This document provides an overview of hypertension including its epidemiology, pathophysiology, risk factors, signs and symptoms, classification, diagnosis, management, and lifestyle modifications. It discusses how both systolic and diastolic blood pressure increase cardiovascular risk. The presentation also reviews the revised definitions of hypertension in American and European guidelines, drug treatment recommendations including initial use of fixed-dose combinations, and potential increased cancer risk with hydrochlorothiazide.

1. PHARMACOTHERAPY
UPDATES
PRESENTATION ON
HYPERTENSION
By Salahadin A. (B.Pharm)
1
6/10/2022
HIWOT FANA COMPREHENSIVE
SPECIALIZED HOSPITAL
CLINICAL PHARMACY and DPIS
UNIT

2. Outline
 Introduction
 Epidemiology and pathophysiology
 Risk factors
 Signs and symptoms
 Classification
 Diagnosis
 Management of hypertension
 Life style modifications
 References
2

3. Introduction
 Arterial hypertension is the most frequent
modifiable risk factor associated with
cardiovascular morbidity and mortality .
Despite the widespread availability of proven
approaches to lower blood pressure (BP), i.e.
lifestyle modification and pharmacotherapy, in
many patients BP control to guideline
recommended targets is not achieved. Current
guidelines have recommended lowering SBP
in most patients (<65 years) to targets of 120–
130 mmHg. The treatment targets in patients
of older age and the neutral effects of lowering
BP ≤ 140/90 mmHg in these patients are
3

4. Epidemiology and
pathophysiology
 The Effect of systolic and diastolic blood pressure on
cardiovascular outcomes.
 High SBP and DBP associate with increased CV events.
However, it remained unclear whether either SBP or DBP
carries more prognostic information. This question was
addressed in a study, which evaluated data from an
integrated health care delivery system in the US. Between
2007 and 2016, more than 36 million office BP
measurements were analyzed from around 1.3 million
people. The study confirmed that both SBP and DBP
increased the risk of CV events such as myocardial
infarction and stroke. Elevated SBP had a greater
prognostic effect on stroke and myocardial infarction.
However, DBP influenced the prognosis independently of
4

5. Cont’d
 The 2017 American College of Cardiology and
American Heart Association Guidelines on the
management of hypertension revised the
definition of hypertension, which has been defined
as >130/>80 mmHg. Contrary, in the 2018
European Guidelines, the definition remained
unchanged (>140/>90 mmHg). Against this
background the prevalence of hypertension
according to the different definition criteria were
analyzed. The prevalence of hypertension
increased from 18.9% with a threshold of >140/90
mmHg to 43.5% with >130/80 mmHg. An SBP of
>130 mmHg was present in almost 50% of the
participants over the age of 60 years.
5

6. Cont’d
 Hypertension not only increases the risk of stroke,
myocardial infarction, and renal failure but also
appears to be associated with heart valve diseases
such as aortic valve stenosis and aortic valve
insufficiency. In a study from the UK, 5.4 million
patients with unknown CV disease or aortic valve
disease at baseline were examined and followed for
9.2 years. A total of 20,680 patients (0.38%) were
diagnosed with aortic valve stenosis and 6440
patients (0.12%) with aortic regurgitation. For each
increase of 20mmHg in SBP, the relative risk [RR] of
aortic valve stenosis increased by 41% (HR 1.41, 95%
CI 1.38–1.45), and 38% for aortic regurgitation (HR:
1.38, CI 1.31–1.45), respectively.
6

7. Cont’d
 The participants were recruited between 2006 and 2010. A
total of 130 gene variants were selected for the genetic
determination of hypertension. A total of 1491 (0.45%)
patients had aortic valve stenosis, 634 (0.19%) aortic
regurgitation and 1736 (0.53%) mitral regurgitation. With
each increase in SBP by 20 mmHg, the RR for aortic valve
stenosis increased by 3.3-fold (odds ratio [OR] 3.26; 95%
CI1.50–7.10, p=0.002), for aortic regurgitation by 2.5 (OR
2.59; 95% CI 0.75–8.92, p=0.13), and for mitral valve
regurgitation by 2.2 (OR 2.19; 95% CI 1.07–4.47, p=0.03),
respectively. An increase in SBP by 20mmHg was
associated with an almost 3-fold higher risk to develop any
of the three valvular diseases (OR 2.85; 95% CI 1.69–4.78,
p < 0.001). These data suggest that lifetime exposure to
elevated SBP appears to be associated with an increased
7

