Hypertension and stroke


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This was lecture given at College of General Practitioner Hyderabad on 16th June 2013 as refresher course on Hypertension

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  • Stroke and hypertension has a triangular relationship. Hypertension causes stroke and stroke aggravates hypertensionWe shall discuss following questions.What is the link between the hypertension and stroke?How to prevent stroke?How to treat BP in Acute ischemic stroke?How to treat BP in Acute hemorrhagic stroke?How to treat BP in Hypertensive Encephalopathy?What is link between hypertension and Cerebral Small Vessel Disease?What is link between hypertension and Cerebral Microbleed?Link between the hypertension and strokeOverviewDiastolic BPSystolic BPAging and hypertensionHypertension and AnticoagulationTherapeutic Benefit - Prevention
  • There is a compelling evidence from observational and interventional studies, suggesting that hypertension is a significant and strong risk factor for stroke. 54% of stroke world wide attributable to Hypertension.Relationship between BP and risk of stroke is continuous, consistent and independent of other risk factors.Earlier studies have shown diastolic pressure as risk factor of stroke (1958-1990)MacMohan et al concluded that as BP decreased so did the risk of Stroke.A decrease in diastolic BP by 5, 7.5, and 10mmHg was associated with a decreased risk of stroke at least by 34, 46 and 56%, respectively. Eastern Stroke and Coronary Heart Disease Collaborative Research Group showed a positive relationship between diastolic BP and the risk of stroke.Diastolic BP 110 had 13times risk of stroke as compared to <79For each 5mm decrease in DBP there is half reduction of both ischemic and hemorrhagic stroke
  • Following 1990 it was found Systolic BP was stronger risk factor than diastolic.61 Prospective cohort studies by the Prospective Study Collaboration (PSC)A greater than twofold reduction in stroke mortality with 20 mmHg decrease in systolic BP for age 40-69 down to 110 mmHg Systolic and 75 mmHg Diastolic
  • Preventive effect of hypertension is less strongly related to age.
  • Brain is about 2.3% of body weight, consumes one fifth of cardiac output and oxygen. Blood flow of the brain tissue is very high, about 50ml per 100gm. There is reflex increase in oxygen extraction with falling blood flow till it reaches critical level of 20ml when there is further fall to stop synaptic transmission to protect neuronal cell death. Any fall below 10ml over time leads to progressive death of nerve cell. Reopening of blocked circulation before there is substantial damage improve chance of recovery, however reperfusion after death of neuronal cell and blood vessel leads to severe reperfusion hemorrhage into the ischemic tissue.O2 Extraction Ratio Is Increased in Low-Flow StatesIt is complicated because we already have heard that the brain can compensate; low flow doesn't mean ischemiaand ischemia doesn't mean infarction, and the brain compensates by extracting more oxygen up to a point. Buthow that is going on in that penumbra, we don't know.
  • Cerebral blood flow is maintained to reasonable level by various reflex between 50-150mmHg systolic BP.
  • Impaired NeurogenicCerebrovascular Control and Dysautoregulation After StrokeCerebral autoregulation was tested in 32 patients with various anatomical locations and stages of ischemic cerebrovascular disease. Cerebral perfusion pressure (CPP) was raised or lowered in a standard manner by the use of head-up tilting (induced hypotension) and head-down tilting (induced hypertension). Any impairment of cerebral autoregulation was analyzed quantitatively by the ratio of the change in cerebral blood flow (CBF) over the change in CPP. There was significant correlation between the degree of dysautoregulation whether CPP was increased or decreased. An inverse correlation was shown between the degree of dysautoregulation and the duration after the ischemic episode during both induced hypotension and hypertension. Patients with brainstem lesions including those with transient ischemic attacks (TIAs) showed a greater impairment of autoregulation which persisted longer than those with hemispheric lesions. Patients with severe cerebral hemispheric infarction showed greater impairment of autoregulation than those with minor hemispheric lesions. Dysautoregulation also was greater in patients with subcortical lesions compared to those with cortical lesions.Hypertensive patients showed significantly greater decreases in CBF and effective MABP during induced hypotension than normotensive patients although autoregulation index was the same. Thus, symptoms are more frequent in hypertensives because of greater changes in CPP.Paradoxical responses in CBF to changes in CPP occurred in six patients. These were noted in moderately severe lesions in relatively young patients with hypertension and deeply located cerebral or brainstem lesions in the subacute stage. The mechanisms which control cerebral autoregulation were discussed and the nervous structures situated in the deep cerebral regions and brainstem, possibly the central structures of the autonomic nervous system, were proposed to control autoregulation of CBF. (Stroke Guide 2013)In poor flow states―which occur with thrombotic and embolic ischemic stroke, as well as with increased ICP dueto cerebral edema―the cerebral vasculature loses vasoregulatory capability and thus relies directly on mean arterial pressure (MAP) and cardiac output for maintenance of cerebral blood flow. Therefore, aggressive efforts to lower blood pressure may decrease perfusion pressure and may prolong or worsen ischemia. Rapid reduction of blood pressure, no matter the degree of hypertension, may in fact be harmful. Both elevated and low blood pressures are associated with poor outcomes in patients with acute stroke. (Medscape)MAP vs CBF vs Ischemia: Defective Autoregulation in Ischemic BrainWhy is that an issue? This is a very important curve; this is the cerebral blood flow autoregulation curve. One of the first things they teach the neurology residents about is cerebral blood flow autoregulation. And as you know, the brain is unique in that cerebral blood flow stays pretty stable at around 50 mL per 100 grams of tissue per minute, between a range of mean arterial pressure of 50 and 150 mm Hg. And the main reason this happens is because of changes in the diameter of the arteriolar resistance vessels. If you have sick arterioles, your curve is shifted to the right. And you can drop into ischemic range with a mean pressure of 100 or 120 mm Hg.
  • AHA Stroke Guide 2013There is moderated elevation of BP during arrival at emergency.
  • AHA Stroke Guide 2013Studies analyzing the extent of in-hospital blood pressure fluctuations during acute ischemic stroke found inconsistent associations with clinical outcomes. Three studies found that decreases in blood pressure were associated with poor clinical outcomes.Two studies found no association between blood pressure fluctuations and clinical outcomes.424,429 One study found that decreases in blood pressure were associated with favorable clinical outcome.422Although these observational studies analyzed data controlling for confounding factors, the blood pressure treatments were not controlled, and it is impossible to ascertain the role of the blood pressure in relation to the outcomes.BP in Acute ischemic strokeExtreme arterial hypotension is clearly detrimental, because it decreases perfusion to multiple organs, especially the ischemic brain, exacerbating the ischemic injury. Thus, an arterial blood pressure range likely exists that is optimal during acute ischemic stroke on an individual basis. Unfortunately, such an ideal blood pressure range has not yet been scientifically determined. It is likely that an ideal blood pressure range during acute ischemic stroke will depend on the stroke subtype and other patientspecificcomorbidities.
  • Medscape debate 2006Lowering BP Is HarmfulAnthony J. Furlan, MD: When I was reviewing this topic, the most consistent statement I came across in the literature is: We have no data on this topic. So a lot of this is based on personal anecdote, personal experience beginning with the fact that I can recall numerous patients when I was a stroke neurologist who promptly converted from a hemiparesis to a hemiplegia when they were given a shot of Hyperstat (diazoxide injection) in the emergency room. I'm sure many of you have had patients like that. So that is an anecdote that makes an impression; you don't want to bottom out the blood pressure. It is not debatable, frankly, that lowering the blood pressure too far in somebody with an acute brain infarct is dangerous.The real issue becomes how low is too low. If you look at the literature for some guidance, I have picked out what I thought were perhaps the most relevant papers on this topic, beginning with the tissue plasminogen activator (t-PA) trial. The big difference with some of the older literature is they all are 24-hour or 48-hour or 72-hour literature, and all the action in stroke now is within 3 to 6 to 9 hours.What are the data on blood pressure control in that time frame? There are few data. The National Institute of Neurological Disorders and Stroke (NINDS) t-PA group did look at this and you probably are more familiar with the role of blood pressure in ICH, which we just heard from Dr. Qureshi and Dr. Mayer, but what about on the low end? The NINDS trial was criticized for overly aggressive management of blood pressure. And indeed, when the NINDS group looked at blood pressure control, there were less favorable outcomes with more aggressive hypertension management, but only in the t-PA-treated patients, interestingly enough, not among the placebo patients. The reason for that is not clear; it could even be an artifact because the trial wasn't really designed to look specifically at blood pressure control, but it is true that the patients treated with intravenous (IV) t-PA in the NINDS trial who had aggressive blood pressure lowering tended to have a worse outcome.If you look at the International Stroke Trial, the heparin trial, another more recent trial on the effect of blood pressure, they found that early death increased by 18% for every 10 mm Hg lowering of systolic blood pressure below 150 mm Hg. And they introduced the notion of the U-shaped curve; blood pressure that is too high is bad and blood pressure that is too low is bad; you want it somewhere in the middle.Another study that looked at the first 24 hours, published in 2003, found a similar trend; outcome was worse for every 10% decrease in systolic blood pressure in the first 24 hours.And there is a nice older study, one of the few studies using imaging, which is part of the problem, from Grotta's group at the University of Texas, Houston, Texas, looking at the change in cerebral perfusion with single photon emission computed tomography (SPECT) scans in acute stroke patients. If you lowered the mean arterial blood pressure greater than 16% below baseline, cerebral perfusion was impaired, regardless of which drug you used.So these might provide some guidelines; you want the blood pressure in the middle, not too low, not too high. You want to look at things like 10% to 15% reductions in systolic or mean pressure. This is what the literature says and that is the literature shown here.Summary: Lowering BP HarmfulIn summary, the key concept is that autoregulation is defective in areas of acute ischemia, but it is timedependent.It is compensated up to a point by extracting more oxygen per uniflow, but in that area of hypoperfusion, positron emission tomography (PET) scans show it is very heterogeneous, so the vulnerability varies. There has been no study correlating blood pressure levels of control with risk in that penumbra zone, which is the target of therapy in acute stroke. So the best thing I can tell you is don't go below 10% to 15% mean systolic pressure, and the fact is we need more imaging-based tissue monitoring data to give you better advice.
