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1. What is the definition of hypertension based on 2020 International Society of Hypertension

Global Hypertension Practice Guidelines? (https://www.ahajournals.org/journal/hyp)

 Recommended that hypertension be diagnosed when

 a person’s systolic blood pressure (SBP) in the office or clinic is ≥140
mm Hg and/or
 diastolic blood pressure (DBP) is ≥90 mmHg following repeated
examination

 High-normal BP is intended to identify individuals who could benefit from lifestyle interventions
and who would receive pharmacological treatment if compelling indications are present.
 Isolated systolic hypertension defined as elevated SBP (≥140 mmHg) and low
DBP (<90 mmHg) is common in young and in elderly people.
 In young individuals, including children, adolescents and young
adults, isolated systolic hypertension is the most common form
of essential hypertension.
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 It is also particularly common in the elderly, in whom it reflects
stiffening of the large arteries with an increase in pulse pressure
(difference between SBP and DBP).
 Individuals identified with confirmed hypertension (grade 1 and grade 2) should receive
appropriate pharmacological treatment

2. How do you diagnose hypertension?

a. Hypertension Diagnosis – Office BP Measurement
 is most commonly the basis for hypertension diagnosis and follow-up.
 Whenever possible, the diagnosis should not be made on a single
office visit.
 Usually 2-3 office visits at 1-4-week intervals (depending
on the BP level) are required to confirm the diagnosis of hypertension.
The diagnosis might be made on a single visit, if BP is ≥ 180/110
mmHg and there is evidence of cardio- vascular disease (CVD)

b. Hypertension Diagnosis – Office Blood Pressure Measurement- Initial Evaluation

 Initial evaluation:
 Measure BP in both arms, preferably simultaneously.
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 If there is a consistent difference between arms >10 mmHg in repeated
measurements, use the arm with the higher BP.
 If the difference is >20 mmHg consider further investigation.

 Standing blood pressure:

 Measure in treated hypertensives after 1 min and again after 3 min when there are
symptoms suggesting postural hypotension and at the first visit in the elderly and
people with diabetes.

 Unattended office blood pressure:

 Multiple automated BP measurements taken while the patient remains alone in the
office provide a more standardized evaluation but also lower BP levels than usual
office measurements with uncertain threshold for hypertension diagnosis.
 Confirmation with out-of-office BP is again needed for most treatment decisions.

c. Hypertension Diagnosis – Out-of-Office Blood Pressure Measurement

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 Out-of-office BP measurements (by patients at home or with 24- hour ambulatory blood
pressure monitoring [ABPM])
 More reproducible than office measurements, more closely associated with
hypertension-induced organ damage and the risk of cardiovascular events and
identify the white coat and masked hypertension phenomena.
 Often necessary for the accurate diagnosis of hypertension and for treatment
decisions.
 In untreated or treated subjects with office BP classified as high normal BP or grade 1
hypertension (systolic 130–159 mmHg and/or diastolic 85–99 mm Hg)
 the BP level needs to be confirmed using home or ambulatory BP monitoring
Clinical Use of Home and
Ambulatory Blood
Pressure (BP) Monitoring
Home Blood Pressure 24-Hour
Monitoring Ambulatory
Condition Routine working day.
Position Avoid strenuous activity.
Arm still and relaxed during
each
measurement.
Device Validated electronic (oscillometric) upper-arm cuff
device
Cuff Size according to the individual’s arm circumference
Measurement Before each visit to the health
protocol professional:
 24-hour monitoring at 15–
 3–7-day monitoring in the
30 min intervals during
morning (before drug intake if Daytime and nighttime.
treated) and the evening.  At least 20 valid daytime
and 7 nighttime BP
 Two measurements on each
readings are required. If
occasion after 5 min sitting rest
less, the test should be
and 1 min between
repeated
Measurements

 Long-term follow-up of
treated hypertension:
 1–2 measurements per
week or month.

Interpretation  Average home blood  24-hour

pressure after excluding readings ambulatory blood
of the first day pressure ≥130/80 mm
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≥135 or 85 mm Hg Hg indicates
indicates hypertension. hypertension (primary
criterion).

