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Latin American guidelines on hypertensionM
Ramiro A. Sanchez, Miryam Ayala, Hugo Baglivo, Carlos Velazquez,
Guillermo Burlando, Oswaldo Kohlmann, Jorge Jimenez,
Patricio López Jaramillo, Ayrton Brandao, Gloria Valdes, Luis Alcocer,
Mario Bendersky, Agustı́n José Ramirez, Alberto Zanchetti,
on behalf of the Latin America Expert Group
Hypertension is a highly prevalent cardiovascular risk factor
in the world and particularly overwhelming in low and
middle-income countries. Recent reports from the WHO and
the World Bank highlight the importance of chronic
diseases such as hypertension as an obstacle to the
achievement of good health status. It must be added that for
most low and middle-income countries, deficient strategies
of primary healthcare are the major obstacles for blood
pressure control. Furthermore, the epidemiology of
hypertension and related diseases, healthcare resources
and priorities, the socioeconomic status of the population
vary considerably in different countries and in different
regions of individual countries. Considering the low rates of
blood pressure control achieved in Latin America and the
benefits that can be expected from an improved control, it
was decided to invite specialists from different Latin
American countries to analyze the regional situation and to
provide a consensus document on detection, evaluation and
treatment of hypertension that may prove to be cost-utility
adequate. The recommendations here included are the
result of preparatory documents by invited experts and a
subsequent very active debate by different discussion
panels, held during a 2-day sessions in Asuncion, Paraguay,
in May 2008. Finally, in order to improve clinical practice, the
Introduction
Hypertension is a highly prevalent cardiovascular risk
factor in the world and particularly overwhelming in low
and middle-income countries. Recent reports from the
WHO [1] and the World Bank [2] highlight the importance
of chronic diseases such as hypertension as an obstacle to
the achievement of good health status. It must be added
that for most low and middle-income countries, deficient
strategies of primary healthcare are the major obstacles for
blood pressure control [3]. Furthermore, the epidemiology
of hypertension and related diseases, healthcare resources
and priorities, the socioeconomic status of the population
vary considerably in different countries and in different
regions of individual countries. Because of this, the documents from the World Health Organization-International
Society of Hypertension [4] and European Society of
Hypertension-European Society of Cardiology [5] encouEndorsed by the Latin America Society of Hypertension.
0263-6352 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
publication of the guidelines should be followed by
implementation of effective interventions capable of
overcoming barriers (cognitive, behavioral and affective)
preventing attitude changes in both physicians and patients.
J Hypertens 27:905–922 Q 2009 Wolters Kluwer Health |
Lippincott Williams & Wilkins.
Journal of Hypertension 2009, 27:905–922
Keywords: diabetes, diagnosis, epidemiology, hypertension, special
populations, treatment
Abbreviations: ABPM, ambulatory blood pressure monitoring; ACEI,
angiotensin-converting enzyme inhibitor; ADMA, asymmetric
dimethylarginine; ARB, angiotensin receptor blocker; BP, blood pressure;
CHD, coronary heart disease; CVD, cardiovascular disease; DALYs,
disability-adjusted life years; DBP, diastolic blood pressure; DM, diabetes
mellitus; ESRD, end-stage renal disease; GFR, glomerular filtration rate;
HbA1c, glycosylated hemaglobin A1c; HDL, high-density lipoprotein; IMT,
intima–media thickness; LDL, low-density lipoprotein; MS, metabolic
syndrome; OGTT, oral glucose tolerance test; PKC, proteinkinase C; ROS,
reactive oxygen species; SBP, systolic blood pressure; TIA, transient
ischemic attack; TOD, target organ damage
Correspondence to Professor Ramiro Sanchez, Sección Hipertensión Arterial y
Unidad Metabólica, Fundación Favaloro. Belgrano 1782 P: 4, Buenos Aires
(1093) Argentina
Tel/fax: +54 11 4378 1337; e-mail: [email protected]
Received 6 February 2009 Accepted 19 February 2009
rage the development of local guidelines taking into
account the above-mentioned conditions.
Considering the low rates of blood pressure control
achieved in Latin America and the benefits that can be
expected from an improved control, it was decided to
invite specialists from different Latin American countries
to analyze the regional situation and to provide a consensus document on detection, evaluation and treatment
of hypertension that may prove to be cost-utility adequate. That is why members of Hypertension, Cardiology
and Diabetes Societies from Latin American countries
met to discuss these new recommendations for prevention and management of hypertension and related diseases, and prepare a consensus document in which
special attention has been paid to the metabolic syndrome in order to alert physicians about this higher-risk
condition, particularly prominent in Latin America but
usually underestimated and undertreated. The resulting
DOI:10.1097/HJH.0b013e32832aa6d2
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
906 Journal of Hypertension
2009, Vol 27 No 5
document is designed to serve as a guide to physicians
assisting patients with hypertension and comorbidities.
The recommendations here included are the result of
preparatory documents by invited experts and a subsequent very active debate by different discussion panels,
held during a 2-day session in Asuncion, Paraguay, in May
2008. After a formal presentation of the final conclusions
reached by each discussion panel, and their approval by
all participants, this final document was prepared by an
appointed Writing Committee. In order to improve
clinical practice, the publication of the guidelines should
be followed by implementation of effective interventions
capable of overcoming barriers (cognitive, behavioral and
affective) preventing attitude changes in both physicians
and patients.
Epidemiology, health economics, education
Prevalence
Diabetes mellitus and hypertension are frequently
associated, thereby increasing their negative impact on
the cardiovascular system [6,7]. More than 80% of the
attributed world burden of these diseases is in low and
middle-income countries. In Latin America, 13% of
deaths and 5.1% disability-adjusted life years (DALYs)
can be attributed to hypertension [1]. The age-adjusted
prevalence of hypertension in the adult general population in different countries of Latin America (national
surveys or systematic randomized samplings) ranges from
26 to 42% [6–9]. In diabetic populations, the prevalence
of hypertension is 1.5–3-fold higher that in nondiabetic
populations in the same age segment [6]. In type 2
diabetes, hypertension may already be present at the
time of diagnosis or may even precede overt hyperglycemia [6].
The following tables show the prevalence, awareness,
treatment and control of hypertension, together with
cardiovascular mortality attributed to hypertension
(Table 1), and the prevalence of the major risk factors
associated with hypertension (Table 2) in various Latin
American countries.
Table 1
Prevalence of risk factors associated with hypertension
Table 2
Overweight
(%)
Sedentary
life (%)
Smoking
(%)
Dyslipidemia
(%)
19,7
13
23.2
47
41
31
54
–
59.7
25.1
nd
nd
90.8
61
34.9
30.8
38
–
64.3
–
38.6
20
42
23
24.8
36.6
34
–
15.7
30
18,7
13
35.4
61
–
36.5
–
10
18
5.7
Argentina
Brazil
Chile
Colombia
Ecuador
México
Paraguay
Perú
Uruguay
Venezuela
nd, Not determined.
Medical economics
Hypertension imposes a huge worldwide economic and
social burden because of the associated comorbidities and
chronic complications that impair survival and quality of
life. Thus, a recent analysis of an international data bank
[1] has shown that a very substantial proportion of cardiovascular disease is attributable to high blood pressure.
The global expenditure on antihypertensive treatment is
about 50 billion dollars each year [10], more than 90% of
which is spent in high-income countries, whereas middle
and low-income countries, having a five times greater
burden of disease than the corresponding high-income
countries, have only access to less than 10% of the global
treatment resources. Hush cost-effectiveness, costbenefit and cost-utility of the treatment of hypertension
in the general population are strongly influenced by the
presence of comorbidities and complications [11–13].
Considering the above-mentioned data, the proposal
for an intensive treatment of hypertension can be
expected to reduce costs and improve survival and quality
of life.
Education
In the context of the large and growing disease burden,
strategies to improve population health require consistent and comprehensive management of the major risk
factors contributing to premature mortality and disability.
