Hypertensive Cardiovascular

Disease
Introduction

 Hypertension is one of the leading

causes of the global burden of disease.

 Hypertension doubles the risk of cardiovascular

diseases, including coronary heart disease (CHD),
congestive heart failure (CHF), ischemic and
hemorrhagic stroke, renal failure, and peripheral
arterial disease.
Mechanism of Hypertension

 Cardiac output and peripheral resistance are

the two determinants of arterial pressure.
Mechanism of Hypertension
 Cardiac output is determined by stroke volume and
heart rate.
 Stroke volume is related to myocardial contractility
and to the size of the vascular compartment.
 Peripheral resistance is determined by functional
and anatomic changes in small arteries (lumen
diameter 100–400 μm) and arterioles.
Intravascular Volume
 Sodium is predominantly an extracellular ion
and is a primary determinant of the
extracellular fluid volume.

 Salt can activate a number of

neural, endocrine/paracrine,
and vascular mechanisms, all
of which have the potential to
increase arterial pressure.
Intravascular Volume
 As arterial pressure increases in response to
a high NaCl intake, urinary sodium excretion
increases
 “Pressure-natriuresis” phenomenon
▪ Increase in the glomerular filtration rate, decreased
absorbing capacity of the renal tubules, and possibly
hormonal factors such as atrial natriuretic factor.

 Individuals with an impaired capacity to excrete

sodium, greater increases in arterial pressure are
required to achieve natriuresis and sodium
balance.
Intravascular Volume

 NaCl-dependent hypertension may be a

consequence of a decreased capacity of the
kidney to excrete sodium, due either to
intrinsic renal disease or to increased
production of a salt-retaining hormone
(mineralocorticoid) -> increased renal tubular
reabsorption of sodium.
Autonomic Nervous System

 Norepinephrine, epinephrine, and dopamine

all play important roles in tonic and phasic
cardiovascular regulation.

 adrenergic receptors have been divided into

two principal types: α and β.
 These types have been differentiated further into
α1, α2, β1, and β2 receptors.
Autonomic Nervous System

 α1 Receptors are located on postsynaptic

cells in smooth muscle and elicit
vasoconstriction.

 α2 Receptors are localized on presynaptic

membranes of postganglionic nerve
terminals that synthesize norepinephrine.
 When activated by catecholamines, α2 receptors
act as negative feedback controllers, inhibiting
further norepinephrine release.
Autonomic Nervous System

 Different classes of antihypertensive agents

either inhibit α1 receptors or act as agonists
of α2 receptors and reduce systemic
sympathetic outflow.
Autonomic Nervous System

 Activation of myocardial β1 receptors

stimulates the rate and strength of cardiac
contraction and consequently increases
cardiac output.

 β1 Receptor activation also stimulates renin

release from the kidney.
Autonomic Nervous System

 Activation of β2 receptors by epinephrine

relaxes vascular smooth muscle and results in
vasodilation.
Autonomic Nervous System
 Reflexes that help
regulate blood
pressure:
 Arterial baroreflex
▪ Mediated by stretch-
sensitive sensory nerve
endings in the carotid
sinuses and the aortic arch.
▪ Increases in arterial
pressure ->increase
baroreceptor firing ->
decrease in sympathetic
outflow ->decreases in
arterial pressure and heart
rate.
Renin-Angiotensin-Adosterone System

 regulation of arterial
pressure primarily via
the vasoconstrictor
properties of
angiotensin II and the
sodium-retaining
properties of
aldosterone.
Vascular Mechanisms
 Vascular radius and compliance of resistance
arteries are important determinants of
arterial pressure.

