American Heart Association

Yearly Archives: 2013

Antihypertensive Medications Slow Progession of Arterial Stiffness due to Aging

Gillian Gordon Perue, MBBS, DM

Gepner AD, Korcarz CE, Colangelo LA, Hom EK, Tattersall MC, Astor BC, et al. Longitudinal Effects of a Decade of Aging on Carotid Artery Stiffness:The Multiethnic Study of Atherosclerosis. Stroke. 2013

In the 65 years since the start of the Framingham Heart Study, our knowledge of atherosclerosis and its risk factors as expanded exponentially. We now understand that stroke is but one of the final clinical outcomes of a prolonged sub-clinical course of atherosclerosis and “hardening of the arteries”. 

In a recent article from Stroke, Stein and colleagues present results from MESA; a large prospective Multi-Ethnic Study on Atherosclerosis. They evaluate the prevalence, cause and progression of subclinical cerebrovascular disease in a population based cohort of 6,814 men and women aged 45-84. They found that age and the use of antihypertensive medications at baseline, independently predicted arterial stiffness over time. Adding antihypertensive medications improved distensibility coefficient (DC) and the Young’s elastic modulus (YEM) of the right common carotid artery which was measured at baseline and follow up exam. For all ethnic groups, the rate of progression of YEM and DC showed no significant difference. It is noteworthy, that whites had a higher DC (better) at baseline than other ethnic groups and blacks had a higher YEM (worse) at baseline than other ethnic groups.

This observation is an important one, especially as it relates to the well known race-ethnic disparities in the effects of hypertension and stroke. The implication is that hypertensive effects on the vessels begin well before the age of 45 in our African American population. Encouraging us as medical Practitioners to screen this group at an earlier age for hypertension and start treatment earlier.

Beyond the effect of aging on the carotid artery, this paper provides insight into the biology of how our vessels respond to hypertension. One can see how YEM and DC can readily fit in a clinical module for management of our hypertensive patients. Imagine, your patient presenting to clinic; rather than making a decision on one blood pressure reading in your office we can measure the DC and YEM at baseline and follow its improvement over time. We can follow the response in the DC to the start of antihypertensive and anticipate the worsening of the DC if these agents are stopped or our patient has poor compliance. If these tools become clinically available (rather than as a research tool) YEM and DC could become to hypertension what HbA1c is to the management of diabetes.

By |November 26th, 2013|Uncategorized|0 Comments

Developing stroke systems of care in Mexico: Many challenges but more opportunities

Jose Merino, MD

Two weeks ago the Mexican Academy of Neurology (AMN) held its 37th Annual Meeting in the beautiful city of Merida, Yucatan, a culinary, musical and archaeological paradise. I was honoured to participate, along with Drs. Antonio  Arauz, José Luis Ruiz-Sandoval  and Marco Antonio Alegría, in a symposium on developing stroke systems of care organized by Dr. Fernando Barinagarrementería.

Mexico is an upper middle-income country (GDP $1.178 trillion) with 121 million inhabitants. It has a long tradition of implementing public health initiatives and now has universal health care coverage. The life expectancy at birth is 77 years. But almost 20 years after the publication of the NINDS tPA study, <3% of patients with a stroke are treated with lytics or other acute interventions, despite the fact that 24% of patientsarrive to the hospital within 3 hours of onset (almost half get to the hospital within 6 hours.) As in many other countries, including the US, many factors contribute to this low treatment rate, including a fragmented health care system, the lack of a coordinated EMS and in-hospital response, unavailability of lytics in some hospitals, limited access to imaging, poor knowledge of stroke signs and symptoms among the general population, and physicians’ fear about the risks of acute stroke treatments.

But these challenges highlight several opportunities for intervention. The symposium participants and the audience agreed on the need to implement a coordinated system of stroke care in Mexico that involves the public, civil society, physician groups, first responders, hospitals, public health organizations and the government. I was encouraged to see that representatives from the Ministry of Health and the Seguro Popular were in the audience, and my hope is that they left the meeting with a greater awareness of the burden of stroke and the human, social and economic benefits of rapid diagnosis, transportation and treatment of stroke patients.

