From Medscape Cardiology

New European Guidelines for Management of Arterial Hypertension

Linda Brookes, MSc

Authors and Disclosures

Posted: 06/25/2003; Updated: 07/03/2003

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Presenter: Professor Giuseppe Mancia, MD, PhD, University of Milan-Bicocca (Milan, Italy) and S Gerardo Hospital
(Monza, Italy)

New guidelines for the management of arterial hypertension were announced by the European Society of
Hypertension (ESH) and the European Society of Cardiology (ESC) and officially presented to the 2003 ESH meeting
by Professor Giuseppe Mancia, MD, PhD,[1] Guidelines Committee chairman, with simultaneous publication in the
Journal of Hypertension.[2] The goal of the new guidelines is to update the 1999 World Health Organization
(WHO)/International Society of Hypertension (ISH) guidelines,[3] which the ESH/ESC had previously endorsed but
then decided to revise.

ESC/ESH felt that a new European set of guidelines was called for since the WHO/ISH guidelines were necessarily
written for a global audience, with a wide range of healthcare needs and resources. By contrast, Europe is a more
homogeneous community with greater expected personal longevity and a higher incidence of cardiovascular disease,
often despite well-developed heathcare systems. In promulgating the revision, the new document follows the
WHO/ISH call for more regional guidelines, and consequently has been endorsed by ISH.

The European guidelines are also noticeably different from the recently announced US guidelines, JNC 7[4,5] [see
related links], in that they are being published as the full document first, followed by the shorter version -- due to be
published in a few months' time, initially in English. (The JNC 7 guidelines were published in May in "express" form,
to be followed by the unabridged publication later this year.) Major differences between the contents of the 2 sets
of guidelines include the method of classification of blood pressure and the treatment recommendations; the
European recommendations intended to establish greater flexibility in their approach.

The new guidelines state that their goal is to offer the best available and most balanced information to all those
involved in the management of arterial hypertension. They were prepared on the principle that guidelines should be
educational rather than merely prescriptive, and the committee has emphasized that it has avoided rigid
classifications for its recommendations. In another departure from JNC 7, the guidelines are based on the strength of
available evidence, with the scientific evidence drawn from many sources and not only from clinical trials and their
meta-analyses. Although the committee acknowledges the value of evidence-based randomized trials, they believe
that they have some limitations, notably:

1. They often select high risk patients.

2. Their power for secondary endpoints is often inadequate.

3. The therapeutic programs often differ from clinical practice.

The committee notes that controlled randomized hypertension trials last for only 4-5 years, whereas middle-aged
hypertensive individuals may be on medication for 20-30 years. Therefore, the data available to date do not
adequately reflect the long-term implications of patient management.
Most importantly for the new guidelines, the committee says it has tried to avoid handing down rigid rules that
would constrain clinical judgment on the management of individual patients, who invariably differ in their personal,
medical, and cultural characteristics.

Classification of Hypertension

The relationship between blood pressure levels and cardiovascular risk is continuous and direct, and this makes any
numerical definition and classification of hypertension arbitrary, the guidelines committee has stressed. Any
numerical definitions must be flexible, resulting from evidence of risk and availability of effective and well-tolerated
drugs. Since no new epidemiologic evidence has emerged since 1999, the WHO/ISH classification (also that of JNC 6,
[6]
but not JNC 7) has been retained (Table 1), with the reservation that the threshold for hypertension must be
considered as flexible -- ie, higher or lower based on the total (global) cardiovascular risk profile of each individual.
Accordingly, the definition of high-normal blood pressure includes values that may be considered as high (ie,
hypertensive) in high-risk individuals or acceptable in those at lower risk.

Table 1. WHO/ISH Definition and Classification of Blood Pressure Levels

Category Systolic (mm Hg) Diastolic (mm Hg)

Optimal < 120 < 80
Normal 120-129 80-84
High-normal 130-139 85-89
Hypertension:
Grade 1 (mild) 140-159 90-99
Grade 2 (moderate) 150-179 100-109
Grade 3 (severe) ≥ 180 ≥ 10
Isolated systolic hypertension ≥ 140 < 90

According to the guidelines, when a patient's SBP and DBP levels fall into different categories, the higher category
should apply. Moreover, in older patients with isolated systolic hypertension, the blood pressure can also be
assessed as grades 1, 2, and 3, according to SBP values in the ranges indicated, provided diastolic values are < 90 mm
Hg.

In another departure, the ESH committee believes that use of the term "hypertension" should be avoided in
classifying blood pressure, and instead used only to promote the case for tight blood pressure control. Notably, they
avoid and do not support the term "prehypertension," as used in JNC 7, although they point out that they were not
aware of the term when the new European guidelines were prepared.

Total Cardiovascular Risk

Total (global) cardiovascular risk makes up an important part of the new guidelines. The committee points out that
hypertension is often accompanied by other risk factors. Total cardiovascular risk quantification allows more
accurate prognostic evaluation of the patient. The timing and type of antihypertensive treatment depend on this
profile, and the blood pressure threshold and targets for therapy are modified, and the need for accompanying
antihypertensive treatment modulated, by it.

Because of this, the classification using stratification for total cardiovascular risk has been expanded from the
scheme in the 1999 WHO/ISH guidelines to indicate the added risk in some groups of individuals with normal or high
blood pressure (Table 2).

Table 2. Stratification of Risk to Quantify Prognosis

Other Risk Factors and Blood Pressure

Disease History
Normal High-normal Grade 1 Grade 2 Grade 3
No other risk factors Average risk Average risk Low added risk Moderately added High added risk
risk
1-2 risk factors Low added risk Low added risk Moderate added Moderate added Very high
risk risk added risk
≥ 3 risk factors, TOD, or Moderate added High added risk High added risk High added risk Very high
diabetes risk added risk
ACC High added risk Very high Very high added Very high added Very high
added risk risk risk added risk

ACC = associated clinical conditions; TOD = target organ damage

The total level of risk is the main indication for intervention, but lower or higher pressure values are also more or
less stringent indicators for blood pressure-lowering intervention. The terms "low added," "moderate added," "high
added," and "very high added" risk are calibrated to indicate an approximate absolute 10-year risk of cardiovascular
disease of < 15%, 15% to 20%, 20% to 30%, and > 30% added risk, respectively, according to Framingham criteria,[7]
or an absolute risk of fatal cardiovascular disease of < 4%, 4% to 5%, 5% to 8%, and > 8%, respectively, according to
the SCORE (Systemic Coronary Risk Evaluation) chart.[8] The word "added" is used because it accounts for an increase
in relative risk and, for example, could negate the misleading impression that patients at "low risk" are below
average risk (they are actually at low added risk).