 Decrease in lumen size = Increase in

resistance

 Nitric oxide - a potent vasodilator released by

vascular endothelium.
 Endothelium dependent vasodilation is impaired
in hypertensive patients.
Pathologic Consequences of
Hypertension

 Heart
 Heart disease is the most common cause of death
in hypertensive patients.
 Left ventricular hypertrophy are at increased risk
for CHD, stroke, CHF, and sudden death.
 CHF may be related to systolic dysfunction,
diastolic dysfunction, or a combination of the two.
Pathologic Consequences of
Hypertension
 Stroke
 Elevated blood pressure
is the strongest risk
factor for stroke.
 The incidence of stroke
rises progressively with
increasing blood
pressure levels,
particularly systolic
blood pressure in
individuals >65 years.
Pathologic Consequences of
Hypertension
 Kidney
 Primary renal disease is the most common
etiology of secondary hypertension.
 Hypertension is a risk factor for renal injury and
ESRD.
 Glomerular injury also may be a consequence of
direct damage to the glomerular capillaries due to
glomerular hyperperfusion.
Pathologic Consequences of
Hypertension

 Peripheral Arteries
 In hypertensive patients, vascular disease is a
major contributor to stroke, heart disease, and
renal failure.
 Peripheral Arterial Disease
▪ An ankle-brachial index <0.90 is considered diagnostic
of PAD and is associated with >50% stenosis in at least
one major lower limb vessel.
▪ An ankle-brachial index <0.80 is associated with
elevated blood pressure, particularly systolic blood
pressure.
Hypertension

 Level of blood pressure at which the

institution of therapy reduces blood
pressure–related morbidity and mortality.
Hypertension
Clinical Disorders of Hypertension

 Primary Hypertension/Essential 95%

 Tends to be familial and is likely to be the
consequence of an interaction between
environmental and genetic factors.
 Likely represents a spectrum of disorders with
different underlying pathophysiologies.
Clinical Disorders of Hypertension

 Obesity and Metabolic Syndrome

 There is a well-documented association between obesity
(body mass index >30 kg/m ) and hypertension.
2

 It has been established that 60–70% of hypertension in

adults may be directly attributable to adiposity.
 Insulin resistance associated with hypertension and
dyslipidemia is associated with an unfavorable imbalance
in the endothelial production of mediators that regulate
platelet aggregation, coagulation, fibrinolysis, and vessel
tone. -> Increased risks for CHD, stroke, diabetes, and
cardiovascular disease mortality.
Clinical Disorders of Hypertension

 Metabolic Syndrome
 Insulin resistance
 Abdominal obesity
 HYypertension
 Dyslipidemia
Clinical Disorders of Hypertension

 Secondary HPN
 Renal Parenchymal Diseases
 Renal disease is the most common cause of secondary
hypertension.
 Hypertension is present in >80% of patients with
chronic renal failure.
 Hypertension may cause nephrosclerosis.
Clinical Disorders of Hypertension

 Primary Aldosteronism
 Increased aldosterone production is independent
of the renin-angiotensin system, and the
consequences are sodium retention, hypertension,
hypokalemia, and low plasma renin activity.
 May be secondary to an aldosterone-producing
adenoma or bilateral adrenal hyperplasia.
Clinical Disorders of Hypertension

 Cushing’s Syndrome
 The mechanism of hypertension may be related
to stimulation of mineralocorticoid receptors by
cortisol and increased secretion of other adrenal
steroids.
Clinical Disorders of Hypertension

 Pheochromocytoma
 Related to increased circulating catecholamines.
 May be associated with multiple endocrine
neoplasia (MEN) type 2A and type 2B, von Hippel-
Lindau disease, and neurofibromatosis.
 Testing consists of measuring catecholamines in
either urine or plasma.
 Surgical excision is the definitive treatment of
pheochromocytoma
Miscellaneous Causes of HCVD
• occurs in >50% of individuals with obstructive sleep
apnea
• It is correlated with the severity of sleep apnea which
are mostly obese (70%)
• Considered in patients with drug-resistant hypertension
and patients with a history of snoring
• Diagnosis : polysomnography
• Management includes:
Obesity - weight loss, Continuous positive airway
pressure (CPAP) or bilevel positive airway pressure
(BiPAP)
Drug-resistant hypertension- antihypertensive
agents

34
Miscellaneous Causes of HCVD

Coarctation of the aorta

- most common congenital cardiovascular cause
of hypertension
- occurs in 35% of children with Turner’s
syndrome
- Hypertension may persist in 30% of patents even
if anatomic lesion is surgically corrected in
infancy with an increased risk of accelerated
coronary artery disease and cerebrovascular
events

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 MONOGENIC HYPERTENSION

 Recognized by their characteristic phenotypes, and

diagnosis may be confirmed by genetic analysis

 Several inherited defects in adrenal steroid biosynthesis

and metabolism result in mineralocorticoid-induced
hypertension and hypokalemia.

