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Monthly Archives: September 2014

Broken Cookie Cutter: The Natural History of Unruptured Intradural Fusiform Aneurysms

Vikas Pandey, MD

Fusiform intracranial aneurysms are an entity that are not well studied, mainly due to the fact that fusiform aneursysms are rarer compared to saccular ones. The concept that the etiology of fusiform aneurysms is multifold leads to questions whether the approach to treat these types of aneuryms should be different based on specific aneurysmal characteristics as well as parts of the patient’s medical history. The authors headed by the interventional neuroradiology group from Toronto challenged the idea that treating fusiform intradural aneurysms carries a poor prognosis, an idea that has been ingrained due to poor prognosis of previously studied populations of veretebrobasilar fusiform aneurysms, and proposed that the natural histories of the different etiologies of fusiform aneurysms may be different.

The author conducted a retrospective study of patients seen between a 13 year period at Toronto Western Hospital cerebrovascular clinic and looked at 121 patients with unruptured intradural aneurysmal dilatation of >50% of the vessel wall circumference. Patients that were excluded were those with diameter >2.5 cm (these have a known poor natural history) and those with entirely extradural aneurysms. The aneurysms were categorized into those that were related to atherosclerosis and those that weren’t based on imaging criteria such as presence of eccentric, calcified plaques present within the aneurysms, as well as with supporting criteria based on risk factors for atherosclerosis (25 out of 121 put into this group). The groups were followed for 193 and 97 person-years for the non-atherosclerotic and atherosclerotic groups respectively. Results showed that the mortality in the atherosclerotic group was higher (5.2%/year vs 0.51%/year) and they had a higher aneurysm progression risk (12%/year vs 1.6%/year compared to the non-atherosclerotic counterparts.

The results provide an interesting dimension to treatment algorithms for fusiform aneurysms. The common sense risk factors such as a size and symptomatic presentation are not to be overshadowed, but looking into aspects of the pathophysiology of aneurysms which may appear similar on initial radiographic studies is an idea that should be applied to all areas of medicine. The authors bring up the very valid point that atherosclerotic aneurysms and non-atherosclerotic fusiform aneurysms should be thought of as entirely different disease entities. “Cookie cutter” medicine is very hard, especially in the field of stroke neurology and the authors provide us with an excellent example of this.


By |September 30th, 2014|prognosis|Comments Off on Broken Cookie Cutter: The Natural History of Unruptured Intradural Fusiform Aneurysms

IV-TPA Continues to be Cost-Effective

Rizwan Kalani, MD

Boudreau DM, Guzauskas GF, Chen E, Lalla D, Darren Tayama D, Fagan SC, and Veenstra DL. Cost-Effectiveness of Recombinant Tissue-Type Plasminogen Activator Within 3 Hours of Acute Ischemic Stroke: Current Evidence. Stroke. 2014

Many years ago, Bill Foege, brought up the idea that potential solutions to many of the existing health system problems can come from repeatedly asking ourselves how to optimally balance costs, quality, and outcomes. It is clear that not all diagnostic tests and treatments we offer and order on patients affects clinical outcomes. Few interventions have as profound of a benefit as intravenous tissue plasminogen activator (TPA) given in the first three hours of symptom onset of suspected acute ischemic stroke. In 2010, an estimated $74 billion was spent on stroke-related medical costs and disability; this is likely going to increase given the rising cerebrovascular disease burden. Analysis from the NINDS TPA Stroke Study supported TPA administration within the first three hours of symptom onset resulting in net cost savings to the health care system; only a single US study evaluated this and it was published in 1998.

Boudreau et al re-evaluated cost-effectiveness of TPA given within three hours of symptom onset using most recent data on its efficacy, safety, and cost. A decision analysis comparing use of TPA vs no TPA from the perspective of a US third party payer (insurance company, Medicare/Medicaid) was completed. This was done by review of recent literature (meta-analyses, secondary stroke prevention trials, health economic evaluations) taking into account post-stroke disability at 3 months (modified rankin score), symptomatic intracerebral hemorrhage rates, long-term outcomes (annual stroke recurrence and mortality rates), as well as acute care and long-term healthcare costs. Subsequently, quality-adjusted life years (QALYs) and lifetime direct health costs were calculated between the TPA and no-TPA groups in the model.