The most common risk factors for cardiovascular disease used for stratification are:

1. Levels of SBP/DBP

2. Men aged > 55 years

3. Women aged > 65 years

4. Smoking

5. Dyslipidemia

o Total cholesterol > 6.5 mmol/L (> 250 mg/dL)

or

o LDL-cholesterol > 4.0 mmol/L (> 155 mg/dL)

or

o HDL-cholesterol :

 Men: < 1.0 mmol/L (< 40 mg/dL);

 Women: < 1.2 mmol/L (< 48 mg/dL)

6. Family history of premature cardiovascular disease (men < 55 years, women < 65 years)

7. Abdominal obesity (abdominal circumference ≥ 102 cm [40 in] in men, 88 cm [35 in] in women)

8. C-reactive protein ≥ 1 mg/dL

Obesity is defined as abdominal obesity to draw attention to an important sign of the metabolic syndrome (carrying
extra weight may not be a problem, unless it is all carried around the abdominal girth). C-reactive protein was added
after increasing evidence pointed to its value as a predictor of cardiovascular events; it has been shown to be as
reliable a predictor as LDL-cholesterol levels, and because of CRP's association with the metabolic syndrome.

The importance of target organ damage (TOD) for determining overall cardiovascular risk is also emphasized. The
practicing physician should seek evidence for organ involvement, including electrocardiogram/echocardiogram
investigations for left ventricular (LV) hypertrophy, ultrasound evidence of arterial wall thickening or atherosclerotic
plaque, slight increase in serum creatinine, and microalbuminuria.

Other factors the guidelines points to as influencing prognosis are the presence/absence of diabetes mellitus and of
associated clinical conditions, including cerebrovascular disease, heart disease, renal disease, peripheral vascular
disease, and advanced retinopathy.

Goals of Treatment

The primary goal of treatment is to achieve the maximum reduction in the long-term total risk of cardiovascular
morbidity and mortality. On the basis of current evidence from trials, blood pressures should be lowered to < 140/90
mm Hg at least, and, if tolerated, to levels < 130/80 mm Hg in diabetic patients.

Therapeutic Approach

The guidelines for initiating antihypertensive treatment are based on 2 criteria:

1. The total level of cardiovascular risk (Table 2), and

2. SBP and DBP levels (Table 1).

The total level of cardiovascular risk is the main indication for intervention, but lower or higher blood pressure
values are also less or more stringent indicators for blood pressure-lowering intervention.

Recommendations for individuals with high normal blood pressure (SBP 130-139 or DBP 85-89 mm Hg on several
occasions) include:

1. Assess other risk factors, TOD (particularly renal), diabetes, associated clinical conditions

2. Initiate lifestyle measures and correction of other risk factors or disease

3. Stratify absolute risk:

Very high/high: begin drug treatment

Moderate: monitor blood pressure frequently

Low: no blood pressure intervention

Recommendations for individuals with grades 1 and 2 hypertension (SBP 140-179 mm Hg or DBP 90-109 mm Hg on
several occasions) include:

1. Assess other risk factors (TOD, diabetes, associated clinical conditions)

2. Initiate lifestyle measures and correction of other risk factors or disease

3. Stratify absolute risk

Very high/high: begin drug treatment promptly

 Moderate: monitor BP and other risk factors for ≥3 months:

-- SBP ≥ 140 or DBP ≥ 90 mm Hg: begin drug treatment

-- SBP < 140 or DBP < 90 mm Hg: continue to monitor

Low: monitor BP and other risk factors for 3-12 months:

-- SBP ≥ 140 or DBP ≥ 90 mm Hg: consider drug treatment and elicit patient's preference

-- SBP < 140 or DBP < 90 mm Hg: continue to monitor

Recommendations for individuals with grade 3 hypertension (SBP ≥ 180 or DBP ≥ 110 mm Hg on repeated
measurements within a few days):

1. Begin drug treatment immediately.

2. Assess other risk factors, TOD, diabetes, associated clinical conditions.

3. Add lifestyle measures and correction of other risk factors or diseases.

Lifestyle Changes

Lifestyle measures recommended include smoking cessation, weight reduction, reduction of excessive alcohol
intake, physical exercise, reduction of salt intake, and increase in fruit and vegetable intake and decrease in
saturated and total fat intake.

Choice of Antihypertensive Agents

The guidelines stress that the main benefits of antihypertensive therapy are due to the lowering of blood pressure
per se. They list the standard major classes of antihypertensive agents suitable for the initiation and maintenance of
therapy:

1. Diuretics

2. Beta-blockers

3. Calcium channel blockers (CCBs)

4. ACE inhibitors

5. Angiotensin-receptor blockers (ARBs).

Regarding a final class, alpha-adrenergic receptor blockers, the arm of the only trial testing an alpha-blocker (the
doxazosin arm of ALLHAT) was terminated early, for an excess of cardiovascular events. Although the termination
has been criticized,[9] evidence favoring alpha-blockers as antihypertensive therapy is more scanty than evidence of
the benefits of other antihypertensive agents. Nevertheless, alpha-blockers should be considered as a therapeutic
option, particularly for combination therapy.

In direct contrast to JNC 7, the European guidelines refrain from recommending specific classes of drugs as initial
treatment; nevertheless, the guidelines recognize that there is evidence to support variable effects of specific drug
classes on special subsets of patients. These include the elderly, pregnant women, diabetic patients; patients with
concomitant cerebrovascular disease, coronary heart disease, or congestive heart failure; deranged renal function;
or resistant hypertension. Specific indications are given for the major classes of antihypertensive drugs (Table 3).

Table 3. Indications for the Major Classes of Antihypertensive Drugs

Drug Conditions Favoring Use
Diuretics (thiazide) CHF; elderly; ISH; hypertensives of African origin
Diuretics (loop) Renal insufficiency; CHF
Diuretics (antialdosterone) CHF; post MI
Beta-blockers Angina pectoris; post MI; CHF (up-titration); pregnancy; tachyarrhythmias
CCBs (dihydropyridine) Elderly; ISH; angina pectoris; peripheral vascular disease; carotid atherosclerosis;
pregnancy
CCBs (verapamil, Angina pectoris, carotid atherosclerosis; supraventricular tachycardia
diltiazem)
ACE inhibitors CHF; LV dysfunction; post MI; nondiabetic nephropathy; type 1 diabetic nephropathy;
proteinuria
ARBs type 2 nephropathy; diabetic microalbuminuria; proteinuria; LV hypertrophy; ACE
inhibitor cough
Alpha-blockers BPH; hyperlipidemia

ARBs, angiotensin receptor blockers; BPH, benign prostatic hyperplasia; CCBs, calcium channel blockers; CHF,
congestive heart failure; ISH, isolated systolic hypertension; MI, myocardial infarction; LV, left ventricular

Finally, if, in the judgment of the physician, treatment can proceed with a single pharmaceutical agent, it is
recommended that monotherapy be started gradually in most patients.

Combination Therapy

In direct contrast to JNC 7, the European guidelines state that emphasis on a preferred class of drugs for "first-line
therapy" is probably outdated, given the need to use 2 or more drugs in combination in order to achieve goal blood
pressure. Taking into account baseline blood pressure and the presence or absence of complications, the guidelines
recommend initiating therapy either with an adequate dose of a single agent or with a low-dose combination of 2
agents.

