Carotid atherosclerotic plaque microcalcification is independently associated with recurrent neurovascular events: A pilot study.

BACKGROUND: Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood. METHODS: We performed a post hoc analysis of data from the ICARUSS (Imaging Carotid Atherosclerosis in the Recovery and Understanding of Stroke Severity) study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ⩾ 50% underwent 18F-sodium fluoride positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBRmax). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for 6 months for recurrent ipsilateral neurovascular events. RESULTS: Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (adjusted odds ratio (aOR) = 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (aOR = 1.12, 1.06-1.17 for each 100 unit increase). CONCLUSIONS: Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts.

Management of carotid atherosclerosis in stroke.

Internal carotid artery atherosclerosis is a major risk factor for stroke, accounting for 15-20% of ischaemic strokes. Revascularisation procedures-either carotid endarterectomy or carotid artery stenting-can reduce the risk of stroke for those with significant (>50%) luminal stenosis but particularly for those with more severe (70-99%) stenosis. However, advances in medical pharmacotherapy have implications for the relative benefit from surgery for symptomatic carotid atherosclerosis, as well as our approach to asymptomatic disease. This review considers the evidence underpinning the current medical and surgical management of symptomatic carotid atherosclerosis, the importance of factors beyond the degree of luminal stenosis, and developments in therapeutic strategies. We also discuss the importance of non-stenotic but high-risk carotid atherosclerotic plaques on the cause of stroke, and their implications for clinical practice.

Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis.

Aims: Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results: Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography-tandem mass spectrometry (LC-MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques' R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd-enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC-MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III-V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC-MSMS. Conclusion: We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.

Adherence to vascular care guidelines for emergency revascularization of chronic limb-threatening ischemia.

Objective: In 2022, the National Health Service Commissioning for Quality and Innovation (CQUIN) indicator for vascular surgery, with its pay-for-performance incentive for timely (5-day) revascularization of chronic limb-threatening ischemia (CLTI), was introduced. We sought to assess its effects in terms of (1) changes in the care pathway process measures relating to timing and patient outcomes; and (2) adherence to the Peripheral Arterial Disease Quality Improvement Framework (PAD-QIF) guidelines for patients admitted with CLTI. Methods: A retrospective before-and-after cohort study was performed from January to June 2022 of nonelective admissions for CLTI who underwent revascularization (open, endovascular, or hybrid) at Cambridge University Hospitals National Health Service Foundation Trust, a regional vascular "hub." The diagnostic and treatment pathway timing-related process measures recommended in the PAD-QIF were compared between two 3-month cohorts-before vs after introduction of the CQUIN. Results: For the two cohorts (before vs after CQUIN), 17 of 223 and 17 of 219 total admissions met the inclusion criteria, respectively. After introduction of financial incentives, the percentage of patients meeting the 5-day targets for revascularization increased from 41.2% to 58.8% (P = .049). Improvements were also realized in the attainment of PAD-QIF targets for a referral-to-admission time of ≤2 days (from 82.4% to 88.8%; P = .525) and admission-to-specialist-review time of ≤14 hours (from 58.8% to 76.5%; P = .139). An increase also occurred in the percentage of patients receiving imaging studies within 2 days of referral (from 58.8% to 70.6%; P = .324). The reasons for delay included operating list pressures and unsuitability for intervention (eg, active COVID-19 [coronavirus disease 2019] infection). No statistically significant changes to patient outcomes were observed between the two cohorts in terms of complications (pre-CQUIN, 23.5%; post-CQUIN, 41.2%; P = .086), length of stay (pre-QUIN, 12.0 ± 12.0 days; post-QUIN, 15.0 ± 21.0 days; P = .178), and in-hospital mortality (pre-QUIN, 0%; post-QUIN, 5.9%). Other PAD-QIF targets relating to delivery of care were poorly documented for both cohorts. These included documented staging of limb threat severity with the WIfI (wound, ischemia, foot infection) score (2.9% of patients; target >80%), documented shared decision-making (47.1%; target >80%), documented issuance of written information to patient (5.9%; target 100%), and geriatric assessment (6.3%; target >80%). Conclusions: The pay-for-performance incentive CQUIN indicators appear to have raised the profile for the need for early revascularization to treat CLTI, engaging senior hospital management, and reducing the time to revascularization in our cohort. Further data collection is required to detect any resultant changes in patient outcomes. Documentation of guideline targets for delivery of care was often poor and should be improved.