Assoc. Prof. Adina Turcu -Stiolica , PhD [619340]

UNIVERSITY OF MEDICINE AND PHARMACY OF
CRAIOVA
FACULTY OF PHARMACY
PHARMACOECONOMICS

ASSESSMENT OF THE
QUALITY OF LIFE OF
HYPERTENSIVE PATIENTS

SCIENTIFIC COORDINATOR :
Assoc. Prof. Adina Turcu -Stiolica , PhD

STUDENT: [anonimizat]

2020

2 TABLE OF CONTENT
INTRODUCTION ………………………….. ………………………….. ………………………….. ………………………. 4
Chapter 1 – Hypertension and Anti -hypertensive drugs. ………………………….. ………………………….. . 7
1.1 Definitions of Hypertension ………………………….. ………………………….. …………………………. 7
1.2 Clinical Significance ………………………….. ………………………….. ………………………….. ………. 9
1.3 Diagnosis ………………………….. ………………………….. ………………………….. …………………….. 9
1.4 Taking your blood pressure at home ………………………….. ………………………….. …………… 10
1.5 Treatment ………………………….. ………………………….. ………………………….. ………………….. 10
1.5.1 Medications to treat high blood pressure ………………………….. ………………………….. . 11
1.5.2 Additional medications sometimes used to treat high blood pressure …………………. 12
1.5.3 Resistant hypertension: When your blood pressure is difficult to control ……………… 12
1.6 Medication Summary ………………………….. ………………………….. ………………………….. …… 13
1.6.1 Diuretics ………………………….. ………………………….. ………………………….. ……………… 13
1.6.2 ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIs) ……………………….. 14
1.6.3 ANGIOTENSIN RECEPTOR BLOCKERS (ARBs): ………………………….. ……………… 15
1.6.4 BETA BLOCKERS, ALPH A BL OCKERS AND SYMPATHOLYTIC DRUGS ………… 16
1.6.5 CALCIUM CHANNEL BLOCKERS (CCBs) ………………………….. ………………………… 17
1.7 OTHER DRUGS ………………………….. ………………………….. ………………………….. …………. 18
1.7.1 NEW DEVELOPMENTS IN HYPERTENSION RESEARCH AT GEORGETOWN
UNIVERSITY HYPERTENSION, KIDNEY AND VASCULAR RESEARCH CENTRE …………. 18
1.8 Regulation of hypertension in Greece ………………………….. ………………………….. …………. 20
1.8.1 Regulation of hypertension in Greece ………………………….. ………………………….. …… 20
Chapter 2 – Questionnaires used to measure Health -related Quality of life. ………………………….. .. 23
Type of questionnaire ………………………….. ………………………….. ………………………….. ……………. 23
Methods ………………………….. ………………………….. ………………………….. ………………………….. …. 24
Study Sites and Sampling ………………………….. ………………………….. ………………………….. …… 24
Data Collection ………………………….. ………………………….. ………………………….. …………………. 25
Data Analysis ………………………….. ………………………….. ………………………….. ……………………. 25
Treatment methods ………………………….. ………………………….. ………………………….. ………………. 26
Chapter 3 – Factors impacting on patient's Health -related Quality of life. ………………………….. …… 28
3.1. Demographic and Socioeconomic Characteristics ………………………….. …………………….. 28
Table 1 ………………………….. ………………………….. ………………………….. ………………………….. … 28
SF-36 Measurement ………………………….. ………………………….. ………………………….. ……………… 30
Table 2 ………………………….. ………………………….. ………………………….. ………………………….. ………. 30
SF-36 Measurement Stratified by Sex ………………………….. ………………………….. ………………….. 32
Table 3 ………………………….. ………………………….. ………………………….. ………………………….. ………. 32
PF (Physical Functioning) ………………………….. ………………………….. ………………………….. …… 34
RP (Role Limitations Due to Physical Problems) ………………………….. ………………………….. …. 34
BP (Body Pain) ………………………….. ………………………….. ………………………….. …………………. 35

3 GH (General Health) ………………………….. ………………………….. ………………………….. ………….. 35
VT (Vitality) ………………………….. ………………………….. ………………………….. ………………………. 35
SF (Social Function) ………………………….. ………………………….. ………………………….. ………….. 35
RE (Role Limitations Due to Emotional Problems) ………………………….. ………………………….. . 35
MH (Mental Health) ………………………….. ………………………….. ………………………….. ……………. 35
PCS (the Physical Component Summary) ………………………….. ………………………….. …………. 35
MCS (t he M ental Component Summary) ………………………….. ………………………….. …………… 35
Conclusions ………………………….. ………………………….. ………………………….. ………………………….. .. 36
REFERENCES ………………………….. ………………………….. ………………………….. ……………………….. 38

4 INTROD UCTION

Hypertension , or high blood pressure, is a very common long-term medical condit ion that
often ca n be a major risk factor for other health implications such as cardiovascular diseases and
stroke . Hypert ension is a chronic condition in which the high blood pressu re running in the
blood vessels weakens over time the w alls of the arteries ca using serious damage to the
circulatory system .
Blood pressure is determined by two things . the amount of blood that the heart pumps and the
resistance of the blood flow inside the arteries. Many factors can contribute in narrowing the
diameter of the blood vessels eventually leading to higher blood pressure.
High blood pressure can pass undetected in patien ts for many years . That poses a m ajor
health risk as e ven wi thout hypertensive symptoms , damage to the blood vessels and the heart
occur s silently and without tre atment may lead to serious heal th complications , even death . Un-
controlled high blood pressure is the cause of many se rious and life threat ening conditions such
as heart a ttack and stroke.
High blood pressure generally develops over the c ourse of many years . Lifestyle can play a
pig part in that but heredi tary factors are also conside red to greatly incr ease the chan ce of devel-
opping in the future. Fortunatel y, high blood pressure can be easily detected. And once detected
it is quite easily monitored and controlled with the proper medication.
Elevated blood pressure is the result the Renin -angiotensin system. Renin is an enzyme s e-
creted by the kidneys. The Ren in enzyme circulates in the bloodstream and hydrolyzes the angi o-
tensinogen secre ted by the live r in the angiotensin I peptide.
Angiotensin I is further broken down in the lungs by angiotensin converting the enzyme
(ACE) into angiotensin II.
Angiotensin II is a potent vasoconstrictor for all blood vessels. It acts on smooth muscle and
therefo re increases the resistance of these arteries to the heart. The heart, trying to overcome this
increase in its "load", works more intensely, causing an increase in blood pressure.
Angiotensin II also acts on the adrenal glands and releases aldosterone (a h ormone that plays
a central role in the homeostatic regulation of blood pressure, plasma sodium and potassium le v-
els) which stim ulates the epithelial cells in the distal tubule and collecting ducts of the kidneys to
increase re -absorption of sodium, exchan ging with potassium to maintain electrochemical ne u-
trality, and water, leading to raised blood volume and raised blood pressure.

Factors that lead to elevated blood -pressure
There are many factors that lead to elevated blood -pressure. The most “common” is
the age of the patient. The increase in blood pressure with age is mostly associated with
structural changes in the arteries and especially with large artery stiffness.
Other reasons of elevated blood -pressure can be:
● Poor diet, with large amounts of so dium intake is also another reason which leads to elevated
blood -pressure as well obesity.
● Family history of hypertension.
-Individuals whose parents have hypertensio n have an elevated risk of developing the
condition.
●Smoking.

5 – Smoking can lead to ma ny diseases that can cause hypertension, such us arteriosclerosis,
atherosclerosis, elevated cardiac rhythm.
●Obesity
– Increased levels of plasma lipids, such as choles terol, LDL, VLDL and triglycerides can have
an impact on arterial wall narrowing, thus elevating blood -pressure
●Stress
●Chronic kidney disease
●Adrenal and thyroid disorders
●Too much alcohol consumption (more than 1 to 2 drinks per day)

Levels of Hypert ension:
To categorize the intensity of elevated blood -pressure, hypertension is divide d in 4 levels :
●Level 1: 120 -130 mm Hg (early stage of hypertension)
●Level 2: 130 -140mm Hg (Hypertension, Stage 1)
●Level 3: 140 -180 mm Hg (Hypertension, Stag e 2)
●Level 4: 180 -220 mm Hg (Hypertensive crisis)

Diagnosis and treatment of hypertension.
The diagnosis is made by the physician, with the use of sphygmomanometer,
in three or more sessions. The doctor then decides the level of hypertension of the patient and
subscribe the recommended treatment.

Medication used in the treatment of hypertension.
●Diuretics (Thiazide -type diuretics, loop diuretics, potassium sparing diuretics)
●Angiotensin -converting enzyme (ACE) inhibitors
●Angiotensin II recept or blockers (ARBs)
●Calcium channel blockers
●Renin inhibitors
●Aldosterone antagonists
●ß and α – adren ergic blockers
●Vasodilators (Hydralazine, Minoxidil, Diazoxide, Sodium Nitroprusside)
●Centrally acting: Clonidine, Methyldopa (not so commonly used)

Non pharmacological treatment of hypertension.
Changing the lifestyle of a patient can go a long way tow ard controlling high blood
pressure. The physician may recommend to the patient to make lifestyle changes including:

6 ●Eating a heart -healthy diet with l ess salt.
●Getting regular physical activity.
●Limiting the amount of alcohol.
●Maintaining a healthy we ight or losing weight if the patient is overweight or obese.
●Quit smoking ( if patient is a smoker)

Quality of life of the patient
Health -related qual ity of life (HRQOL) can be affected by symptoms, whether from
illness or treatment. The term HRQOL refer s to the physical, emotional and social
impact of the disease and the treatments and differs from the normal measures of the
disease. HRQOL in hypertens ive patients may be affected by blood pressure, side
effects of medications used to treat hypertension, or other factors, such as the labeling
effect, or beliefs and attitudes about the disease and treatment. Controversial is the
determination of the varia ble or set of variables that has the greatest effect on HRQOL.
Relationships between patient, disease, t reatment variables, symptoms, and HRQOL
were described by a model published in 1995. This model suggests that physiological
changes due to illness or tr eatment lead to symptoms, which in turn affect the functional
state or HRQOL. These relationships are af fected by patient and environmental
variables that may affect the patient's perception of symptoms and changes in HRQOL.
This general model can be appli ed to data from clinical trials to verify the strength of
the relationship between HRQOL and patients, d iseases, and treatment variables.

This subject of this graduate thesis is study of the effects of hypertension and the
impact it has on the patient's r elated quality of life.
At first, we have the description of the condition and the agents of controlling it. In the
second chapter we have the study, that was made in China on 2017, about the health –
related quality of life in the hypertensive patient's usi ng a SF -36 questionnaire. Next is the
results of the study based upon the questionnaire to determine the HRQOL of the patient
and the impact that it has on their lives. Finally, we have the conclusions of the study.

7
CHAPTER 1 – HYPERTENSION AND ANTI-HYPERTENSIVE DRUGS .
1.1 DEFINITIONS OF HYPERTENSION

Hypertension is another name for high blood pressu re. It can lead to serious health
complications and increase the risk of heart disease, stroke and sometimes death.
Blood pressure is the force exerted by a person's blood on the walls of their blood vessels. This
pressure depends on the resistance of the blood vessels and how hard the heart must function.
Almost half of adults have high blood pressure, but many are unaware of this fact.
Hypertension is a primary risk factor for cardiovascular disease, such as stroke, heart attack,
heart failure and aneurys m. Keeping your blood pressure under control is vital to maintaining
good health and reducing the risk of these dangerous conditions.