8. Risk factors
 Personal history of CVD (myocardial infarction,
heart failure [HF], stroke, transient ischemic
attacks [TIA], diabetes, dyslipidemia, chronic
kidney disease [CKD], smoking status, diet,
alcohol intake, physical activity, psychosocial
aspects, history of depression).
 Family history of hypertension, premature
CVD, (familial) hypercholesterolemia,
diabetes.
8

9. Signs and symptoms
 Symptoms/signs of
hypertension/coexistent illnesses:
 Chest pain
 shortness of breath
 palpitations
 claudication
 peripheral edema
 headaches, blurred vision
 nocturia, hematuria, dizziness.
9

10. Classification
 Primary Hypertension
 Most individuals with high BP (over 90%) have
essential or primary hypertension. Numerous
potential mechanisms have been identified that
contribute to the pathogenesis of essential
hypertension, so identifying the exact underlying
abnormality is not possible. Genetic factors may
play a role in the development of essential
hypertension by affecting sodium balance or other
BP regulating pathways.
10

11. Cont’d
 Secondary Hypertension
 Secondary hypertension, where either a comorbid
disease or a drug (or other product) is responsible
for elevating BP is much less common than
primary hypertension (up to 10%).1 In most of
these cases, renal dysfunction resulting from
severe chronic kidney disease (CKD) or
renovascular disease is the most common
secondary cause. Certain agents (drugs or other
products), either directly or indirectly, can
increase BP and cause or exacerbate
hypertension.
11

12. Cont’d
 Isolated systolic hypertension is considered
to be present when the blood pressure is
≥140/<90 mmHg.
 Isolated diastolic hypertension is
considered to be present when the blood
pressure is <140/≥90 mmHg.
12

13. Cont’d
 WHITE COAT HYPERTENSION — Many patients
are anxious when visiting the physician, leading to
an office blood pressure (BP) that may be
substantially higher than BP during normal daily
activities. The diagnosis of white coat
hypertension (also called isolated clinic or office
hypertension) is applied to patients with office
readings that average more than 140/90 mmHg
and reliable out of office readings that average
less than 140/90 mmHg. Having the BP in the
office taken by a nurse or technician, rather than
the physician, may minimize the white coat
effect.
13

14. Cont’d
 Hypertensive urgency — Severe
hypertension (as defined by a diastolic blood
pressure above 120 mmHg) in asymptomatic
patients is referred to as hypertensive urgency.
 A hypertensive emergency is defined as
severe hypertension that is associated with
acute end-organ damage.
 Specific clinical presentations of hypertensive
emergencies include:
14

15. Hypertensive emergency
 Hypertensive encephalopathy: Severe BP elevation
associated with lethargy, seizures, cortical blindness and
coma in the absence of other explanations.
 Malignant hypertension — Severe BP elevation
(commonly>200/120 mm Hg) associated with advanced
bilateral retinopathy (hemorrhages, cotton wool spots,
papilledema).
 Hypertensive thrombotic microangiopathy: Severe BP
elevation associated with hemolysis and thrombocytopenia in
the absence of other causes and improvement with BP-
lowering therapy.
 Other presentations of hypertensive emergencies include
severe BP elevation associated with cerebral hemorrhage,
acute stroke, acute coronary syndrome, cardiogenic
15

16. Drug induced hypertension
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17. Cont’d
17

18. Cont’d
18
 When BP is evaluated using both office and
out-of officemeasurements (HBPM or ABPM),
patients are classified into four categories :
 Normotension (OBP and out-of-office BP not
elevated)
 Sustained hypertension (elevated OBP and out-
of-office BP)
 White coat hypertension (WCH) (elevated OBP
but not out-of-office BP)
 Masked hypertension (MH) (elevated out-of-
office but not OBP)