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MONOGENIC HYPERTENSION
 17α-hydroxylase deficiency
- Synthesis of sex hormones and cortisol is decreased.

-Do not mature sexually; males may present with

pseudohermaphroditism and females with primary
amenorrhea and absent secondary sexual characteristics.
- Hypertension and hypokalemia - consequences of increased
synthesis of mineralocorticoids proximal to the enzymatic
block .

Treatment -Low-dose glucocorticoids

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 MONOGENIC HYPERTENSION
 11β-hydroxylase deficiency
- Results in a salt-retaining adrenogenital syndrome

- Decreased cortisol synthesis and increased synthesis of

mineralocorticoids and shunting of steroid biosynthesis into the
androgen pathway.

-Impaired capacity to metabolize cortisol to its inactive

metabolite, cortisone, and hypertension is related to activation of
mineralocorticoid receptors by cortisol.

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MONOGENIC HYPERTENSION
 Liddle’s syndrome
- results from constitutive activation of amiloride-
sensitive epithelial sodium channels on the distal renal
tubule, resulting in excess sodium reabsorption.
- ameliorated by amiloride

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 Hypertension Burden

“ Hypertension is the most common

condition seen in primary care and leads to
myocardial infraction, stroke, renal failure, and
death if not detected early and treated
appropriately.
“
James, PA, Oparil S, et al. JAMA. doi:10.1001/jama.2013.284427. Published online Dec 18, 2013.
 WHO
2005

2030

Global Atlas on Cardiovascular Disease Prevention and Control. Mendis S. Puska P.

Norriving B. Editors WHO Geneva 2011
Why is
HYPERTENSION
increasing?
• Patients
• Economics
• Doctors
 PATIENT FACTOR

Most of the patients do not

consult a doctor when
asymptomatic.
Highlights
 ECONOMICS FACTOR

Socialized Medicine –
BETTER?
 Worldwide Prevalence of HPN

*Defined as systolic/diastolic blood pressure ≥140/90, (≥160/95 for Taiwan) or receiving treatment.
†South Korea is defined as men, aged 30-59.
7. Wolf-Maier et al. JAMA 2003;289:2363-2369; 8. Data on file, Pfizer, Inc, New York, NY;
9. WHO Collaborating Center on Surveillance of Cardiovascular Disease Web site. Available at
www.cvdinfobase.ca. Accessed Feb. 22, 2005
10. National Nutrition & Health Survey (NNHeS:2003-2004). Phil J Int Med, May-June 2005
 DOCTOR FACTOR

Doctor Fatigue
SYNDROME ????
Where is the Love?
PRESYON 3 2013
Report of the Council on Hypertension PHA

Results: Prevalence of Hypertension in Adults (>18 yrs)*

- 28% (F: 50%, M: 50%)*
30

25

20

% 15
10 28
25
22 22.5 21
5
11
0
1992-92 97-98 2003 2007 2008 2012-13

Nationwide PRESYON 1 NHES PRESYON 2 NHES PRESYON 3

Registry

* n = 933/3334
 Benefits of Lowering BP
Myocardial Stroke
Infarction Heart
(20-25%) (30-35%) Failure
(>50%)

Chobanian AV, et al. JNC 7. JAMA. 2003;289:2560-2572.

