American Heart Association

Monthly Archives: December 2014

Donut Daily for Stroke Prevention?

Duy Le, MD

Li W, Katzmarzyk PT, Horswell R, Zhang Y, Zhao W, Wang Y, et al. Body Mass Index and Stroke Risk Among Patients With Type 2 Diabetes Mellitus. Stroke. 2014

It sounds like a paradox, and it probably is. Much like my recent trip to the movie theater to watch Interstellar (without spoiling the movie), I’m having a hard time making sense of how things can happen in the future without ever having happened in the past. I’m being told that 1+1 = infinity. This is the stuff of black holes, singularities and Tesseracts!




Much work has been done regarding the evaluation of obesity and all cause and CVD mortality in diabetic patients. Results have wildly varied from positive, inverse, U-shape to no associations. Most notably however is the recurring result where obesity pre-disposes to a certain chronic disease state, yet the more obese you are, the more you are protected against that disease. This phenomenon is called the Obesity Paradox and has been seen time and time again in different studies. Li et al jump into this spaceship of a concept and add a twist; they evaluate obesity in stroke among diabetic patients.

From 1997-2013 patients from LSU health care services, with diabetes diagnosed by ICD-9 code within 5 years, were included in this study. Patients with CAD, smoking history or incomplete data sets were excluded to avoid potential confounders. Over 29,000 patients were included. ICD-9 codes were also used in determination of stroke as an endpoint for these patients. BMI was evaluated as both a continuous and categorical variables. During a follow up period of 8.3 years, 2,883 subjects developed stroke (2,821 ischemic and 109 hemorrhagic). Hazard ratios associated with different levels of BMI at baseline 18.5-24.9 [reference group], 25-29.9, 30-34.5, 35-39.9, >40) were 1.00, 0.86, 0.83, 0.76 and 0.70 for total stroke. The same patterns were apparent individually for both ischemic stroke and hemorrhagic stroke. Several factors including HTN, A1c, GFR, age, sex ,race were controlled for, yet there still remained an inverse relationship.

Many have argued that the obesity paradox is not true and offer up some of the following reasons for refuting such a claim: The sample sizes in the reports of the obesity paradox are generally small; however Li et al have a fair strong sample size to evaluate. There are others who argue that chronic disease states cause wasting and so naturally those who are more severely effected by a disease will have decreased weight/BMI. In this argument, BMI is determined by the illness, and not the other way around. Stroke however unlike other chronic processes comes suddenly; and thus one could argue that this claim is not valid. Ultimately, however, the most powerful argument against the obesity paradox a broad sweeping umbrella of an argument that is not interested in explaining any specifics. It is a mathematical argument that reminds us that statistical techniques show association between factors; not cause effect. Yet, if this is the case, how do we explain seeing this paradox over and over again? One is left to believe that there must be a specific reason.

For the record, I absolutely loved Interstellar. The complexity of the concepts and its inability to be flushed out on screen caused some to criticize it for being sloppy. Sometimes though we don’t want all of life’s answers laid out on a silver platter; it’s more exciting to think through concepts and revel in the potential explanations. The same can be said of the obesity paradox. We may OR we may not ever know the reason; maybe it’s not a paradox after all. But we should let this simmer a little longer and try to entertain why and how it exists. And in the process we may discover broader implications of science and health. But until we figure it out, I wouldn’t endorse eating donuts to protect against stroke just yet.

Residual High Grade Stenosis of the Extracranial ICA after Treatment

A. Kaleel, MD, MSc

Luitse MJA, Velthuis BK, Dauwan M, Dankbaar JW, Biessels GJ, and Kappelle LJ. Residual High-Grade Stenosis After Recanalization of Extracranial Carotid Occlusion in Acute Ischemic Stroke. Stroke. 2014

The guidelines for secondary prevention after an acute ischemic stroke are under constant revision as new data becomes available. This study sought to provide insight into the future management of residual high-grade stenosis of the extracranial ICA after treatment of a symptomatic occlusion. This prospective study evaluated 126 patients (86 had adequate follow up imaging and were included in the analysis) from the prospective Dutch acute stroke study (DUST) between May 2009 and May 2013 who suffered an acute occlusion of the internal carotid artery followed by treatment with rtPA, endovascular treatment, mechanical clot disruption or retrieval, or a combination of these. Among these patients, 57.4% were treated with intravenous rtPA and 12.8% underwent endovascular treatment.



