Transcript HYPERTENSIVE CRISIS AND BRAIN NATRIURETIC PEPTIDE

HYPERTENSIVE CRISIS AND
BRAIN NATRIURETIC PEPTIDE
Presented by Ben Sherrill
Doctor of Pharmacy Candidate
UGA College of Pharmacy
Class of 2012
Introduction

Purpose:
◦ Define Hypertensive Crisis and their
guideline-based treatments
◦ Explain the relationship of BNP and
Hypertensive Crisis
◦ Discuss recent studies relevant to the subject
Hypertensive Crisis

Epidemiology
◦ Affects ≈500,000 Americans annually
◦ 1-2% of patients with essential hypertension will
experience hypertensive crisis

Age/gender
◦ Peak incidence for urgencies and emergencies:
 Male – 51 to 60 years / 61 to 70 years
 Female – 61 to 70 years / 81 to 90 years
◦ Rarely occurs in children, however…
 Nearly 25% of children presenting with hypertension
require emergency treatment compared to only 1% of
adults
Hypertensive Crisis

Two types
◦ Hypertensive urgency
 BP >180/120
◦ Hypertensive emergency
 BP >180/120 with acute or immediately progressing
target organ damage
 Examples of target organ damage:
 encephalopathy, intracranial hemorrhage, unstable angina,
dissecting aortic aneurysm, etc.
Hypertensive Crisis
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Pathophysiology
◦ Can be caused by any disorder that causes
hypertension
 Rate of change in BP will determine likelihood that
an acute hypertensive syndrome develops
Contributing factors
Genetic predisposition
Catecholamines
Smoking
Kininogen deficiency
Oral contraceptives
Kinin deficiency
High renin/angiotensin II
Prostacyclin deficiency
Antidiuretic hormone
Immunologic factors
Hypertensive Crisis
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Pathophysiology cont.
◦ Arteriolar changes can occur in multiple
organs
 Necrotizing arteriolitis is most prominent in the
kidneys, brain, heart, and eyes
◦ Inflammation and necrosis of the arterioles
 Worsened by platelet plugging, fibrin deposition, and
hemolysis
 Very prominent in the kidneys
 Leads to renal failure and activation of the renin-angiotensin
system
Hypertensive Crisis
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Complications
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Myocardial infarction
Hypertensive encephalopathy
Left ventricular hypertrophy
Retinopathy
Cerebrovascular accident
Chronic renal failure
Aortic dissection
Hypertensive Crisis
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Diagnosis
◦ Not made on basis of BP alone
 Rate of increase in BP is more important than absolute
BP
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Presentation
◦ Varies depending on disease state
◦ Textbook symptom is “BP >180/120”
◦ Other symptoms:
Back pain
Chest pain
Dyspnea
Neurologic deficits
Seizures
Altered mental status
Hypertensive Crisis
Differential Diagnosis
Blunt head trauma
Intracranial hemorrhage
Thromboembolic stroke
Acute coronary
syndrome
Subarachnoid
hemorrhage
Aortic dissection
Bacterial meningitis
Malignant hypertension
Alcohol withdrawal
syndrome
Pulmonary edema
Pre-eclampsia
Acute renal failure
Poisoning
Drug ADR
Chronic renal failure
Cerebral metastases
Primary malignant
neoplasm of cerebrum
Viral encephalitis
Pheochromocytoma
Hypertensive Crisis
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Prognosis
◦ Mortality
 Related to the degree of renal dysfunction and
severity of retinopathy
 Lowest survival is associated with renal insufficiency
and severe hypertensive retinopathy
 Renal insufficiency is the strongest predictor of
mortality
Hypertensive Crisis: Treatment

Hypertensive urgency
◦ Ideally managed by adjusting maintenance therapy,
adding a new antihypertensive, or increasing the
dose of a current medication
 Preferred approach because it allows for a gradual
decrease in BP
 Rapid decreases in BP are discouraged due to potential
risks
 CVA, MI, acute kidney failure
 Requires reduction in BP with oral meds over the
course of several hours to several days
Hypertensive Crisis: Treatment
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Hypertensive urgency cont.
◦ Possible to use acute administration on shortacting oral agents, such as captopril, clonidine,
or labetalol. And carefully monitor the patient
 Lacking data to support
Drug
Dose
Time
Captopril
25mg to 50mg
1 to 2 hour intervals
Clonidine
0.2mg initially, followed by 0.2mg hourly, to a max Given hourly until
of 0.7mg
DBP is <110
Labetalol
200mg to 400mg
Additional dose every
2 to 3 hours
Hypertensive Crisis: Treatment
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Hypertensive emergency
◦ Target organ damage
◦ Require parenteral therapy
◦ The goal is not to lower BP to less than 140/90
 Initial target is a reduction in Mean Arterial Pressure of up to
25% within minutes to hours
 Once stable, BP can then be reduced to 160/100 – 160/110
within the next 2 to 6 hours
 If taper is tolerated, more reduction can be made over the next 24 to
48 hours
 Slow approach is due to the risk of end-organ ischemia or
infarction
 There is one exception to this approach
 Patients presenting with acute ischemic stroke
 Elevated BP is required for an extended period of time
Hypertensive Crisis: Treatment
Brain Natriuretic Peptide

