Hypertension and Cardiac

Disease

UII Lecture Series

Yogyakarta
7th May 2015
 Flow of Lecture

Epidemiology of Hypertension
Pathophysiology of Hypertension
Diagnostic Work up
Therapeutics of Hypertension and
Hypertension Guidelines
Conclusion
 Flow of Lecture

Epidemiology of Hypertension
Pathophysiology of Hypertension
Diagnostic Work up
Therapeutics of Hypertension and
Hypertension Guidelines
Conclusion
 Prevalence of hypertension in the
Asia-Pacific region

Martiniuk ALC, for the Asia-Pacific Cohort Studies Collaboration, J Hypertens 2007; 25:7379.
 Hypertension in Malaysia from the National Health
and Morbidity Surveys
( > 30 years )

1996 2006 2011

Sample size 23,007 33,976 18,098

Prevalence 33 % 43% 44%

Aware 33 % 36% 39%

 Deaths attributed to 19 leading factors,
by country income level, 2004

Health Statistics and Informatics

 HYPERTENSION IN THE ASIA PACIFIC
REGION AND CV RISK

Contributes to two thirds ( 66% ) of all

cardiovascular events compared to
46% worldwide )1

Main cause of premature death in

China2
1. Asia Pacific Cohort Studies Collaboration: Blood pressure and cardiovascular diseases in the Asia Pacific
region. J Hypertens 2003;21:707-716.
2. He J , Gu D , Chen J et al Premature deaths attributable to blood pressure in China: a prospective cohort
study. Lancet 2009 Nov 21; 374 ( 9703 ):1765-72
 Dangers of Hypertension

In 2010 hypertension remains the

leading cause of death

WHO estimates it kills 17 million per

year

Hypertension shortens life by 5 years

 Why Hypertension Kills

Stroke
Ischaemic Heart Disease
Chronic Heart Failure
Chronic Kidney Disease
Peripheral Vascular Disease
Dementia
 WORLD HEALTH STATISTICS 2014
( WHO )
What were the leading cause of Years
of Life Lost ( YLL ) due to premature
mortality ?

1. Ischaemic Heart Disease

2. Lower Respiratory Tract Infection
3. Stroke
 Flow of Lecture

Epidemiology of Hypertension
Pathophysiology of Hypertension
Diagnostic Work up
Therapeutics of Hypertension and
Hypertension Guidelines
Conclusion
Physiology of BP Control

BP = CO x TPVR

CO = SV x HR

TPVR is controlled by arteriolar

vascular tone
Pathophysiology of Hypertension
95% are Essential Hypertension
No identifiable Cause; Genetic
Predisposition and Unhealthy Lifestyle
5% are Secondary Hypertension
Commonest is Obstructive Sleep Apnoea
( OSA )
Renal Disease ( Parenchymal and RAS )
Endocrine Disease
Others ( Co Arctation, Iatrogenic )
 Pathophysiology of Essential
Hypertension
Interplay of

Renin Angiotensin Aldostrone System

Sympathetic Nervous System
Salt and Water Retention
Inbalance between Endogenous
Vasodilators and Vasoconstrictors
The Renin-Angiotensin-Aldosterone (RAA) System
Kidneys Adrenal cortex
Liver secretes secrete secretes
angiotensinogen renin aldosterone

Angiotensin
converting
Blood Renin enzyme
(ACE)

Angiotensinogen Angiotensin I Angiotensin II Aldosterone

Growth NA+ retention

Sympathetic Vascular
factor H2O retention
activation smooth muscle
stimulation
constriction K+ excretion
Mg+ excretion
Angiotensin effects on the nephron

Angiotensin II
+ + +
+
-
Pglom

Aldosterone

+
Proximal Na+-
reabsorption Na+-reabsorption
 Arterial Ageing - Pathophysiology
Advanced Glycation
Mechanical Strain- (AGEs):
induced: Endothelial Dysfunction: Impaired Glucose
Elastin Fragmentation Reactive Oxygen Species Tolerance
Collagen Deposition Oxidised LDL Modification of Collagen
Angiotensin II

Aortic Dilatation
Wall Hypertrophy

Aortic Stiffening Increased Pulse Wave Velocity

Accelerators
Williams B, J Am Coll Cardiol 2009
Importance of Arterial Pulse Waveform
Age 25 years
Importance of Arterial Pulse Waveform

Age 47 yrs
Importance of Arterial Pulse Waveform

Age 80 yrs
 RAAS in cardiovascular pathology
Risk factors: diabetes, obesity, smoking, age
RAAS
Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction
Arteriosclerosis Apoptosis Arrhythmia
LVH Heart failure
Fibrosis MI