Drug combinations found to be effective and well tolerated include:

1. Diuretic and beta-blocker

2. Diuretic and ACE inhibitor or ARB

3. CCB (dihydropyridine) and beta-blocker

4. CCB and ACE inhibitor or ARB

5. CCB and diuretic

6. Alpha-blocker and beta-blocker

7. Other combinations (eg, with centrally acting agents, including alpha2-adrenoceptor agonists and
imidazoline-I2 receptor modulators, or ACE inhibitors or ARBs) can be used, if necessary.

8. In many cases, 3 or 4 drugs may be necessary.

There are advantages and disadvantages associated with both monotherapy and combination therapy, the
guidelines state. A disadvantage of combination therapy is the potential exposure of patients to unnecessary drugs,
but control of blood pressure and its complications is more likely. Use of low-dose combinations are more likely to
be free of side effects, and fixed-dose combinations available in Europe are likely to have the practical advantage of
optimizing compliance. The decision as to which approach should be prescribed in which patients will likely depend
on the initial blood pressure, risk factors, and the presence or possibility of TOD.

Other Aspects of the Guidelines

As well as detailed sections on treatment of special populations, other hypertension treatment areas covered in the
guidelines include the present status of genetic analysis, relative benefits of ambulatory/home blood pressure,
follow-up strategies, the importance of long-acting agents, evaluation of adverse effects, and
implementation/compliance/adherence. Treatments for associated risk factors include lipid-lowering agents,
antiplatelet therapy, and glycemic control.

Implementation of Guidelines

The importance of closing the gap between experts' recommendations and the poor blood pressure control seen in
European medical practice is emphasized in the new guidelines. It is hoped that translations of the guidelines into
the many European languages will be sanctioned by the national hypertension societies and leagues, so that the
guidelines can be widely disseminated to improve blood pressure control in Europe.

References

1. Mancia G. Presentation of the ESH-ESC Guidelines for the management of arterial hypertension. Program
and abstracts of the 13th European Meeting on Hypertension; June 13-17, 2003; Milan, Italy.
2. Guidelines Committee. 2003 European Society of Hypertension -- European Society of Cardiology guidelines
for the management of arterial hypertension. J Hypertens. 2003;21;1011-1053. Available online at:
http://www.eshonline.org/ documents/2003_guidelines.pdf
3. Guidelines Sub-Committee. 1999 World Health Organization - International Society of Hypertension
guidelines for the management of hypertension. J Hypertens. 1999;17:151-183.
4. US Department of Health and Human Services. JNC 7 Express. The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Available on the
NHLBI Web site at http://www.nhlbi.nih.gov or from the NHLBI Health Information Center, PO Box 30105,
Bethesda, MD 20824-0105. Phone 301-592-8573 or 240-629-3255 (TTY); Fax: 301-592-8563.
5. Chobanian AV, Bakris GL, Black HR, et al, and the National High Blood Pressure Education Program
Coordinating Committee, The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. The JNC 7 report. JAMA. 2003;289:3560-3572.
6. Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure. The sixth report
of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure (JNC VI).
Arch Intern Med. 1997;157:2413-2446.
7. Anderson KM, Wilson PW, Odell PM, et al. An updated coronary risk profile. A statement for health
professionals. Circulation. 1991;83:356-362.
8. Conroy RM, Pyörälä K, Fitzgerald AP, et al, on behalf of the SCORE project group Prediction of ten-year
risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. In press.
9. The ALLHAT Officers and Co-ordinators for the ALLHAT Collaborative Group. Major cardiovascular events in
hypertensive patients randomized to doxazosin vs chlorthalidone. JAMA. 2000;283:1967-1975.
New European Hypertension Guidelines 2007
 
    2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the
Management of Arterial Hypertension [Guidelines]
 
OF NOTE to read below:
13. Goals of treatment
14. Lifestyle changes
20. Antihypertensive treatment in special groups (elderly, diabetic, renal dysfunction, cerebrovascular disease,
coronary heart disease and heart failure 22. The metabolic syndrome
25. Treatment of associated risk factors
25.1 Lipid lowering agents
25.3 Glycaemic control
 
Journal of Hypertension:Volume 25(9)September 2007p 1751-1762
 
Authors/Task Force Members:; Mancia, Giuseppea; Co-Chairperson (Italy); De Backer, Guyb; Co-Chairperson
(Belgium); Dominiczak, Annac; (UK); Cifkova, Renatad; (Czech Republic); Fagard, Roberte; (Belgium); Germano,
Giuseppef; (Italy); Grassi, Guidog; (Italy); Heagerty, Anthony Mh; (UK); Kjeldsen, Sverre Ei; (Norway); Laurent,
Stephanej; (France); Narkiewicz, Krzysztofk; (Poland); Ruilope, Luisl; (Spain); Rynkiewicz, Andrzejm; (Poland);
Schmieder, Roland En; (Germany); Boudier, Harry AJ Struijkero; (Netherlands); Zanchetti, Albertop; (Italy)
aUniversity of Milano-Bicocca, Ospedale San Gerardo, Milan, Italy bDepartment of Public Health, University Hospital,
Ghent, Belgium cUniversity of Glasgow, Glasgow, UK dInstitute for Clinical Experimental Medicine, Prague, Czech
Republic eCatholic University, Leuven, Belgium fUniversity La Sapienza, Policlinico Umberto 1, Roma, Italy
gUniversity of Milano-Bicocca, San Gerardo Hospital, Milan, Italy hUniversity of Manchester, Manchester, UK
iUllevaal University Hospital, Oslo, Norway jPharmacology Department, Hopital Europeen Georges Pompidou, Paris,
France kDepartment of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland lHospital 12 de
Octubre, Madrid, Spain mDepartment of Cardiology, Medical University of Gdansk, Gdansk, Poland nMedizinische
Klinik, University Erlangen Nuernberg, Erlangen, Germany oDept. of Pharmacology, University of Limburg in
Maastricht, Maastricht, The Netherlands pUniversity of Milan, Istituto Auxologico Italiano, Milan, Italy Special thanks
to Jose L. Rodicio Diaz for his contribution. *Adapted from the 2007 Guidelines for the Management of Arterial
Hypertension (J Hypertens 2007; 25:1105-1187).
 
New European Guidelines on Treatment of Hypertension
News Author: Lisa Nainggolan
CME Author: Laurie Barclay, MD
from Heartwire - a professional news service of WebMD
 
June 20, 2007 - New guidelines for the management of arterial hypertension have been issued at the European
Society of Hypertension (ESH) meeting in Milan, Italy. The recommendations, which were drawn up jointly by task
forces from ESH and the European Society of Cardiology, also appear in the Journal of Hypertension.
 
Co-chair of the task forces, Dr Guy de Backer (University Hospital, Ghent, Belgium) told heartwire the guidelines are
essentially an update to 2003 recommendations. The new document is 82 pages long, and lists 825 references,
reflecting the vast amount of data published on the subject of hypertension in the past 4 years, he noted.
 
