Cerebrovascular Disease: Natural History, Diagnostic Evaluation, Plaque, and Medical Therapy

29.1Definition and presentation

Carotid atherosclerosis may be discovered incidentally or during assessment of retinal or cerebral ischaemia. An incidental plaque finding alone is not an acute-stroke emergency. New focal neurological symptoms require immediate stroke assessment; suspected transient ischaemic attack (TIA) requires urgent evaluation even after symptoms resolve.

Symptomatic carotid disease can present with ipsilateral retinal ischaemia, including amaurosis fugax, or a corresponding hemispheric event with motor, sensory or language dysfunction. Cerebral presentations range from TIA and non-disabling stroke to major, disabling stroke. The severity and extent of the presenting injury affect the safety of subsequent carotid intervention; they do not determine whether the disease is symptomatic. ESVS 2023 · ESO 2021

Recurrent stroke risk varies by population and follow-up period. In the TIAregistry.org cohort of 4,789 patients with recent TIA or minor stroke managed through specialist services, cumulative stroke risk was 3.7% at 90 days and 5.1% at one year. These are not untreated severe-carotid-stenosis estimates or a constant annual risk. Amarenco et al. (2016)

In EXPRESS, introduction of rapid assessment and treatment was associated with a reduction in 90-day recurrent stroke from 32/310 patients (10.3%) to 6/281 (2.1%). This before-and-after pathway study supports prompt secondary prevention but does not isolate the effect of carotid surgery. EXPRESS · 2007

29.2Diagnosis and imaging classification

Diagnostic evaluation determines symptom attribution, stenosis severity, and the underlying stroke mechanism.

• Neurological history establishes symptom laterality, territory (retinal, anterior, or posterior circulation), and time elapsed since onset.
• Brain imaging defines infarct distribution and burden and identifies haemorrhage. It contributes to mechanism assessment but cannot by itself establish carotid causation or exclude cardiac embolism.
• Assess alternative and coexisting causes, including atrial fibrillation and other cardiac embolic sources. Rhythm monitoring for occult atrial fibrillation is particularly relevant when the cause remains unidentified. When atrial fibrillation and ipsilateral carotid stenosis coexist, integrate the clinical event, imaging and cardiac findings rather than assuming either abnormality is necessarily causal. ESVS 2023 · AHA/ASA 2021
• Carotid duplex ultrasound is an initial vascular investigation. Report the grading scheme and interpret peak systolic velocity (PSV), end-diastolic velocity, the internal/common carotid PSV ratio, and visible plaque and lumen findings together. The legacy SRU criteria should not be reduced to an isolated PSV rule. IAC validation found overestimation of ≥50% stenosis with the 125 cm/s threshold alone; a higher threshold or additional ratio criterion improved performance. Apply a locally validated multiparameter scheme rather than automatically substituting a new universal cutoff. ICA 2021 · SRU 2003
• Before CEA, corroborate duplex grading with CTA, MRA or repeat duplex by a second operator. When CAS is being considered, follow duplex with CTA or MRA to assess the aortic arch and the extra- and intracranial circulation. Select the modality according to the clinical question and patient-specific contraindications. ESVS 2023

Report stenosis using an identified measurement method. NASCET compares the narrowest residual lumen with the normal distal cervical internal carotid artery; its 50–69% and 70–99% categories must not be interchanged with ECST percentages. Identify near-occlusion separately, because distal calibre reduction undermines ordinary percentage grading. ESVS 2023 · ECST · 1998

29.3Baseline medical therapy

Medical management is the foundation of cerebrovascular care, acting as both primary treatment and the baseline against which intervention is evaluated.

• Antiplatelet therapy: Single antiplatelet therapy is the standard maintenance regimen. Short-course dual antiplatelet therapy is used early after minor stroke or high-risk TIA. A 21-day course of clopidogrel and aspirin reduces 90-day recurrent stroke CHANCE · 2013. A 90-day course of clopidogrel and aspirin reduces ischemic events but increases major hemorrhage POINT · 2018. A 30-day course of ticagrelor and aspirin reduces the composite of stroke or death at the expense of more severe bleeding THALES · 2020. Indefinite dual therapy is contraindicated; 18 months of clopidogrel and aspirin increases life-threatening bleeding to 2.6% compared with 1.3% for clopidogrel alone, with no recurrent stroke benefit MATCH · 2004.
• Lipid-lowering therapy: High-intensity statin therapy reduces long-term recurrence. Atorvastatin 80 mg daily reduces 5-year recurrent stroke rates to 11.2% versus 13.1% on placebo, accompanied by a small hemorrhagic stroke signal SPARCL · 2006. The treatment target is an LDL-C below 70 mg/dL (1.8 mmol/L), achieved with a high-intensity statin and add-on ezetimibe or a PCSK9 inhibitor when the target is not met AHA/ASA 2021.
• Blood-pressure control, glycemic management, and lifestyle modification (including smoking cessation) are universally required components of primary and secondary stroke prevention AbuRahma et al. (2022) · AHA/ASA 2021 · AHA Primary Prevention (2014).

