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Small but vulnerable carotid plaques appear to be a more important cause of stroke than previously thought, a new study suggests.

Results of the Carotid Plaque Imaging in Acute Stroke (CAPIAS) study show that patients with complicated carotid artery plaques ipsilateral to acute ischemic anterior circulation stroke had an increased risk for recurrent ischemic stroke or transient ischemic attack (TIA).

“This study found ipsilateral complicated carotid artery plaques as detected by high-resolution MRI within 10 days from ischemic stroke onset to be associated with a higher risk of recurrent ischemic stroke or TIA. The results were driven by the results in cryptogenic stroke patients and by events ipsilateral to the index stroke,” the authors report.

“Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials,” they conclude.

The study, led by Anna Kopczak, MD, University Hospital, lupron warfarin LMU Munich, is published in the June 7 issue of the Journal of the American College of Cardiology.

In an accompanying editorial, Joshua Z. Willey, MD, and Gerard Pasterkamp, MD, say the study “highlights the importance of considering substenotic atherosclerotic plaques as a cause of ischemic stroke and the subsequent risk of recurrence, and it broadens our understanding of the concept of ESUS (embolic stroke of undetermined source).”

Willey explained to theheart.org | Medscape Cardiology that about 30% of patients with stroke have an embolic stroke of undermined source, and although there is quite a good understanding of cardiac sources of embolic stroke, this study suggests carotid plaques could be contributing more than previously thought to these types of strokes.

Willey noted that, at present, only patients with carotid stenosis greater than 50% are considered for surgery or more aggressive treatment.

“This study has done a very nice job showing that smaller plaques can be a source of stroke, and patients with these smaller but vulnerable plaques may need to be considered for more tests and secondary preventative treatments,” he added.

Recurrent Events

The CAPIAS study prospectively recruited patients in the 10 days after an ischemic stroke restricted to the territory of a single carotid artery who underwent multisequence, contrast-enhanced MRI to identify complicated carotid artery plaques. These were defined by the presence of a ruptured fibrous cap, intraplaque hemorrhage, or mural thrombus.

Among 196 patients enrolled, 104 patients were found to have had a cryptogenic stroke and had smaller nonstenosing carotid artery plaques.

During a mean follow-up of 30 months, recurrent ischemic stroke or TIA occurred in 21 patients.

Recurrent events were significantly more frequent in patients with complicated carotid artery plaques than in those without such plaques, both in the overall cohort (incidence rate, 9.50 vs 3.61 per 100 patient-years) and in patients with cryptogenic stroke (10.92 vs 1.82 per 100 patient-years). The results were driven by ipsilateral events.

Among patients with cryptogenic stroke, those with ipsilateral complicated carotid artery plaques had a 5.6-fold increased risk for recurrent ischemic stroke or TIA compared with those without such plaques, the authors report, with the presence of an ipsilateral ruptured fibrous cap and of intraplaque hemorrhage significantly associated with recurrent ischemic stroke or TIA.

Patients with cryptogenic stroke and with plaques with a ruptured fibrous cap or intraplaque hemorrhage had a four to five times increased risk for recurrent events.

The researchers say the most important finding in terms of clinical implications in the study is the association between intraplaque hemorrhage and an increased risk for recurrent ischemic stroke or TIA in patients with cryptogenic stroke.

They point out that unlike other features of complicated carotid artery plaques, intraplaque hemorrhage can be reliably detected by standard coils and conventional native T1-weighted sequences, indicating that MRI for intraplaque hemorrhage detection could be integrated into the diagnostic workflow of anterior circulation stroke.

“The prevalence of ipsilateral intraplaque hemorrhage in our cohort was relatively high (27% of cryptogenic stroke patients, 26% of the overall sample), thus further highlighting the potential utility of this marker for risk stratification and the selection of patients into clinical trials,” they report.

But they note that the current study participants had been selected for the presence of carotid artery plaque and had had relatively mild strokes, which emphasizes the need for additional studies.

They suggest that the next step should be a multicenter study to determine the precise prevalence of intraplaque hemorrhage and associated recurrence rates in unselected patients with anterior circulation stroke.

“Such a study would enable analyses in relevant subgroups to prepare for future prevention trials,” they add.

“At present, there is a perception that if the carotid plaque is causing less than a 50% stenosis, then this is not directly related to the stroke,” Willey commented to theheart.org | Medscape Cardiology. “But this study shows this not to be the case and that we need to think more carefully about patients with smaller carotid plaques. This study showed that vulnerable carotid plaques are particularly dangerous, and, at the moment, these plaques are not being identified and treated.

“This opens up a new group of patients for whom more aggressive secondary preventative therapy may be required. This observation makes sense as it parallels what we know about coronary disease,” he added.

Willey noted that this study raises the issue of whether patients with smaller carotid plaques could benefit from more advanced imaging to identify those with vulnerable plaques, but he pointed out that the study needs to be replicated in a more diverse population of patients to better understand the degree to which this affects different groups.

He explained that the proportion of embolic strokes of unknown source that will originate from vulnerable carotid plaques is hard to define and will vary between different populations.

“Older patients are more likely to have a stroke caused by undiagnosed AF. But patients with a high burden of risk factors, such as smoking, diabetes, or high cholesterol, are more likely to have vulnerable plaque. I suspect rates of vulnerable carotid plaques among ESUS patients could be around 30% or more in these types of patients,” Willey said.

This study was supported by the Vascular Dementia Research Foundation and the German Research Foundation. The authors and editorialist report no disclosures.

J Am Coll Cardiol. Published online May 30, 2022. Full text, Editorial   

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