Death
Stroke
Vascular
Hypertension Cognitive
disease
dysfunction

Pro-thrombotic Decreased GFR

state
Proteinuria/albuminuria Renal failure
Glomerulosclerosis

Adapted from: Chung O. & Unger T., Am J Hypertens 1999;12:150S156S

Endogenous Vasodilators vs Constrictors

vasoconstrictors
RAAS
SNS
Endothelin
vasodilators
Arginine
Natriuretic Vasopressin
peptides
Bradykinin
Nitric oxide
Adrenomedullin
 Flow of Lecture

Epidemiology of Hypertension
Pathophysiology of Hypertension
Diagnostic Work up
Therapeutics of Hypertension and
Hypertension Guidelines
Future Hypertension Research
 Diagnosis depends accurate
measurements of Blood Pressure
 Measure BP Properly
Within doctors control

Ask patient to sit up straight

Lean back against the chair
Arm expose
Put the bladder over the brachial artery
Wait 5 minutes ideally, minimum 1 minute
Estimate the SBP by palpation ideally
Deflate cuff at rate of 2 mmHg per second
Record to the nearest 2 mmHg
Take at least 2 readings
 Measure BP Properly
Outside doctors control

Calibration of sphygmomanometer
Appropriate bladder size
Be proactive and do the above
Diagnosis of hypertension in the
adult DOES NOT depend on age
Definition of hypertension is
>140/90 mmHg

Normal SBP is NOT 100 + age

Diagnosed only after taking the BP at

least twice on at least 2 occasions at
least a week apart
 Types of Hypertension
Persistent Systolic diastolic
hypertension
Persistent Isolated Systolic
Hypertension
Isolated Diastolic Hypertension
Office or white coat Hypertension
Masked Hypertension
 Diagnostic Criteria using
CLINIC BP , ABPM and HBPM

White coat Persistent

hypertension Hypertension
CBP > 140/90 mmHg CBP > 140/90 mmHg
HBP/ABP < 135/85mmHg HBP/ABP >135/85mmHg

Normotension Masked
Hypertension
CBP <140/90mmHg
HBP/ABP < 135/85mmHg CBP < 140/90mmHg
HBP/ABP > 135/85mmHg
 History Taking the specifics

Is there long standing hypertension ?

Is there a likely secondary cause?
Are there target organ complications
Are there any other cardiovascular risk
factors
Assess Global Cardiovascular Risk
In the history ( the essentials)

History of diabetes,
hyperlipidaemia,IHD, CVA/TIA, PVD ,
heart failure, renal failure
Smoking status
Family history of pre mature CV
events
History to suggest undiagnosed IHD,
CVA/TIA, PVD
 Physical Examinations the
specifics

Is there long standing hypertension?

Is there evidence for a secondary
cause ?
Are there target organ damage ?
Are there target organ complication?
Assess Global Cardiovascular Risk
In the examination
Corneal arcus, xanthelasma,
xanthoma
Peripheral pulse
Carotid bruit
Displaced apex
Ankle edema
Fundoscopy
Investigation the specifics

Look for target organ damage

Look for target organ complication
Look for secondary cause
Assess Global Cardiovascular Risk
In the investigation
ECG
Urinalysis
Electrolyte
CXR
ECHO if available
 Flow of Lecture

Epidemiology of Hypertension
Pathophysiology of Hypertension
Diagnostic Work up
Therapeutics of Hypertension and
Hypertension Guidelines
Conclusion
Dont Forget the Holistic Approach
to Management
Advice on Healthy Lifestyle

Healthy eating
Physical activity
Coping with stress
Patients education
 Pharmacology of BP Reduction
BP = CO x TPVR

CO = SV (diuretic, B )x HR (NDHP CCB, B )

TPVR = arteriolar vascular tone

(RAS Blocker , DHP CCB, Blocker )

Arterial stiffness (RAS Blocker, CCB )

When to start drug treatment?

