PATHOGENESIS OF

PRIMARY HYPERTENSION
AND ITS MANAGMENT
Presenters – Dr. Hayder Abdella (IMR1)
Dr. Hailu Desalegn (IMR2)

Moderator –
Outline
• Definition
• Epidemiology
• Blood pressure measurement
• Pathogenesis
• Risk factors for hypertension
• Complications
• Clinical evaluation and investigation
 Definition
• ‘Hypertension’ is defined as the level of BP at which the benefits of
treatment (either with lifestyle interventions or drugs) unequivocally
outweigh the risks of treatment
• Hypertension is defined as a persistent elevation in office systolic BP
≥140 and/or diastolic BP ≥90 mmHg, which is equivalent to a 24-hr
ABPM average of ≥130/80 mmHg or an HBPM average of ≥135/85
mmHg.
• Based on average of 2 or more properly measured seated BP readings
at each of 2 or more clinic visits, with the patient seat comfortably for
at lease 10-15 minuets and Does not Owe to specific cause.
Historical Perspective
• Hypertension was first discovered by Scipione Riva-Rocci, an Italian
physician, in 1896 following the invention of the cuff-based
mercury sphygmomanometer and measurement of the peak systolic
blood pressure by noting the cuff pressure at which the radial
pulse was no longer palpable.
• In 1905, the sound after cuff deflation of sphygmomanometer was first
identified by Russian physician Nikolai.
• Between 1910 and 1914, essential hypertension and malignant
hypertension were described.
Historical Perspective…
• In early 1900 this life insurance industry they had learned that even in
asymptomatic men the measurement of BP was the best way to predict the
premature death and the disability.
• that means as early as early 1900 they never used to consider the men or
women for the life insurance if they are hypertensives because they think or
they thought that hypertension used to die early so it will not work out to
include them in the Life Insurance.
• the goal of the life insurance industry that time was to ensure the people who
are going to live the longest and not to ensure those who are at risk of dying
prematurely.
• that's how old and hypertension is being detected as an important marker of an
early premature death
Natural History
• Hypertension is one of the most important risk factors for
cardiovascular disease (CVD).8 Although hypertension is often
discussed as though it is a disease entity, it is more appropriately
categorized as a continuous risk factor that is a strong predictor of
poor health
• The natural history of uncontrolled hypertension is progression to end-
organ damage, including the heart, brain, kidneys, eyes and arteries
with clinical sequelae including myocardial infarction, stroke, vascular
dementia, renal failure, blindness, and peripheral artery disease
Classification of Hypertension (JNC-7)
 Classification of hypertension
Hypertension Guideline 2017 ACC/AHA 2018 ESC/ESH guidelines

Definition of hypertension (mmHg) ≥130/80 ≥140/90

•Optimal:<120/80
•Normal: <120/80
Normal blood pressure range (mmHg) •Normal:120-129/80-84
•Elevated:120-129/<80
•High normal:130-139/85-89
•Grade1:140-159/90-99
•Stage1:130-139/80-89
Hypertension stage (mmHg) •Grade2:160-179/100-109
•Stage2: ≥140/90
•Grade3: ≥180/110

•<65 years:<130/80 •<65years:<120-129/70-79

Age specific blood pressure targets(9mmHg)
•≥65 years:<130/80 •>65 years:<130-139/70-79

 there is a continuous relationship between BP and CV or renal morbid or fatal events starting from an
office SBP >115mmHg and a DBP >75mmHg
 Classification of office BP and definitions of hypertension grades

Stage 1: Uncomplicated hypertension (i.e. without HMOD or established CVD, including

CKD stage 1 and 2).
Stage 2: Presence of HMOD or CKD grade 3 or diabetes.
Stage 3: Established CVD or CKD stages 4 or 5.
Cardiovascular risk according to grade and stage of hypertension.
White-coat hypertension

• White-coat hypertension is defined as an elevated office untreated BP, but

is normal when measured by ABPM, HBPM, or both .
• The difference between the higher office and the lower out-of-office BP is
referred to as the “white coat effect”, and is believed to reflect mainly the
pressor response to an alerting reaction elicited by office BP measurements
by a doctor or a nurse, although other factors are probably also involved
• It's called white coat hypertension because people who measure blood
pressure usually wear white coats.
Masked hypertension