Asked to pick out highlights for heartwire, de Backer said this was a difficult task, "as there has been no one dramatic
change, rather small changes in each area. The most important thing is that this is an update and the numerous
references have been critically evaluated. We have kept the general framework and added what we think is most
important from the literature."
 
For the clinician, the main messages can be found in a number of boxes in the paper, which contain position
statements, he noted. "All you need to do is look at the position statements in the boxes, and only read the text if
you want more detail." The task forces are working hard to produce a pocket version of the new guidelines for
release at the ESC meeting in Vienna in September, he added.
 
No One Choice of First-Line Therapy
The overall goal for blood-pressure reduction has remained the same - to get BP to 140/90 mm Hg in the large
majority of people. However, there has been a change in the recommendation for those with comorbidities, de
Backer said. For example, there is a new goal of 130/80 mm Hg for people with established cardiovascular disease
or diabetes.
 
In terms of treatment recommendations, he said the new guidelines shy away from recommending one particular
class of antihypertensive over another as first-line therapy, rather they emphasize the importance of selecting
therapy for each individual, according to any comorbidities they may have.
 
"We have noted the five important drug classes - diuretics, calcium-channel blockers, ACE-inhibitors, beta-blockers
and angiotensin-receptor blockers," he said. But from then on, "if we have to make a choice it should depend on
comorbidities."
 
For example, the best choice of first-line agent for someone with hypertension who also has diabetes is either an
ACE inhibitor or an angiotensin-receptor blocker. For those who have suffered a myocardial infarction, the most
appropriate drug to use first is a beta-blocker and in the elderly, the first-line drug of choice is generally a calcium-
channel blocker to reduce the risk of stroke, he noted.
 
He added, however, that the emphasis on identification of first-line therapy is often pretty futile, because the
majority of patients require multiple blood pressure medications.
 
Other subjects on which there is more information in the new guidelines include the taking of ambulatory BP
measurements, and those performed at home by patients themselves, de Backer noted, adding that the advice for
interpreting ambulatory and home BP measurements "is more detailed now."
 
Extra information can be found on subclinical organ damage, including details about novel markers for renal damage
and for arterial stiffness.
 
J Hypertens. 2007;25:1105-1187.
 
GUIDELINES from Jnl publication
 
1. Definition and classification of hypertension
 
Blood pressure has a unimodal distribution in the population as well as a continuous relationship with CV risk.
 
For practical reasons the term hypertension is used in daily practice and patients are categorized as shown in Table
1. However the real threshold for defining hypertension must be considered as flexible, being high or low based on
the total CV risk of each individual.

* All patients should be classified not only in relation to the grades of hypertension but also in terms of the total CV
risk resulting from the coexistence of different risk factors, organ damage and disease.
 
* Decisions on treatment strategies (initiation of drug treatment, BP threshold and target for treatment, use of
combination treatment, need of a statin and other non-antihypertensive drugs) all importantly depend on the initial
level of risk.
 
* There are several methods by which total CV risk can be assessed, all with advantages and limitations.
Categorization of total risk as low, moderate, high, and very high added risk has the merit of simplicity and can
therefore be recommended. The term 'added risk' refers to the risk additional to the average one.
 
* Total risk is usually expressed as the absolute risk of having a CV event within 10 years. Because of its heavy
dependence on age, in young patients absolute total CV risk can be low even in the presence of high BP with
additional risk factors. If insufficiently treated, however, this condition may lead to a partly irreversible high risk
condition years later. In younger subjects treatment decisions should better be guided by quantification of relative
risk, i.e. the increase in risk in relation to average risk in the population.
 
* Using rigid cut-offs of absolute risk (e.g. > 20% within 10 years) in order to decide on treatment is discouraged.
 
3. Stratification of total CV risk
 
In the Figure 1 total CV risk is stratified in four categories. Low, moderate, high and very high risks refer to 10 year
risk of a fatal or non-fatal CV event. The term added indicates that in all categories risk is greater than average. The
dashed line indicates how the definition of hypertension (and thus the decision about the initiation of treatment) is
flexible, i.e. may be variable depending on the level of total CV risk.

 
5. Diagnostic evaluation
5.1 Aims
 
* Establishing BP values
 
* Identifying secondary causes of hypertension
 
* Searching for
 
* other risk factors;
 
* subclinical organ damage;
 
* concomitant diseases;
 
* accompanying CV and renal complications.
 
5.2 Procedures
 
* repeated BP measurements
 
* family and clinical history
 
* physical examination
 
* laboratory and instrumental investigations.
 
6. Blood pressure (BP) measurement
 
When measuring BP, care should be taken to:
 
* Allow the patients to sit quietly for several minutes;
 
* Take at least two measurements spaced by 1-2 minutes;
 
* Use a standard bladder (12-13 cm long and 35 cm wide) but have a larger bladder available for fat arms and a
smaller one for thin arms and children;
 
* Have the cuff at the level of the heart, whatever the position of the patient;
 
* Deflate the cuff at a speed of 2 mmHg/s;
 
* Use phase I and V (disappearance) Korotkoff sounds to identify SBP and DBP, respectively;
 
* Measure BP in both arms at first visit to detect possible differences due to peripheral vascular disease. In this
instance, take the higher value as the reference one;
 
* Measure BP 1 and 5 min after assumption of the standing position in elderly subjects, diabetic patients, and when
postural hypotension may be frequent or suspected;
 
* Measure heart rate by pulse palpation (at least 30 sec).
 
7. Ambulatory and home BP measurements
7.1 Ambulatory BP
 
* Although office BP should be used as the reference, ambulatory BP may improve prediction of CV risk in untreated
and treated patients.
 
* 24-h ambulatory BP monitoring should be considered, in particular, when
 
- considerable variability of office BP is found
 
- high office BP is measured in subjects otherwise at low total CV risk
 
- there is a marked discrepancy between BP values measured in the office and at home
 
- resistance to drug treatment is suspected
 
- hypotensive episodes are suspected, particularly in elderly and diabetic patients
 
- sleep apnoea is suspected
 
- office BP is elevated in pregnant women and pre-eclampsia is suspected
 
Normal values for 24 hour average BP are lower than for office BP, i.e. < 125-130 mmHg systolic and < 80 mmHg
diastolic. Normal values of daytime BP are < 130-135 mmHg systolic and < 85 mmHg diastolic.
 
7.2 Home BP
 
* Self-measurement of BP at home is of clinical value. Home BP measurements should be encouraged in order to:
 
- provide more information on the BP lowering effect of treatment at trough, and thus on therapeutic coverage
throughout the dose-to-dose time interval
 
- improve patient's adherence to treatment regimens
 
- understand technical reliability/environmental conditions of ambulatory BP data
 
* Self-measurement of BP at home should be discouraged whenever:
 
- it causes anxiety to the patient
 
- it induces self-modification of the treatment regimen
 
* Normal values for home BP are lower than for office BP, i.e. < 130-135 mmHg systolic and < 85 mmHg diastolic.
 