  • AHA Stroke Guide 2013A few preliminary randomized trials of blood pressure lowering in acute ischemic stroke have been published.A placebo-controlled randomized trial tested oral nimodipine starting within 48 hours after ischemic stroke onset in 350 patients.The systolic and diastolic blood pressures were both significantly lower in the nimodipine group. Functional outcome at 3 months was similar in the 2 treatment groups, but mortality was significantly higher in the nimodipine group.
  • AHA 2013One acute ischemic stroke treatment trial, the Intravenous Nimodipine West European Stroke Trial (INWEST),430 set out to test the calcium channel blocker nimodipine as cytoprotective therapy within 24 hours after ischemic stroke onset and found complications related to blood pressure lowering.408 Adecrease in blood pressure was associated with intravenous nimodipine therapy and worse clinical outcome at 21 days.Also, a decrease in diastolic blood pressure >10 mm Hg, but not in the systolic pressure, was significantly associated with worse outcome.
  • AHA 2013However, a larger efficacy trial (n=2004) of candesartan therapy with a similar study design showed a mean blood pressure reduction of 7/5 mm Hg at day 7 and no improvement in functional outcome.432 Favorable outcomes at 6 months, however, were less likely with candesartan than with placebo (modified Rankin Scale [mRS] score 0–2 in 75% versus 77%; significant by shift analysis [P=0.048]).
  • AHA 2013The Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) compared the continuation of antihypertensive therapy to stopping preexisting antihypertensive drugs during acute hospitalization for ischemic stroke.Patients were enrolled within 48 hours of stroke onset and the last dose of antihypertensive medication and were maintained in the 2 treatment arms for 2 weeks. The study was terminated prematurely; however, continuation of antihypertensive medications did not reduce 2-week mortality or morbidity and was not associated with 6-month mortality or cardiovascular event rates.
  • Rationale for Treating HTN in AISWhy am I going to say that? Well, defective autoregulation may not be present in all patients. And in fact, there are very few data; we talk about autoregulation, you see the curve, but has it really been measured in that many stroke patients, and in how many patients is it defective? It is very unclear. We know that the ischemic penumbra is not present in all patients; if you reperfuse all patients, they don't all get better and that is because they don't all have an ischemic penumbra. In fact, it may be just a small minority of patients who have this magical ischemic penumbra that is supposed to be harmed by dropping the blood pressure; we don't know.Clinical experience indicates that many patients tolerate gentle treatment of high blood pressure, so I agree that gentle lowering of the blood pressure may, in fact, be okay. But the natural history studies demonstrate no deleterious effects because in the vast majority of patients, when they come into the hospital, their blood pressure falls on its own, spontaneously, and most of those patients -- in fact, the vast majority -- do just fine.Effect of Blood Pressure During the Acute Period of Ischemic Stroke on Stroke Outcome: A Tertiary Analysis of the GAIN International TrialThis was a study looking at the effect of blood pressure during the acute period of ischemic stroke on stroke outcomes; this was a tertiary analysis from the Glycine Antagonist (Gavestinel) in Neuroprotection (GAIN) study.GAIN was a prospective randomized trial of a neuroprotective agent that was negative for its neuroprotective effect, but it does give us some indication about what happens with the blood pressure. They enrolled over 1400 patients with acute ischemic stroke; blood pressure treatment was at the discretion of the primary investigator (PI). They basically didn't follow any guidelines; they just did whatever they wanted to do and then they looked at outcomes at the end of the day.Acute BP Changes in GAIN In terms of tertiles in these patients, whether they get treated or not, the blood pressure falls on its own and there is no evidence of a deleterious effect. You can see that over the hours after they were admitted, the mean blood pressure in terms of upper, middle, or lower tertile falls on its own, spontaneously, and most of those patients clinically did just fine.BP Changes and OutcomesWhat about blood pressure changes and outcomes? What they found was that higher blood pressures were, in fact, associated with a worse outcome in this study. In those patients who had a 30% increase from baseline in their mean arterial pressure, there were worse outcomes overall. So, if higher blood pressures are bad, then lower blood pressures may be good, and at least these are data from a prospective, randomized trial where patients were closely monitored.Cleveland Health Quality ChoiceThese are data from the Cleveland Health Quality Project where they looked at protocol deviations in patients who received IV t-PA. Over 12% of patients had protocol deviations because of high blood pressure. What did that high blood pressure lead to? It led to increased frequency of bleeding complications.IV t-PA Protocol Deviations: Connecticut Community Hospitals 1996-98Dr. Alberts: These are data from Connecticut Community Hospitals, and you can see that a significantpercentage of the patients did not have their blood pressure monitored or treated per recommendations, and these tended to be the patients who get into trouble.Risk of ICH by Deviation From NINDS ProtocolSo those patients who had protocol deviations (again, not monitoring and treating the blood pressure was a major cause of protocol deviations) were more likely to have any ICH; and they were more likely to have symptomatic ICH.The ACCESS Study: Evaluation of Acute CandesartanCilexetil Therapy in Stroke SurvivorsFinally, we have the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) study, which was a prospective study of candesartanvs placebo; 342 patients with acute ischemic stroke were randomized, treated with candesartan acutely. This trial was stopped early because of the great efficacy.Blood Pressure in ACCESSHere you can see that whether they got candesartan or placebo, their blood pressure fell fairly dramatically (these are average systolics and average diastolics), even within the first 24 to 48 hours. And these patients did great; in fact, the ones who got the candesartan had improved outcomes.ConclusionsIn conclusion, let me say that higher blood pressure may be deleterious in some stroke patients, particularly those receiving lytic therapy. Gentle lowering of blood pressure, even in the acute setting, appears to be well tolerated in many patients because most patients don't have this magical ischemic penumbra. We don't have data from prospective, randomized trials, but we know that high blood pressure is bad for the heart and many of these patients have underlying heart disease; so you don't want to cause heart damage in the acute setting. The other aspect is that by starting the blood pressure medications early while the patient is in the hospital, you can see if they tolerate it; you can make sure it doesn't bottom out their blood pressure and you can have a continuum of care where they get started on a blood pressure medicine in the hospital; it continues through rehab, and through the outpatient, so that the ball is not dropped.
  • AHA Stroke Guide 2013Extreme arterial hypertension is clearly detrimental, because it leads to encephalopathy, cardiac complications, and renal insufficiency. Theoretically, moderate arterial hypertension during acute ischemic stroke might be advantageous by improving cerebral perfusion of the ischemic tissue, or it might be detrimental by exacerbating edema and hemorrhagic transformation of the ischemic tissue.
  • AHA Stroke Guide 2013A placebo-controlled randomized trial of therapy with the angiotensinreceptor blocker candesartancilexetil, starting an average of 30 hours after ischemic stroke onset in 342 patients with elevated blood pressure,431 was stopped early. Although blood pressure and the Barthel index score at 3 months were similar in the 2 study groups, patients who received the active drug had significantly lower mortality and fewer vascular events at 12 months.