Arterial hypertension, sex and cardiovascular mortality
Countries
Hypertension
prevalence (%)
Hypertension
awareness (%)
Treated
hypertension (%)
Controlled
hypertension (%)
Argentina
Brazil
Chile
Colombia
Ecuador
México
Paraguay
Peru
Uruguay
Venezuela
28.1
25–35
33.7
23
28.7
30.5
35
24
33
33
54
50.8
59.8
41
41
56,4
31
39
68
55
42
40.5
36.3
46
23
23
27
14.7
48
30
18
10.2
11.8
15
6.7
19.2
7
14
11
12
, (%)
< (%)
–
–
30.8
36.7
27.5
26.3
30.9
34.2
56.9
43.1
Cardiovascular
mortality (%)
23.5
27.5
28.4
28
28
–
28
–
29.5
20.6
Columns 2, 3, and 4 percentage values refer to the corresponding hypertensive population (column 1).
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Latin American guidelines on hypertension Sanchez et al. 907
Education should be considered an important tool for
improving hypertension treatment strategies. To this
scope, the recently published WHO/ISH guidelines on
preventive cardiology are greatly helping general practitioners in the management of global risk strategies, by
the use of pocket guidelines that can be easily obtained in
different languages (http://www.who.int/cardiovascular_
diseases/guidelines/Pocket_GL_information/en/index.
html). Systematic education of hypertensive patients is
strongly recommended. Such educational effort should
involve patients in their own environment, and provide
training in patient education to health teams. Some
educational programs for Latin America have been
proposed [14]. The promotion of education in the general
population and, particularly, among high-risk patients, is
greatly advisable. Formal education for children and
adolescents should include information about healthy
lifestyles.
pressure is markedly elevated (mean arterial pressure
50% or more above average) life expectancy is reduced
by 30–40%, unless hypertension is appropriately treated
[15].
Blood pressure classification
After considering the classifications proposed by the
Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure [16], the 2007 European Guidelines
for the Management of Hypertension [5], and the
previous Latin American Consensus on Arterial Hypertension [17], it was decided, as shown in Table 3, to
maintain the concept that hypertension is diagnosed
when blood pressure values are at least 140/90 mmHg.
Above this value, hypertension can be subdivided in
grade 1, 2 or 3. This classification also applies to isolated
systolic hypertension, which must be diagnosed and
treated especially in older patients.
The following strategies are strongly recommended:
(1) Community educational programs,
(2) Operational strategies to promote lifestyle changes
especially in children, teen-agers and young adults,
(3) Educational programs for practitioners and health
teams (nurses, nutritionists, etc.),
(4) Hypertension early detection programs, and
(5) Guidelines for optimal control of blood pressure
values.
Clinical characteristics
Definition
Established hypertension is a medical condition implying
a higher risk for cardiovascular events and impairment of
different organ functions in which the blood pressure is
chronically elevated above values considered in the
optimal or normal range. Hypertension is frequently
associated with comorbidities such as diabetes mellitus,
coronary heart disease (CHD), chronic heart failure,
stroke, transient ischemic attack (TIA), peripheral vascular disease, chronic renal impairment. Persistent hypertension is considered one of the risk factors for stroke,
heart attack, heart failure and arterial aneurysm, and is
one of the leading causes of chronic renal failure and
dialysis. Even moderate elevation of arterial blood pressure leads to shortened life expectancy. When blood
Table 3
Classification of blood pressure
Blood pressure
Optimal
Normal
High-normal
Hypertension
Grade 1
Grade 2
Grade 3
Isolated systolic hypertension
<120/80 mmHg
120/80–129/84 mmHg
130/85–139/89 mmHg
140–159/90–99 mmHg
160–179/100–109 mmHg
180/110 mmHg
140/<90 mmHg
Considering that blood pressure is a continuous variable,
and that higher are the blood pressure values higher is
cardiovascular risk [18,19], it was decided that the
patients with blood pressure values between 120/80
and 129/84 mmHg can be considered as normal blood
pressure, whereas those with values between 130/85 and
139/89 mmHg as high-normal blood pressure. Blood pressure values lower than 120/80 mmHg are considered as
optimal values. However, it should be emphasized that
high-normal and normal blood pressure are of a higher
risk than optimal blood pressure despite of being in the
normal range. By this way, blood pressure values lower
than 120/80 mmHg are considered as optimal values.
Arterial hypertension is actually classified as: primary,
essential or idiopathic when blood pressure is consistently higher than normal with no known underlying
cause. It represents 85–90% of all cases of hypertension.
Hypertension is defined as secondary when blood pressure is elevated as a result from an underlying, identifiable, often correctable cause (the remaining 10–15% of
the total hypertensive patients).
Resistant or refractory to treatment hypertension
Resistant or refractory to treatment hypertension is when
blood pressure remains above target values despite
institution of nonpharmacological treatment and pharmacological treatment including full doses of three or more
medications, one of these being a diuretic. These patients
must be referred to a specialist or a hypertension center
because this type of hypertension is often associated with
subclinical organ damage, and has high added cardiovascular risk [20].
White-coat hypertension
Also known as isolated office hypertension it is the
condition in which blood pressure, measured in the office,
is consistently in the hypertensive range, whereas either
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908 Journal of Hypertension
2009, Vol 27 No 5
the ambulatory blood pressure monitoring (ABPM) mean
values [21] or home values [22] are always in the normotensive range. Its prevalence is around 10%. Its overall
risk is not clearly established [23], but it appears to be
associated with more cardiac, renal and metabolic functional and/or structural abnormalities than full normotension [24,25].
Hidden or masked hypertension
Also known as isolated ambulatory hypertension, it
represents the opposite condition to white-coat hypertension, that is patients have normal office blood pressure, whereas mean ABPM or home blood pressure
values are in the hypertensive range. It is found in every
one out of seven to eight patients with office normotensive values [25]. The cardiovascular risk in these patients
seems to be similar to that of established hypertensive
patients [26,27]. Thus, care must be taken to avoid that
these patients remain undiagnosed if ABPM or home
blood pressure are not measured.
Isolated systolic hypertension
Is sustained systolic blood pressure (SBP) at least
140 mmHg with diastolic blood pressure (DBP) less than
90 mmHg. As SBP tends to rise with age, the prevalence
of systolic hypertension increases with age and, above the
age of 60 years, systolic hypertension represents a common form of hypertension. Impressive evidence has been
accumulated on the importance of SBP as a major risk
factor for cardiovascular diseases [28].
Similar emphasis should be given to a low educational
level, because of the high percentage of the native population with low opportunities of an adequate education.
Figure 1 does not only include blood pressure values above
the conventional 140/90 mmHg cut-off values, but also
those considered optimal or normal, or high-normal. At all
blood pressure levels, including optimal ones, the total risk
increase progressively with the addition of other risk
factors, organ damage, diabetes and previous outcomes.
Diagnostic evaluation of the hypertensive patient
The time required for the initial evaluation of a hypertensive patient is of at least 30 min. The main objectives
of diagnosis are:
(1) Confirming the existence of high blood values,
(2) Determining the grade of hypertension and the
existence of target organ damage,
(3) Evaluating the presence of comorbidities,
(4) Identifying treatments previously received or currently in use,
(5) Quantifying the global risk including its social
components,
(6) Diagnosing or excluding possible secondary causes
of hypertension.
Clinical history and physical examination
To manage a hypertensive patient not only blood pressure levels should be considered but also total cardiovascular risk. In order to stratify total cardiovascular risk, the
number of risk factors, the presence of target organ
damage and of previous or concurrent clinical conditions
or outcomes (Table 4) in association with blood pressure
grading should be taken into account, as shown in Fig. 1.
Not only the grade of hypertension should be defined but
also the time at which hypertension was diagnosed. Information on age, sex and race should be recorded. The physical exam must include measurement of height, weight,
waist, hip and calculation of waist to hip ratio and body mass
index (BMI), the evaluation of pulses, heart rate, blood
pressure values, heart auscultation, search of carotid, thoracic or periumbilical bruits and a funduscopic examination.
Search should be made for associated risk factors and
possible complications such as peripheral edema, angina
pectoris, dyspnea, headache, ectopic heart beats.
Among traditional risk factors, socioeconomic conditions
should be given particular attention in Latin America.