Inclusion criteria were clinical diagnosis of acute stroke; non-contrast head CT (NCCT), CT perfusion (CTP), and CT angiogram (CTA) studies performed within 9 hours of symptoms onset; and no known history of renal failure or allergy to contrast agents. Following treatment with one of the aforementioned approaches, assessment was recommended with NCCT, CTP, and CTA within three days after stroke onset with a required follow up imaging window of the carotid artery to be done within seven days of admission.

In 39.5% of the 86 patients the occluded ICA was completely recanalized following treatment, 17.4% had residual stenosis of <30%, 3.5% had residual stenosis of 40-49%, 2.3% had residual stenosis of 50-69%, 16.3% had residual high-grade stenosis of ≥70%, 3.5% had near occlusion, and 57% had persistent occlusion. Of the 14 patients with ≥70% stenosis, 8 were later treated with carotid endarterectomy, indicating that prompt follow up imaging after initial treatment led to added treatment options.

This study concluded that in one out of six patients, there is persistent residual high grade stenosis despite treatment, suggesting that follow up imaging within a week was needed to determine if further treatment may be indicated to prevent recurrent events.

Risk stratification for paroxysmal atrial fibrillation using EKG metric a useful tool in acute ischemic stroke patients

Chirantan Banerjee, MD

Hoshino T, Nagao T, Shiga T, Maruyama K, Toi S, Mizuno S, et al. Prolonged QTc Interval Predicts Poststroke Paroxysmal Atrial Fibrillation. Stroke. 2014

There has been significant research interest in the last few years focusing on cryptogenic stroke patients and the need for long term cardiac ambulatory telemetry to maximize the chance of detecting paroxysmal atrial fibrillation (PAF) in the cohort. CRYSTAL AF and EMBRACE trials were published in June this year and made a strong case for 30 day monitoring, especially in patients above age 55. For vascular neurologists, tools that help stratify a patient’s pretest probability assume special relevance as they may help tailor how long should a patient be monitored for PAF. In the cardiac literature, several EKG markers have been shown to be associated with future risk of PAF including P wave dispersion (difference between the longest and the shortest P-wave duration), P wave duration, and P-wave index (SD of P-wave duration across all leads). 


In the current study, Hoshino et al assessed the predictive value of prolonged QT interval corrected for heart rate (QTc) in acute ischemic stroke patients with future detection of PAF. The retrospective analysis was carried out on the Tokyo Women’s Medical University stroke registry which includes 1038 consecutive acute ischemic stroke patients between April 2003 and Nov 2013. After exclusions, 744 patients were eligible for analysis. Mean age in the cohort was 67 years, and 9.3% patients had PAF detected post-stroke with median latency of 3 days. Age, absence of vascular etiology, congestive heart failure, left atrial dilation on TTE, and higher admission NIHSS score were associated with PAF. Longer QTc interval was an independent predictor of PAF, with OR 1.41 per 10ms increase in QTc. Despite important limitations of the study such as its retrospective nature and limited external validity in the US population (QTc has been shown to have ethnic differences), it replicates data from cardiac patients in the ischemic stroke population for the first time. Detecting PAF is extremely important in appropriate stroke patients as it leads to a change in management, and a potential for drastic risk reduction for future strokes. Biomarkers like QTc enable us to reliably predict or identify these patients, and thus help advance acute clinical stroke care.