Definitely if SBP > 160mmHg and or

DBP > 100 mmHg ( consider
combination therapy )

SBP > 130 mmHg and DBP> 85 mmHg

and patient with moderate ,high or
very high 10yr CV risk
Figure 1. Algorithm for the Management of Hypertension
BLOOD PRESSURE
(Repeated Readings)

SBP = 120 159 mmHg SBP 160 mmHg

and/or and/or
DBP = 80 99 mmHg DBP 100 mmHg

Assess global cardiovascular Drug treatment, (combination

risk Medium / High / therapy preferred)*
(refer to Table 4&5) Very High
* Either free or single pill
combination

Low

3 6 monthly follow-up with advice on non-pharmacological management

SBP < 140 mmHg SBP 140 mmHg

and and/or
DBP < 90 mmHg DBP 90 mmHg

6-monthly follow-up Drug treatment

 Risk Stratification
Co-existing No RF TOD TOC Previous MI
Condition No TOD or or or
RF (1 2) RF ( 3) Previous stroke
No TOC No TOC or or
BP Levels Clinical Diabetes
(mmHg) atherosclerosis

SBP 130 139

and/or
DBP 80 89 Medium
Low High Very high

SBP 140 159

and/or
DBP 90 99 Low Medium High Very high

SBP 160 179

and/or
DBP 100 109
Medium High Very high Very high

SBP >180
and/or
DBP >110 High Very high Very high Very high
Choice of anti-hypertensive drugs with concomitant conditions
Concomitant Condition Diuretics -blockers ACEIs CCBs Peripheral ARBs
-blockers
Diabetes mellitus + +/- +++ + +/- ++
(without nephropathy)
Diabetes mellitus (with ++ +/- +++ ++* +/- +++
nephropathy)
Gout +/- + + + + ++
Dyslipidaemia +/- +/- + + + +

Coronary heart disease + +++ +++ ++ + +++

Heart failure +++ +++ +++ +@ + +++
Asthma + - + + + +
Peripheral vascular + +/- + + + +
disease
Non-diabetic renal ++ + +++ +* + ++
impairment
Renal artery stenosis + + ++$ + + ++$
Elderly with no co-morbid +++ + + +++ +/- +
conditions
Very elderly (>80yrs)
with no co-morbidity +++ + +++ ++ +/- ++
The grading of recommendation from (+) to (+++) is based on increasing levels of evidence and/or
current widely accepted practice
+/- Use with care
- Contraindicated
* Only non-dihydropyridine CCB
Metoprolol, bisoprolol, carvedilol, nebivolol dose needs to be gradually titrated
@ Current evidence available for amlodipine and felodipine only
$ Contraindicated in bilateral renal artery stenosis
 First line Monotherapy in Patients with No
Compelling Indications

NICE UK ESC/ESH AHA ASH/ISH JNC 8 MSH

2011 2013 2013 2013 2014 2013

1.RAAS 1. RAAS 1. RAAS

blockers for RAAS RAAS blockers blockers RAAS
young and blockers, blockers for young or CCB or Blockers ,
non blacks CCB, , CCB , non diuretics CCB,
diuretics diuretics blacks for non diuretics
2. CCB for or beta blacks or beta
elderly and blockers 2. CCB or blockers
blacks diuretics 2.
for elderly Diuretics
or blacks or CCB
for blacks
 Combination therapy

NICE UK ESC/ESH ASH/ISH JNC 8 MSH

2011 2013 2013 2014 2013

Use as First line in First line Optional First line in

second line stage 2 and in stage 2 first line in stage 2 and
high risk all groups high risk

RAAS + Various RAAS + Based on Evidence

CCB possible CCB or age and driven
permutations thiazide ethnicity patient
with some group
preferred
Effective anti-hypertensive combinations used in outcome trials

Effective combination Patients studied

ACEI + thiazide like Post stroke
ARB + thiazide Hypertensive with Left Ventricular
Hypertrophy
CCB + ACEIs or B-blocker + Patients with Coronay Artery Disease
thiazide
ARB + thiazide or CCB High risk hypertenives
+thiazide
CCB +ACEI Medium risk hypertensives with no overt
vascular diseases
ACEI + Thiazide like Single Pill High risk hypertensives with Diabetics
Combintion
ACEI + CCB Single Pill High risk hypertensives
Combination
Thiazide like + ACEI Very elderly ( >80 years old )
 Drug Combinations in Hypertension: Recommendations

Preferred (based on outcome trials)

ACEI /thiazide or thiazide like
ARB/ thiazide
ACEI /CCB
B-Blocker /thiazide
Thiazide diuretics/K+ sparing diuretics

Acceptable( no outcome trial evidence yet )

ARB/CCB
B-Blocker/ thiazide like
DRI/diuretic

ARB = angiotensin receptor blocker

ACE = angiotensin-converting enzyme
CCB = calcium channel blocker
DRI = direct renin inhibitor
 Combination Therapy in Hypertension: An
Asian Pacific Viewpoint