29.4Revascularization and treatment choice

Revascularization supplements medical therapy when its expected stroke-prevention benefit outweighs procedural harm. CEA is generally preferred for suitable symptomatic patients; CAS selection also depends on anatomy, timing and procedural risk. The ESVS 2023 recommendations for CEA in recently symptomatic 50–99% stenosis specify a documented 30-day stroke-or-death risk below 6%. For selected average-surgical-risk patients with asymptomatic 60–99% stenosis, its CEA/CAS recommendations require 30-day stroke-or-death rates no greater than 3%, life expectancy exceeding five years, and additional clinical or imaging selection criteria. These safety thresholds are not stand-alone indications and should be interpreted alongside contemporary trial results and individual preferences. Keep 30-day outcome measures separate from in-hospital measures. ESVS 2023 · ESO 2021

Crescendo TIAs are recurrent transient events with recovery between episodes; stroke in evolution describes a fluctuating or worsening persistent deficit. Neither label replaces assessment of infarct burden and haemorrhagic risk. A reported association with infarct area >4 cm² is not a validated 4-cm-diameter rule for choosing CEA or CAS. ESVS 2023 · E10 2022

Decision logic for revascularization:

1. Interpret symptomatic benefit using the trial population and endpoint. NASCET reported two-year ipsilateral stroke risks of 26% with trial-era medical therapy and 9% with CEA in symptomatic 70–99% stenosis. In pooled trial data for ≥50% stenosis, the estimated five-year number needed to treat to prevent one ipsilateral ischaemic stroke or any stroke/death within 30 days of trial surgery was approximately 5 when randomization occurred within two weeks of the last event and 125 after more than 12 weeks. These historical subgroup estimates demonstrate time-sensitive benefit; they are not individualized predictions or precise comparisons of operation-day schedules. Rothwell et al. (2004) · NASCET · 1991
2. Individualize moderate-stenosis decisions. In NASCET’s 50–69% group, five-year ipsilateral stroke risk was 22.2% with medical therapy and 15.7% with CEA. The often-quoted NNTs of 9 for men and 36 for women came from pooled patients with ≥50% stenosis, not exclusively the moderate group. Sex may inform assessment but should not be used as a stand-alone exclusion. Rothwell et al. (2004) · NASCET 1998
3. Separate historical asymptomatic benefit from contemporary selection. ACAS estimated five-year ipsilateral stroke plus perioperative stroke/death at 11.0% with medical treatment and 5.1% with CEA. ACST-1 reported ten-year net risks, including perioperative events, of 13.4% with immediate CEA and 17.9% with deferred intervention. These comparisons establish historical benefit but do not determine the incremental benefit over present-day intensive medical management for every patient. ACAS · 1995 · ACST-1 (2010)
4. Apply morphology modifiers. In contemporary practice, asymptomatic intervention decisions integrate stenosis severity with imaging-defined plaque morphology, patient life expectancy, and stroke risk despite optimal medical therapy ESVS 2023 · ESO 2021. Imaging findings reported as markers of increased stroke risk during medical management include echolucent or predominantly hypoechoic plaque (Gray-Weale/Geroulakos type 1 to 2), a juxtaluminal black area greater than 8 mm2 on ultrasound, plaque ulceration, intraplaque haemorrhage on MRI, clinically silent ipsilateral infarction on CT or MRI, spontaneous embolisation (microembolic signals) on transcranial Doppler, stenosis progression, and impaired cerebrovascular reserve. These associations do not establish that each marker independently predicts benefit from intervention; a numerical imaging cutoff should not function as an automatic treatment indication.
5. Reassess when benefit is uncertain. Medical management remains essential when intervention is not appropriate. Limited survival, excessive procedural risk or patient preference may favour non-procedural care. Uncertain symptom attribution or a competing mechanism requires etiologic assessment rather than automatic permanent exclusion of carotid treatment. AHA/ASA 2021

29.5Surveillance

Surveillance targets patients managed medically who may cross an intervention threshold, and tracks the durability of completed procedural care.

• Routine follow-up relies on actionable imaging to identify progressive stenosis or the emergence of high-risk plaque morphology that triggers reconsideration of surgery.
• Clinical evaluation verifies adherence to the baseline medical strategy, specifically statin dose intensity, blood-pressure target attainment, and smoking cessation.
• Surveillance is discontinued when the patient is no longer a candidate for future intervention due to limited life expectancy or severe competing medical risks AbuRahma et al. (2022).

29.6Areas of controversy

Contemporary trials qualify the applicability of historical asymptomatic intervention evidence.

CREST-2 comprised separate randomized comparisons of intensive medical management alone against medical management plus CAS or CEA in ≥70% asymptomatic stenosis. Its primary outcome combined stroke/death through day 44 with subsequent ipsilateral ischaemic stroke to four years. Rates were 6.0% versus 2.8% in the medical-versus-stenting comparison (P=0.02), and 5.3% versus 3.7% in the medical-versus-endarterectomy comparison (P=0.24). These were not randomized comparisons between CAS and CEA. The results neither establish CAS superiority over CEA nor prove absence of CEA benefit. CREST-2 (2026)

ECST-2’s two-year interim report addressed a different population: ≥50% stenosis with asymptomatic or selected symptomatic disease and low-to-intermediate predicted risk. It found no significant advantage from adding revascularization to optimized medical therapy on its hierarchical clinical-and-imaging outcome. This does not establish equivalence or settle treatment for higher-risk recently symptomatic patients. ECST-2 2025

Application requires attention to patient selection, procedural strategy, medical-treatment intensity and endpoint severity. Results from asymptomatic cohorts should not be transferred directly to early post-stroke intervention or to an untested procedural approach. Plaque-based selection remains an area of uncertainty rather than a set of universally validated intervention triggers.

Further reading

• Carotid Disease and Management. (2025). Carotid disease, diagnosis and medical-management overview; predates publication of CREST-2 results. Carotid Disease 2025