 Daytime (awake)
ambulatory blood
pressure ≥135/85 mm
Hg and nighttime
(asleep)
≥120/70 mm Hg
indicates hypertension

3. What are the risk factors of hypertension?

a. Obesity and weight gain
 Obesity and weight gain are strong, independent risk factors for hypertension.
 It has been estimated that 60% of hypertensives are >20% overweight.
 Among populations, hypertension prevalence is related to dietary NaCl intake, and the
age-related increase in blood pressure may be augmented by a high NaCl intake
 Low dietary intakes of calcium and potassium also may contribute to the risk of
hypertension.
 The urine sodium-to-potassium ratio (an index of both sodium and potassium intakes) is a
stronger correlate of blood pressure than is either sodium or potassium alone.
 Alcohol consumption, psychosocial stress, and low levels of physical activity also may
contribute to hypertension

b. Genome
 Although specific genetic variants have been identified in rare Mendelian forms of
hypertension, those variants are not applicable to the vast majority (>98%) of patients
with hypertension.

 Different subsets of genes may lead to different phenotypes associated with

hypertension
 Obesity
 Dyslipidemia
 Insulin resistance

 Adoption, twin, and family studies document a significant heritable component to BP

levels and hypertension.
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 Clinically, although replication has been a challenge, results of candidate gene studies
and genome-wide association studies in large numbers of individuals have also
identified a number of hypertension-related genes, several of which are involved in
pathways that regulate arterial pressure:
 Genes that encode components of the RAAS
 Atrial natriuretic peptide
 Beta-2 adrenoreceptor
 Alpha adducin (associated with inc. renal tubular reabsorption of sodium)
 
 Identified genetic determinants account for ~1% of BP variance, whereas based on
family studies; heritability of hypertension is estimated to be in the range of 30–40%.

 One hypothesis to account for the “missing heritability” is that epigenetic modifications of
DNA contribute to the heritability of BP.
 Epigenetic processes are changes in gene expression that occur without changes
in DNA sequence.
 In contrast to DNA sequence, the epigenome is relatively susceptible to
modification by environmental exposures.
 Epigenetic dysregulation has emerged as a hallmark of several complex diseases.
 Recent studies have described epigenetic modifications of specific genes
associated with hypertension. However, current results of detailed genome-wide
epigenetic modifications of DNA are limited and conflicting.

 There may also be genetic determinants of target organ damage and vascular disease
attributed to hypertension.
 Family studies indicate significant heritability of left ventricular mass, and there is
considerable individual variation in the responses of the heart to hypertension.
 Candidate genes associated with renal damage suggest that genetic factors also
may contribute to hypertensive nephropathy.
 Specific genetic variants have been linked to CHD and stroke.

  In the future, it is possible that DNA and epigenetic analyses may predict individual risk
for hypertension and target organ damage and will identify responders to specific
classes of antihypertensive agents.

4. What is the Mechanism of Hypertension? (Assignment Individual readings)

 Useful to understand factors involved in the regulation of both normal and elevated arterial
pressure.
 Two determinants of arterial pressure.
o 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
1. Peripheral resistance
is determined by functional and anatomic changes in small arteries
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(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.
 When NaCl intake exceeds the capacity of the kidney to excrete sodium,
vascular volume may initially expand and cardiac output may increase.
 Salt can activate a number of neural, endocrine/paracrine, and vascular mechanisms, all of which
have the potential to increase arterial pressure.
 The effect of sodium on blood pressure is related to the provision of sodium
with chloride; non-chloride salts of sodium have little or no effect on blood
pressure.
 “pressure-natriuresis” phenomenon
 As arterial pressure increases in response to a high NaCl intake, urinary sodium excretion
increases and sodium balance is maintained at the expense of an increase in arterial
pressure.
 involve a subtle increase in the glomerular filtration rate, decreased
absorbing capacity of the renal tubules, and possibly hormonal factors
such as atrial natriuretic factor.
 In individuals with an impaired capacity to excrete sodium, greater increases in
arterial pressure are required to achieve natriuresis and sodium balance.
 Renal tubular sodium reabsorption also may be augmented by increased
neural activity to the kidney.

