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.

Near-Infrared Autofluorescence in Atherosclerosis Associates With Ceroid and Is Generated by Oxidized Lipid-Induced Oxidative Stress.

[Figure: see text].

An Assessment of Available Information on the World Wide Web for Patients with Lower Limb Arterial Disease.

OBJECTIVE: The quality of patient information relating to intermittent claudication (IC) and peripheral arterial disease (PAD) on the World Wide Web was assessed. METHODS: The quality of websites and YouTube videos was assessed using the search terms "intermittent claudication" and "peripheral arterial disease". The first 50 hits screened for each search term from the three largest search engines by market share, and the first 20 videos from YouTube were screened. Website quality was scored using the University of Michigan Consumer Health Website tool (maximum score 80). Readability was calculated using the Flesch Reading Ease (FRE) score (maximum score 100). Videos were classified by content and upload source. Video reliability was assessed using the JAMA benchmark criteria. Video educational content was assessed using the Global Quality Score (GQS). Subjective content assessment was undertaken. RESULTS: Seventy-six websites were analysed. The majority of websites for both IC (51.7%) and PAD (72.3%) were rated as weak. The median Michigan score for IC (27; interquartile range [IQR] 15, 32.5) was lower that the score for PAD (31; IQR 25.5, 38.8; p = .030). The majority of websites for both IC (69%) and PAD (68.1%) were rated as requiring an above average reading level. The overall median FRE score was 55.9 (IQR 46.6, 60.6) for IC and 55.3 (IQR 44.6, 59.3) for PAD. Twenty-two videos were analysed. Of the 14 videos evaluated as part of the PAD search, the median JAMA score was 2 (2 - 3), the median GQS score was 3 (3 - 3) and the evaluation of content score was 8.5 (7.25 - 11.5). The equivalent scores for the IC search were 2 (2 - 2), 3 (3 - 4), and 5.5 (5 - 8). CONCLUSION: The educational quality and reliability of information both in written and video form on the internet is low. Attention needs to focus on improving the quality of all forms of information delivery to allow proper advocacy for patients.

Effects of Statin Therapy and Dose on Cardiovascular and Limb Outcomes in Peripheral Arterial Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: Statin therapy is indicated in patients with peripheral arterial disease (PAD). National Institute for Health and Care Excellence guidelines suggest the use of "high intensity" statins, although evidence with PAD specific data are lacking. The effect of statin therapy and dose on outcomes in PAD is investigated. DATA SOURCES: Studies measuring statin use in PAD patients and outcomes were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The EMBASE and MEDLINE databases were interrogated from January 1957 until February 2020. Twenty-two observational cohort studies and two randomised control trials were included (n = 268 611). REVIEW METHODS: Pooled estimates of dichotomous outcome data were calculated using the odds/hazard ratios (OR/HR) and 95% confidence interval (CI). Meta-analysis was conducted using the inverse variance or Mantel-Haenszel method. Outcomes included all cause mortality (ACM), cardiovascular mortality (CVM), major adverse cardiac events (MACE), and amputation. Subgroup analysis was performed on studies comparing patients taking high dose vs. combined low and moderate doses of statins. The GRADE criteria assessed the quality of evidence for outcomes. RESULTS: Statin therapy (vs. no statins) was significantly protective for ACM: OR 0.68 (95% CI 0.60 - 0.76) (number needed to treat [NNT] = 48), HR 0.74 (95% CI 0.70 - 0.78) (NNT = 10 - 91); MACE: OR 0.84 (95% CI 0.78 - 0.92) (NNT = 53), HR 0.78 (95% CI 0.65 - 0.93) (NNT = 167); and amputations: OR 0.59 (95% CI 0.33 - 1.07) (NNT = 333), HR 0.74 (95% CI 0.62 - 0.89) (NNT = 50). High doses of statins (vs. combined low and moderate doses) were significantly better protective against ACM OR 0.69 (95% CI 0.43 - 1.09) (NNT = 17), HR 0.74 (95% CI 0.62 - 0.89) (NNT = 16 - 200) but work less significantly for MACE OR 0.77 (95% CI 0.49 - 1.21) (NNT = 25). Amputations were less frequent in patients on high doses HR 0.78 (95% CI 0.69 - 0.90) (NNT = 53 - 1 000). CONCLUSION: Higher dosing of statins confers a significant improvement in patient outcomes, especially ACM and amputations, although the quality of the evidence was variable. Such findings require confirmation in larger, PAD specific trials.

