ESSENTIAL (PRIMARY)

HYPERTENSION

Lectгurer – prof. Yu.R.

Kovalev
 ESSENTIAL HYPERTENSION
Essential hypertension is an independent nosological
form. The main clinical manifestation of this disease
involves increase in the arterial pressure. Contrary to
secondary arterial hypertensions, the increased arterial
pressure in EH is no consequence of a renal lesion,
endocrine gland diseases or other pathological
processes when increase in the BP is but one of the
symptoms of the main disease

Using only in Russia term «Hypertensive disease» is

a synonym of the terms «Essential hypertension»,
«Primary hypertension» and «Idiopathic
hypertension»
A considerable role in development of the EH is
played by a congenital predisposition, i.e. an
aggregate of genetic influences associated with
resistive vessel dilatation reserve insufficiency as
manifested in an inability for adequate dilatation
of the end arteries and arterioles in response to
increase of cardiac output (a minute blood
volume). Environmental, neurogenic, and numeral
effects entailing an enhancement of the blood
output from the heart and/or augmenting the
vessel reactivity to pressor effects (an excessive
sodium administration, enhanced activity of the
sympathetic nervous system. smoking, and a
number of other factors) are regarded as factors
prompting the EH development.
Superimposing upon the genetic influences, they
prompt actual manifestation of a latent defect in
the vascular bed portion which determines the
major part of peripheral vascular resistance, and
hasten occurrence of the disease clinical signs.
 STRUCTURE OF ARTERIAL
HYPERTENSIONS
Secondary (symptomatic)
arterial hypertensions make
only 5-10%. They include
nephrogenic, renovascular,
endocrine, drug-induced,
hypertension in pregnancy.
EH and others

In different populations EH occurs in 10 – 30% of adults

The age group between 40 and 60 years is
affected most, but considerable part of
teenagers and young people in St.
Petersburg and other great cities have the
BP values exceeding the normal those.
Along with atherosclerosis, the EH is one
of the most important causes of
disablement and premature mortality of the
population.
 Frequency of increased BP between
children and adolescences in St-Petersburg

35
%
30
25
20
15
10
5
0
8 9 10 11 12 13 14 15 16 17

Ages (y.)
 CLASSIFICATION OF ARTERIAL
HYPERTENSIONS (WHO, 1996)
Stage I. Objective manifestations of lesion of the organ-
target are absent.
Stage II. As a minimum, one of the following signs of the
organ-target lesion is present:
• hypertrophy of the left ventricle (according to the X-
ray, ECG or echocardiography examinations);
• generalized or focal constriction of the retina vessels:
• microalbuminuria", protein in the urine" and/or trivial
increase in the creatinine concentration in the blood
plasma (1.2-2.0 mg/dL or 105-176 mcmol/L);
• atherosclerotic changes (plaques), according to the
ultrasonic investigation or angiography (in the carotid
arteries, aorta, ileac or femoral arteries).
 CLASSIFICATION OF ARTERIAL
HYPERTENSIONS (WHO, 1996)
Stage ///. Apart from the above signs of the organ-target
lesions, clinical manifestations are present as follows:
• the heart: angina; myocardial infarction; cardiac failure;
• the brain: stroke; transient disorders of cerebral
circulation; hypertensive encephalopathy; vascular
dementias;
• the retina: hemorrhage or exudates with concomitant
swelling (or without it) of the optic nerve - these signs are
specific for malignant or fast developing arterial
hypertension;
• the kidneys: the plasma creatinine over 2 mg/dL; renal
failure;
• vessels: a dissecting (intramural) aneurysm of the aorta;
occlusive lesions of arteries with clinical manifestations.
 CLASSIFICATION OF BLOOD
PRESSURE MEASURMENTS
Category SBP mm Hg DBP mm Hg
Optimal <120 <80
Normal <130 <85
High normal 130-139 85-89
I stage (mild) 140-159 90-99
II stage (moderate 160-179 100-109
III stage (severe) ≥ 180 ≥ 110
Isolated systolic hypertension ≥ 140 <90

When systolic and diastolic pressures fall into different

categories, the higher category should be selected.
The etiology of EH base on hereditary
predisposition. The EH rate among the patient
family members will be significantly increased,
the main contribution to the disease
development being made by the hereditary
charge on mother or both parents' side. In recent
years, the hereditary predisposition for the EH
has been studied with the aid of molecular
genetics methods.
Correlation coefficients for relationships in
blood pressure among parents and children

