hypertension and stroke
DESCRIPTION
This was lecture given at College of General Practitioner Hyderabad on 16th June 2013 as refresher course on HypertensionTRANSCRIPT
Hypertension and CVA
Dr PS Deb MD, DM
Director Neurology Guwahati Neurological Research Center, Assam
Hypertension
CVA
Hypertension
Hypertension and Stroke (WHO 2013)
Hypertension and Stroke (WHO 2013)
Diastolic BP as Risk Factor of Stroke (< 1990)
Diastolic BP as Risk Factor of Stroke (< 1990)
5 mm
Hg
7.5 m
mHg
10 m
mHg
0
10
20
30
40
50
60
Stroke Prevention MacMohan
Stroke Prevention
Systolic BP as Risk factor for Stroke (>1990)
Systolic BP was more strongly correlated with 12-year risk of stroke mortality than diastolic BP in Framingham Heart Study
Prospective population based Copenhagen City Heart study also reported systolic BP is a better predictor of stroke than diastolic
Asia Pacific Cohort Studies Collaboration analyzing 37 cohort studies reported a continuous, log-linear association between systolic BP and risk 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
Age and Stroke with Hypertension
Elevated BP and risk of stroke is weaker in older age compared to middle age
The Asia Pacific Cohort Studies Collaboration (APCSC)
Treating BP is still important due to increased incidence of stroke with aging.
Below 60
60-6
9
Above
700
10
20
30
40
50
60
Stroke after 10mmHg Decrease of Systolic BP
Stroke Prevention
Pathogenesis of Stroke due to Hypertension
1. Large vessel Atherosclerosis
2. Medium vessel Arteriosclerosis
3. Small Vessel Lipohyalanosis
4. Cardioembolic stroke
Cerebral Ischemic Stroke
Normal flow, normal function
Synaptic transmission failure
Membrane pump failure
20
50
10
0Time in hours
CB
F (
ml/1
00g
brai
n)
Low flow, raised O2 extraction, normal function
1 2 3 4 5
Cerebral Autoregulation
Dys-autoregulation after Ischemic Stroke
Dys-autoregulation after Ischemic Stroke
Blood Pressure in Acute Ischemic Stroke
Systolic 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 with a history of hypertension
Blood pressure decreases spontaneously within 90 minutes after onset
BP control in Acute Ischemic Stroke
Is lowering of BP harmful?
Yes Is raising BP beneficial?
Yes
No
No What class of drug?
CC Blocker
AB Blocker
Vasodilators
Is lowering BP is harmful? Yes
Autoregulation is defective in acute ischemia but it is time dependent.
Oxygen extraction compensate to a point
BP control hamper perfusion of penumbra region
Lowering BP below >10-15% is potentially harmful
Hypertensive patient shows more significant decrease in MBP after induced hypotension than hypertension
Oral Nimodipine in acute ischemic stroke
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
Intravenous Nimodipine West European Stroke Trial (INWEST)
Nimodipine as cytoprotective therapy within 24 hours after ischemic stroke onset and found complications related to blood pressure lowering
Decrease in blood pressure was associated with intravenous Nimodipine therapy and worse clinical outcome at 21 days.
A decrease in diastolic blood pressure >10 mm Hg, but not in the systolic pressure, was significantly associated with worse outcome
Candesartan in Acute Stroke
An efficacy trial (n=2004) of candesartan showed a mean blood pressure reduction of 7/5 mm Hg at day 7
Favorable outcomes at 6 months, were less likely with candesartan than with placebo.
The Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS)
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.
Is lowering BP in AIS harmful? No
Defective autoregulation may not be present in all patients
Ischemic penumbra may not be present in all patients
Clinical experience indicates that many patients tolerates gentle treatment of high BP
Natural history studies demonstrate no deleterious effects of lowering BP
High BP at onset has poor prognosis
Hypertension during acute ischemic stroke
Extreme hypertension -> Encephalopathy, Cardiac complication, renal insufficiency
Moderate arterial hypertension during acute ischemic stroke might be advantageous by improving cerebral perfusion of the ischemic tissue
It might be detrimental by exacerbating edema and hemorrhagic transformation of the ischemic tissue
Candesartan in Acute Stroke
Starting an average of 30 hours after ischemic stroke onset in 342 patients with elevated blood pressure.