7.3 Particular conditions
 
Isolated office hypertension (White coat hypertension)
 
Office BP persistently ≥ 140/90 mmHg
 
Normal daytime ambulatory (< 130-135/85 mmHg) or home (< 130-135/85 mmHg) BP
 
In these subjects CV risk is less than in individuals with raised office and ambulatory or home BP but may be slightly
greater than that of individuals with in and out-of-office normotension.
 
Isolated ambulatory hypertension (Masked hypertension)
 
Office BP persistently normal (< 140/90 mmHg)
 
Elevated ambulatory (≥ 125-130/80 mmHg) or home (≥ 130-135/85 mmHg) BP
 
In these subjects CV risk is close to that of individuals with in and out-of-office hypertension
 
8. Diagnostic evaluation: medical history and physical examination 8.1 Family and clinical history
 
1. Duration and previous level of high BP
 
2. Indications of secondary hypertension
 
3. Risk factors
 
4. Symptoms of organ damage
 
5. Previous antihypertensive therapy (efficacy, adverse events)
 
6. Personal, family, environmental factors.
 
8.2 Physical examinations
 
1. Signs suggesting secondary hypertension
 
2. Signs of organ damage
 
3. Evidence of visceral obesity.
 
9. Laboratory investigation
9.1 Routine tests
 
* Fasting plasma glucose
 
* Serum total cholesterol
 
* Serum LDL-cholesterol
 
* Serum HDL-cholesterol
 
* Fasting serum triglycerides
 
* Serum potassium
 
* Serum uric acid
 
* Serum creatinine
 
* Estimated creatinine clearance (Cockroft-Gault formula) or glomerular filtration rate (MDRD formula)
 
* Haemoglobin and haematocrit
 
* Urinalysis (complemented by microalbuminuria dipstick test and microscopic examination)
 
* Electrocardiogram.
 
9.2 Recommended tests
 
* Echocardiogram
 
* Carotid ultrasound
 
* Quantitative proteinuria (if dipstick test positive)
 
* Ankle-brachial BP Index
 
* Fundoscopy
 
* Glucose tolerance test (if fasting plasma glucose > 5.6 mmol/L (100 mg/dL)
 
* Home and 24h ambulatory BP monitoring
 
* Pulse wave velocity measurement (where available).
 
9.3 Extended evaluation (domain of the specialist)
 
* Further search for cerebral, cardiac, renal and vascular damage. Mandatory in complicated hypertension.
 
* Search for secondary hypertension when suggested by history, physical examination or routine tests:
measurement of renin, aldosterone, corticosteroids, catecholamines in plasma and/or urine; arteriographies; renal
and adrenal ultrasound; computer-assisted tomography; magnetic resonance imaging.
 
10. Searching for subclinical organ damage
 
Due to the importance of subclinical organ damage as an intermediate stage in the continuum of vascular disease
and as a determinant of total CV risk, signs of organ involvement should be sought carefully by appropriate
techniques:
 
10.1 Heart
 
Electrocardiography should be part of all routine assessment of subjects with high BP in order to detect left
ventricular hypertrophy, patterns of strain, ischaemia and arrhythmias. Echocardiography is recommended when a
more sensitive method of detection of left ventricular hypertrophy is considered useful as well as assessment of left
ventricular systolic function. Geometric patterns can be defined echocardiographically, of which concentric
hypertrophy carries the worse prognosis. Diastolic dysfunction can be evaluated by transmitral Doppler.
 
10.2 Blood vessels
 
Ultrasound scanning of the extracranial carotid arteries is recommended when detection of vascular hypertrophy or
asymptomatic atherosclerosis is deemed useful. Large artery stiffening (leading to isolated systolic hypertension in
the elderly) can be measured by pulse wave velocity. It might be more widely recommended if its availability were
greater. A low ankle-brachial BP index signals advanced peripheral artery disease.
 
10.3 Kidney
 
Diagnosis of hypertension-related renal damage is based on a reduced renal function or an elevated urinary
excretion of albumin. Estimation from serum creatinine of glomerular filtration rate (MDRD formula, requiring age,
gender, race) or creatinine clearance (Cockroft-Gault formula, requiring also body weight) should be routine
procedure. Urinary protein should be sought in all hypertensives by dipstick. In dipstick negative patients low grade
albuminuria (microalbumniuria) should be determined in spot urine and related to urinary creatinine excretion.
 
10.4 Fundoscopy
 
Examination of eye grounds is recommended in severe hypertensives only. Mild retinal changes are largely non-
specific except in young patients. Haemorrhages, exudates and papilloedema, only present in severe hypertension,
are associated with increased CV risk.
 
10.5 Brain
 
Silent brain infarcts, lacunar infarctions, microbleeds and white matter lesions are not infrequent among
hypertensives, and can be detected by MRI or CT. Availability and costs do not allow indiscriminate use of these
techniques. In elderly hypertensives, cognitive tests may help to detect initial brain deterioration.
 
The Table 3 summarizes availability, prognostic value and cost of procedures to detect subclinical organ damage.
 
11. Evidence on the benefit of antihypertensive treatment
 
* Placebo controlled trials have provided uncontroversial evidence that BP lowering reduces fatal and non-fatal
cardiovascular events. Beneficial effects have been found when treatment is initiated with a thiazide diuretic, a β-
blocker, a calcium antagonist, an ACE-inhibitor or an angiotensin receptor blocker.
 
* Trials comparing different antihypertensive drugs have not been able to conclusively demonstrate that for the
same reduction in BP different antihypertensive drugs (or drug combinations) reduce to different degree CV events.
These trials (and their meta-analysis and meta-regressions) underline the crucial role of BP lowering in reducing all
kinds of CV events, i.e. stroke, myocardial infarction and heart failure, independently of the agents used.
 
* BP-independent effects related to use of specific drugs have been reported for cause-specific events, e.g. stroke,
heart failure and coronary events, but these effects are smaller than the dominant effect of BP lowering
 
* BP-independent effects attributable to specific drugs have been more consistently shown for events that occur
earlier in the continuum of CV disease, e.g. protection against subclinical organ damage and prevention of high risk
conditions such as diabetes, renal failure and atrial fibrillation.
 
12. Initiation of BP lowering therapy
 
* Initiation of BP lowering therapy should be decided on two criteria:
 
1. The level of SBP and DBP
 
2. The level of total CV risk
 
* This is detailed in the Figure 2 which considers treatment based on lifestyle changes and antihypertensive drugs
with, in addition, recommendations on the time delay to be used for assessing the BP lowering effects.
 
The following points should be emphasized:
 
* Drug treatment should be initiated promptly in grade 3 hypertension as well as in grade 1 and 2 when total CV risk
is high or very high.
 
* In grade 1 or 2 hypertensives with moderate total CV risk drug treatment may be delayed for several weeks and in
grade 1 hypertensives without any other risk factor for several months. However, even in these patients lack of BP
control after a suitable period should lead to initiation of drug treatment.
 