  • AHA 2013Adding to the complexity and uncertainty of arterial blood pressure management during acute ischemic stroke, small pilot trials have carefully raised the blood pressure in acute ischemic stroke patients without apparent complications. It remains unclear what the risk-benefit ratio is for lowering or raising the blood pressure during acute ischemic stroke. Larger trials with well-defined criteria are needed. At this time, the previous recommendation not to lower the blood pressure during the initial 24 hours of acute ischemic stroke unless the blood pressure is >220/120 mm Hg or there is a concomitant specific medical condition that would benefit from blood pressure lowering remains reasonable.Medscape 2006Here is my last anecdote on this topic. This is the kind of patient in whom you want to raise the blood pressure; ifyou have this kind of vascular anatomy, left internal carotid occluded. This shows the flow to the left side of thebrain; the right carotid, occluded. Right vertebral out and the patient you can see is supplying the entire brainthrough a 90% distal left vertebral stenosis. In that kind of patient I think you want to raise the blood pressure. Sothe point I'm making from my 2 talks is you have to know what is going on in the tissue and you have to know thestatus of the vessels to make any rational decision about raising or lowering blood pressure.Raising Blood Pressure in Acute Ischemic Stroke May Be Beneficial Raising BP in Acute Ischemic Stroke May Be BeneficialDr. Furlan: Now I have to counterattack -- I have said lowering blood pressure is harmful; now I have to convinceyou that actually raising it is helpful. And like so many things in stroke, it all depends. Let's start with theliterature, and again there is little literature on this subject. But here we have some animal data and an animalmodel of middle cerebral artery (MCA) infarction, using laser flow Doppler to look at cerebral blood flow, actuallyraising mild-induced hypertension in acute infarct models. And if done within 1 hour of ischemia it benefits theanimal model; infarct volume is reduced.What about humans? There is an interesting study I want to go into a little bit of detail about by Schwarz andcolleagues where they raised mean arterial pressure with norepinephrine and were able to show an effect onmiddle cerebral velocities. I want to show you a little bit of how they did this.One of the reasons we don't have data is we don't have numbers; we don't have real-time longitudinal numbers.We have numbers at points in time, every 8 hours or whatever, but not continuous monitoring. And one way to geta handle on cerebral perfusion without putting a catheter into the brain is to look at continuous transcranialDoppler (TCD) monitoring with this kind of a device, and this is what they used in the Schwarz study.These are all patients with large MCA infarcts; these aren't small infarcts. And these patients were monitored within 72 hours of onset and they looked at the effect of giving norepinephrine on MCA velocities on the side of the infarct and contralaterally. And since autoregulation is defective and velocities and blood flow tend to passively follow perfusion pressure on the infarct side, you give norepinephrine, the velocities go up.Now that is not the same as cerebral blood flow; it is a surrogate of cerebral blood flow. But you can see, on theinfarct side, if you give norepinephrine, large MCA infarct; cerebral perfusion pressure essentially passively followsthe mean arterial pressure. So there is no question you can raise it. In this study, they show that this did notincrease intracranial pressure, did not cause hemorrhages, but they didn't do clinical outcomes; they didn't saythat this physiologic change made patients better.SlideShould Blood Pressure Be Raised To Treat Acute Ischemic Stroke?Here is a study out of Massachusetts General Hospital, Boston, Massachusetts, Koroshetz's group, where theygave phenylephrine and they raised blood pressure by 20%, not to go over 200 mm Hg; they only treated 13patients. This is the best study I could find in the literature, a clinical study. Seven patients improved by 2 pointson the National Institutes of Health (NIH) Stroke Scale; I don't know what that means, literally. What they showedwas you could raise the pressure and the patients maybe get a little bit better; that is what you can find in the
  • AHA Stroke Guide 2013Multiple studies investigated various blood pressure parameters during the admission for acute ischemic stroke and clinical outcomes. Some studies found a U-shaped relation between the admission blood pressure and favorable clinical outcomes, with an optimal systolic blood pressure ranging from 121 to 200 mm Hg and diastolic blood pressure ranging from 81 to 110 mm Hg among these studies. However, elevated in-hospital blood pressure during acute ischemic stroke has been associated with worse clinical outcomes in a more linear fashion.Medscape 2006 Raising Blood Pressure in Acute Ischemic Stroke May Not Be Beneficial Raising BP in Acute Ischemic Stroke May Be Beneficial: No!Dr. Alberts: I have to take the converse side: Raising blood pressure in acute ischemic stroke may be beneficial?No, it is not beneficial.What did you hear from my esteemed colleague? You heard about rats, bats, TCD in 13 patients. What does that mean? We know a lot of stuff works in rats, but it doesn't work in humans.Blood Pressure Decrease During the Acute Phase of Ischemic Stroke Is Associated With Brain Injury and Poor Stroke OutcomeThere was this study that was published in Strok e a couple of years ago, looking at blood pressure decreasing during the acute phase being associated with brain injury and poor stroke outcome. They looked at 304 patients with acute ischemic hemispheric stroke, 67 were treated with blood pressure medications in the emergency department (ED), not according to any guidelines -- they basically did what they wanted. Thirty-one were treated with blood pressure medications in their stroke unit, presumably according to guidelines.Outcome by Admission BPHere you can see there is sort of a U-shaped curve, and this is looking at early neurologic deterioration, poor neurologic outcome. These are systolic blood pressures and diastolic blood pressures. And what you see here is very similar, sort of a U-shaped pattern that shows that at high blood pressure or, in fact, at lower blood pressures, patients tend to do worse in terms of neurologic deterioration and poor outcome. There seems to be sort of a sweet spot with blood pressures in the 160- to 200-mm Hg range, and if you bumped up the blood pressure above that, they tended not to do as well; they tended to do worse. And as Dr. Furlan said,autoregulation is defective and there are concerns that raising the blood pressure above this level, particularly in patients with defective autoregulation, could lead to cerebral hemorrhage, as we saw from the lytic literature; could lead to increased cerebral edema; and could lead to hypertensive encephalopathy -- all of which are bad outcomes.
  • Medscape 2006 Effects of Changing BPLooking further at the effects of changing the blood pressure, any increase in the systolic blood pressure was associated with a 12% increase in terms of size of infarction. A decrease in blood pressure, dramatically, was also associated with an increase in the size of infarction, but again, an increase in blood pressure may not necessarily be a good thing.Other Problems With Raising BPOther problems associated with raising the blood pressure: we talked about the risk of ICH; it may increase the amount and formation of cerebral edema; and it may adversely affect cardiac function. The other issue is that we run the risk of confusing our patients. We all know that treating blood pressure is one of the main modifiable risk factors that we have for reducing the incidence and mortality of stroke. And by taking a laissez-faire attitude --"Oh, you don't really need to worry about it; we are going to let your blood pressure run to 200 mm Hg; we are going to actually give you medications to increase your blood pressure and that will be a good thing" -- you run the risk of sending a mixed message to patients. But I think Dr. Furlan and I are saying the same thing, that gentle lowering in some settings and increasing in the settings of significant precerebral or multivesselhigh-grade stenosisare probably reasonable things to do.
  • Extreme arterial hypotension is clearly detrimental, because it decreases perfusion to multiple organs, especially the ischemic brain, exacerbating the ischemic injury. Thus, an arterial blood pressure range likely exists that is optimal during acute ischemic stroke on an individual basis. Unfortunately, such an ideal blood pressure range has not yet been scientifically determined. It is likely that an ideal blood pressure range during acute ischemic stroke will depend on the stroke subtype and other patientspecificcomorbidities.
  • It is reasonable to temporarily discontinue or reduce (to prevent the rare occurrence of antihypertensive withdrawal syndrome,primarily seen in β-blocker discontinuation) premorbid antihypertensive medications at the onset of acute ischemic stroke, because swallowing is often impaired, and responses to the medications may be less predictable during the acute stress.AHA 2013
  • The optimal time after the onset of acute ischemic stroke to restart or start long-term antihypertensive therapy has not been established. The optimal time may depend on various patient and stroke characteristics. Nonetheless, it is reasonable to initiate long-term antihypertensive therapy after the initial 24 hours from stroke onset in most patients. An optimal long-term antihypertensive therapy for patients after stroke has not been definitively established, and it might be best to individualize such therapy based on relevant comorbidities, ability to swallow, and likelihood to continue with the prescribed therapy.AHA 2013
  • Relationship between hypertension causing intra-cerebral hemorrhage and ICH induces reflex hypertension is more stronger than ischemic stroke.
  • Elevated Systolic Blood Pressure May Predispose to Hematoma EnlargementSo the next question is, has this anything to do with blood pressure and at which level of blood pressure do you actually see a relationship with hematoma expansion? This summarizes the results of a study looking at the initial systolic blood pressure in patients with ICH and the subsequent hematoma expansion. And if you look at patients with hematoma enlargement and look at the proportion of patients with systolic blood pressure 200 mm Hg or greater, you see a substantially higher rate of this elevated blood pressure at baseline compared with the patients who do not show hematoma enlargement. So what you see here is 2 things: first, the relationship with the systolic blood pressure and second, the relationship that is seen only with systolic blood pressure 200 mm or greater. So it makes more sense to use this as a threshold for treatment.Systolic Blood Pressure Is Most Sensitive in Identifying Hypertension Among Patients With ICH (N=45,330)I want to show you this because of all the controversy of what to use to treat blood pressure: systolic bloodpressure, mean arterial pressure, or diastolic blood pressure. This is a large series of patients, 45,000+ patientswith ICH, and this is their initial blood pressure. If you use the cutoff of systolic blood pressure to definehypertension, 70% of these patients would be hypertensive; if you use mean arterial pressure, only 40% of thesepatients would be classified as hypertensive, and diastolic clearly has the lowest, less than 30%. So clearlysystolic blood pressure seems to be the most sensitive index of treating blood pressure or diagnosinghypertension in patients with an ICH. And that is my rationale for using systolic blood pressure of 200 mm Hg orgreater for treatment.
  • Less Aggressive Treatment of Blood Pressure Using Systolic Blood Pressure Goals (cont'd)Hematoma Expansion Is the Major Cause of Neurological DeteriorationDr. Qureshi: Does hematoma expansion have consequences for the patient or is it just a radiologic finding? If you look at neurologic deterioration, what you see here is that hematoma expansion, regardless of the study that you see, is the main course of neurologic deterioration in patients with ICH.Volume of Intracerebral HemorrhageA Powerful and Easy-to-Use Predictor of 30-Day MortalityJoseph P. Broderick, MD; Thomas G. Brott, MD; John E. Duldner, MD;Thomas Tomsick, MD; Gertrude Huster, MHSBackground and Purpose: The aim of this study was to determine the 30-day mortality and morbidity of intracerebral hemorrhage in a large metropolitan population and to determine the most important predictors of 30-day outcome.Methods: We reviewed the medical records and computed tomographic films for all cases of spontaneous intracerebral hemorrhage in Greater Cincinnati during 1988. Independent predictors of 30-day mortality were determined using univariate and multivariate statistical analyses.Results: The 30-day mortality for the 188 cases of intracerebral hemorrhage was 44%, with half of deaths occurring within the first 2 days of onset. Volume of intracerebral hemorrhage was the strongest predictor of 30-day mortality for all locations of intracerebral hemorrhage. Using three categories of parenchymal hemorrhage volume (0 to 29 cm3, 30 to 60 cm3, and 61 cm3 or more), calculated by a quick and easy-to-use ellipsoid method, and two categories of the Glasgow Coma Scale (9 or more and 8 or less), 30-daymortality was predicted correctly with a sensitivity of 96% and a specificity of 98%. Patients with a parenchymal hemorrhage volume of 60 cm3 or more on their initial computed tomogram and a Glasgow Coma Scale score of 8 or less had a predicted 30-day mortality of 91%. Patients with a volume of less than 30 cm3 and a Glasgow Coma Scale score of 9 or more had a predicted 30-day mortality of 19%o. Only one of the 71 patients with a volume of parenchymal hemorrhage of 30 cm3 or more could functionindependently at 30 days.Conclusions: Volume of intracerebral hemorrhage, in combination with the initial Glasgow Coma Scale score, is a powerful and easy-to-use predictor of 30-day mortality and morbidity in patients with spontaneous intracerebral hemorrhage. (Stroke 1993;24:987-993)KEY WoRDs * intracerebral hemorrhage * survival * tomo
  • Acute Hypertension Should Be TreatedAnd why do I reduce blood pressure? For years, we thought that there was this concept of perihematomaischemia, the hematoma by compression of the surrounding microvessels inducing a zone of ischemia. Now weknow that that is not true. But we also have learned that there is this phenomenon of hematoma expansion; this issomething that is happening frequently enough that we need to put it in the equation.Periclot Flow, Metabolism, and OEFNow is it safe? We have worried for a long time that there is low cerebral blood flow (CBF) around these hematomas and if we lower perfusion pressures too much, maybe the patient will get ischemia. But the Washington University, St. Louis, Missouri, group (Powers and Diringer) have a positron emission tomography (PET) scanner next to their intensive care unit (ICU) and they have done very elegant studies, as illustrated here, showing the flow is reduced but so is the cerebral metabolic rate of oxygen consumption. There is no increase in the oxygenic extraction fraction, which would be indicative of an ischemic state.