Within the affere nt arterioles of the kidney, specialized cells called juxtaglomerular (JG)
cells contain prorenin. While prorenin is secreted in its inactive form, JG cell activation causes
the breakdown of prorenin in the renin. Activation of these cells takes place in r esponse to
reduced blood pressure, beta -activation or activation by macula densa cells in response to a
reduced sodium load in the distant complicated tube.
Once the renin is released into the bloodstream, it can act on its target, angiotensinogen.
Angiote nsinogen is produced in the liver and is constantly circulating in plasma. Renin then acts
to break down angiotensinogen to angiotensin I. Angiotensin I is normally inactive but acts as a
precursor to angiotensin II.
The conversion of angiotensin I to angi otensin II is catalyzed by an enzyme called
angiotensin converting enzyme (ACE). ACE is mainly found in the vascular endothelium of the
lungs and kidneys. Once angiotensin I is converted to angiotensin II, it has effects on the
kidneys, adrenal cortex, art eries and brain, binding to type II (AT) and type II (AT) angiotensin
II receptors. The results discusse d below are the result of commitment to AT receptors. The role
of AT receptors is still being investigated, but they have been shown to cause vasodilati on by the
production of nitric oxide. In plasma, angiotensin II has a half -life of 1 -2 minutes, so pepti dases
degrade it to angiotensin III and IV. Angiotensin III has been shown to have 100% of the
aldosterone stimulating effect of angiotensin II, but 40% of the pressures are affected, while
angiotensin IV has further reduced the systemic effect.
In the pro ximal renal tubule, angiotensin II acts to increase Na -H exchange, increasing
sodium absorption. Elevated Na levels in the body act to increase blood os molality, leading to
fluid displacement in the blood volume and in the extracellular space (ECF). This r aises the
patient's blood pressure.
Angiotensin II also acts on the adrenal cortex, specifically in the glomerular angle. Here, it
stimulates the releas e of aldosterone. Aldosterone is a steroid hormone that causes an increase in
sodium absorption and pota ssium secretion in the distal duct and in the nephron collection duct.
Aldosterone acts by stimulating the introduction of Na -channel channels and key N a-K ATPase
proteins. The net result is an increased level of sodium reabsorption. This has the same effe ct as
mentioned earlier: increased total body sodium leads to an increase in osmolality and then an

8 increase in blood volume and ECF. Unlike angiotensin II, aldosterone is a steroid hormone. As a
result, it imposes change by binding on nuclear receptors an d altering gene transcription. Thus,
the effects of aldosterone can take hours to days to begin, while the effects of angiotensin II are
rapid.
The effe ct of angiotensin II on vasoconstriction takes place in systemic arteries. Here,
angiotensin II binds to receptors associated with O protein, leading to secondary messenger
cataracts leading to strong arterial vasoconstriction. This works to increase overa ll regional
resistance, causing an increase in blood pressure.
Finally, angiotensin II acts on the brain . Here, it has three effects. First, it binds to the
hypothalamus, stimulating thirst and increased water intake. Second, it stimulates the release of
antidiuretic hormone (ADH) from the posterior pituitary gland. ADH, or vasopressin, works to
increase wat er absorption by the kidneys by introducing aquarin channels into the collection
duct. Finally, angiotensin II reduces the sensitivity of the reflex bar ometer. This reduces the
response of weight gainers to an increase in blood pressure, which would be cou nterproductive
to the RAAS target.
The net result of these interactions is an increase in total body sodium, total body water and
vascular tone.

9 1.2 CLINICAL SIGNIFICANCE

The RAAS (renin –angiotensin –aldosterone system) acts to manage blood volume and arterio-
lar tone in long -term basis. While small and rapid shifts are usually treated through the reflex
weight receptor, RAAS can alter blood volume over years. Although RAAS serves a critical fun c-
tion, it can be inappropriately activated in various situatio ns that can then lead to the development
of hypertension. For example, narrowing of the renal artery leads to a reduced blood volume that
reaches one (o r both) kidneys. As a result, antiparasitic cells will feel a decrease in blood volume,
activating RAAS. This can lead to an inadequate increase in blood volume and arterial tone due to
poor renal perfusion.
Pharmacologically, RAAS is a commonly used syste m for managing heart failure, hyperte n-
sion, diabetes, and acute myocardial infarction. ACE inhibitors (e g, enalapril), angiotensin receptor
blockers (ARBs, eg losartan), and aldosterone antagonists (eg, spironolactone) all work to reduce its
effect. RAAS.
The various mechanisms of these drugs allow their use in different scenarios. ACE inhibitors
inhibit the action of angiotensin -converting enzymes, thus reducing the production of angi otensin II.
ARBs act to block AT receptors, thus inhibiting the effect of angiotensin while maintaining normal
levels of the compound. Aldosterone inhibitors have two specific v arieties. The first (eg, spironola c-
tone or epileronone) acts as aldosterone antagonists. These work by preventing aldosterone from
binding to renal conn ections, preventing the introduction of Na channels. The second group (eg,
amiloride or triamterene) act s to block the inserted Na channels into the distant complicated tube.
A common use for ACE or ARBs inhibitors is in the management of hypertension. In these cases,
blocking or lowering angiotensin II levels will lead to a drop in blood pressure. They achi eve this
goal by reducing the absorption of sodium and water, leading to a decrease in blood volume and a
decrease in arterial tone. In addition, these drugs are often used to ma nage diabetes. Patients with
diabetes often have kidney problems such as prote inuria due to the excess glucose that damages the
sebum. The use of ACE inhibitors or ARBs can reduce a ctive arterial tone, leading to a reduction in
glomerular pressure. Thus, they are often used to prevent the worsening of diabetic nephropathy.

1.3 DIAGNOS IS

To measure your blood pressure, your doctor or specialist will usually place an inflatable cuff in
your hand and measure your blood pressure using a pressure gauge.
The indicator of blood pressure, given in millimeters of mercury (mm Hg), has two numbe rs.
The first or higher number measures the pressure in your arteries when your heart beats (systolic
blood pressure). The second or lower number measur es the pressure in your arteries between the
beats (diastolic pressure).
Blood pressure measurements are divided into four categories:
• Normal blood pressure. Your blood pressure is normal if it's below 120/80 mm Hg.
• Elevated blood pressure. Elevated blood pressure is a systolic pressure ranging from 120
to 129 mm Hg and a diastolic pressure below 80 mm Hg. E levated blood pressure tends to get
worse over time unless steps are taken to control blood pressure.
• Stage 1 hypertension. Stage 1 hypertension is a sy stolic pressure ranging from 130 to 139
mm Hg or a diastolic pressure ranging from 80 to 89 mm Hg.
• Stage 2 hypertension. More severe hypertension, stage 2 hypertension is a systolic pressure
of 140 mm Hg or higher or a diastolic pressure of 90 mm Hg or hig her.

10 Both numbers in a blood pressure reading are important. But after age 50, the systolic reading is
even more significant. Isolated systolic hypertension is a condition in which the diastolic
pressure is normal (less than 80 mm Hg) but systolic pressure is high (greater than or equal to
130 mm Hg). This is a common type of high blood pressure among people older than 65.
Your doctor will probably take two to three blood pressure measurements each at three or
more separate appointments before diagnosing hi gh blood pressure. This is because blood pre s-
sure fluctuates normally during the day and may increase du ring visits to the doctor (white ma t-
ter hypertension).
Your blood pressure should generally be measured on both arms to determine if there is a
diffe rence. It is important to use a bracelet of the right size.
Your doctor may ask you to record your blood pr essure at home to provide additional info r-
mation and to confirm if you have high blood pressure.
Your doctor may recommend a 24 -hour blood pressure mon itor called a blood pressure
monitor to confirm if you have high blood pre ssure. The device used for thi s test measures your
blood pressure at regular intervals for a period of 24 hours and provides a more accurate picture
of changes in blood pressure on a verage day and night. However, these devices are not available
in all medical centers and may not be r eturned.
If you have any type of high blood pressure, your doctor will review your medical history
and perform a physical exam.
Your doctor may also recom mend routine tests, such as a urine test, a blood test, a chole s-
terol test, and an electrocardiogram – a test that measures your heart's electrical activity. Your
doctor may also recommend additional tests, such as an echocardiogram, to check for more sign s
of heart disease.
1.4 TAKING YOUR BLOOD PRESSURE AT HOME

An important way to check if your blood pressur e is working, to confirm if you have high blood
pressure or to diagnose high blood pressure, is to monitor your blood pressure at home.
Home blood press ure monitors are widely available and inexpensive and you do not need a pr e-
scription to buy one. Monitor ing your blood pressure at home is not a substitute for visits to your
doctor, and monitoring your blood pressure at home may have some limitations.
Make sure you use a validated device and make sure the cuff fits. Bring the screen with you to
your doctor' s office to check its accuracy once a year. Talk to your doctor about how to start co n-
trolling your blood pressure at home.
Devices that measure your bl ood pressure on your wrist or finger are not recommended by the
American Heart Association.
1.5 TREATMENT

Changing your lifestyle can go a long way toward controlling high blood pressure. Your doctor
may recommend you make lifestyle changes including:
• Eating a heart -healthy diet with less salt
• Getting regular physical activity
• Maintaining a healthy weight or lo sing weight if you're overweight or obese
• Limiting the amount of alcohol you drink

11 But sometimes lifestyle changes aren't enough. In addition to diet an d exercise, your doctor may
recommend medication to lower your blood pressure.
Your blood pressure treat ment goal depends on how healthy you are.
Your blood pressure treatment goal should be less than 130/80 mm Hg if:
• You're a healthy adult age 65 or older
• You're a healthy adult younger than age 65 with a 10 percent or higher risk of developing
cardiovascula r disease in the next 10 years
• You have chronic kidney disease, diabetes or coronary artery disease
Although the ideal blood pressure target is 120/80 m m Hg or lower, doctors are not sure if you
need treatment (medication) to reach this level.
If you are 6 5 years of age and older and your medication is causing lower systolic blood pressure
(such as less than 130 mm Hg), your medication should not be chang ed unless it has a negative
effect on your health or quality of life.
The class of medications your doct or prescribes depends on your blood pressure measurements
and other medical problems. It is helpful to work with a team of medical professionals who hav e
experience in providing high blood pressure therapy to develop a personalized treatment plan.

1.5.1 Medicat ions to treat high blood pressure

• Thiazide diuretics . Diuretics, sometimes called water pills, are drugs that work on your
kidneys to help your body el iminate sodium and water, reducing blood volume.
Thiazide diuretics are often the first, but not the onl y, choice in high blood pressure medications.
Thiazide diuretics include chlorthalidone, hydrochlorothiazide (Microzide) and others.
If you're not takin g a diuretic and your blood pressure remains high, talk to your doctor about
adding one or replacing a medication you currently take with a diuretic. Diuretics or calcium
channel blockers may work better for people of African heritage and older people than do
angiotensin -converting enzyme (ACE) inhibitors alone. A common side effect of diuretics is
increased urination.
• Angiotensin -converting enzyme (ACE) inhibitors. These medications — such as
lisinopril (Zestril), benazepril (Lotensin), captopril (Capoten) and others — help relax blood
vessels by blocking the formation of a natural chemical that narrows bloo d vessels. People with
chronic kidney disease may benefit from having an ACE inhibitor as one of their medications.

• Angiotensin II receptor blockers (A RBs). These medications help relax blood vessels by
blocking the action, not the formation, of a natural chemical that narrows blood vessels. ARBs
include candesartan (Atacand), losartan (Cozaar) and others. People with chronic kidney disease
may benefit f rom having an ARB as one of their medications.
• Calcium channel blockers. These medications — including a mlodipine (Norvasc),
diltiazem (Cardizem, Tiazac, others) and others — help relax the muscles of your blood vessels.
Some slow your heart rate. Calcium channel blockers may work better for older people and
people of African heritage than do ACE inhibitors alone.
•

12 Grapefruit juice interacts with some calcium channel blockers, increasing blood levels of the
medication and putting you at higher risk of side effects. Talk to your doctor or pharmacist if
you're concerned about interactions.
1.5.2 Additional medications sometimes used to treat high blood pressure

If you're having trouble reaching your blood pressure goal with combinations of the above
medications, yo ur doctor may prescribe:
• Alpha blockers . These medications reduce nerve impulses to blood vessels, reduci ng the
effects of natural chemicals that narrow blood vessels. Alpha blockers include doxazosin
(Cardura), prazosin (Minipress) and others.

• Alpha -beta blockers. In addition to reducing nerve impulses to blood vessels, alpha -beta
blockers slow the heartbea t to reduce the amount of blood that must be pumped through the
vessels. Alpha -beta blockers include carvedilol (Coreg) and labetalol (Trandate).

• Beta blockers . These medications reduce the workload on your heart and open your blood
vessels, causing your heart to beat slower and with less force. Beta blockers include acebutolol
(Sectral), atenolol (Tenormin) and others.
Beta blockers aren't usually reco mmended as the only medication you're prescribed, but they
may be effective when combined with other bloo d pressure medications.
• Aldosterone antagonists . Examples are spironolactone (Aldactone) and eplerenone
(Inspra). These drugs block the effect of a nat ural chemical that can lead to salt and fluid
retention, which can contribute to high blood pressure.

• Renin inhibitors . Aliskiren (Tekturna) slows down the production of renin, an enzyme
produced by your kidneys that starts a chain of chemical steps that increases blood pressure.
Aliskiren works by reducing the ability of renin to begin this process. Due to a risk of serious
complications, including stroke, you shouldn't take aliskiren with ACE inhibitors or ARBs.
• Vasodilators . These medications, including hydralazine and minoxidil, work directly on the
muscles in the walls of your arteries, preventing the mu scles from tightening and your arteries
from narrowing.

