hta,curs 2 med int

8/14/2019 HTA,Curs 2 Med Int

1/98

2007 Guidelinesfor the Management of

Arterial Hypertension

Journal of Hypertension2007;25:1105-1187

European Society of HypertensionEuropean Society of Cardiology


2/98

New guidelines, represent the common groundbetween the major organizations involved in their

production:

ESC, represented by its European Association of Preventionand Rehabilitation and Working Group on CardiovascularNursing;

European Society of Atherosclerosis; European Society of Hypertension (ESH);

European Heart Network; Family Practice (World Organization of National Colleges,

Academies and Academic Associations of GeneralPractitioners/Family Physicians - WONCA);

International Society of Behavioral Medicine; European Association for the Study of Diabetes

(EASD)/International Diabetes Federation Europe; and European Stroke Initiative


3/98

August 24, 2007 With an estimated 1.5 billion people

expected to be hypertensive by 2025,an argument making the case that

hypertension is "uncontrolled andconquering the world" is not hyperbole.

This staggering number, as well as the factthat the risk of becoming hypertensive is

greater than 90% for individuals indeveloped countries, highlights thegrowing problem of uncontrolledhypertension, both in developed as well asundeveloped countries, according to an

editorial appearing in the August 18, 2007


4/98

"Many people still believe that hypertension is a disease thatcan be cured, and stop or reduce medication when blood-

pressure levels fall," "Physicians need to convey the

message that hypertension is thefirst and easily measurableirreversible sign that many organs inthe body are under attack. Perhapsthis message will also make people

think more carefully about theconsequences of an unhealthylifestyle and help to give preventive

measures a real chance of success."


5/98

Authors/Task Force Members: Giuseppe Mancia, Co-Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium),Anna Dominiczak (UK), Renata Cifkova (Czech Republic),

Robert Fagard (Belgium), Giuseppe Germano (Italy), GuidoGrassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen(Norway), Stephane Laurent (France), Krzysztof Narkiewicz(Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland),Ronald E. Schmieder (Germany), Harry A.J. Struijker Boudier(Netherlands),

Alberto Zanchetti (Italy)

ESC Committee for Practice Guidelines (CPG): Alec Vahanian, Chairperson (France),John Camm (UK), Raffaele De Caterina (Italy), Veronica Dean (France), KennethDickstein (Norway), Gerasimos Filippatos (Greece), Christian Funck-Brentano(France), Irene Hellemans (Netherlands), Steen Dalby Kristensen (Denmark), KeithMcGregor (France), Udo Sechtem (Germany), Sigmund Silber (Germany), MichalTendera (Poland), Petr Widimsky (Czech Republic), Jose Luis Zamorano (Spain)

ESH Scientific Council: Sverre E. Kjeldsen, President (Norway), Serap Erdine, Vice-President (Turkey), Krzysztof Narkiewicz, Secretary (Poland), Wolfgang Kiowski,Treasurer (Switzerland), Enrico Agapiti-Rosei (Italy), Ettore Ambrosioni (Italy), RenataCifkova (Czech Republic), Anna Dominiczak (UK), Robert Fagard (Belgium), AnthonyM. Heagerty, Stephane Laurent (France), Lars H. Lindholm (Sweden), GiuseppeMancia (Italy), Athanasios Manolis (Greece), Peter M. Nilsson (Sweden), Josep Redon(Spajn), Roland E. Schmieder (Germany), Harry A.J. Struijker-Boudier (Netherlands),Margus Viigimaa (Estonia)

Document Reviewers:Gerasimos Filippatos (CPG Review Coordinator) (Greece),Stamatis Adamopoulos (Greece), Enrico Agabiti-Rosei (Italy), Ettore Ambrosioni(Italy), Vincente Bertomeu (Spain), Denis Clement (Belgium), Serap Erdine (Turkey),Csaba Farsang (Hungary), Dan Gaita (Romania), Wolfgang Kiowski (Switzerland),

Gregory Lip (UK), Jean-Michel Mallion (France), Athanasios J. Manolis (Greece), PeterM. Nillson (Sweden), Eoin OBrien (Ireland), Piotr Ponikowski (Poland), Josep Redon

Journal of Hypertension


6/98

Definitions and Classificationof Blood Pressure Levels

(mmHg)


7/98

Stratification of CV risk in fourcategories

SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT:hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal ornon-fatal event. The term added indicates that in all categories risk is greater thanaverage. OD: subclinical organ damage; MS: metabolic syndrome.