The Mexican Stroke Association (AMEVASC) is the largest organization of stroke physicians in the country. It is a small but very active group whose members work together to increase public awareness of stroke and its warning signs, promote high quality stroke care in hospitals, and engage in stroke research. They have established national ischemic stroke and ICH registries and participate in investigator-led and multicentre international stroke studies such as IST-3 and SPS3. They have also developed practice guidelines for stroke treatment and prevention. All the speakers at the symposium (myself included) are members of AMEVASC, the organization that is leading the effort to improve care at the state and national level.

At the end of the symposium participants endorsed the Merida Declaration, a call to action to physicians, hospitals, EMS providers, the public, NGOs and state and national governments to work together to develop stroke systems of care throughout the country. This is the first step in the development of a system of care that will identify stroke centres and promote the rapid and accurate identification of stroke patients, swift transport to hospitals, prompt attention in the emergency room, and access to effective treatments for patients with stroke in Mexico.
By |November 25th, 2013|Uncategorized|0 Comments

Small unruptured aneurysms – a new pipeline for flow diverting stents?

Matthew Edwardson, MD

Chalouhi N, Starke RM, Yang S, Bovenzi CD, Tjoumakaris S, Hasan, D, et al. Extending the Indications of Flow Diversion to Small, Unruptured, Saccular Aneurysms of the Anterior Circulation. Stroke. 2013

The Pipeline Embolization Device (PED) is a stent designed for insertion across the mouth of an aneurysm. It diverts cerebral blood flow and promotes aneurysm occlusion often without any adjunctive coiling. PEDs offer benefits in terms of reduced procedure times and possibly higher rates aneurysm obliteration when compared to coiling. The FDA, however, has approved the PED only to treat large and giant wide-necked aneurysms in the cavernous or superior hypophyseal ICA. Interventionalists remain leery of clinical PED use in other types of aneurysms due to lingering safety concerns. In this article, Chalouhi and colleagues seek to allay some of these fears.

The authors performed a case-control study in patients with small (<10mm), unruptured, saccular aneurysms in the anterior circulation. 40 patients treated with one or more PEDs were matched in a 1:4 ratio with 160 patients treated with stent-assisted coiling based on age, aneurysm size, aneurysm location, and gender. The authors found similar procedural complications rates (5% with PED, 3% with stent-assisted coiling, p = 0.7) and clinical outcomes (mRS ≤ 2 in 100% with PED, 98% with stent-assisted coiling at follow-up). Those receiving PEDs had a trend toward higher rates of aneurysm obliteration at follow-up (80% with PED, 70% with stent-assisted coiling, p = 0.2).

This is the first study directly comparing flow-diverting stents with stent-assisted coiling to treat small, unruptured aneurysms. The results are encouraging and provide preliminary evidence that PEDs may have a similar safety profile to stent-assisted coiling in this patient population. A few caveats to opening the pipeline to widespread PED use in this population remain. The average follow-up in the PED group in this study was only 7 months and PEDs are known to have a higher risk of delayed aneurysm rupture and stent migration. This study was performed at one site with a great deal of clinical experience; whether these low complication rates generalize to other treatment centers remains uncertain. It should be stressed that the risk of subarachnoid hemorrhage with unruptured aneurysms < 10mm is fairly low, with most studies estimating a rate < 1% per yr. Therefore even low complication rates may negate the benefit of intervening on these patients. Calouhi and colleagues provide encouraging results on the safety of PED use in this patient population. They lay the groundwork for future trials involving multiple centers and longer follow-up to determine whether more widespread use of PEDs is appropriate for treating small unruptured aneurysms.

By |November 22nd, 2013|Uncategorized|0 Comments

Using Thin-Section Non-Contrast CT to Identify a Biomarker for IV-tPA Resistance in the setting of Anterior Circulation Stroke

Hassanain Toma, MD

Kamalian S, Morais LT, Pomerantz SR, Aceves M, Sit SP, Bose A, et al. Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-arterial Therapy. Stroke. 2013

In ischemic strokes, clot length impacts the effectiveness of IV tPA. Kamalian et al. sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. They retrospectively analyzed thin-section non-contrast CT (NCCT) of anterior circulation strokes, involving the internal carotid (ICA), middle cerebral M1 and M2 arteries. Through multivariate analysis, they showed that occlusion location was the strongest predictor of clot length.  Clot length was >8mm in 94%, 73%, and 22% of ICA-terminus, M1, and M2 occlusions, respectively.