• Central -acting agents. These medications prevent your brain from signaling your nervous
system to increase your heart rate and narrow your blood vessels. Examples include clonidine
(Catapres, Kapvay) , guanfacine (Intuniv, Tenex) and methyldopa.
To reduce the number of daily medication doses you need, your doctor may prescribe a
combination of low -dose medications rather than larger doses of one single drug. In fact, two or
more blood pressure drugs of ten are more effective than one. Sometimes finding the most
effective medication or combination of drugs is a matter of trial and error.
1.5.3 Resistant hype rtension: When your blood pressure is difficult to control

If your blood pressure remains persistently h igh despite taking at least three different types of
high blood pressure medications, one of which should usually be diuretic, you may have persi s-
tent hypertension.
People who have been tested for high blood pressure but are taking four different types of medi-
cations at the same time to achieve this test are also considered to have resistant hypertension. In

13 general, the possibility of a secondary cause of high blood pressure should be reconsidered.
Having resistant hypertension does not mean that your bloo d pressure will never drop. In fact, if
you and your doctor can determine what is behind your persistently high blood pressure, there is
a good chance that you will achieve your goal with the help of the treatment that is most effe c-
tive.
Your doctor or hyp ertension specialist can:
• Evaluate potential causes of your condition and determine if those can be treated
• Review medications you're taking for other conditions and recommend you not take any that
worsen your blood pressure
• Recommend that you monitor your blood pressure at home to see if you may have higher
blood pressure in the doctor's office (white coat hypertension)
• Suggest healthy lifestyle changes , such as eating a healthy diet with less salt, maintaining a
healthy weight and limiting how much alcoho l you drink
• Make changes to your high blood pressure medications to come up with the most effective
combination and doses
• Consider adding an aldosteron e antagonist such as spironolactone (Aldactone), which may
lead to control of resistant hypertension
1.6 MEDICATION SUMMARY

Many therapeutic agents can be used to treat hypertension pharmacologically. The general
recommendation set by the Seventh Exhibition o f Prevention, Detection, Evaluation and
Treatment of the Mixed National High Blood Pressure Committee (JN C 7) is to initiate a
thiazide diuretic initially for patients with hypertensive stages 1 without impressions. indications
for other treatments. Drugs such as angiotensin converting enzyme inhibitors (ACEIs), calcium
channel blockers (CCBs), angiotensin re ceptor blockers (ARBs), beta -blockers, and diuretics are
considered acceptable alternative therapies in patients. However, the available antihypertensi ve
agents are generally just as effective in lowering blood pressure. there may be variability
between pa tients that may affect how one patient responds to one treatment over another.

1.6.1 Diuretics

There are three classes of diuretic drugs that are used to t reat hypertension. Most commonly used
are thiazide diuretics such as hydrochlorothiazide or chlorthalidon e. There is not usually an
increased urine flow after the first one or two days of taking these medications. Nevertheless, it
is best to take them in t he morning to prevent annoying urine production overnight. They are
effective in lowering blood pressure in the great majority of patients, especially those over 60,
African Americans, and those with diabetes. Diuretics increase the effectiveness of all ot her
categories of antihypertensives. That is why they are an essential part of almost any multidrug
regim en for hypertension.

Adverse Effects : Diuretics increase the excretion of potassium and can lead to hypokalemia
(low blood potassium concentration) wh ich predisposes to irregular heart beats, and muscular
weakness. However, a combination of a thiazide or loop diuretic with a distal, potassium sparing
agent (such as in the combined medications, Maxzide or Moduretic), prevents potassium loss
and obviates this problem. Diuretics lead to some increase in uric acid and should not normally
to be used in patients with gout. They cause a small increase in blood glucose, but it is unclear

14 whether this predisposes to diabetes in the long term. Over treatment with diuretics can lead to
low blood pressure, orthostatic hypotension (weakness, dizziness and possibly faint ing on
standing) and a feeling of tiredness and lethargy, all of which can be prevented or reversed by
holding the diuretic for a day or two and resumi ng, if necessary, at a lower dosage.
Different Drugs : Thiazide diuretics include: hydrochlorothiazide (us ual starting dose 12.5 to 25
mg daily) or chlorthalidone (similar dose range). Loop diuretics include: furosemide (Lasix),
bumetanide (Bumex), and tors emide (Demadex), torsemide has a rather longer duration and is
preferred in patients with heart failure. Ethacrinic acid (Edecrin) is used in the rare patients who
are allergic to diuretics. Loop diuretics are not as effective as thiazides in lowering bloo d
pressure in patients with hypertension. They are used especially to treat edema (swelling of the
ankles ) or heart failure. However, unlike thiazides, they effective in patients with poor kidney
function in lowering blood pressure or treating edema.
Dista l, potassium retaining diuretics include: amiloride (Midamor) and Triamterene (Dyrenium),
together with s pironolactone (Aldactone) and eplerenone (Inspra). All these agents can raise
serum potassium. This is usually beneficial in patients receiving thiazid e or loop diuretics who
have increased loss of potassium in the urine. Thus these drugs are often prescri bed together.
However an increase in serum potassium predisposes to cardiac arrhythmias and can be
especially dangerous in patients with a thickened he art (left ventricular hypertrophy) or coronary
artery disease. Spironolactone causes problems with sexual performance and sometimes breast
swelling in males, but is free of these kinds of effects in females. Eplerenone does not have these
adverse effects, but is more expensive.

1.6.2 ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIs)

ACEIs are widely used to treat hypertension because they are effective, have relatively few side
effects and in reduce the complications of hypertension such as heart attacks and str okes. They
have a special use in patients with diabetes mellitus who have protein the urine (“diabetic
nephropathy”) and in patients with chronic kidney disease (CKD) in whom they appeared to
have beneficial actions in slowing the loss of kidney function a bove that achieved by other
agents.
ACEIs block the action of the renin angiotensin system (RAS). Renin i s released from the
kidney during low blood pressure, low salt intake or diuretic usage and generates angiotensin II,
which constricts blood vessels, r etains salt and water by the kidneys and raises blood pressure.
Therefore, these drugs target important h ypertensive mechanisms. Younger and white subjects
are particularly likely to have an activated RAS whereas elderly and African American subjects
are less likely. Therefore, ACEIs are especially effective in the former. They interact very well
with diureti cs. Diuretics enhance the action of ACEIs, whereas ACEIs themselves act on the
kidney to retain some potassium, thereby reducing the adverse affect of low blood potassium
that can occur during diuretic therapy. Indeed, there are a number of combination dru gs in which
an ACEI and a diuretic are included in the same medication.

Individual Drugs : The following are examples of ACEIs in clinical practice: be nazepril
(Mylan), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), Lisinopril (Prinivil),
moexipril (Univasc), quinapril (Accupril), ramipril (Altace) and trandolapril (Mavik). There are
some small differences in how long these drugs act in the circulation, they are relatively small

15 and, with the exception of the very short acting captopril, a ny of these agents are usually
affective when given once or sometimes twice daily as antihypertensive agents.
Adverse Effects : The quality of life of p atients receiving ACE inhibitors is not impaired. They
do not affect concentration, sleep, exercise abili ties, sexual performance or wellbeing. However,
10 to 20 percent of subjects develop an irritant cough. If this occurs, the drug should be
withdrawn an d the patient advised that they should not have long term therapy with an ACEI
since this is an effect co mmon to all drugs of this class. Very rarely, they can cause a dangerous
swelling of the tongue, lips and throat, which, in extreme circumstances, can seriously interfere
with breathing and requires emergent treatment. Patients with chronic kidney disease often have
a temporary worsening of kidney function as shown by a rise in blood urea nitrogen (BUN) or
creatinine concentration, but this is temporary and modest, and is not necessarily a
contraindication to prolonged therapy. Indeed, ACEI treatment has be en shown in some, but not
all studies do delay the onset of end stage renal disease (ESRD). ESRD is the requirements for
dialysis or renal transplant i n patients with progressive kidney disease.
Biochemical changes with ACEIs are usually insignificant in p atients with normal kidney
function. However, in those with impaired kidneys, they can raise the serum potassium
concentration to levels that are dange rous and require either a change in therapy, or increasing
thiazide or loop diuretic dosage to promote po tassium loss. Such patients should discuss with
their physician or a nutritionist how to restrict of dietary potassium intake. Generally, ACEIs
improve blood glucose and maybe beneficial in patients at risk for developing diabetes mellitus.
These drugs can reduce the thickness of the heart (left ventricular hypertrophy), which occur
after prolonged hypertension and predisposes to congestive heart failure (CHF). ACEIs are
strongly indicated in patients who have congestive heart failure since numerous studies have
shown that cardiac performance and life expectancy is improved in patients who receive these
drugs even if they are not hypertensive.
Special Ind ications : As these include patients with chronic kidney disease (but see the adverse
effects above), earl y diabetes mellitus, congestive heart failure, or left ventricular hypertrophy.

1.6.3 ANGIOTENSIN RECEPTOR BLOCKERS (ARBs):

ARBs also block the renin angi otensin system (RAS), like ACEIs, but have a different
mechanism of action by blocking the actions of angiotensin II in the tissues rather than the
generation of angiotensin II, which is the action of ACEIs. These drugs also have an excellent
acceptab ility and preservation of quality of life. Moreover, they do not cause an irritant cough or
the rare dan ger of swelling of the lips, tongue and throat, that can occur with ACEIs. In general,
the indications for their use, their effectiveness and beneficial interactions with thiazides and
loop diuretics are similar to ACEIs. Some studies have suggested they a re particularly effective
in preventing stroke and that they may have an additional action to diminish the progression of
Alzheimer’s disease in those w ith early dementia, but this requires conformation.
Individual Drugs ARBs include : candesartan (Atacand) , eprosartan (Teveten), irbesartan
(Avapro), losartan (Cozaar), olmesartan (Benicar), telmisartan (Micardis) and valsartan
(Diovan). As with ACEIs, ther e are only minor differences between agents in this class of drugs.
All are effective in lowering blood pressure when given once, or perhaps twice daily.
Adverse Effects : As discussed, these drugs do not cause irritant cough, but otherwise have a
similar s pectr um of adverse actions to ACEIs.

16 Special Indications : These are similar to ACEIs except that they ha ve not been shown to be
beneficial in patients with congestive heart failure and maybe particularly helpful in preventing
stroke and progression of Alzh eimer ’s disease.

1.6.4 BETA BLOCKERS, ALPHA BLOCKERS AND SYMPATHOLYTIC DRUGS

This group of drugs was intr oduced next after diuretics, to be used for hypertension. They act on
a part of the nervous system that controls blood pressure, known as the sympatheti c ner vous
system. Blockade of the sympathetic nervous system reduces blood pressure by relaxing blood
vessels, and decreasing the rate and force of contraction of the heart. Therefore, beta blockers
and sympatholytics typically slow the heart rate which ca n occ asionally cause problems in
subjects with a slow heart rate.
The actions of these agents are enhanc ed in patients taking diuretic drugs and therefore are a
good second or third line selection in those patients who are not controlled with a diuretic an d an
ACEI or ARB. Unfortunately, alpha blockers have been shown to be less effective than other
groups o f blood pressure lowering agents in preventing the complications of heart failure and
heart attacks in hypertensive subjects. Therefore, they are not ro utine ly used and so will not be
discussed further.
Beta blockers are affective in lower blood pressure a nd reducing its complications. However,
their popularity has diminished because of a large range of annoying adverse effects. Although
these are rarely serio us, they do adversely impact the quality of life of some patients, and this
limits their popularity . Nevertheless, beta blockers have been shown in many trials to prevent the
probability of a recurrence in patients who have had a heart attack. Therefo re, they are strongly
indicated in these patients even if they cause some side effects or the patient do es not have high
blood pressure.
Sympatholytic agents act in the brain to decrease the drive to the sympathetic nerves. In this
sense, the effects are s omewh at similar to beta blockers, but because of their action in the brain,
they have a different, and o ften rather worse, spectrum of adverse effects.
Individual Agents : The following are some beta blockers that are in current use: nadolol
(Corgard), prop ranol ol (Inderal), atenolol (Tenormin), metoprolol (Toprol), carvedilol (Coreg)
and labetalol.
There are significant differences between many of the drugs in this class. Some such as atenolol
abd metoprolol work on a selective part of the sympathetic nervo us sy stem and do not have so
many adverse effects regarding precipitating asthma. Others such as carvedi lol and labetalol act
on additional parts of the sympathetic nervous system and are therefore more potent. The
physician may change therapy from one to anoth er beta blocker if it is insufficient or producing
adverse effects.
Adverse Effects : The most frequ ent adverse effects of beta blockers are: slow heart rate,
depression and irritability, impaired sleep, decreased exercise capacity, wheezing and
precip itation of asthma, sexual dysfunction, and an increase in serum potassium (hyperkalemia).
These effects are mostly dose dependent and, if encountered, may be amendable to reduction in
dosage.

17 Special Indications : Beta blockers have some additional effects that make them attractive
therapy for certain of patients. Thus, they are effective in reducing the freq uency of migraine
attacks, their slowing of the heart can be beneficial in people who have fast and irregular heart
rates or atrial fibrillation, they r educe the symptoms and bad outcome in patients who have
angina (chest pain on exertion due to narrowed c oronary arteries), they reduce tremor of the
hands in patients with essential tremor and they are protective in patients who have had a prior
heart atta ck. T hey are used increasingly in patients with congestive heart failure.
Central Sympatholytic Agent : These agents include the following: clonidine (Catapres), and
alpha methyldopa (Aldomet). Catapres is available as a patch similar to a band -aid which
provide s slow release of the drug over the course of a week. This is especially beneficial in
patients who have difficulty in remembering to take the medication, but often leads to allergic
skin troubles after some months.
Adverse Effects of Central Sympatho lytic Agent : These include many of the problems
encountered with beta blockers. In addition, these agent s can cause a dry mouth, difficulty in
focusing the eyes, constipation, and sleepiness during the daytime.