* When initial BP is in the high normal range the decision on drug intervention heavily depends on the level of risk. In
the case of diabetes, history of cerebrovascular, coronary or peripheral artery disease, the recommendation to start
BP lowering drugs is justified by the results of controlled trials. Subjects with BP in the high normal range in whom
total CV risk is high because of a subclinical organ damage should be advised to implement intense lifestyle
measures. In these subjects BP should be closely monitored and drug treatment considered in the presence of a
worsening of the clinical condition.
 
13. Goals of treatment
 
* In hypertensive patients, the primary goal of treatment is to achieve maximum reduction in the long-term total risk
of CV disease.
 
* This requires treatment of the raised BP per se as well as of all associated reversible risk factors.
 
* BP should be reduced to at least below 140/90 mmHg (systolic/diastolic), and to lower values, if tolerated, in all
hypertensive patients.
 
* Target BP should be at least < 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).
 
* Despite use of combination treatment, reducing systolic BP to < 140 mmHg may be difficult and more so if the
target is a reduction to < 130 mmHg. Additional difficulties should be expected in the elderly, in patients with
diabetes, and in general, in patients with CV damage.
 
* In order to more easily achieve goal BP, antihypertensive treatment should be initiated before significant CV
damage develops.
 
14. Lifestyle changes
 
* Lifestyle measures should be instituted, whenever appropriate, in all patients, including those who require drug
treatment. The purpose is to lower BP, to control other risk factors and to reduce the number or the doses of
antihypertensive drugs.
 
* Lifestyle measures are also advisable in subjects with high normal BP and additional risk factors to reduce the risk
of developing hypertension.
 
* The lifestyle measures that are widely recognized to lower BP and/or CV risk, and that should be considered are:
 
- smoking cessation
 
- weight reduction (and weight stabilization)
 
- reduction of excessive alcohol intake
 
- physical exercise
 
- reduction of salt intake
 
- increase in fruit and vegetable intake and decrease in saturated and total
 
- fat intake
 
* Lifestyle recommendations should not be given as lip service but instituted with adequate behavioural and expert
support, and reinforced periodically.
 
* Because long-term compliance with lifestyle measures is low and the BP response highly variable, patients under
non-pharmacological treatment should be followed-up closely to start drug treatment when needed and in a timely
fashion.
 
15. Choice of antihypertensive drugs
 
* The main benefits of antihypertensive therapy are due to lowering of BP per se
 
* Five major classes of antihypertensive agents - thiazide diuretics, calcium antagonists, ACE-inhibitors, angiotensin
receptor blockers and β-blockers - are suitable for the initiation and maintenance of antihypertensive treatment,
alone or in combination. β-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 many patients more than one drug is needed, so emphasis on identification of the first class of drugs to be used
is often futile. Nevertheless, there are conditions for which there is evidence in favour of some drugs versus others
either as initial treatment or as part of a combination.
 
* The choice of a specific drug or a drug combination, and the avoidance of others should take into account the
following:
 
1. The previous favourable or unfavourable experience of the individual patient with a given class of compounds.
 
2. The effect of drugs on CV risk factors in relation to the CV risk profile of the individual patient.
 
3. The presence of subclinical organ damage, clinical CV disease, renal disease or diabetes, which may be more
favourably 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 conditions.
 
6. The cost of drugs, either to the individual patient or to the health provider. However, cost considerations should
never predominate over efficacy, tolerability, and protection of the individual patient.
 
* Continuing attention should be given to side-effects of drugs, because they are the most important cause of non-
compliance. Drugs are not equal in terms of adverse effects, particularly in individual patients.
 
* The BP lowering effect should last 24 hours. This can be checked by office or home BP measurements at trough or
by ambulatory BP monitoring.
 
* Drugs which exert their antihypertensive effect over 24 hours with a once-a-day administration should be
preferred because a simple treatment schedule favours compliance.
 
16. Conditions favouring the use of some antihypertensive drugs versus other
* Regardless of the drug employed, monotherapy allows to achieve BP target in only a limited number of
hypertensive patients.
 
* Use of more than one agent is necessary to achieve target BP in the majority of patients. A vast array of effective
and well tolerated combinations is available.
 
* Initial treatment can make use of monotherapy or combination of two drugs at low doses with a subsequent
increase in drug doses or number, if needed.
 
* Monotherapy could be the initial treatment for mild BP elevation with low or moderate total CV risk. A
combination of two drugs at low doses should be preferred as the first step in treatment when the initial BP is in the
grade 2 or 3 or total CV risk is high or very high with mild BP elevation.
 
* Fixed combinations of two drugs can simplify the treatment schedule and favour compliance.
 
* In several patients BP control is not achieved by two drugs, and a combination of three of more drugs is required.
 
* In uncomplicated hypertensives and in the elderly, antihypertensive therapy should normally be initiated gradually.
In higher risk hypertensives, goal BP should be achieved more promptly, which favours initial combination therapy
and quicker adjustment of doses.
 
20. Antihypertensive treatment in special groups
 
Antihypertensive treatment may differ from the one recommended in the general hypertensive population, in
special groups of patients or in specific clinical conditions. The specific requirements under these circumstances are
detailed below.
 
20.1 Elderly patients
 
* Drug treatment can be initiated with thiazide diuretics, calcium antagonists, angiotensin receptor antagonists, ACE-
inhibitors, and β-blockers, in line with general guidelines. Trials specifically addressing treatment of isolated systolic
hypertension have shown the benefit of thiazides and calcium antagonists but subanalysis of other trials also show
efficacy of angiotensin receptor blockers.
 
* Initial doses and subsequent dose titration should be more gradual because of a greater chance of undesirable
effects, especially in very old and frail subjects.
 
* BP goal is the same as in younger patients, i.e. < 140/90 mmHg or below, if tolerated. Many elderly patients need
two or more drugs to control blood pressure and reductions to < 140 mmHg systolic may be difficult to obtain.
 
* Drug treatment should be tailored to the risk factors, target organ damage and associated cardiovascular and non-
cardiovascular conditions that are frequent in the elderly. Because of the increased risk of postural hypotension, BP
should always be measured also in the erect posture.
 
* In subjects aged 80 years and over, evidence for benefits of antihypertensive treatment is as yet inconclusive.
However, there is no reason for interrupting a successful and well tolerated therapy when a patient reaches 80 years
of age.
 
20.2 Diabetic patients
 
* Where applicable, intense non-pharmacological measures should be encouraged in all patients with diabetes, with
particular attention to weight loss and reduction of salt intake in type 2 diabetes.
 
* Goal BP should be < 130/80 mmHg and antihypertensive drug treatment may be started already when BP is in the
high normal range.
 
* To lower BP, all effective and well tolerated drugs can be used. A combination of two or more drugs is frequently
needed.
 
* Available evidence indicates that lowering BP also exerts a protective effect on appearance and progression of
renal damage. Some additional protection can be obtained by the use of a blocker of the renin-angiotensin system
(either an angiotensin receptor antagonist or an ACE-inhibitor).
 