AUTONOMIC NERVOUS SYSTEM

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 Adrenergic reflexes modulate blood pressure over the short term, and adrenergic function, in
concert with hormonal and volume-related factors, contributes to the long-term regulation of
arterial pressure.
 Norepinephrine, epinephrine, and dopamine all play important roles in tonic and phasic
cardiovascular regulation.
 The activities of the adrenergic receptors are mediated by guanosine
nucleotide-binding regulatory proteins (G proteins) and by
intracellular concentrations of downstream second messengers.
 In addition to receptor affinity and density, physiologic responsiveness to
catecholamines may be altered by the efficiency of receptor-effector
coupling at a site “distal” to receptor binding.
 The receptor sites are relatively specific both for the transmitter substance
and for the response that occupancy of the receptor site elicits.
 Based on their physiology and pharmacology, 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. Recent molecular cloning studies have identified several
additional subtypes.
 α Receptors are occupied and activated more avidly by
norepinephrine than by epinephrine, and the reverse is true for β
receptors.
 α1 Receptors are located on postsynaptic cells in smooth
muscle and elicit vasoconstriction.
 In the kidney, activation of α1-adrenergic receptors increases
renal tubular reabsorption of sodium.
 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.

 Different classes of antihypertensive agents either inhibit α1 receptors

or act as agonists of α2 receptors and reduce systemic sympathetic
outflow.
 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.
 Activation of β2 receptors by epinephrine relaxes vascular smooth
muscle and results in vasodilation.
 Downregulation of receptors may be a consequence of sustained high levels of
catecholamines and provides an explanation for decreasing responsiveness, or
tachyphylaxis, to catecholamines.
 For example, orthostatic hypotension frequently is observed in patients
with pheochromocytoma, possibly due to the lack of norepinephrine-
induced vasoconstriction with assumption of the upright posture.
 Reflexes modulate blood pressure on a minute-to-minute basis.
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 arterial baroreflex is mediated by stretch-sensitive sensory nerve
endings in the carotid sinuses and the aortic arch.
 The rate of firing of these baroreceptors increases with arterial
pressure, and the net effect is a decrease in sympathetic outflow,
resulting in decreases in arterial pressure and heart rate.
 This is a primary mechanism for rapid buffering of acute fluctuations of
arterial pressure that may occur during postural changes, behavioral or
physiologic stress, and changes in blood volume.
 However, the activity of the baroreflex declines or adapts to sustained increases
in arterial pressure such that the baroreceptors are reset to higher pressures.
 Patients with autonomic neuropathy and impaired baroreflex function may have
extremely labile blood pressures with difficult-to-control episodic blood pressure
spikes associated with tachycardia.

RENIN-ANGIOTENSIN-ALDOSTERONE
The renin-angiotensin-aldosterone system contributes to the regulation of arterial pressure primarily via the vasoconstrictor
properties of angiotensin II and the sodium-retaining properties of aldosterone.
RENIN
§  an aspartyl protease that is
synthesized as an enzymatically
inactive precursor, prorenin
§  Prorenin may be secreted directly
into the circulation or may be
activated within secretory cells and
released as active renin
§  Most renin in the circulation is
synthesized in the renal afferent
renal arteriole
§  In human plasma, 2-5x more
prorenin than renin, no evidence
that prorenin contributes to the
physiologic activity of this system
§  3 primary stimuli for renin
secretion:
-          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)
-          decreased pressure or stretch
within the renal afferent arteriole
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ANGIOTENSIN
§  a substrate, angiotensinogen, is cleaved by
renin to form an inactive decapeptide, angiotensin
I amiloride-sensitive epithelial sodium
§  A converting enzyme, ACE kinase, located
primarily but not exclusively in the pulmonary
circulation, converts angiotensin I to the active
octapeptide, angiotensin II, by releasing the C-
terminal histidyl-leucine dipeptide; the same
converting enzyme cleaves a number of other pep-
tides, including and thereby inactivating the
vasodilator bradykinin
§  Angiotensinogen, renin, and angiotensin II are
also synthesized locally in many tissues, including
the brain, pituitary, aorta, arteries, heart, adrenal
glands, kidneys, adipocytes, leukocytes, ovaries,
testes, uterus, spleen, and skin
 