Blood pressure measurements must be performed
in accordance with the American Heart Association
Risk stratification
Table 4
Factors to be taken into account to quantify cardiovascular risk
Risk factors
Subclinic TOD
Clinical events
Age, sex (male)
Hypertension
High total cholesterol
Tobacco smoking, impaired glucose tolerance, diabetesM
Family history of cardiovascular events
Low HDL cholesterol
High LDL cholesterol
High triglycerides
Overweight/obesity (BMI > 25 kg/m2),
Menopause
Social/economic positionMM
Education
Left ventricular hypertrophy
Microalbuminuria
Creatinine > 1.3 mg/dl
Increased carotid IMT
Hypertensive retinopathy (grades III/IV)
Increased vascular stiffness
Coronary heart disease
Myocardial infarction
Stroke
Peripheral arterial disease
Chronic heart failure
Chronic renal disease
BMI, body mass index; HDL, high-density lipoprotein; IMT, intima–media thickness; LDL, low-density lipoprotein; TOD, target organ damage.
Diabetes Association, International Diabetes Federation. MM Homeless, primary degree education, jobless.
M
According to the American
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Latin American guidelines on hypertension Sanchez et al. 909
Fig. 1
Risk related to blood pressure values. DM, diabetes mellitus; MS, metabolic syndrome; RF, risk factor; TOD, target organ damage.
recommendations, in two different positions (sitting and
standing), with the aim to discover orthostatic hypotension (decreases greater than 20 mmHg in SBP and/or
10 mmHg in DBP), especially frequent in older patients
[29]. When SBP and DBP values correspond to different
grades, the higher grade should be used to define the
patient’s hypertension.
Home blood pressure measurements, performed by
instructed persons with either a mercury sphygmomanometer or preferably by automatic or semiautomatic
validated devices, are an important tool for the control
and follow-up of hypertensive patients. Upper normal
values are similar for home and day-time ABPM, that is
135/85 mmHg [30].
Laboratory examinations
The main objectives are to detect other cardiovascular
risk factors, to assess target organ damage and to identify
secondary causes of hypertension. A complete blood
count, fasting plasma glucose, blood urea nitrogen, serum
and urinary creatinine, serum electrolytes, uric acid, total
high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, liver function tests,
T3, T4 and TSH, added to a complete urinanalysis,
estimated glomerular filtration rate [from serum creatinine with the Modification of Diet in Renal Disease
Study Equation for Estimating Glomerular Filtration
Rate with Standardized Serum Creatinine Values
(MDRD) formula], and an electrocardiogram must
always be performed at the first visit.
Recommended examinations
Vascular, cardiac and renal ultrasound and Doppler examinations are recommended to evaluate left ventricular
mass and to identify subclinic atherosclerosis in different
vascular territories, renal arterial stenosis or kidney alterations. Measurement of the pulse wave velocity is helpful
to assess large artery stiffness. Microalbuminuria (in a 24h urine collection or as albumin/creatinine ratio) is
highly recommended.
Ambulatory blood pressure monitoring
The method, which does not replace conventional
measurements, gives more detailed information on mean
24-h, daytime or night-time values [31,32]. The 24-h
mean values are more closely related to target organ
damage and outcomes than office values. ABPM is indicated when:
(1) White coat hypertension is suspected,
(2) Hidden (masked) hypertension is suspected,
(3) Normal blood pressure is accompanied by total high
risk,
(4) Evaluation of the 24-h blood pressure profile
(dipping, nondipping, etc.) is desirable,
(5) Refractory hypertension is suspected,
(6) Hypotensive or hypertensive episodic events are
looked for,
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910 Journal of Hypertension
2009, Vol 27 No 5
Fig. 2
Blood pressure evaluation algorithm. TOD, target organ damage.
(7) Autonomic dysfunction is present,
(8) Target organ damage progresses or does not regress
despite apparently good control of blood pressure.
Finally, the flowchart of Fig. 2 can be followed to evaluate hypertensive patients in whom possible causes of
secondary hypertension are searched for.
Metabolic syndrome, diabetes mellitus 1 or 2
and hypertension
Definition of metabolic syndrome
The metabolic syndrome is an entity with easily detectable features and prognostic relevance, yet largely underrecognized, that may become a diagnostic target to identify
subjects at increased cardiovascular risk [33–36]. The
International Diabetes Federation (IDF, https://www.idf.
org/webdata/docs/IDF_Meta_def_final.pdf) considers
abdominal obesity as one of the major cardiovascular risk
predictor. However, since there are no data on normal
cut-offs for abdominal circumference and visceral fat in
Latin American populations, the use of the South Asian
data is suggested until more specific data become available. Some small studies support this proposal [37–39].
Cooperative studies are under way and the new information may give more reliable information in this regard.
Although evidence about cardiovascular benefits of intervention is still lacking [40], it makes sense, from a clinical
and epidemiological standpoint, to focus on this population for the primary prevention of diabetes mellitus.
Definitions of metabolic syndrome range from the more
stringent definition based on insulin resistance (World
Health Organization) to that only based on clinical
criteria [National Cholesterol Education Program
(NCEP) [41]]. The NCEP definition has been adopted
in hypertension guidelines [5], presumably favoring a
higher sensitivity to identify populations at risk but at
the cost of decreased specificity in detecting true insulin
resistance [5,6]. An additional asset of the NCEP definition is clinical simplicity, as it may be applied almost
anywhere despite the limited resources available in Latin
America. However, the IDF classification seems to be
more appropriate for Latin America populations than the
other classifications in terms of the ethnic differences
[37,38]. The prevalence of metabolic syndrome varies in
terms of the classification criteria, age, sex, race and
socioeconomic status, but it is approximately 25–50%
in Latin America according to IDF criteria [37]. Recent
estimates of the prognostic value of metabolic syndrome
showed relative risk ratios for cardiovascular events or
mortality ranging from 2.0 to 3.3, whether or not diabetes
mellitus is included [36,42].
Definition of diabetes mellitus in Latin America
A growing body of evidence support the view that, like
blood pressure, fasting plasma glucose is a continuous
variable increasing the risk of cardiovascular disease,
independent of the fact that plasma levels reach or do
not reach the cut-off point used to establish the diagnosis
of diabetes [43,44]. The diagnostic criteria for diabetes
(confirmed fasting plasma glucose of at least 126 mg/dl or
plasma glucose of at least 200 mg/dl 2 h after an oral
glucose load) were chosen because they identified individuals at high risk of retinopathy. Recently, the terms of
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Latin American guidelines on hypertension Sanchez et al. 911
dysglicemia or prediabetes have been proposed to define
a condition in which the levels of fasting glucose range
between 100 and 125.9 mg/dl or the value of plasma
glucose 2 h after an oral glucose load of 75 g is between
140 and 199.9 mg/dl. It has been demonstrated that
the risk of developing diabetes mellitus and CVD is
increased in patients with prediabetes [45], especially
in populations of developing countries [14,46], who are
prone to develop insulin resistance associated with epigenetic adaptations to the rapid economic transition and
with changes in the lifestyle experienced by these populations [14,47].
The population prevalence of diabetes mellitus in Latin
America is 5–9%, being lower in rural areas and higher in
areas over an altitude of 3000 m, where around 100 000
individuals live. Prevalence of prediabetes is similar to
that of diabetes mellitus. The prevalence of hypertension
in the diabetic population is 1.5-fold to 3-fold higher than
among nondiabetic patients in the same age segment [6].
Prevalence of hypertension in diabetes is close to 30%; it
develops many years after the onset of diabetes, usually
as a consequence of diabetic nephropathy [48,49]. On the
contrary, in type 2 diabetes, hypertension may be present
at the time of diagnosis or may even precede overt
hyperglycemia [50]. In newly diagnosed type 2 diabetics,
the prevalence of hypertension is around 60%. In type 2
diabetes, it is difficult to determine whether hypertension
is secondary to diabetes, since patients are usually older
and more frequently obese than nondiabetic patients.
Because in western populations the prevalence of diabetes increases with age and degree of obesity [51], a
higher frequency of hypertension could be expected.
