Literature-review

1/ Ahmed mohmmed thabet al-aghbrai

2/ Aqeel Abdulhaq

1.0 Introduction

→ Hypertension and other related complications are recognized as emerging clinical and public
health problems in Several recent reports have shown an increasing bed occupancy in hospitals
from angina, myocardial infarction, nephropathy and stroke.of affluent societies, such as CHD ,
hypertension, stroke, DM and malignant diseases,
has caused a lot of concern among health providers and policy makers. Lifestyle and dietary
factors have been incriminated worldwide as being contributory factors of some of these
diseases. The Kingdom has witnessed dramatic changes in these aspects during the last three
decades that followed the economical development in the country.

→ National Nutrition Survey of the people of the Kingdom of Saudi Arabia showed that the
prevalence of arterial hypertension (BP >/= 160/95 mmHg) among the adult population is 5.3%
and 7.3% for systolic and diastolic hypertension,¹ (Al-Nozha et al. 1998)

→ Comparison of recent national survey data on prevalence, awareness, treatment and control
of hypertension in England, - USA - Canada, and with stroke and (IHD) mortality.
Mean (SBP) was higher in England than in the USA and Canada in all age-gender groups.
Mean (DBP) was similar in the three countries before age 50 and then fell more rapidly in the
USA, being the lowest in the USA. Only 34% had a BP under 140/90 mm Hg
in England, compared with 50% in the USA and 66% in Canada.

Prehypertension and stages 1 and 2 hypertension prevalence figures were the highest in
England.
Hypertension prevalence (≥140 SBP / ≥90 DBP) was lower in Canada than in the USA and
England
Hypertension awareness was higher in the USA and Canada than in England
England also had lower levels of hypertension treatment and control (<140/90 )
Canada had the lowest stroke and IHD mortality rates,
England the highest and the rates were inversely related to the mean SBP in each country and
strongly related to the blood pressure indicators, the strongest relationship being between low
hypertension awareness and stroke mortality.³ (Hajjar I, Kotchen JM, Kotchen et al 2006)

→ The global economic burden of increased blood pressure was estimated to consume US$370
billion worldwide and 10% of healthcare expenditure.³ (Hajjar I, Kotchen JM, Kotchen et al 2006)

→ Hypertension is the leading cause of cardiovascular disease worldwide.⁴ (Ihab Hajjar et al 2006)

→ Hypertension is increasing in prevalence in KSA affecting more than one fourth of the adult
Saudi population..(Mansour M et al.. 2007 Jan.)
→ Hypertension is a premier risk factor for cardiovascular disease.⁵ ( Chythra R Rao et al 2012 )

2.0 GOALS OF TREATMENT

Primary goal
-achieve the maximum reduction in total risk of CV and renal morbidity and mortality (Grade A).
This requires two steps:
1. Reducing BP to the target level
2. Controlling all other reversible CV risk factors,
which include but not limited to: • Diabetes, • Smoking, • Dyslipidemia, • Obesity, • Alcoholism, •
Physical inactivity, • Stressful life style, and • Unhealthy diet.
The target BP should be <140/90 mm Hg for most patients with HTN.
For pt with specific co-morbidities, the target BP should be as that.

Age <80 years 140/90

Age >80 years 150/90
Diabetes 140/90 (130/80 may be warranted)
CKD without Protienuria* 140/90
CKD with Protienuria** 130/80 IHD 140/90
CHF 140/90 Old Stroke 140/90
2.1- PHARMACOLOGICAL APPROACH Saudi Hypertension
Guideline 2017
Current evidence from randomized controlled trials indicates that several classes of drugs, low-
low dose thiazides (Level Ia),
ACEI (Level Ia),
long-acting dihydropyridine CCBs (Level Ia),
ARBs (Level Ia) will lower BP and reduce the complications of HTN.

Low-dose thiazide/thiazide-like agents are still considered among the first-line agents for the
treatment of most patients with HTN. In addition, diuretics enhance the efficacy of other
antihypertensive drugs and are affordable and widely available.