ALDOSTERONE
§  a potent mineralocorticoid that
increases sodium reabsorption by
channels (ENaC) on the apical surface of
the principal cells of the renal cortical
collecting duct
§  Synthesized and secreted by the zona
glomerulosa of the adrenal cortex
§  also dependent on potassium; may be
decreased in potassium-depleted indi-
viduals
§  Electric neutrality is maintained by
exchanging sodium for potassium and
hydrogen ions
§  increased aldosterone secretion may
result in hypokalemia and alkalosis
§  Beyond its renal effects, aldosterone
can exert deleterious effects on the
cardiovascular system, including fibrosis,
endothelial dysfunction, inflammation,
and oxidative stress, as well as an overall
increase in cardiovascular morbidity and
mortality.
§  Secondary aldosteronism (i.e.,
increased aldosterone secondary to

(baroreceptor mechanism)
-           sympathetic nervous system
stimulation of renin-secreting cells via
β1 adrenoreceptors
§  renin secretion increases in
response to pharmacologic blockade
of either angiotensin-converting
enzyme (ACE) or angiotensin II
receptors
§  directly inhibited by angiotensin II
due to type 1 receptors on
juxtoglomerular cells
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increased renin-angiotensin), but not
Angiotensin II hypertension, also is observed in
edematous states such as CHF and liver
§  Acting primarily through angiotensin II type 1
disease.
(AT1) receptors on cell membranes:
- a potent pressor substance,
- the primary tropic factor for the synthesis &
secretion of aldosterone by the adrenal zona glo-
merulosa
§  Angiotensin II in tissues may be formed by the
enzymatic activity of renin or by other proteases,
e.g., tonin, chymase, and cathepsins
§  a mitogen that stimulates growth and contributes
to modeling and repair
§  Excess tissue angiotensin II may contribute to
atherosclerosis, cardiac hypertrophy, and renal
failure; a target for pharmacologic therapy to
prevent target organ damage
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Renin-dependent hypertension
  Clear examples are renin-secreting tumor
 @ Kidney: hemangiopericytomas of the juxtaglomerular apparatus, renal carcinomas (ie.
Wilms’ tumors)
 Renin-producing carcinomas in lung, liver, pancreas, colon, and adrenals

  Renovascular hypertension
 another renin-mediated form of hypertension
  Obstruction of the renal artery leads to decreased renal perfusion pressure, thereby
stimulating renin secretion. Over time, possibly as a consequence of secondary renal
damage, this form of hypertension may become less renin-dependent
Mineralocorticoid-mediated hypertension
 Primary aldosteronism is a compelling example
 adrenal aldosterone synthesis and release are independent of renin-angiotensin, and renin
release is suppressed by the resulting volume expansion
 Mineralocorticoid receptors are expressed in a number of tissues in addition to the
kidney, and mineralocorticoid receptor activation induces structural and functional
alterations in the heart, kidney, and blood vessels, leading to myocardial fibrosis,
nephrosclerosis, and vascular inflammation and remodeling, perhaps as a consequence of
oxidative stress
 These effects are amplified by a high salt intake. In animal models, high circulating
aldosterone levels stimulate cardiac fibrosis and left ventricular hypertrophy, and
spironolactone (an aldosterone antagonist) prevents aldosterone-induced myocardial
fibrosis.
  Due to a renal hemodynamic effect, in patients with primary aldosteronism, high
circulating levels of aldosterone also may cause glomerular hyperfiltration and
albuminuria.

Increased activity of the renin-angiotensin-aldosterone axis is not invariably associated

with hypertension. In response to a low-NaCl diet or to volume contraction, arterial pressure and
volume homeostasis may be maintained by increased activity of the renin-angiotensin-
aldosterone axis.