0,27 0,21
0,26 0,24

SBP DBP SBP DBP

It is now a widely spread idea that the EH develops in
result of a generalized defect of cellular membranes
manifested in disorders of their structure and cation-
transporting functions. Molecular basis of these disorders
has not yet been fully studied but intensive search is under
way in this direction. In the EH patient and their close
relatives (with both normal and increased BP), accelerated
velocity of Na/Li counterflow trough the cellular
membranes will be observed. In erythrocytes, leucocytes,
and other tissues of the EH patient, the Na/H
transmembrane exchange is enhanced.
As a consequence of the membrane disorders, in
the EH a functional insufficiency of the ATP-
dependent system of calcium transport occurs. In
the end, this leads to an increased concentration of
free calcium in the cytoplasm which, in particular,
promts enhancement of tonus of the smooth muscle
cell’s vessels and increase in the peripheral vascular
resistance. One cannot rule out the fact that the
consequence of the membrane defect might involve
also a disorder in the mechanisms of synaptic
transmission which entails enhancement of
adrenergic effects upon the vessel smooth muscles.
In some patient with the EH (as well as in some
healthy people), the BP level is clearly increased in
consumption of excessive amounts of table salt (the
salt-sensitive persons). It is assumed that in these
patients a genetically stipulated functional
insufficiency of kidneys exists in respect to excretion
of water and sodium that becomes more evident along
with ageing of the organism. Such a hyperhydration
(volume-, Na-dependent form) form of the EH occurs
mostly in persons over 40-45 years of age.
Accumulation of sodium in vascular wall enhances
reactivity of the vessels in respect to pressor
substances. Increase of the BP in these patients
prompts excretion of adequate amounts of sodium
and water from the organism.
 ID POLYMORPHISM ACE GENE
An example of the polymorphism associated with
variants of the gene functional activity includes a
polymorphism of the angiotensin-converting enzyme
gene stipulated by either presence or absence of the
Alu-repetition: an insert 287-nucleotide couple long
localized in the 16th intron. The persons having this
repetition are designated as insertion carriers (l-allele);
in absence of such a repetition - as having a deletion
(D-allele). In majority of the populations, the l-allele
homozygotes (II genotype) constitute about 25%;
heterozygotes (ID genotype) - about 50%: the
remaining 25% of the population are represented by
D-allele homozygotes (DD genotype).
 ID POLYMORPHISM ACE GENE

Genotype DD ID II
Population rate ~ 25 % ~ 50 % ~ 25 %
ACE level High Intermediate Low
normal normal
 ID POLYMORPHISM ACE GENE
It has been found that activity of the
angiotensin-converting enzyme (ACE) is the
least in the II-genotype carriers; in DD-
genotype carriers it is twice as great, on the
average, while heterozygotes (ID genotype)
reveal an intermediate activity of this enzyme.
 RISK FACTORS OF EH
Heredity
Obesity
Diabetes mellitus
High Na+ uptaking or insufficient K+, Mg++, Ca+
uptaking
Psychological stress
Low physical activity
Smoking
Alcohol or coffee abuse
 PATHOGENESIS OF EH
In increase of the BP, pulses from
baroreceptors in the aorta and carotid
arteries increase. This is accompanied by
inhibition of the vascular-motor centre and
a drop in total peripheral resistance which
usually leads in healthy people to
normalizing of the BP. This mechanism,
however, induces no drop of the BP in the
EH patients which is due to their
inability for adequate dilatation of the
resistive vessels.
 PATHOGENESIS OF EH
Spasm of arterioles and increasing of heart
output
Adaptation of baroreceptors in aorta to
increased BP
Compensatory mechanisms: increasing of
secretion of aldosterone, vasopressin a.o.
Hypertrophy of vessel smooth muscles and
myocardium of left ventricle (stabilization of
hypertension)
Arteriosclerosis with accelerated
atherosclerotic vascular lesions
Nephrosclerosis with activation of renin-
angiotensin system
 PATHOGENESIS OF EH
In due time, the EH patients develop hypertrophy
of resistive vessel smooth muscles which makes
the labile AH a stable one. Following many years
of the disease proceeding, manifestations of
arteriosclerosis occur, and atherosclerotic
vascular lesions develop in an accelerated way.
All this may lead to a decrease in the renal blood
supply and activation of the renin-angiotensin
system. Thus, in the final stage of the disease, the
AH may be maintained by renal mechanisms.
 DIAGNOSTIC CRITERIA OF EH