BNP is a hormone secreted by the heart
ventricles
◦ Secreted in response to stretching of
cardiomyocytes
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Systemically, BNP decreases vascular
resistance and central venous pressure
◦ It also increases netriuresis
◦ The net effect is a decrease in blood volume,
which in turn lowers systemic blood pressure and
afterload
◦ This helps increase cardiac output (increased
ejection fraction
Brain Natriuretic Peptide
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Significance
◦ Used for screening and diagnostic purposes
 Acute decompensated heart failure
 Higher levels have been associated with worse prognosis
◦ Unfortunately, there is no clearly defined level
which separates patients with or without heart
failure
 CHF patients – BNP is typically >100pg/mL
 Diagnostic gray area in the 100-500pg/mL range
◦ Many studies have been designed to test the
significance of BNP in various disease states
Brain Natriuretic Peptide
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Studies
◦ BNP demonstrated to increase during acute
decompensated heart failure and ACS
 Result of direct myocyte injury from pressure or
volume overload
◦ Release of BNP results in improved
myocardial relaxation
 Also serves a regulatory role in response to acute
increases in ventricular vol.
 Opposes vasoconstriction, Na+ retention, and antidiuretic
effect of the RAAS
STUDY 1: ELEVATED B-TYPE
NATRIURETIC PEPTIDE
BLOOD LEVELS DURING
HYPERTENSIVE CRISIS
Di Somma, et al. High Blood Pressure & Cardiovascular Prevention.
January 1 2008,Vol. 15. 1: 23-28
Study 1
Observational study
 Objectives
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◦ Assess the role of BNP in the course of
hypertensive crisis
◦ Evaluate the possible role of BNP in the
differential diagnosis between HE or HU
◦ Investigate the relationship between BNP
concentration and BP acute burden with
consequent myocardial ischemia or brain
damage
Study 1
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Rationale
◦ Recent studies found increased levels of BNP
in hypertensive crisis compared with patients
with normal BP
◦ Studies had also demonstrated increased BNP
associated with heart strain due to acute
increased after load (as in HE)
Study 1
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Methods
◦ 57 patients admitted to ED for acute elevated BP
between March 2006 and July 2007
◦ All patients received:
 12 lead EKG
 CBC
Funduscopy
CMP
Chest X-ray
Cardiac enzymes
◦ If indicated, patients also received echocardiogram
and brain CT
◦ Inclusion criteria:
 Hypertensive crisis and admitted to 1 of 2 ED’s
◦ Exclusion criteria:
 Pregnant, age <18 or >90, BMI >30, neoplasms, chronic kidney
failure, atrial fibrillation, traumatic chest events, heart failure
Study 1
Study 1
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Methods
◦ Patients were divided into 2 groups: 25 with HE
(target organ damage) and 32 with HU
◦ SBP and DBP were measured from both right and
left arms
 Average of 2 readings taken 30 s apart
◦ MAP calculated as DBP + 1/3 Pulse Pressure
 PP = SBP – DBP
◦ Student t-test was used for comparison of
characteristics between the two groups, and to
find statistical differences in BNP between HE
and HU
STUDY 1
This chart is a breakdown of
the statistical distribution of
the target-organ lesions
associated with hypertensive
emergencies in the study
population.
ACS = Acute coronary
syndrome
Hen = Hypertensive
encephalopathy
HS = Hemorrhagic stroke
IS = Ischemic stroke
TIA = Transient ischemic
attack
Study 1
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Results
◦ 44% incidence of HE, 56% incidence of HU
◦ 2 subgroups were distinguished in HE
 Cardiac involvement (40%)
 10 pts with ACS (8 w/ unstable angina, 2 w/ acute MI)
 Neurological involvement (60%)
 15 pts total (7 w/ IS, 2 w/ TIA, 4 w/ HS, 2 w/ Hen)
◦ No significant difference at the ED admission in
SBP, DBP, MBP, PP, age, SCr, CrCl, BMI, or gender
distribution
◦ Avg hospital stays were 5 days for HE and 12
hours for HU
Study 1
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Results
◦ Mean BNP for all pts was 62.85 +/- 74.24 pg/mL
 In HE, mean BNP was 113.22 +/- 87 pg/mL (p<0.01)
 In HU, mean BNP was 23.5 +/- 21.3 pg/mL (p<0.01)
◦ Mean BNP for myocardial ischemia sub-group was 162.02 +/95.7 pg/mL (p<0.01)
◦ Mean BNP for neurological sub-group was 80.7 +/- 65.2 (p<0.01)
◦ No correlation between BNP and SBP, DBP, MAP, PP, and BMI
◦ A statistical correlation between BNP and PP (r=0.37; p<0.05)
was found for the HU group
◦ A significant negative relationship was found between renal
clearance in BNP (r=-0.36, p<0.01)
◦ A positive correlation was found between age and BNP (r=0.4,
p<0.05)
Study 1
Study 1
Study 1
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Discussion
◦ BNP can help distinguish between HE (with heart
or brain damage) and HU
◦ Authors speculate that BNP is released into the
blood during HE with heart involvement due to
acute ischemic disease
 Recent studies show possibility of BNP release during a
sudden increase in BP as a result of heart involvement
(such as in pre-eclampsia) due to increase of systemic
vascular resistance
◦ Also speculate that rise of BNP in HE should be
attributed to the high increase of afterload due to
sudden acute rise in systemic vascular resistance
Study 1
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Limitations
◦ Small study
◦ Circulating levels of BNP before the
hypertensive crisis are unknown
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Conclusion
◦ BNP has a role as a diagnostic tool in the ED
for the screening of HE due to myocardial
involvement or brain injury