* A blocker of the renin-angiotensin system should be a regular component of combination treatment and the one
preferred when monotherapy is sufficient.
 
* Microalbuminuria should prompt the use of antihypertensive drug treatment also when initial BP is in the high
normal range. Blockers of the renin-angiotensin system have a pronounced antiproteinuric effect and their use
should be preferred.
 
* Treatment strategies should consider an intervention against all CV risk factors, including a statin.
 
* Because of the greater chance of postural hypotension, BP should also be measured in the erect posture.
 
20.3 Patients with renal dysfunction
 
* Renal dysfunction and failure are associated with a very high risk of CV events.
 
* Protection against progression of renal dysfunction has two main requirements: a) strict blood pressure control (<
130/80 mmHg and even lower if proteinuria is > 1g/day); b) lowering proteinuria to values as near to normal as
possible.
 
* To achieve the BP goal, combination therapy of several antihypertensive agents (including loop diuretics) is usually
required.
 
* To reduce proteinuria, an angiotensin receptor antagonist, an ACE-inhibitor or a combination of both are required.
 
* There is controversial evidence as to whether blockade of the renin-angiotensin system has a specific beneficial
role in preventing or retarding nephrosclerosis in non-diabetic non-proteinuric hypertensives, except perhaps in
Afro-American individuals. However, inclusion of one of these agents in the combination therapy required by these
patients appears well founded.
 
* An integrated therapeutic intervention (antihypertensive, statin and antiplatelet therapy) has to be frequently
considered in patients with renal damage because, under these circumstances, CV risk is extremely high.
 
20.4 Patients with cerebrovascular disease
 
* In patients with a history of stroke or transient ischaemic attacks, antihypertensive treatment markedly reduces
the incidence of stroke recurrence and also lowers the associated high risk of cardiac events.
 
* Antihypertensive treatment is beneficial in hypertensive patients as well as in subjects with BP in the high normal
range. BP goal should be < 130/80 mmHg.
 
* Because evidence from trials suggests that the benefit largely depends on BP lowering per se, all available drugs
and rational combinations can be used. Trial data have been mostly obtained with ACE-inhibitors and angiotensin
receptor antagonists, in association with or on the top of diuretic and conventional treatment, but more evidence is
needed before their specific cerebrovascular protective properties are established.
 
* There is at present no evidence that BP lowering has a beneficial effect in acute stroke but more research is under
way. Until more evidence is obtained antihypertensive treatment should start when post-stroke clinical conditions
are stable, usually several days after the event. Additional research in this is necessary because cognitive dysfunction
is present in about 15% and dementia in 5% of subjects aged ≥ 65 years.
 
* In observational studies, cognitive decline and incidence of dementia have a positive relationship with BP
values. There is some evidence that both can be somewhat delayed by antihypertensive treatment.
 
20.5 Patients with coronary heart disease and heart failure
 
* In patients surviving a myocardial infarction, early administration of β-blockers, ACE-inhibitors or angiotensin
receptor blockers reduces the incidence of recurrent myocardial infarction and death. These beneficial effects can be
ascribed to the specific protective properties of these drugs but possibly also to the associated small BP reduction.
 
* Antihypertensive treatment is also beneficial in hypertensive patients with chronic coronary heart disease. The
benefit can be obtained with different drugs and drug combinations (including calcium antagonists) and appears to
be related to the degree of BP reduction. A beneficial effect has been demonstrated also when initial BP is < 140/90
mmHg and for achieved BP around 130/80 mmHg or less.
 
* A history of hypertension is common while a raised BP is relatively rare in patients with congestive heart failure. In
these patients, treatment can make use of thiazide and loop diuretics, as well as of β-blockers, ACE-inhibitors,
angiotensin receptor antagonist and antialdosterone drugs on top of diuretics. Calcium antagonists should be
avoided unless needed to control BP or anginal symptoms.
 
* Diastolic heart failure is common in patients with a history of hypertension and has an adverse prognosis. There is
at present no evidence on the superiority of specific antihypertensive drugs.
 
20.6 Patients with atrial fibrillation
 
* Hypertension is the most important risk factor for atrial fibrillation. Atrial fibrillation markedly increases the risk of
CV morbidity and mortality, particularly of embolic stroke.
 
* Increased left ventricular mass and left atrium enlargement are independent determinants of atrial fibrillation, and
require intense antihypertensive therapy.
 
* Strict blood pressure control is required in patients under anticoagulant treatment to avoid intracerebral and
extracerebral bleeding.
 
* Less new onset and recurrent atrial fibrillation has been reported in hypertensive patients treated with angiotensin
receptor antagonists.
 
* In permanent atrial fibrillation, β-blockers and non-dihydropyridine calcium antagonists (verapamil, diltiazem) help
controlling ventricular rate.
 
21. Hypertension in women
21.1 Treatment
 
Response to antihypertensive agents and beneficial effects of BP lowering appear to be similar in women and in
men. However, ACE-inhibitors and angiotensin receptor antagonists should be avoided in pregnant and women
planning pregnancy because of potential teratogenic effects during pregnancy.
 
21.2 Oral contraceptives
 
Even oral contraceptives with low oestrogen content are associated with an increased risk of hypertension, stroke
and myocardial infarction. The progestogen-only pill is a contraceptive option for women with high BP, but their
influence on cardiovascular outcomes has been insufficiently investigated.
 
21.3 Hormone replacement therapy
 
The only benefit of this therapy is a decreased incidence of bone fractures and colon cancer, accompanied, however,
by increased risk of coronary events, stroke, thromboembolism, breast cancer, gallbladder disease and dementia.
This therapy is not recommended for cardioprotection in postmenopausal women.
 
21.4 Hypertension in pregnancy
 
* Hypertensive disorders in pregnancy, particularly pre-eclampsia, may adversely affect neonatal and maternal
outcomes.
 
* Non-pharmacological management (including close supervision and restriction of activities) should be considered
for pregnant women with SBP 140-149 mmHg or DBP 90-95 mmHg. In the presence of gestational hypertension
(with or without proteinuria) drug treatment is indicated at BP levels > 140/90 mmHg. SBP levels ≥ 170 or DBP ≥ 110
mmHg should be considered an emergency requiring hospitalization.
 
* In non-severe hypertension, oral methyldopa, labetalol, calcium antagonists and (less frequently) β-blockers are
drugs of choice.
 
* In pre-eclampsia with pulmonary oedema, nitroglycerine is the drug of choice. Diuretic therapy is inappropriate
because plasma volume is reduced.
 
* As emergency, intravenous labetalol, oral methyldopa and oral nifedipine are indicated. Intravenous hydralazine is
no longer the drug of choice because of an excess of perinatal adverse effects. Intravenous infusion of sodium
nitroprusside is useful in hypertensive crises, but prolonged administration should be avoided.
 
* Calcium supplementation, fish oil and low dose aspirin are not recommended. However, low dose aspirin may be
used prophylactically in women with a history of early onset pre-eclampsia.
 