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.
Is Raising Blood Pressure in Acute Ischemic Stroke Beneficial? Yes
Is Raising Blood Pressure in Acute Ischemic Stroke Beneficial? Yes
Is Raising Blood Pressure in Acute Ischemic Stroke Beneficial? No
Is Raising Blood Pressure in Acute Ischemic Stroke Beneficial? No
Other problem of raising BP
Increase risk of ICH after lytic therapy
May increase amount and formation of cerebral edema
A 12% increase in terms of size of infarction.
May adversely affect cardiac function
Optimal BP during acute ischemic stroke
Extreme arterial hypotension is clearly detrimental, because it decreases perfusion to multiple organs, especially the ischemic brain, exacerbating the ischemic injury.
An ideal blood pressure range has not yet been scientifically determined for individual patient.
An ideal blood pressure range during acute ischemic stroke will depend on the stroke subtype and other patient specific co-morbidities.
Recommendation (AHA 2013)
1. Not for thrombolysis > 220/120 mmHg,
2. For Thrombolysis >185/100 mmHg
3. Severe cardiac failure, Aortic dissection, Hypertensive encephalopathy
4. Cautious blood pressure lowering when (IV Labetalol, IV Enalepril, Nitrendepine) avoid venodilators
When to Temporary discontinuation of AHT?
Because swallowing is often impaired, and responses to the medications may be less predictable during the acute stress.
When to Re-start Antihypertensive Therapy
After the initial 24 hours from stroke onset in most patients.
Individualize such therapy based on relevant co-morbidities, ability to swallow.
Hemorrhagic Strokes
Hypertension
ICH
Hypertension
Early hemorrhage growth in patients with intra-cerebral hemorrhage.
Time in Hours
0
5
10
15
20
25
30
35
Hematoma Expansion
0-3 hr03-6 hr16-12 hr212-24 hr24-48 hr
Time
Num
ber
Elevated Systolic Blood Pressure May Predispose to Hematoma Enlargement
BP >200 BP <2000
5
10
15
20
25
30
35
40
45
.Hematoma Enlargement
Hematoma volume and outcome
Type ICH Vol. mL Coma Prognosis
I < 30 - Good
II 30-60 - Fair
III 30-60 + Poor
>60 +
(Joseph P. Broderick et al Stroke 1993;24:987-993)
Is there Risk of treating Acute Hypertension?
How to treat Hypertension in ICH?
When should we treat Hypertension
What is the target mean arterial pressure for patients with intracerebral 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: 24 hours or 72 hours?
Primary aim
Primary aim
33
Protocol schema: from INTERACT1 (Lancet Neurol 2008) and (Int J Stroke 2010)
Acute spontaneous ICH confirmed by CT/MRI
Definite time of onset within 6 hours
Systolic BP 150 to 220 mmHg
No indication/contraindication to treatment
In-hospital vital signs, NIHSS, GCS and BP over 7 days
Intensive BP lowering SBP <140 mmHg
Standard BP management Guidelines SBP <180 mmHg)
R
34
Acute spontaneous ICH confirmed by CT/MRI
Definite time of onset within 6 hours
Systolic BP 150 to 220 mmHg
No indication/contraindication to treatment
N=2800 gives 90% power for 7% absolute (14% relative) decrease (50% standard vs 43% intensive) in outcome
Patient Flow – 2839 patients recruited October 2008 to August 2012
1382 (98.5%) for primary outcome
1412 (98.3%) for primary outcome
2839 Randomised
28,829 Total estimated screened
3 no consent 1 missing baseline data 2 lost to follow-up 3 withdrew consent12 alive without mRS data
Reasons for exclusion (n=3572) 39% Outside time window 16% Judged unlikely to benefit 11% BP outside criteria 8% Planned early surgery 5% Refused 21% Other reasons
6411 Screening logs completed
35
1403 Intensive BP lowering
1436 Standard BP lowering
5 no consent1 missing baseline data5 lost to follow-up4 withdrew consent9 alive without mRS data
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 hours
Mea
n S
ysto