They concluded that 1) the majority of anterior circulation proximal occlusions are >8mm long, 2) ICA-terminus occlusion is an excellent marker for clot length >8mm, 3) Thin-section NCCT appears useful for patients with MCA occlusion due to the wide variability of clot lengths.

In essence, the authors have utilized NCCT to identify a biomarker for IV-tPA resistance in the setting of anterior circulation stroke. Although a hyperdense thrombus was reportedly visible in 96% of patients, their patient selection was unfortunately biased by excluding anterior cerebral artery strokes, albeit a small fraction. In addition, I’ve learned that “hyperdense” areas are not as synonymous with “clot length”.  It is expected that when an artery, such as proximal M1, is occluded then there will be static blood along its whole distal segment until it meets a collateralized branch. For this reason I raise the following question to the authors: How did they distinguish static blood from “clot” ?  Perhaps the location of occlusion is more meaningful. Nonetheless, this finding may have important implications in selecting appropriate patients for intravascular intervention such as intra-arterial tPA and thombectomy.

By |November 21st, 2013|Uncategorized|0 Comments

Mirror, mirror on the wall, is priming helping stroke patients to recover faster?

Tareq Kass-Hout, MD

Stinear CM, Petoe MA, Anwar S, Barber PA, Byblow WD. Bilateral Priming Accelerates Recovery of Upper Limb Function After Stroke: A Randomized Controlled Trial. Stroke. 2013

Stinear et al. conducted a single center controlled randomized trial, recently published online in stroke, to evaluate the hypothesis of promoting re-balancing of cortico-motor cortex excitability, which in turn leads to accelerated upper extremities recovery post stroke, utilizing bilateral priming with active-passive movements before upper limb physiotherapy. This study shed a light on a key question, as the recovery of the upper limb function is a predictor of the ability of living independently post-stroke.

Patients, a total of 57, in this prospective controlled and randomized trial were randomized during the sub-acute phase post-stroke to either a priming group, who received a device-assisted mirror symmetric bimanual movements every weekday for 4 weeks, or a control group, who received intermittent cutaneous electrical stimulation of the paretic forearm for the same period of time. Assessment at 6, 12, and 26 weeks, measured with the Action Research Arm Test showed that the priming group were 3 times more likely than controls to achieve their recovery plateau by 12 weeks. Also, primed participants had greater re-balancing of cortico-motor excitability than controls at 12 and 26 weeks and inter-hemispheric inhibition at 26 weeks.

In short, this trial suggests that patients who receive bilateral priming using device-assisted mirror symmetric bimanual movements have a faster recovery of upper extremity function in the initial weeks post-stroke, which will lead to a better chance of living independently. This is yet to be proven by larger scale randomized trials.  

By |November 20th, 2013|Uncategorized|0 Comments

Hypoperfusion increases ischemia in carotid stenting vs. CEA

Nirali Vora, MD

Altinbas A, Algra A, Bonati LH, Brown MM, Kappelle LJ, de Borst, et al. Periprocedural Hemodynamic Depression Is Associated With a Higher Number of New Ischemic Brain Lesions After Stenting in the International Carotid Stenting Study-MRI Substudy. Stroke. 2013

Carotid stenting lost the revascularization battle to carotid endarterectomy largely due to increased 30-day risk of stroke and death, as demonstrated in ICSS (international carotid stenting study). In an MRI sub-study of ICSS where pre- and post-procedural MRIs were compared, stenting (CAS) patients had more (3x) new DWI lesions compared to the endarterectomy (CEA) group. What was the role of hypoperfusion among these patients?

In this analysis of the ICSS-MRI substudy, Bonati et al counted the number and volume of new DWI lesions POD#1-3 and looked for associations with “hemodynamic depression.” This was defined as periprocedural bradycardia, asystole, or hypotension requiring treatment. The group found that there were more DWI lesions among patients with hemodynamic depression undergoing CAS rather than CEA.  There was no difference in DWI lesion volume. The pattern of the lesions may be available in the supplement, but not available to me for review. There were no functional outcomes studied. 