TREATMENT
 LIFESTYLE INTERVENTIONS
Weight loss
Reduced NaCl intake
Increased potassium intake
Moderation of alcoholconsumption
Overall healthy dietary pattern

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TREATMENT

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TREATMENT

 PHARMACOLOGIC THERAPY

 recommended for individuals with blood pressures

≥140/90 mmHg

 Lowering systolic blood pressure by 10–12 mmHg

and diastolic blood pressure by 5–6 mmHg confers
relative risk reductions of 35–40% for stroke and 12–
16% for CHD within 5 years of the initiation of
treatment

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 PHARMACOLOGIC THERAPY

 Blockers of the Renin–Angiotensin System

 ACE INHIBITORS
 decrease the production of angiotensin II, increase bradykinin
levels, and reduce sympathetic nervous system activity

 ARBs
 provide selective blockade of AT1 receptors, and the effect of
angiotensin II on unblocked AT2 receptors may augment their
hypotensive effect

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 PHARMACOLOGIC THERAPY
 Blockers of the Renin–Angiotensin System
 ACEIs and ARBs improve insulin action and ameliorate
the adverse effects of diuretics on glucose metabolism

 SIDE EFFECTS
• Functional renal insufficiency
• Dehydration
• Hyperkalemia
• Dry cough and Angioedema (ACEIs)

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 PHARMACOLOGIC THERAPY
 Aldosterone Antagonists
 Spironolactone
 Nonselective aldosterone antagonist
 Used alone or in combination with a thiazide diuretic
 Conventional therapy with ACEIs, digoxin,and loop diuretics
 Side effects:
gynecomastia However circumvented by a newer agent
EPLERENONE, which is a selective
impotence aldosterone antagonist.
menstrual abnormalities

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 PHARMACOLOGIC THERAPY
 α-Adrenergic Blockers
 Lower blood pressure by decreasing peripheral vascular
resistance
 This may also be used treating lower urinary tract symptoms in
men with prostatic hypertrophy.
 Nonselective α-adrenoreceptor antagonists bind to
postsynaptic and presynaptic receptors and are used primarily
for the management of patients with pheochromocytoma.

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 PHARMACOLOGIC THERAPY
 Sympatholytic Agents
 Centrally acting α 1625 2 sympathetic agonists
Decrease peripheral resistance by inhibiting sympathetic
outflow.
Side Effects :somnolence, dry mouth, and rebound
hypertension on withdrawal.

 Peripheral sympatholytics
 Decrease peripheral resistance and venous constriction by
depleting nerve terminal norepinephrine
 Side Effects:orthostatic hypotension and sexual dysfunction

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 PHARMACOLOGIC THERAPY

 Beta Blockers
 decreases cardiac output, due to a reduction of heart
rate and contractility, central nervous system effect
and inhibition of renin release.

 remain appropriate therapy for hypertensive patients

with concomitant heart disease and related
comorbidities

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 PHARMACOLOGIC THERAPY
 Calcium Channel Blockers

 Reduce vascular resistance through L-channel blockade,

which reduces intracellular calcium and blunts
vasoconstriction
 Used alone or in combination with ACEIs, beta blockers,
α1-adrenergic blockers

 Side Effects: flushing,headache, and edema

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 PHARMACOLOGIC THERAPY
 DIURETICS
 Low-dose thiazide diuretics may be used alone or in combination
with other antihypertensive drugs.
 Thiazides inhibit the Na+/Cl−pump in the distal convoluted
tubule and hence increase sodium excretion

 Produces additive effects when combined with beta blockers,

angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin
receptor blockers (ARBs)

 But would be less effective with calcium channel blockers (CCBs)

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 PHARMACOLOGIC THERAPY
 Direct Vasodilators

 decreases peripheral resistance and concomitantly

activate mechanisms that defend arterial pressure,
notably the sympathetic nervous system, the renin-
angiotensin-aldosterone system, and sodium retention
 most effective when added to a combination that
includes a diuretic and a beta blocker

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 PHARMACOLOGIC THERAPY
 Direct Vasodilators
 Hydralazine
 Potent direct vasodilator that has antioxidant and nitric oxide–enhancing
actions
 This may induce a lupus-like syndrome

 Minoxidil
 Potent agent used most frequently in patients with renal insufficiency who
are refractory to all other drugs
 Side Effects: hypertrichosis and pericardial effusion.

 Intravenous nitroprusside
 Used to treat malignant hypertension and life-threatening left ventricular
heart failure associated with elevated arterial pressure.