Responsiveness after Hemorrhagic Stroke – Role of the Frontal Networks

Rizwan Kalani, MD

Mikell CB, Banks GP, Frey HP, Youngerman BE, Nelp TB, Karas PJ, et al. Frontal Networks Associated With Command Following After Hemorrhagic Stroke. Stroke. 2014

We often assess level of arousal by a patient’s ability to follow commands. In this study, Mikell et al evaluated which brain structures are necessary to follow commands in the setting of acute intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) using a multimodality approach – a combination of structural and functional MRI (fMRI) as well as continuous EEG monitoring.


Data from 25 patients with spontaneous ICH or SAH that completed all components of the multi-modality testing were analyzed from a prospective, single-center database. 9 patients (36%) were unresponsive (unable to follow simple, 1-step commands) and 16 were awake at time of testing. Structural injury to the pons, midbrain, and thalamus was initially evaluated (by lesion volume quantification) using structural MRI. Resting state fMRI was then used to identify which brain networks were disrupted in the unresponsive patients compared to those who were awake. The relationship between the default mode network (DMN – the brain regions active when a person is awake and at rest) and the task-positive network (TPN – areas responding to attention-demanding tasks) were evaluated. Lastly, continuous EEG was used to confirm changes in functional connectivity seen.

There was no significant difference between the hemorrhage sizes of the unresponsive and awake patients. 6 functional networks were impaired in unresponsive patients by fMRI – these were located in the premotor, dorsal anterior cingulate, and supplementary motor areas. Connectivity between the DMN and right orbitofrontal cortex was decreased in unresponsive patients. Interestingly, new connections between the TPN and DMN were seen in unresponsive patients that were not seen in those who were awake. These findings were supported by EEG coherence data.

This manuscript suggests that disruption of frontal network connectivity (instead of the actual structural injury) accounts for unresponsiveness in the setting of ICH/SAH. It supports the idea that altered connectivity to (rather than within) the DMN is lost in an unresponsive state. Future studies will need to evaluate the mechanisms by which these network connectivity changes occur and how each individual network involved affects consciousness. The principal limitations of this study are the small number of patients included and inability to evaluate the effect of intracranial pressure on the findings.

By |December 10th, 2014|prognosis|0 Comments

Does an ER admission and CT scan examination for peripheral vertigo reflect an increased risk for stroke in the short term?

Prachi Mehndiratta, MD


Grewal K, Austin PC, Kapral MK, H, and Atzema CL. Missed Strokes Using Computed Tomography Imaging in Patients With Vertigo:Population-Based Cohort Study. Stroke. 2014

Is the vertigo of peripheral or central origin? This is always the dilemma in patients that present with the non-specific symptom of dizziness to the emergency room. About 3% of patients per year that present to the ER with dizziness and vertigo symptoms are diagnosed with stroke. History and examination are not foolproof in ascertaining the origin of vertigo and work up is often at the discretion of the physician in charge.



This Canadian study attempted to determine if there were differences in the number of short or long-term strokes in patients admitted to the ER with “peripheral vertigo” and underwent a non-contrast CT head for screening. The investigators utilized the Canadian Institutes of Health Information National Health Care Ambulatory Reporting System (CIHI-NACRS), which is an anonymized database of all ER visits in Ontario, Canada. Patients aged 18-105 years, with a ICD 10 diagnosis of peripheral vertigo, admitted to the ER between April 2006 and March 2011 were included.  Patients admitted to urgent care centers; those who died in the ER or were admitted to the hospital from the ER and those with recurrent ER visits were excluded. It was assumed that those who were discharged from the ER had a negative CT scan of the head.

Propensity-score matching a.k.a. the likelihood of receiving a CT head based on comorbidities was performed for the two groups of patients- those who underwent a CT head and those who did not. Multivariate logistic regression was used to estimate this propensity score. Outcomes of strokes within 30 day, 90 days and 365 days as well all cause mortality were calculated between the two groups.

A total of 8,596 (20.6%) received head CT imaging in the ED out of 41,794 total patients. The majority were without contrast (96.9%). Median age in both groups was 63.0 years (IQR 51.0-74.0) and 62% were female. Risk factor distribution was similar in the two groups and amongst the exposed patients these strokes occurred markedly earlier after ED discharge (median 32 days, IQR 4.0-133.0) than among unexposed patients (median 105 days, IQR 11.5-204.5). The relative risk of stroke at 30 days among exposed patients was twice (2.27; 95% CI, 1.12-4.62) that of unexposed patients.