The primary analysis demonstrated that lifetime medical costs and QALYs were: $287,400 & 4.29 for the TPA group and $312,400 & 3.90 in the no-TPA group, respectively. Thus, TPA treatment increased QALYs by 0.39 and decreased cost by $25,000. The results of the model held true with sensitivity analyses.

This report demonstrates TPA given within 3 hours of symptom onset is cost-effective from the viewpoint of a US payer, taking into consideration more recent data on outcomes and medical costs. From this analysis, for every 100 patients treated, 39 years of QALYs are gained and $2.5 million are saved. It reiterates the importance of efforts targeting improvement in TPA delivery, such as telestroke and Get With the Guidelines Stroke program.
By |September 29th, 2014|treatment|3 Comments

This could be a game-changer for predicting stroke in asymptomatic CAS!

Daniel Korya, MD

Kirkpatrick AC, Tafur AJ, Vincent AS, Dale GL, and Prodan CI. Coated-Platelets Improve Prediction of Stroke and Transient Ischemic Attack inAsymptomatic Internal Carotid Artery Stenosis. Stroke. 2014

In his published lectures of 1886, Sir William Osler, the “Father of Modern Medicine”, described platelets as colorless protoplasmic discs. He called them “blood plates” and defined them as the third corpuscle.  In the mid-1800’s, the French physician Albert Donne may have been one of the first to identify platelets as a distinct entity when he claimed there was a more elusive third component to blood other than erythrocytes and leukocytes. 

In 2005, Dale introduced a subset of platelets that were produced after co-activation with collagen and thrombin, called “coated-platelets”. This population of platelets was more likely to be elevated in patients with large vessel ischemic strokes as compared with small vessel ischemic strokes. Coated-platelets comprised about 30% of the total platelet population in average persons, while they made up 39.4% of platelets in patients with large vessel strokes and only 21.8% in patients with small vessel strokes. Patients with symptomatic large-artery atherosclerosis with coated-platelet levels of 50% or greater were almost 7 times more likely to have recurrent strokes as compared with patients with less than 50% coated-platelet levels.

The most famous large artery to cause ischemic stroke is the carotid artery. We know from prior studies that patients with symptomatic carotid artery stenosis (CAS) stand to benefit from carotid stenting or endarterectomy. The benefits of revascularization for patients with asymptomatic disease are less certain. In fact, the risk of stroke in patients with asymptomatic CAS has recently been reported to be as low as 1%. Predicting who the 1% will be has proved challenging.  Now, thanks to Kirkpatrick and her colleagues, we may have a new weapon in the fight against stroke.

This prospective study evaluated 329 patients with asymptomatic CAS who had adequate Doppler ultrasound performed with the percentage of stenosis documented.  These patients were then followed up to 39.8 months with a median of 10.1 months to determine rates of stroke, TIA, vascular death and revascularization (repeated Doppler).  A coated-platelet assay was used to determine the percent of coated-platelets in these patients.  Important information pertaining to these patients was also recorded; such as, use of medications that can influence coated-platelet levels (SSRI, statin or anti-platelet agent), history of hypertension, diabetes, dyslipidemia, CAD, PAD or ESRD.

The major findings of this study were quite powerful. The “magic numbers” to keep in mind here are 50% and 45%. There were patients with 50% or greater CAS and patients with less than 50% CAS. Some of these patients had 45% or greater coated-platelets and some of them had less than 45% coated-platelets. Patients who had 45% or greater coated-platelets were compared based on their level of CAS, and the patients with 50% or greater CAS had a 45.2 hazard ratio (p=.0004) and an incidence of 21.54 events (ipsilateral stroke or TIA) per 100 person-years.  Patients who had less than 45% coated-platelets were then split up into their respective two groups: 50% or greater CAS versus less than 50% CAS. In patients with less than 45% coated-platelets the level of carotid artery stenosis did not make a difference (i.e. there was no difference in the hazard ratio), and the event rate was 1.27 per 100 person-years. 

Based on these results, Kirkpatrick was able to stratify asymptomatic patients with 50% or greater CAS into a “low-risk” category if their coated-platelets were less than 45%.  Conversely, they were also able to determine which patients may benefit from early revascularization despite not having a significant degree of stenosis. With this regard, this study is potentially a game-changer and may warrant the inclusion of coated-platelet assays in the work-up and treatment strategy of all patients with CAS.

By |September 25th, 2014|prevention|Comments Off on This could be a game-changer for predicting stroke in asymptomatic CAS!