However, after adjusting for age and overweight/obesity,
the prevalence of hypertension was still 1.5-fold higher in
diabetic patients relative to nondiabetic patients [52]. In
certain ethnic groups [53], diabetic nephropathy could be
the primary cause of hypertension in type 2 diabetes, as is
the case among Pima Indians and African-American
individuals. Patients with diabetes and hypertension
are at a high risk for both macrovascular disease (coronary
artery, cerebrovascular and peripheral vascular disease),
and microvascular (renal failure, retinopathy). Although
the relation between diabetic neuropathy and high blood
pressure remains unclear, some epidemiologic evidence
suggests that hypertension may facilitate the development of neuropathy [6].
Complications of diabetes
Diabetic nephropathy
The prevalence of nephropathy is 20–30% in patients
with type 1 diabetes mellitus, and 30–50% in those with
type 2 diabetes mellitus [54]. Three stages are described.
Incipient nephropathy
Incipient nephropathy features a supranormal glomerular
filtration rate (GFR) for about 10 years, followed by an
increased urinary albumin excretion (30–300 mg/day) for
about 5 years. Presence of increased urinary albumin
excretion in both type 1 and type 2 diabetes mellitus
identifies patients at risk for progressive renal disease,
and is considered an independent predictor of cardiovascular disease. Twenty to forty percent of individuals with
abnormal microalbuminuria are reported to progress to
frank albuminuria, and 20% of them to end-stage renal
disease (ESRD).
Clinical nephropathy
Clinical nephropathy is characterized by more than
300 mg/day urinary albumin excretion and hypertension
in almost 100% of patients. In type 1 diabetes mellitus,
80% of patients may develop albuminuria greater than
300 mg/day within 10–15 years, and many of them will
progress to ESRD. Without intervention, progression to
this condition may be faster; in fact, 50% of patients will
have developed ESRD in 10 years and 75% in 20 years
[55]. On the contrary, therapeutic interventions in both
types of diabetes mellitus can slow down GFR decline.
Progressive renal insufficiency
Progressive renal insufficiency may be defined as
macroalbuminuria (300 mg/day) and a reduced GFR
(<30 ml/min per 1.73 m2). Macroalbuminuria identifies
diabetic patients with substantial histological damage
and predicts a linear decline in GFR. Newly diagnosed
type 2 diabetes mellitus patients should be screened
for albuminuria on a yearly basis. In type 1 diabetes
mellitus patients, albuminuria should be searched for
after 5–7 years from diagnosis, since increased urinary
albumin excretion rarely occurs earlier in the course of
the disease.
The management of diabetes and hypertension in
patients with nephropathy mandates strict glucose and
blood pressure control. The target for glycosylated hemaglobin A1c (HbA1c) should be less than 6.5–7%, since
this has been shown to delay progression from microalbuminuria to macroalbuminuria [5]. The recommended
blood pressure goal is less than 130/80 mmHg, and less
than 120/75 mmHg in patients with proteinuria more than
1 g and/or reduced GFR.
Randomized intervention trials have demonstrated
that the management of hypertension in patients with
diabetic nephropathy should include blockade of the
renin–angiotensin system [56–58] with agents such as
angiotensin-converting enzyme inhibitors (ACEIs,
greater evidence in type 1 diabetes mellitus) or angiotensin receptor blockers (ARBs, greater evidence in
type 2 diabetes mellitus). If the blood pressure target
is not achieved, other drugs should be added, such as
diuretics (thiazides), calcium antagonists or b-blockers.
The combination of three or more drugs is often necessary to meet blood pressure targets. Although there are
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912 Journal of Hypertension
2009, Vol 27 No 5
data favoring the combined use of ACEIs and ARBs in
patients with type 2 diabetes mellitus and proteinuria,
the recently published results of this combination in the
large ONTARGET trial [59] call for caution, and require
a careful reappraisal of this approach.
Patients with diabetic nephropathy require dietary protein
restriction in addition to the pharmacological treatment
since a reduced dietary protein intake (0.6 g/kg per day)
may delay the progression to ESRD [60].
Cardiovascular complications
Patients with diabetes and hypertension are at increased
risk for cardiovascular diseases such as CHD, heart failure, stroke, peripheral vascular disease. Comorbidities,
including dyslipidemia, prothrombotic state and autonomic dysfunction, may contribute to poorer outcomes,
thereby increasing morbidity and mortality. The incidence of cardiovascular disease in men and women with
diabetes mellitus 2 is up to three to four times higher
that in unaffected individuals. Furthermore, diabetes
mellitus is associated with a cardiovascular disease
mortality rate that exceeds 70%, and people with diabetes
mellitus 2 are two to three times more likely to die from
cardiovascular disease than people with no history of
diabetes mellitus, even after controlling for other cardiovascular risk factors [61,62]. They are also at high risk
of renal failure, limb amputation, cognitive decline, premature death, retinal disease leading to blindness and
erectile dysfunction.
Coronary heart disease
Several factors account for the increased risk, including
increased fibrinogen levels (particularly during poor glycemic control), increased levels of plasminogen activator
inhibitor-1, and increased platelet aggregation [63].
Screening for CHD should include exercise stress testing
and myocardial perfusion single-photon emission computed tomography imaging, when necessary.
The management of CHD is similar for hypertensive
patients with or without diabetes mellitus. Smoking
cessation should be strongly encouraged. Treatment
targets include re-establishment of coronary flow and
myocardial perfusion, plaque stabilization, prevention
of recurrent ischemia, limitation of left ventricular
(LV) remodeling, suppression of arrhythmias and secondary prevention. Treatment should include b-blockers. Antiplatelet therapy with aspirin [64] is the mainstay
of treatment for diabetic patients with CHD, and is also
recommended during and after acute myocardial infarction. It is important to achieve an adequate glycemic
control as early as possible, since blood glucose levels on
admission are an independent predictor of early and late
mortality of patients with myocardial infarction [65].
Statins should be administered to protect vulnerable
plaques even in patients with a normal lipid profile [65].
Left ventricular dysfunction and heart failure
Diabetes is a major risk factor for LV dysfunction and
heart failure. In the Glasgow Monica study, the incidence
of LV dysfunction was higher in diabetic patients (29%)
compared with nondiabetic patients (7%) [66]. In the
Framingham study [67], the relative risk for clinical heart
failure in patients with diabetes was 3.8 in men and 5.5 in
women, relative to nondiabetic patients. The prevalence
of heart failure in elderly diabetic patients has been
recently reported to be 39% [68]. The rate of heart failure
was found to be 4.2/1000 patients/year for diabetic
patients with HbA1c less than 7.0%, and to increase to
9.2/1000 patients/year for those with HbA1c greater than
10% [69]. Diabetic and hypertensive patients often
develop the so-called ‘diastolic heart failure’, that is, heart
failure with preserved systolic ejection fraction [70]. The
high prevalence of heart failure and the significant morbidity and mortality associated with it mandate the early
identification of risk factors and clinical signs to allow the
appropriate treatment. Although an electrocardiogram
and X-rays may be helpful, two-dimensional and pulsed
Doppler echocardiography is recommended whenever
heart failure is suspected in order to visualize the changes
in heart structure and function that underlie heart failure. A
24-h electrocardiographic monitoring is also important to
screen for arrhythmias, since heart failure is a proven
predictor of sudden cardiac death.
Large clinical trials have documented the benefits of
drugs blocking enhanced neuro-hormonal systems (sympathetic and renin–angiotensin) in attenuating cardiac
remodeling, improving ventricular function, and reducing morbidity and mortality. Treatment should include a
diuretic (furosemide), an ACEI or ARB and a b-blocker,
unless contraindicated. Spironolactone can also be considered in absence of severe renal dysfunction.
Stroke
The rates of stroke-related disability are higher in diabetic than in nondiabetic patients [71]. The risk of fatal
vs. nonfatal stroke is associated with higher levels of
HbA1c many years before the event [72]. Hence, blood
pressure and glycemic control, together with other proven therapies such as aspirin and statins [73], are warranted for stroke prevention.