  • Intra-cerebral hemorrhage (ICH)> 10% of all strokes much higher in NE 30-40%Risk FactorsHTNIncreasing AgeRace: Asians and Blacks Amyloidosis- esp. in the elderlyAVMs or tumorsAnticoagulants/Thrombolitic useHistory of previous strokeTobacco, AlcoholMark J. Alberts, MD: My name is Mark Alberts; I'm Professor of Neurology and Director of the Stroke Program at NorthwesternUniversity in Chicago, Illinois, and I want to welcome you to this important educational program entitled "Debating Hypertensive Management Approaches in Acute Hemorrhagic and Ischemic Stroke." As you know, this issue about what to do with blood pressure when somebody comes in with an intracerebralhemorrhage, a subarachnoid hemorrhage, or an ischemic stroke is one of the vexing issues that we have in clinical neurology, neurosurgery, and neurointensive care. And with the expert panel that we've assembled, we hope to address some of these issues.For Debate: In IntracerebralHemorrhageThey are going to debate 3 questions: 1) What is the target mean arterial pressure for patients with intracerebralhemorrhage(ICH)? Do we want to be aggressive or conservative? 2) What should first-line therapy be: beta blockers or calcium-channel blockers? 3) What should the duration of intravenous (IV) therapy be: 24 hours or 72 hours?
  • BP lowering in acute ICH is safe, soGo early Go intensive (target systolic BP 140 mmHg)Go sustained (≥24 hours)in most patients improves chances of better recovery in survivors
  • The specific aims of this study are to:Definitively determine the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of patients with death and disability (mRS 4-6) at 3 months among subjects with ICH who are treated within 4.5 hours of symptom onset.Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the subjects' quality of life as measured by EuroQol at 3 months.Evaluate the therapeutic benefit of the intensive treatment relative to the standard treatment in the proportion of hematoma expansion (defined as increase from baseline hematoma volume of > 33%) and in the change from baseline peri-hematoma volume at 24 hours on the serial computed tomographic (CT) scans.Assess the safety of the intensive treatment relative to the standard treatment in the proportion of subjects with treatment-related serious adverse events (SAEs) within 72 hoursStudy Type:InterventionalStudyDesign:Allocation: RandomizedEndpoint Classification: Efficacy StudyIntervention Model: Parallel AssignmentMasking: Open LabelPrimary Purpose: TreatmentOfficialTitle:Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II)Resource links provided by NLM:Genetics Home Reference related topics: COL4A1-related brain small-vessel diseaseMedlinePlus related topics: Blood Pressure MedicinesDrug Information available for: Nicardipine hydrochloride NicardipineU.S. FDA Resources Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:Primary Outcome Measures:A pragmatic, streamlined randomized design to evaluate the efficacy of intensive SBP reduction and its effect on outcomes measures at 24 h and at 3 m from randomization in subjects with ICH [ Time Frame: August, 2010- July 2015 ] [ Designated as safety issue: No ]Primary outcome is death or disability, defined by modified Rankin scale (mRS) of 4-6 at 3 m following treatment. We chose the mRS because of its high inter-observer reliability, superiority to other indices (e.g., Barthel index), and consistency with previous trials in patients with ICH. Further reliability will be increased by training raters in using the structured interview and obtaining a mRS grade. A dichotomous outcome was chosen to reduce the rate of misclassification and increase the sensitivity of detecting meaningful difference.Secondary Outcome Measures:Secondary outcomes [ Time Frame: August, 2010- July 2015 ] [ Designated as safety issue: No ]EuroQOL: EuroQOL, is a simple, standardized non-disease-specific instrument for describing and valuating health-related quality of life. Its components are a printed 'thermometer'-type visual analogue scale and EQ-5D, which consists of 5 questions in 5 different domains and allows for responses from 1 (the best outcome) to 3 (the worst). Hematoma expansion as determined by serial CT scans: Hematoma expansion will be defined as an increase in the volume of intraparenchymalhemorrhage of >33% as measured by image analysis on the 24-h CT compared with the baseline CT scan.Estimated Enrollment:1280Study Start Date:January 2011Estimated Study Completion Date:July 2016Estimated Primary Completion Date:July 2015 (Final data collection date for primary outcome measure)ArmsAssigned InterventionsActive Comparator: Standard SBP Reduction ArmThe goal for the standard BP reduction group will be to reduce and maintain SBP < 180 mmHg for 24 h from randomization. 180 mmHg is the target SBP for this arm.Drug: NicardipinehydrochlorideIVnicardipine will be initiated at a rate of 5 mg/hr and increased by 2.5 mg/hr increments will continue every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is > target SBP despite infusion of the maximum nicardipine dose for 30 min, a second agent can be used (Labetalol 5-20 mg IV bolus every 15 min) for another h.Other Name: Cardene® I.V.Active Comparator: Intensive SBP Reduction ArmThe goal for the intensive BP reduction group will be to reduce and maintain SBP < 140 mmHg for 24 h from randomization. 140 mmHg is the target SBP for this arm.Drug: NicardipinehydrochlorideIVnicardipine will be initiated at a rate of 5 mg/hr and increased by 2.5 mg/hr increments will continue every 15 min until the target SBP or maximum dose of 15 mg/hr is reached. If SBP is > target SBP despite infusion of the maximum nicardipine dose for 30 min, a second agent can be used (Labetalol 5-20 mg IV bolus every 15 min) for another h.Other Name: Cardene® I.V.Detailed Description:The report from a National Institute of Neurological Disorders and Stroke Workshop on priorities for clinical research in intracerebralhemorrhage (ICH) in December 2003 recommended clinical trials for evaluation of blood pressure (BP) management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertension in ICH. Consequently, we propose to conduct a five-year international, multicenter, open-labeled, randomized, controlled, Phase III trial to determine the efficacy of early, intensive antihypertensive treatment using intravenous nicardipine for acute hypertension in subjects with co-morbid hypertension and spontaneous supratentorial ICH. The primary hypothesis of this large, streamlined, focused trial is that the group treated with intensive BP reduction (systolic BP [SBP] of 140 mmHg or less - hereafter referred to as the intensive treatment) using intravenous nicardipine infusion for 24 hours reduces the proportion of death and disability at 3 months by 10% or greater compared with the group treated with the standard BP reduction (SBP of 180 mmHg or less - hereafter referred to as the standard treatment) among patients with ICH treated within 4.5 hours of symptom onset. The underlying mechanism for this expected beneficial effect of intensive treatment is mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 38% of patients with acute ICH. The trial will recruit a maximum of 1,280 subjects with ICH who meet the eligibility criteria. The primary outcome is the proportion of death and disability at 3 months defined by modified Rankin scale (mRS) score of 4 to 6. The proposed clinical trial is the natural extension of numerous case series, a subsequent pilot trial funded by the National Institutes of Health National Institute of Health (NIH), and a preliminary randomized controlled trial in this patient group funded by the Australian National Health and Medical Research Council, that have recently confirmed the safety and tolerability of both the regimen and goals of the antihypertensive treatment in acutely hypertensive patients with ICH proposed in the present trial. The proposed trial will have important public health implications by providing necessary information regarding the efficacy and safety of antihypertensive treatment of acute hypertension observed in up to 75% of the subjects with ICH. BP treatment represents a strategy that can be made widely available without the need of specialized equipment and personnel and therefore can make a major impact upon outcome in patients with ICH. Substantial reduction in morbidity and mortality appears possible if the estimates of treatment effect sizes from our current pilot trials are accurate.  EligibilityAges Eligible for Study:  18 Years and olderGenders Eligible for Study:  BothAccepts Healthy Volunteers:  NoCriteriaInclusion Criteria:Age 18 years or olderIV nicardipine can be initiated within 4.5 hours of symptom onset.Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.Total GCS score (aggregate of verbal, eye, and motor response scores) of 5 or greater at time of ED arrival.INR value < 1.5CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement <60 cc.For subjects randomized prior to IV antihypertensive administration: SBP greater than 180 mmHg* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT spontaneous SBP reduction to below 180 mmHg at the time of randomization ORFor subjects randomized after IV antihypertensive administration: SBP greater than 180 mmHg* prior to IV antihypertensive treatment (this includes pre-hospital treatment) AND WITHOUT SBP reduction to below 140 mmHg at the time of randomization.Informed consent obtained by subject, legally authorized representative, or next of kin.Note: Patients with SBP < 180mmHg should be monitored for 4.5 hours from symptom onset as their SBP may rise to eligible levels before the eligibility window closes.Exclusion Criteria:ICH is due to previously known neoplasms, AVM, or aneurysms.Intracerebral hematoma considered to be related to trauma.ICH located in infratentorial regions such as pons or cerebellum.IVH associated with intraparenchymalhemorrhage and blood completely fills one lateral ventricle or more than half of both ventricles.Patient to receive immediate surgical evacuation.Current pregnancy, or parturition within previous 30 days, or active lactation.Use of dabigatran within the last 48 hours.A platelet count less than 50,000mm3Known sensitivity to nicardipine.Pre-morbid disability requiring assistance in ambulation or activities of daily living.Subject's living will precludes aggressive ICU management.Subject is currently participating in another interventional clinical trial