Monotherapy is recommended for first line

treatment of patients with stage 1 hypertension,
with the preferred drug classes varying by
indication
Patients with stage 2 hypertension should receive
combination therapy with two drugs, plus a third
antihypertensive agent if necessary to achieve BP
control
Recommended combinations vary according to
indication and most include an ACEI
Abdul Rashid Abdul Rahman et al Curr Med Res Opin 2015
May;31(5) :865-74
 The Follow up visits

See within 4-6 weeks (enough time for

optimum drug effect to take place )

Review investigation results

Aim for target BP

 Follow up visits
Target BP

Uncomplicated hypertension <

140/90
Diabetics < 140/80
Renal Failure, IHD, Post CVA <
130/80
 Follow up Visits
What if BP not controlled on
monotherapy ?
Any reduction at all ?
if yes - increase dose or add a
second drug

if not at all - swab drugs after

checking on compliance
 Follow up visits
Which combinations in uncomplicated
patients ?

If patients is already on ACEi or ARB, add

CCB or diuretics ( A+C atau A+D )
If patients is on CCB , add ACEI or ARB
( C+D )
If patients is on diuretics, add ACEI or ARB
(D+A)
If patients is on Beta Blockers, add CCB or
diuretics ( B+C or B + D )
 UK guidelines for high blood pressure medicines - (NICE)

Younger than 55 years or older, or black*

55 years patients of any age

A C
Step 1 (ACE inhibitor or Angiotensin Calcium channel blocker
receptor blocker ) )

Step 2 A+C

http://www.bpassoc.org.uk/information/nice2006.htm
*Black means a person of African or
http://www.nice.org.uk/page.aspx?o=CG34
Caribbean descent, not mixed race or Asian
 Follow up visits
What if BP still not controlled after 2
drugs?

Is the patients complying?

Is the patients already on diuretics ?
1. if NO add diuretics ( A+ C+D )
2. if YES add the appropriate 3rd drug
( A+D+C)
 UK guidelines for high blood pressure medicines - (NICE)

Younger than 55 years or older, or black*

55 years patients of any age

A C
Step 1 (ACE inhibitor or Angiotensin Calcium channel blocker
receptor blocker ) )

Step 2 A+C

Step 3 A+C +D

http://www.bpassoc.org.uk/information/nice2006.htm
*Black means a person of African or
http://www.nice.org.uk/page.aspx?o=CG34
Caribbean descent, not mixed race or Asian
 Follow up visits
What if BP is still not controlled after
3 drugs , including a diuretics

Is the patient complying?

Could the patient have resistant
hypertension ?
 Follow up visits
What if BP is still not controlled after
3 drugs , including a diuretics

Is the patient complying?

Could the patient have resistant
hypertension ?
 Approaching Resistant
Hypertension
Check on
Compliance
Concomitant drug/ food intake
which makes BP control difficult
Concomitant conditions which makes
BP control difficult
Secondary hypertension found in
only 5 % of resistant hypertension
UK guidelines for high blood pressure medicines - (NICE)

Younger than 55 years or older, or black*

55 years patients of any age

A C
Step 1 (ACE inhibitor or Angiotensin Calcium channel blocker
receptor blocker ) )

Step 2 A+C

Step 3 A+C +D

Add
Step 4 Further diuretic therapy or
Alpha-blocker or
Beta-blocker
Consider seeking specialist advice
 To Admit or Not ?
Urgency is when there is NO
emergency and patients are NOT
asymptomatic

Asymptomatic is when they are truly

asymptomatic and do not have
evidence of organ failure ( not target
organ damage )
To Admit or Not to Admit Patient
with Uncontrolled BP
Emergency - must admit

Urgency better to admit

Severe asymptomatic - most do not

need admission
 To Admit or Not ?
Emergency is when patients have
concurrent

Acute coronary syndrome

Acute Heart Failure
Dissecting aortic aneurysm
Acute Glomeluronephritis
Hypertensive encephalopathy
Subarachnoid hemorrhage
Eclampsia
 Hypertensive Emergency
Admit
Reduce BP with intravenous agents
Speed of reduction depends on clinical
scenario
Aim for 25% reduction with 12 hours
Dissecting aneursym, hypertensive
encephalopathy, SAH,eclampsia - within 3
hours
Acute coronary syndrome, APO, Acute
Glomerulonephritis within 12 hours
 Hypertensive Emergency
iv nitroprusside
Suitable for very rapid reduction(
onset of action in seconds, lasting 1-
5 minutes )
Needs ICU/CCU monitoring
BP can be labile
Beware of prolonged use ( cyanide
poisoning )
Caution in heart failure
 Hypertensive Emergency

iv nitroglycerine
Suitable for a more gradual
reduction( onset 2-5 min lasting 3-5
min )
especially useful with ACS and APO
 Hypertensive Emergency
iv nimodipine/nicardipine
suitable for a fairly rapid reduction (
onset 5-10min and lasting 1-4 hours
)
esp in SAH ( nimodipine )
Caution with nicardipine in AHF and
ACS
 Hypertensive Emergency
iv labetolol
suitable for a more gradual
reduction( onset less than 5 minutes
lasting 3-6 hrs)
especially useful in ACS and
Eclampsia
Care with AHF
 Hypertensive Emergency
iv esmolol