Prevention of cardiovascular disease in diabetic patients
To prevent cardiovascular disease in patients with diabetes mellitus and hypertension, strict control of glycemia
[74,75] and blood pressure is fundamental. The Diabetes
Control and Complications Trial (DCCT) in people with
type 1 diabetes found that a 6-year period of intensive
glycemic control (HbA1C 7.2 vs. 9.0%) led to a 42%
reduction in cardiovascular outcomes after 11 more years
of passive follow-up. Interestingly, during passive followup, glycemic control was not different between the groups
[74]. In type 2 diabetes mellitus the evidence is less clear:
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Latin American guidelines on hypertension Sanchez et al. 913
the UK Prospective Diabetes Study (UKPDS) [75]
showed only benefit in preventing microvascular disease
by reducing HbA1C to 7.0 vs. 7.9%, and three recent trials
(ACCORD [76], ADVANCE [77] and DIGAM 1–2 [78])
lowering HbA1C to below 7% failed to reduce macrovascular disease significantly, although ADVANCE reported
a small but significant improvement in microvascular outcomes. However, these studies indicated that the cardiovascular risk of a diabetic patient is directly related to the
duration of diabetes, and the efficacy of hypoglycemic
therapy in reducing cardiovascular risk might be affected
by the duration of diabetes [79]. Early intensive treatment
should be encouraged in diabetic patients, especially in
those at high risk of developing cardiovascular disease, as
are the hypertensive diabetic patients.
Risk of diabetes in hypertension
Epidemiologic evidence suggests that hypertension is a
risk factor for the development of diabetes. One prospective study found that people with hypertension had a
2.4 higher incidence of diabetes than people without
hypertension [80]. One explanation for the increased risk
of diabetes in hypertension is activation of the renin–
angiotensin system. Both angiotensin II-mediated pancreatic vasoconstriction [81] and aldosterone-mediated
hypokalemia [82] inhibit glucose-induced insulin release
from the beta cell. In addition, angiotensin II and insulin
share signal transduction pathways. Thus, insulin activates proteinkinase C (PKC) through the tyrosine phosphorylation of insulin receptor substrate type 1 and 2
(IRS-1 and IRS-2) and stimulates the mitogen-activated
protein (MAP)-kinase pathway signaling, whereas angiotensin II inhibits PKC signaling that alters the intracellular signaling of insulin, producing insulin resistance [83].
Blockade of the renin–angiotensin system reduces the
contraregulatory hormone norepinephrine [84], improves
peripheral insulin sensitivity [85], and prevents the
development of diabetes in people with hypertension,
heart disease, or heart failure, and reduces glucose levels
[86–88]. For these reasons the recommendation of the
2007 European Guidelines for the Management of Arterial Hypertension recommend that in hypertensive
patients with metabolic syndrome and type 2 diabetes
ARB or ACE inhibitors [5] should be used as first antihypertensive drugs. In Latin American populations
similar recommendations should be given for this kind
of patients, especially in face of their higher proneness to
develop insulin resistance at lower levels of abdominal
obesity [89,90], a condition with epidemic characteristics
in Latin America [91], and associated with changes in
vascular function independently of other cardiovascular
risk factors [92].
Treatment of hypertension
General principles
Middle-income and low-income regions, such as most of
the Latin American countries, have a five times greater
burden of disease than do high-income countries, with
access to less than 10% of the global treatment resource.
Therefore, priority should be given to those at the highest
risk of fatal events, because most hypertensive patients
receive no treatment whatsoever. Particular attention
should be given to those individuals with social risk
conditions such as homelessness, poverty, lack of education, or unemployment.
In hypertensive patients, the primary goal of treatment is
to achieve maximum reduction in the long-term total risk
of cardiovascular disease with maintenance of good quality of life. This requires treatment of the elevated blood
pressure values per se as well as all associated reversible
risk factors in order to reduce the associated cardiovascular risk. In this way, any reduction in blood pressure,
even if not optimal, helps toward total risk reduction.
However, blood pressure should be reduced to at least
below 140/90 mmHg (systolic/diastolic), and to lower
values, if tolerated, in all hypertensive patients. Target
blood pressure should be at least less than 130/80 mmHg
in patients with diabetes and in high or very-high-risk
patients such as those with associated clinical conditions
(stroke, myocardial infarction, renal dysfunction, proteinuria) [5,73].
Systolic blood pressure is a better predictor of risk in
elderly patients, and also in these patients the goal of
treatment should be achieving less than 140 mmHg,
although in no-intervention trial these low values have
been achieved. In very elderly hypertensive patients
important cardiovascular risk reduction was found in
the HYVET study with a blood pressure target of 150/
80 mmHg [93]. Despite the use of combination treatment, reducing SBP to less than 140 mmHg may be
difficult and more so if the target is a reduction to less
than 130 mmHg. Additional difficulties should be
expected in the elderly, in patients with diabetes, and
in general, in patients with cardiovascular damage.
In order to more easily achieve goal blood pressure,
antihypertensive treatment should be initiated before
significant cardiovascular damage develops. 24-h ABPM
is a useful tool that should be recommended, when
available, to reinforce or correct treatment [94–97].
Lifestyle changes
Lifestyle measures should be instituted, whenever
appropriate, in all hypertensive patients, including those
who require drug treatment. The purpose is to lower
blood pressure, to control other risk factors, and to reduce
the number or the doses of antihypertensive drugs.
Lifestyle measures are also advisable in patients with
normal and high-normal blood pressure to reduce the risk
of developing hypertension. Lifestyle recommendations
should not be given as lip service but instituted with
adequate behavioral and expert support, and reinforced
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
914 Journal of Hypertension
2009, Vol 27 No 5
periodically. The lifestyle measures that are widely
recognized to lower blood pressure and/or cardiovascular
risk, and that should be considered are:
pressure should be closely monitored and drug treatment
considered in the presence of increasing blood pressure or
worsening of the clinical condition.
(1)
(2)
(3)
(4)
(5)
(6)
(7)
Selection of antihypertensive drugs
Smoking cessation
Weight reduction (and weight stabilization)
Reduction of excessive alcohol intake
Physical exercise
Reduction of salt intake (<6 g NaCl)
Increase of Kþ intake (>6 g)
Increase in fruit and vegetable intake and decrease in
saturated and total fat intake.
Body mass index and abdominal circumference are
reliable clinical markers in cardiovascular prevention.
Optimal BMI for the hypertensive population is between
18.5 and 25 kg/m2. Likewise, an adequate abdominal
circumference is less than 90 cm in male and less than
80 cm in women [37–39,98], but no tables of normality
values based on epidemiological studies of sufficient
power are available in Latin America.
Aerobic exercise is an important complement of diet
for weight and blood pressure reduction. It should be
implemented in all hypertensive patients and particularly
in those with additional risk factors for at least 30 min daily.
Because long-term compliance with lifestyle measures is
low and the blood pressure response highly variable,
patients under nonpharmacological treatment should
be followed up closely.
Initiation of blood pressure-lowering therapy
Initiation of blood pressure-lowering therapy should be
decided on two criteria: the level of SBP and DBP and the
level of total cardiovascular risk. Drug treatment should
be initiated promptly in grade 3 hypertension as well as in
grade 1 and 2, when total cardiovascular risk is high or
very high. In grade 1 or 2 hypertensive patients with
moderate total cardiovascular risk drug treatment may be
delayed for a few weeks and in grade 1 hypertensive
patients without any other risk factor for several months.
However, it is important to pay particular attention to
those individuals who are at risk because of their social
environment (homeless, poor, the uneducated, or the
unemployed), in whom a prompter initiation of therapy
should be considered and a close monitoring of health is
mandatory. When initial blood pressure is in the highnormal range the decision on drug intervention heavily
depends on the individual clinical condition. In the case
of diabetes, history of cerebrovascular, coronary, or peripheral artery disease, the recommendation to start blood
pressure-lowering drugs finds some support in the results
of controlled trials. Patients in the normal blood pressure
range but at very high cardiovascular risk because of
associated clinical disease should be advised to implement intense lifestyle measures. In these patients blood
The main benefits of antihypertensive therapy are due to
lowering of blood pressure per se. Five major classes of
antihypertensive agents – thiazide diuretics, calcium
antagonists, ACE inhibitors, angiotensin receptor blockers, and ß-blockers – are suitable for the initiation and
maintenance of antihypertensive treatment, alone or in
combination [5]. ß-blockers, especially in combination
with a thiazide diuretic, should not be used in patients
with the metabolic syndrome or at high risk of incident
diabetes. In these patients carvedilol, nebivolol, or slowrelease indapamide may be suitable [99–101]. Renin
inhibitors, such as aliskiren, although not yet available
in all countries, have been shown to be effective antihypertensive agents [102]. However, results of outcome
trials are still waited, and the cost/benefit ratio of these
agents is still unknown. In many patients more than one
drug is needed, so fixed combinations might be useful in
order to improve compliance and increase successful
control of blood pressure [103].