  • Recommendations 20101. Until ongoing clinical trials of BP intervention for ICH are completed, physicians must manage BP on the basis of the present incomplete efficacy evidence.Current suggested recommendations for target BP in various situations are listed in Table 6 and may be considered (Class IIb; Level of Evidence: C). (Unchanged from the previous guideline)2. In patients presenting with a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe (Class IIa; Level ofEvidence: B). (New recommendation)TABLE 2. Suggested Recommended Guidelines for Treating Elevated Blood Pressure in Spontaneous ICH1. If SBP is 200 mm Hg or MAP is 150 mm Hg, then consider aggressive reduction of blood pressure with continuous intravenous infusion, with frequent blood pressure monitoring every 5 minutes.2. If SBP is 180 mm Hg or MAP is 130 mm Hg and there is evidence of or suspicion of elevated ICP, then consider monitoring ICP and reducing blood pressure using intermittent or continuous intravenous medications to keep cerebral perfusion pressure 60 to 80 mm Hg.3. If SBP is 180 mm Hg or MAP is 130 mm Hg and there is not evidence of or suspicion of elevated ICP, then consider a modest reduction of blood pressure (eg, MAP of 110 mm Hg or target blood pressure of 160/90 mm Hg) using intermittent or continuous intravenous medications to control blood pressure, and clinically reexamine the patient every 15 minutes.SBP indicates systolic blood pressure; MAP, mean arterial pressure.The following algorithm adapted from guidelines for antihypertensive therapy in patients with acute stroke may be used in the first few hours of ICH (level of evidence V, grade C recommendation): If systolic BP s > 230 mmHg or diastolic BP > 140 mm Hg on 2 readings 5 minutes apart, institute nitroprusside. If systolic BP is 180 to 230 mmHg, diastolic BP 105 to 140mm Hg, or mean arterial BP >= 130 mm Hg on 2 readings 20 minutes apart, institute intravenous labetalol, esmolol, or enalapril. Avoid oral or sublingual nifedipine. If systolic BP is < 180 mmHg and diastolic BP is < 105mmHg, defer antihypertensive therapy unless concurrent coronary ischemia is suspected. Choice of medication depends on other medical contraindications (e.g., avoid labetalol in patients with asthma). If ICP monitoring is available, cerebral perfusion pressure should be kept at > 70 mmHg at all times. Any clinical deterioration in association with reduction of BP should prompt reconsideration of ongoing BP management strategy. 210 guideBlood PressureBlood Pressure and Outcome in ICHBlood pressure (BP) is frequently, and often markedly, elevated in patients with acute ICH; these elevations in BP are greater than that seen in patients with ischemic stroke.72,73Although BP generally falls spontaneously within several days after ICH, high BP persists in a substantial proportion of patients.72,73 Potential pathophysiologic mechanisms include stress activation of the neuroendocrine system (sympathetic nervous system, renin-angiotensin axis, or glucocorticoid system) and increased intracranial pressure. Hypertension theoretically could contribute to hydrostatic expansion of the hematoma, peri-hematoma edema, and rebleeding, all of which may contribute to adverse outcomes in ICH, although a clear association between hypertension within the first few hours after ICH and the risk of hematoma expansion (or eventual hematoma volume) has not been clearly demonstrated.25,74A systematic review75 and a recent large multisite study in China73 show that a measurement of systolic BP above 140 to 150 mm Hg within 12 hours of ICH is associated with more than double the risk of subsequent death or dependency.Compared with ischemic stroke, where consistent U- or J-shaped associations between BP levels and poor outcome have been shown,76 only 1 study of ICH has shown a poor outcome at very low systolic BP levels (140 mm Hg).77 For both ischemic stroke and possibly ICH, a likely explanation for such association is reverse causation, whereby very low BP levels occur disproportionately in more severe cases, so that although low BP levels may be associated with a high case fatality, it may not in itself be causal.AbstractObjective: To determine the feasibility and acute (i.e., within 72 hrs) safety of three levels of systolic blood pressure reduction in subjects with supratentorialintracerebral hemorrhage treated within 6 hrs after symptom onset.Design: A traditional phase I, dose-escalation, multicenter prospective study.Settings: Emergency departments and intensive care units.Patients: Patients with intracerebral hemorrhage with elevated systolic blood pressure ≥170 mm Hg who present to the emergency department within 6 hrs of symptom onset.Intervention: Intravenous nicardipine to reduce systolic blood pressure to a target of: (1) 170 to 200 mm Hg in the first cohort of patients; (2) 140 to 170 mm Hg in the second cohort; and (3) 110 to 140 mm Hg in the third cohort.Primary outcomes of interest were: (1) treatment feasibility (achieving and maintaining the systolic blood pressure goals for 18–24 hrs); (2) neurologic deterioration within 24 hrs; and (3) serious adverse events within 72 hrs.A total of 18, 20, and 22 patients were enrolled in the respective three tiers of systolic blood pressure treatment goals. Overall, 9 of 60 patients had treatment failures (all in the last tier). A total of seven subjects with neurologic deterioration were observed: one (6%), two (10%), and four (18%) in tier one, two, and three, respectively. Serious adverse events were observed in one subject (5%) in tier two and in three subjects (14%) in tier three. However, the safety stopping rule was not activated in any of the tiers. Three (17%), two (10%), and five (23%) subjects in tiers one, two, and three, respectively, died within 3 monthsConclusions: The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds, and the 3-month mortality rate was lower than expected in all systolic blood pressure tiers. The results form the basis of a larger randomized trial addressing the efficacy of systolic blood pressure reduction in patients with intracerebral hemorrhage.Effects of BP-Lowering TreatmentsThe strong observational data cited previously and sophisticated neuroimaging studies that fail to identify an ischemic penumbra in ICH78 formed the basis for the INTensive BloodPressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) pilot study, published in 2008.79 INTERACT was an open-label, randomized, controlled trial undertaken in404 mainly Chinese patients who could be assessed, treated, and monitored within 6 hours of the onset of ICH; 203 were randomized to a treatment with locally available intravenous BP-lowering agents to target a low systolic BP goal of 140 mm Hg within 1 hour and maintained for at least the next 24 hours, and 201 were randomized to a more modest systolic BP target of 180 mm Hg, as recommended in an earlier AHA guideline.80 The study showed a trend toward lower relative and absolute growth in hematoma volumes from baseline to 24 hours in the intensive treatment group compared with the control group. In addition, there was no excess of neurological deterioration or other adverse events related to intensive BP lowering, nor were there any differences across several measures of clinical outcome, including disability and quality of life between groups, although the trial was not powered to detect such outcomes. The study provides an important proof of concept for early BP lowering in patients with ICH, but the data are insufficient to recommend a definitive policy.
  • After first 24-48 hours oral medication can be initiatedWhen Can Oral Antihypertensive Medications Be Initiated?I just wanted to quickly point out that there are certain guidelines. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has come up with some guidelines regarding this particular scenario, and what they recommend is that after the first 24 hours, you may want to keep the blood pressure in what they call its intermediate levels -- somewhere between 160 to 100 mm Hg -- and they acknowledge that you can start oral antihypertensive medication. They do want you to achieve a more aggressive goal as neurologic stability is achieved and, on average, that is around 7 days, but clearly there is variation among patients. And then you want to reduce blood pressure below 140 mm Hg, and in diabetics you want to be even more aggressive; you want to keep it below 130/ 80 mm HG. In our experience, it takes about a month of titration of medication before these goals are achieved.The Duration of Intensive Blood Pressure Control (cont'd)Transitioning From IV to PO BP ControlDr. Mayer: So we have throughput issues. So we drop a duotube right away; that gets us our enteral access. On rounds, we may take that target systolic of 160 mm Hg and liberalize it to 170 or 180 mm Hg and allow that blood pressure to be up in the 170s. Obviously, we would be watching them closely; that's less need for infusion medications. And then we start to give oral medications through the duotube and we do it in staggered doses throughout the day; so you get a dose of 50 mg of metoprolol and if the patient still is on your drip 6 hours later, you give 75 mg. Then 6 hours after that, you go to 100 mg and now at 100 mg every 6 hours of metoprolol you are maxed. Then we go to the next agent, and we are going to add an angiotensin-converting enzyme (ACE) inhibitor or something like that. So doses are split up throughout the day; every time the next dose comes, it escalates if the patient still is on the drip. The goal is to come to rounds the next day and have a bloodpressure of about 170 mm Hg with the patient off the labetalol drip or the nicardipine drip and go to a step-down approach.Oral BP MedicationsWe add these agents by class and these are the different classes you can use. Beta blockers and ACE inhibitors -- we use these a lot. We know from the Heart Outcomes Prevention Evaluation (HOPE) study that ACE inhibitors are an excellent class of agent to be on when recovering the first year after a stroke. And in fact, much of the effect of that study was actually on preventing recurrent ICH. Calcium-channel blockers include amlodipineor diltiazem, and then we go to these other agents that we don't use so much, usually when we have maxed out on those 3 main classes of drugs.