• Refers to untreated patients in whom BP is normal in the office but is

elevated when measured by HBPM or ABPM . It can be found in
approximately 15% of patients with a normal office BP.
• The prevalence is greater in younger people, males, smokers, and those
with higher levels of physical activity, alcohol consumption, anxiety,
and job stress.
• In a 2015 study involving 3,027 people, 3.3% had white coat
hypertension, and 17.8% had masked hypertension.
Prevalence of hypertension
• The most common modifiable risk factors for CKD stroke & CAD
• Based on office BP, the global prevalence of hypertension was
estimated to be 1.13 billion in 2015, with a prevalence of over 150
million in central and eastern Europe
• prevalence in most population increases with age
• Raised BP remains the leading cause of death globally, accounting for
10.4 million deaths per year.
• BP trends show a clear shift of the highest BPs from high-income to
low-income regions, with an estimated 349 million with hypertension
in HIC and 1.04 billion in LMICs
14

Public Health Reviews (2015)

• Based on NCDI commission
report, approximately 60% of
patients with high blood pressure
in Ethiopia were never diagnosed
and among those identified
cases, only 28% were taking
medications.
• Of those on treatment 74% had
poorly controlled hypertension.
The Impact of hypertension
• Of the 17.9 million global CVD deaths in 2016, hypertension was responsible for
the 10.5million deaths. For every CVD death, there are approximately two people
who survive a heart attack and stroke.
• Hypertension is a major driver of CVD in Africa, especially stroke and hypertensive
heart disease. For every increase in 20 mmHg systolic or 10 mmHg diastolic blood
pressure the lifetime risk of heart disease DOUBLES.
• Hospital based studies have shown that hypertension was the cause of 70% of the
strokes.
• Additionally, the studies indicated HTN and HHD are second commonest causes of
cardiac follow ups in Hospitals
• Stroke, IHD and hypertensive heart diseases were the three leading causes of CVD
deaths in Ethiopia in 2019.
Types of Hypertension
Determinant of Blood Pressure
Blood Pressure Regulation
• Many neurohormonal, renal, and vascular mechanisms interact to
varying degrees to the pathogenesis and progression of the different
hemodynamic forms of hypertension.

• The Primary Factors determining BP are

1. Autonomic Nervous system
2. Renin –Angiotensin-Aldosterone system
3. Vascular mechanism
4. Chemoreceptors
5. ADH & ANP
Autonomic Nervous system
• BP Sensed by Baroreceptors from carotid & Aortic sinuses to Medulla
(NRS) through Cranial Nerves
• NRS acts on
• cardio inhibitory area
• cardio accelerator area
• vasomotor center
• venous
• artery
• adrenal medulla
• sympathetic outflow to the kidney
Hormonal Mechanisms: RAAS system
• RAAS is one of the most important mechanisms contributing to
endothelial cell dysfunction, vascular remodeling, and
hypertension.
• There are three primary stimuli for renin secretion:
1. Decreased NaCl transport in the distal portion of the thick ascending
limb of the loop of Henle that abuts the corresponding afferent
arteriole (macula densa). (Chemoreceptor mechanism),
2. Decreased pressure or stretch within the renal afferent arteriole
(baroreceptor mechanism), and
3. Sympathetic nervous system stimulation of renin-secreting cells via
β1 adrenoreceptors
Vascular mechanism
• Vascular radius and compliance of resistance arteries are important
determinants of arterial pressure.
• Hypertrophic (increased cell size, and increased deposition of
intercellular matrix) or eutrophic vascular remodeling results in
decreased lumen size and, hence, increased peripheral resistance.
• Apoptosis, low-grade inflammation, and vascular fibrosis also
contribute to remodeling.
• In hypertensive patients, structural, mechanical, or functional changes
may reduce the lumen diameter of small arteries and arterioles.
Endothelial dysfunction
• The endothelium of blood vessels produces an extensive range of
substances that influence blood flow and, in turn, is affected by
changes in the blood and the pressure of blood flow.
• For example, local nitric oxide and endothelin, which are secreted
by the endothelium, are the major regulators of vascular tone and
blood pressure.
• In patients with essential hypertension, the balance between the
vasodilators and the vasoconstrictors is upset, which leads to changes
in the endothelium and sets up a "vicious cycle" that contributes to the
maintenance of high blood pressure
Chemoreceptors
ADH & ANP
Blood Pressure Measurement
“The Most important skill you will learn in the medical career is to
measure blood pressure. do it correctly and you will be help more
patients to Better Health than any other skill you learn. do it wrong you
will harm more patients than any other medical errors you make over
your career.”
Dr Clarence E.Grim MD Endocrinologist &Hypertension Specialist
(1991)
percentage of the
U.S. population
(in 1983)
British Regional Heart Study

interindividual
variability
Factors Affecting BP Readings
Recommendations for Office Blood Pressure Measurement
32

