4.9% (88/1787) <.0001
Death + stroke 11.0% (37/336) 8.4% (48/571) 3.2% (6/188) 4.3% (77/1787) <.0001
Thirty-day adverse event CEA patients
P valuea
Symptom in last 12 months (mutually exclusive)
Stroke ipsilateral (n = 611) TIA ipsilateral (n = 878) TMB ipsilateral (n = 320) ASX (n = 3949)
Death 1.8% (11/611) 0.8% (7/878) 0.0% (0/320) 0.8% (30/3949) .0277
Stroke 4.6% (28/611) 3.3% (29/878) 1.6% (5/320) 1.6% (64/3949) <.0001
MI 0.8% (5/611) 1.6% (14/878) 0.9% (3/320) 1.2% (49/3949) .6213
Death + stroke + MI 6.7% (41/611) 5.0% (44/878) 2.5% (8/320) 3.1% (124/3949) <.0001
Death + stroke 6.2% (38/611) 4.0% (35/878) 1.6% (5/320) 2.2% (87/3949) <.0001

ASX, Asymptomatic; CAS, carotid artery stenting; CEA, carotid endarterectomy; MI, myocardial infarction; TIA, transient ischemic attack; TMB, transient monocular blindness.

Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. The event rates in the table are per patient.

a

P values were based on Fisher exact test.

After application of the stringent risk-adjusting methods described before, multiple symptom group comparisons were conducted in bivariate fashion, illuminating the effect of presenting symptom type on each of the major periprocedural outcomes measures (Tables IV and V). Of note is that 30-day outcomes of TMB and ASX presentation are indistinguishable for both CAS and CEA patients. The significant findings from Tables IV and V regarding symptom type presentation on periprocedural adverse event outcomes measure are summarized here.

Table IV.

Risk-adjusted bivariate comparison of outcomes based on presenting symptom types within the carotid artery stenting (CAS) treatment group

Thirty-day outcome CAS: Multivariable (adjusted) logistic models
Adjusted covariates
Ipsilateral symptom
OR 95% CI P value
Comparison group Reference group
Death/stroke/MI outcome Stroke vs TIA 1.08 0.69–1.71 .7274 Controls for age, white race, diabetes, ASA grade, clopidogrel, and CPD use
vs TMB 2.03 0.95–4.37 .0689
vs ASX 2.30 1.52–3.47 <.0001a
TIA vs TMB 1.88 0.90–3.92 .0941
vs ASX 2.12 1.48–3.04 <.0001a
TMB vs ASX 1.13 0.55–2.30 .7386
Death/stroke outcome Stroke vs TIA 1.16 0.72–1.86 .5481 Controls for age, white race, diabetes, ASA grade, aspirin, clopidogrel, and CPD use
vs TMB 2.88 1.17–7.07 .0209
vs ASX 2.43 1.58–3.73 <.0001a
TIA vs TMB 2.49 1.04–5.99 .0412
vs ASX 2.10 1.43–3.08 .0002a
TMB vs ASX 0.84 0.36–1.98 .6933
Death outcome Stroke vs TIA 5.21 2.04–13.33 .0006a Controls for ASA grade, aspirin, and CPD use
vs TMB 10.03 1.32–76.25 .0259
vs ASX 3.87 2.08–7.23 <.0001a
TIA vs TMB 1.92 0.23–16.27 .5476
vs ASX 0.74 0.30–1.85 .5238
TMB ASX 0.39 0.05–2.90 .3549
Stroke outcome Stroke vs TIA 0.97 0.58–1.61 .9050 Controls for age, white race, diabetes, ASA grade, clopidogrel, and CPD use
vs TMB 2.20 0.88–5.47 .0905
vs ASX 2.59 1.60–4.18 <.0001a
TIA vs TMB 2.27 0.94–5.45 .0674
vs ASX 2.67 1.77–4.03 <.0001a
TMB vs ASX 1.18 0.50–2.79 .7102
MI outcome Stroke vs TIA 1.04 0.30–3.58 .9514 Controls for CAD
vs TMB 0.75 0.17–3.42 .7150
vs ASX 1.12 0.38–3.32 .8324
TIA vs TMB 0.73 0.19–2.84 .6461
vs ASX 1.08 0.45–2.57 .8595
TMB vs ASX 1.49 0.44–5.07 .5241