  • Minimizing Acute Brain Injury After Subarachnoid HemorrhageSubarachnoid Hemorrhage: Approaches to Optimize Prevention and Treatment of VasospasmSAH incr ICP & decr cerebral perfusion causing global ischemia Induces intense vasospasm in neighbouring vessels (4- 12 days) after initial bleed. Goal-dec 20-25% of MAP over 6-12 hrs but not <160/100. If vasospasm occurs later-inc BP with 3H(not proven) Preffred - lobetAvoid- nitrodilatorsNo data to support oral nimodipdec vasospasmSAH: Vasospasm ProphylaxisAnd then there is medical therapy to approach this problem, and the medical therapy that everyone uses is oral nimodipine. If you think back, after they did the antifibrinolytic strategies with Amicar (aminocaproic acid) and found that did reduce rebleeding over 2 weeks but increased the risk of ischemia, neurosurgical centers did a number of studies, 10 randomized controlled trials looking at oral nimodipine. Everyone thought it was neuroprotective and, in fact, this drug is approved for the prophylactic prevention of delayed cerebral ischemia from spasm. What the meta-analyses tell us is that, essentially, under normal conditions, 7 in 10 patients develop arterial spasm; 3 of those 7 are going to develop delayed cerebral ischemia clinically, and if you put them on nimodipine, it will decrease to 2 in 7. It is a 33% relative reduction of symptomatic vasospasm, a 20% relative reduction in computed tomography (CT)-documented infarction, and a 24% relative reduction in themeaningful patient-centered outcome of death or severe disability.
  • Posterior reversible encephalopathy syndrome (PRES), also known asreversible posterior leukoencephalopathy syndrome (RPLS), is a syndrome characterized by headache, confusion, seizures and visual loss. It may occur due to a number of causes, predominantly malignant hypertension, eclampsia and some medical treatments. On magnetic resonance imaging(MRI) of the brain, areas of edema (swelling) are seen. The symptoms tend to resolve after a period of time, although visual changes sometimes remain.[1][2] It was first described in 1996.[3]
  • AHM in prevention of stroke trialsDiuretics – ALLHATCCBs - ASCOT (Lancet 2005), ALLHAT (JAMA 2002)ACE-I - HOPE, PROGRESS (Lancet 2001)ARBs -ACCESS (Stroke 2003) , MOSES (Stroke 2006)Minimizing Acute Brain Injury After Subarachnoid HemorrhageAntihypertensive Classes That Prevent StrokeFurthermore, in terms of class of antihypertensive agents, we have all of these different classes that have been studied. The diuretics were studied in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) study. Guess what? It worked and it was inexpensive.Calcium-channel blockers also were studied in 2 large studies, the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) trial and again in the ALLHAT trial. Guess what? Calcium-channel blockers worked, too.What about ACE inhibitors? These were studied in the Heart Outcomes Prevention Evaluation (HOPE) trial and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) study, both of which worked. So ACE inhibitors work.What about ARBs? These were studied in the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) trial, and in the Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipinefor Secondary Prevention (MOSES) trial; it was a trial of eprosartan which is used mostly in Europe, but this showed that the ARBs work.So just a cursory review of the literature shows that there is abundant evidence that diuretics, calcium-channel blockers, ACE inhibitors, and ARBs all work. I do agree with Dr. Furlan, you have to pick the right agent for the right patient, and there are data in the literature showing that African Americans, for example, tend to respond better to diuretics and calcium-channel blockers, whereas Caucasians tend to respond better to diuretics and ACE inhibitors, in general. And everybody seems to respond to ARBs, so that is a good thing.Stable patients, ACE inhibitors & thiazide diuretics are recommended to lower BP to <130/80 mm Hg (Table 1) and to reduce the incidence of stroke (JNC 7).Acute ischemic stroke: the optimal level of BP control is controversial. Acute lowering of BP can result in reduction of blood flow to areas of the brain with altered autoregulation of blood flow, with worsening of neurologic function. Control of BP to intermediate levels of 160/100 mm Hg is considered appropriate in the acute setting (Hart & Bakris, 2009).PROGRESS Trial
  • Due to strong association of Stroke and Hypertension it is a therapeutic target5-6mmHg in diastolic reduction of BP after 2-3 years there was 35-40% less strokeHypertension Detection and Follow-up Program study after treating hypertension for 5 years there was 1.9% stroke compared to 2.9% in non treated group.In Systolic Hypertension in the Elderly Program the 5 year incidence of all strokes was 5.2% with treated group versus 8.2% with placebo Hypertension in the Very Elderly Trial suggest that patients with above 80 years also benefited with anti-hypertension treatment to prevent stroke.AHA Guideline 2011 JCA 7HypertensionHypertension is a major risk factor for both cerebral infarction and ICH (Table 4). The relationship between blood pressure (BP) and stroke risk is strong, continuous, graded,consistent, independent, predictive, and etiologically significant. 90 Throughout the usual range of BPs, including the nonhypertensive range, the higher the BP, the greater the riskof stroke.91 The risk of stroke increases progressively with increasing BP, and a substantial number of individuals have a BP level below the current drug treatment thresholds recommended in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).90 For these reasons, nondrug or lifestyle approaches are recommended as a means of reducing BP in nonhypertensive individuals with elevated BP (ie, “prehypertension,” 120 mm Hg to 139 mm Hg systolic or80 mm Hg to 89 mm Hg diastolic).92 The prevalence of hypertension is high and increasing. On the basis of national survey data from 1999 to 2000, it was estimated that hypertension affected at least 65 million persons in the United States.93,94 The prevalence of hypertension is increasing, in part as a result of the increasing prevalence of overweight andobesity.95,96 BP, particularly systolic BP, rises with increasing age, both in children97 and adults.98 Persons who are normotensive at 55 years of age have a 90% lifetime riskof developing hypertension.99 More than two thirds of persons 65 years of age are hypertensive.90 Behavioral lifestyle changes are recommended in the JNC 7 as part of a comprehensive treatment strategy.90 A compelling body of evidence from the results of 40 years ofclinical trials has documented that drug treatment of hypertension prevents stroke as well as other BP-related target organ damage, including heart failure, coronary heart disease,and renal failure.90 In a meta-analysis of 23 randomized trials with stroke outcomes, antihypertensive drug treatment reduced risk of stroke by 32% (95% CI, 24% to 39%; P0.004)in comparison with no drug treatment.100 Several meta-analyses have evaluated whether specific classes of antihypertensive agents offer special protection against stroke beyondtheir BP-lowering effects.100–103 One of these meta-analyses evaluated different classes of agents used as first-line therapy in subjects with a baseline BP 140/90 mm Hg. Thiazidediuretics [risk ratio (RR) 0.63; 95% CI, 0.57 to 0.71], -blockers (RR, 0.83; 95% CI, 0.72 to 0.97), angiotensinconverting enzyme inhibitors (ACEIs; RR, 0.65; 95% CI, 0.52 to 0.82), and calcium channel blockers (RR, 0.58; 95% CI, 0.41 to 0.84) each reduced risk of stroke compared with placebo or no treatment.103 Another meta-analysis found that diuretic therapy was superior to ACEI therapy.100 Subgroup analyses from 1 major trial suggest that the benefit of diuretic therapy over ACEI therapy is especially prominent in blacks.104 Therefore, although the benefits of lowering BP as a means to prevent stroke are undisputed, there is no definitive evidence that that any class of antihypertensive agents offers special protection against stroke.Current guidelines recommend a systolic/diastolic BP goal of 140/90 mm Hg in the general population and 130/80 mm Hg in persons with diabetes.90 Whether a lower targetBP has further benefits is uncertain. One meta-analysis that compared trials with more-intensive goals with those with less-intensive goals found a 23% reduced risk of stroke withmore-intensive therapy, as well as a pattern of greater reduction in stroke risk with greater BP reduction.101 In most trials, however, the less-intensive therapy did not test a goal140/90 mm Hg. There was no difference in rates of stroke among groups of hypertensive persons who achieved mean diastolic BPs of 85.2 mm Hg, 83.2 mm Hg, or 81.1 mm Hgin the largest trial that evaluated different BP goals.105 Controlling isolated systolic hypertension (systolic BP 160 mm Hg and diastolic BP 90 mm Hg) in the elderly is also important. The Systolic Hypertension in Europe (Syst-Eur) Trial randomized 4695 patients with isolated systolic hypertension to active treatment with a calcium channel blocker or placebo and found a 42% risk reduction (95% CI, 18% to 60%; P0.02) in the actively treated group.106 The Systolic Hypertension in the Elderly Program (SHEP) Trial found a 36% reduction in the incidence of stroke (95% CI, 18% to 50%; P0.003) from a diuretic-based regimen.107 No trial has focused on persons with lesser degrees of isolated systolic hypertension (systolic BP between 140 mm Hg and 159 mm Hg with diastolic BP 90 mm Hg). Of considerable importance is a trial that documented the benefit of BP therapy in elderly hypertensive adults (80 years of age), a group excluded from most other trials of antihypertensive therapy.106Despite the efficacy of antihypertensive therapy and the ease of diagnosis and monitoring, a large proportion of the population still has undiagnosed or inadequately treated hypertension.108 Trend data suggest a modest improvement.95 According to the most recent national data, 72% of hypertensive persons were aware of their diagnosis, 61% receivedtreatment, and 35% had BP that was controlled (140/90 mm Hg). Still, it is well documented that BP control can be achieved in most patients, but the majority require therapywith 2 drugs.109,110 Lack of diagnosis and inadequate treatment are particularly evident in minority populations and the elderly.90,111The JNC 7 report provides a comprehensive, evidencebased approach to the classification and treatment of hypertension. 90 JNC 7 classifies persons into 1 of 4 groups on thebasis of BP, and treatment recommendations are based on this classification scheme (Table 6). Systolic BP should be treated to a goal of 140 mm Hg and diastolic BP to 90 mm Hg,because these levels are associated with a lower risk of stroke and cardiovascular events. In hypertensive patients with diabetes or renal disease, the BP goal is 130/80 mm Hg(also see section on diabetes).90Summary and GapsHypertension remains the most important well-documented, modifiable risk factor for stroke, and treatment of hypertension is among the most effective strategies for preventingboth ischemic and hemorrhagic stroke. Across the spectrum of age groups, including adults 80 years of age, the benefit of hypertension treatment in preventing stroke is clear.Reduction in BP is generally more important than the specific agents used to achieve this goal. Hypertension remains undertreated in the community, and additional programs toimprove treatment compliance need to be developed, tested, and implemented.Recommendations1. In agreement with the JNC 7 report, regular BP screening and appropriate treatment, including both lifestyle modification and pharmacological therapy,are recommended (Class I; Level of Evidence A)2. Systolic BP should be treated to a goal of <140 mm Hg and diastolic BP to <90 mm Hg because these levels are associated with a lower riskof stroke and cardiovascular events (Class I; Level of Evidence A). In patients with hypertension with diabetes or renal disease, the BP goal is <130/80 mm Hg (also see section on diabetes) (Class I; Level of Evidence A).