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 BLOOD PRESSURE GOALS OF
ANTIHYPERTENSIVE THERAPY
 Maximum protection :
 <135– 140 mmHg for systolic blood pressure
 <80–85 mmHg for diastolic blood pressure

Recent evidence suggests that overly aggressive targets for blood

pressure control may not be advantageous, particularly in high-risk
patients.

 Caution should be exercised in lowering blood pressure <130/80

mmHg in patients with diabetes, CHD, and other high-risk
patients. In patients with chronic renal insufficiency, small
nonprogressive increase in the serum creatinine concentration
may occur

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 BLOOD PRESSURE GOALS OF
ANTIHYPERTENSIVE THERAPY

In achieving recommended blood pressure goals,

the majority of individuals with hypertension will
require treatment with more than one drug.

Three or more drugs frequently are needed in

patientswith diabetes and renal insufficiency.

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RESISTANT HYPERTENSION
 Patients with blood pressures persistently >140/90
mmHg despite taking three or more antihypertensive
agents, including a diuretic

 More common in patients >60 years of age

 Related to :
 Pseudoresistance- high office blood pressures and lower
home blood pressures
 Nonadherence to therapy
 Identifiable causes of hypertension (including obesity and
excessive alcohol intake)
 Use of any nonprescription and prescription drugs
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HYPERTENSIVE EMERGENCIES
 Malignant hypertension
 Syndrome associated with an abrupt increase of blood pressure
in a patient with underlying hypertension or related to the
sudden onset of hypertension in a previously normotensive
individual
 Absolute level of blood pressure is not as important as its rate of rise

 Associated with diffuse necrotizing vasculitis, arteriolar thromb, fibrin

deposition in arteriolar walls, progressive retinopathy (arteriolar spasm,
hemorrhages, exudates, and papilledema), deterioratingrenal function with
proteinuria, microangiopathic hemolyticanemia, and encephalopathy

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 HYPERTENSIVE EMERGENCIES

With Hypertensive Encelopathy

 In hypertension the upper and lower limits of
autoregulation of cerebral blood flow are shifted to
higher levels of arterial pressure, and rapid lowering of
blood pressure to below the lower limit of autoregulation
RESULTING TO:
 Decreased Renal and coronary blood flow
 Cerebral ischemia or infarction

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HYPERTENSIVE EMERGENCIES

INITIAL GOAL OF THERAPY:

Reduce mean arterial blood pressure by no

more than 25% within minutes to 2 h or to a
blood pressure in the range of 160/100–110
mmHg.

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 HYPERTENSIVE EMERGENCIES

Without Hypertensive Encelopathy

 TREATMENT: Reduce blood pressure over hours or
longer rather than minutes.
Achieved initially with frequent dosing of short-acting
oral agents such as captopril, clonidine, and labetalol.

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 HYPERTENSIVE EMERGENCIES

Acute Cerebrovascular Events

 aggressive reductions of blood pressure are to be
avoided

 For patients with cerebral infarction who are not

candidates for thrombolytic therapy
institute antihypertensive therapy only for patients
with a systolic blood pressure >220 mmHg or a diastolic
blood pressure >130 mmHg

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 HYPERTENSIVE EMERGENCIES
 Patients with Cerebral Infarction who are candidates for
thrombolytic therapy
 recommended goal blood pressure is <185 mmHg systolic
pressure and <110 mmHg diastolic pressure

 Patients with hemorrhagic stroke

 initiate antihypertensive therapy for are systolic pressure >180
mmHg or diastolic pressure >130 mmHg.

 Patient with subarachnoid hemorrhage

 Cautious reduction of blood pressure is indicated if mean arterial
pressure is >130 mmHg.
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What do the
LATEST
Guidelines Say?
• ESC 2013
• JNC 8 2013

What is the GUIDE

to the guidelines?
Latest Guidelines in Hypertension
Management

• 2013 ESH/ESC GUIDELINE

• JNC 8 [2014 EB-GUIDELINE]
2013 ESH / ESC guidelines in
hypertension management
Definition of HPN

Mancia et al. Journal of Hypertension 2013, 31:1281–1357

ESC 2013
 High DETERMINING
BP CARDIOVASCULAR RISK

ESC 2013 HPN Guidelines

Initiation of lifestyle changes and antihypertensive drug
treatment with Targets of treatment
High WHAT ARE THE
BP TARGET BP GOALS?