Blood pressure (mmHg)

Very highaddedrisk

Very highadded risk

Very highadded risk

Very highadded risk

Very highadded risk

EstablishedCV or renaldisease

Very highaddedrisk

High addedrisk

High addedrisk

High addedrisk

Moderateadded risk

3 or morerisk factors,MS, OD ordiabetes

Very highaddedrisk

Moderateadded risk

Moderateadded risk

Low

added risk

Low

added risk

1-2 riskfactors

Highadded

risk

Moderateadded risk

Low

added risk

Average

risk

Average

risk

No otherrisk factors

Grade 3HT SBP180 orDBP110

Grade 2 HT

SBP 160-179 or DBP100-109

Grade 1 HT

SBP 140-159 or DBP90-99

Highnormal

SBP 130-139 or DBP85-89

Normal

SBP 120-129 orDBP 80-84

Other riskfactors, ODor disease


8/98

Factors influencing Prognosis

Microalbuminuria 30-300 mg/24h oralbumin-creatinine ratio: 22 (M), or 31(W) mg/g creatinine

Abdominal obesity(Waist circumference >102cm (M), 88cm(W))

Family history of premature CV disease(M at age 65 years)

Echocardiographic LVH(LVMI M 125g/m, W 110 g/m)

Levels of pulse pressure (in the elderly)

Electrocardiographic LVH(Sokolow-Lyon >38 mm; Cornell >2440mm*ms) or

Systolic and diastolic BP levels

Subclinical Organ DamageRisk Factors

(Cont)


9/98

Factors influencing PrognosisRisk Factors

Dyslipidaemia

TC>5.0 mmol/l (190 mg/dL) orLDL-C >3.0 mmol/l (115 mg/dL) orHDL-C:M 55 years;W>65 years)

SmokingFasting plasma glucose5.6-6.9 mmol/L

(102-125 mg/dL)

normal glucose tolerance test

Abdominal obesity

>102cm (M),

88cm (W)

AHC prematureCV disease(M at age


10/98

Factors influencing PrognosisSubclinical Organ Damage

Slight increase in plasmacreatinine:M: 115-133 mol/l (1.3-1.5mg/dL);W: 107-124 mol/l (1.2-1.4

Carotid-femoral pulse

wave velocity >12 m/sec

Carotid wall thickening(IMT >0.9 mm) or plaque

Echocardiographic LVH

(LVMI M 125g/m, W110 g/m)

Electrocardiographic LVH(Sokolow-Lyon >38 mm;Cornell >2440 mm*ms) or

Microalbuminuria 30-300

mg/24horalbumin-creatinine ratio:22 (M), or 31 (W) mg/gcreatinine

Ankle/Brachial BP index


11/98

Factors influencingPrognosis

Postload plasmaglucose >11.0 mmol/l(198 mg/dL)

Fasting plasma 7.0mmol/l

(126 mg/dL) on repeatedmeasurement, or

Diabetes Mellitus

Advanced retinopathy:

haemorrhages or exudates,

Peripheral artery disease

Renal disease: diabeticnephropathy; renal impairment

(serum creatinineM >133, W >124 mmol/l);proteinuria (>300 mg/24 h)

Heart disease: myocardialinfarction; angina; coronaryrevascularization; heart failure

Cerebrovascular disease:ischaemic stroke; cerebralhaemorrhage; transient

ischaemic attack

Established CV or

renal disease


12/98

a) High/ Very High RiskSubjects

BP

180 mmHg systolic

and/or

110 mmHg diastolic

Systolic BP >160 mmHg with low diastolic BP

(


13/98

b). High/ Very High RiskSubjects One or more of the following subclinical organ

damages:- Electrocardiographic (particularly with strain)or echocardiographic(particularly concentric) left

ventricular hypertrophy- Ultrasound evidence of carotid artery wallthickening or plaque

- Increased arterial stiffness

- Slight increase inserum creatinine- Reduced estimated glomerular filtration rateor creatinine clearance