  • Brain infarction due to small vessel cerebrovascular disease (SVCD)—also known as small vessel infarct (SVI) or “lacunar” stroke—accounts for 20% to 25% of all ischemic strokes. Historically, SVIs have been associated with a favorable short-term prognosis.However, studies over the years have demonstrated that SVCD/SVI is perhaps a more complex and less benign phenomenon than generally presumed. The currently employed diagnostic and therapeutic strategies are based upon historical and contemporary perceptions of SVCD/SVI.What is discovered in the future will unmask the true countenance of SVCD/SVI and help furnish more accurate prognostication schemes and effective treatments for this condition. This paper is an overview of SVCD/SVI with respectto the discoveries of the past, what is known now, and what will the ongoing investigations evince in the future.
  • Panminerva Med. 2012 Sep;54(3):149-60.Cerebral microbleeds: a review.Loitfelder M, Seiler S, Schwingenschuh P, Schmidt R.SourceDepartment of Neurology, Medical University of Graz, Graz, Austria.AbstractCerebral microbleeds (CMBs) are frequent findings in MRI scans of elderly subjects. Depending on the MRI protocols applied 4.7% to 24.4% of community-based subjects show incidental CMBs. The rates reported for various types of ischemic strokes and intracerebralhemorrhages vary between 19.4% and 68.5%. Most studies also demonstrated CMBs in approximately one third of Alzheimer cases. A lobar distribution of CMBs is considered to relate to cerebral amyloidangiopathy, while CMBs located in the basal ganglia or in infratentorial brain regions are thought to relate to hypertensive vasculopathy. Besides age, hypertension, diabetes mellitus, and low serum cholesterol have so far been identified as risk factors for CMBs. Presence of an APOE ε4 allele is There are only few longitudinal studies on the predictive value of CMBs. For incident ischemic strokes and intracerebralhemorrhages hazard ratios of 4.48 and 50.2 have been reported. CMBs also doubled the risk for conversion to dementia in MCI patients, and there are indications for CMBs being possible predictors of increased mortality. Given the small number of longitudinal investigations with often small sample sizes the role of CMBs as predictors of disease needs to be further elucidated. CMBs were significantly more common in warfarin-treated stroke patients who developed intracerebralhemorrhages (ICH). These data are cross-sectional. They do not provide enough evidence to consider CMBs as a contraindication for antithrombotic agents in primary and secondary stroke prevention. CMBs are likely to unfavourably affect cognitive functioning. It remains to be determined if direct lesion-related effects are responsible for this finding or if CMBs are sole markers of more extensive tissue damage in the wake of cerebral small vessel disease leading to widespread visible but also non-visible tissue destruction with a high likelihood for cognitive consequences.only genetic factor that was consistently shown to increase the risk for CMB development. the Panminerva Med. 2012 Sep;54(3):149-60.Cerebral microbleeds: a review.
  • Hypertension and stroke

    1. 1. Hypertension and CVADr PS Deb MD, DMDirector Neurology Guwahati NeurologicalResearch Center, AssamHypertensionCVAHypertension
    2. 2. Hypertension and Stroke (WHO 2013)Hypertension causes 10%death in India• 51% death due to CVA• 45% due to CADStroke >25 years• 34% men• 32% womenPreventable by Rx• 35-45% Stroke• 25% CAD
    3. 3. Diastolic BP as Risk Factor of Stroke (< 1990)Eastern Stroke and CoronaryHeart Disease CollaborativeResearch Group• Diastolic BP 110 mmHg had13times risk of stroke as comparedto <79 mmHg0102030405060Stroke PreventionMacMohanStrokePrevention
    4. 4. Systolic BP as Risk factor for Stroke (>1990)Systolic BP was more strongly correlated with 12-year risk of strokemortality than diastolic BP in Framingham Heart StudyProspective population based Copenhagen City Heart study alsoreported systolic BP is a better predictor of stroke than diastolicAsia Pacific Cohort Studies Collaboration analyzing 37 cohort studiesreported a continuous, log-linear association between systolic BP andrisk of stroke down at least 115 mmHg.After a 10 mmHg decrease in systolic BP was associated with a 41%lower risk of stroke in Asia and a 30% in Australia
    5. 5. Age and Stroke with HypertensionElevated BP and risk of stroke is weakerin older age compared to middle ageThe Asia Pacific Cohort StudiesCollaboration (APCSC)Treating BP is still important due toincreased incidence of stroke with aging.0102030405060Stroke after 10mmHgDecrease of Systolic BPStrokePrevention
    6. 6. Pathogenesis of Stroke due to Hypertension1. Large vessel Atherosclerosis2. Medium vessel Arteriosclerosis3. Small Vessel Lipohyalanosis4. Cardioembolic stroke
    7. 7. Cerebral Ischemic StrokeNormal flow, normal functionSynaptic transmissionfailureMembrane pump failure2050100Time in hoursCBF(ml/100gbrain)Low flow, raised O2 extraction, normalfunction1 2 3 4 5
    8. 8. Cerebral Autoregulation
    9. 9. Dys-autoregulation after Ischemic StrokeBrainstem strokeLarge HemisphericstrokeSubcortical stroke
    10. 10. Blood Pressure in Acute Ischemic StrokeSystolic blood pressure on arrival at Emergency• >139 mm Hg in 77%• >184 mm Hg in 15%.The blood pressure is often higher in acute stroke patients witha history of hypertensionBlood pressure decreases spontaneously within 90 minutes afteronset
    11. 11. BP control in Acute Ischemic StrokeIs lowering ofBP harmful?YesIs raising BPbeneficial?YesNoNoWhat class ofdrug?CC BlockerAB BlockerVasodilators
    12. 12. Is lowering BP is harmful? YesAutoregulation is defective in acute ischemia but it is timedependent.Oxygen extraction compensate to a pointBP control hamper perfusion of penumbra regionLowering BP below >10-15% is potentially harmfulHypertensive patient shows more significant decrease in MBPafter induced hypotension than hypertension
    13. 13. Oral Nimodipine in acute ischemic strokeA placebo-controlled randomized trial tested oral Nimodipinestarting within 48 hours after ischemic stroke onset in 350patients.The systolic and diastolic blood pressures were bothsignificantly lower in the Nimodipine group.Functional outcome at 3 months was similar in the 2 treatmentgroups, but mortality was significantly higher in theNimodipine group
    14. 14. Intravenous Nimodipine West European StrokeTrial (INWEST)Nimodipine as cytoprotective therapy within 24 hours after ischemicstroke onset and found complications related to blood pressureloweringDecrease in blood pressure was associated with intravenousNimodipine therapy and worse clinical outcome at 21 days.A decrease in diastolic blood pressure >10 mm Hg, but not in thesystolic pressure, was significantly associated with worse outcome
    15. 15. Candesartan in Acute StrokeAn efficacy trial (n=2004) of candesartan showed amean blood pressure reduction of 7/5 mm Hg at day 7Favorable outcomes at 6 months, were less likely withcandesartan than with placebo.
    16. 16. The Continue or Stop Post-Stroke AntihypertensivesCollaborative Study (COSSACS)Patients were enrolled within 48 hours of strokeonset and the last dose of antihypertensivemedication and were maintained in the 2 treatmentarms for 2 weeks.The study was terminated prematurely;however, continuation of antihypertensivemedications did not reduce 2-week mortality ormorbidity and was not associated with 6-monthmortality or cardiovascular event rates.
    17. 17. Is lowering BP in AIS harmful? NoDefective autoregulation may not be present in all patientsIschemic penumbra may not be present in all patientsClinical experience indicates that many patients tolerates gentletreatment of high BPNatural history studies demonstrate no deleterious effects oflowering BPHigh BP at onset has poor prognosis
    18. 18. Hypertension during acute ischemic strokeExtreme hypertension -> Encephalopathy, Cardiaccomplication, renal insufficiencyModerate arterial hypertension during acute ischemic stroke mightbe advantageous by improving cerebral perfusion of the ischemictissueIt might be detrimental by exacerbating edema and hemorrhagictransformation of the ischemic tissue
    19. 19. Candesartan in Acute StrokeStarting an average of 30 hours after ischemic stroke onsetin 342 patients with elevated blood pressure.Blood pressure and the Barthel index score at 3 monthswere similar in the 2 study groups,Patients who received the active drug had significantlylower mortality and fewer vascular events at 12 months.
    20. 20. Is Raising Blood Pressure in Acute IschemicStroke Beneficial? YesSmall pilot trials have carefullyraised the blood pressure in acuteischemic stroke patients withoutapparent complications.Severe intracranial atherosclerosisor stenosis may require BPelevation to maintain ICcirculation
    21. 21. Is Raising Blood Pressure in Acute IschemicStroke Beneficial? NoU shaped relation betweenadmission BP and outcomeElevated in-hospital blood pressureduring acute ischemic stroke hasbeen associated with worse clinicaloutcomes in a more linear fashion.