The authors justify the higher rate of strokes in the group receiving CT imaging by the increased risk for a stroke in the peri-TIA period. It is also conceivable that these patients had cerebellar or brainstem stroke that was poorly visualized on a non contrast CT. These results must be understood in light of its limitations. This is a retrospective cohort, albeit with a large number of patients. Both groups were similar in terms of risk factors but not much is known about their clinical presentation, difference in exam and the reason for CT examination. Additionally any study utilizing ICD 10 codes is subject to inaccuracies in coding. The finding of increased number of strokes in the short term after an ER admission and CT scanning for vertigo highlights that these patients should instead be imaged by means of a MRI scan that is more sensitive for stroke in the posterior fossa.

Getting Hot in Here: Increased Temperature Difference Values in Culprit Carotid Arteries by Microwave Radiometry

Vikas Pandey, MD


Toutouzas K, Benetos G, Drakopoulou M, Deligianni C, Spengos K, Stefanadis C, et al. Incremental Predictive Value of Carotid Inflammation in Acute Ischemic Stroke. Stroke. 2014

Carotid artery disease is a major risk factor for ischemic strokes and one that is important to discover during a patient’s stroke workup due to the striking benefit of treating symptomatic carotid disease. Current imaging modalities however, are limited to either measurement of blood velocities to determine hemodynamic significance (ultrasound) or anatomical structure based imaging (MRA or CTA). The group out of Greece felt that a different dimension would be added to qualifying a carotid plaque if it were possible to measure some indicator of carotid inflammation. They decided to use microwave radiometry (MWR) to non-invasively assess the internal temperature of carotid artery plaques (as an indicator of plaque inflammation) and wondered if there was a difference in those temperature measurements in patients who had ischemic strokes due to extracranial carotid disease and bilateral carotid plaques. 


The group collected patients with anterior circulation strokes in whom the isolated cause of their stroke was determined to be carotid disease with bilateral carotid plaques present on ultrasound. Patients with atrial fibrillation were excluded. These patients underwent MWR of bilateral carotid arteries within the first 24 hours of their admission. Patients would undergo a second brain imaging study (usually MRI) to rule out lacunar infarctions and TIAs, and also excluded patients found to have alternative causes of stroke. A total of 50 patients were analyzed in the study. MWR measurements were performed on culprit (side of the stroke) and nonculprit carotid arteries at target segments of the carotid artery (segment of each carotid artery with the highest plaque thickness). The temperature difference was defined as the temperature of the target segment minus the minimal temperature of each carotid.

The culprit arteries had thicker plaque segments compared to nonculprit sides (3.76 vs 2.53 mm, p <0.001), and this difference was also present after adjustment for sex, age, vascular risk factors and temperature difference values. Culprit carotid arteries had a higher temperature difference values compared to asymptomatic carotid arteries (0.93 vs 0.58 degress C, p<0.001). This would signify more plaque inflammation in culprit carotid arteries. The study provides key information regarding qualities of the culprit carotid artery in reference to plaque inflammation, a dimension currently unable to be measured reliably. This measurement may also have promise in determining the vulnerability of rupture of asymptomatic plaques. The group offers a great noninvasive technique that is a feasible additive to the information stroke neurologists obtain during a stroke workup, and a tool for use in stroke prevention.