- Microalbuminuria or proteinuria

Established cardiovascular or renal disease


14/98

Availability, Prognostic Value and Costof some markers of organ damage

(scored from 0 to 4 pluses)

++++++++Microalbuminuria

++++++++Est. Glomerular FiltrationRate orCreatinine Clearance

++++++?Cerebral lacunae/ Whitematter lesions

++++++Endothelial dysfunction

+++?Circulatory collagenmarkers

+++?Cardiac/Vascular tissuecomposition

++++++Coronary calcium content

+++++Ankle-Brachial index

++++++Arterial stiffness(Pulse wave velocity)

++++++++Carotid Intima-MediaThickness

++++++++Echocardiography

+++++++ElectrocardiographyCostAvailabilityCV predictive

valueMarkers


15/98

Blood Pressure (BP)MeasurementWhen measuring blood pressure, care should

be taken to:

Allow the patients to sit for several minutes ina quiet room before beginning blood pressuremeasurement

Take at least two measurements spaced by 1-2 minutes, and additional measurements ifthe first two are quite different

Use a standard bladder (12-13 cm long and35 cm wide) but have a larger and a smallerbladder available for fat and thin arms,respectively. Use the smaller bladder inchildren

Have the cuff at the heart level, whatever the(Cont)


16/98

Blood Pressure (BP)Measurement Use phase I and V (disappearance) Korotkoff

sounds to identify systolic and diastolic bloodpressure, respectively

Measure blood pressure in both arms at firstvisit to detect possible differences due toperipheral vascular disease. In this instance,take the higher value as the reference one

Measure blood pressure 1 and 5 min afterassumption of the standing position inelderly subjects, diabetic patients and inother conditions in which postural hypotensionmay be frequent or suspected (Cont)


17/98

Ambulatory BPMeasurements Although office BP should be used as reference,

ambulatory BP may improve prediction ofcardiovascular risk

Normal values are different for office and ambulatoryBP

24-h ambulatory BP monitoring should beconsidered, in particular, when:

- considerable variability of office BP isfound over the same ordifferent visits

- high office BP is measured in subjectsotherwise at low CV risk

- there is a marked discrepancy betweenBP values measured in theoffice and at home

- resistance to drug treatment is suspected-

(Cont)


18/98

Home BP Measurements

Self-measurement of BP at home is ofclinical value

and its prognostic significance is now demonstrated.These measurements should be encouraged in orderto:- provide more information on the BP lowering effect

of treatment at trough and thus on therapeuticcoverage throughout the dose- to-dose timeinterval- improve patients adherence to treatment regimens- there are doubts on technical reliability/

environmental conditions of ambulatory BP dataL Self-measurement of BP at home should be

discouraged whenever:- it causes anxiety to the patient

- it induces self-modification of the treatment regimen (Cont)


19/98

Blood Pressure Thresholds (mmHg)for Definition of Hypertension

with Different Types ofMeasurement

85130-135Home

70120Night

85130-135Day

80125-13024-hour90140Office orClinic

DBPSBP


20/98

Guidelines for Family andClinical History

1. Duration and previous level of high bloodpressure

2. Indications of secondary hypertension:

- family history of renal disease (polycystickidney)

- renal disease, urinary tract infection,haematuria, analgesic abuse (parenchymalrenal disease)

- drug/substance intake: oral contraceptives,

liquorice, carbenoxolone, nasal drops,cocaine, amphetamines, steroids, non-steroidalanti-inflammatory drugs, erythropoietin,cyclosporine

- episodes of sweating, headache, anxiety,

palpitation (phaeochromocytoma)

(Cont)


21/98

drug/substance intake:

oral contraceptives, liquorice, carbenoxolone,

nasal drops, cocaine, amphetamines, steroids,

non-steroidal anti-inflammatory drugs, erythropoietin, cyclosporine

(Cont)


22/98


1. Risk factors:- family and personal history of hypertensionand cardiovascular disease

- family and personal history dyslipidaemia

- family and personal history of diabetesmellitus

- smoking habits

- dietary habits

- obesity; amount of physical exercise

- snoring; sleep apnoea ( information alsofrom partner)