KDIGO 2021 Clinical Practice Guideline for the Management of

Blood Pressure in Chronic Kidney Disease
Recommendations for Office Blood Pressure Measurement

KDIGO 2021 Clinical Practice Guideline for the Management of

Blood Pressure in Chronic Kidney Disease
Blood pressure measurement
1.Office blood pressure
measurement

2.Out-of-office blood pressure

measurement

Home blood pressure

monitoring (HBPM)

Ambulatory blood
pressure monitoring
(ABPM)
Out-of-office blood pressure
measurement
• This refers to the use of either
HBPM or ABPM (Which usually
over 24 hrs.)
ABPM
• ABPM provides the average of BP readings over a defined period. It is
the preferred method for confirming the diagnosis of hypertension and
white coat hypertension but has limited availability in routine clinical
practice.

• The device is typically programmed to record BP at usually every 15

to 20 minutes during the day and every 30 to 60 minutes during sleep)
and average BP values are usually provided for daytime, night-time,
and 24 h.
 BP Circadian changes
• BP has a reproducible
"circadian" profile with higher
values while awake and
mentally and physically active,
much lower values during rest
and sleep, and early morning
increases for 3 or more hours
during the transition of sleep to
wakefulness.
Nocturnal Dipping
• A Dipping pattern is • BP normally follows a circadian
characterized by nighttime BP pattern characterized by a decline
reduction of 10% to 20% of ≥ 10% in mean BP levels from
Relative to the “awake” Period day to night (dipping).
and is consistently Found in the • BP is highly variable during the
Majority of normotensive and day and to a lesser extent during
hypertensive people. the night due to the interplay
between central factors, humoral
influences, local vasoactive
mechanisms and the buffering
influences of the baro-reflex.
HBPM
• Home BP is the average of all BP readings performed with a semiautomatic,
validated BP monitor, for at least 3 days and preferably for 6–7 consecutive
days before each clinic visit, with readings in the morning and the evening,
taken in a quiet room after 5 min of rest, with the patient seated with their
back and arm supported.
• Two measurements should be taken at each measurement session, performed
1–2 min apart.
• Home readings should be used to complement office readings to determine
whether a patient's blood pressure is under control. If there is a discrepancy
between office and home blood pressures (ie, white coat or masked
hypertension), ABPM should be obtained, if possible, to confirm the accuracy
of home blood pressure measurements.
• If ABPM is not available, Automated office blood pressure measurement
(AOBPM) can be used.
Clinical indications for home and ambulatory BP
monitoring
Conditions in which white-coat hypertension is more common, e.g.:
• Grade I hypertension on office BP measurement
• Marked office BP elevation without HMOD
Conditions in which masked hypertension is more common, e.g.:
• High-normal office BP
• Normal office BP in ind ivid uals with HMOD or at high total CV risk
In treated individuals:
• Confirmation of uncontrolled and true resistant hypertension
• Evaluation of 24 h BP control (especially in high-risk patients)
• Evaluating symptoms ind icating hypotension (especially in old er patients)
Suspected postural or postprandial hypotension in treated patients
Exaggerated BP response to exercise
Considerable variability in office BP measureme nts
Specific indications for ABPM rather than HBPM:
• Assessment of nocturnal BP and dipping status (e.g. sleep apnea, CKD, diabetes,
end ocrine hypertension, or autonomic dysfunction)
• Patients incapable or unwilling to perform reliable HBPM, or anxious with self-
measurement
• Pregnancy
Specific indications for HBPM rather than ABPM:
• Long-term follow-up of treated ind ivid uals to improve adherence with treatment
and hypertension control
• Patients unwilling to perform ABPM, or with consid erable discomfort during the
record ing
Indications for repeat out-of-office BP evaluation (same or alternative method –
HBPM/ABPM)
• Confirmation of white-coat hypertension or masked hypertension in untreated or
treated ind ivid uals
Clinical indications for home and ambulatory BP
monitoring
Conditions in which white-coat hypertension is more common, e.g.:
• Grade I hypertension on office BP measurement
• Marked office BP elevation without HMOD
Conditions in which masked hypertension is more common, e.g.:
• High-normal office BP
• Normal office BP in ind ivid uals with HMOD or at high total CV risk
In treated individuals:
• Confirmation of uncontrolled and true resistant hypertension
• Evaluation of 24 h BP control (especially in high-risk patients)
• Evaluating symptoms ind icating hypotension (especially in old er patients)
Suspected postural or postprandial hypotension in treated patients
Exaggerated BP response to exercise
Considerable variability in office BP measureme nts
Specific indications for ABPM rather than HBPM:
• Assessment of nocturnal BP and dipping status (e.g. sleep apnea, CKD, diabetes,
end ocrine hypertension, or autonomic dysfunction)
• Patients incapable or unwilling to perform reliable HBPM, or anxious with self-
measurement
• Pregnancy
Specific indications for HBPM rather than ABPM:
• Long-term follow-up of treated ind ivid uals to improve adherence with treatment
and hypertension control
• Patients unwilling to perform ABPM, or with consid erable discomfort during the
record ing
Indications for repeat out-of-office BP evaluation (same or alternative method –
HBPM/ABPM)
• Confirmation of white-coat hypertension or masked hypertension in untreated or
treated ind ivid uals
Definition of hypertension based on blood
pressure measurement strategy
SBP/DBP Clinic SMBP Daytime Nighttime 24-hour
ABPM ABPM ABPM

