Research Article| Volume 65, ISSUE 3, P339-345, March 2023

Multivariable Analysis of Pre-operative Brain Atrophy as a Predictor of Long Term Mortality After Carotid Endarterectomy

Published:October 06, 2022DOI:


      Brain atrophy is associated with an increased mortality rate in elderly trauma patients and in patients treated with mechanical thrombectomy for acute ischaemic stroke. In the setting of ischaemic stroke, the association between brain atrophy and death is stronger than that of sarcopenia. It has previously been shown that lower masseter area, as a marker of sarcopenia, is linked to lower survival after carotid endarterectomy (CEA). The aim of this study was to investigate whether brain atrophy is also associated with long term mortality in patients undergoing CEA.


      A cohort of patients treated with CEA between 2004 and 2010 was retrieved from the Tampere University Hospital vascular registry and those with available pre-operative computed tomography (CT) imaging were analysed retrospectively. CT images were evaluated for brain atrophy index (BAI) and masseter muscle surface area and density. The association between BAI and mortality was investigated with Cox regression.


      Two hundred and thirty-three patients with a median (interquartile range [IQR]) age of 71 years (64.0, 77.0) were included. Most patients were operated on for symptomatic stenosis (n = 203; 87.1%). The median (IQR) duration of follow up was 115.0 months (66.0, 153.0), and 155 patients (66.5%) died during follow up. BAI was statistically significantly correlated with age (r = .489), average masseter density (r = –.202), and smoking (r = –.186; all p <.005). Increased BAI was statistically significantly associated with overall mortality (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.25 – 1.68, per one standard deviation [SD] increase) in the univariable analysis, and the association remained (HR 1.23, 95% CI 1.04 – 1.46, per one SD increase) in the multivariable models. Age, peripheral artery disease, and chronic obstructive pulmonary disease were also independently associated with mortality. The optimal cutoff value for BAI was 0.133.