1.6.5 CALCIUM CHANNEL BLOCKERS (CCBs)

These are very effective in lowering blood pressure. They act directly on the blood vessels to
cause relaxation. T hey are used sometimes as first line therapy but more often with diuretics or
ACEIs or ARBs as second or third line therapy. They are especially effecti ve in lowering blood
pressure in elderly, black, obese, and diabetic patients. They are excellent in pre venting stroke
but rather less effective than diuretics, ACEIs, and ARBs in preventing heart failure.
Individual drugs : They are devided into two categories. The first category are called
dihydropyridine CCBs and include
• amlodipine (Norvasc),
• felodipine (Plendil),
• nifedip ine (Procardia),
• nicardipine (Cardene).
The second, termed nondihydropyridine CCBs consist of two drugs,
• diltiazem (Dilacor, Cardizem, Cartia, and Tiaz ac),
• verapamil (Calan, Covera, Isoptin, Verelan).
Both two groups are usefu l in lowering the blood pr essure but they have different effects on the
heart and different adverse effects. Dihydropyridine drugs generally do not diminish the function
of the h eart and do not cause bradycardia but can cause swelling of the ankles.
Nondihydropyridine drug s, especially verapamil, can cause bradycardia , similar to beta blockers
and can cause constipation, especially in the elderly .
Adverse Effects : They are usua lly well tolerated, and most of the patients have few er side
effects. However, dihydropyridine CCBs can lead t o swelling of the ankles (edema), which is
worse in hot weather with high te mperature and at higher dosage. This usually does not ind icate
a major problem such as heart failure but an increased passage of fluid from the plasma into the
tissues of the skin. The only way to avoid ha ving edem a of this type is the reduction of the dose

18 or switching to another agent like an antigotensin co nverting en zyme inhibitor that will be more
beneficial.
Non-dihydropyridine CCBs cause bradycardia . This commonly is reduc ing the heart rate by
about 10%. It can be beneficial in some patients with a fast heart rate or who have irregular
heartbeat (atrial fi brillation), but in those with a slow initial heart rate, it can cause symptoms of
decreased cardiac output (tiredness, lethargy, and dizziness on exertion). This group of drugs
also can cause con stipation, especially in the elderly but rarely cause edema.
1.7 OTHER DRUGS

There are numer ous other drugs available to for the treatment of hypertension, but are either
quite new and expensive or suffer from certain specific adverse effects and are therefore usually
only intended for exceptional circumstances, for example, when patients remain hypertensive
despite taking 3 or 4 other drugs from the established categories described above.
These drugs will not be discussed in detail as they are rarely used.

1.7.1 NEW DEVELOPMENTS IN HYPERTENSION RESEARCH

https://medicin e.georgetown.edu/hypertension -drugs/#
Hypertension is at the heart of many research studies shedding more light to the factors
contri buting t o the condition and ho w it can be successfully managed. It is a rapidly developing
field with many interesting and promising new paths and breakthroughs.
Below , some of the key finding s of the Hypertension , Kidney and Vascular Research center
of Georgetown University are prese nted. Researchers have categorized the factors causin g
hyper tension in to 3 major groups , oxidative stress, genetics and dietary salt intake.
The role of Oxidative Stress
Oxidative stress is the resul t of oxygen r eactions a nd to xic molecules formation. T hese are
disruptive factor s in t he nor mal signaling processe s between cells causing a lterations in the
DNA. Oxidative stress is a de velop ing condition that happe ns naturally with age and has
widespread effects in the organism. It is known that o xidative st ress can be the roo t of all
common conditions that appe ar with age. Several s tudies suggest that oxidativ e stress is
increased in hy pertension and coronary ar tery d isease patients , making it a key target for treating
hypertension .
In the past, clinical trials ha ve focused in an tioxidant vitamins such as E and C but results
have been usually di sappoi nting. Researchers at Georgetown have chose n a different path and
they have focused on the d rug tempo l. Tempol is a highl y effective drug found in animal s ystems
that has great detoxifying action, preventing or even reve rsing oxidative stress. B y lowering
oxidative stress, blo od pressure is also lowered preventing damage to the blood vessels , kidneys,
heart and brain. A t the mom ent, tempol is not ye t available a s a human drug and it requires a lot
of work be fore it hit s the market but researchers at Georget own are wo rking on develo ping
potential tempol based th erapies in collaboration with Georgetown Drug Development Program .
Genetic Basis of Hypertension
It is well known to the research community that genetics is a m ajor factor leading to
hypertension. Research shows that a lmost half the risk of a person developing hypertension is

19 attributed to heredi tary genes. However , the key genes that acts as a precursor for hypertension
have not yet been determined. Recently, other kind of genes have been put under t he
micros cope. Research at Georgetown have been focusing on identifying small gene fragments
called mi cro RNAs . These circulating fragments have been found in blood p lasma of humans
and a nima ls and they are responsi ble for regulating a lot of different genes in cells i nside the
body. These m icro RNAs are activated and affected by oxidative stress . By regu lating and
redirecting these genes and the process that they control we ca n interfere in the ad verse
unwanted effe cts of ox idative stress such as hyp ertension and other complications. T his is the
key strategy in the research team of Ge orgetown and even though it is very promising , it still
requires much investment and further research and development.
Dietary Salt Intake
Genetics and age induced oxidative stress are factors contributing to the appear ance of
hypertension that are beyond our control. Amongst those things we can a ctually step in in o rder
to proactively protect ourse lves the excessive dietary salt intake is probably the most important.
Recent r esearch in animal s at Georgetown has linke d excessive salt intake with oxidative stress .
Persistent increased sal t intake have been proven to exacerbate o xidative stress in the body
leading to hypertension and othe r complications. Lifestyle changes are necessary to patients that
are already vulnerable in developing hypertension due to age and geneti cs.
Novel Treatment Strategies
As already menti oned, new strategies are being developed in the bat tle against hypertension .
Novel a ntioxidants be yond vitamins such as tempol are being tested in anima ls in the hopes of
reaching at some point a market ready status . In addition to that new finding s in the research
world suggest that a treatment for hyper tension can be found beside s substances. Researc h
indicates , first report ed by Australi an scientists that hy pertension patie nts exhibiting resistance
in medication have been showing a significant drop in blood pressures after having the nerves
running to the kidney removed. T his procedure can even be performed without the need of a
surgical operation . The tech nique is performed by pas sing a cathe ter in an artery in the groin
area all the way up to the aorta and through the arteries in the kid neys. With the he lp of
radiofrequency pulses to the cathe ter tip , small damag e in the ner ves around the art ery that ends
in the ki dneys are achie ved and therefore denervating the kidneys . The s tudy has passed the
initial phase with approximately 100 pati ents showing very encouraging results. At the moment
researchers at Georget own ar e collaborating with an Am erican company on a radiofrequency
device for renal nerve ablation with a hop e of that the clinical trial s phase will start in the next
couple of years.
As with eve ry condition of unknown causes , the way we are dea ling with idi opathic
hypertension is to try to regulate with drugs the various mechanisms that are su spected to cause
hypertension . The di fficulties l ie not only in the n ecessary on going change of antihypertensive
drugs that a patient need s to take to regulate their blood pressure but also in the ever-changing
hemodynamic profile of the pat ients that inevitably changes with age .
For instance , a patien t at the of 20 has increased cardiac output and "normal" peripheral
resistances that should be also increased in order not to have hypertension. A patient at the of 40
though, has a heart rate that returns to normal, while peripheral resistance increases. With age
the peripheral resistances are increasing greatly , while the cardiac output is decreas ing and
eventually leads to the congestive heart failure .
Hypertension trea tment should be adapted and personalized to the unique chara cteristics and
requirements of each patie nt taking into account the all the demographic and clinical data of the
patient alon g with the coexisting r isk factors and d iseases. There is no cure for a ll in

20 hypertension . Every treatment s hould be unique and frequently monitored and regulated over the
course of years in order to adapt to the everchanging profile of the patient.
The effectiveness of the treatment effects greatly the patients’ quality of life and shoul d
be monitored in all patients regardless of age. The key objective of an anti hypertensive therapy
is not only to increase the survival of hypertensi on but also to achieve the best possible qua lity
of life for patients at the same time.

1.8 REGULATION OF HYPERTENSION IN GREECE

Hype rtension is as common in our country as in other developed countries and affects about
25% of the adult population. The rates of recognition, treatment and regulation of hypertension
in our country (Figure 1) are similar to similar studies in p opulations i n other developed
countries. Many people are unaware that they have high blood pressure, but even those who
know it are less like ly to get it. The percentage of good reg ulation, both in Greece and abroad
does not exceed 20 -25%. The above result s show that there is a lot of room both for the
reduction of the cases of undiagnosed hypertension in our country, as well as for their more
effective treatment.

Benefits of treatm ent
Both systolic and diastolic blood pressure are strong and independent r isk factors for
cardiovascular disease. For every 20 mmHg increase in systolic blood pressure, or 10 mmHG of
diastolic blood pressure, the ri sk is doubled for both lethal stroke and fatal coronary stroke. In
particular, however, for people over the age of 50, systolic blood pressure is a much stronger
indicator of cardiovascular risk than diastolic.

Antihypertensive therapy reduces the risk of stroke by about 40%, coronary heart dis ease by
25% and heart failure by 50%. This reduction corresponds to a compl ete neutrali zation of the
risk for a stroke attributed to hypertension and a 2/3 neutralization of the corresponding risk for a
coronary stro ke. In patients with target organ damage or cardiovascular disease, the benefit of
treatment is greater than in pat ients with u ncomplicated hypertension.

1.8.1 Regulation of hypertension in Greece

Decision for treatment – pharmacotherapy strategy
In order for antihypertensive therapy to be effective , certain rules must be followed for
which patients must be informed by the treating physi cian.

The decision to start drug therapy is made depending on the level of overall cardiovascular
risk that the patient is ex periencing. Therefore, for each stage of hypertension, the decision to
intervene is determined by whether the overa ll cardiovascul ar risk is small, moderate or large.

21 At the beginning of treatment the doctor must determine the target pressure to be achiev ed
with the treatment.
A combination of 2-3 drugs is usually needed to achieve excellent blood pressure
regulation .

As a rule, t reatment is started with a small dose of a drug. Treatment with a combination of
two drugs can be started when the blood press ure is> 160/100 mmHg (in at least 2 visi ts with at
least 2 measurements per visit), especially in patients with hig h cardiovascula r risk

The effectiveness of any intervention is usually assessed after a month of stable treatment.
If the response to pressu re is low or side effects are observed, replacement with another class of
drug is recommended. In most cases there is a good respo nse but the pressure remains above the
target, so it is recommended to add other drugs until the therapeutic goal is achieved. Long –
acting drugs are preferred so that they are given only once a day

As a rule, the drugs are administered
a) daily
b) during the morning wake and
c) for life.

Objectives of treatment
In all hypertensive individuals, the pressure pursued with the trea tment (target pressure) is
<140/90 mmHg or lower if tolerated.
In hypertensive> 65 -year-old, the target pressure i s also <140/90 mmHg. In diabetics and
kidney patients, the target is lower (<130/80 mmHg).
At the same time, other cardiovascular risk factor s (smoking, hypercholesterolemia,
diabete s, etc.) must be treated effectively.

Decision to start drug treatment
The decision to s tart drug therapy is made depending on the level of overall cardiovascular
risk that the patient is experiencing. Therefore, f or each stage of hypertension, the decisi on to
intervene is determined by whether the overall cardiovascular risk i s small, modera te or large
(Figure 2).

Cardiovascular risk calculation
The risk of cardiovascular disease depends not only on the level of b lood pressure, but also
on the presence o f other cardiovascular risk factors (dyslipidemia, smoking, diabetes, obes ity),
damage to target organs (hypertrophy of the left ventricle, left ventricular arrhythmia),
atherosclerosis established cardiovascular da mage (coronary heart disease, stroke, kid ney
damage, peripheral arterial disease).

22 Depending on the stage of hypert ension and the coexistence of other risk factors,
hypertensive individuals are divided into normal, small, medium or large cardiovascular ris k . It
is obvious that people with the sa me stage of hypertension, e.g. stage 1, they may be at very
different risk (small, medium or large). Determining the overall risk is necessary in each patient
in order to decide whether to start treatment.

General principles
As mentioned at the beginning, hypertension is causally divided into 2 major categories:
idiopathic or p rimary hyperten sion and secondary hypertension. The causes of idiopathic
hypertension are unknown and therefore the diagnosis is sufficient o nly at the level of
determining the press ure, while in the second, ie in secondary hypertension, the causes are
known and therefor e the treatment is directed to the treatment of the cause.