@DrVikasNeuro

Ischemia on CT is Predictive of Recurrent Stroke within 90 days for TIA/non-disabling Stroke Patients

Duy Le, MD

Wasserman JK, Perry JJ, Sivilotti MLA, Sutherland J, Worster A, Émond M, et al. Computed Tomography Identifies Patients at High Risk for Stroke After Transient Ischemic Attack/Nondisabling Stroke: Prospective, Multicenter Cohort Study. Stroke. 2014

Wasserman et al evaluate the predictive value of CT findings and risk of stroke. Specifically, they evaluate 2028 patients who presented to the hospital within 48 hours of symptoms, who had either a TIA or non-disabling stroke, receiving a scan within 24 hours. Head CT’s were evaluated by local neuro-radiologist as either being present or absent for evidence of acute ischemia, chronic ischemia and microagniopathy. Do these aforementioned patients with recent TIA or non-disabling stroke predict a higher likelihood of stroke in the forthcoming days? Wasserman et al answer: Yes! Stroke risk at 90 days was greater if baseline CT showed acute ischemia alone (10.6%; p = 0.002), acute + chronic ischemia (17.4%; p = 0.007), acute ischemia + microangiopathy (17.6%; p=0.019), or acute + chronic + microangiopathy (25.0%; p =0.029). The average age of patient’s was 67.9 +/- 14.5. 



Limitations of this study include the fact that only CT’s were used. CT’s are known to be less sensitive at detecting ischemia as compared to MRI’s. However some may argue that this models real world practical evaluation of strokes in the acute and early sub-acute strokes. A second limitation is that there was no distinction made between symptomatic and non-symptomatic acute lesions on head CT. Although acute ischemia seen on imaging in those with TIA symptoms or non-disabling stroke was shown to have higher risk of repeat ischemic event, from the data, we are unable to determine if patient’s new event was secondary to a new stroke or progression of the original stroke. This potentially may skew the data.

This study nonetheless, does show that imaging is useful in predicting future stroke in 90 days. Some may argue that imaging used as single parameter in this clinical setting may not be too useful. However, if used in conjunction with the ABCD2 score (as is seen in the new ABCD2I score), there may be clinical application. As with the ABCD2 score which stratifies risk of an immediate stroke, using imaging as a stroke risk marker will act to dictate management. Should a patient be admitted for expedited stroke work up inpatient, or can the patient have an outpatient work up? For those who mull over this question, imaging can act as an additional data point. It does seem intuitive otherwise that having a prior stroke would increase the risk of a subsequent stroke. However, now we can quantify that risk within 90 days and specify that to imaging findings.

By |December 5th, 2014|prognosis|0 Comments

Prostacyclin changes properties of blood vessels but not outcomes in SAH

Rajbeer Singh Sangha, MD

Rasmussen R, Wetterslev J, Stavngaard T, Juhler M, Skjøth-Rasmussen J, Grände PO, and Olsen NV. Effects of Prostacyclin on Cerebral Blood Flow and Vasospasm After Subarachnoid Hemorrhage: Randomized, Pilot Trial. Stroke. 2014

Delayed ischemic neurologic deficit (DIND) is a serious complication of aneurysmal subarachnoid hemorrhage. Although advances in treatment have improved prognosis for these patients, long-term clinical outcomes remain disappointing and the causes of DNID still remain largely understood. In the past it was thought to be secondary to angiographic vasospasm however current research models have debunked this theory suggesting that the factors that cause DNID may be more complex. The condition may manifest itself anytime within the first two weeks but most incidences occur between Day 5 and Day 10 and a peak incidence around Day 8. Factors related to the vascular endothelium and the smooth muscle cells are believed to play an important role. Prostacyclin is an endogenous substance released from the vascular endothelium. It is a potent vasodilator and inhibitor of leukocyte activation, platelet aggregation and leukocyte-endothelial interactions, all of which have been postulated to have an impact on the development of DIND. The authors of this study conducted a randomized, placebo-controlled trial, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH. 