A Stitch in Time? Onset to Imaging Time Does Not Correlate with DWI Volume in Large Anterior Circulation Occlusions

Mark McAllister, MD

Hakimelahi R, Vachha B, Copen W, Papini G, He J, Higzai M, et al. Time and Diffusion Lesion Size in Major Anterior Circulation Ischemic Strokes. Stroke. 2014

“Time is brain” has been a vigorously repeated motto among vascular neurologists since the early 1990s. When evaluating acute strokes we emphasize urgency, lest more brain undergoes irreversible damage. The primary reason patients don’t receive therapy for acute ischemic stroke is presentation outside of the established time windows for intervention. In this paper the authors investigate the relationship between time from symptom onset and infarct size in patients with anterior circulation occlusions.

The study included both retrospectively (47) and prospectively identified (139) acute stroke patients who had CTA or MRA evidence of occlusion at the terminal ICA, proximal MCA, or T-lesion with and DWI performed within 30 hours of symptom onset. The group calculated DWI infarct volumes for each of the patients, and found that there was no correlation between infarct volume and time from symptom onset (R²=0.001, p=0.71). When analyzed by occlusion location (ICA, MCA, or both), there remained no correlation, which was also true when considering only patients with witnessed symptom onset. 

The authors conclude that time is not the most important determinant of infarct size.  Variability in collaterals among patients likely plays a significant role, which is dramatically demonstrated in radiographs from two patients in the included figures. This paper does not evaluate changes in infarct size within individual patients, but previous work by the same group has suggested perfusion deficits may be stable in an individual

The authors suggest that the individuals with low DWI burdens and good collaterals may be potential candidates for intervention beyond currently established windows, consistent with other cited reports of positive outcomes in such circumstances. What remains to be seen is whether such patients are at risk of infarct expansion and thus would benefit from intervention, or whether these patients are destined to do well regardless of our actions.  

All These Years Later, it Still Seems Safer to “Hug the Scylla Side.”

Mark N Rubin, MD

Gould B, McCourt R, Gioia RC, Kate M, Hill MD, Asdaghi N, et al. Acute Blood Pressure Reduction in Patients With Intracerebral Hemorrhage Does Not Result in Borderzone Region Hypoperfusion. Stroke. 2014

“’Is there no way,’ said I, ‘of escaping Charybdis, and at the same time keeping Scylla off when she is trying to harm my men?
 “’…Neptune himself could not save you [from Charybdis]; you must hug the Scylla side and drive ship by as fast as you can, for you had better lose six men than your whole crew.’”
–          Odysseus & Circe, Book XII, The Odyssey, Homer, circa 800 B.C.E.

Intracerebral hemorrhage, as previously discussed, is bad disease. Patients are rather unwell in the acute setting, are susceptible to a host of complications during their prolonged recovery, and frequently have a poor long-term outcome.

One of the myriad concerns in the acute setting is blood pressure management. Systemic blood pressure is typically through the roof when we meet patients with intracranial hemorrhage, and systolic blood pressure >200 mmHg – frequently achieved in this cohort – is an independent predictor of hematoma expansion (and, thereby, worsening neurologic injury). On the other hand, some have noted diffusion-weighted MRI changes in the perihematoma region, suggesting this may represent a region of hypoperfusion after intracerebral hemorrhage. Thus, the suggestion is we must navigate between Scylla and Charybdis: the importance of keeping blood pressure below an unclear threshold must be balanced by the potential injury from overly aggressive antihypertensive therapy, or so the controversy stated.

The ICH ADAPT investigators, however, have contributed an important piece of information to this discussion. The trial, which tested the hypothesis that cerebral blood flow (as measured by multiparametric CT) is not significantly affected by antihypertensive treatment, demonstrated that mean blood flow is not significantly affected by aggressive antihypertensive treatment. This more recent contribution, a subanalysis, focused on whether or not aggressive blood pressure reduction was more likely to tip individual patients into an ischemic threshold; a subgroup that may have escaped the original analysis. In brief, their sophisticated cerebral blood flow analysis did not suggest that those aggressively treated were any more likely to have regions of ischemia around their hematoma or arterial borderzone regions, at least at 2 hours after their original assessment.