Non-pharmaceuticals – lifestyle changes
Weight Loss Reduction : The most effective non -pharmacological means of reducing blood
pressure is to reduce body weight in overweight hyperte nsives. Even a small weight loss (5 kg)
can help reduce blood pressure and improve other risk factors (dyslipidemia, diabetes). You need
a low-calorie diet until you have the normal weight you need.
Other effective means are diet (with fruits, vegetables and dairy produ cts without fat to be
rich in potassium and calcium), limiting alcohol consumption (at most 2 -3 drinks a day for men
and 1 -2 for women) and physical exercise.
Perceptio ns such as that hypertensives should not consume oranges or coffee, or i nstead
should c onsume garlic or garlic preparations, are widespread myths without scientific evidence.

• Salt restriction : They should avoid adding salt to cooking food or the table. T hey should
eat more plant foods that contain a small amount of sodium an d a higher amou nt of
potassium. Also, whole foods, especially canned foods and salty foods of any origin,
should be avoided altogether.
• Exercise : Regular daily exercise can reduce blo od pressure by 5 -10 mm. This includes
gentle running, cycling, swimming and v arious gymnastic exercises. Weight loss will be
followed by fatigue and constant tiredness, as this can lead to large and sudd en increases
in blood pressure, especially in hyperte nsive patients.
• Smoking : Smoking cessation because, along wit h stress, is a major risk factor for
cardiovascular events. Although smoking has little effect on blood pressure, stopping it is
the first go al for hypertensive smokers, as it is just as importan t – and in some cases more
important – risk factors for cardi ovascular event s.
If blood pressure still exceeds the allowable limit, then these patients should be treated. The
initiation of medication d epends on the stage of hypertension and the effects of hypertension on
the various organs.
The patient should comp ly with the doc tor's instructions and not change either the amount of
medication or the hours prescribed by the doctor without first informin g him.

Special principles of antihypertensive treatment

23 Although hypertension is a major risk factor for heart dis ease, only 50% of hypertensive patients
manage to maintain their blood pressure satisfactorily.
The goal of treatment is to lower blood press ure below 140/90 mmHg, and in diabetics those
with chron ic kidney disease below 130/80 mmHg.

CHAPTER 2 – QUESTIONNAIRES USED TO MEASURE HEALTH –
RELATED QUALITY OF LIFE .
TYPE OF QUESTIONNAIRE

In 2019 there was a study about the Heal th-related quality -of-life of life for hypertensive
patient, that took place in Chongqing, China.
The aim of this s tudy was to inv estigate the factors affecting the health -related quality of life
(HRQoL) among hypertensive patients in Chongqing, China, and to provide documented
strategies to improve their HRQoL.
This cross -sectional survey was conducted in Chongqing, C hina. Of the 60 0 randomly
selected patients, 586 patients agreed to participate and 567 patients completed the study.
An SF -36 questionnaire was used for the survey.
The Sf -36 Health Survey (Summary Form 36) is a 36-item survey of patients' health. It is a
measure of th e state of health and a shortened version of it. Sf -36 is commonly used in health
economics as a variable in calculating quali ty of life with quality adjustment to determine the
cost-effectiveness of a health treatment and for the determin ation of evalu ating individual
patients health status.
The SF -36 included eight domains :
➢ physical functioning
➢ role limitations due to physic al problems
➢ body pain
➢ general health
➢ vitality

24 ➢ social function
➢ role limi tations due to emotional problems
➢ mental hea lth
All of the above was used to measure health -related quality -of-life of the patients.

Linear regressions were used; each domain of HRQoL was measured in the stratification of sex.
METHODS
Study Sites and Sa mpling

The municipality of Chongqing consis ts of 19 distri cts and 21 counties. The cross -sectional
survey was conducted in Dianjiang County and Yubei area of Chongqing, which represe nts
relatively less developed and developed areas according to socioeco nomic development levels.
The multi -stage ra ndom sampling m ethod was used. A street and a city were randomly selected
in the selected area and county. Then, three communities and three villages on each street and
city were selected. Finally, a total of six communities and six villages were included. Local
primary care facilities are responsible for creating a hypertension management profile for all
diagnosed hypertensive patients. Hypert ension management profiles include patients' personal
information, heal th records, and information about each follo w-up visit. The eligible participants
in this study were hypertensive patients who had been diagnosed mainly with hypertension for at
least o ne year, were over 18 years of age, and did not have psychiatric disord ers or disturbances
of consciousness. Patien ts with hyperte nsion with other chronic diseases (such as stroke, liver
dysfunction, etc.) and pregnant women were excluded. We used the hype rtension management
files to randomly select 50 participants from each site and downloaded their profiles after
obtaining permissi on from the chronic disease department of the main health facilities in the
selected communities. (Figure 1)

*Figure 1

1 district
1 street and 1 town
3 communities and 3 villages 21 counties
1 countie
1 street and 1 town
3 communities and 3 villages

Chongqing Municipality
19 Disctricts

25

About 50 hypertensive in dividuals at each point, 600 patients in tot al

Data Co llection

Educated postgraduate medical students and professors conducted a personal interview
with patients who meet the crit eria using a structured questionnaire in addition to patient
management files. The questions included patients' soc io-demographic information and
their health -related behaviors. The village doctor or community health center staff
called the eligible patien ts who came to the community health center for research. A
total of 586 patients participated in the study.

SF-36 was used as a m easure of HRQoL in this study. SF -36 is a self -administered scale that is
widely used in the area of HRQoL study .
SF-36 conta ins eight domains as mentioned above.
The items were coded and transfor med into a scale from zero (worst quality of life) to 100 ( best
quality of life). In addition, the eight domains were grouped into two summary components: the
physical component summary (PCS, including physical function, role physical, bodily pain and
gene ral health), and the mental component summar y (MCS, includi ng vitality, social function,
role emotional, and mental health).
In addition, the eight domains were grouped into two summary components: the physical
component summary (PCS, including physical fu nction, role physical, bodily pain and gener al
health), and the mental component summary (MCS, including vitality, social function, role
emotional, and mental health)

Data Analysis

The explanatory variables in this study included :
➢ sex 6 comm unities and 6
villages

26 ➢ age
➢ location (urba n or rural)
➢ hypertension lasting for years
➢ treatment metho ds
➢ marital status
➢ education level
➢ employment status
➢ type of medical insurance
➢ number of family members living together
➢ income category
➢ self-perceived economic burden
➢ self-reported physical activit y, smoking, drinking, and emotional self -regulation

Age
Age was grouped as per the World Health Organization (WHO) age classification criteria (≤59,
60–74, ≥75). Patients that were ag ed at 60 –74 were regarded as “the young old”.
TREATMENT METHODS

The tr eatment methods were asked whether patients took diet contr ol, exercise, medical
treatment, and/or Chinese medicine for hypertension management and treatment. It was grouped
into single treatment if patients reported one of those methods; it was grouped in to multiple
treatment if patients reported t wo or more meth ods. Income category was divided into three
equal parts according to annual per capital income: low, medium and high. It was grouped into
single treatment if patients reported one of those methods; it was grouped into multiple treatment
if patients reporte d two or more methods. Income category was divided into three equal parts
according to annual per capital income: low, medium and high. The data were double entered
into EpiData 3.1 software (EpiDa ta Associations, Odense, Denmark) and analyz ed while using
the STATISTICAL ANALYSIS SYSTEM (SAS) 9.1 software program (SAS Institute, Cary,
NC, USA). A multi -variate regression analysis was performed to study the association between
the explanatory variabl es and each domain for the HRQoL measures. T he multivariate stepwise
regression analysis was conducted to examine the factors related to HRQoL in the stratification
of sex. The level of significance was set at a two -sided p < 0.05.
The Ethical Committee of Chongqing Medical University approved this study . The ora l
consent of all participants were obtained prior to the survey.

27

28
CHAPTER 3 – FACTORS IMPACTING ON PATIENT 'S HEALTH –
RELATED QUALITY OF LIFE .

3.1. DEMOGRAPHIC AND SOCIOECONOMIC CHARAC TERISTICS

Nineteen patients out of 586 pati ents who agreed to participate in the study did not complete the
questionnaire. A total of 567 participants were included in the analysis. Table 1 presents the d e-
mographic and socioeconomic characteristics of pat ients. There were more women (60.14%)
than m en (39.86%) in this study. More than three -quarters of patients (83.42%) were over the
age of 60 and most of them lived in rural areas. Most of them (57.32%) had primary education
and about a third of patients (3 6.33%) were illiterate. Half of them (55.38% ) were employed .
About two -thirds of patients (63.49%) have been diagnosed with hypertension for more than five
years. More than half of patients (53.97%) used at least two methods to control their blood pre s-
sure. The vast majority of patients (78.13%) wer e married and m ore than half (58.73%) lived
with two or fewer family members (including themselves). More than half of the patients
(57.67%) were found to have a high financial burden caused by hypertension. The vast majority
of patients did physical activ ity at least on ce a week for more than 30 minutes, did not smoke or
drink alcohol, and most of them had emotional self -regulation, according to their report.
Table 1
Demographic and socioeconomic characteristics of hypertensive patients, survey in 2017.
Variable n %
Sex Male 226 39.86
Female 341 60.14
Age ≤59 94 16.58
60–74 351 61.90
≥75 122 21.52
Location Rural 349 61.55
Urban 218 38.45
Course of hypertension (year) 1–5 207 36.51
>5 360 63.49
Treatment a Single treatment b 261 46.03
Various treatment methods (≥2) c 306 53.97
Marital status Married 443 78.13
Single 12 2.12

29 Variable n %
Divorced/widowed 112 19.75
Education d Illiteracy 206 36.33
Primary/junior high school 325 57.32
High school and higher 36 6.35
Employed e Yes 314 55.38
No 253 44.62
Insurance UEBMI 129 22.75
URRBMI 438 77.25
Family members living together ≤2 333 58.73
≥3 234 41.27
Income category Low (<3600 RMB) 186 32.80
Medium (3600 –10,560 RMB) 194 34.22
High (>10,560 RMB) 187 32.98
Perceived economic burden caused by hypertension Low 91 16.05
Middle 149 26.28
High 327 57.67
Physical activity At least once a week 413 72.84
No 154 27.16
Smoke Yes 92 16.23
No 475 83.77
Alcohol Yes 43 7.58
No 524 92.42
Emotional self -regulation Yes 408 71.96
No 159 28.04
• a Patients were asked if they took diet control, exercise, medi cal treatment, and/or Chinese
medicine for hypertension management and treatment;
• b Single treatment: one of the above four treatment methods;
• c Various treatment methods (≥2): two or more of the above four treatment methods;
• d Those who had never received or completed school education were categorized as “illiteracy”. In
general, the primary school entrance age was around 6 –7 years old; junior hi gh school was around
12–13 years old and high school was around 15 –16 years old;
• e Patients who were retired were grouped into unemployed.

30
SF-36 MEASUREMENT

Table 2 presents the explanatory variables that were statistically significantly correlated with SF-
36 scores from each domain and component summary (p <0.05). The self -perceived financial
burden caused by hypertension showed the relationship with all sectors. Sex was associated with
Physical Function (PF), Body Pain (BP), Vitality (VT), Social Funct ion (SF), Mental Health
(MH) and Summary of Natural Ingredients (PCS). Men had significantly higher scores than
women for all six of these areas. Age was significantly associated with PF, BP and PCS.
Younger patients had higher scores than the elderly in t hese three areas. Physical activity has
played an important role in PF, role constraints due to physical problems (RP) and PCS. People
who exercised at least once a week had higher scores in those areas related to the physical
component. In addition, indiv iduals who reported alcohol consumption were associated with
higher scores in the PF, RP, BP, General Health (GH), SF, and Role limitations due to emotional
problems (RE), PCS, and Mental Component Summary (MCS). These regulated emotions
actively received higher scores in the GH and MH sectors.