Patient subgroups SBP DBP

>80 years old <150 <90

<80 years old <140 <90
CKD, DM, CAD <140 <90
ESC/ESH 2013 HYPERTENSION GUIDELINES
 Choice of antihypertensive drugs
• The main benefits of antihypertensive treatment are due to
lowering of BP per se and are largely independent of the
drugs employed.

• Diuretics, beta-blockers, calcium antagonists, ACE inhibitors

and angiotensin receptor blockers are all suitable for the
initiation and maintenance of antihypertensive treatment.

• Any all-purpose ranking of drugs for general

antihypertensive usage is not evidence-based.
 Possible combinations of classes of
antihypertensive drugs

Green continuous lines: preferred combinations; green dashed line: useful combination (with some limitations);
black dashed lines: possible but less well tested combinations; red continuous line: not recommended combination.
ESC/ESH2013
Preferred drugs:
(not in order of ranking)

ACEI or ARB
Alpha Blocker
Beta Blocker
CCB
Diuretic
(Chlorthalidone, Thiazide, and
Indapamide)
JNC 8
 Recommendation 1
• In the general population aged ≥ 60 years
– Target goal:
• SBP <150 mmHg and/or
• DBP < 90mmHg
(Strong Recommendation – Grade A)
– if pharmacologic treatment for high BP results in
lower achieved SBP, may continue treatment if well
tolerated
 Recommendation 2
• In the general population <60 years,
– Goal SBP<140mmHg
– Goal DBP <90mmHg
• (For ages 30-59 years, Strong Recommendation – Grade
A)
• (For ages 18-29 years, Expert Opinion – Grade E)
 Recommendation 3
• In the population aged ≥ 18 years with chronic
kidney disease (CKD)
– Goal SBP<140 mmHg
– Goal DBP<90mmHg
(Expert Opinion – Grade E)
 Recommendation 4
• In the population aged ≥ 18 years with
diabetes
– Goal SBP<140 mmHg
– Goal DBP<90mmHg
(Expert Opinion – Grade E)
 Recommendation 5
• In the general nonblack population, including
those with diabetes, initial antihypertensive
treatment
– thiazide-type diuretic, CCB, ACEI, or ARB
(Moderate Recommendation – Grade B)
 Recommendation 6
• In the general black population, including those with
diabetes, initial antihypertensive treatment should
include
– a thiazide-type diuretic or CCB
(For general black population: Moderate
Recommendation –Grade B; for black patients with
diabetes: Weak Recommendation – Grade C)
 Recommendation 7
• In the population aged ≥ 18 years with CKD,
initial (or add-on) antihypertensive treatment
should include
– ACEI or ARB to improve kidney outcomes
– This applies to all CKD patients with hypertension
regardless of race or diabetes status. (Moderate
Recommendation – Grade B)
 Recommendation 8
• The main objective of hypertension treatment is to attain
and maintain goal BP.

• If goal BP is not reached within a month of treatment,

increase the dose of the initial drug or add a second drug
from one of the classes in recommendation 5.

• The clinician should continue to assess BP and adjust the

treatment regimen until goal BP is reached.

• If goal BP cannot be reached with 2 drugs, add and

titrate a third drug from the list provided.
JNC 8 2013
GUIDELINE COMPARISONS OF GOAL BP AND INITIAL DRUG THERAPY FOR
ADULTS WITH HYPERTENSION
What is the GUIDE
to the guidelines?
What is desirable
may not be
ideal…..

What is ideal may

not be desirable…..
It would be nice to
be both IDEAL and
DESIRABLE
What is the ROLE
of the Healthcare
Provider in the
treatment of HTN?
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 JNC 8 HYPERTENSION GUIDELINES

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