The authors appropriately list the limitations of this study, namely that they only see a very early point in time and that there was substantial heterogeneity in patients and scanners, but this is still an important contribution. This is one more piece of evidence to suggest that the supposed controversy of blood pressure reduction (Scylla) vs hypoperfusion (Charybdis) is perhaps overstated and that Circe’s advice still stands: hug the Scylla side. 


By |September 23rd, 2014|treatment|Comments Off on All These Years Later, it Still Seems Safer to “Hug the Scylla Side.”

How Accessible is IV-tPA and Intra-arterial Thrombectomy to the US population?

Duy Le, MD

Opeolu A, Albright K, Carr B, Wolff C, Mullen MT, Abruzzo T, et al. Geographic Access to Acute Stroke Care in the United States. Stroke. 2014.

Opeolu et al evaluate how accessible acute stroke care treatment is to the US population. In order to tackle this task, they evaluated the MEDPAR database from 2011 using ICD-9 codes seeking out patients who recieved IV-tPA and or intra-arterial therapy (IA-therapy). Time duration from the field to ED arrival was calculated by employing the ArcMap 10.1, a proven EMS ground model used to estimate call to ED arrival time. For helicopters, the Atlas and Database of Air Medical Services (ADAMS) model was used. 370,351 patients were diagnosed with a primary diagnosis of acute ischemic strokes (AIS). 4% of patients received IV-tPA and 0.5% received IA therapy. Of the 4,583 acute care hospitals in the MEDPAR database, 2,895 (63%) did not give any doses of IV-tPA while 4,252 (93%) did not perform any thrombectomy procedures for stroke. 327 (7%) of hospitals gave at least one dose of IV-tPA and performed at least one thrombectomy for stroke. 455 hospitals (9.9%) gave IV-tPA more than ten times during the year. 

Results showed that 81% of the US population had 60 minute access to IV-tPA capable hospitals; 66% had access to primary stroke centers and 56% had access to endovascular capable hospitals. By air, 97% had 60-minute access to IV capable hospitals, 91% had access to primary stroke centers and 85% had access to endovascular capable hospitals.

Between 2008, the same group reported that 55% of the US population had ground access and 79% had air access to primary stroke centers within 60 minutes. Those numbers have increased as noted in the results above. This is likely owing to the increased number of primary stroke centers. No data remains available yet regarding comprehensive stroke center certification.

While it is a practical way to evaluate the data, use of the Medicare database may not be truly reflective of the US population as a whole. Patients omitted include carriers of private insurance, those younger than 65 years of age and those without insurance. Additionally, much of the time to hospital is inferred through models and calculations; and not actual monitored times. However, due to practicality, these methods were employed; and this data does provide us with a national perspective on acute stroke care and show us that there has been an improvement with regards to increasing access since 2008. The increase in access can be loosely tied to an increase in number of primary stroke centers. However, a question that remains at large is whether or not comprehensive stroke center certification will have an effect on patient care outcomes and improving access to acute stroke interventions.

By |September 22nd, 2014|treatment|1 Comment

Sickle Cell Trait and Incident Ischemic Stroke

Rajbeer Singh Sangha, MD 

Caughey MC, Loehr LR, Key NS, Derebail VK, Gottesman RF, Kshirsagar AV, et al. Sickle Cell Trait and Incident Ischemic Stroke in the Atherosclerosis Risk inCommunities Study. Stroke. 2014

The correlation between sickle cell anemia and stroke has been well established and patients with the condition are considered at risk for ischemic stroke. In contrast, the role of the Sickle cell trait (SCT), the heterozygous carrier state of sickle cell anemia, is still debated as a risk factor for stroke. With a heterozygous allelic frequency of 7 – 9% in African Americans, SCT is estimated to affect over 3 million Americans. Increasing evidence along with numerous case reports suggest the heterozygous carrier state may be associated with thromboembolism as a potential cause for stroke. The authors of the study conducted a prospective epidemiological investigation of SCT and ischemic stroke, by analyzing a cohort of African Americans followed in the Atherosclerosis Risk in Communities (ARIC) Study.

3497 patients were analyzed for the study and of those 223 (6.4%) were identified with SCT. Other than smoking history (lower prevalence) and a higher prevalence of hypercholesterolemia, cerebrovascular risk factors of the study did not differ by SCT classification. In multivariable regression analysis adjusted for traditional risk factors, the stroke rate among those with SCT was significantly higher than those with HbAA, resulting in approximately 2 extra strokes per 1000 person-years (IRD: 1.9, p=0.03). When risk was analyzed as a relative measure, SCT remained associated with incident ischemic stroke, but estimates were more marginal (HR: 1.4, p=0.08).