TABLE 2
Factors associated with the scores of Medical Outcomes Study Short Form Health Survey questio n-
naire (SF -36) among participants.
Variables Factors β BETA SE t p *
PF Age 7.83724 0.20561 1.49023 5.26 <0.0001
Sex 8.83008 0.18435 1.90685 4.63 <0.0001
Insurance 8.37670 0.14975 2.90230 2.89 0.0040
Self-perceived economic burden caused
by hypertension 7.19362 0.23036 1.21296 5.93 <0.0001
Physical activity 9.59954 0.18207 2.06773 4.64 <0.0001
Alcohol −7.25962 −0.08195 3.46427 −2.10 0.0366
RP Location 11.65367 0.12308 3.82828 3.04 0.0024
Education 14.39468 0.18140 3.15188 4.57 <0.0001
Self-perceived economic burden caused
by hyp ertension 14.10584 0.22999 2.38992 5.90 <0.0001
Physical activity 9.84206 0.09504 4.07352 2.42 0.0160

31 Variables Factors β BETA SE t p *
Alcohol −23.01350 −0.13228 6.91768 −3.33 0.0009
BP Age 2.79476 0.09181 1.22662 2.28 0.0231
Sex 4.47809 0.11707 1.57062 2.85 0.0045
Insuran ce 5.30729 0.11881 2.38457 2.23 0.0264
Self-perceived economic burden caused
by hypertension 5.07383 0.20346 0.99828 5.08 <0.0001
Alcohol −5.61383 −0.07936 2.85002 −1.97 0.0494
GH Course of hypertension 3.26230 0.08918 1.44498 2.26 0.0243
Educ ation 3.35821 0.11067 1.22914 2.73 0.0065
Insurance 3.57809 0.08517 1.73104 2.07 0.0392
Self-perceived economic burden caused
by hypertension 5.62434 0.23981 0.94052 5.98 <0.0001
Alcohol −5.75528 −0.08651 2.63412 −2.18 0.0293
Emotional self -regulation 4.36437 0.11131 1.56993 2.78 0.0056
VT Sex 3.62593 0.09244 1.62195 2.24 0.0258
Insurance 5.65417 0.12343 2.07809 2.72 0.0067
Income category 2.12625 0.08980 1.07526 1.98 0.0485
Self-perceived economic burden caused
by hypertension 6.36889 0.24905 1.02317 6.22 <0.0001
SF Sex 5.09871 0.11311 1.91781 2.66 0.0081
Economic burden of hypertension 4.63086 0.15757 1.20565 3.84 0.0001
Alcohol −7.76904 −0.09319 3.48916 −2.23 0.0264
RE Location 14.80345 0.15947 3.77104 3.93 <0.0001
Self-perceived economic burden caused
by hypertension 10.67508 0.17753 2.44563 4.36 <0.0001
Alcohol −16.50909 −0.09678 7.04800 −2.34 0.0195
MH Sex 4.23116 0.11362 1.48788 2.84 0.0046
Treatment 3.01691 0.08247 1.48899 2.03 0.0432
Self-perceived economic burden caused
by hypertension 5.87608 0.24202 0.98918 5.94 <0.0001
Emotional self -regulation 3.64788 0.08987 1.63416 2.23 0.0260
PCS Age 3.53404 0.10699 1.29707 2.72 0.0066
Sex 4.29669 0.10352 1.68420 2.55 0.0110

32 Variables Factors β BETA SE t p *
Education 4.71062 0.13455 1.44752 3.25 0.0012
Insurance 7.55796 0.15592 1.86144 4.06 <0.0001
Self-perceived economic burden caused
by hypertension 7.92674 0.29293 1.01058 7.84 <0.0001
Physical activity 6.04096 0.13222 1.69411 3.57 0.0004
Alcohol −10.62399 −0.13840 2.88293 −3.69 0.0003
MCS Insurance 6.11371 0.12758 1.95083 3.13 0.0018
Self-perceived economic burden caused
by hypertension 6.98583 0.26114 1.06693 6.55 <0.0001
Alcohol −7.12307 −0.09387 3.04094 −2.34 0.0195

• Significant p (p < 0.05).

SF-36 MEASUREMENT STRATIFIED BY SEX

Table 3 presents the factors that are associated with SF -36 of eight domains and two component
summaries by man an d woman.

TABLE 3
Factors associated with the SF -36 scores stratified by sex, multiple liner regression.
Variables Men Women
β p * β p *
PF Age − − 8.00824 <0.0001
Family members living together − − 4.91059 0.0445
Self-perceived economic burden cau sed by hype r-
tension 9.20862 <0.0001 6.79047 <0.0001
Physical activity 8.27001 0.0088 9.83381 0.0003
RP Location − − 19.38252 <0.0001
Education − − 5.64705 0.0387
Insurance 14.06069 0.0455 − −

33 Variables Men Women
β p * β p *
Family members living together − − 13.29323 0.0040
Self-perceived economic burden caused by hype r-
tension 12.30444 0.0026 15.43663 <0.0001
Physical activity 15.91683 0.0167 − −
Alcohol −23.11539 0.0063 − −
BP Age − − 3.97340 0.0092
Location 8.03367 0.0021 − −
Insurance − − 7.85190 0.0008
Self-perce ived economic burden caused by hype r-
tension 5.64928 0.0006 4.72231 0.0002
Physical activity 7.25903 0.0090 − −
GH Education − − 2.72569 0.0083
Insurance 7.53731 0.0068 − −
Self-perceived economic burden caused by hype r-
tension 5.19251 0.0011 5.81299 <0.0001
Alcohol −7.21157 0.0270 − −
Emotional self -regulation 5.57995 0.0313 − −
VT Insurance 8.47617 0.0186 − −
Income category 4.15787 0.0256 − −
Self-perceived economic burden caused by hype r-
tension 6.23001 0.0001 6.50171 <0.0001
Physical act ivity − − 4.22616 0.0592
SF Self-perceived economic burden caused by hype r-
tension 4.84363 0.0132 4.10999 0.0081
Physical activity 8.87981 0.0071 − −
Alcohol −8.40125 0.0415 − −
RE Location − − 20.07046 <0.0001
Family members living together − − 12.20182 0.0117
Self-perceived economic burden caused by hype r-
tension 10.74271 0.0048 11.85178 0.0002
Physical activity 14.52730 0.0218 − −
Alcohol −18.67523 0.0211 − −

34 Variables Men Women
β p * β p *
MH Income category 9.16073 0.0004 − −
Treatment − − 4.96459 0.0120
Self-perceiv ed economic burden caused by hype r-
tension 6.70308 <0.0001 5.62970 <0.0001
Emotional self -regulation − − 3.84501 0.0734
PCS Age − − 4.16804 0.0147
Insurance − − 7.80464 0.0019
Family members living together − − 3.98402 0.0433
Income category 8.5344 2 0.0039 − −
Self-perceived economic burden caused by hype r-
tension 8.02238 <0.0001 8.04824 <0.0001
Physical activity 8.25833 0.0031 4.89480 0.0255
Alcohol −10.94985 0.0020 − −
MCS Location − − 6.39821 0.0027
Income category 6.67924 0.0219 − −
Self-perceived economic burden caused by hype r-
tension 7.24929 <0.0001 7.14114 <0.0001
Physical activity 6.91718 0.0120 − −
Alcohol −7.97098 0.0225 − −

* Significant p (p < 0.05).

PF (Physical Functioning)
For men, those who are aware of the low e conomic burden caused by hypertension and are phy s-
ically active at least once a week have been associated with higher self -esteem scores. Women in
the same age group, living with more than three family members, were experiencing low fina n-
cial burden caused by hypertension and were more physically active were associated with higher
scores on PF.
RP (Role Limitations Due to Physical Problems)
For men, those who are aware of the low financial burden caused by hypertension, have UEBMI
coverage, have physical ac tivity at least once a week, and alcohol consumption had higher scores
than their counterparts. Women who lived in urban areas, received high school or higher educ a-
tion, lived with more than three family members, and experienced a low financial burden caus ed
by hypertension achieved higher RP scores.

35 BP (Body Pain)
Men who experienced a low financial burden caused by hypertension, exercised at least once a
week and lived in urban areas had higher results in this area. For women, younger people were
found to have a low financial burden caused by hypertension, and having a UEBMI coverage
had higher BP scores.
GH (General Health)
For men, those who experienced a low financial burden caused by hypertension, having UEBMI
coverage, alcohol consumption and emotiona l self -regulation received higher GH scores. For
women, those with a low financial burden caused by hypertension and well -educated had higher
scores in this area.
VT (Vitality)
For men, those who experienced a low financial burden caused by hypertension, w ith UEBMI,
and a high -income group received higher VT scores. For women, those who experienced a low
financial burden caused by hypertension and exercised at least once a week had higher scores.
SF (Social Function)
Both men and women who experienced a low financial burden caused by hypertension had hig h-
er SF scores. In addition, male patients who had physical activity and alcohol had higher scores
in this area.
RE (Role Limitations Due to Emotional Problems)
Male patients who experienced a relatively low f inancial burden caused by hypertension had
more than one physical activity per week and alcohol consumption had higher scores. For wo m-
en, those who were considered to have relatively low financial burdens caused by hypertension,
lived with more than three family members and lived in urban areas had higher results.
MH (Mental Health)
For men, people who experienced a relatively low financial burden caused by hypertension and
were from a high -income group had higher scores. Female patients experienced a relat ively low
financial burden caused by hypertension, using more than two treatment methods, and emotional
self-regulation received higher scores in this area.
PCS (the Physical Component Summary)
In the physical component summary, men were found to have a re latively low financial burden
caused by hypertension, having physical activity more than once a week, drinking alcohol and
getting a higher score from a high -income group. Among women, those of the older age group,
experienced a relatively low financial bu rden caused by hypertension, had UEBMI coverage, and
lived with more than three family members received higher PCS results.
MCS (the Mental Component Summary)
Male patients who experienced a relatively low financial burden caused by hypertension, had a l-
cohol, and were from a high -income group were associated with higher scores on mental health.
Women who experienced a relatively low financial burden caused by hypertension and lived in
urban areas had higher results.

CONCLUSIONS
This study showed that age, gender, perceived financial burden caused by hypertension,
alcohol use, physical activity and the emotional state of patients were associated with their
quality of life. In gender stratification, the self -perceived economic burden caused by
hypertension an d physical activity were the common factors that affected HRQoL in both men
and women.
It shows that elderly hypertensive patients and female patients were more likely to have
poor health -related lifestyle, which is consistent with the findings in Alexandr ia, Egypt and
Shanxi, China. Previous studies in South Korea and Pakistan have reported that hypertensive
patients in the low -income group were associated with worse HRQoL. In this study, it shows that
low income was associated with lower vitality and ment al health scores for male patients. The
people who conducted this study asked about the self -perceived financial burden of patients with
hypertension in this study and found that the perception of the low financial burden caused by
hypertension in both men and women is related to better quality of life related to health. In
China, patients with NCD, including hypertensive patients, need long -term treatments, and many
of them have suffered heavy financial burdens in both urban and rural areas. In 2009, the
Chinese government launched a new round of national health care reform and set the goal of
universal health coverage. In 2010, three major medical insurances, NCMS, URBMI and
UEBMI, in China have achieved almost universal coverage. Previous studies in China have
found that basic medical insurance, particularly NCMS and URBMI, provided a relatively high
rate of compensation for hospitalization, but limited coverage for outpatient care.
Promoting a healthy lifestyle will improve the quality of life of patient s with hypertension.
According to other studies, I found that regular physical activity had positive roles in relation to
patients' physical and social functions. In addition, I found that emotion regulation was actively
associated with HRQoL, although sev eral previous studies have reported this effect in
hypertensive patients. However, it is surprising that alcohol use among male patients was
associated with higher scores on physical and mental health measures, which can be attributed to
local culture, giv en the use of alcohol for relaxation and other social activities. In addition, a
previous study in Hong Kong found that occasional and moderate alcohol use was associated
with lower mortality than never before.
Living with family members was also positive ly correlated with HRQoL, especially for
female patients. Similar results have been found in previous studies. A 2009 study in Chongqing
found that relationships with family or friends could affect the quality of life associated with
health among hypertens ive patients. It has also been shown that lower social support is
associated with poor quality of life related to health among people with chronic diseases, such as
hypertension among Korean American patients. Family support has played an important role in
compliance with hypertension treatment, and patients may derive HRQoL benefits from
emotional support.

This study examined the relationship between demographic and socioeconomic
characteristics of hypertensive patients and the lifestyle and quality of li fe associated with health.
However, some variables, such as tobacco and alcohol use, were not quantified, and the type of
drugs and the number of drugs used to treat hypertension were not investigated, which may to
some extent affect HRQoL measures. In add ition, the sample size is relatively small. This study
can be considered a case study and a generalization in other areas should be made with caution.

37 The perceived economic burden caused by hypertension was the most common factor
affecting patients' HRQoL . Female patients were more sensitive than male patients. The study
suggested that a healthy lifestyle, such as regular exercise and support from family members,
would have a positive effect on HRQoL among hypertensive patients. Health intervention
strateg ies need to be further explored and adapted to improve HRQoL for patients with
hypertension and other chronic non -communicable diseases.
In another study conducted in Sweden, the result was the same. The aim of this study was to
describe the relationship b etween hypertension and health -related quality of life (HRQL) in a
Swedish general population using the 36 -item short -form questionnaire (SF -36). The study is
based on a postal questionnaire sent to a random sample of 8,000 residents aged 20 -84 (68%
respon se rate) in Uppsala County, Sweden, in 1995. The results showed that those with
hypertension scored lower on linear regression analyzes. more than eight SF -36 fields than those
without hypertension after age, gender, sociodemographic factors, and comorbidi ty. Diabetes
and angina are associated with lower scores in most areas of SF -36. The previous myocardial
infarction was associated with lower overall health and vitality. Those with a previous stroke had
lower scores on physical function, general health, v itality and social functioning. The findings
show that hypertension is a vulnerable population that deserves special attention from providers
and healthcare systems. This is particularly important as low HRQL can be a risk factor for
subsequent cardiovascu lar events or complications.
There are many other factors besides those included in the study that affect the reported HRQL
among hypertension, including the severity of hypertension, side effects from antihypertensive
drugs and other drugs, and / or optim al drug therapy. Compatibility with other diseases relatively
common in the population, in addition to those included in this study, such as asthma, back
problems and mental health problems, can also affect the way people with high blood pressure
increase their HRQL. In addition, some studies have also observed and discussed a remarkable
"notation" among hypertensive patients, which means that knowledge of the diagnosis affects the
prevalence of reported symptoms, absence, and general well -being. A revised article on
"functional physical syndromes" lists four psychosocial factors that may affect the quality of life
associated with health among those diagnosed with hypertension.