ACC/AHA
Guidelines ≥130/80 ≥130/80 ≥130/80 ≥110/65 ≥125/75
2017[1]

ESC/ESH
Guidelines ≥140/90 ≥135/85 ≥135/85 ≥120/70 ≥130/80
2018[2]

© 2024 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Screening for the detection of hypertension
45

ESC/ESH guidelines 2018.

Confirming the diagnosis of hypertension
• Because of the variability of BP, an elevation of office BP (SBP
140mmHg or DBP 90mmHg) should be confirmed by at least two to
three visits, unless the BP values recorded during the first visit are
markedly elevated (grade 3 hypertension) or CV risk is high,
including the presence of HMOD.
• ABPM, HBPM or data should be collected whenever feasible when
office BP is elevated, to confirm the diagnosis of hypertension and
identify specific BP phenotypes. ABPM and/or HBPM can be
especially important when office BP data visit provide variable results.
 Risk factors for primary
hypertension
Although the exact etiology of primary hypertension remains unclear, genetics
and environmental and so many risk factors strongly and independently
associated with its development.
• Genetics • Smoking
• Family history • Stress
• Age • High-sodium diet
• Race • Excessive alcohol consumption
• Reduced Nephron mass • Physical inactivity
• Obesity, weigh gain • Sleep Apnea
• DM
 Risk factors for primary hypertension
• Although the exact etiology of primary hypertension remains unclear, genetics and environmental
and so many risk factors strongly and independently associated with its development.
• Genetics:- study suggested that in 85% of case it has been identified that it is more commonly due
to genetic abnormality which is associated with the decrease in excretion of sodium from the
kidenies is primarly responsible for the development of PHTN.
• Family history – There is greater similarity in blood pressure within families than between
families, which indicates a form of inheritance. HTN is about twice as common in subjects who
have one or two hypertensive parents, and genetic factors account for approximately 30% of the
variation in BP.
• Age (calcification ass. Vascular wall thickening)– particularly systolic bp. Senile degeneration
atherosclerosis.
• Race – Hypertension tends to be more common, be more severe, occur earlier in life, and be
associated with greater target-organ damage in blacks.
• Reduced Nephron mass:- UO decrease Na excretion decrease, may be related to genetic factors or
may associated to Intra Uterine developmental disturbance like Hypoxia, drugs, Nutritional
deficiency, premature birth, Postnatal malnutrition, infection are agents in decrease no of nephrons
leads to decrease Na excretion
Cont...
• Obesity, weigh gain = are determinants for the rise in BP that is commonly
observed in aging. So when it combined with aging then RF will increases
further another 10 -20 folds further development of HTN.
• DM : Effect on the kidney scaring, atherosclerosis
• Smoking :(active ingredient in cigarette smoke — stimulates the
release of epinephrine and norepinephrine) alter the structure
of the wall hardens their walls
• Stress = increase cytokines and stress hormones release
• High-sodium diet:- Approximately >3gm per day
• Excessive alcohol consumption : because of atherosclerosis, changes in
structure of arteries, lipid paraphile, development of obesity
• Physical inactivity
• Sleep Apnea
Hypertension Mediated Organ Damage
Heart
Increased left ventricular workload in hypertensive patients can result in
• LVH,
• Impaired LV relaxation,
• Left atrial enlargement,
• An increased risk of arrhythmias, especially AF,
• An increased risk of heart failure with preserved ejection fraction (HFpEF)