VASCULAR MECHANISM
 Vascular radius and compliance of resistance arteries are important determinants of arterial
pressure.
 In hypertensive patients, structural, mechanical, or functional changes may reduce the lumen
diameter of small arteries and arterioles.
 Remodeling refers to geometric alterations in the vessel wall without a change in vessel volume.
o Hypertrophic (increased cell size, and increased deposition of intercellular
matrix) or eutrophic vascular remodeling results in decreased lumen size
and, hence, increased peripheral resistance.
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o Apoptosis, low-grade inflammation, and vascular fibrosis also contribute to
remodeling.
o Lumen diameter also is related to elasticity of the vessel.
 A high degree of elasticity can accommodate an increase of
volume with relatively little change in pressure
 A semi-rigid vascular system, a small increment in volume induces a
relatively large increment of pressure
o A stiffened vasculature is less able to buffer short term alterations in flow.
 Arterial stiffness is a manifestation of hypertension
 Vascular stiffness may also represent a cause of hypertension
o Non-invasive determination of pulse wave velocity between the carotid and
femoral arteries is often interpreted as an index of arterial stiffness.
 Due to arterial stiffness, central blood pressures (aortic, carotid) may not
correspond to brachial artery pressures.
 Ejection of blood into the aorta elicits a pressure wave that is propagated at
a given velocity.
o The aortic augmentation index, a surrogate index of arterial stiffening, is calculated as the
ratio of central arterial pressure-to-pulse pressure.
 Central blood pressure and the aortic augmentation index are strong,
independent predictors of cardiovascular disease and all-cause mortality.
 Central blood pressure also appears to be more strongly associated with
pre-clinical organ damage than brachial blood pressure.
o Ion transport by vascular smooth muscle cells may contribute to hypertensionassociated
abnormalities of vascular tone and vascular growth, both of which are
modulated by intracellular pH (pHi).
o Three ion transport mechanisms participate in the regulation of pHi:
i. Na+-H+ exchange
ii. Na+-dependent HCO3–-Cl– exchange
iii. cation-independent HCO3–-Cl– exchange

 Based on measurements in cell types that are more accessible than vascular smooth muscle (e.g.,
leukocytes, erythrocytes, platelets, skeletal muscle), activity of the Na+-H+ exchanger is
increased in hypertension, and this may result in increased vascular tone by two mechanisms.
o First, increased sodium entry may lead to increased vascular tone by
activating Na+-Ca2+ exchange and thereby increasing intracellular calcium.
o Second, increased pHi enhances calcium sensitivity of the contractile
apparatus, leading to an increase in contractility for a given intracellular
calcium concentration.
o Additionally, increased Na+-H+ exchange may stimulate growth of vascular
smooth muscle cells by enhancing sensitivity to mitogens

IMMUNE MECHANISMS, INFLAMMATION, AND OXIDATIVE STRESS

 Patients with primary hypertension have increased circulating levels of autoantibodies.
 Both hypertension and aortic stiffness are associated with activation of innate and adaptive
immunity.
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 Many forms of hypertension in experimental animals are associated with an
inflammatory component requiring T lymphocytes.
 Inflammation and exudative injury are closely coupled.
 Inflammation, vascular stretch, angiotensin II, and salt have all been shown to result in the
generation of reactive oxygen species (ROS), which modify T cell function and further enhance
inflammation.
 ROS also attenuate the effects of endogenous small-molecule vasodilators.
 ROS within the renal medulla is a key determinant of the set point of the renal pressure-
natriuresis curve.
 Increasing evidence suggests that infiltration of T cells into the renal interstitium
contributes to inflammation and oxidative stress.
 Renal medullary oxidative stress disrupts pressure-natriuresis and contributes to the
development of hypertension in experimental models.
 Clinically, markers of oxidative stress have been described in both hypertensive and pre-
hypertensive patients.