The factors are :
1. The belief that one has a serious disease,
2. the expectation tha t one’s condition is likely to get worse,
3. the “sick -role” ,
4. the portrayal of the condition as catastrophic and disabling.
In conclusion, this study showed that people with hypertension in a general population have
lower HRQL than normal reactions, even afte r adjustment for diabetes, angina, previous heart
attack and stroke. The findings here show that comorbidity is important to consider when
evaluating HRQL among hypertensive patients. Those with hypertension represent a vulnerable
population that deserves special attention from providers and healthcare systems. This is especially
important as low HRQL can be a risk factor for subsequent cardiovascular events or complications,
which in turn can lead to a higher mortality rate.

38 REFERENCES

1. Blood Pressure Lowering Treatment Tri alists' Collaboration, Turnbull F, Neal B, et al.
Effects of different regimens to lower blood pressure on major cardiovascular events in older
and younger adults: meta -analysis of randomised trials. BMJ 2008; 336:1121.
2. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of
cardiovascular disease: meta -analysis of 147 randomised trials in the context of expectations
from prospective epidemiological studies. BMJ 2009; 338:b1665.
3. Staessen JA, Wang JG, Thijs L. Cardiovascular prevention and blood pressure reduction : a
quantitative overview updated until 1 March 2003. J Hypertens 2003; 21:1055.
4. Neaton JD, Grimm RH Jr, Prineas RJ, et al. Treatment of Mild Hypertension Study. Final
results. Treatment of Mild Hypertension Study Research Group. JAMA 1993; 270:713.
5. Materson BJ, Reda DJ, Cu shman WC, et al. Single -drug therapy for hypertension in men. A
comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs
Cooperative Study Group on Antihypertensive Agents. N Engl J Med 1993; 328:914.
6. Whelton PK, Carey RM, Aronow WS, et al. 2017
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the
Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report
of the American College of Cardiology/American Heart Association Task Force on Clinical
Practice Guidelines. Hypertension 2018; 71:e13.
7. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension Global
Hypertension Practice Guidelines. Hypertension 2020; 75:1334.
8. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of
arterial hypertension. Eur Heart J 2018; 39:3021.
9. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of
cardiovascular di sease and death: a systematic review and meta -analysis. Lancet 2016; 387:957.
10. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hyp ertension in the prevention and
management of ischemic heart disease: a scientific statement from the American Heart
Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology
and Epidemiology and Prevention. Circulation 2007; 115:2761.
11. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management
of arterial hypertension: the Task Force for the management of arterial hypertension of the
European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J
Hypertens 2013; 31:1281.
12. Xie W, Zheng F, Evangelou E, et al. Blood pressure -lowering drugs and secondary
prevention of cardiovascular disease: systematic review and meta -analysis. J Hypertens 2018;
36:1256.
13. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure -lowering treatment on
cardiovascular outcomes and mortality: 14 – effects of different classes of antihypertensive drugs
in olde r and younger patients: overview and meta -analysis. J Hypertens 2018; 36:1637.
14. Neal B, MacMahon S, Chapman N, Blood Pressure Lowering Treatment Trialists'
Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood -pressure –
lowering drugs: results of pr ospectively designed overviews of randomised trials. Blood
Pressure Lowering Treatment Trialists' Collaboration. Lancet 2000; 356:1955.
15. Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular
events in patients with coronary disease and no rmal blood pressure: the CAMELOT study: a
randomized controlled trial. JAMA 2004; 292:2217.
16. Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an
antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding

39 bend roflumethiazide as required, in the Anglo -Scandinavian Cardiac Outcomes Trial -Blood
Pressure Lowering Arm (ASCOT -BPLA): a multicentre ra ndomised controlled trial. Lancet
2005; 366:895.
17. Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, et al.
Effects of an angiotensin -converting -enzyme inhibitor, ramipril, on cardiovascular events in
high-risk patients. N Engl J Med 2000; 342:14 5.
18. Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary
Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among
patients with stable coronary artery disease: randomised, double -blind, placebo -controlled,
multicentre trial (the EUROPA study). Lancet 2003; 362:782.
19. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high
cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE
randomised trial. Lancet 2004; 363:2022.
20. Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects
of antihypertensive treatment on clinical events in the VALUE Trial. Lancet 2004; 363:2049.
21. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The
Antihypertensive and Lipid -Lowering Treatment to Prevent Heart Attack Trial. Major outcomes
in high -risk hypertensive patients randomized to angiotensin -converting enzyme inhibitor or
calcium channel blocker vs diuretic: The Antihypertensive and Lipid -Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288:2981.
22. Roush GC, Ernst ME, Kostis JB, et al. Head -to-head comparisons of hydrochlorothiazide
with ind apamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension 2015;
65:1041.
23. Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone: evidence
supporting their interchangeability. Hypertension 2004; 43:4.
24. Ernst ME, Carter BL, Goerdt CJ, et al. Comparative antihypertensive effects of
hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hyperten sion
2006; 47:352.
25. Sica DA. Chlorthalidone: has it always been the best thiazide -type diuretic? Hypertension
2006; 47:321.
26. Peterzan MA, Hardy R, Chaturv edi N, Hughes AD. Meta -analysis of dose -response
relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood
pressure, serum potassium, and urate. Hypertension 2012; 59:1104.
27. Pareek AK, Messerli FH, Chandurkar NB, et al. Efficacy of Low -Dose Ch lorthalidone and
Hydrochlorothiazide as Assessed by 24 -h Ambulatory Blood Pressure Monitoring. J Am Coll
Cardiol 2016; 67:379.
28. Carlsen J E, Køber L, Torp -Pedersen C, Johansen P. Relation between dose of
bendrofluazide, antihypertensive effect, and adverse biochemical effec ts. BMJ 1990; 300:975.
29. Flack JM, Cushman WC. Evidence for the efficacy of low -dose diuretic monotherapy. Am J
Med 1996; 101:53S.
30. Franse LV, Pahor M, Di Bari M, et al. Hypokalemia associated with diuretic use and
cardiovascular events in the Systolic Hypertension in the Elderly Program. Hypertension 2000;
35:1025.
31. Finkielman JD, Schwartz GL, Chapman AB, et al. Lack of agreement between office and
ambulatory blood pressure responses to hydrochlorothiazide. Am J Hypertens 2005; 18:398.
32. Olde Engberink RH, Frenkel WJ, van den Bogaard B, et al. Effects of thiazide -type and
thiazide -like diuretics on cardiovascular events and mortality: systematic review and meta –
analysis. Hyper tension 2015; 65:1033.

40 33. Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in
reducing cardiovascular eve nts: systematic review and network meta -analyses. Hypertension
2012; 59:1110.
34. Dorsch MP, Gillespie BW, Erickson SR, et al. Chlorthalidon e reduces cardiovascular events
compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension 2011; 57:689.
35. Hripcsak G, Suchard MA, S hea S, et al. Comparison of Cardiovascular and Safety
Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Intern Med
2020.
36. Dhalla IA, Gomes T, Yao Z, et al. Chlorthalidone versus hydrochlorothiazide for the
treatment of hypertension in older adul ts: a population -based cohort study. Ann Intern Med
2013; 158:447.
37. Messerli FH, Bangalore S. Antihypertensive efficacy of aliskiren: is hydrochlorothiazide an
appropriate benchmark? Circulation 2009; 119:371.
38. Ernst ME, Carter BL, Basile JN. All thiazide -like diuretics are not chlorthalidone: putting
the ACCOMPLISH study into perspective. J Clin Hypertens (Greenwich) 2009; 11:5.
39. A diuretic for initial treatment of hypertension. Med Lett Drugs Ther 2009; 51:9.
40. Lacourcière Y, Poirier L, Lefebvre J, et al. Antihypertensive effects of amlodipine and
hydrochlorothiazide in elderly patients with ambulatory hypertension. Am J Hypertens 1995;
8:1154.
41. Kaplan NM. The choice of thiazide diuretics: why chlorthalidone may replace
hydrochlorothiazide. Hypertension 2009; 54:951.
42. Oparil S, Cushman WC, Lederle FA. Chlorthalidone versus hydrochlorothiazide in
hypertension treatment: do we have the evidence to decide? Am J Kidney Dis 2014; 63:387.
43. Ram CV, Garrett BN, Kaplan NM. Moderate sodium restriction and various diuretics in the
treatment of hypertension. Arch Intern Med 1981; 141:1015.
44. Langford HG, Schlundt D, Levine K. Sodium restriction in hypertension. Compr Ther 1984;
10:6.
45. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or
hydrochlorothiazide for hypertension in high -risk patients. N Engl J Med 2008; 359:2417.
46. Jamerson KA, Bakris GL, Wun CC, et al. Rationale and design of the avoiding
cardiovascular events through combination therapy in patients living with systolic hypertensio n
(ACCOMPLISH) trial: the first randomized controlled trial to compare the clinical outcome
effects of first -line combination therapies in hypertension. Am J Hypertens 2004; 17:793.
47. Weber MA, Jamerson K, Bakris GL, et al. Effects of body size and hypertension treatments
on cardiovascular event rates: subanalysis of the ACCOMPLISH randomised controlled trial.
Lancet 2013; 381:537.
48. Bakris GL, Sarafidis PA, Weir MR, et al. Renal outcomes with different fixed -dose
combination therapies in patients with hypertension at high risk for cardiovascular events
(ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet
2010; 375:1173.
49. Jamerson KA, Devereux R, Bakris GL, et al. Efficacy and duration of benazepril plus
amlodipine or hydrochlorothiazide on 24-hour ambulatory systolic blood pressure control.
Hypertension 2011; 57:174.
50. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management
of hypertension in the community a statement by the American Society of Hypertension and the
International Society of Hype rtension. J Hypertens 2014; 32:3.
51. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the
JNC 7 report. JAMA 2003; 289:2560.

41 52. Appel LJ. The verdict from ALLHAT –thiazide di uretics are the preferred initial therapy for
hypertension. JAMA 2002; 288:3039.
53. Messerli FH, Bangalore S, Julius S. Risk/benefit assess ment of beta -blockers and diuretics
precludes their use for first -line therapy in hypertension. Circulation 2008; 117:2706.
54. Dickerson JE , Hingorani AD, Ashby MJ, et al. Optimisation of antihypertensive treatment
by crossover rotation of four major classes. Lancet 1999; 353:2008.
55. Williams B, Poulter NR, Brown MJ, et al. British Hypertension Society guidelines for
hypertension management 2004 (BHS -IV): summary. BMJ 2004; 3 28:634.
56. Morgan TO, Anderson AI, MacInnis RJ. ACE inhibitors, beta -blockers, calcium blockers,
and diuretics for the control of systolic hypertension. Am J Hypertens 2001; 14:241.
57. James PA, Oparil S, Carter BL, et al. 2014 evidence -based guideline for the management of
high blood pressure in adults: report from the panel members appointed to the Eighth Joint
National Committee (JNC 8). JAMA 2014; 311:507.
58. Materson BJ, Red a DJ, Preston RA, et al. Response to a second single antihypertensive
agent used as monotherapy for hypertension after failure of the initial drug. Department of
Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Arch Intern Med 1995;
155:1757.
59. Epstein M, Bakris G. Newer approaches to antihypertensive therapy. Use of fixed -dose
combination therapy. Arch Intern Med 1996; 156:1969.
60. Kaplan NM. The appropriate goals of antihypertensive therapy: neither too much nor too
little. Ann Intern Med 1992; 116:686.
61. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the
Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial
against atenolol. Lancet 2002; 359:995.
62. Lindholm LH, Ibsen H, Dahlöf B, et al. Cardiovascular morbidity and mortality in patients
with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE):
a randomised trial against atenolol. Lancet 2002; 359:1004.
63. Low-dose captopril for the treatment of mild to moderate hypertension. I. Results of a 14 –
week trial. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Arch
Intern Med 1984; 144:1947.
64. Salvetti A, Arzilli F. Chronic dose -response curve of enalapril in essential hypertensives. An
Italian multicenter study. Am J Hypertens 19 89; 2:352.
65. Saunders E, Weir MR, Kong BW, et al. A comparison of the efficacy and safety of a beta –
blocker, a calcium channel blocker, and a converting enzyme inhibitor in hypertensive blacks.
Arch Intern Med 1990; 150:1707.
66. Neutel JM, Schnaper H, Cheung DG, et al. Antihypertensive effects of beta -blockers
administered once daily: 24 -hour measurements. Am Heart J 1990; 120:166.
67. Sarafidis P, Bogojevic Z, Basta E, et al. Co mparative efficacy of two different beta -blockers
on 24 -hour blood pressure control. J Clin Hypertens (Greenwich) 2008; 10:112.
68. Meredith PA, Donnelly R, Elliott HL, et al. Prediction of the antihypertensive response to
enalapril. J Hypertens 1990; 8:1085.
69. Eguchi K, Kario K, Hoshide Y, et al. Comparison of valsartan and amlodipine on
ambulatory and morning blood pressure in hypertensive patients. Am J Hypertens 2004; 17:112.
70. Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed? A
novel assessment technique. JAMA 1989; 261:3273.
71. ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice
guidelines for the management of arterial hypertension of the European Society of Hypertension
(ESH) and the European Society of Cardiology (ESC): ESH/ESC Ta sk Force for the
Management of Arterial Hypertension. J Hypertens 2013; 31:1925.