(BBs) are no longer recommended as first-line agents in patients over 60 years of age with
uncomplicated HTN. Recent evidence worse outcomes in pt treated with ßBs compared to
other antihypertensive agents/classes,in addition to an associated risk of diabetes mellitus.
Patients who have been on BBs, with stable and well-controlled HTN, may continue treatment
regimen unchanged. However, if there was a compelling indication to use BB, such as CAD,
then it should be used.

2.1.0 Principles of drug treatment:

2.1.1-Hypertension without any compelling indications (Target BP

<140/90 mm Hg):

 Thiazide diuretics, ACEI, ARBS, or long-acting dihydropyridine CCBs are considered

first-line antihypertensive agents.
 Combination of first line agents (2-3 agents) should be considered if SBP ≥20 mm Hg or
DBP ≥10 mm Hg above target or in patients at high CV-R.

 Combination of ACEI and ARBs is contraindicated. ACEI and ARBs are potential
teratogens. Avoid use in pregnancy,.

 Isolated systolic hypertension without other compelling indications (target BP

 for age <80 is <140/90 mm Hg;

 for age ≥80 the target systolic BP is <150 mm Hg):

  Thiazide/thiazide-like diuretics, ARBs, or CCBs. For isolated diastolic HTN follow the
same treatment isolated systolic HT in addition to ACEIs.

2.1.2. Diabetes Mellitus (Target BP <140/90; however, <130/80 may be

warranted)
A- DM with microalbuminuria*, renal disease, CVD, or additional CV risk factors:
ACEi or ARBs. Addition of long-acting dihydropyridine CCBs is preferred over
thiazide/thiazidelike diuretics.
loop diuretic could be considered in hypertensive CKD patients with extracellular fluid overload.
B- Diabetes mellitus without microalbuminuria or other comorbidities:
ACEi or ARBs, long-acting dihydropyridine CCBs or thiazide/thiazide-like diuretics.
Combination of ACEI with CCB is preferred over combination with thiazide/thiazide-like diuretic.
2.1.3. Cardiovascular Disease (Target <140/90 mm Hg):

a- Coronary artery disease: ACEi or ARBs; ßBs and LA-DHP-CCBs for patients with stable
angina. When combination therapy is being used for high risk patients,
ACEi with DHP CCB is preferred. Avoid short-acting nifedipine.
Combination of an ACEI with an ARB is contraindicated.
Exercise caution when lowering SBP to target if DBP is ≤60 mm Hg.

b- Recent MI : ßBs and ACEi (ARBs if ACE inhibitor intolerant).

LA CCBs if ßB contraindicated or not effective.
NDHP CCBs should not be used with concomitant heart failure.

c- Heart failure: ACEi (ARBs if ACE inhibitor intolerant) and BBs.

Aldosterone antagonists may be added for patients with recent CV hospitalization,
-acute MI ,
-elevated Brain natriuretic peptide (BNP),
-N-terminal pro BNP level or NYHA Class II to IV symptoms.
Secondline agents may include hydralazine/isosorbide dinitrate combination if ACE inhibitor
and ARB contraindicated or not tolerated.
Thiazide/thiazide-like or loop diuretics are recommended as additive therapy. DHP CCB can
also be used.

d- Left ventricular hypertrophy: ACEI, ARB, LA CCB, or thiazide /thiazidelike diuretics.

Combination with other agents may be used.
Hydralazine and minoxidil should not be used as they can increase left ventricular hypertrophy.
e- Past stroke or TIA: ACEI and a thiazide /thiazide-like diuretic combination.
Combination with other agents may be used. Treatment of hypertension should not be routinely
undertaken in acute stroke unless extreme BP elevation is observed.

2.1.4. Non-diabetic chronic kidney disease—Target <140/90 mm Hg:

 a- Nondiabetic chronic kidney disease with proteinuria: ACEI (ARBs if ACEI intolerant).
Diuretics as additive therapy. Combinations with other agents may be used. Carefully monitor
renal function and potassium for those on an ACEI or ARB. Combinations of an ACEI and ARB
are not recommended.
b- Renovascular disease: Does not affect initial treatment recommendations. Combinations with
other agents may be used. Avoid ACEI or ARBs if bilateral renal artery stenosis or unilateral
disease with solitary kidney.
2.1.5. To achieve optimal blood pressure targets: •
Multiple drugs are often required to reach target levels, especially in patients with type 2
diabetes • Replace multiple antihypertensive agents with fixed dose combination therapy when
available • Low doses of multiple drugs may be more effective and better tolerated than higher
doses of fewer drugs • Reassess patients with uncontrolled blood pressure at least every 2
months • The most preferable combinations are ACEIs or ARBs plus LA-DHP-CCBs and/or
thiazide diuretics as required