5. What are the Pathologic consequences of hypertension?

a. Heart
 Heart disease is the most common cause of death in hypertensive
patients.
 Hypertensive heart disease is the result of structural and functional adaptations leading to
left ventricular hypertrophy, CHF, atherosclerotic coronary artery disease and
microvascular disease, and cardiac arrhythmias, including atrial fibrillation.
 Aggressive control of hypertension can regress or reverse left ventricular
hypertrophy and reduce the risk of cardiovascular disease.
 Diastolic dysfunction is an early consequence of hypertension-related heart
disease and is exacerbated by left ventricular hypertrophy and ischemia.
 Cardiac catheterization provides the most accurate assessment of diastolic
function.
 Alternatively, diastolic function can be evaluated by several noninvasive

b. Brain
 Stroke is the second most frequent cause of death in the world
 Elevated blood pressure is the strongest risk factor for stroke.
 Approximately 85% of strokes are due to infarction, and the remainder are due to either
intracerebral or sub-arachnoid hemorrhage.
 The incidence of stroke rises progressively with increasing blood pressure
levels, particularly systolic blood pressure in individuals aged >65 years.
 Treatment of hypertension decreases the incidence of both ischemic and
hemorrhagic strokes.
 Hypertension also is associated with impaired cognition in an aging population,
and longitudinal studies support an association between midlife hypertension
and late-life cognitive decline.
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 Hypertension is associated with beta amyloid deposition, a major pathologic
factor in dementia.
 In addition to actual blood pressure level, arterial stiffness and visit-to-visit
blood pressure variability may be independently related to subclinical small
vessel disease and subsequent cognitive decline.
 Cerebral blood flow remains unchanged over a wide range of arterial pressures
(mean arterial pressure of 50–150 mmHg) through a process termed
autoregulation of blood flow.
 In patients with the clinical syndrome of malignant hypertension, encephalopathy
is related to failure of autoregulation of cerebral blood flow at the upper pressure
limit, resulting in vasodilation and hyperperfusion.
 Untreated, hypertensive encephalopathy may progress to stupor, coma,
seizures, and death within hours.
 It is important to distinguish hypertensive encephalopathy from other
neurologic syndromes that may be associated with hypertension, e.g.,
cerebral ischemia, hemorrhagic or thrombotic stroke, seizure disorder, mass
lesions, pseudotumor cerebri, delirium tremens, meningitis, acute
intermittent porphyria, traumatic or chemical injury to the brain, and uremic
encephalopathy.
c. Kidney
 The kidney is both a target and a cause of hypertension.
 Primary renal disease is the most common etiology of secondary hypertension.
 Mechanisms of kidney-related hypertension include
 diminished capacity to excrete sodium
 excessive renin secretion in relation to volume status
 sympathetic nervous system overactivity
 Hypertension is a risk factor for renal injury and ESRD
 The increased risk associated with high blood pressure is graded, continuous, and present
throughout the distribution of blood pressure above optimal pressure.
 Renal risk appears to be more closely related to systolic than to diastolic blood pressure,
and black men are at greater risk than white men for developing ESRD at every level of
blood pressure.
 With progressive renal injury there is a loss of autoregulation of renal blood flow and
glomerular filtration rate
 resulting in a lower blood pressure threshold for renal damage and a steeper slope
between blood pressure and renal damage.
 The result may be a vicious cycle of renal damage and nephron loss leading to more
severe hypertension, glomerular hyperfiltration, and further renal damage.
 Glomerular pathology progresses to glomerulosclerosis, and eventually the
renal tubules may also become ischemic and gradually atrophic.
 The renal lesion associated with malignant hypertension consists of fibrinoid necrosis of
the afferent arterioles, sometimes extending into the glomerulus, and may result in focal
necrosis of the glomerular tuft.
 Clinically, macroalbuminuria (a random urine albumin/creatinine ratio >300 mg/g) or
microalbuminuria (a random urine albumin/creatinine ratio 30–300 mg/g) are early markers
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of renal injury.
 These are also risk factors for renal disease progression and cardiovascular disease

d. Peripheral arteries
 In hypertensive patients
 vascular disease is a major contributor to stroke, heart disease, and renal failure.
 Hypertensive patients with arterial disease of the lower extremities are at increased risk
for future cardiovascular disease.
 Although patients with stenotic lesions of the lower extremities may be asymptomatic,
intermittent claudication is the classic symptom of PAD.
 The ankle-brachial index is a useful approach for evaluating PAD and is defined as the ratio
of noninvasively assessed ankle to brachial (arm) systolic blood pressure.
 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

