Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke

Abstract

Atherosclerosis is a major cause of ischemic stroke that can be effectively prevented with appropriate lifestyle modifications and control of cardiovascular risk factors. Medical advances in recent years along with aggressive cardiovascular risk factor modifications have resulted in decreased recurrence rates of atherosclerotic stroke. Non-statin lipid-lowering molecules have recently shown clinical benefit and are recommended for very high-risk patients to reduce their risk of stroke. Aggressive hypertension treatment is crucial to reduce atherosclerotic stroke risk. Advances in antithrombotic treatments include combinations of antiplatelets and new antiplatelet agents in the acute phase post-stroke, which carries a high risk of recurrence. Intensive medical treatment has also limited the indications for carotid interventions, especially for asymptomatic disease. Intracranial atherosclerotic disease may provoke stroke through various mechanisms; it is increasingly recognized as a cause of ischemic stroke with advanced imaging and is best managed with lifestyle modifications and medical therapy. The diagnostic search for the vulnerable culprit atherosclerotic plaque is an area of intense research, from the level of the intracranial arteries to that of the aortic arch. Ultrasonography and novel magnetic resonance imaging techniques (high-resolution vessel-wall imaging) may assist in the identification of vulnerable atherosclerotic plaques as the underlying cause in cryptogenic or misdiagnosed non-atherosclerotic ischemic stroke. Vertebrobasilar atherosclerotic disease is less common than carotid artery disease; thus, high-quality data on effective prevention strategies are scarcer. However, aggressive medical treatment is also the gold standard to reduce cerebrovascular disease located in posterior circulation.

Keywords: Atherosclerosis; Atherosclerotic stroke; Dyslipidemia; Extracranial; Hypertension; Intracranial.

Figure 1.

Symptomatic extracranial internal carotid artery (ICA) atherosclerotic plaque: (A, B) ultrasound imaging, (C) computed tomography (CT) angiography, and (D) pathology specimen. A 52-year-old male smoker with history of hypertension presented with transient aphasia and right hemiparesis lasting for 24 minutes. He reported two similar transient episodes of neurological dysfunction during the last week lasting <10 minutes. Brain CT was normal. Carotid duplex showed a heterogeneous mostly hypoechogenic plaque causing a hemodynamically significant (>70%) stenosis of the left ICA (peak systolic velocity 229 cm/sec, end diastolic velocity 106 cm/sec, ICA/ common carotid artery [CCA] peak systolic velocity ratio 4.4). Ultrasound findings were confirmed on CT angiography. The patient received loading dose of clopidogrel (300 mg) and aspirin (100 mg) and underwent uneventfully carotid endarterectomy the next day of his hospital admission. He was discharged with no residual neurological symptoms on the fifth day of ictus.

Figure 2.

Symptomatic intracranial non-stenotic atherosclerotic plaque. A 67-year-old male with hypertension and diabetes mellitus, presented with acute-onset diplopia. On neurological examination Parinaud syndrome and incomplete left internuclear opthalmoplegia was identified. (A) Diffusion-weighted imaging showed two acute left mesencephalic ischemic lesions (oval). (B) Time-of-flight showed a focal stenosis of the distal basilar artery (asterisk). (C) 3-Tesla high-resolution vessel wall-imaging disclosed a diffuse uptake of gadolinium by the atherosclerotic plaque in the wall of the basilar artery indicative of active inflammation (arrows). Artery-to-artery embolism to distal paramedian midbrain branches of an unstable non-atherosclerotic plaque in distal basilar artery was considered the underlying mechanism of acute cerebral ischemia. The patient was treated with dual antiplatelet therapy (clopidogrel load of 300 mg followed by clopidogrel 75 mg once a day and aspirin) for 3 months and colchicine (0.5 mg once a day; off-label use for inflammatory atherosclerosis). Dual antiplatetet therapy was later substituted with single antiplatelet therapy (clopidogrel 75 mg). The patient experienced no recurrence during the 6-month follow-up period.

Figure 3.

Branch-occlusive disease of the pons. (A) Diffusion-weighted image showing a left medial pontine infarction (arrow) along the left paramedian pontine artery territory (penetrating branch of basilar artery). (B) Post-contrast T1-weighted SPACE (Sampling Perfection with Application optimized Contrast using different angle Evolutions) image showing mural enhancement of both vertebral arteries (arrows). Patchy, eccentric pattern of contrast enhancement is consistent with atheromatous lesions. (C) Preand (D) post-contrast T1-weighted SPACE images showing uneven mural enhancement of the basilar artery (D, arrow) indicating atheromatosis at the level of the pons.