3.0 Diuretics as first line treatment for hypertension

Most of the available evidence justifying treatment of patients with elevated BP used a thiazide
as the first‐line drug.
First‐line low‐dose thiazides were more effective than first‐line high‐dose thiazides and first‐line
beta‐blockers.
The treatment effect for first‐line ACE inhibitors was similar to low‐dose thiazides but less
robust, and ACE inhibitors are more expensive than thiazides.

-Primary prevention
(mild to moderate hypertension)
There were five first‐line high‐dose thiazide trials in this category,
average baseline SBP of 160 mmHg.
-Secondary prevention:
For the three secondary prevention trials using thiazides, and the one secondary trial using an
ACE inhibitor,
average baseline BP was approximately 155/94 mmHg.
demonstrates the benefits of starting with a low‐dose thiazide as first‐line therapy for elevated
BP
The pooled data showed a reduction in total mortality when using a thiazide as the first‐line
choice, and suggested that as first‐line therapy, low‐dose thiazide, reduced coronary heart
disease events, whereas high‐dose thiazide did not.18 (Wise J. 2009 )
3.1 Thiazide-type diuretics and BB as first-line drug
treatments for hypertension

The British Medical Research Council (BMRC) trial of treatment of mild hypertension was the
first clinical events trial with a β-blocker–based arm (propanolol) in addition to a thiazide arm
(bendrofluazide).6 Compared with placebo, only the thiazide significantly reduced stroke, likely
as a result of the greater BP reduction than with the β-blocker. Both active treatment arms
showed reductions in major cardiovascular events. Along with trials that found improved survival
in post-MI patients with β-blockers, this experience was sufficient for guidelines to begin
recommending thiazides and β-blockers as relatively equivalent alternatives for initiating
treatment.19 (Cutler JA, Davis BR et al 2008 )

3.2 Combination Therapy for the Treatment of Hypertension /

Sevikar®: Combination Therapy for the Treatment of
Hypertension
In the United States only 36.8% of hypertensive patients achieve the goal of <140/90 mmHg.
Poor adherence to antihypertensive medication regimens contributes to the practice-outcome
gap. In most hypertensive patients it is difficult or impossible to control BP with one drug, thus
current guidelines have recommended the use of combination therapy as first-line treatment, or
early in the management of hypertension. Blocking two or more BP regulatory systems provides
a more effective and more physiologic reduction in BP. 21 (Pimenta E. et al 2009 )
Fixed-dose combinations offer many advantages over free-drug combinations, such as
convenience of use, fewer adverse events, and greater antihypertensive potency. Similar to
other combinations, fixed-dose combination tab containing the dihydropyridine CCB amlodipine
and the angiotensin receptor blocker olmesartan bring together two distinct and complementary
mechanisms of action, resulting in improved BP control and potential for improved target organ
protection relative to either class of agent alone.21(Pimenta E. et al 2009 )

3.3 Choice of Combination Therapy

According to the JNC 7 guidelines, the use of a thiazide or thiazide-like diuretic is first-line therapy in most
hypertensive patients.6 If the patient has a compelling indication, then treatment decisions are relatively
straightforward—
patients with DM should receive an ACEi
or post-MI or (CHF) should get a BB ; and so on. Sometimes, however, the decision is not so clear, and
careful consideration is required when recommending combination therapy. TABLE 1 provides a list of
FDA-approved combination products.

(RAAS-i)+ CCB
ACEi , ARBs, and (DRIs) , inhibit the (RAAS). Dihydropyridine (CCBs), such as amlodipine, block the
influx of calcium into coronary and systemic arteries, allowing for VD Together, a RAAS inhibitor and a
CCB lower BP additively. Moreover, the addition of an ACEi to a CCB alleviates peripheral edema
associated with the CCB,11
and thus may improve compliance for PT who are bothered by this side effect.