Even in heterozygous carriers, hemoglobin S is associated with hypercoagulability, which may be an etiologic pathway to stroke. The authors describe numerous conditions such as exertion, dehydration, and high altitude, where SCT erythrocytes are known to sickle and polymerize. The sickling deformation in turn can lead to a cascade of events which may eventually lead to a stroke. Given the increased risk of stroke in patients with SCT, it would be pertinent to consider more aggressive education and testing of patients with a family history of sickle cell disease. Screening measures and appropriate education protocols may help reduce the burden of disease and risk in this patient subpopulation. Further studies should also be conducted into the epidemiology and pathophysiology of stroke mechanisms in the sickle cell trait population going forward.  
By |September 19th, 2014|epidemiology and genetics|Comments Off on Sickle Cell Trait and Incident Ischemic Stroke

Dual Antiplatelet Therapy – Not just a bleeding risk

Ali Saad, MD

Sharma M, Pearce LA, Benavente OR, Anderson DC, Connolly SJ, Palacio S, et al. Predictors of Mortality in Patients With Lacunar Stroke in the Secondary Prevention of Small Subcortical Strokes Trial. Stroke. 2014

In this substudy of the SPS3 (The Secondary Prevention of Small Subcortical Strokes) trial, the authors looked for risk factors that predicted mortality and nonfatal bleeding. For those unfamiliar with the original study, SPS3 randomized patients with small subcortical strokes to ASA plus clopidogrel or placebo as well as two different levels of SBP control (130-149 vs <130).

Interestingly, they found patients had significantly greater mortality rates independent of the rate of fatal hemorrhages. some of the predictors found were unique to the dual antiplatelet group. Here are the numbers:

191 deaths over 10,758 patient years (1.78% annual mortality rate)
113 dual antiplatelet  vs 78 ASA only patients died (HR 1.5, 95% CI 1.1 to 2.0). This mortality rate was not affected by the BP arm assignment or by excluding a history of hypertension

The trial also had 161 major hemorrhages, 13 were fatal (9 of these were on dual antiplatelet). dual antiplatelet patients also had a higher rate of nonfatal major hemorrhages
dual: 1.9% (n=96), p<0.001
mono: 1% (n=52), p<0.001

dual: 4.2%/pt-yr vs. 1.8%, p=0.002
mono: 3.1% vs. 1.3%, p=0.03

7 predictors of mortality of patients in either dual antiplatelet or asa only groups:
Factor                                                                                            HR 1.6 (95% CI), p value
Diabetes                                                                                        2.0 (1.5, 2.7) < 0.001
Age, per 10 y increase                                                                  1.6 (1.3, 1.8) < 0.001
Body mass index per 10 kg/m2 decrease                                     1.8 (1.4, 2.4) < 0.001
History of hypertension                                                                 1.7 (1.1, 2.7) 0.02
Systolic blood pressure per 20 mmHg increase                           1.3 (1.1, 1.5) 0.003
Hemoglobin < 13 g/dL                                                                  1.6 (1.2, 2.1) 0.001
eGFR per 20 mL/min/1.73m2 decrease                                       1.3 (1.1, 1.5) 0.02

2 predictor of mortality unique to the dual antiplatelet group:
Factor                                                                                            HR 1.6 (95% CI)
Ischemic heart disease                                                                  2.7 (1.8, 4.1)
Normotenstive/prehypertensive                                                     2.5 (1.5, 4.0)

In other words, dual antiplatelet may lead to greater mortality in ways other than bleeding. Vascular mortality did not differ between the two antiplatelet groups so MI’s alone should not account for this difference. The 7 risk predictors of mortality in both groups aren’t surprising as they are all characteristics of “sicker” patients. However, we don’t have an explanation for the 2 predictors in the dual antiplatelet group. Meta-analysis with other dual antiplatelet trials showed this effect to be unique to the SPS-3 population. This data may caution practitioners when instituting dual therapy in similar populations. The authors suggest that this dual antiplatelet related mortality risk may be a unique feature of lacunar stroke populations as a similar trend was seen in CHARISMA.

This data is limited by the relatively small number of deaths in the total population and an older mean age.