- personality(Cont)


23/98


1. Symptoms of organ damage:- brain and eyes: headache, vertigo, impairedvision, transient ischaemic attacks, sensoryor motor deficit

- heart: palpitation, chest pain, shortness ofbreath, swollen ankles

- kidney: thirst, polyuria, nocturia, haematuria

- peripheral arteries: cold extremities,intermittent claudication

6. Previous antihypertensive therapy:

- Drug(s) used, efficacy and adverse effects (Con


24/98

Physical Examination for SecondaryHypertension, Organ Damage and

Visceral ObesitySigns suggesting secondary hypertension andorgan damage

Features of Cushing Syndrome Skin stigmata of neurofibromatosis(phaeochromocytoma)

Palpation of enlarged kidneys (polycystic kidney)

Auscultation of abdominal murmurs (renovascularhypertension)

Auscultation of precordial or chest murmurs (aorticcoarctation or aortic disease)

Diminished and delayed femoral pulses femoral (Cont)


25/98

Signs of organ damage

Brain: murmurs over neck arteries, motor orsensory defects

Retina: fundoscopic abnormalities

Heart: location and characteristics of apicalimpulse, abnormal cardiac rhythms, ventriculargallop, pulmonary rates, peripheral oedema

Peripheral arteries: absence, reduction, orasymmetry of pulses, cold extremities, ischaemicskin lesions

Carotid arteries: systolic murmurs


Visceral Obesity

(Cont)


26/98

Evidence of visceral obesity

Body weight

Increased waist circumference (standing position)

M: >102 cm, W: >88 cm

Increased body mass index [body weight (Kg)/

height (m)] Overweight 25 Kg/m, Obesity 30

Kg/m


Visceral Obesity


27/98

Laboratory Investigations

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 (MDRDformula)

Haemoglobin and haematocrit Urinalysis (complemented by microalbuminuria

dipstick test and microscopic examination) Electrocardiogram



28/98

Laboratory InvestigationsRoutine tests

Fasting plasma

glucose

Serum totalcholesterol

Serum LDL-cholesterol

Serum HDL-cholesterol

Fasting serumtriglycerides

Serum potassium

Serum uric acid

Estimated creatinine

clearance (Cockroft-Gault formula) orglomerular filtrationrate (MDRD formula)

Haemoglobin andhaematocrit

Urinalysis(complemented by

microalbuminuriadipstick test andmicroscopicexamination)

Electrocardiogram(Cont)


29/98


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 (102 mg/dL) Home and 24h ambulatory BP monitoring

Pulse wave velocity measurement (where

available)

(Cont)

a ora ory nves ga ons


30/98

a ora ory nves ga onsExtended evaluation (domain of the

specialist)

Further search forcerebral, cardiac,renal and vascular

disease, mandatory incomplicated

hypertension

Search for secondary

hypertension whensuggested by history,physical examination

or routine tests:

measurement of :

renin,

aldosterone,

corticosteroids,

catecholamines inplasma and/or urine;

arteriographies;

renal and adrenalultrasound;

computer-assisted

tomography;

magnetic resonance

S hi f b li i l


31/98

Searching for subclinical organdamage

HeartElectrocardiography

Echocardiography

Doppler

hypertrophy, patterns of

strain, ischaemiccondition defects andarrhythmias

detection ofleft ventricularhypertrophy is considereduseful. Geometric patterns(concentric and eccentrichypertrophy, concentric

remodeling)

Diastolic dysfunction canalso be evaluated byDoppler measurement of

transmitral blood pressure

(Cont)


32/98

Searching for subclinical organ damage

Blood vessels Ultrasoundscanning of theextracranial carotidarteries

Pulse wave velocity

Ankle- brachial BP

index signals

vascular hypertrophy(increased thickness ofcommon carotid intima-media)

asymptomatic

atherosclerosis (thickeningof carotid bifurcation andinternal carotid arteries,presence of plagues)

Large artery stiffening(vascular alteration leadingto isolated systolichypertension in theelderly)

peripheral artery disease(Cont)