The use of combination therapy by a single-dosage form via rational fixed-dose formulations or by
selection of complementary drug classes in the management of hypertension allows PT to achieve their
BP goal quickly,
Improves ADR , and is supported by prospective data.22 & 23 (Sever PS,et al 2011 ) (Rubio-Guerra A F, et al 2011)

4.0 STUDY 1
The Prevalence of Hypertension in Different Geographical Regions of Saudi Arabia
.this study reveals that in adult Saudis there are differences in the prevalence of hypertension in
relation to gender, age and geographical regions. The prevalence increases with age, and it
is highest among the 40-75-year age group.
The females higher prevalence than males in that age group.1 (Al-Nozha et al. 1998)

5.0- STUDY 2

Hypertension prevalence, awareness, treatment and control in national surveys from England,
the USA and Canada, and correlation with stroke and ischaemic heart disease mortality: a
cross-sectional study
this study found marked differences in hypertension prevalence, awareness, treatment and
control rates in England, the USA and Canada. Canada has the lowest prevalence of
hypertension at 19% followed by England and the USA at about 30% each. A previous study
based on earlier cycles of these surveys also found little difference in the prevalence of
hypertension between England and the USA.The main determinants of hypertension are known.
These include poor dietary habits, excess sodium intake, physical inactivity, obesity, excess
alcohol consumption, as well as age, gender, race and sociodemographic factors.2 (Joffres M,et al
2013)

6.0 study 3
Hypertension: trends in prevalence, incidence, and control
Prior to 1990, population data suggest that hypertension prevalence was decreasing; however,
recent data suggest that it is again on the rise. In 1999-2002, 28.6% of the U.S. population had
hypertension. Hypertension prevalence has also been increasing in other countries, and an
estimated 972 million people in the world are suffering from this problem. Incidence rates of
hypertension range between 3% and 18%, depending on the age, gender, ethnicity, and body
size of the population studied. Despite advances in hypertension treatment, control rates
continue to be suboptimal. Only about one third of all hypertensives are controlled in the United
States. Programs that improve hypertension control rates and prevent hypertension are urgently
needed. 3 (Hajjar I, et al 2006 )

7.0 STUDY 4
High blood pressure prevalence and significant correlates: a quantitative analysis from coastal
karnataka, India

The prevalence of hypertension was 43.3%, with the prevalence being more among males
(51.6%) as compared to females (38.9%). Of the total prevalence 23.1% (287) were known
cases, and 20.2% (250) were newly detected cases. Based on the seventh report of the Joint
National Committee (JNC VII) on high blood pressure, prehypertension was noted among
38.7%. Advancing age, male gender, current diabetic status, central obesity, overweight and
obesity as defined by body mass index, and family history of hypertension were identified as
significant correlates for hypertension by multivariate logistic regression.4 (Rao C R,et al 2013 )

8.0 STUDY 5

Evaluation and treatment of severe asymptomatic hypertension

Poorly controlled hypertension is a common finding in the outpatient setting. When patients
present with severely elevated blood pressure (i.e., systolic blood pressure of 180 mm Hg or
greater, or diastolic blood pressure of 110 mm Hg or greater), physicians need to differentiate
hypertensive emergency from severely elevated blood pressure without signs or symptoms of
end-organ damage (severe asymptomatic hypertension). Most patients who are asymptomatic
but have poorly controlled hypertension do not have acute end-organ damage and, therefore,
do not require immediate workup or treatment (within 24 hours). However, physicians should
confirm blood pressure readings and appropriately classify the hypertensive state. A
cardiovascular risk profile is important in guiding the treatment of severe asymptomatic
hypertension; higher risk patients may benefit from more urgent and aggressive evaluation and
treatment. Oral agents may be initiated before discharge, but intravenous medications and fast-
acting oral agents should be reserved for true hypertensive emergencies. High blood pressure
should be treated gradually. Appropriate, repeated follow-up over weeks to months is needed to
reach desired blood pressure goals.5 (Kessler CS,et al 2010 )