Clinical practice patterns and ascertainment bias for cardiovascular events in a randomized trial: A survey of investigators in the BEST-CLI trial.

Ascertainment bias is a well-recognized source of bias in research, but few studies have systematically analyzed sources of ascertainment bias in randomized trials in which blinding is not possible and endpoint assessment is not protocolized. In the current study, we sought to evaluate differences in the clinical practice patterns of trial investigators with respect to bias in the ascertainment of pre-revascularization patient risk and the incidence of secondary endpoints post-revascularization. We conducted a cross-sectional survey of active investigators (n = 936) from the Best Endovascular Versus Best Surgical Therapy for Patients with Critical Limb Ischemia (BEST-CLI) trial. The total survey response rate was 19.6% (183/936). Vascular surgeons were more likely than nonsurgical interventionalists to order tests for cardiac complications after both surgical bypass (p < 0.001) and endovascular revascularization (p = 0.038). Post-procedure, investigators were more likely to order additional testing for cardiac complications in open surgery versus endovascular cases (7% vs 16% never, 41% vs 65% rarely, 43% vs 17% sometimes, 9% vs 2% always, respectively; p < 0.0001). Significant variation in practice patterns exist in the pre- and post-procedure assessment of cardiac risk and events for patients with CLI undergoing revascularization. Variation in the ascertainment of risk and outcomes according to the type of revascularization procedure and physician specialty should be considered when interpreting the results of clinical studies, such as the BEST-CLI trial. ClinicalTrials.gov Identifier: NCT02060630.

Patient and Institutional Costs of Failure of Angioplasty of the Superficial Femoral Artery.

BACKGROUND: Debate surrounds the optimal management of superficial femoral artery (SFA) disease. Randomized trial data rarely reflect real world findings, specifically the consequences to the patient of angioplasty failure. We observed the effect of a failed SFA angioplasty on the need for repeated clinic visits, hospital readmissions, imaging requirements, and reinterventions. METHODS: We reviewed a consecutive series of 148 patients (94 men, median age 72 years) undergoing solely SFA angioplasty over a 2-year period. Patient preangioplasty demographics and 2-year post-PTA follow-up data were collated, including hospital attendances (inpatient/outpatient), further imaging (including radiation exposure) and revascularization attempts. We defined "failed angioplasty" as presence of clinical symptoms with radiological evidence of significant restenosis after an initial successful primary SFA angioplasty. RESULTS: Fifty-four patients represented with a failed angioplasty (median time of 4 months after index PTA). In this group, failure of index angioplasty resulted in a further 185 restenosis-related clinic visits and a total of 537 bed days of inpatient stay. This group underwent a further 149 imaging events and required a further 34 endovascular revascularization procedures and 12 infrainguinal bypass procedures. These interventions and investigations corresponded to overall effective radiation dose across all patients of 190.69 mSv. Of the cohort of 99 patients who did not have a "failed angioplasty," they required 100 clinic visits, 21 further scans (total radiation dose 6.42 mSv), and 36 bed days of inpatient admission. CONCLUSIONS: Failed angioplasty results in significant additional consequences for patients and health-care systems. Further work should focus on refining decision-making, providing the right procedure to the right patient at the right time.

The Effect of Frailty on Long Term Outcomes in Vascular Surgical Patients.