The choice of a specific drug or drug combination, and
the avoidance of others should take into account the
following:
(1) The previous favorable or unfavorable experience of
the individual patient with a given class of compounds.
(2) The effect of drugs on cardiovascular risk factors in
relation to the cardiovascular risk profile of the
individual patient.
(3) The presence of subclinical organ damage, clinical
cardiovascular disease, renal disease or diabetes,
which may be more favorably treated by some drugs
than others.
(4) The presence of other disorders that may limit the
use of particular classes of antihypertensive drugs.
(5) The possibilities of interactions with drugs used for
other comorbidities.
(6) The cost of drugs, either to the individual patient or
to the health provider.
Cost considerations, however, should never predominate
over efficacy, tolerability, and protection for the individual patient.
Continuing attention should be given to side-effects of
drugs, because these are the most important causes of
noncompliance. Drugs are not equal in terms of adverse
effects, particularly in individual patients. Drugs which
exert their antihypertensive effect over 24 h with a oncea-day administration should be preferred because a
simple treatment schedule favors compliance [104].
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Latin American guidelines on hypertension Sanchez et al. 915
In hypertensive patients with moderate or high cardiovascular risk and specific accompanying conditions, the following pharmacological interventions are recommended:
(1) ACE inhibitors or ARBs in patients with metabolic
syndrome or type 2 diabetes because metabolic
parameters are not affected or may even be
improved.
(2) ACE inhibitors or ARBs in patients with renal
dysfunction and microalbuminuria or proteinuria
because these agents slow down progression to
chronic renal failure and dialysis.
(3) ACE inhibitors or ARBs in patients with systolic and
diastolic left ventricular dysfunction even if asymptomatic.
(4) ACE inhibitors, ARBs, and calcium channel blockers in patients with left ventricular hypertrophy
because these agents facilitate left ventricular
regression.
(5) Beta blockers in patients with CHD.
(6) Calcium channel blockers (dyhydropyridines) in
elderly hypertensive patients and African Americans hypertensive patients.
(7) a-Adrenergic blocking agents in patients with
prostatic hypertrophy.
(8) Thiazides and chlortalidone in African American
hypertensive patients, elderly hypertensive patients,
or low-income people who cannot afford the cost of
other drugs.
(9) In hypertensive patients with heart failure diuretics,
ACE inhibitors, bisoprolol, carvedilol or nebivolol,
and spironolactone.
(10) In postmyocardial infarction patients ACE inhibitors and beta blockers.
(11) Recurrency of stroke is better prevented with
diuretics (slow-release indapamide) and ACE
inhibitors.
(12) Patients with peripheral vascular disease should be
encouraged to quit smoking and perform aerobic
exercise. Calcium channel blockers are suitable
to lower blood pressure without exacerbation of
symptoms.
(13) ACE inhibitors or ARBs in patients with recurrent
atrial fibrillation. Beta blockers or verapamil in
sustained atrial fibrillation.
(14) Statins and antiplatelet agents in very-high-risk
hypertensive patients (secondary prevention).
Special populations
blood pressure when blood pressure is over the 90th and
under the 95th percentiles in three or more occasions.
Adolescents with blood pressure values at least 120/
80 mmHg should be considered as prehypertensive.
White-coat hypertension is defined when blood pressure
values are equal or over the 95th percentile and in the
normal range out of the office. For diagnosis confirmation,
ABPM or home blood pressure is required.
Blood pressure measurement The demonstrated link
between childhood blood pressure values and essential
hypertension in adult life supports the recommendation
that blood pressure must be routinely measured in the
pediatric physical evaluation. The old concept that hypertension in children and adolescents is predominantly
secondary is untrue. Thus, it is recommended that blood
pressure must be measured since the first days of life and
at least once in a year even in children, especially in the
obese ones, as hypertension is closely related to obesity in
children [106–111].
Measurement of blood pressure is mandatory in diseases
or conditions accompanied by higher risk of arterial
hypertension, such as renal diseases, diabetes, insulin
resistance, long-term steroid therapy, nonsteroidal antiinflammatory drugs, oral contraceptives, cyclosporine,
neurofibromatosis, newborns with pathological umbilical
vessels, Turner syndrome, corrected aortic coarctation,
hemolytic–uremic syndrome, unexplained congestive
heart failure, dilated myocardiopathy, and seizures of
unknown cause.
Blood pressure measurements should follow these recommendations:
(1) The child must be sitting in a chair that enables him
to have the arm supported. If this is not possible, the
child must sit on mother’s lap.
(2) No measurement of blood pressure must be
performed if the child is crying or moving the arm
from which the measurement is to be performed.
(3) To choose the correct arm-cuff, the arm circumference must be measured at mid distance between the
acromium and olecranon (Table 5). The air bladder,
not the cuff, must cover 80% of the arm circumferRecommended cuff length for blood pressure
measurement
Table 5
Inflatable bladder
Hypertension in children
Definition of hypertension in children
Hypertension in pediatrics is defined by percentile tables
related to sex, age, and height provided in the Report
from the Working Group on High Blood Pressure in
Children and Adolescents [105]. Normal blood pressure
is defined when blood pressure, depending on sex, age,
and height, is under the 90th percentile, high-normal
Newborn
Breast feeding
Child
Adult
Obese
Thigh
Width (cm)
Length (cm)
Flexible cuff length (cm)
4
8
10
13
16
20
8
13
18
22
34
40
23
30
40
52
65
76
Calculated to cover, al least 80% of the arm circumference.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
916 Journal of Hypertension
2009, Vol 27 No 5
ence and 2/3 of the olecranum–acromion distance. In
case of unavailability of the correct cuff, the next size
can be used. If only an adult cuff is available, the
thigh of the children can be used with the child lying,
performing the auscultation in the popliteal fossa.
From 6–7 years of age a small adult cuff can be used.
Diagnostic evaluation Children with marked and persistent arterial hypertension should be evaluated for
secondary hypertension. Inquiry should be made about
newborn diseases and history of urinary infection, feeding
habits, energizer drinks, and illicit drugs. Physical exam
should include heart rate, peripheral pulses, vascular and
cardiac bruits, and blood pressure in both arms and legs.
ABPM or home blood pressure readings may help to
confirm the diagnosis and to discard white-coat hypertension, which is frequent in adolescents [112,113], thus
avoiding unnecessary studies. The 24-h ABPM classification related to sex and age could be performed by using
tables reported elsewhere [114].
Blood count, serum and urinary creatinine, serum uric
acid, serum and urinary electrolytes, acid–base evaluation, plasma renin activity, serum aldosterone, fasting
glycemia, serum lipids, a full urine test with microalbuminuria, cardiac and renal Doppler ultrasound should be
performed whenever there is a consistent suspicion of
secondary hypertension.
Special tests according to type of suspected secondary
hypertension can be considered, such as renal scintigraphy before and after ACEI, magnetic angio-resonance
and/or aorto-renal arteriography (renovascular disease),
urinary catecholamines and metanephrine (pheochromocytoma), aldosterone : renin ratio, cortisol plasma levels
(primary hyperaldosteronism or Cushing disease).
vegetables and fruits, foods with high potassium content,
may also help to prevent a blood pressure increase. Recommendations should be given against active or passive
exposition to tobacco smoking, since there is a straight
relationship between parental and children’s smoking
habits. Childhood is a specific window in which prevention
of hypertension and cardiovascular risk factors should
be started.
Treatment Nonpharmacological treatment is the major
measure to lower blood pressure in children. It is similar
to that recommended above for prevention of hypertension.