The trial was a single-center, randomized, placebo controlled, parallel group, blinded, clinical, pilot trial. The primary outcome measured was change in global CBF from baseline calculated as CBF during intervention minus CBF at baseline. Secondary outcomes included occurrence of one or more DIND during the intervention, cerebral vasospasm qualified as severe, moderate, mild, or absent on a CT angiography, change from baseline in regional blood flow in each of the six vascular territories, and Glasgow Outcome Score (GOS) at three months after SAH. 111 patients met the inclusion criteria and of these 90 patients were included. The mean change in CBF for the placebo group was -4.65 ml/100g/min (95% CI, -8.64 to -0.17). The mean change in CBF for the groups receiving prostacyclin 1 ng/kg/min and 2 ng/kg/min were -2.05 (95% CI, -5.58 to 1.47) and -0.066 (95% CI, -3.59 to 3.46), respectively. Unadjusted analysis showed no statistically significant difference between the 3 groups (P =0.20). The highest incidence of DIND was observed in the placebo group (38%) and the lowest incidence was observed in the group receiving prostacyclin 1 ng/kg/min (21%); however, the difference between the three groups was not statistically significant (P =0.28). Analysis adjusted for baseline covariates was also not statistically significant (P =0.36).

This study was the first randomized, clinical trial investigating the possible pharmacological effects of prostacyclin on the human brain after subarachnoid hemorrhage. Based on the primary outcome in this trial, global CBF, was not markedly affected by administration of prostacyclin and does not seem to increase the net perfusion of the brain after SAH. While not statistically significant, the group receiving 1 ng/kg/min only approximately half of the DIND incidences and angiographic vasospasm was observed compared with the group receiving placebo. This could mean that the study was not powered to detect a difference. Given the safety of prostacyclin that was established from this trial, future trials investigating low-dose prostacyclin in relation to SAH should consider focusing on doses around 1 ng/kg/min and should be powered to detect changes in clinical outcome. Furthermore, patient outcomes should be analyzed using more sensitive scales such as validated self reported measures of quality of life (Neuro QOL); this would allow for smaller changes in functional outcomes to be detected as opposed to the glasgow coma scale.

By |December 4th, 2014|treatment|0 Comments

Algorithmic Stroke Neurology In All Its Glory

Ali Saad, MD

Ay H, Arsava EM, Andsberg G, Benner T, Brown Jr RD, Chapman SN, et al. Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network. Stroke. 2014

This group created an online tool where you can enter data containing a patient’s demographics, neuroimaging, vessel imaging, cardiac workup, and other diagnostics.The tool then uses an algorithm to determine the most likely stroke phenotype (by TOAST criteria) and cause. Users were stroke attendings, fellows, or neurology residents and from the US and Europe. They found that there was good inter-rater reliability between users for phenotype (kappa 0.73, 95%CI:0.70-0.75) and etiology (kappa 0.72, 95%CI:0.69-0.75). They also found that cause and phenotype did not necessarily correlate, as expected, because a patient might have a stroke risk factor found on work up that was not the immediate cause of the incident stroke. you can try the tool out for free right here.



So what’s the big deal? The fact that we can create such an algorithm for stroke diagnosis is a good thing. It means stroke neurology, as a field, has (for the most part) adequate randomized control trials to make evidence-based decisions AND has easy-to-use and reliable diagnostic tools (neuro and vascular imaging). as long as the user has the necessary data to input and some basic knowledge of neurology, they have a good chance of figuring out the stroke type and thus guide treatment. the same cannot be said for all neurological subspecialties. 


Is this a bad thing? Are we becoming automatons rather than critical thinkers? As with most technologies, there is the risk of falling into that behavior. The good thing about it is, it is proof that we have standards of practice that come from evidenced-based medicine that anyone can use anywhere on any patient. It levels the playing field by providing a reliable diagnostic tool to anyone with an internet connection.

With the advent of evidence-based medicine and algorithmic protocols, algorithms will likely be created for other diseases. These algorithms can then be converted into online tools and eventually virtual (or physical) robot doctors. For those interested, check out this podcast, Will computers replace doctors?

Robots aside, does this mean the vascular neurologist = internist + online tool or ER physician + online tool? although the tool can give an etiology, treatment choice still depends on several things the tool doesn’t address. This includes patient preference and provider experience with direct acting oral anticoagulants, choice of immunosuppressant for things like CNS vasculitis, and consideration of patient comorbidities in prescribing some treatments. a vascular neurologist would be more experienced with such literature and decision making.

