Stroke risk and prevalence of asymptomatic carotid stenosis

Carotid artery stenosis (ultrasound, CTA, MRA, DSA)
  • besides increased risk of stroke, patients with asymptomatic carotid stenosis have a higher risk of MI as well ⇒ intensive systemic therapy is essential
  • the prevalence of asymptomatic stenosis > 50% is 2-8%, the prevalence of asymptomatic stenosis > 80% is 1-2%
  • the prevalence of stenosis > 50% increases with age
    • < 60 years – 0.5% ,   > 80 years – 10%
  • risk of stroke in patients with asymptomatic carotid stenosis > 50% is about 1-2%/year
    • according to population-based study and meta-analysis, the risk of stroke increases with the degree of stenosis – the risk of 80-99% stenosis is higher than that of 50-79% stenosis   [Howard, 2021]
    • see below for individual parameters of high-risk plaques
  • relevant revascularization trials  Relevant trials regarding the asymptomatic carotid stenosis
    • ACAS
      • ARR 6% /5 years (5.1% vs 11%)
    • ACST-1
    • ACST-2
      • n=3625 ( 1811 allocated to CAS, 1814 to CEA)
      • procedural stroke: 1%  disabling stroke/death,  2% had a non-disabling procedural stroke 
      • Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke
      • the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable
    • SPACE-2 trial was terminated prematurely due to the lack of funding
  • major ongoing trials:
    • CREST-2 (medication vs. CEA+medication/CAS + medication)

→ management of patients with carotid stenosis undergoing surgery in GA or in ECC

Best medical therapy

  • best medical therapy (BMT) is the mainstay of carotid stenosis management (at the same time it leads to a reduced risk of MI)
    • antiplatelet drugs
    • intensive vascular risk factors treatment
  • a relatively low risk of stroke was reported with such approach  (~1.68%/year)  [Raman, 2013]

Antiplatelet drugs

  • aspirin 100-300 mg/d
  • aspirin intolerance or contraindication:  clopidogrel or ticlopidine
  • clopidogrel resistance/allergy: consider ticagrelor (BRILIQUE)

→ antiplatelet drugs

Management of vascular risk factors

  • target BP < 135/85 mm Hg (130/80 mm Hg in diabetes)
    • prefer ACE-I or sartans
  • statin → target lipid values
  • target glycolysated Hb < 53 mmol/mol in diabetes + management of insulin resistance
  • no smoking
  • obesity control
    • according to some recommendations target BMI <20!)
    • waist circumference female/ male <80/<94 cm
  • physical activity (>30 min/day)

→ overview of vascular risk factors

Carotid artery revascularisation

  • carotid artery revascularisation (CAR) = carotid endarterectomy (CEA) or carotid angioplasty with stenting (CAS)
  • carotid revascularisation should be performed only in a ward with low perioperative complications (<3% in asymptomatic stenoses)
  • CEA/CAS has similar safety, but CEA seems to be a bit safer (ACST-2)
    • the SAPPHIRE and CREST  trials demonstrated the similar safety of CAS and CEA
    • ACT 1 and ACST-2 trials demonstrated comparable safety even in asymptomatic stenoses [Rosenfield, 2016]
    • on the other hand, according to an analysis of 5 randomized trials, CEA appears somewhat safer than CAS  [Moresoli, 2017]
  • patients with more extensive white matter lesions on CT/MRI (ARWMC score ≥ 7) should rather be managed with CEA (ICSS trial)
  • when considering an intervention, take into account several aspects which may help to select patients with the highest profit from revascularisation (→ see here)
    • degree of stenosis + plaque vulnerability should be evaluated  (Brinjikji, 2016)
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All cited markers of high stroke risk in relation to asymptomatic carotid stenosis:

  • lack specificity
  • have not been assessed in conjunction with current optimal medical intervention
  • have not been shown in randomized trials to identify those who benefit from a carotid revascularization procedure in addition to optimal medical intervention

Stenosis degree

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Progression over time

  • risk of progression of carotid stenosis is substantial and increases with time
  • several studies show a higher risk of stroke in progressive stenoses > 80%
  • rapidly progressive stenoses, in particular, seem to be associated with a higher risk of ischemic stroke
  • the data justify the use of serial duplex scans to follow carotid stenosis; there is no consensus on appropriate intervals
    • according to different recommendations, the scan should be repeated every 6-12 months in case of stenosis > 50% (AHA/ASA 2014 IIa/C)

Plaque morphology

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Proof of microembolization on TCD/TCCD

  • the association of embolic signals with the risk of infarction has been demonstrated in both symptomatic and asymptomatic stenoses  Microembolic signal detected on TCCD Microembolic signal detected on power motion-mode Doppler (PMD-TCD)  [Markus, 2017]
    • detection of ≥ 2 embolic signals per hour is indicative of an unstable plaque or plaque with thrombosis
    • annual stroke risk is up to 8%
  • embolic signals are more common in unstable, hypoechoic, exulcerated, poorly calcified plaques
  • the use of TCD Holter could be benefitial in these conditions

Evidence of silent ischemia

  • according to some authors, the incidence of silent ischemia on CT/MRI correlates with the degree of stenosis and the type of plaque (especially exulcerated plaques)
    • MRI is more sensitive than CT
    • according to the ACSRS trial, for stenosis > 60%, the average incidence of stroke in patients with silent ischemia is 3.6%/year compared to 1.3%/year in those without silent ischemia
    • no difference was demonstrated for stenosis < 60%
  • in contrast, in the ACAS trial, there was no correlation of silent ischemia with the degree of stenosis
  • although the benefit of revascularisation in patients with silent lesions has not been demonstrated by studies, in clinical practice, their findings is usually considered as a supportive factor for the indication of CEA/CAS

Effect of contralateral carotid stenosis or occlusion

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Gender

  • in the ACAS trial, women had a higher operative risk than men ( 3.6% vs. 1.7%), some other smaller studies have reported similar results
  • other studies have not confirmed those findings
  • there is no solid consensus, but there is a tendency towards greater restraint in women

Age

  • the advanced age is not an absolute contraindication to CEA/CAS; the patient’s biological status, life expectancy, and other factors must be taken into account
  • there is a tendency to operate patients < 75 years of age
    • in the ACAS trial,  age > 80 years was a contraindication
    • in the ACST trial, the benefit was relatively small in patients > 75 years (ARR 3.3%/5 years)
    • for asymptomatic stenoses, a higher mortality rate was reported in patients >75 years compared to those <75 years of age  [Rajamani, 2013]

Intracranial flow and vasomotor reactivity (CVR)

  • the data show a higher risk of stroke in patients with impaired cerebral vasomotor reactivity (VMR or CVR) and impaired intracranial flow Impaired intracranial flow in a patient with high-grade carotid stenosis [Gupta, 2012]
    • ~4x higher risk of stroke/TIA (5.7% per year with an average follow-up of 24 months)
  • methods used to assess VMR:
    • neurosonological examinations
      • hyperventilation/apnea test during TCCD examination
      • acetazolamide (ACZ) test
    • MRA+MR perfusion
    • CT perfusion performed after i.v. acetazolamide challenge  CT perfusion with acetazolamide shows decreased CVR in the left hemisphere [Kang, 2008]
      • severe stenosis may sometimes manifest as a false ischaemic penumbra (FIP) on baseline CTP  [Mosqueira, 2017]
    • SPECT performed after i.v. acetazolamide challenge SPECT with acetasolamide challenge ACZ administration shows decreased CVR (Kang,2008)
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