Suitable for a rapid BP reduction (

(onset 1min lasting 10-20 min )
especially useful in peri operative
situations and tachyarrthymias)
 Hypertensive Urgency
Consider admission
No need for rapid BP reduction (
especially NO sublingual capsule
nifedipine )
If admitted aim to reduce BP by 25%
within 24 hours
Drugs used include oral captopril ,
oral nifedipine and oral labetolol
Onset within 0.5 to 2 hours and
lasting 3-6 hours
 Asymptomatic Severe
Hypertension
No reason to admit
Start combination oral therapy
Combinations of RAAS blockade and
diuretics or RAAS blockade and CCB
is preferred ( available as Single Pill
Combination )
Other option include combination of
BB and CCB
Review patient within 2 weeks
 Asia: Prevalence awareness and treatment
of hypertension
Country Patients Prevalence Awareness Treated Controlled
(n) (%) (%) (%) (%)
China1 13,364 43.8 26.2 22.2 3.9

India2 4,711 36.0 22.1 36.7

Korea3 6,388 43.8 60.1 91.7 27.2

(> 40 years, rural areas)
Korea4 8,485 24.9 63.5 54.8 38
( 30 years)
Malaysia5 33,976 32.2 35.8 31.4 26.3
(> 18 years)
Philippines6 3,415 21.0 16.0 65.0 20.0

Singapore7 5,022 41.5 51.8 84.4 27.1

1. Li H, et al. J Hypertens 2010;28:432-8. 2. Sharma AK, et al. Indian Heart J 2006;58:21-7. 3. Lee HS, et al. Clin Exp
Hypertens 2010;32:166-78. 4. Korean National Health and Nutrition Examination Survey (KNHANES) 2008 [Korean].
Available at: http://knhanes.cdc.go.kr. 5. Institute of Public Health (IPH) 2008. The Third National Health and Morbidity
Survey 2006 Vol. 2. Ministry of Health Malaysia pp 199-316 ISBN 978-983-3887-30-9. 6. Sison J, et al. Philipp J
Cardiol 2007;35:1-9. 7. Wu Y, et al. J Hypertens 2009;27:190-7.
 Flow of Lecture

Epidemiology of Hypertension
Pathophysiology of Hypertension
Diagnostic Work up
Therapeutics of Hypertension and
Hypertension Guidelines
Conclusion
 Evolution of
Antihypertensive Therapies
Effectiveness

Tolerability

1940s 1950 1957 1960s 1970s 1980s 1990s 2001

Direct 1-blockers ARBs VPIs

ACE
vasodilators inhibitors
Peripheral Thiazides
sympatholytics diuretics
Central 2
Ganglion agonists Calcium
blockers antagonists-
Calcium
Veratrum DHPs
antagonists-
alkaloids non DHPs
-blockers
 CONCLUSION 1
Hypertension is the number 1 cause of
premature death world wide
It is very common and is almost always
asymptomatic
Assess patients comprehensively for
global CV risk
Treat other accompanying Risk Factors
when indicated
Once treated ( including TLC ) aim for
target BP
Combination therapy is needed by most
 CONCLUSION 2
If BP is still not controlled on 3 drugs or
more ( including diuretics ) re- check
compliance, think of secondary causes and
consider resistant hypertension
Most severe hypertension are
asymptomatic and no need to panic
Hypertensive urgency requires oral
combination treatment and may need
admission
All hypertensive emergencies requires
admission and initial iv medications
 Hypertension in Malaysia
( > 30 years )

1996 2006 2011

Sample size 23,007 33,976 18,098

Prevalence 33 % 43% 44%
Aware 33 % 36% 39%
Diagnosed & Rx 23% 88% 79%
Rx & controlled 26% 26% 35%
Overall control 6% 8% 14%
 Hypertension in Malaysia
( > 30 years )

1996 2006 2011

Sample size 23,007 33,976 18,098

Prevalence 33 % 43% 44%

Aware 33 % 36% 39%