Some takeaway clinical pearls from this study: patients over age 50 are 4 times more likely to have cardioembolic stroke and 6 times less likely to have stroke from other uncommon causes compared to those under age 50. The incidence of large artery athero peaked between ages 50-70, but the incidence of cardioembolic stroke as the likely etiology continuously increased with age. the chance of meeting criteria for “Evident” as a level of confidence for stroke subtype was between 40-50% across all stroke etiologies. limitations of the study include a population that was around 80% white and no use of extended cardiac monitoring.

How does this tool change current practice? I believe it is best used primarily in 2 situations: training purposes for residents/fellows and when you’re stumped about the diagnosis. going down the list of stroke etiologies and diagnostic tools reminds you of all the tools you have in your belt and makes you think of things that may not have been on your initial differential. when someone has a flame shaped ICA dissection on CTA and ipsilateral watershed infarcts, filling out the checkboxes in the tool seems unnecessary and cumbersome.

Does plaque echolucency increase risk for ipsilateral stroke in patients with asymptomatic Carotid stenosis?

Prachi Mehndiratta, MD

Gupta A, Kesavabhotla K, Baradaran H, Kamel H, Pandya A, Giambrone AE, et al. Plaque Echolucency and Stroke Risk in Asymptomatic Carotid Stenosis: A Systematic Review and Meta-Analysis. Stroke. 2014

In light of improvement in intensive medical therapy, many question the need for asymptomatic carotid intervention and surgery despite two large positive clinical trials. Carotid plaque characteristics might help identify a sub population within this cohort of asymptomatic carotid stenosis patients that may have a higher risk of ipsilateral stroke. Carotid ultrasound is a tried and tested non invasive test employed to describe plaque characteristics such as plaque echolucency that is an imaging surrogate for hispathological core necrosis and intraplaque hemorrhage.



The authors performed meta-analyses of 7 studies evaluating whether ultrasound characterization of carotid plaque echogenicity is a predictor of ipsilateral stroke in asymptomatic carotid atherosclerotic disease. Manuscripts written in the English language, with atleast 30 or more asymptomatic patients, with follow up data available for >12 months on atleast 85%of the cohort were included. An effort was made to assess outcome ascertainment bias that relies on blinding of investigators, confounding by other variables and completeness of follow up data. A meta-analysis of studies that met two criteria was performed – 1) a relative risk (RR) was calculable; 2) echolucency test results were presented in a dichotomized or categorical fashion. Random effects modeling was used for statistical analysis as the included studies did not have the same effect size, 3 pre specified subgroup analyses were performed to evaluate studies with blinded adjudicators, studies in which plaque echolucency determination was made by subjective visual interpretation and newer studies published since 2000.

A total of 8 articles that were all prospective, longitudinal, non-randomized observational studies met criteria for qualitative review and pooling. Mean age ranged from 64.0-72.6 years and there was a male preponderance. Seven articles met criteria for calculation of relative risk and mean follow up period was 37.2 months. When subjects with and without carotid stenosis on medical management were evaluated, a positive relationship between plaque echolucency and the risk of future ipsilateral stroke was found with random effects (RR of 2.31, 95% confidence interval [CI], 1.58-3.39, P<.001). This relationship was true for risk across all stenosis severities. No statistically significant heterogeneity or publication bias was present in any of the meta-analyses.

This study has several important clinical implications. Patients with echogenic plaques have a 2.3 fold greater risk for ipsilateral stroke. This risk is present across all degrees of carotid stenosis and does not vary when adjustments were made for studies that utilized subjective visual interpretation of plaques, or studies with ascertainment and confounding bias were excluded. The authors concede that the studies included in this meta-analysis are fraught with some serious limitations due to unclear loss to follow up, ascertainment bias and selection bias due to inclusion of only medically managed patients. Despite these limitations, this study provides significant evidence in favor of detailed plaque evaluation in patients with asymptomatic carotid stenosis. An avenue for growth would be development of a standardized and validated technique for doing so.