and heart failure with reduced ejection fraction (HFrEF).
• shearing force lead to Aortic dissection or Aneurysm
• Atherosclerosis can lead to CAD, PAD
BRAIN
• Elevated blood pressure is the strongest risk factor for stroke both
thrombotic and embolic stroke
• HTN can cause Cerebral Vessels to rupture … ICH/SAH
• Small Vessel Disease:- Microbleeds or Small Subcortical Infarcts is
associated with impaired cognition in an aging population.
• associated with beta amyloid deposition, a major pathologic factor in
dementia.
Kidney
• The kidney is both a target and a cause of hypertension
• Atherosclerotic, hypertension-related vascular lesions in the kidney primarily
affect preglomerular arterioles, resulting in ischemic changes in the glomeruli and
post glomerular structures.
• direct damage to the glomerular capillaries & Loss of autoregulation.
• Increase GFR leads to Afferent arteriolar Constriction & Sclerosis … Ischemia …
renal injury…AKI … CKD
• This All Leads to
1. diminished capacity to excrete sodium,
2. excessive renin secretion in relation to volume status, and
3. sympathetic nervous system overactivity.
Peripheral arteries
• In addition to contributing to the pathogenesis of hypertension, blood
vessels are a target organ for atherosclerotic disease.
• hypertensive patients with arterial disease of the lower extremities are
at increased risk for future cardiovascular disease.
Retinal arteries
Series of retinal microvascular changes called hypertensive retinopathy
The classification of hypertensive retinopathy is based on fundoscopy,
which permits the detection of retinal lesions such as hemorrhages,
microaneurysms, hard exudates and cotton wool spots (grade 3),
papilledema and/or macula edema (grade 4)
 Clinical evaluation and investigation
• Most cases of Primary hypertension are asymptomatic and are diagnosed incidentally
on blood pressure recording or measurement.
• Some cases present directly with symptoms of end-organ damage as stroke-like
symptoms or hypertensive encephalopathy, chest pain, shortness of breath, and acute
pulmonary edema.
• Very Few may come with Fatigue, Decreased activity tolerance, Dizziness,
Palpitations, Headache.
• The ACC recommends at least two office measurements on at least two separate
occasions to diagnose hypertension.
• The ESC/ESH recommends three office BP measurements at least 1 to 2 minutes apart
and additional measurements only if the initial two readings differ by greater than or
equal to 10 mm Hg. BP is then recorded as the average of the last two readings.
Clinical evaluation and
investigation
• The purpose of the clinical evaluation is

 To establish the diagnosis and grade of hypertension,

 Screen for potential secondary causes of hypertension,
 Identify factors potentially contributing to the development of
hypertension (lifestyle, concomitant medications, or family history),
Identify concomitant CV risk factors (including lifestyle and family
history),
Identify concomitant diseases,
Establish whether there is evidence of HMOD or existing CV,
cerebrovascular, or renal disease.
Medical History
• Duration of hypertension
• Previous and Highest BP Levels
• Previous and Current treatment
• Evaluation Of risk Factors
• Symptoms of 2ry Hypertension
• History And Symptoms of TOD
Physical examination and clinical investigations
Investigations & Assessment of HMOD
Differential Diagnosis
• Secondary hypertension should always be sought for as the
differential, especially if the patient is at extremes of age (young or
older).

• Hyperaldosteronism, coarctation of the aorta, renal artery stenosis,

chronic kidney disease, and aortic valve disease should always be kept
in the differential.
THANK YOU