1. Hypertension and CVA
Dr PS Deb MD, DM
Director Neurology Guwahati Neurological
Research Center, Assam
Hypertension
CVA
Hypertension
2. Hypertension and Stroke (WHO 2013)
Hypertension causes 10%
death in India
• 51% death due to CVA
• 45% due to CAD
Stroke >25 years
• 34% men
• 32% women
Preventable by Rx
• 35-45% Stroke
• 25% CAD
3. Diastolic BP as Risk Factor of Stroke (< 1990)
Eastern Stroke and Coronary
Heart Disease Collaborative
Research Group
• Diastolic BP 110 mmHg had
13times risk of stroke as compared
to <79 mmHg
60
50
40
30
20
10
0
Stroke Prevention
MacMohan
Stroke
Prevention
4. 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% inAustralia
5. 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.
60
50
40
30
20
10
0
Stroke after 10mmHg
Decrease of Systolic BP
Stroke
Prevention
6. Pathogenesis of Stroke due to Hypertension
1. Large vesselAtherosclerosis
2. Medium vesselArteriosclerosis
3. Small Vessel Lipohyalanosis
4. Cardioembolic stroke
7. Cerebral Ischemic Stroke
Synaptic transmission
failure
Membrane pump failure
20
10
0
Time in hours
CBF
(ml/100g
brain)
Normal flow, normal function
Low flow, raised O2 extraction, normal
function
1 2 3 4 5
10. Blood Pressure in Acute IschemicStroke
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
11. BP control in Acute IschemicStroke
Is lowering of
BP harmful?
Y
es Is raising BP
beneficial?
Y
es
No
No What class of
drug?
CC Blocker
AB Blocker
Vasodilators
12. 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
13. 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
14. 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 inthe
systolic pressure, was significantly associated with worse outcome
15. 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.
16. The Continue or Stop Post-StrokeAntihypertensives
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.
17. 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
18. 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
19. 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.
20. Is Raising Blood Pressure in Acute Ischemic
Stroke Beneficial? Yes
Small pilot trials have carefully
raised the blood pressure in acute
ischemic stroke patients without
apparent complications.
Severe intracranial atherosclerosis
or stenosis may require BP
elevation to maintain IC
circulation
21. Is Raising Blood Pressure in Acute Ischemic
Stroke Beneficial? No
U shaped relation between
admission BP and outcome
Elevated in-hospital blood pressure
during acute ischemic stroke has
been associated with worse clinical
outcomes in a more linear fashion.
22. 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
23. 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.
24. 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
25. When to Temporary discontinuation ofAHT?
Because swallowing is often impaired, and
responses to the medications may be less
predictable during the acute stress.
26. When to Re-start AntihypertensiveTherapy
After the initial 24 hours from stroke onset in
most patients.
Individualize such therapy based on relevant co-
morbidities, ability to swallow.
30. 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)
32. 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?
33. Primary aim
1. Early intensive blood pressure (BP) lowering (target of
<140 mmHg systolic) as compared to the
2.Guideline-recommended ‘standard’ control of BP
(target of <180 mmHg systolic) improves
3.Survival free of major disability in acute spontaneous
intracerebral haemorrhage (ICH)
Standardised treatment protocols – locally available
intravenous (IV) BP lowering agents of physician’s choice
33
34. Protocol schema: from INTERACT1 (Lancet Neurol 2008)
and (Int J Stroke 2010)
Acute spontaneous ICH confirmed by CT/MRI
Definite time of onset within 6hours
Systolic BP 150 to 220mmHg
No indication/contraindication to treatment
In-hospital vital signs, NIHSS, GCS and BP over 7 days
Intensive BPlowering
SBP <140 mmHg
Standard BPmanagement
Guidelines SBP <180 mmHg)
R
34
Independent 90 day outcome with
modified Rankin scale (mRS)
N=2800 gives 90% power for
7% absolute (14% relative)
decrease (50% standard vs 43%
intensive) in outcome
35. Patient Flow – 2839 patients
recruited October 2008 to August
2012
1382 (98.5%) for
primary
outcom
e
1412 (98.3%) for
primary
outcom
e
2839
Randomised
28,829 Total estimated
screened
3 no consent
1 missing baselinedata
2lost to follow-up
3 withdrew consent
12 alive without mRSdata
Reasons for exclusion
(n=3572)
39%Outside timewindow
16% Judgedunlikely to benefit
11% BPoutsidecriteria
8% Plannedearly surgery
5% Refused
21% Other reasons
6411 Screening logs
completed
1403 Intensive BP lowering 1436 Standard BP lowering
5 no consent
1 missingbaselinedata
5 lost to follow-up
4 withdrew consent
9 alive without mRSdata
36. Systolic BP time trends
1 hour - Δ14mmHg(P<0.0001)
6 hour - Δ14mmHg(P<0.0001)
Systolic BP control
Median (iqr) time to treatment, hr - intensive 4 (3-5), standard 5 (3-7)
Intensive group to target
(<140mmHg)
462 (33%)at 1hour
731 (53%)at 6hours
Mean
Systolic
Blood
Pressure
(mm
Hg)
0
110
130
120
140
150
160
180
170
190
200
Standard
Intensive
//
//
Days / Time
164
153
150
139
am pm am pm am pm am pm
2 3 4 5
am pm am pm
6 7
P<0.0001
beyond 15mins
R 15 30 45 60 6 12 18 24
Minutes Hours
Targetlevel
36
37. safe - no increase in death or harms
effective – borderline significant effect on the primary
endpoint
• secondary analyses - improved recovery of physical functioning and
health-related quality of life in survivors
Early intensive BP lowering treatment is
37
38. 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 rtPAin
ischaemic stroke)
No clear time-dependent relationship of treatment
• potential mechanisms beyond haematoma growth
• benefits of BP control may take several hours tomanifest
• effects on haematoma growth and other results outlined in Symposium
this afternoon
INTERACT2 - issues
38
39. 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
41. Recommendation AHA2010
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
42. When to initiate oral antihypertensive
medication?
After first 24-48 hours
43. Subarachnoid Hemorrhage
Asia Pacific Cohort Studies Collaboration demonstrated thathypertension was
an independent risk of SAH increased sharply with increase in systolicBP
SAH 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 6-12hrs but not <160/100.
If vasospasm occurs later-inc BP with 3H(notproven)
Preffred - lobet
Avoid- nitrodilators
44. 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.
45. 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.
48. Prevention of Stroke - Trials
Diuretics CCBs ACE-I ARBs
ALLHAT ALLHAT HOPE ( ACCESS (Stroke 2003)
(JAMA (JAMA 2002)
2002)
ASCOT (Lancet PROGRESS MOSES (Stroke 2006)
2005) (Lancet 2002)
Long term control of Hypertension following stroke
reduces recurrence of stroke
49. 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).
50. Cerebral Small Vessel Disease (SVCD)
n Incidence: 20-25% of Small vessel Infarcts (SVI) lacunarinfarcts
n Short term better prognosis but not longterm
51. Cerebral Microbleeds (CMBs)
n MRI – 4.7% - 24.4% in community
n Ischemic stroke 19.4%
n Hemorrhagic stroke: 68.5%
n Lobar distribution in Amyloid Angiopathy
n Basal and Infratentorial in Hypertensive Vasculopathy
n 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.