    22. 22. Other problem of raising BPIncrease risk of ICH after lytic therapyMay increase amount and formation of cerebral edemaA 12% increase in terms of size of infarction.May adversely affect cardiac function
    23. 23. Optimal BP during acute ischemic strokeExtreme arterial hypotension is clearly detrimental, becauseit decreases perfusion to multiple organs, especially theischemic brain, exacerbating the ischemic injury.An ideal blood pressure range has not yet been scientificallydetermined for individual patient.An ideal blood pressure range during acute ischemic strokewill depend on the stroke subtype and other patient specificco-morbidities.
    24. 24. Recommendation (AHA 2013)1. Not for thrombolysis > 220/120 mmHg,2. For Thrombolysis >185/100 mmHg3. Severe cardiac failure, Aortic dissection, Hypertensiveencephalopathy4. Cautious blood pressure lowering when (IVLabetalol, IV Enalepril, Nitrendepine) avoid venodilators
    25. 25. When to Temporary discontinuation of AHT?Because swallowing is often impaired, andresponses to the medications may be lesspredictable during the acute stress.
    26. 26. When to Re-start Antihypertensive TherapyAfter the initial 24 hours from stroke onset inmost patients.Individualize such therapy based on relevant co-morbidities, ability to swallow.
    27. 27. Hemorrhagic StrokesHypertensionICHHypertension
    28. 28. Early hemorrhage growth in patients with intra-cerebral hemorrhage.05101520253035Time inHoursNumberTimeHematoma Expansion0-3 hr03-6 hr16-12 hr212-24 hr24-48 hr
    29. 29. Elevated Systolic Blood Pressure May Predisposeto Hematoma Enlargement051015202530354045BP >200 BP <200.Hematoma Enlargement
    30. 30. Hematoma volume and outcomeType ICH Vol. mL Coma PrognosisI < 30 - GoodII 30-60 - FairIII 30-60 + Poor>60 +(Joseph P. Broderick et al Stroke 1993;24:987-993)
    31. 31. Is there Risk of treating Acute Hypertension?
    32. 32. How to treat Hypertension in ICH?When should we treat HypertensionWhat is the target mean arterial pressure for patients withintracerebral hemorrhage (ICH)?Do we want to be aggressive or conservative?What should first-line therapy be: beta blockers or calcium-channel blockers?What should the duration of intravenous (IV) therapy be: 24hours or 72 hours?
    33. 33. Primary aim1. Early intensive blood pressure (BP) lowering (target of<140 mmHg systolic) as compared to the2. Guideline-recommended ‘standard’ control of BP(target of <180 mmHg systolic) improves3. Survival free of major disability in acute spontaneousintracerebral haemorrhage (ICH)Standardised treatment protocols – locally availableintravenous (IV) BP lowering agents of physician’s choice33
    34. 34. Protocol schema: from INTERACT1 (Lancet Neurol 2008)and (Int J Stroke 2010)Acute spontaneous ICH confirmed by CT/MRIDefinite time of onset within 6 hoursSystolic BP 150 to 220 mmHgNo indication/contraindication to treatmentIn-hospital vital signs, NIHSS, GCS and BP over 7 daysIntensive BP loweringSBP <140 mmHgStandard BP managementGuidelines SBP <180 mmHg)R34Independent 90 day outcome withmodified Rankin scale (mRS)N=2800 gives 90% power for7% absolute (14% relative)decrease (50% standard vs 43%intensive) in outcome
    35. 35. Patient Flow – 2839 patients recruitedOctober 2008 to August 20121382 (98.5%) for primaryoutcome1412 (98.3%) for primaryoutcome2839 Randomised28,829 Total estimated screened3 no consent1 missing baseline data2 lost to follow-up3 withdrew consent12 alive without mRS dataReasons for exclusion (n=3572)39% Outside time window16% Judged unlikely to benefit11% BP outside criteria8% Planned early surgery5% Refused21% Other reasons6411 Screening logs completed1403 Intensive BP lowering 1436 Standard BP lowering5 no consent1 missing baseline data5 lost to follow-up4 withdrew consent9 alive without mRS data
    36. 36. Systolic BP time trends1 hour - Δ14 mmHg (P<0.0001)6 hour - Δ14 mmHg (P<0.0001)Systolic BP controlMedian (iqr) time to treatment, hr - intensive 4 (3-5), standard 5 (3-7)Intensive group to target (<140mmHg)462 (33%) at 1 hour731 (53%) at 6 hoursMeanSystolicBloodPressure(mmHg)0110120130140150160170180190200R 15 30 45 60 6 12 18 24 2 3 4 5 6 7StandardIntensive////Minutes Hours Days / Time164153150139am pm am pm am pm am pm am pm am pmP<0.0001beyond 15minsTarget level36
    37. 37. safe - no increase in death or harmseffective – borderline significant effect on the primaryendpoint• secondary analyses - improved recovery of physical functioning andhealth-related quality of life in survivorsEarly intensive BP lowering treatment is37
    38. 38. Treatment effect smaller (4%) than expected 7% absolute,but:• active-comparison study on background therapies, some with BPlowering properties (i.e. mannitol)• equates to NNT 25 (greater than aspirin and near late use of rtPA inischaemic stroke)No clear time-dependent relationship of treatment• potential mechanisms beyond haematoma growth• benefits of BP control may take several hours to manifest• effects on haematoma growth and other results outlined in Symposiumthis afternoonINTERACT2 - issues38
    39. 39. INTERACT2 resolves longstanding uncertainty over the management ofelevated BP in acute ICHProvides evidence regarding safety and efficacy in a broad range of patientswith ICHDefines for the first time a medical therapy for the management of acuteICHAs BP lowering treatment is low cost, simple to implement, and widelyapplicable, the treatment should become standard of care to patients withICH in hospitals all over the worldConclusions39
    40. 40. Baseline 24 hrsSBP<180 mm HgSBP<140 mm Hg3 m
    41. 41. Recommendation AHA 2010Hypertension is common during earlystates of ICH -> Expansion, Peri-hematoma edema and re-bleedingA systolic BP above 140 to 150 mmHg within 12 hours of ICH isassociated with more than double therisk of subsequent death ordependency.Association of low BP anddeterioration is not consistent likeischemic stroke.In patientspresenting with asystolic BP of 150to 220 mm Hg,acute lowering ofsystolic BP to 140mm Hg is probablysafe• Class IIa; Level ofEvidence: B
    42. 42. When to initiate oral antihypertensivemedication?After first 24-48 hours
    43. 43. Subarachnoid HemorrhageAsia Pacific Cohort Studies Collaboration demonstrated that hypertension wasan independent risk of SAH increased sharply with increase in systolic BPSAH incr ICP & decr cerebral perfusion causing global ischemiaInduces intense vasospasm in neighbouring vessels (4- 12 days) afterinitial bleed.Goal-dec 20-25% of MAP over 6-12 hrs but not <160/100.If vasospasm occurs later-inc BP with 3H(not proven)Preffred - lobetAvoid- nitrodilators
    44. 44. Hypertensive EncephalopathyWhen high perfusion pressure overwhelms cerebralautoregulation.Can lead to blindness, seizures, coma, gradually worseningheadache.Pathologically-cerebral edema, petechial hemorrhg,microinfarcts.Immediate Neuroimagng - to rule out ischemicstroke/hemorrhageHallmark is improvement in 12-24 hrs of BP redn.
    45. 45. HTN ENCEPH… DIFFN POINTSFocal neurological deficit is unusual withoutcerebral bleedPapilledema is almost always assoc with HtnencephMental staus improves by 24-48hrs-delayed in CNSbleedBrain dysfunction develops by 12-24 hrs in Htn butmore acutely with ischemic stroke/bleed.
    46. 46. Posterior Reversible Encephalopathy Syndrome(PRES)
    47. 47. HTN ENCEPH…Treatmentshort acting parenteral agents used.MAP should decrease by 15-20% over 2-3 hrs. .
    48. 48. Prevention of Stroke - TrialsDiuretics CCBs ACE-I ARBsALLHAT(JAMA2002)ALLHAT(JAMA 2002)HOPE ( ACCESS (Stroke 2003)ASCOT (Lancet2005)PROGRESS(Lancet 2002)MOSES (Stroke 2006)Long term control of Hypertension following strokereduces recurrence of stroke
    49. 49. BP Control as Primary Prevention of StrokeBoth lifestyle modification and pharmacological therapy, arerecommended (Class I; Level of Evidence A)Systolic BP should be treated to a goal of <140 mm Hg anddiastolic BP to <90 mm Hg because these levels are associatedwith a lower risk of stroke and cardiovascular events (Class I;Level of Evidence A).In patients with hypertension with diabetes or renal disease, theBP goal is <130/ 80 mm Hg (also see section on diabetes) (ClassI; Level of Evidence A).
    50. 50. Cerebral Small Vessel Disease (SVCD)n Incidence: 20-25% of Small vessel Infarcts (SVI) lacunar infarctsn Short term better prognosis but not long term
    51. 51. Cerebral Microbleeds (CMBs)n MRI – 4.7% - 24.4% in communityn Ischemic stroke 19.4%n Hemorrhagic stroke: 68.5%n Lobar distribution in Amyloid Angiopathyn Basal and Infratentorial in Hypertensive Vasculopathyn Hypertension, Diabetes and Low serum Cholesterol as predispositionA gradient-recalled echoandB susceptibility weightedimaging maps.Susceptibility-weightedimaging is more sensitivethan gradient-recalledecho to venous structures.
    52. 52. THANKS