Diabetes, intracranial stenosis and microemboli in asymptomatic carotid stenosis.

BACKGROUND: The risk of stroke in patients with asymptomatic carotid stenosis (ACS) is now so low that it is important to have methods to identify those patients most likely to benefit from intervention, or who may require special consideration in choice of medical therapy. We studied the prediction of stroke, death or transient ischemic attacks (stroke/death/TIA) in patients with ACS by intracranial arterial stenosis, and microemboli on transcranial Doppler (TCD), and the effect of diabetes mellitus on microemboli, intracranial stenosis and risk of events. METHODS: Patients with ACS > 60% by Doppler ultrasound were recruited from the Stroke Prevention Clinic of University Hospital, London, Canada. All 339 participants underwent TCD for detection of intracranial stenosis and detection of microemboli, and carotid ultrasound to measure extracranial stenosis and total carotid plaque area. Participants were followed for three years, to determine the risk of stroke/death/TIA. RESULTS: Stroke/death/TIA occurred in 38% of patients with microemboli versus 10% without (p=0.0001), and in 18% of patients with intracranial stenosis, versus 10% without (p=0.042). Diabetics were significantly more likely to have intracranial stenosis (45% vs. 29%, p =0.014), microemboli (38% vs. 10%, p <0.0001), and had significantly higher risk of stroke/death/TIA over three years (21% vs. 11% without; p=0.024). Survival free of stroke, TIA or death was significantly better without microemboli or intracranial stenosis (p<0.0001). CONCLUSIONS: Diabetes, microemboli and intracranial stenosis predicted higher risk of stroke, death or TIA than did extracranial stenosis or total plaque area; diabetics may need more intensive therapy.

The impact of mechanical devices for lifting and transferring of patients on low back pain and musculoskeletal injuries in health care personnel-A systematic review and meta-analysis.

OBJECTIVES: Heavy lifting in nursing is highly associated with low back pain (LBP) and musculoskeletal injuries (MSI). We aimed to evaluate the impact of mechanical devices used for patient lifting and transferring on risk of LBP and MSI of health care personnel. METHODS: We conducted a systematic review and meta-analysis. The literature search was performed during 1st and 12th September 2021 using 17 electronic databases and handsearching of bibliographies of included studies. Twenty studies were included in the qualitative synthesis and eight studies with in total 2087 participants in the meta-analysis. Dependent on the study design, risk of bias was assessed by Cochrane RoB 2.0, EPOC, and MINORS. We conducted random-effects meta-analyses assessing Hedges's g and 95% CI of MSI rate, perceived LBP, and peak compressive spinal load. We calculated prediction intervals and conducted a cost-benefit analysis (CBA). RESULTS: All outcomes showed significant, adjusted pooled effect sizes (MSI rate: g = 1.11, 95% CI 0.914-1.299; perceived LBP: g = 1.54, 95% CI -0.016-3.088; peak compressive spinal load: g = 1.04, 95% CI -0.315 to 2.391). True effect sizes in 95% of all comparable populations fell in the following prediction intervals: MSI rate = -1.07-3.28, perceived LBP = -0.522-3.594, and peak compressive spinal load = -15.49 to 17.57. CBA revealed cost-benefit ratios of 1.2 and 3.29 between cumulative total savings and investment costs of intervention. CONCLUSIONS: Prediction intervals confirmed strong true effect sizes for MSI rate and perceived LBP in 95% of all comparable populations but not for peak compressive spinal load. Mechanical lifting and transferring devices displayed a favorable cost-benefit ratio and should be considered for clinical implementation.

Clinical and Imaging Phenotypes and Outcomes in a Costa Rican Cohort of Acute Ischemic Stroke Survivors: A Retrospective Study.