19. Cont’d
19

20. Diagnosis
20

21. Cont’d
21

22. Cont’d
22

23. Cont’d
23

24. Management of hypertension
 Most patients with hypertension require
lifelong medical therapy to achieve optimal BP
control. The 2018 European Guidelines
equally recommend five classes of
antihypertensive drugs; these include ACE
inhibitors (ACE-I),angiotensin receptor
blockers (ARB), beta blockers (BB), calcium
channel blockers (CCB), and diuretics
(thiazides and thiazide-like diuretics).
24

25. Cont’d
 Given the high rates of non-adherence to
antihypertensive medication, the treatment
regimen should be effective and above all
uncomplicated. Hence, the importance of
combination treatment is particularly
highlighted to improve adherence to therapy
and BP control. Therefore, the 2018 European
Guidelines recommend, especially in the
context of lower BP targets, to start
antihypertensive therapy with an initial dual
fixed-dose combination of ACE-I or ARB+CCB
or diuretic.
25

26. Cont’d
26

27. Cont’d
27

28. 28

29. Cont’d
 These combinations should be the primary
therapy for most patients. Exceptions are
patients with grade 1 hypertension (especially
with SBP values <150 mmHg), low risk as well
as elderly (≥80 years of age) or frail patients. If
BP is not controlled with a two-drug
combination, it is recommended escalating to a
three-drug combination of ACE-I or
ARB+CCB+diuretic (i.e. a triple combination).
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30. Cont’d
 If BP still remains uncontrolled, despite triple
therapy in sufficient doses, treatment should
be increased by addition of spironolactone 25–
50 mg or, if no tolerated, other diuretics such
as amiloride or higher doses of other diuretics,
a BB, or an alpha-blocker should be added.
Therapy with BB is recommended especially
for patients with cardiac comorbidities (heart
failure, angina pectoris postmyocardial
infarction, atrial fibrillation, or younger women).
30

31. Hydrochlorothiazide and the
increased the risk of cancer
31
 The warning published by the European Medicines Agency (EMA)
and the Federal Institute for Drugs and Medical Devices in Germany
regarding the potential risk of basal cell carcinoma (BCC) and
squamous cell carcinoma (SCC) of skin should be considered when
prescribing HCT-containing drugs.
 This letter was triggered by data from the Danish Cancer Registry
and the National Prescription Registry. These studies from Denmark
showed a cumulative dose-related relationship between HCT and
non-melanoma skin cancer (NMSC).
 The Danish study documented a dose dependent association
between HCT and the risk for BCC, ranging between 1.29 (95%CI
1.23–1.35) times for ≥50 g of HCT and 7.7 (95%CI 5.7–10.5) times
for ≥100 g of HCT for SCC.
 Chlorthalidone and indapamide are possible alternatives, but no
data are available on the potential risk for skin cancer of these

32. Valsartan recall
32
 The reason is the detection of a known carcinogen,
namely N-nitrosodimethylamine (NDMA), which can be
found in candesartan, irbesartan, losartan, olmesartan,
and valsartan.
 NDMA has been classified by the WHO International
Agency for Research on Cancer to be carcinogenic in
humans.
 If 100,000 patients would have received NDMA-
contaminated valsartan from Zhejiang Huahai
(manufacturing site where the highest levels of
contaminants were found) every day for 6 years in the
highest dose, it could result in 22 additional liver cancers
over the lifetime of these patients. The presence of

33. Life style modifications
33

34. Cont’d
34

35. References
 Hussam Al Ghorani etal. Hypertension trials
update journal of human hypertension Published
online: 12 January 2021
 2020 International Society of Hypertension Global
Hypertension Practice Guidelines
 2021European Society of Hypertension practice
guidelines for office and out-of-office blood
pressure measurement
 Dipiro pharmacotherapy 11th edition
 Uptodate
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36. Thank you
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