      Brain atrophy independently predicts the long term post-operative mortality rate after CEA in a cohort containing mainly symptomatic patients. Future studies are needed to validate the results in prospective settings and in asymptomatic patients.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Vascular and Endovascular Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Naylor A.R.
        • Ricco J.-B.
        • de Borst G.J.
        • Debus S.
        • de Haro J.
        • Halliday A.
        • et al.
        Editor’s Choice – Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS).
        Eur J Vasc Endovasc Surg. 2018; 55: 3-81
        • AbuRahma A.F.
        • Avgerinos E.D.
        • Chang R.W.
        • Darling 3rd, R.C.
        • Duncan A.A.
        • Forbes T.L.
        • et al.
        Society for Vascular Surgery clinical practice guidelines for management of extracranial cerebrovascular disease.
        J Vasc Surg. 2022; 75: 4S-22S
        • Reed A.B.
        • Gaccione P.
        • Belkin M.
        • Donaldson M.C.
        • Mannick J.A.
        • Whittemore A.D.
        • et al.
        Preoperative risk factors for carotid endarterectomy: defining the patient at high risk.
        J Vasc Surg. 2003; 37: 1191-1199
        • DeMartino R.R.
        • Brooke B.S.
        • Neal D.
        • Beck A.W.
        • Conrad M.F.
        • Arya S.
        • et al.
        Development of a validated model to predict 30-day stroke and 1-year survival after carotid endarterectomy for asymptomatic stenosis using the Vascular Quality Initiative.
        J Vasc Surg. 2017; 66: 433-444
        • Wallaert J.B.
        • Cronenwett J.L.
        • Bertges D.J.
        • Schanzer A.
        • Nolan B.W.
        • De Martino R.
        • et al.
        Optimal selection of asymptomatic patients for carotid endarterectomy based on predicted 5-year survival.
        J Vasc Surg. 2013; 58: 112-119
        • Oksala N.
        • Jaroma M.
        • Pienimäki J.-P.
        • Kuorilehto T.
        • Vänttinen T.
        • Lehtomäki A.
        • et al.
        Preoperative white matter lesions are independent predictors of long-term survival after internal carotid endarterectomy.
        Cerebrovasc Dis Extra. 2014; 4: 122-131
        • Kim T.I.
        • Zhang Y.
        • Amin H.P.
        • Ochoa Chaar C.I.
        Presentation and outcomes of carotid endarterectomy in active smokers.
        J Vasc Surg. 2020; 72: 1720-1727
        • Xue Q.-L.
        The frailty syndrome: definition and natural history.
        Clin Geriatr Med. 2011; 27: 1-15
        • Afilalo J.
        • Alexander K.P.
        • Mack M.J.
        • Maurer M.S.
        • Green P.
        • Allen L.A.
        • et al.
        Frailty assessment in the cardiovascular care of older adults.
        J Am Coll Cardiol. 2014; 63: 747-762
        • Rockwood K.
        • Mitnitski A.
        Frailty in relation to the accumulation of deficits.
        J Gerontol A Biol Sci Med Sci. 2007; 62: 722-727
        • Hoogendijk E.O.
        • Afilalo J.
        • Ensrud K.E.
        • Kowal P.
        • Onder G.
        • Fried L.P.
        Frailty: implications for clinical practice and public health.
        Lancet. 2019; 394: 1365-1375
        • Houghton J.S.M.
        • Nickinson A.T.O.
        • Morton A.J.
        • Nduwayo S.
        • Pepper C.J.
        • Rayt H.S.
        • et al.
        Frailty factors and outcomes in vascular surgery patients: a systematic review and meta-analysis.
        Ann Surg. 2020; 272: 266-276
        • Rothenberg K.A.
        • George E.L.
        • Barreto N.
        • Chen R.
        • Samson K.
        • Johanning J.M.
        • et al.
        Frailty as measured by the Risk Analysis Index is associated with long-term death after carotid endarterectomy.
        J Vasc Surg. 2020; 72: 1735-1742
        • Banning L.B.D.
        • Benjamens S.
        • Bokkers R.P.H.
        • Zeebregts C.J.
        • Pol R.A.
        Role of pre-operative frailty status in relation to outcome after carotid endarterectomy: a systematic review.
        Ann Transl Med. 2021; 9: 1205
        • Drudi L.M.
        • Phung K.
        • Ades M.
        • Zuckerman J.
        • Mullie L.
        • Steinmetz O.K.
        • et al.
        Psoas muscle area predicts all-cause mortality after endovascular and open aortic aneurysm repair.
        Eur J Vasc Endovasc Surg. 2016; 52: 764-769
        • Antoniou G.A.
        • Rojoa D.
        • Antoniou S.A.
        • Alfahad A.
        • Torella F.
        • Juszczak M.T.
        Effect of low skeletal muscle mass on post-operative survival of patients with abdominal aortic aneurysm: a prognostic factor review and meta-analysis of time-to-event data.
        Eur J Vasc Endovasc Surg. 2019; 58: 190-198
        • Oksala N.K.J.
        • Lindstrom I.
        • Khan N.
        • Pihlajaniemi V.J.
        • Lyytikainen L.-P.
        • Pienimaki J.-P.
        • et al.
        Pre-operative masseter area is an independent predictor of long-term survival after carotid endarterectomy.
        Eur J Vasc Endovasc Surg. 2019; 57: 331-338
        • Kant I.M.J.
        • de Bresser J.