BACKGROUND: We characterized clinical and imaging phenotypes and their association with clinical outcomes in acute ischemic stroke (AIS) survivors in the understudied region of Costa Rica. METHODS: We conducted a retrospective cohort study in AIS patients treated at a tertiary stroke center in Costa Rica from 2011-2015. Participants underwent detailed phenotyping for cardiovascular risk factors and stroke etiology. We assessed the association of ischemic brain lesion features and clinical outcomes using the Oxfordshire Community Stroke Project (OCSP) classification. RESULTS: We included 684 AIS survivors (60.2% males, aged 68.1 ± 13.6 years, mean ± SD). While the cardiovascular risk profiles and mortality rates of our patients were similar to populations in European and North American countries, only 20.2% of patients with atrial fibrillation (AF) received anticoagulation. On multivariable analysis, patients with total anterior circulation infarct (TACI) displayed an increased risk of complications (OR: 4.2; 95% CI: 2.2-7.8; p < 0.001), higher mortality (OR: 6.9; 95% CI: 2.9-16.1; p < 0.001) and lower chance of functional independence at discharge (OR: 8.9; 95% CI: 4.1-19; p < 0.001) compared to non-TACI. The comorbidity of bronchopneumonia increased the probability of death by 14.5 times. CONCLUSIONS: Our observations in a Costa Rican cohort of AIS survivors might help improve local measures for preventing and managing AIS.

Regulation of Blood Flow in the Cerebral Posterior Circulation by Parasympathetic Nerve Fibers: Physiological Background and Possible Clinical Implications in Patients With Vertebrobasilar Stroke.

Posterior circulation involves the vertebrobasilar arteries, which supply oxygen and glucose to vital human brainstem structures and other areas. This complex circulatory- perfusion system is not homogenous throughout the day; rather, its hemodynamic changes rely on physiological demands, ensuring brainstem perfusion. This dynamic autoregulatory pattern maintains cerebral perfusion during blood pressure changes. Accumulative evidence suggests that activity within the autonomic nervous system is involved in the regulation of cerebral blood flow. Neither the sympathetic nor parasympathetic nervous systems work independently. Functional studies have shown a tight and complicated cross talk between these systems. In pathological processes where sympathetic stimulation is present, systemic vasoconstriction is followed, representing the most important CNS parasympathetic trigger that will promote local vasodilation. Stroke is a clear example of this process. The posterior circulation is affected in 30% of strokes, causing high morbidity and mortality outcomes. Currently, the management of ischemic stroke is focused on thrombolytic treatment and endovascular thrombectomy within an overall tight 4.5 to 6 h ischemic time window. Therefore, the autonomic nervous system could represent a potential therapeutic target to modulate reperfusion after cerebral ischemia through vasodilation, which could potentially decrease infarct size and increase the thrombolytic therapeutic ischemic window. In addition, shifting the autonomic nervous system balance toward its parasympathetic branch has shown to enhance neurogenesis and decrease local inflammation. Regretfully, the vast majority of animal models and human research on neuromodulation during brain ischemia have been focused on anterior circulation with disappointing results. In addition, the source of parasympathetic inputs in the vertebrobasilar system in humans is poorly understood, substantiating a gap and controversy in this area. Here, we reviewed current available literature regarding the parasympathetic vascular function and challenges of its stimulation in the vertebrobasilar system.

Cerebrovascular Risk Profiles in a Saudi Arabian Cohort of Young Stroke Patients.

Background: The constantly increasing incidence of stroke in younger individuals substantiates an urgent need for research to elucidate underlying risk factors and etiologies. Heretofore, the vast majority of studies on stroke in the young have been carried out in European and North American regions. We aimed to characterize cerebrovascular risk profiles in a Saudi Arabic cohort of consecutive young stroke patients. Methods: We retrospectively analyzed data from consecutive ischemic stroke patients aged 15 to 49 years who underwent detailed cardiocerebrovascular evaluation at a tertiary stroke care center in Makkah, Saudi Arabia. Distributions of risk factors and stroke etiologies were assessed in the entire cohort and in two strata of very young (15-40 years) and young to middle-aged patients (41-49) to account for variability in suggested age cutoffs. Results: In the entire cohort [n = 63, ages 44 (34-47) median, interquartile range], dyslipidemia (71.4%) and small vessel occlusion (31.7%) displayed highest prevalence followed by diabetes (52.4%) and cardioembolism (19%). In very young patients, cardioembolism was the most prevalent etiology (27.3%). Risk profiles were similar between both age strata except for a higher prevalence of diabetes among the older cohort (31.8 vs. 63.4%, p = 0.01). Logistic regression identified diabetes as strongest predictor for association to the older strata (odds ratio = 4.2, 95% confidence interval = 1.2-14.1, p = 0.02). Conclusion: Cerebrovascular risk profiles and stroke etiologies in our cohort of young stroke patients differ from those of previous cohorts, suggesting the need for tailored prevention strategies that take into account local epidemiological data on cerebrovascular health.