If this data can be reproduced in other trials, it may cast serious doubt on the merits of dual antiplatelet therapy and influence the way future studies are designed. more to come with the completion of POINT. POINT patients are being treated with dual antiplatelet within 12 hours of incident stroke/TIA whereas SPS-3 patients were randomized at least 2 weeks out from their strokes. Perhaps the benefits of dual antiplatelet may end up outweighing the risks if started early.

By |September 18th, 2014|treatment|Comments Off on Dual Antiplatelet Therapy – Not just a bleeding risk

One short of a Baker’s dozen: A Twelve-SNP Genetic Risk Score Identifies Individuals at Increased Risk for Future Atrial Fibrillation and Stroke

Michelle Christina Johansen, MD

Tada H, Shiffman D, Smith JG, Sjögren M, Lubitz SA, Ellinor PT, et al. Twelve–Single Nucleotide Polymorphism Genetic Risk Score Identifies Individuals at Increased Risk for Future Atrial Fibrillation and Stroke. Stroke. 2014

The role of genetics in determining fate is no longer a topic reserved for science fiction. For decades the practicing neurologist has recognized the importance of understanding genetically based disease processes and strived for potential treatment targets. Modern science is ushering in improved ways to probe the human genome allowing for a new frontier where genes are used to predict disease and assess risk. 

Melander et al utilized a community based cohort in Malmo Sweden of over 30,000 patients in search of a biomarker that could identify individuals at increased risk for atrial fibrillation (AF).  The team designed a population based prospective study to test two hypotheses:

1) a AF genetic risk score (AF-GRS) combining 12 single nucleotide polymorphisms (SNPs) would associate with risk for AF beyond the established risk factors (hypertension, smoking, obesity, diabetes, age, male sex and heart disease)

2) AF-GRS composed of the same 12 SNPs would also be associated with risk of ischemic stroke.

The study was composed of 27,471 patients from the Malmo Diet and Cancer observational cohort excluding only those who did not provide enough DNA for genotyping, those with prevalent AF and one lost to follow up. When assessing for stroke risk, those with TIAs, prevalent ischemic stroke or hemorrhagic strokes were excluded from analysis. Patient characteristics such as hypertension, diabetes, body mass index, cigarette use, prevalence of AF/ischemic stroke/coronary heart disease at time of enrollment were determined by medical record and ICD 9 codes.

The primary end point was time to first occurrence of AF and time to first occurrence of stroke.  These outcomes were determined by diagnosis code and stroke was validated within the Malmo stroke registry. 

During the follow up period (median 14yrs), 2,160 participants suffered a first AF event and 1,495 had a first ischemic stroke. The AF-GRS was significantlyassociated with incident AF after adjusting for established risk factors. The genetic risk score was separated into quintiles based on the contribution of differently weighted SNPs. The 12 SNPs were chosen based on prior literature suggesting a linkage to AF. Those patients in the top quintile of the AF-GRS had a two-fold increased risk of AF compared to the bottom quintile. 

The authors interestingly compared this risk of AF to that caused by hypertension. The magnitude was equivalent or having a high AF-GRS appeared to confer the same risk as having hypertension. 

Similarly, those in the top quintile of the AF-GRS had about 23% greater risk of ischemic stroke compared to the bottom quintile. This risk was not as strong as that conferred by a diagnosis of hypertension. The authors took the data one step further and investigated the association between AF-GRS and ischemic stroke in patients WITH a diagnosis of AF that preceded or coincided with the stroke. There was felt to be an association between the AF-GRS and these stroke events (HR 1.81).

The authors unfortunately did not perform a head to head comparison of CHADS2 to the AF-GRS but did find that adding AF-GRS to CHADS2 improved reclassification of patients into a higher degree of risk. 

So where does this leave the practicing Vascular Neurologist? Are these results generalizable? 

The authors acknowledge that the study was limited to a population in Malmo Sweden. They discuss another recently performed study where the same SNPs were associated with risk in Europeans as well as a case-control study that demonstrated association in a Japanese population. 

Is this enough? Can these results be applied in other countries including the United States? A review of the demographics of the Malmo participants demonstrates that the mean age was 58 and the BMI was 25. In America, we face an increasingly aging and obese population. We know that genetics as well as environment play a role in the pathophysiology of stroke. While the results of this study are exciting and promising, a similar study would need to be performed to ensure its clinical utility.