OBJECTIVE: Frailty is a multidimensional vulnerability due to age associated decline. The impact of frailty on long term outcomes was assessed in a cohort of vascular surgical patients. METHODS: Patients aged over 65 years with a length of stay greater than two days admitted to a tertiary vascular unit over a single calendar year were included. Demographics, mode of admission, and diagnosis were recorded alongside a variety of frailty specific characteristics. Using the previously developed Addenbrookes Vascular Frailty Score (AVFS - 6 point score: anaemia on admission, lack of independent mobility, polypharmacy, Waterlow score > 13, depression, and emergency admission) the effect of frailty on five year mortality and re-admission rates was assessed using multivariable regression techniques. The AVFS was further refined to assess longer term outcomes. RESULTS: In total, 410 patients (median age 77 years) were included and followed up until death or five years from the index admission. One hundred and thirty-four were treated for aortic aneurysm, 75 and 96 for acute and chronic limb ischaemia respectively, 52 for carotid disease, and 53 for other pathologies. The in hospital mortality rate was 3.6%. The one, three, and five year survival rates were 83%, 70% and 59%; and the one, three, and five year re-admission free survival rates were 47%, 29%, and 22% respectively. Independent predictors of five year mortality were age, lack of independent mobility, high Charlson score, polypharmacy, evidence of malnutrition, and emergency admission (p < .010 for all). Patients with AVFS 0 or 1 had restricted mean survival times which were one year longer than those with AVFS 2 or 3 (p < .001), who in turn had restricted mean survival times over one year longer than those with AVFS of 4 or more (p < .001). CONCLUSION: Frailty factors are strong predictors of long term outcomes in vascular surgery. Further prospective studies are warranted to investigate its utility in clinical decision making.

Site and Burden of Lower Limb Atherosclerosis Predicts Long-term Mortality in a Cohort of Patients With Peripheral Arterial Disease.

OBJECTIVE/BACKGROUND: Lower limb peripheral arterial disease (PAD) is becoming increasingly common. Lower limb perfusion, as determined by the ankle brachial pressure index (ABPI), is a recognised predictor of overall mortality. The increasing role of non-invasive imaging in patient assessment may aid in the ability to predict poor patient outcomes. METHODS: This study included all patients undergoing a lower limb arterial duplex over a period of 20 months. The site and burden of atherosclerosis within the lower limb was determined using the well validated Bollinger score. Patient demographic data were also collated. The primary outcome measure was all cause mortality. RESULTS: A total of 678 patients were included (median age 74 years). The overall median follow up period was 69.9 months. Of these, 307 patients reached the primary end point, which was death. Independent predictors of all cause mortality included total Bollinger score (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.18 [p < .001]; OR per 10 points), femoropopliteal Bollinger score (OR 1.34, 95% CI 1.11-1.08 [p = .05]; OR per 10 points), and crural Bollinger score (OR 1.03, 95% CI 1.01-1.03 [p = .03]). There was also a significant association between mortality and age, a prior history of ischaemic heart disease, a history of congestive cardiac failure and chronic renal failure (chronic kidney disease ≥ 3). Statin and antiplatelet therapy were protective. CONCLUSION: This contemporary study confirms poor long-term outcomes still exist in patients with PAD. The site and severity of lower limb atherosclerosis are independent predictors of long-term mortality.

Editor's Choice - Calcification of Thoracic and Abdominal Aneurysms is Associated with Mortality and Morbidity.

INTRODUCTION: Cardiovascular events are common in people with aortic aneurysms. Arterial calcification is a recognised predictor of cardiovascular outcomes in coronary artery disease. Whether calcification within abdominal and thoracic aneurysm walls is correlated with poor cardiovascular outcomes is not known. PATIENTS AND METHODS: Calcium scores were derived from computed tomography (CT) scans of consecutive patients with either infrarenal (AAA) or descending thoracic aneurysms (TAA) using the modified Agatston score. The primary outcome was subsequent all cause mortality during follow-up. Secondary outcomes were cardiovascular mortality and morbidity. RESULTS: A total of 319 patients (123 TAA and 196 AAA; median age 77 [71-84] years, 72% male) were included with a median follow-up of 30 months. The primary outcome occurred in 120 (37.6%) patients. In the abdominal aortic aneurysm group, the calcium score was significantly related to both all cause mortality and cardiac mortality (odds ratios (OR) of 2.246 (95% CI 1.591-9.476; p < 0.001) and 1.321 (1.076-2.762; p = 0.003)) respectively. In the thoracic aneurysm group, calcium score was significantly related to all cause mortality (OR 6.444; 95% CI 2.574-6.137; p < 0.001), cardiac mortality (OR 3.456; 95% CI 1.765-4.654; p = 0.042) and cardiac morbidity (OR 2.128; 95% CI 1.973-4.342; p = 0.002). CONCLUSIONS: Aortic aneurysm calcification, in either the thoracic or the abdominal territory, is significantly associated with both higher overall and cardiovascular mortality. Calcium scoring, rapidly derived from routine CT scans, may help identify high risk patients for treatment to reduce risk.