Cost-effectiveness of edoxaban vs low-molecular-weight heparin and warfarin for cancer-associated thrombosis in Brazil.

BACKGROUND: Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. In Brazil, even though low-molecular-weight heparin (LMWH) is the gold standard of care for the management of cancer-associated thrombosis (CAT), its cost limits its use and therefore warfarin is commonly prescribed. Direct oral anticoagulants (DOACs), such as edoxaban, have been introduced as an alternative in this setting. OBJECTIVE: The aim of this study was to compare the cost-effectiveness of edoxaban with LMWH (Model 1) and warfarin (Model 2) to support clinicians and hospitals when choosing an anticoagulant to manage CAT. MATERIALS AND METHODS: Cost-effectiveness analyses were performed using Markov state-transition models over a timeframe of 5 years, in a hypothetical, 64 years-old patients cancer population with an index VTE event. Transition probabilities, costs, quality-adjusted life years (QALYs) and risk reductions were either derived from the literature, estimated or calculated. A willingness-to-pay limit of 3 Gross Domestic Product (GDP) per head was used. Deterministic and probabilistic sensitivity analyses were performed for robustness. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per QALY gained. RESULTS: Model 1 base case analysis demonstrated dominance of edoxaban compared to LMWH, with an ICER of $5204.46, representing cost saved per QALY lost. In Model 2, edoxaban was associated with a $736.90 cost increase vs. warfarin, with an ICER of $2541.03. Sensitivity analyses confirmed base-case results. CONCLUSION: Edoxaban represents a cost-saving alternative to LMWH for the management of CAT and is cost-effective vs. warfarin.

Deep Penetrating Nevus and Borderline-Deep Penetrating Nevus: A Literature Review.

Deep penetrating nevi (DPN) are rare melanocytic nevi, which can exhibit atypical histological features hampering the differentiation from malignant melanoma. DPN are considered benign melanocytic lesions, but rare spread to lymph nodes and unfavorable clinical outcomes associated with borderline/atypical DPN (B-DPN) has been reported. Since no guidelines are available for DPN and B-DPN, we aimed to review the literature on DPN and B-DPN to assess the management and prognosis. We screened 3,513 references from EMBASE, Scopus and Medline databases, and included 15 studies with a total of 355 DPN patients and 48 B-DPN patients. Therapeutic interventions ranged from simple excision to wide excisions and sentinel lymph node biopsy (SLNB), with block lymph node dissection in some positive SLNB cases. Follow-up periods ranged from 3 months to 23 years during which a total of five recurrences, two in DPN and three in B-DPN group, and three metastases, in B-DPN group, were reported. While some of the included studies comprised clinical and histopathological correlation, few included genetic assessment. The present review highlights the need for prospective cohort studies applying composite measures to identify effective regimens of diagnostic workup and treatment in DPN and B-DPN.

Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism.

BACKGROUND: Patent foramen ovale (PFO) is an independent risk factor for cerebral infarction. Since ~25% of the population have a PFO, the simple association of PFO with stroke is not enough to establish the diagnosis of paradoxical embolism. We evaluated possible clinical clues to the diagnosis of paradoxical embolism. METHODS: Among patients with cryptogenic ischemic stroke (CS) who were investigated for a right-to-left shunt (RLS), we compared clinical, coagulation and biochemical parameters in patients with PFO versus without PFO. RESULTS: Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and 2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism (OR, 4.39; 95% CI, 1.23-15.69; p=0.023), prolonged travel (OR, 8.77; 95% CI, 1.775-43.3; p=0.008) , migraine (OR, 2.30: 95% CI, 1.07-4.92; p=0.031), a Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33; 95% CI, 1.15-9.64; p=0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26-16.2; p=0.018) were independently associated with PFO-associated cerebrovascular events. Patients with PFO had higher plasma total homocysteine levels than patients without PFO (8.9+/-3 versus 7.9+/-2.6 micromol/L respectively; p=0.021). CONCLUSIONS: A history of DVT or pulmonary embolism, migraine, recent prolonged travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver preceding the event are clinical clues to the diagnosis of paradoxical embolism among patients with CS.