9.0 STUDY 6

-Poor hypertension control: let's stop blaming the patients

Physician behavior--not patient noncompliance--is the major cause of poor hypertension control
in the United States, many studies show. Hypertension control is unlikely to improve unless
physicians become more aggressive in treating mildly elevated systolic blood pressure.6 (Hyman
DJ et al 2002)

10-STUDY 7
Impact of poorly controlled hypertension on healthcare resource utilization and cost
Study design: A retrospective database study of managed care patients in New Mexico from
January 1, 1996, to December 31, 1997.
Poor control of hypertension is associated with higher drug costs and more physician visits.
Aggressive treatment might help reduce managed care costs and resource utilization.
7 (Paramore LC, et al 2001)

11-STUDY 8

Hypertension in Saudi Arabia

Hypertension is increasing in prevalence in KSA affecting more than one fourth of the adult
Saudi population. We recommend aggressive management of hypertension as well as
screening of adults for hypertension early to prevent its damaging consequences if left
untreated. Public health awareness of simple measures, such as low salt diet, exercise, and
avoiding obesity, to maintain normal arterial blood pressure need to be implemented by health
care providers. 8 (Al-Nozha MM, 2007)
12-STUDY 9
Hypertension in Asir region, southwestern Saudi Arabia: an epidemiologic study
A population study was carried out to determine the prevalence of hypertension among Saudis
at primary health care level in the Asir region, Southwestern Saudi Arabia. All primary health
care centers (PHCCs) were visited (238 PHCCs). Data were collected in relation to the updated
Saudi population census for 1991. Chronic case registries were revised to identify existing
cases of hypertension by age and sex till the end of 1991. Results showed that the prevalence
of hypertension amounted to 2.4% among Saudis aged 45 years and more. Males and females
aged 45 years and more living at high altitude had a significantly higher risk of developing
hypertension (p < 0.05) compared to those living at sea level.9 (Mahfouz AA,1993 )

13-STUDY 10
Prevalence of physical inactivity in Saudi Arabia: a brief review
Major lifestyle changes in recent years in Saudi Arabia may be leading to physical inactivity and
a low level of physical fitness. This paper reviews the current literature about physical inactivity
in the Saudi Arabian population and discusses its implications for health. Available data from a
small number of studies suggests a high prevalence (43.3%-99.5%) of physical inactivity among
Saudi children and adults alike. Furthermore, the proportion of Saudi children and adults who
are at risk due to inactivity is much higher than for any other coronary heart disease risk factor.
It is recommended that a national policy encouraging activity in daily life be established and
more studies are carried out to address physical activity patterns with representative samples of
the Saudi Arabian population.10 (Al-Hazzaa HM. 2004 )

14-STUDY 11
Risk factors of coronary artery disease in different regions of Saudi Arabia

A national nutrition survey was carried out in Saudi Arabia between 1989 and 1994. One
objective was to investigate the prevalence of well established atherogenic risk factors among
adults 18 years and older, namely obesity, hypercholesterolaemia, hypertriglyceridaemia,
diabetes mellitus and high systolic and diastolic blood pressure. Obesity prevalence was
positively correlated with all five coronary artery disease risk factors investigated. Variation
among regions in relation to the prevalence of these risk factors was observed. Saudi Arabia's
ecology has resulted in variation in the lifestyle and food consumption patterns of the people of
the different regions, which might be a major underlying cause of the variation and high
prevalence of coronary artery disease risk factors.11(Osman AK et al 2000 )

15-STUDY 12
Prevalence, Awareness, Treatment, and Control of Hypertension among Saudi Adult
Population: A National Survey
This cross-sectional study aimed at estimating prevalence, awareness, treatment, control, and
predictors of hypertension among Saudi adult population. Multistage stratified sampling was
used to select 4758 adult participants. Three blood pressure measurements using an automatic
sphygmomanometer, sociodemographics, and antihypertensive modalities were obtained. The
overall prevalence of hypertension was 25.5%. Only 44.7% of hypertensives were aware, 71.8%
of them received pharmacotherapy, and only 37.0% were controlled. Awareness was
significantly associated with gender, age, geographical location, occupation, and comorbidity.
Applying drug treatment was significantly more among older patients, but control was
significantly higher among younger patients and patients with higher level of physical activity.
Significant predictors of hypertension included male gender, urbanization, low education, low
physical activity, obesity, diabetes, and hypercholesterolemia. In conclusion prevalence is high,
but awareness, treatment, and control levels are low indicating a need to develop a national
program for prevention, early detection, and control of hypertension.12(Saeed AA, et al 2011 )