Pharmacological treatment should not start before
4–6 months of an unsatisfactory response to lifestyle
changes, when target organ damage is present and in
patients with secondary hypertension.
Clinical studies with antihypertensive drugs in children
are not numerous nor large, but they have provided some
information about doses and safety of drugs. Treatment
should be started with a single drug, all classes (ACEIs,
ARBs, beta blockers, calcium antagonists, and diuretics)
being suitable. Small doses should initially be used and
subsequently titrated until blood pressure control is
reached. In case of failure, a second drug can be added
in order to avoid too large doses of any single drug.
Cautions when treating hypertension in children Avoid
the use of ACEIs and ARBs in female adolescents at risk
of pregnancy (specific contraindication). Beta blockers
can cause some reduction in physical performance and
diuretics increase the risk of electrolyte disturbances.
Hypertension in pregnancy
Prevention Pediatricians should measure blood pressure
as part of the physical examination in all children. Physicians in charge of adult hypertensive patients or adult
cardiac patients should measure blood pressure in their
patients’ offspring also, since hypertension presents
familiar aggregation [115]. Lifestyle changes should be
elicited in the entire family, these greatly contributing to
the primary prevention of hypertension and cardiovascular
morbi-mortality. Healthy eating changes and increased
physical activities should be promoted in schools, in view
of actively antagonizing the overweight and obesity epidemics induced by trash food intake and sedentarism due
to the time spent at the computer and in front of the
television. Obesity is one of the major components of the
metabolic syndrome that also include other cardiovascular
risk factors like arterial hypertension, insulin resistance,
and dyslipidemia [107,116]. High salt intake through processed foods and sugar intake in sweetened beverages also
contribute to weight gain [117]. A reduced salt intake is a
simple measure to prevent weight gain. A greater intake of
In pregnancy hypertension has a prevalence of about 5–
10%, and is more prevalent in high-risk pregnancies, such
as those with a previous history of preeclampsia or chronic
severe hypertension, or in primiparous women. In Latin
America a higher prevalence of hypertension in pregnancy
has been documented than in high-income countries [118].
Therefore, special attention is given to this topic in the
present guidelines. Indeed, most of the complications of
hypertension in pregnant women are preventable, and the
best prevention is based on early detection of hypertension
through a careful measurement of blood pressure.
Definition and classification
Hypertension in pregnancy is defined as blood pressure
values of at least 140/90 mmHg in two or more readings at
a 4-h interval [119]. Proteinuria in pregnancy is defined as
urinary protein excretion of at least 300 mg/24 h. Among
the different hypertensive syndromes in pregnancy
particular attention is called to preeclampsia because
of its prevalence in Latin America.
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Latin American guidelines on hypertension Sanchez et al. 917
Preeclampsia is frequently associated with fetal complications. It starts through an anomalous placentation
before the 20th week [120], and usually presents clinically after the 28th week, with an increase in blood
pressure, proteinuria, and hyperuricemia. Edema,
impaired renal function, hemolysis and platelet aggregation, attributed to endothelial dysfunction secondary to
placental ischemia, can also occur. Endothelial dysfunction may release different toxins into the maternal blood,
such as cytokines, reactive oxygen species (ROS), asymmetric dimethylarginine (ADMA), antibodies against
angiotensin II receptors, and so on [121]. Factors favoring
the abnormal placentation are: first pregnancy before age
18 years or after 40 years age, previous history of preeclampsia (especially if before the 32nd week [122]),
history of spontaneous abortion or severe intrauterine
growth retardation, pregnancy resulting from assisted
fertilization, multiple pregnancies, close familiar
(mother, sister) history of preeclampsia, Rh isoimmunization, subclinical infections, chronic arterial hypertension, renal failure, obesity, autoimmune diseases.
Differences between developed countries in the causes
of preeclampsia and in the strategies to prevent it have
been described [123]. Inflammation secondary to vaginal
and urinary subclinical infection [124,125], periodontal
disease [126], insulin resistance [127] are considered as
possible risk factors for the development of preeclampsia.
Therefore, it is important that pregnant women with
the above-mentioned risk factors be carefully followed
to detect hypertension and proteinuria early, prevent
severe complications requiring hospitalization, and, if
necessary, perform cesarean delivery to preserve mother
and child.
Diagnostic studies
Prevention
Drugs with absolute contraindications are renin inhibitors, ACE inhibitors, and ARBs [137,138]. Relative
contraindications are beta blockers (mostly atenolol),
because of reduced placental perfusion and untoward
effects in the newborn (reduction in weight, bradycardia,
and hypooglycemia) [139]. Diuretics are also relatively
contraindicated, unless when cardiac failure is present,
because pregnancy is characterized by reduced plasma
volume, which may be further reduced by diuretic
therapy.
Low-dose aspirin The efficacy is lower than initially
expected [128] and its use is still controversial. Nevertheless in patients at high risk of preeclampsia early
aspirin administration (100 mg/day from the 8th week
until 2 weeks before probable delivery) may delay onset
of preeclampsia.
Calcium supplementation An inverse relationship has
been shown between calcium intake and preeclampsia
[129]. Although a number of trials of calcium supplementation have failed to consistently show benefits, some
low and middle-income populations of Latin America
have low calcium diets and in these groups beneficial
effects on preeclampsia and premature delivery have
been obtained by giving a 1 g daily supplement of
calcium [130–132].
Subclinical infections Because of the strong relationship between urinary and periodontal infections and
preeclampsia [133], it is imperative to search for and
treat bacteriuria, urinary, and/or vaginal and periodontal
infections in pregnant women.
Biochemical tests during pregnancy should include blood
count, glycemia, serum electrolytes, creatinine and uric
acid, urinalysis and 24-h proteinuria. These measurements must be repeated at the 20th, 28th, 32nd, and
36th weeks and more frequently when hypertension or
complications are present. Pregnant women at high risk
of preeclampsia may be advised to have a uterine arterial
Doppler ultrasound at weeks 10–12 and 20–28.
In women with a history of preeclampsia before the 32nd
week, or of recurrent abortions, hematological abnormalities are two to three times more frequent than in the
general population [134,135]. A search for anticardiolipin
antibodies, homocysteine, antithrombin III deficit, lupus
inhibitor, activated C protein resistance, protein S deficit,
helps in the identification of women that, in a future
pregnancy, may require aspirin or heparin to prevent
complications. Likewise, in any pregnant woman
with high fasting plasma glucose an OGTT should be
performed.
Treatment
Pharmacological treatment must be started when
blood pressure is at least 150/100 mmHg. Treatment
can be initiated orally, and the patient recontrolled after
48–72 h.
Based on 40 years experience and 7.5 years follow-up of
children of treated mothers, alpha methyl-DOPA (500–
2000 mg/day) is the drug of first choice. Second-line drugs
are labetalol (100–400 mg/day), long-acting nifedipine
(30–60 mg/day), and hydralazine (50–200 mg/day) [136].
Emergency hospitalization and treatment (often intravenously) is required when DBP is at least 110 mmHg or
remains above 100 mmHg despite treatment, proteinuria
is greater than 1 g/24 h, there is the HELLP syndrome or
eclampsia. Even in emergency situations blood pressure
must be reduced gradually during the first 24 h. Recommended drugs are: labetalol – initial dose 20 mg i.v., with
subsequent doses at 10-min intervals, if necessary, up to a
maximal dose of 220 mg; long-acting nifedipine – if the
patient is conscious, 10 mg every 30 min orally, with a
maximal dose of 40 mg (magnesium sulfate can be associated although some reduction in uterine contractility has
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
918 Journal of Hypertension
2009, Vol 27 No 5
been reported); – 0.15 mg intravenously followed by
0.75 mg in 500 ml 5% dextrose solution (five drops per
min); nitroglycerine infusion if there is pulmonary
edema. Sodium nitroprussiate should be infused only
postpartum, due to the risk of thyocianate intoxication
of the fetus. Intravenous hydralazine is now discouraged
because it appears to be associated with more perinatal
adverse effects. In absence of an adequate therapeutic
response, decisions depend on gestational time: when
this is more than 36 weeks, pregnancy should be interrupted. When gestational time is less than 36 weeks,
corticoids should be administered to induce pulmonary
maturation, and pregnancy interrupted after 48 h.