Canadian stroke best practice recommendations: Secondary prevention of stroke, sixth edition practice guidelines, update 2017.

The 2017 update of The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke is a collection of current evidence-based recommendations intended for use by clinicians across a wide range of settings. The goal is to provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations include those related to diagnostic testing, diet and lifestyle, smoking, hypertension, hyperlipidemia, diabetes, antiplatelet and anticoagulant therapies, carotid artery disease, atrial fibrillation, and other cardiac conditions. Notable changes in this sixth edition include the development of core elements for delivering secondary stroke prevention services, the addition of a section on cervical artery dissection, new recommendations regarding the management of patent foramen ovale, and the removal of the recommendations on management of sleep apnea. The Canadian Stroke Best Practice Recommendations include a range of supporting materials such as implementation resources to facilitate the adoption of evidence to practice, and related performance measures to enable monitoring of uptake and effectiveness of the recommendations. The guidelines further emphasize the need for a systems approach to stroke care, involving an interprofessional team, with access to specialists regardless of patient location, and the need to overcome geographic barriers to ensure equity in access within a universal health care system.

ASPECT scoring to estimate >1/3 middle cerebral artery territory infarction.

PURPOSE: To compare the inter-observer reliability of Alberta Stroke Programme Early CT Scoring (ASPECTS) with the ICE (Idealize-Close-Estimate) method of estimating > 1/3 middle cerebral artery territory (MCAT) infarction amongst stroke neurologists and to determine how well ASPECT Scoring predicts > 1/3 MCAT infarctions in acute ischemic stroke (AIS). BACKGROUND: The European Cooperative Acute Stroke Study suggested that > 1/3 involvement of the MCAT on early CT scan was a risk factor for symptomatic intracerebral hemorrhage (SICH) following treatment with tissue plasminogen activator (tPA) for AIS but, in the absence of a systematic method of estimation had poor interobserver reliability (Kappa 0.49). The ICE method was developed to standardize the approach to estimating early MCAT infarct size and has very good interobserver reliability (Kappa 0.72). ASPECTS has comparable interobserver reliability and is reported to predict both neurological outcome and SICH. METHODS: Five stroke neurologists were tested with 40 AIS CT scans. Each performed blinded independent assessments of early ischemic changes with both ASPECTS and ICE. The reference standard was majority opinion of 1/3 MCAT determination of five neuroradiologists. A receiver operator curve (ROC) was constructed and likelihood ratios (LR) were calculated. Chance corrected agreement (kappa) and chance independent agreement (phi) were calculated for both methods, and analysis of variance was used to calculate reliability by intraclass correlation coefficient (ICC) for ASPECTS. RESULTS: The LR for a positive test (> 1/3 MCAT) were extremely large and conclusive (approaching infinity) for ASPECTS of 0-3; were large and conclusive (30, 20, and 10) for ASPECTS of 4, 5, and 6 respectively; was an unhelpful 1 for ASPECTS of 7, and were again extremely large and conclusive (approaching zero) for ASPECTS of 8-10. A ROC plot supported an ASPECTS cutoff of < 7 as best for 1/3 MCAT estimation (94% sensitivity and 98% specificity). Kappa and Phi statistics were moderately good for both ASPECTS and ICE (0.7). ICC for ASPECTS was 0.8. CONCLUSIONS: When experienced stroke neurologists utilize a formalized method of quantifying early ischemic changes on CT, either ASPECTS or ICE, the interobserver agreement and reliability are satisfactory. ASPECTS allows for a strong and conclusive estimation of the presence of 1/3 MCAT involvement and a cutoff point of < 7 results in best test performance.

Transcranial Doppler is Complementary to Echocardiography for Detection and Risk Stratification of Patent Foramen Ovale.