18F-FDG Uptake on PET/CT in Symptomatic versus Asymptomatic Carotid Disease: a Meta-Analysis.

INTRODUCTION: The role of positron emission tomography (PET)/computed tomography (CT) in the determination of inflammation in arterial disease is not well defined. This can provide information about arterial wall inflammation in atherosclerotic disease, and may give insight into plaque stability. The aim of this review was to perform a meta-analysis of PET/CT with 18F-FDG (fluorodeoxyglucose) uptake in symptomatic and asymptomatic carotid artery disease. METHODS: This was a systematic review, following PRISMA guidelines, which interrogated the MEDLINE database from January 2001 to May 2017. The search combined the terms, "inflammation", "FDG", and "stroke". The search criteria included all types of studies, with a primary outcome of the degree of arterial vascular inflammation determined by 18F-FDG uptake. Analysis involved an inverse weighted variance estimate of pooled data, using a random effects model. RESULTS: A total of 14 articles (539 patients) were included in the meta-analysis. Comparing carotid artery 18F-FDG uptake in symptomatic versus asymptomatic disease yielded a standard mean difference of 0.94 (95% CI 0.58-1.130; p < .0001; I2 = 65%). CONCLUSIONS: PET/CT using 18F-FDG can demonstrate carotid plaque inflammation, and is a marker of symptomatic disease. Further studies are required to understand the clinical implication of PET/CT as a risk prediction tool.

Morphometric Assessment as a Predictor of Outcome in Older Vascular Surgery Patients.

BACKGROUND: Frailty is a recognized predictor of poor outcome in patients undergoing surgical intervention. Frailty is intricately linked with body morphology, which can be evaluated using morphometric assessment via computerized tomographic (CT) imaging. We aimed to assess the predictive power of such objective assessments in a broad cohort of vascular surgical patients. METHODS: A consecutive series of patients aged over 65 years admitted to a vascular unit, who had undergone CT imaging of the abdomen, were analyzed. Demographic and patient-specific data were collated alongside admission relevant information. Outcomes included mortality, length of stay, health care-related costs, and discharge destination. Images were analyzed for 4 morphometric measurements: (1) psoas muscle area, (2) mean psoas density, (3) subcutaneous fat depth, and (4) intra-abdominal fat depth, all taken at the level of the fourth lumbar vertebra. RESULTS: Two hundred and ten patients were initially analyzed. Forty-four patients had significant retroperitoneal and abdominal abnormalities that limited appropriate CT analysis. Decreased subcutaneous fat depth was significantly associated with mortality, readmission within 12 months, and increased cost of health care (P < 0.01, adjusted for confounders). Psoas muscle area was significantly associated with readmission-free survival. CONCLUSIONS: Morphometric analysis predicts poorer outcome in a broad cohort of vascular surgery patients. Such assessment is likely to enhance patient counseling regarding individual risk as well as enhancing the ability to undertake risk-modified surgical audit.

Mechanochemical Ablation for Treatment of Truncal Venous Insufficiency: A Review of the Current Literature.

Mechanochemical ablation (MOCA) is a nonthermal nontumescent technique used in the treatment of superficial venous disease. This review analyzed the available data on the efficacy and safety of MOCA. A systematic literature search was performed. Of 101 studies identified, 14 were suitable for inclusion. The studies were found to be heterogeneous in design, and the quality of evidence was found to be low or very low. MOCA was demonstrated to be effective in the short-term with minimal complications. Consensus guidelines and definitions of reporting outcome measures must be standardized to allow comparison with other techniques.