6. Discuss White Coat and Masked Hypertension?

White Coat Hypertension

 Composed of 15-20% of patients with stage 1 hypertension based on office blood pressures have
average ambulatory reading <135/85 mmHg.
 Blood pressure of >140-90 in medical settings and mean awake ambulatory readings
<135/85.
 are more similar to normotensive individuals than to individuals with sustained hypertension
(elevation of both office and out-of-office blood pressures).
 Carries normal to slightly increased cardiovascular risk and does not require treatment;
attributed to a condition anxiety response.
 are at intermediate cardiovascular risk between normotensives and sustained
hypertensives.
 To confirm hypertension, some authorities recommend ambulatory blood pressure monitoring in
all individuals with elevated clinic blood pressure, and postponing therapy with careful follow-
up in those individuals with normal out-of-office blood pressures who are at low cardiovascular
risk.
 If their total cardiovascular risk is low and there is no hypertension-mediated organ
damage (HMOD), drug treatment may not be prescribed.
 They should be followed with lifestyle modification, as they may develop sustained
hypertension requiring drug treatment.

·Masked Hypertension
 Blood pressure <140/90, but an elevated daytime blood pressure of >135/85 on home or
ambulatory testing. It is reported in an estimated 10-30% of the general population.
 These patients are at similar risk of cardiovascular events as sustained hypertensives (has a
normal office blood pressure and elevated out-of-the-office blood pressure).
 Diagnosis needs confirmation with repeated office and out-of-office measurements
 May require drug treatment aiming to normalize out-of-office BP.
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 If untreated, it increases the risk of cardiovascular disease and end-organ damage

7. What are the causes of Secondary hypertension? Features of secondary hypertension.

Secondary Hypertension
 A specific cause of secondary hypertension can be identified in 5%–10% of hypertensive
patients (Table 11). 
 Early diagnosis of secondary hypertension and the institution of appropriate targeted treatment
have the potential to cure hypertension in some patients or improve BP control/reduce the
number of prescribed antihypertensive medications in others. 
 The most common types of secondary hypertension in adults are renal parenchymal disease,
renovascular hypertension, primary aldosteronism, chronic sleep apnea, and substance/drug-
induced
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Secondary Clinical History and Physical Basic Biochemistry and Urine Analysis Further Diagnostic Tests
Hypertension Examination

Renal  Personal/familial history of  Proteinuria, hematuria,  Kidney ultrasound

parenchymal CKD leukocyturia on dipstick urine
disease analysis
 Decreased estimated GFR

Primary  Symptoms of hypokalemia  Spontaneous hypokalemia or  Confirmatory testing (eg,

aldosteronism (muscle weakness, muscle diuretic-induced hypokalemia
cramps, tetany) on blood biochemistry (50%–
60% of patients are
normokalemic).
 Elevated plasma aldosterone-
renin activity ratio
intravenous saline
suppression test)
 Imaging of adrenals
(adrenal computed
tomography)
 Adrenal vein sampling

Renal artery  Abdominal bruit  Decrease in estimated GFR  Imaging of renal arteries
stenosis  Bruits over other arteries (ie, (duplex ultrasound,
carotid and femoral arteries) abdominal computed
 Drop in estimated GFR >30% tomography or magnetic
after exposure to ACE- resonance angiograms
inhibitors/ARBs depending on availability
 For suspected atherosclerotic and patient’s level of renal
RAS, history of flash function)
pulmonary edema or history
of atherosclerotic disease or
presence of cardiovascular
risk factors
 For suspected fibromuscular
dysplasia, young women with
onset of hypertension <30
years

Pheochromocyto  Headaches  Increased plasma levels of  Abdominal/pelvic

ma  Palpitations metanephrines computational tomography
 Perspiration  Increased 24-hour urinary or MRI
 Pallor fractional excretion of
 History of labile hypertension metanephrines and
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catecholamines

Cushing’s  Central obesity  Hypokalemia  Dexamethasone

syndrome and  Purple striae  Increased late-night salivary suppression tests
disease  Facial rubor cortisol  24 hour urinary free
 Signs of skin atrophy cortisol
 Easy bruising  Abdominal/ pituitary
 Dorsal and supraclavicular fat imaging
pad
 Proximal muscle weakness