BACKGROUND: In patients with patent foramen ovale (PFO), strategies are needed to identify patients at higher risk, who might benefit from PFO closure. METHODS: We studied the frequency of detection of a right-to-left shunt (RLS) using transesophageal echocardiography (TEE) among patients with cryptogenic stroke and transcranial Doppler (TCD) to detect RLS, and analyzed the prediction of recurrent stroke according to TCD shunt grade, by detection of RLS on TEE, and by atrial septal aneurysm or mobility. RESULTS: Among 334 patients with TCD, 69.8% were female, with a mean (SD) age of 53 (14) years, with a median follow-up of 420 days. There were 284 cases with TCD and TEE; 54 (19%) had atrial septal aneurysm or mobility. Echocardiography failed to show a RLS in 43 (15.1%) of the patients who had TCD and TEE, even in some patients with high-grade shunts on TCD: 18 (42%) were grade 3 or higher on TCD. Survival free of stroke or transient ischemic attack was predicted significantly by TCD shunt grade < 2 (P = 0.028), shunt grade < 3 (P = 0.03), and shunt grade < 4 (P < 0.0001); this was attenuated by adjustment for risk factors in Cox regression (P = 0.08). Neither RLS on TEE (P = 0.47), or atrial septal aneurysm or mobility (P = 0.08), predicted events. CONCLUSIONS: Our findings suggest that TCD might be more sensitive than TEE for detection of RLS, which misses some cases with substantial RLS, and might be valuable for prediction of recurrent stroke or transient ischemic attack in patients with PFO. TCD complements TEE for management of suspected paradoxical embolism.

Absence of microemboli on transcranial Doppler identifies low-risk patients with asymptomatic carotid stenosis.

BACKGROUND AND PURPOSE: Carotid endarterectomy clearly benefits patients with symptomatic severe stenosis (SCS), but the risk of stroke is so low for asymptomatic patients (ACS) that the number needed to treat is very high. We studied transcranial Doppler (TCD) embolus detection as a method for identifying patients at higher risk who would have a lower number needed to treat. METHODS: Patients with carotid stenosis of > or =60% by Doppler ultrasound who had never been symptomatic (81%) or had been asymptomatic for at least 18 months (19%) were studied with TCD embolus detection for up to 1 hour on 2 occasions a week apart; patients were followed for 2 years. RESULTS: 319 patients were studied, age (standard deviation) 69.68 (9.12) years; 32 (10%) had microemboli at baseline (TCD+). Events were more likely to occur in the first year. Patients with microemboli were much more likely to have microemboli 1 year later (34.4 versus 1.4%; P<0.0001) and were more likely to have a stroke during the first year of follow-up (15.6%, 95% CI, 4.1 to 79; versus 1%, 95% CI, 1.01 to 1.36; P<0.0001). CONCLUSIONS: Our findings indicate that TCD- ACS will not benefit from endarterectomy or stenting unless it can be done with a risk <1%; TCD+ may benefit as much as SCS if their surgical risk is not higher. These findings suggest that ACS should be managed medically with delay of surgery or stenting until the occurrence of symptoms or emboli.

3D ultrasound measurement of change in carotid plaque volume: a tool for rapid evaluation of new therapies.

BACKGROUND AND PURPOSE: New therapies are being developed that are antiatherosclerotic but that lack intermediate end points, such as changes in plasma lipids, which can be measured to test efficacy. To study such treatments, it will be necessary to directly measure changes in atherosclerosis. The study was designed to determine sample sizes needed to detect effects of treatment using 3D ultrasound (US) measurement of carotid plaque. METHODS: In 38 patients with carotid stenosis >60%, age+/-SD 69.42+/-7.87 years, 15 female, randomly assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by disc segmentation of voxels representing carotid artery plaque, after 3D reconstruction of parallel transverse duplex US scans into volumetric 3D data sets. RESULTS: There were no significant differences in baseline risk factors. The rate of progression was 16.81+/-74.10 mm3 in patients taking placebo versus regression of -90.25+/-85.12 mm3 in patients taking atorvastatin (P<0.0001). CONCLUSIONS: 3D plaque volume measurement can show large effects of therapy on atherosclerosis in 3 months in sample sizes of approximately 20 patients per group. Sample sizes of 22 per group would be sufficient to show an effect size of 25% that of atorvastatin in 6 months. This technology promises to be very useful in evaluation of new therapies.

Extending tissue plasminogen activator use to community and rural stroke patients.