ASA, American Society of Anesthesiologists; ASX, asymptomatic; CAD, coronary artery disease; CI, confidence interval; CPD, cerebral protection device; MI, myocardial infarction; OR, odds ratio; TIA, transient ischemic attack; TMB, transient monocular blindness.

a

P < .0083 considered significant after Bonferroni correction for multiple comparisons.

Table V.

Risk-adjusted bivariate comparison of outcomes based on presenting symptom types within the carotid endarterectomy (CEA) treatment group

Thirty-day outcome CEA: Multivariable (adjusted) logistic models
Adjusted Covariates
Ipsilateral symptom
OR 95% CI P value
Comparison group Reference group
Death/stroke/MI outcome Stroke vs TIA 1.30 0.83–2.03 .2466 Controls for age, white race, CAD, diabetes, ASA grade, and aspirin use
vs TMB 2.56 1.18–5.57 .0174
vs ASX 2.12 1.46–3.08 <.0001a
TIA vs TMB 1.97 0.91–4.25 .0844
vs ASX 1.63 1.14–2.33 .0073a
TMB vs ASX 0.83 0.40–1.72 .6120
Death/stroke outcome Stroke vs TIA 1.50 0.93–2.41 .0935 Controls for ASA grade and aspirin use
vs TMB 3.85 1.50–9.91 .0052a
vs ASX 2.73 1.84–4.05 <.0001a
TIA vs TMB 2.56 0.99–6.62 .0517
vs ASX 1.82 1.22–2.72 .0035a
TMB vs ASX 0.71 0.29–1.76 .4598
Death outcome Stroke vs TIA 2.07 0.79–5.41 .1361 Controls for ASA grade and aspirin use
vs ASX 2.10 1.04–4.23 .0388
TIA vs ASX 1.01 0.44–2.32 .9796
Stroke outcome Stroke vs TIA 1.36 0.80–2.32 .2546 Controls for diabetes, TMB, and ASA grade
vs TMB 4.58 1.36–15.42 .0140
vs ASX 2.79 1.77–4.40 <.0001a
TIA vs TMB 3.36 1.01–11.17 .0478
vs ASX 2.05 1.31–3.20 .0016a
TMB vs ASX 0.61 0.19–1.98 .4113
MI outcome Stroke vs TIA 0.51 0.18–1.42 .1972 Controls for age, white race, CAD, and diabetes
vs TMB 0.84 0.20–3.55 .8098
vs ASX 0.67 0.27–1.71 .4041
TIA vs TMB 1.65 0.47–5.83 .4346
vs ASX 1.33 0.73–2.43 .3584
TMB vs ASX 0.80 0.25–2.61 .7156

ASA, American Society of Anesthesiologists; ASX, asymptomatic; CAD, coronary artery disease; CI, confidence interval; MI, myocardial infarction; OR, odds ratio; TIA, transient ischemic attack; TMB, transient monocular blindness.

a

P < .0083 considered significant after Bonferroni correction for multiple comparisons.

Composite outcome: Death + stroke + MI

For both CAS and CEA treatment groups, stroke or TIA presentation predicted a higher risk of this composite outcome than ASX presentation.

Composite outcome: Death + stroke

For both CAS and CEA treatment groups, stroke or TIA presentation predicted a higher risk than ASX presentation.

Individual components of the composite outcomes

Death

In the CAS treatment group only, stroke presentation predicted a higher risk than TIA or ASX presentation.

Stroke

For both CAS and CEA treatment groups, stroke or TIA presentation predicted a higher risk than ASX presentation, as was reflected in the composite outcomes.