Why wasn’t the effect of hypoperfusion seen among CEA patients? It’s unclear to me, but perhaps this is a compounded effect on top of the intrinsic risk of stroke from the CAS procedure. Other determinants of stroke may also be present (but not studied) since the number of patients undergoing CAS with higher DWI lesions was more than those who had hemodynamic depression.

Despite limitations to this study, the results do re-emphasize the importance of maintaining blood pressures during and after CAS. Though I don’t know when the exact hypoperfusion is happening, I wonder if standardizing use of neuroanesthesia with intraoperative monitoring would help ensure adequate functional perfusion during the procedure itself. Afterwards, we and our vascular surgery colleagues, must ensure stringent monitoring of MAPs and attention to keeping the patient closer to their pre-op baseline. There are too many cases of both CEA and CAS where we walk in on post-op stroke codes and the MAP is >60 but the patient lives closer to MAP>80.  

What do you do at your institution to avoid post-procedure hypotension in your carotid revascularization patients?
By |November 19th, 2013|Uncategorized|0 Comments

Glyburide for acute ischemic stroke

Jennifer Dearborn, MD

Sheth KN, Kimberly WT, Elm JJ, Kent TA, Mandava P, Yoo AJ, et al. Pilot Study of Intravenous Glyburide in Patients With a Large Ischemic Stroke. Stroke. 2013

Sheth et al. recently published the pilot trial of glyburide for acute ischemic stroke (AIS). This study is a safety and feasibility study performed on ten patients at two academic centers. The rationale behind glyburide for AIS is that the sulfonylurea receptor 1 (SUR1) and the transient receptor potential melastatin 4 are upregulated in acute ischemia, leading to osmotic swelling from the uptake of sodium and water. Glyburide acts on the SUR1 receptor and is an inhibitor, therefore acute intravenous administration may reduce edema acutely. In this phase IIa trial, the rates of recruitment and the ability to manage blood glucose levels with administration of IV glyburide were assessed. Subjects to 18 to 80 years old with a DWI infarct volume 82 to 210 cm3 who were less than ten hours from stroke onset were included. 

It was exciting that there were no instances of hypoglycemia reported and that recruitment rates were higher than expected. Glyburide seems feasible as an acute treatment of stroke and future studies will need to assess the efficacy of the treatment. Based on historical controls, the subjects had lower increases in hemispheric volumes after stroke. The authors correctly point out that there is an urgent need to bring this therapy to larger scale trials to see if it can improve post stroke outcomes and functional recovery.
By |November 18th, 2013|Uncategorized|0 Comments

How much is too much? White matter hyperintensity burden on MRI

Pete Hannon, MD

King KS, Peshock RM, Rossetti HC, McColl RW, Ayers CR, Hulsey KM, et al. (HCR)Effect of Normal Aging Versus Hypertension, Abnormal Body Mass Index,and Diabetes Mellitus on White Matter Hyperintensity Volume. Stroke. 2013

“White matter changes consistent with non-specific chronic microvascular disease.” These words, or something similar, grace a very large percentage of our MRI reads, and have caused much consternation to patients, not to mention any number of Neurology referrals. When it comes to white matter changes, how much is too much? What is normal?

To help answer these questions, authors Dr. Kevin King and colleagues have compared age-related differences in MRI white matter hyperintesity (WMH) volume in healthy individuals vs. those with comorbid hypertension, abnormal BMI and/or diabetes. From 2007 to 2009, MRIs of 2011 participants were evaluated for WMH volume. Of that number, 285 lacked the pre-specified comorbidities (relative healthy controls), 973 had hypertension, 245 had diabetes, and 1578 had abnormal BMI. Participants were subgrouped by ethnicity, sex and age. Per authors, there was a linear association between age and a greater log WMH volume. Before age 50 there was no significant difference between the two groups, however after age 50 a more rapid increase in WMH volume was noted in the group with comorbidities (p=0.0008).

Within the scope of the subgroups selected, it is evident that “normal” aging carries with it some increase in WMH burden. Unfortunately within the control group, there is no mention of smoking history, cholesterol levels, or other cardiovascular risk factors, and the two groups had significant difference at baseline regarding sec and race, making it difficult to generalize what WMH volume can be attributed to normal aging, free of other comorbities. The marked cutoff after age 50 does highlight the role that HTN, DM and obesity to play in WMH burden, however, especially as we age.