16-STUDY 13
Gender differences in the regulation of blood pressure
Men are at greater risk for cardiovascular and renal disease than are age-matched,
premenopausal women. Recent studies using the technique of 24-hour ambulatory blood
pressure monitoring have shown that blood pressure is higher in men than in women at similar
ages. After menopause, however, blood pressure increases in women to levels even higher
than in men. Hormone replacement therapy in most cases does not significantly reduce blood
pressure in postmenopausal women, suggesting that the loss of estrogens may not be the only
component involved in the higher blood pressure in women after menopause. In contrast,
androgens may decrease only slightly, if at all, in postmenopausal women. In this review the
possible mechanisms by which androgens may increase blood pressure are discussed.
Findings in animal studies show that there is a blunting of the pressure-natriuresis relationship
in male spontaneously hypertensive rats and in ovariectomized female spontaneously
hypertensive rats treated chronically with testosterone. The key factor in controlling the
pressure-natriuresis relationship is the renin-angiotensin system (RAS). The possibility that
androgens increase blood pressure via the RAS is explored, and the possibility that the RAS
also promotes oxidative stress leading to production of vasoconstrictor substances and
reduction in nitric oxide availability is proposed.13(Reckelhoff JF 2001)

17-STUDY 14
The progression from hypertension to congestive heart failure

Multivariable analyses revealed that hypertension had a high population-attributable risk for
CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects,
myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were
predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive
CHF was bleak; only 24% of men and 31% of women survived 5 years
Hypertension was the most common risk factor for CHF, and it contributed a large proportion of
heart failure cases in this population-based sample. Preventive strategies directed toward
earlier and more aggressive blood pressure control are likely to offer the greatest promise for
reducing the incidence of CHF and its associated mortality.15 (Levy D, et al 1996 )

18-STUDY 15
Hypertension and hyperlipidemia]

Hypertension and hyperlipidemia are well-established and partially overlapping risk factors for
cardiovascular disease. Analyses of cardiovascular morbidity in relationship to changes in blood
pressure and in serum cholesterol levels have shown that combined reduction of both risk
factors are important to achieve a reduction in morbidity. Statins have been shown to be
effective in preventing both coronary and cerebrovascular events in both hypertensive and
normotensive cases. Consequently, most recent guidelines recommend that statin treatment be
considered in hypertensive patients aged less than 80 years who have an estimated risk of
cardiovascular death of 5% or more based on the Systematic Coronary Risk Evaluation
(SCORE) model.16 (Hansen HS, et al 2009 )

19-STUDY 16
Death rates from ischemic heart disease in women with a history of hypertension in pregnancy

There is an indication of increased death rates among women with a history of hypertension in
pregnancy, where ischemic heart disease may be more common than in the general population.
17(Jónsdóttir LS, et al 1995 )
REFERENCES

1-Al-Nozha MM, Osman AK. The prevalence of hypertension in different Geographical regions
of Saudi Arabia. Ann Saudi Med 1998;18(5):401-7.

2-Joffres M, Falaschetti E, Gillespie C. Hypertension prevalence,

awareness, treatment and control in national surveys from England, the
USA and Canada, and correlation with stroke and ischaemic heart
disease mortality: a cross-sectional study. BMJ Open 2013; 3:e003423.
doi: 10.1136/bmjopen-2013-003423.

3- Hajjar I, Kotchen JM, Kotchen TA. Hypertension: trends in prevalence,

incidence, and control. Annu Rev Public Health 2006;27:465-90.

4-Rao C R, Kamath V G, Shetty A, Kamath A. High blood pressure

prevalence and significant correlates. A quantitative analysis from
coastal Karnataka, India. ISRN Preventive Medicine. Volume 2013,

5-Kessler CS, Joudeh Y. Evaluation and treatment of severe

asymptomatic hypertension. Am Fam Physician 2010;81(4):470-476.
7. Paramore LC, Halpern MT, Lapuerta P. Impact of poorly controlled
hypertension on healthcare resource utilization and cost. Am J Manag
Care 2001;7(4):389-98.