MI

No effect of presenting symptom type was noted on this outcome.

DISCUSSION

These data challenge practitioners to reconsider whether the binary classification of carotid lesions as either “asymptomatic” or “symptomatic” oversimplifies a more complex spectrum of disease. Our analyses demonstrate that specific presenting symptom types are powerful predictors of 30-day outcomes for CEA and CAS. In particular, the broad umbrella of symptomatic carotid disease encompasses several presenting symptoms with widely divergent perioperative risk profiles. Familiarity with these additional prognostic factors may allow clinicians to better counsel patients about treatment options and expected outcomes.

Are these expected outcomes broadly applicable to the multiple specialties that engage in performance of CEA and CAS? In their recent analysis of CREST, Timaran et al15 demonstrated that vascular surgeon outcomes were statistically similar to those generated by other participating specialties. Thus, although vascular surgeons represent the majority of clinicians entering patient data into the SVS-VR, we expect that the influence of presenting symptom type on periprocedural outcomes would be a durable finding, regardless of the physician operator.

There are weaknesses of this study that deserve mention. The cohort of patients presenting with TMB (n = 508) is less well powered than in the other study groups, relatively limiting the strength of bivariate comparisons in those instances. The SVS-VR data are self-reported, with inherent potential for bias. In addition, the CEA and CAS patient groups are unmatched, and thus direct comparisons between such cohorts must be conducted with caution, even after concerted efforts at risk adjustment. For that reason, we have primarily sought to identify the prognostic significance of symptom type within the separate CAS and CEA treatment groups and limited comparisons between the therapeutic modalities. Longer term outcomes data would be desirable, but beyond the 30-day perioperative period, the SVS-VR data collection for carotid subjects becomes attenuated.

With regard to risk adjustment techniques, we strove to maximally risk adjust these populations before engaging in bivariate comparisons (Tables IV and V). The rationale for not using a cerebral protection device (CPD) is often not found within the SVS-VR. Thus, the reviewer cannot reliably determine whether failure to use a CPD was secondary to the elective choice of the interventionalist or due to anatomic constraints that rendered CPD use impossible. Of the 2882 CAS procedures examined, 71 (2.5%) did not use a CPD. The refusal or inability to use a CPD was associated with higher risk of stroke (11.3% vs 4.6 % with CPD use; P = .009). As we could not be certain whether CPD nonuse was elective or mandated by anatomy, we chose to risk adjust for CPD use in these analyses; that decision may have introduced bias favoring the outcomes of CAS. In light of the higher adverse event rates seen when CPDs were not used for CAS, CEA should be preferentially employed when this constraint is anticipated.

Acknowledgments

The analysis of the Society for Vascular Surgery Vascular Registry carotid data set was supported exclusively by funds from the Society for Vascular Surgery.

The authors would like to express their gratitude to Sarah Murphy of the Society for Vascular Surgery for her assistance throughout this project and would also like to thank the other members of the Society for Vascular Surgery Outcomes Committee, including Rodney White, MD (Chair), Ellen Dillavou, MD, David Gillespie, MD, Jeffrey Jim, MD, Nicholas Osborne, MD, and Joseph Ricotta, MD.

Footnotes

Author conflict of interest: none.

Presented during the Plenary and Peripheral Vascular Surgery Society Program at the2013 Vascular Annual Meeting of the Society for Vascular Surgery, San Francisco, Calif, May 30–June 1, 2013.

The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.

AUTHOR CONTRIBUTIONS

Conception and design: PJG, PPG

Analysis and interpretation: PJG, PPG, FS, CK

Data collection: FS, CK

Writing the article: PJG, TB, DG, GU, MS, FS, CK, PPG

Critical revision of the article: PJG, TB, DG, GU, MS, FS, CK, PPG

Final approval of the article: PJG, TB, DG, GU, MS, FS, CK, PPG

Statistical analysis: FS, CK

Obtained funding: PJG, PPG

Overall responsibility: PJG

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