Assuming that the results do apply to all demographics, how should this impact our practice? If results indicate a patient falls into the top quintile of the AF-GRS, how does one proceed? The authors suggest that this cohort might be placed on more intensive monitoring for AF but should we wait to confirm to treat knowing that the incidence of paroxysmal AF increases with age? Should we subject these patients to implantable loop recorders? How aggressive do we need to be balancing investigation with the risks of presumptive anticoagulation?

Melander et al has provided the Stroke community with a thought provoking study, the nature of which will continue to increase in the upcoming years as the cost of genome sequencing declines. While the prospect of learning more about the genetics behind a disease process is thrilling, the neurologist of today needs to become acutely attuned to the ethical and practical implications of these results.
By |September 17th, 2014|epidemiology and genetics|Comments Off on One short of a Baker’s dozen: A Twelve-SNP Genetic Risk Score Identifies Individuals at Increased Risk for Future Atrial Fibrillation and Stroke

Keep your friends close to keep stroke away!

Chirantan Banerjee, MD

Nagayoshi M, Everson-Rose SA, Iso H, Mosley, Jr TH, Rose KM, and Lutsey PL. Social Network, Social Support, and Risk of Incident Stroke:Atherosclerosis Risk in Communities Study. Stroke. 2014

Man is a social animal. In the age of social networks, when dynamics of social interactions are morphing, we know very little about how social variables affect stroke risk. Association between social stress and coronary artery disease has been previously reported. But prospective data on social support and incident stroke has been scant, as most studies have focused on social support post stroke and recovery outcomes. The Atherosclerosis Risk in Communities (ARIC) is a bi-racial prospective epidemiologic study which was started in 1989 to investigate the etiology and sequelae of atherosclerosis and its variation in cardiovascular risk factors, medical care, and disease by race, sex, place, and time in four US communities–Forsyth County, North Carolina, Jackson, Mississippi, suburbs of Minneapolis, Minnesota, and Washington County, Maryland. Data from the cohort has led to several important papers in stroke risk factor epidemiology over the years.

In the current study, Nagayoshi tested the hypothesis that a small social network and poor social support are associated with increased risk of incident stroke. They also tested whether vital exhaustion (fatigue, irritability, and feeling of demoralization) and systemic inflammation (hsCRP was used as the biomarker) were mediators of the association. After excluding participants with stroke and incomplete data, 13,686 and 13,683 participants were included in analyses for social network and social support respectively. Social network was measured using the 10-item Lubben Social Network Scale, and perceived social support was measured using a modified version of the Interpersonal Support Evaluation List-Short Form (ISEL-SF), previously used by ARIC investigators. Vital exhaustion was measured by the 21-item Maastricht Questionnaire. Appropriate statistical models were used. Stroke incidence was 4 per 1000 person-years. Those with a very small social network had increased risk of incident stroke, despite adjustment for age, sex, demographic, behavioral and stroke risk factors, with a HR of 1.44 (1.02-2.04). Vital exhaustion and hsCRP were then added to the model to test for mediation, and only vital exhaustion changed the beta enough to justify mediation. Lack of perceived social support was not associated with increased stroke risk after adjustment for other variables.

The findings are in concordance with 2 prior studies, which also supported association between small social network and incident stroke. The effect size in this study is striking, as those who self-reported a small social network had a 40% increased risk of stroke.  The fact that the authors tested hsCRP and vital exhaustion to get at the underlying mechanism of the relationship deserves praise, as it shed light on how mental stress and its somatic correlates have potential to disturb homeostatic mechanisms and cause cerebrovascular disease. There has been a plethora of literature linking chronic stress and subsequent activation of hypothalamic pituitary axis with neuroimmune and inflammatory markers. Given the observational nature of the data, only association (and not causation) can be inferred from the study. The scales used to measure social network and social support need further validation in neurologic populations, and the self-reported nature of data collection makes measurement error and big drawback.  Also, the actual prevalence of small social network and poor social support was very low in the cohort (2.8% and 0.5% respectively), significantly under powering it.
These results bring into limelight the fact that while we focus most of our efforts on traditional behavioral, demographic and medical risk factors for stroke, social interventions also have an important role in stroke prevention. WHO defines health as a state of complete physical, mental and social well-being. And we should try our best to help all our patients achieve this noble goal. 
By |September 16th, 2014|epidemiology and genetics|Comments Off on Keep your friends close to keep stroke away!