lic B
loo
d P
ress
ure
(mm
H
g)
0
110
120
130
140
150
160
170
180
190
200
R 15 30 45 60 6 12 18 24 2 3 4 5 6 7
StandardIntensive
////
Minutes Hours Days / Time
164
153
150
139
am pm am pm am pm am pm am pm am pm
P<0.0001beyond 15mins
Target level
36
safe - no increase in death or harms
• secondary analyses - improved recovery of physical functioning and health-related quality of life in survivors
effective – borderline significant effect on the primary endpoint
Early intensive BP lowering treatment is
37
Treatment effect smaller (4%) than expected 7% absolute, but:
• active-comparison study on background therapies, some with BP lowering properties (i.e. mannitol)• equates to NNT 25 (greater than aspirin and near late use of rtPA in ischaemic 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 Symposium this afternoon
INTERACT2 - issues
38
INTERACT2 resolves longstanding uncertainty over the management of elevated BP in acute ICH
Provides evidence regarding safety and efficacy in a broad range of patients with ICH
Defines for the first time a medical therapy for the management of acute ICH
As BP lowering treatment is low cost, simple to implement, and widely applicable, the treatment should become standard of care to patients with ICH in hospitals all over the world
Conclusions
39
Baseline
24 hrs
SBP<180 mm Hg
SBP<140 mm Hg
3 m
Recommendation AHA 2010
Hypertension is common during early states of ICH -> Expansion, Peri-hematoma edema and re-bleeding
A 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.
Association of low BP and deterioration is not consistent like ischemic stroke.
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 of Evidence: B
When to initiate oral antihypertensive medication?
After first 24-48 hours
Subarachnoid Hemorrhage
Subarachnoid Hemorrhage
Hypertensive Encephalopathy
When high perfusion pressure overwhelms cerebral autoregulation.
Can lead to blindness, seizures, coma, gradually worsening headache.
Pathologically-cerebral edema, petechial hemorrhg, microinfarcts.
Immediate Neuroimagng - to rule out ischemic stroke/hemorrhage
Hallmark is improvement in 12-24 hrs of BP redn.
HTN ENCEPH… DIFFN POINTS
Focal neurological deficit is unusual without cerebral bleed
Papilledema is almost always assoc with Htn enceph
Mental staus improves by 24-48hrs-delayed in CNS bleed
Brain dysfunction develops by 12-24 hrs in Htn but more acutely with ischemic stroke/bleed.
Posterior Reversible Encephalopathy Syndrome (PRES)
HTN ENCEPH…Treatment
short acting parenteral agents used.
MAP should decrease by 15-20% over 2-3 hrs. .
Prevention of Stroke - Trials
Diuretics CCBs ACE-I ARBs
ALLHAT (JAMA 2002)
ALLHAT (JAMA 2002)
HOPE ( ACCESS (Stroke 2003)
ASCOT (Lancet 2005)
PROGRESS (Lancet 2002)
MOSES (Stroke 2006)
Long term control of Hypertension following stroke
reduces recurrence of stroke
BP Control as Primary Prevention of Stroke
Both lifestyle modification and pharmacological therapy, are recommended (Class I; Level of Evidence A)
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 (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).
Cerebral Small Vessel Disease (SVCD)
Incidence: 20-25% of Small vessel Infarcts (SVI) lacunar infarcts Short term better prognosis but not long term
Cerebral Microbleeds (CMBs)
MRI – 4.7% - 24.4% in community Ischemic stroke 19.4% Hemorrhagic stroke: 68.5% Lobar distribution in Amyloid Angiopathy Basal and Infratentorial in Hypertensive Vasculopathy Hypertension, Diabetes and Low serum Cholesterol as predisposition
A gradient-recalled echo and B susceptibility weighted imaging maps. Susceptibility-weighted imaging is more sensitive than gradient-recalled echo to venous structures.
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