Variability in Atherosclerotic Disease Progression within the Infrainguinal Arterial Circulation is Dependent on Both Patient and Anatomical Factors.

BACKGROUND: Studies suggest 25% of patients with symptomatic peripheral arterial disease develop symptom progression over time, yet there is minimal data related to actual atherosclerotic progression. METHODS: Patients who underwent consecutive duplex imaging of the lower limb arteries, at least 6 months apart with no intervening arterial intervention, were identified. Atherosclerotic burden was determined for both femoropopliteal (FP) and crural (CR) arterial segments utilizing the Bollinger score (BoS). Overall change in BoS over time was determined, and patients were divided into group 1: disease progression and group 2: no change/disease regression. Patient demographics, comorbidities, and long-term outcomes were collated. RESULTS: A total of 215 FP segments (155 men; median age 74 years) were assessed with 82 limbs showing atherosclerotic disease progression. FP atherosclerotic progression was associated with increased age, a diagnosis of ischemic heart disease and hypertension, and a lack of prescription of both an antiplatelet therapy and an angiotensin-converting enzyme inhibitor (all P < 0.05). FP atherosclerotic progression was also associated with an increased longer term mortality rate. A total of 272 CR arterial segments (190 men; median age 74 years) were assessed with 86 limbs showing atherosclerotic disease progression. CR atherosclerotic disease progression was associated with a diagnosis of diabetes mellitus at baseline (P = 0.019). CONCLUSIONS: A number of variable factors predict atherosclerotic progression. Differences exist between factors and the arterial segments affected (FP/CR). This suggests that underlying atherosclerotic processes may vary depending on arterial segment, warranting further investigation.

Premorbid function, comorbidity, and frailty predict outcomes after ruptured abdominal aortic aneurysm repair.

OBJECTIVE: Strategies to improve outcomes for patients with ruptured abdominal aortic aneurysm (rAAA) are becoming more evident. The aging population, however, continues to make the decision to intervene often difficult, especially given that traditional risk models do not reflect issues of aging and frailty. This study aimed to integrate measures of function alongside comorbidity- and frailty-specific factors to determine outcome. METHODS: Patients treated for a rAAA between January 2006 and April 2014 were assessed. Demographics, mortality, and requirement for care after discharge as well as a variety of measures of function (physical, social, and psychological) and comorbidity were recorded. The primary outcome was 1-year mortality. Outcome models were generated using multivariate logistic regression and were compared with models of vascular frailty and AAA-related outcome. RESULTS: Of 184 patients treated, 108 (59%) underwent an open surgical repair. The overall 30-day and 1-year mortality were 21.5% and 31.4%, respectively, with an overall median hospital length of stay of 13 days (interquartile range, 6-27 days). An optimal logistic regression model for 12-month mortality used Katz score, Charlson score, number of admission medicines, visual impairment, hearing impairment, hemoglobin level, and statin use as predictors, achieving an area under the receiver operating characteristic curve of 0.84. CONCLUSIONS: This novel rAAA model incorporating function and comorbidity offers good predictive power for mortality. It is quick to calculate and may ultimately become helpful for both counseling and selection of patients and comparative audit at a time when outcome in patients with rAAA increasingly comes under the spotlight.

PET Imaging of Atherosclerotic Disease: Advancing Plaque Assessment from Anatomy to Pathophysiology.

Atherosclerosis is a leading cause of morbidity and mortality. It is now widely recognized that the disease is more than simply a flow-limiting process and that the atheromatous plaque represents a nidus for inflammation with a consequent risk of plaque rupture and atherothrombosis, leading to myocardial infarction or stroke. However, widely used conventional clinical imaging techniques remain anatomically focused, assessing only the degree of arterial stenosis caused by plaques. Positron emission tomography (PET) has allowed the metabolic processes within the plaque to be detected and quantified directly. The increasing armory of radiotracers has facilitated the imaging of distinct metabolic aspects of atherogenesis and plaque destabilization, including macrophage-mediated inflammatory change, hypoxia, and microcalcification. This imaging modality has not only furthered our understanding of the disease process in vivo with new insights into mechanisms but has also been utilized as a non-invasive endpoint measure in the development of novel treatments for atherosclerotic disease. This review provides grounding in the principles of PET imaging of atherosclerosis, the radioligands in use and in development, its research and clinical applications, and future developments for the field.