•Stage by stage changing

•Exclusion of secondary hypertension
•Hereditary charge
 TARGET ORGANS

•Heart
•Brain
•Retina
•Kidneys
 TARGET ORGANS
Heart damage is associated with the myocardium
hypertrophy and progression of coronary
atherosclerosis. Apart from angina pectoris, in the EH
patient myocardial infarction and other manifestations
of the IHD may occur.
Lesion of the myocardium as a consequence of the
EH itself or of concomitant IHD serves as a cause of
chronic cardiac failure in considerable number of the
EH patients.
The EH is the main cause of aneurism delamination
(hematoma) of the aorta. Disruption of the aorta
usually occurs above the valves, and most patients
with this complication die within a few days. More
rarely a subacute or chronic proceeding of the
aneurism delamination of the aorta occurs.
 TARGET ORGANS
The brain lesions are manifested in the initial
stage by headaches, dizziness, noise in the
head and ears, reduction of mental working
ability, sometimes by memory disorders. In
later stages, the patients develop transitory
disorders of cerebral circulation or more grave
disorders: in the form of subarachnoid
hemorrhage, hemorrhagic stroke, or cerebral
infarction (ischemic stroke).
 TARGET ORGANS
Changes in the eye fundus are characterized by
manifestations of hypertensive angioretinopathy.
According to classification by Keis, Wegener and
Barker, 4 grades of vessel lesions are distinguished,
estimating at that the changes due to hypertension
itself, and the changes stipulated by graveness of
arteriolosclerosis. The vessel changes due to
hypertension are represented by increasing spasm
of arteries and arterioles; at the grades 3 and 4,
hemorrhages and exudates on the eye fundus will
join. Swelling of the optical nerve disc only occurs at
the 4th grade and is mainly specific for malignant
form of the EH.
 TARGET ORGANS
The ophthalmoscopy-determined manifestations
of the retina vessel arteriolosclerosis with
thickening of arteries walls and narrowing of their
lumen correlate quite well with vessel changes in the
internal organs.
The changes in the kidneys are associated with
arteriolosclerosis of afferent and efferent arteries,
lesion of the glomerule capillary system which leads to
deceleration of the glomerule filtration and dysfunction
of the tubules. In the EH patients, often a moderate
proteinuria and microhematuria are noted. Chronic
renal failure may develop. At present, however, death
in the EH mostly occurs as a consequence of
myocardial infarction or a congestiv hard failure.
NON PHARMACOLOGICAL TREATMENT
At the BP level above 140/90 mm Hg, the patient is
recommended to change his or her way of life. This
includes:
• loss of body mass (if it is excessive)
• limitation of alcohol drink consumption (to 30 g a
day calculated for ethanol)
• regular physical exercises of a dynamic character
(well measured out, preferably on the fresh air)
• reducing salt consumption to 6 g a day
• giving up smoking
• sufficient potassium, calcium and magnesium
consumption
• Normalising of sleep and rest
If in a few months time the BP does not drop then,
following all the above steps, the patient is
prescribed a drug treatment.
PRINCIPLES OF DRUGS TREATMENT

•Correction of risk factors

•Affectation of different pathogenesis
mechanisms by combined therapy
•Prevention of side effects
•Using the reduced dosage of each drug
 АNTIHYPERTENSIVE
TREATMENT
The antihypertensive therapy must combine with
correction of the main risk factors involved in
atherosclerosis and IHD (smoking, diabetes,
dyslipidemia, excessive body mass, etc.). Only
under these conditions, maintenance of the BP at
the optimal level can lead to a reliable reduction
of general risk of cardiovascular morbidity and
mortality.
The combined therapy using two and sometimes
three drugs has its advantages as compared with
the monotherapy.
• The capacity to affect different pathogenetic
mechanisms of the EH development in
patients.
• Prevention of undesirable effects of the
compensatory responses (e.g., with the aid of
diuretic drugs, reducing of manifestations of
secondary hyperaldosteronism occurring in
monotherapy with practically any
antihypertensive drug).
• The possibility to use each drug in reduced
dosage which decreases the number of dose-
dependent side effects. This is particularly
important in respect to continuous treatment
during several years.
MAIN GROUPS OF ANTIHYPERTENSIVE
DRUGS

• beta-adrenoblocking agents
• diuretic agents;
• agents inhibiting the ACE;
• the agents blocking slow calcium
canals (calcium antagonists);
• alpha-adrenoblocking agents;
• antagonists of the angiotensin II
receptors of the first type
 COMBINATIONS OF
ANTIHYPERTENSIVE DRUDS
• beta-adrenoblocking + diuretic agents;
• agents inhibiting the ACE + diuretic agents;
• calcium antagonists (Nifedlpine) + beta-
adrenoblocking agents;
• calcium antagonists + agents inhibiting the
ACE;
• beta-adrenoblocking + alpha-adrenoblocking
agents;
• agents inhibiting the ACE + diuretic agents +
beta-adrenoblocking agents.

Choosing of combination depends on age, stage of

hypertension and concomitant diseases
It is necessary to start therapy with using
moderate closes of antihypertensive
drugs, with their subsequent increase (if
necessary) to the optimal doses enabling
to attain the "target" level of the BP, i.e.
the level which is considered acceptable
by the physician in a concrete clinical
situation.
RESULTS OF TREATMENT

TREATED, n=1701
UNTREATED, n=1706

STROKE OR
MYOCARDIAL INFARCTION
Number of cases

DEATH

DAYS