BACKGROUND AND PURPOSE: Guidelines for intravenous tissue plasminogen activator (tPA) use in stroke emphasize the importance of limiting its use to facilities with imaging capabilities and stroke expertise. This prospective case series set out to evaluate the safety of tPA use in patients referred from rural communities to a tertiary center. METHODS: Prospective data of 82 consecutive patients treated with tPA in London, Ontario, were reviewed. RESULTS: Twenty-three patients were transferred to London from a rural hospital (non-London patients); 49 were first evaluated in a London emergency room (London ER); and 10 were inpatients in a London hospital at the time of stroke onset. Mean transfer time and distance to London for non-London patients were 89 minutes and 41 miles. Although symptom onset to London ER times were longer for non-London than for London ER patients (123 versus 53 minutes), the door to needle times were significantly shorter for the former (49 versus 95 minutes, P<0.005). Imaging to needle times were longer for London inpatients compared with London ER patients (55 versus 36 minutes, P=0.16). The proportion of patients with >4-point improvement on the NIH Stroke Scale or cure at 24 hours was 57%, with no difference among groups (P=0.46). The overall symptomatic hemorrhage rate at 36 hours was 2%. No significant differences in outcomes were observed at 3 months. CONCLUSIONS: This prospective study suggests that it is feasible and safe to treat rural patients referred to a tertiary care center with tPA, thus extending the benefits of thrombolysis for acute stroke to a wider population.

Long-term risk of recurrent stroke in young cryptogenic stroke patients with and without patent foramen ovale.

BACKGROUND: Among patients with a patent foramen ovale and cryptogenic ischemic stroke, the long-term prognosis is unclear. AIMS: This study aims to estimate the recurrence rate in young cryptogenic stroke patients with and without patent foramen ovale. PATIENTS AND METHODS: One hundred eighty-six cryptogenic stroke patients (aged 18-45 years) were prospectively followed for up to five-years. They were divided into two groups according to the echocardiographic presence of patent foramen ovale. All patients received aspirin (100 mg/day) for secondary prevention. RESULTS: Mean age was 32·3 (standard deviation 7·9) years. During the mean follow-up of 66 months five patients with patent foramen ovale had recurrent strokes compared with 11 patients without patent foramen ovale. The average annual rate of recurrent cerebral ischemia was 1·1% and 1·6% for patients with and without patent foramen ovale, respectively. The recurrence rate did not increase with the presence of patent foramen ovale, atrial septal aneurysm or other variables. More than 60% of the reported cases achieved a good functional outcome. CONCLUSIONS: Young patients with cryptogenic ischemic stroke with and without patent foramen ovale have a low recurrence rate in a long-term follow-up and most present a favorable outcome. Patent foramen ovale with or without atrial septal aneurysm did not increase the risk of recurrence.

Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis.

OBJECTIVE: To assess the effect of more intensive medical therapy on the rate of transcranial Doppler (TCD) microemboli and cardiovascular events in patients with asymptomatic carotid stenosis (ACS). DESIGN: A prospective study. SETTING: A teaching hospital. PATIENTS: Four hundred sixty-eight patients with ACS greater than 60% by Doppler peak velocity. MAIN OUTCOME MEASURES: We compared (1) the proportion of ACS patients who had microemboli on TCD, (2) cardiovascular events, (3) rate of carotid plaque progression, and (4) baseline medical therapy, before and since 2003. RESULTS: Among 468 ACS patients, 199 were enrolled between January 1, 2000, and December 31, 2002; and 269 were enrolled between January 1, 2003, and July 30, 2007. Microemboli were present in 12.6% before 2003 and 3.7% since 2003 (P < .001). The decline in microemboli coincided with better control of plasma lipids and slower progression of carotid total plaque area. Since 2003, there have been significantly fewer cardiovascular events among patients with ACS: 17.6% had stroke, death, myocardial infarction, or carotid endarterectomy for symptoms before 2003, vs 5.6% since 2003 (P < .001). The rate of carotid plaque progression in the first year of follow-up has declined from 69 mm(2) (SD, 96 mm(2)) to 23 mm(2) (SD, 86 mm(2)) (P < .001). CONCLUSIONS: Cardiovascular events and microemboli on TCD have markedly declined with more intensive medical therapy. Less than 5% of patients with ACS now stand to benefit from revascularization; patients with ACS should receive intensive medical therapy and should only be considered for revascularization if they have microemboli on TCD.