Imaging unstable plaque.

Recent advances in imaging technology have enabled us to utilise a range of diagnostic approaches to better characterise high-risk atherosclerotic plaque. The aim of this article is to review current and emerging techniques used to detect and quantify unstable plaque in the context of large and small arterial systems and will focus on both invasive and non-invasive imaging techniques. While the diagnosis of clinically relevant atherosclerosis still relies heavily on anatomical assessment of arterial luminal stenosis, evolving multimodal cross-sectional imaging techniques that encompass novel molecular probes can provide added information with regard to plaque composition and overall disease burden. Novel molecular probes currently being developed to track precursors of plaque rupture such as inflammation, micro-calcification, hypoxia and neoangiogenesis are likely to have translational applications beyond diagnostics and have the potential to play a part in quantifying early responses to therapeutic interventions and more accurate cardiovascular risk stratification.

Angioplasty versus bare metal stenting for superficial femoral artery lesions.

BACKGROUND: Lower limb peripheral arterial disease (PAD) is a common, important manifestation of systemic atherosclerosis. Stenoses or occlusions in the superficial femoral artery may result in intermittent claudication or even critical ischaemia, which may be treated by balloon angioplasty with or without stenting. This is the first update of a review published in 2009. OBJECTIVES: The primary aim was to determine the effect of percutaneous transluminal angioplasty (PTA) compared with PTA with bare metal stenting for superficial femoral artery (SFA) stenoses on vessel patency in people with symptomatic (Rutherford categories1 to 6; Fontaine stages II to IV) lower limb peripheral vascular disease.In addition, we assessed the efficacy of PTA and stenting in improving quality of life, ankle brachial index and treadmill walking distance. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 6). SELECTION CRITERIA: Randomised trials of angioplasty alone versus angioplasty with bare metal stenting for the treatment of superficial femoral artery stenoses. DATA COLLECTION AND ANALYSIS: Two review authors (MC, CT) independently selected suitable trials, assessed trial quality and extracted data. Furthermore, these two review authors performed assessments of methodological quality and wrote the final manuscript. The third review author (ADM) cross-checked all stages of the review process. MAIN RESULTS: We include three new studies in this update, making a total of 11 included trials with 1387 participants. The average age was 69 years and all trials included men and women. Participants were followed for up to two years. There was an improvement in primary duplex patency at six and 12 months in participants treated with PTA plus stent over lesions treated with PTA alone (six months: odds ratio (OR) 2.90, 95% confidence interval (CI) 1.17 to 7.18, P = 0.02, six studies, 578 participants; 12 months: OR 1.78, 95% CI 1.02 to 3.10, P = 0.04, nine studies, 858 participants). This was lost by 24 months (P = 0.06). There was a significant angiographic patency benefit at six months (OR 2.49, 95% CI 1.49 to 4.17, P = 0.0005, four studies, 329 participants) which was lost by 12 months (OR 1.30, 95% CI 0.84 to 2.00, P = 0.24, five studies, 384 participants). Ankle brachial index (ABI) and treadmill walking distance showed no improvement at 12 months (P = 0.49 and P = 0.57 respectively) between participants treated with PTA alone or PTA with stent insertion. Three trials (660 participants) reported quality of life, which showed no significant difference between participants treated with PTA alone or PTA with stent insertion at any time interval. Antiplatelet therapy protocols and inclusion criteria regarding affected arteries between trials showed marked heterogeneity. AUTHORS' CONCLUSIONS: Although there was a short-term gain in primary patency there was no sustained benefit from primary stenting of lesions of the superficial femoral artery in addition to angioplasty. Future trials should focus on quality of life for claudication and limb salvage for critical ischaemia.

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.

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.