22. The metabolic syndrome
 
* The metabolic syndrome is characterized by the variable combination of visceral obesity and alterations in glucose
metabolism, lipid metabolism and BP. It has a high prevalence in the middle age and elderly population.
 
* Subjects with the metabolic syndrome also have a higher prevalence of microalbuminuria, left ventricular
hypertrophy and arterial stiffness than those without metabolic syndrome. Their CV risk is high and the chance of
developing diabetes markedly increased.
 
* In patients with metabolic syndrome diagnostic procedures should include a more in-depth assessment of
subclinical organ damage. Measuring ambulatory and home BP is also desirable.
 
* In all individuals with metabolic syndrome intense lifestyle measures should be adopted. When there is
hypertension drug treatment should start with a drug unlikely to facilitate onset to diabetes. Therefore a blocker of
the renin-angiotensin system should be used and followed, if needed, by the addition of a calcium antagonist or a
low-dose thiazide diuretic. It appears desirable to bring BP to the normal range.
 
* Lack of evidence from specific clinical trials prevents firm recommendations on use of antihypertensive drugs in all
metabolic syndrome subjects with a high normal BP. There is some evidence that blocking the renin-angiotensin
system may also delay incident hypertension.
 
* Statins and antidiabetic drugs should be given in the presence of dyslipidemia and diabetes, respectively. Insulin
sensitizers have been shown to markedly reduce new onset diabetes, but their advantages and disadvantages in the
presence of impaired fasting glucose or glucose intolerance as a metabolic syndrome component remain to be
demonstrated.
 
23. Resistant hypertension
23.1 Definition
 
BP ≥ 140/90 mmHg despite treatment with at least three drugs (including a diuretic) in adequate doses and after
exclusion of spurious hypertension such as isolated office hypertension and failure to use large cuffs on large arms.
 
23.2 Causes
 
* Poor adherence to therapeutic plan;
 
* Failure to modify lifestyle including:
 
weight gain
 
heavy alcohol intake (NB: binge drinking);
 
* Continued intake of drugs that raise blood pressure (liquorice, cocaine, glucocorticoids, non-steroid anti-
inflammatory drugs, etc.);
 
* Obstructive sleep apnea;
 
* Unsuspected secondary cause;
 
* Irreversible or limited reversibility of organ damage;
 
* Volume overload due to:
 
inadequate diuretic therapy
 
progressive renal insufficiency
 
high sodium intake
 
hyperaldosteronism.
 
23.3 Treatment
 
* Adequate investigation of causes
 
* If necessary, use of more than three drugs, including an aldosterone
 
* antagonist.
 
24. Hypertensive emergencies
 
* Hypertensive encephalopathy
 
* Hypertensive left ventricular failure
 
* Hypertension with myocardial infarction
 
* Hypertension with unstable angina
 
* Hypertension and dissection of the aorta
 
* Severe hypertension associated with subarachnoid haemorrhage or cerebrovascular accident
 
* Crisis associated with phaeochromocytoma
 
* Use of recreational drugs such as amphetamines, LSD, cocaine or ecstasy
 
* Hypertension perioperatively
 
* Severe pre-eclampsia or eclampsia
 
25. Treatment of associated risk factors
25.1 Lipid lowering agents
 
* All hypertensive patients with established CV disease or with type 2 diabetes should be considered for statin
therapy aiming at serum total and LDL cholesterol levels of, respectively, < 4.5 mmol/L (175 mg/dL) and < 2.5
mmol/L (100 mg/dL), and lower, if possible.
 
* Hypertensive patients without overt CV disease but with high CV risk (≥ 20% risk of events in 10 years) should also
be considered for statin treatment even if their baseline total and LDL serum cholesterol levels are not elevated.
 
25.2 Antiplatelet therapy
 
* Antiplatelet therapy, in particular low-dose aspirin, should be prescribed to hypertensive patients with previous CV
events, provided that there is no excessive risk of bleeding.
 
* Low-dose aspirin should also be considered in hypertensive patients without a history of CV disease if older than
50 years and with a moderate increase in serum creatinine or with a high CV risk. In all these conditions, the benefit-
to-risk ratio of this intervention (reduction in myocardial infarction greater than the risk of bleeding) has been
proven favourable.
 
* To minimize the risk of haemorrhagic stroke, antiplatelet treatment should be started after achievement of BP
control.
 
25.3 Glycaemic control
 
* Effective glycaemic control is of great importance in patients with hypertension and diabetes.
 
* In these patients dietary and drug treatment of diabetes should aim at lowering plasma fasting glucose to values 6
mmol/L (108 mg/dL) and at a glycated haemoglobin of < 6.5%.
 
26. Patients' follow-up
 
* Effective and timely titration to BP control requires frequent visits in order to timely modify the treatment regimen
in relation to BP changes and the appearance of side-effects.
 
* Once the target BP has been reached, the frequency of visits can be considerably reduced. However, excessively
wide intervals between visits are not advisable because they interfere with a good doctor-patient relationship, which
is crucial for patient's compliance.
 
* Patients at low risk or with grade 1 hypertension may be seen every 6 months and regular home BP measurements
may further extend this interval. Visits should be more frequent in high or very high risk patients. This is the case also
in patients under non-pharmacological treatment alone due to the variable antihypertensive response and the low
compliance to this intervention.
 
* Follow-up visits should aim at maintaining control of all reversible risk factors as well as at checking the status of
organ damage. Because treatment-induced changes in left ventricular mass and carotid artery wall thickness are
slow, there is no reason to perform these examinations at less than 1 year intervals.
 
* Treatment of hypertension should be continued for life because in correctly diagnosed patients cessation of
treatment is usually followed by return to the hypertensive state. Cautious downward titration of the existing
treatment may be attempted in low risk patients after long-term BP control, particularly if non-pharmacological
treatment can be successfully implemented.
 
27. How to improve compliance with blood pressure lowering therapy
 
* Inform the patient of the risk of hypertension and the benefit of effective treatment.
 
* Provide clear written and oral instructions about treatment.
 
* Tailor the treatment regimen to patient's lifestyle and needs.
 
* Simplify treatment by reducing, if possible, the number of daily medicaments.
 
* Involve the patient's partner or family in information on disease and treatment plans.
 
* Make use of self measurement of BP at home and of behavioural strategies such as reminder systems.
 
* Pay great attention to side-effects (even if subtle) and be prepared to timely change drug doses or types, if needed.
 
* Dialogue with patient regarding adherence and be informed of his/her problems.
 
* Provide reliable support system and affordable prices.
 
* Arrange a schedule of follow-up visits.
 
Disclaimer: The ESH Guidelines represent the views of the ESH and were arrived at after careful consideration of the
available evidence at the time they were written. Health professionals are encouraged to take them fully into
account when exercising their clinical judgment. The guidelines do not, however, override the individual
responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients,
in consultation with that patient, and where appropriate and necessary the patient's guardian or carer. It is also the
health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of
prescription.