Coarctation of the  Higher blood pressure in  Echocardiogram

aorta upper than lower extremities  Computational
 Delayed or absent femoral tomography angiogram
pulses  Magnetic resonance
angiogram

Obstructive sleep  Increased BMI  Home sleep apnea testing

apnea  Snoring (eg, level 3 sleep study)
 Daytime sleepiness  Overnight
 Gasping or choking at night polysomnography testing
 Witnessed apneas during
sleep
 Nocturia

Thyroid disease  Symptoms of  TSH, Free T4

hyperthyroidism: heat
intolerance, weight loss,
tremor, palpitations
 Symptoms of hypothyroidism:
cold intolerance, weight gain,
dry brittle hair
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Recommendations
a. ESSENTIAL
 Consider screening for secondary hypertension in: 
(1) patients with early onset hypertension (<30 years of age) in particular in the
absence of hypertension risk factors (obesity, metabolic syndrome, familial
history etc.), 
(2) those with resistant hypertension, 
(3) individuals with sudden deterioration in BP control, 
(4) hypertensive urgency and emergency, 
(5) those presenting with high probability of secondary hypertension based on strong
clinical clues.
 In patients with resistant hypertension: 
o investigations for secondary hypertension should generally be preceded by
exclusion of pseudoresistant hypertension and drug/substance-induced
hypertension.
 Basic screening for secondary hypertension should include: 
o a thorough assessment of history, 
o physical examination (see clinical clues), 
o basic blood biochemistry (including serum sodium, potassium, eGFR, TSH), and
dipstick urine analysis.
b. OPTIMAL
 Further investigations for secondary hypertension (additional
biochemistry/imaging/others) should be carefully chosen based on information from
history, physical examination and basic clinical investigations
 Consider referring for further investigation and management of suspected secondary
hypertension to a specialist center with access to appropriate expertize and resources

8. How do you approach a patient with hypertension?

a. History and PE
 Initial assessment of a hypertensive patient should include:
 complete history
 screen for other cardiovascular disease risk factors
 screen for secondary causes of hypertension,
 identify cardiovascular consequences of hypertension and other comorbidities,
 assess blood pressure–related lifestyles, and determine the potential for intervention
 physical examination to confirm a diagnosis of hypertension
 Circulation and heart: Pulse rate/rhythm/character, jugular venous pulse/pressure, apex
beat, extra heart sounds, basal crackles, peripheral edema, bruits (carotid, abdominal,
femoral), radio-femoral delay.
 Other organs/systems: Enlarged kidneys, neck circumference >40 cm (obstructive sleep
apnea), enlarged thyroid, increased body mass index (BMI)/waist circumference, fatty
deposits and colored striae
(Cushing disease/syndrome).
 Reliable measurements of blood pressure depend on attention to the details of the technique and
conditions of the measurement.
 Proper training of observers, positioning of the patient, and selection of cuff
size are essential.
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Relevant History and Physical
History
 Duration of hypertension
 Previous therapies: responses and side effects
 Family history of hypertension and cardiovascular disease
 Dietary and psychosocial history
 Other risk factors: weight change, dyslipidemia, smoking, diabetes, physical inactivity
 Evidence of secondary hypertension: history of renal disease; change in appearance;
muscle weakness; spells of sweating, palpitations, tremor; erratic sleep, snoring, daytime
somnolence; symptoms of hypo- or hyperthyroidism; use of agents that may increase
blood pressure
Physical
 Body habitus
 Blood pressure in both arms
 Supine and standing blood pressures
 Funduscopic examination of retina
 Quality of femoral and pedal pulses
 Vascular and abdominal bruits
 Cardiac rate and rhythm
 Signs of congestive heart failure
 Signs of secondary hypertension
b. Laboratory testing
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9. What are the treatment options of hypertension?

a. Lifestyle interventions- discuss the different studies intervention
b. Pharmacologic Therapy
c. Comparisons of antihypertensives
d. Blood pressure goals of antihypertensive therapy- Discuss in different population
10. What is resistant hypertension and its causes:
11. Discuss Hypertensive urgencies and emergencies, its clinical presentation, and treatment
Discuss Malignant Hypertension