Complications of hypertension in pregnancy
HELLP syndrome HELLP is an abbreviation of the
main findings [140]: hemolytic anemia, elevated liver
enzymes, and low platelet count. This, together with
eclampsia, is the most frequent cause of maternal death.
It can follow a severe preeclampsia or represent the first
manifestation of the disease. The three diagnostic criteria
are microangiopathic anemia with hyperbilirubinemia,
increased lactic acid dehydrogenase and hepatic
enzymes, and thrombocytopenia. The patient must be
hospitalized, possibly in an intensive care unit, and
interruption of pregnancy is recommended independently of gestational time.
Eclampsia Eclampsia is characterized by seizures. It
generally follows preeclampsia when this is inadequately
treated. Hospitalization in an intensive care unit is
required to provide adequate therapy [141,142]. Magnesium sulfate i.v. has been proved effective in the prevention of eclampsia and treatment of seizures [143].
Recommendation for follow-up of women and children after
a hypertensive pregnancy
Breast feeding Blood pressure less than 150/100 mmHg
does not require treatment and salt restriction can be the
only measure to normalize blood pressure. If antihypertensive drugs are needed, those with low breast milk
excretion should be used, such as methyldopa, nitrendipine, captopril, or enalapril [144]. Special caution must be
taken with diuretics since a reduction in breast milk
production can be induced; diuretics are also excreted
in breast milk and can cause electrolytic alterations in
the newborn.
Long-term maternal blood pressure control All women
presenting hypertension during pregnancy should have
their blood pressure followed up subsequently, since they
are prone to show or develop continuing hypertension.
Furthermore, a number of retrospective studies have
shown an increased cardiovascular risk in women with
preeclampsia and intrauterine undernutrition [145–147].
Child blood pressure control Several epidemiological
studies have shown a strong association between low
birth weight and prevalence of hypertension and cardiovascular diseases in adulthood. These findings support
the concept that cardiovascular diseases may start in
intrauterine life [148]. Therefore, children of mothers
with a hypertensive pregnancy should have their blood
pressure controlled up to adulthood.
Hypertension in the elderly
Hypertension is known to be one of the most important
treatable risk factors in patients older than 65 years.
Isolated systolic hypertension which is very frequent in
the elderly [149] carries an additional risk because the
increased pulse pressure (>65 mmHg) has been found to
be associated with increased cardiovascular morbidity
and mortality [150]. The elderly are prone to orthostatic
hypotension and pseudo hypertension due to a reduced
arterial compliance, therefore blood pressure measurements must also be done with the patient in the erect
posture. Twenty-four hour ABPM may also be a valuable
adjunct to the clinical evaluation [151,152].
Diagnosis
In elderly hypertensive patients, especially those resistant to treatment, renovascular hypertension due to
abdominal aorta atherosclerosis must be searched for.
Doppler ultrasound examinations of the renal artery
and abdominal aorta are a useful screening tool.
Treatment
In the elderly, blood pressure should be reduced to a
target similar to that recommended for younger people,
that is below 140/90 mmHg. This goal, however, is more
difficult to achieve. In the elderly, blood pressure
decrease must be gradual to ensure good tolerability
and guarantee a good quality of life.
A number of large trials (SHEP, STOP, MRC, Syst-Eur,
and Syst-China [153–157]) provided strong evidence of
the benefits of lowering blood pressure in older patients
either with systolic–diastolic or isolated systolic hypertension, showing decreases in stroke (25–47%), coronary
events (13–30%), heart failure (29–55%), and cardiovascular death (17–40%), in actively treated vs. placebotreated patients. The recent HYVET trial [93], which
included 3800 patients older than 80 years randomized to
either placebo or active treatment with indapamide and
perindopril, showed that even in these very elderly
patients blood pressure reduction is associated with a
significant reduction in fatal and nonfatal stroke (30%),
stroke deaths (39%), all-cause mortality (21%), cardiovascular deaths (23%), and heart failure deaths (64%).
Pharmacological treatment
When selecting antihypertensive drugs for older people,
the frequent presence of comorbidities and, consequently,
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Latin American guidelines on hypertension Sanchez et al. 919
of multiple drug intake, must be taken into account, and
the risk of pharmacological interactions considered. To
avoid excessive or sudden falls in blood pressure, due to
impaired pharmacokinetics, overestimation of blood pressure values, the postprandial and orthostatic hypotension,
reduced blood flow autoregulation, and so on, agents must
be started at low doses, and doses adjusted every 4–6
weeks after evaluating side-effects. The first-step drugs in
older people without complications are diuretics and
calcium antagonists, as more frequently used in randomized trials, but favorable data are also available for other
agents (see HYVET results for the use of ACEI in combination with a diuretic). In elderly hypertensive patients
with associated risk factors, hypertensive complications, or
comorbidities, drugs must be chosen depending on the
concomitant disease. Long-acting drugs are preferred due
to better patient compliance (an aspect particularly valuable in the elderly in whom a simplified drug delivery is
recommended) and a smoother antihypertensive effect.
Latin American Guidelines on Hypertension
Expert Groups
Chairpersons: Ramiro A Sánchez (Argentina); Miryam
Ayala (Paraguay).
(Paraguay), Dra Rosa Simsolo (Argentina), Dr Luis
Hernan Zárate (Chile).
Group 5: Metabolic syndrome and diabetes mellitus:
Dr Jorge Jimenez (Paraguay), Dr Guillermo Burlando
(Argentina), Dra Felizia Cañete (Paraguay), Dr Pablo
Aschner (Colombia), Dr Luis Barriocanal (Praguay), Dr
Aldo Benı́tez (Paraguay), Dra Gilda Benı́tez (Paraguay),
Dra Susan Benı̀tez (Paraguay), Dr Manuel Garcı́a de los
Rı́os (Chile), Dr Patricio López Jaramillo (Colombia),
Dra Ana Marı́a Jorge (Uruguay), Dra Mafalda Palacios
(Paraguay), Dra Maricela Vidrio (Mexico).
References
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2
3
4
5
Advisor: Professor Alberto Zanchetti (Istituto Auxológico
Italiano, Milan Italy).
6
Group 1: Epidemiology: Dr Oswaldo Kohlman (Brazil),
Dr José Ortellado (Paraguay), Dra Ximena Berrios
(Chile), Dra Maria Paniagua (Paraguay), Dr Angel González Caamaño (México). Dr Carlos Ponte (Venezuela),
Dra Martha Sereday (Argentina), Dr Sano Masao (Paraguay), Dr Fernando Montenegro (Ecuador), Dr Juan
Carlos Schettini (Uruguay).
Group 2: Diagnostic and Risk Stratification: Dr Hugo
Pascual Baglivo (Argentina), Dr Carlos J Velazquez (Paraguay), Dr Javier Galeano (Paraguay), Dr Miguel Adorno
(Paraguay), Dr Ernesto Cardona (México), Dr Dagomar
Aristizabal (Colombia), Dr Diego Garcı́a Garcı́a (Colombia), Dr Alejandro Iriarte (Paraguay), Dr Ernesto Peñaherrera (Ecuador), Dr Gabriel Waissman (Argentina).
Group 3: Treatment: Dr Mario Bendersky (Argentina), Dr
Luis Alcocer (Mexico), Dr Gustavo Olmedo (Paraguay),
Dr Jose A Manfredi (Uruguay), Dr José Parra Carrillo
(Mexico), Dr Rafael Hernández Hernández (Venezuela),
Dr Alfonso Bryce Moncloa (Perú), Dr Alberto Villamil
(Argentina), Dr Pablo Rodrı́guez (Argentina), Dr Raul
Ortiz-Guerrero (Paraguay), Dr Walter N Nissen (Paraguay), Dr Hernan Prat-Martorell (Chile).
Group 4: Special populations (Children and adolescents,
pregnancy, elderly): Dra Gloria Valdes (Chile), Dr Ayrton
Brandao (Brazil), Dra Leticia Gutierrez (Paraguay), Dr
Guillermo Fábregues (Argentina), Dr Roberto Ciciolli
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