8. Al-Nozha MM, Abdullah M, Arafah MR. Hypertension in Saudi Arabia.

Saudi Med J 2007;28(1):77-84.

9. Mahfouz AA, al-Erian RA. Hypertension in Asia region, southwestern

Saudi Arabia: an epidemiologic study. Southeast Asian J Trop Med
Public Health 1993;24(2):284-6.

10. Al-Hazzaa HM. Prevalence of physical inactivity in Saudi Arabia: a brief

review. East Mediterr Health J 2004;10(4-5):663-70.

11. Osman AK, Al-Nozha MM. Risk factors of coronary artery disease in
different regions of Saudi Arabia. East Mediterr Health J 2000;6(2-
3):465-74.
12. Saeed AA, Al-Hamdan NA, Bahnassy AA. Prevalence Awareness,
Treatment, and Control of Hypertension among Saudi Adult Population:
A National Survey. Int J Hypertens 2011; 2011:174135. doi:
10.4061/2011/174135. Epub 2011 Sep 6.

13. Reckelhoff JF. Gender differences in the regulation of blood pressure.

Hypertension 2001;37(5):1199-1208.

15 . Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression
from hypertension to congestive heart failure. JAMA
1996;275(20):1557-1562.

16. Hansen HS, Larsen ML. Hypertension and hyperlipidemia. Ugeskr

Laeger 2009; 171(24):2028-2030.

17. Jónsdóttir LS, Arngrímsson R, Geirsson RT, Sigvaldason H, Sigfússon

N. Death rates from ischemic heart disease in women with a history of
hypertension in pregnancy. Acta Obstet Gynecol Scand
1995;74(10):772-6.
18. Wise J. Researchers stand by diuretics as first line treatment for
hypertension BMJ 2009; 339 doi: http://dx.doi.org/10.1136/bmj.b5119.

19. Cutler JA, Davis BR. Thiazide-type diuretics and beta-adrenergic

blockers as first-line drug treatments for hypertension. Circulation
2008;117(20):2691-2704.

21. Pimenta E. Single Sevikar ®: Combination Therapy for the Treament of Hypertension.
Clinical Medicine Therapeutics 2009;1:703-709

22. Sever PS, Messerli FH. Hypertension management 2011: optimal

combination therapy. European Heart Journal doi:10.1093/
eurheartj/ehr177

23. Rubio-Guerra A F, Serna DC, Barrera CIE, Ramos-Brizuela LM. Current

concepts in combination therapy for the treatment of hypertension:
combined calcium channel blockers and RAAS inhibitors. Integrated
Blood Pressure Control 2009;2:55-62
References
Saudi Hypertension Guidelines 2018

24-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

25. 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.

26. 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 Hypertension. J Hypertens 2014; 32:3.

27. Leung, Alexander A. et al. Hypertension Canada’s 2016 Canadian hypertension education
program guidelines for blood pressure measurement, diagnosis, assessment of risk, prevention,
and treatment of hypertension. Can J Cardiol. 2016; 32:569-88.

28. SPRINT Research Group. A randomized trial of intensive versus standard blood pressure
control. N Engl J Med. 2015;2015: 2103-16.

29. American Diabetes Association. Standards of Medical Care in Diabetes-2017. Diabetes

Care 2017; 40: S1-135.

30. The National Guidelines for Management of Cardiometabolic Risk Factors in Primary
Health Care. Saudi MOH, Riyadh 2014.

31. Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, Cloutier
L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P. Hypertension Canada’s 2016 Canadian
Hypertension Education Program Guidelines for blood pressure measurement, diagnosis,
assessment of risk, prevention, and treatment of hypertension. Canadian Journal of Cardiology.
2016 May 31;32(5):569-88.

32. New Zealand Guidelines Group. New Zealand Primary Care Handbook 2012. 3rd ed.
Wellington: New Zealand Guidelines Group; 2012.

33. National Heart Foundation of Australia. Guideline for the diagnosis and management of
hypertension in adults, 2016.