42 72. Puttnam R, Davis BR, Pressel SL, et al. Association of 3 Different Antihypertensive
Medications With Hip and Pelvic Fracture Risk in Older Adults: Secondary Analysis of a
Randomized Clinical Trial. JAMA Intern Med 2017; 177:67.
73. Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on
mortality and reinfarction after myocardial infarction. N Engl J Med 1988; 319:385.
74. National Institute for Health and Clinical Excellence. Hypertension: management of
hypertension in adults in primary care (NICE clinical guideline update). http://www.nice.org.uk
(Acce ssed on January 21, 2009).
75. Cutler JA, Davis BR. Thiazide -type diuretics and beta -adrenergic blockers as first -line drug
treatments for hy pertension. Circulation 2008; 117:2691.
76. Wiysonge CS, Bradley HA, Volmink J, et al. Beta-blockers for hypertension. Cochrane
Database Sys t Rev 2012; 11:CD002003.
77. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the
treatment of primary hypertension? A meta -analysis. Lancet 2005; 366:1545.
78. Gupta A, Mackay J, Whitehouse A, et al. Long -term mortality after blood pressure -lowering
and lipid -lowering treatment in patients with hypertension in the Anglo -Scandinavian Cardiac
Outcomes Trial (ASCOT) Legacy study: 1 6-year follow -up results of a randomised factorial
trial. Lancet 2018; 392:1127.
79. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice?
Lancet 2004; 364:1684.
80. Medical Research Council trial of treatment of hypertension in older adults: principal
results. MRC Working Party. BMJ 1992; 304:405.
81. Khan N, McAlister FA. Re -examining the efficacy of beta -blockers for the treatment of
hypertension: a meta -analysis. CMAJ 2006; 174:1737.
82. Messerli FH, Grossman E, Goldbourt U. Are beta -blockers efficacious as first -line therapy
for hypertension in the elderly? A systematic review. JAMA 1998; 279:1903.
83. Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolo l in
patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA
2004; 292:2227.
84. Sarafidis PA, Bakris G L. Antihypertensive treatment with beta -blockers and the spectrum of
glycaemic control. QJM 2006; 99:431.
85. Davis BR, Cutler JA, Furberg C D, et al. Relationship of antihypertensive treatment
regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly
assigned to doxazosin or chlorthalidone: further analyses from the Antihypertensive and Lipid –
Lowering tr eatment to prevent Heart Attack Trial. Ann Intern Med 2002; 137:313.
86. Major cardiovascular events in hypertensive patients randomized to doxazosin vs
chlorthalidone: the antihypertensive and lipid -lowering treatment to prevent heart attack trial
(ALLHAT). ALLHAT Collaborative Research Group. JAMA 2000; 283:1967.
87. Garjón J, Saiz LC, Azparren A, et al. First -line combination therapy versus first -line
monotherapy for primary hypertension. Cochrane Database Syst Rev 2020; 2:CD010316.
88. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed -dose combinations improve
medication compliance: a meta -analysis. Am J Med 2007; 120:713.
89. Brixner DI, Jackson KC 2nd, Sheng X, et al. Assessment of adhere nce, persistence, and
costs among valsartan and hydrochlorothiazide retrospective cohorts in free -and fixed -dose
combinations. Curr Med Res Opin 2008; 24:2597.
90. Brown MJ, McInnes GT, Papst CC, et al. Aliskiren and the calcium channel blocker
amlodipine combination as an initial treatment strategy for hypertension control
(ACCELERATE): a randomised, parallel -group trial. Lancet 2011; 377:312 .
91. Egan BM, Bandyopadhyay D, Shaftman SR, et al. Initial monotherapy and combination
therapy and hypertension control the first year. Hyp ertension 2012; 59:1124.

43 92. Thom S, Poulter N, Field J, et al. Effects of a fixed -dose combination strategy on adherence
and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial.
JAMA 2013; 310:918.
93. Laurent S, Mancia G, Poulter N. Perindo pril 3.5 mg/aml odipine 2.5 mg versus renin –
angiotensin system inhibitor monotherapy as first -line treatment in hypertension: a combined
analysis. J Hypertens 2018; 36:1915.
94. Webster R, Salam A, de Silva HA, et al. Fixed Low -Dose Triple Combination
Antihypertensive Medication vs Usual Care for Blood Pressure Control in Patients With Mild to
Moderate Hypertension in Sri Lanka: A Randomized Clinical Trial. JAMA 2018; 320:566.
95. Chrysant SG, Littlejohn T 3rd, Izzo JL Jr, et al. Triple -Combination therapy with
olmesartan, amlodipine, and hydrochlorothiazide in black and non -black study participants with
hypertension: the TRINITY randomized, double -blind, 12 -week, parallel -group study. Am J
Cardiovasc Drugs 2012; 12:233.
96. Calhoun DA, Lacourcière Y, Chiang YT, Glazer RD. Triple antihypertensive therapy with
amlodipi ne, valsartan, and hydrochlorothiazide: a randomized clinical trial. Hypertension 2009;
54:32.
97. Düsing R, Waeber B, Destro M, et al. Trip le-combination therapy in the treatment of
hypertension: a review of the evidence. J Hum Hypertens 2017.
98. Chow CK, Thakkar J, Bennett A, et al. Quarter -dose quadruple combination therapy for
initial treatment of hypertension: placebo -controlled, crossover, randomised trial and systematic
review. Lancet 2017; 389:1035.
99. Gradman AH. A quarter -dose quadpill for initial treatment of hypertension. Lancet 2017;
389:989.
100. Bakris GL. Maximizing Cardiorenal Benefit in the Management of Hypertension:
Achieve Blood Pressure Goals. J Clin Hypertens (Greenwich) 1999; 1:141.
101. Pickering TG. The use of angiotensin converting enzyme inhibitors in combination
with other antihypertensive agents. Am J Hypertens 1991; 4:73S.
102. Minutolo R, Gabbai FB, Borrelli S, et al. Changing the timing of antihypertensive
therapy to reduce no cturnal blood pressure in CKD: an 8 -week uncontrolled trial. Am J Kidney
Dis 2007; 50:908.
103. Hermida RC, Calvo C, Ayala DE, et al. Admini stration time -dependent effects of
valsartan on ambulatory blood pressure in elderly hypertensive subjects. Chronobiol Int 2005;
22:755 .
104. Hermida RC, Ayala DE, Fernández JR, Calvo C. Chronotherapy improves blood
pressure control and reverts the nondipper pattern in patie nts with resistant hypertension.
Hypertension 2008; 51:69.
105. Kasiakogias A, Tsioufis C, Thomopoulos C, et al. Evening versus morning dosi ng of
antihypertensive drugs in hypertensive patients with sleep apnoea: a cross -over study. J
Hypertens 2015; 33:393.
106. Zhao P, Xu P, Wa n C, Wang Z. Evening versus morning dosing regimen drug
therapy for hypertension. Cochrane Database Syst Rev 2011; :CD004184.
107. Rossen NB , Knudsen ST, Fleischer J, et al. Targeting nocturnal hypertension in type
2 diabetes mellitus. Hypertension 2014; 64:1080.
108. Rahman M, Greene T, Phillips RA, et al. A trial of 2 strategies to reduce nocturnal
blood pressure in blacks with chronic kidney disease. Hyperten sion 2013; 61:82.
109. Zappe DH, Crikelair N, Kandra A, Palatini P. Time of administration important?
Morning versus evening dosing of valsa rtan. J Hypertens 2015; 33:385.
110. White WB, Mansoor GA, Pickering TG, et al. Differential effects of morning and
evening dosing of nisold ipine ER on circadian blood pressure and heart rate. Am J Hypertens
1999; 12:806.

44 111. Poulter NR, Savopoulos C, Anjum A, et al. Randomized Crossover Trial of the
Impact of Morning or Evening Dosing of Antihypertensive Agents on 24 -Hour Ambulatory
Blood Pressure. Hypertension 2018; 72:870.
112. Black HR, Elliott WJ, Grandits G, et al. Principal results of the Controlled Onset
Verapamil Investigation of Cardiovascular End Poin ts (CONVINCE) trial. JAMA 2003;
289:2073.
113. https ://www .medicalnewstoday .com/articles /150109
114. https ://en.wikipedia .org/wiki/SF-36
115. https ://www .ncbi.nlm.nih.gov/pmc/articles /PMC 6652141/
116. World Health Organization Global Status Report on Noncommunicable Diseases
2014. [(accessed on 28 June 2019)];2014 Available online:
http://www.who.int/nmh/publications/ncd -status -report -2014/en/
117. Qi S.F., Zhang B., Wang H.J., Yan J., Mi Y.J., Liu D.W., Tian Q.B. Prevalence of
hypertension subtypes in 2011 and the trends from 1991 to 2011 among Chinese adults. J.
Epidemiol. Community Health. 2015;70:444. doi: 10.1136/jech -2015 -206492. [ PMC free
article ] [PubMed ] [CrossRef ] [Google Scholar ]
118. Turnbull F., Neal B., N inomiy a T., Algert C., Arima H., Barzi F., Bulpitt C.,
Chalmers J., Fagard R., Gleason A., et al. Effects of different regimens to lower blood pressure
on major cardiovascular events in older and younger adults: Meta -analysis of randomised trials.
BMJ Br. Med. J . 2008;336:1121 –1123. [ PMC free article ] [PubMed ] [Google Scholar ]
119. Shambesh M.K.A., Emahbes T.M., Saleh Z.E., Elosta M.A.A., Shambesh I.M. Role
of hypertension as a major risk factor of stroke in africa; libya: Community based survey. Br. J.
Med. Med. Res. 2015;9:1 –11. doi: 10.9734/BJMMR/2015/18897. [ CrossRef ] [Google Sc holar ]
120. Nelson M., Reid C., Krum H., McNeil J. A systematic review of predictors of
maintenance of normotension after withdrawal of antihypertensive drugs. Am. J. Hypertens.
2001;14:98 –105. doi: 10.1016/S0895 -7061(00)01246 -2. [PubMed ] [CrossRef ] [Google Scholar ]
121. Goldberg H., Baniel J., Mano R., Rotlevy G., Kedar D., Yossepowitch O. Orthotopic
neobladder vs. ileal conduit urinary diversion: A long -term quality -of-life comparison. Uro logic
Oncol. 2016;34:121.e1 –121.e7. doi: 10.1016/j.urolonc.2015.10.006. [ PubMed ] [CrossRef ]
[Google Scholar ]
122. Hara I., Miyake H., Hara S., Gotoh A., Nakamura I., Okada H., Arakawa S.,
Kamidono S. Health -related quality of life after radical cystectomy for bladder cancer: A
compar ison o f ileal conduit and orthotopic bladder replacement. J. Urol. 2015;21:167. doi:
10.1016/S1078 -1439(03)00035 -8. [PubMed ] [CrossRe f] [Google Scholar ]
123. Wallander J.L., Koot H.M. Quality of life in children: A critical examination of
concepts, approaches, issues , and future directions. Clin. Psychol. Rev. 2016;45:131 –143. doi:
10.1016/j.cpr.2015.11.007. [ PubMed ] [CrossRef ] [Google Scholar ]
124. Ware J.E.J., Sherbourne C.D. The MOS 36 -item short -form health survey (SF -36). I.
Conceptual framework and item selection. Med. Care. 1992;30:473 –483. doi:
10.1097/00005650 -19920600 0-00002. [ PubMed ] [CrossRef ] [Google Scholar ]
125. Shi H., Yu H. , Bell munt J., Leow J.J., Chen X., Guo C., Yang H., Zhang X.
Comparison of health -related quality of life (HRQoL) between ileal conduit diversion and
orthotopic neobladder based on validated questionnaires: A systematic review and meta –
analysis. Qual. Life Res. 2018;27:2759 –2775. doi: 10.1007/s11136 -018-1902 -8. [PubMed ]
[CrossRef ] [Google Scholar ]

45 126. Chongqing Wikipedia. [(accessed on 28 June 2019)]; Available online:
https://en.wikipedia.org/wiki/Chongqing .
127. Liu X., Gu W., Li Z., Lei H., Li G., Huang W. Hypertension prevalence, awareness,
treatment, control, and associated factors in southwest China: An update. J. Hypertens.
2017;35:637. doi: 10.10 97/HJH .0000000000001203. [ PubMed ] [CrossRef ] [Google Scholar ]
128. https://www.ncbi.nlm.nih.gov/books/NBK470410/
129. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med1999;130:910 –
21