        • van Montfort S.J.T.
        • Aarts E.
        • Verlaan J.-J.
        • Zacharias N.
        • et al.
        The association between brain volume, crtical brain infarcts, and physical frailty.
        Neurobiol Aging. 2018; 70: 247-253
        • Del Brutto O.H.
        • Mera R.M.
        • Cagino K.
        • Fanning K.D.
        • Milla-Martinez M.F.
        • Nieves J.L.
        • et al.
        Neuroimaging signatures of frailty: a population-based study in community-dwelling older adults (the Atahualpa Project).
        Geriatr Gerontol Int. 2017; 17: 270-276
        • Tanabe C.
        • Reed M.J.
        • Pham T.N.
        • Penn K.
        • Bentov I.
        • Kaplan S.J.
        Association of brain atrophy and masseter sarcopenia with 1-year mortality in older trauma patients.
        JAMA Surg. 2019; 154: 716-723
        • Diprose W.K.
        • Diprose J.P.
        • Wang M.T.M.
        • Tarr G.P.
        • McFetridge A.
        • Barber P.A.
        Automated measurement of cerebral atrophy and outcome in endovascular thrombectomy.
        Stroke. 2019; 50: 3636-3638
        • Lauksio I.
        • Lindström I.
        • Khan N.
        • Sillanpää N.
        • Hernesniemi J.
        • Oksala N.
        • et al.
        Brain atrophy predicts mortality after mechanical thrombectomy of proximal anterior circulation occlusion.
        J Neurointerv Surg. 2021; 13: 415-420
        • Pedraza M.I.
        • de Lera M.
        • Bos D.
        • Calleja A.I.
        • Cortijo E.
        • Gómez-Vicente B.
        • et al.
        Brain atrophy and the risk of futile endovascular reperfusion in acute ischemic stroke.
        Stroke. 2020; 51: 1514-1521
        • Lindström I.
        • Protto S.
        • Khan N.
        • Hernesniemi J.
        • Sillanpää N.
        • Oksala N.
        Association of masseter area and radiodensity with three-month survival after proximal anterior circulation occlusion.
        J Neurointerv Surg. 2021; 13: 25-29
        • Alamowitch S.
        • Eliasziw M.
        • Algra A.
        • Meldrum H.
        • Barnett H.J.M.
        Risk, causes, and prevention of ischaemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis.
        Lancet. 2001; 357: 1154-1160
        • van Buuren S.
        • Groothuis-Oudshoorn K.
        mice: Multivariate imputation by chained equations in R.
        J Stat Softw. 2011; 45: 1-67
        • Visser L.
        • Banning L.B.D.
        • El Moumni M.
        • Zeebregts C.J.
        • Pol R.A.
        The effect of frailty on outcome after vascular surgery.
        Eur J Vasc Endovasc Surg. 2019; 58: 762-769
        • Muller M.
        • Appelman A.P.A.
        • van der Graaf Y.
        • Vincken K.L.
        • Mali W.P.T.M.
        • Geerlings M.I.
        Brain atrophy and cognition: interaction with cerebrovascular pathology?.
        Neurobiol Aging. 2011; 32: 885-893
        • Jokinen H.
        • Lipsanen J.
        • Schmidt R.
        • Fazekas F.
        • Gouw A.A.
        • van der Flier W.M.
        • et al.
        Brain atrophy accelerates cognitive decline in cerebral small vessel disease: the LADIS study.
        Neurology. 2012; 78: 1785-1792
        • Olesen P.J.
        • Guo X.
        • Gustafson D.
        • Borjesson-Hanson A.
        • Sacuiu S.
        • Eckerstrom C.
        • et al.
        A population-based study on the influence of brain atrophy on 20-year survival after age 85.
        Neurology. 2011; 76: 879-886
        • van der Veen P.H.
        • Muller M.
        • Vincken K.L.
        • Mali W.P.T.M.
        • van der Graaf Y.
        • Geerlings M.I.
        Brain volumes and risk of cardiovascular events and mortality. The SMART-MR study.
        Neurobiol Aging. 2014; 35: 1624-1631
        • Arba F.
        • Testa G.D.
        • Limbucci N.
        • Nappini S.
        • Renieri L.
        • Pracucci G.
        • et al.
        Small vessel disease and clinical outcomes after endovascular treatment in acute ischemic stroke.
        Neurol Sci. 2019; 40: 1227-1235
        • Vikatmaa P.
        Prediction is difficult, especially if it is about the future – old Danish proverb.
        Eur J Vasc Endovasc Surg. 2019; 58: 770

      Linked Article

      • Measurement of the Brain Atrophy Index To Predict Mortality: a ‘No-Brainer’?
        European Journal of Vascular and Endovascular SurgeryVol. 65Issue 3
        • Preview
          In this issue of the European Journal of Vascular and Endovascular Surgery, Lauksia et al. present a multivariable analysis of pre-operative brain atrophy as a predictor of long term mortality after carotid endarterectomy (CEA).1 In the field of carotid revascularisation, various prediction models have been developed in the past to assist stratifying patients into groups at high and low risk of peri-procedural complications or long term stroke risk. An evaluation of the external performance of 23 short and seven long term outcome models showed that these models do not reliably predict outcome after carotid revascularisation, and concluded that new prediction models are needed.
        • Full-Text
        • PDF