Level of evidence
◦ IIIa
STUDY 2: D-DIMER AND BNP
LEVELS IN ACUTE AORTIC
DISSECTION
Sbarouni, et al. International Journal of Cardiology. January 17 2007,Vol.
122; 170-172
Study 2
Letter to the editor
 Prospective observational study
 Objectives

◦ To test if there is a simple and quick
laboratory test to rule out AAD
◦ They looked at D-dimer, C-reactive protein,
BNP, and white blood cell count in patients
with established AAD
Study 2
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Methods
◦ Patients
 18 consecutive patients with diagnosed AAD admitted
for surgery
 21 consecutive patients with chronic aortic aneurysm
 8 normal subjects
◦ Diagnosis performed for all with computed
tomography and echocardiogram
◦ Dissection was classified according to Stanford
classification
◦ Serum levels of study substances were drawn as
soon as the patient came to the hospital
Study 2
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Results
◦ Significant difference between 3 study groups for
all 4 parameters
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WBC: p=0.0005
D-dimer : p<0.0001
CRP: p=0.0121
BNP: p=0.0012
◦ For BNP: plasma levels were significantly higher in
AAD and CAD groups compared to normal
patient group (p=0.0005 and p=0.0016)
 No significant difference between AAD and CAD group
(p=0.32)
Study 2
Study 2
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Discussion and Conclusion related to BNP
◦ Small sample size
◦ To authors’ knowledge, first study comparing BNP
with AAD and CAD
◦ Elevated in both groups compared to control
◦ AAD and CAD associated with longstanding HTN,
which is often accompanied with diastolic
abnormalities of the left ventricle and aortic
regurgitation
 Incompetence of the aortic valve presents with increased
pulse pressure, which correlates positively with BNP levels in
healthy adults
◦ BNP is not a good diagnostic marker for AAD
compared to D-dimer
Study 2
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Limitations
◦ Very small
◦ BP was not measured
◦ Larger sample sizes needed with more
involvement from multiple study centers

Level of evidence
◦ IIIb
Conclusion
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BNP has potential for use as a diagnostic
marker in hypertensive emergency
◦ Needs more evaluation with better designed
studies
◦ Circulating BNP levels pre-hypertensive event
would provide a better idea of relationship
 Impossible to predict
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Many questions are left to be answered in
the future
Sources
1.
2.
3.
4.
5.
6.
Pharmacotherapy: A pathophysiologic approach, 8th edition.
Joseph T. Dipiro, et al. 2011 McGraw Hill
Hypertensive Crisis, Micromedex 2.o. Last update August 9, 2011
Clinical Features in the Management of Selected Hypertensive
Emergencies. William J. Elliot. Progress in Cardiovascular Diseases,
March/April 2006.Vol. 48, 5; 316-325
Hypertensive Crisis: Hypertensive Emergencies and Urgencies. M.
Aggarwal, I. Khan. Cardiology Clinics, 2006,Vol. 24; 135-146
Elevated B-Type Natriuretic Peptide Blood Levels During
Hypertensive Crisis. S. Di Somma, et al. High Blood Pressure &
Cardiovascular Prevention. January 1 2008,Vol. 15. 1: 23-28
D-dimer and BNP Levels in Acute Aortic Dissection. Sbarouni, et
al. International Journal of Cardiology. January 17 2007,Vol. 122;
170-172