It’s commendable that this study aims to find what WMH can be attributed to normal aging, and that which may be attributed to other causes. In the future it will be nice to have specific criteria for what burden of WMH burden can be considered “within normal limits.”

By |November 15th, 2013|Uncategorized|0 Comments

Intracerebral Hemorrhage due to Oral Anticoagulant use in the Netherlands

Vivek Rai, MD

Schols AMR, Schreuder FHBM, van Raak EPM, Schreuder THCML, Rooyer FA, van Oostenbrugge RJ, et al. Incidence of Oral Anticoagulant–Associated Intracerebral Hemorrhage inthe Netherlands. Stroke. 2013.

Bleeding, especially Intra-cerebral hemorrhage (ICH), is a serious complication of oral anticoagulant (OAC) use. In the Netherlands, acenocoumarol and phenprocoumon are mainly used under dose regulation guided by specialized anticoagulation clinic. Schols and colleagues retrospectively analyzed all adult cases of confirmed non-traumatic ICH while on OAC between 2007 and 2009. 

Authors report that acenocoumarol was used by 134 (79.8%) patients, 20 (11.9%) patients were using phenprocoumon and 14 (8.3%) patients used a combination of OAC with another antithrombotic drug. Of all ICH cases, 168 (25.8%) were OAC-associated and 153 of these (91.1%) were first-ever OAC- ICH. The absolute risk of OAC-ICH was 0.46% per patient-year of OAC treatment.

This reported absolute risk, although slightly higher than previously reported rate, is well within the range of bleeding risk reported in clinical trials using Warfarin. It is to be kept in mind that this is an estimated risk only and that usually controlled environment of trials tends to underestimate the risk. 

I think that slightly higher annual risk in this study is reflective of increasing number of patients using anticoagulants in a more controlled (specialized clinics) environment through which adverse event reporting tends to be more accurate. While the exact numbers may not be applicable to population is the United States, this study provides good estimation of OAC-ICH risk that can be used in discussion with the patients while making decision about use of OAC.

By |November 14th, 2013|Uncategorized|0 Comments

Adiponectin and Risk of Stroke

Hassanain Toma, MD

Arregui M, Buijsse B, Fritsche A, di Giuseppe R, Schulze MB, Sabine Westphal, et al. Adiponectin and Risk of Stroke: Prospective Study and Meta-analysis. Stroke. 2013

Adiponectin is a hormone that is derived from adipose tissue. It is believed to have anti-inflammatory, anti-atherogenic and insulin-sensitizing properties. Due to these favorable cardiovascular effects, Arregui et al. sought to study the relationship between plasma adiponectin and stroke, through a prospective case-cohort design, and meta-analysis of 9 prospective studies.

The authors found that in their study population, adiponectin was associated with higher HDL-cholesterol and lower C-reactive protein, triglyceride levels, and diabetes, interestingly however, they found adiponectin to be directly associated with stroke, with a hazard ratio of 1.31 (95% CI 1.04-1.64).

The association between adiponectin and stroke was lost when combining their data with 9 other studies through a meta-analysis, with a pooled relative risk was 1.08 (1.01-1.15).

I totally expected adiponectin to be inversely related to stroke risk because of its ability to provide overall favorable cardiovascular effects; improved lipid profile, anti-inflammatory and anti-diabetic effects. However, the results of the cohort study showed the complete opposite. The authors did a good job in providing possible explanation for this discrepancy. On the other hand, the pooled meta-analysis did not show an association between adiponectin and stroke. I am not a statistician, but on reviewing the pooled studies, I feel more confident in the results of their cohort population than in the meta-analysis. The previous studies were adjusted for different variables, and one study was unadjusted for any variables. This may have resulted in the loss of association between adiponectin and stroke. Perhaps an individual patient-level data meta-analysis would be a more meaningful study in this case.

Furthermore, adiponectin exists as globular-adiponectin and as full-length fractions of low-, medium-, and high-molecular weight. The authors noted that they only assessed the total adiponectin, and provided partial rationalization for it. This would be analogous to assessing your patients’ cardiovascular risk based on total cholesterol and omitting the value of LDL-cholesterol. As far as I am concerned, the race for understanding the relationship between adiponectin and stroke continues.

By |November 13th, 2013|Uncategorized|0 Comments