33/98

Searching for subclinical organ damageKidney

reduced renal function or the detection of anelevated urinary excretion ofalbumin inhypertensive patients serum creatinine

as well estimationfrom serum

creatinine values ofglomerular

filtration creatinine

clearance

The presence ofurinary protein

This allowsclassification ofrenal dysfunction

and

stratification ofcardiovascular risk

(Cont)


34/98

Searching for subclinical organ damageFundoscopy

Examination of eye grounds is recommended in hypertensive with severe

disease, only

grade 1:

arteriolar narrowing;

grade 2:arterio venousnipping

grade 3

(haemorrhages andexudates)

grade 4

(papilloedema),

appear to belargely non-specific

alterations exceptin young patients

present in severe

hypertension, areassociated with anincreased risk ofcardiovascular

events

(Con


35/98

Searching for subclinical organ damageBrain

MRI or

CT

(MRI being generallysuperior to CT)

Availability and costs donot allow asymptomaticuse of these techniques,however

Cognitive tests

Silent brain infarcts,

lacunar infarction,

microbleeds and

white matter lesionsare not infrequentamong hypertensives

In elderlyhypertensive, mayalso help to detectinitial braindeterioration

CT

TAC

+


36/98

Initiation of antihypertensivetreatment

Lifestylechanges +drugtreatment

Lifestylechanges

Diabetes

Lifestylechanges+immediat

e drugtreatment

Lifestylechanges +immediatedrugtreatment




Established CV orrenal

disease

Lifestylechanges+immediate drugtreatment



Lifestylechanges andconsider

drugtreatment

Lifestylechanges

3 or moreriskfactors,

MS, OD ordiabetes

Lifestyle

changes+immediate drugtreatment

Lifestylechanges for

severalweeks thendrugtreatment ifBPuncontrolled

Lifestylechanges for

severalweeks thendrugtreatment ifBPuncontrolled

Lifestylechanges

Lifestylechanges

1-2 riskfactors

Lifestylechanges+immediate drugtreatment

Lifestylechanges forseveralweeks thendrugtreatment ifBPuncontrolled

Lifestylechanges forseveralmonths thendrugtreatment ifBPuncontrolled

No BPintervention

No BPintervention

No otherriskfactors

Grade 3HT SBP180 orDBP 110

Grade 2 HT

SBP 160-179

or DBP 100-109

Grade 1 HT

SBP 140-159

or DBP 90-99

High normal

SBP 130-139

or DBP 85-89

Normal

SBP 120-129

or DBP 80-84

Other riskfactors, OD

or disease


37/98

Stratification of CV risk in fourcategories

SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT:hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or

non-fatal event. The term added indicates that in all categories risk is greater thanaverage. OD: subclinical organ damage; MS: metabolic syndrome.

Blood pressure (mmHg)

Very highaddedrisk

Very highadded risk

Very highadded risk

Very highadded risk

Very highadded risk

EstablishedCV or renaldisease

Very highaddedrisk

High addedrisk

High addedrisk

High addedrisk

Moderateadded risk

3 or morerisk factors,MS, OD ordiabetes

Very highaddedrisk

Moderateadded risk

Moderateadded risk

Low

added risk

Low

added risk

1-2 riskfactors

Highadded

risk

Moderateadded risk

Low

added risk

Average

risk

Average

risk

No otherrisk factors

Grade 3HT SBP180 orDBP110

Grade 2 HT

SBP 160-179 or DBP100-109

Grade 1 HT

SBP 140-159 or DBP90-99

Highnormal

SBP 130-139 or DBP85-89

Normal

SBP 120-129 orDBP 80-84

Other riskfactors, ODor disease


38/98

Goals of Treatment

In hypertensive patients, the primary goal of

treatment is to achieve maximumreduction in the long-term total risk ofcardiovascular disease

This requires treatment of the raised BP perse as well as ofall associated reversible riskfactors

BP should be reduces to at least below140/90 mmHg (systolic/diastolic) and to

lower values, if tolerated, in all hypertensive(Cont)


39/98

Goals of Treatment

Target BP should be at least


40/98

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 otherrisk factors and to reduce the number of

doses of antihypertensive drugs to besubsequently administered

Lifestyle measures are also advisable insubjects with high normal BP and additionalrisk factors to reduce the risk of developinghypertension

Lifestyle recommendations should not begiven as lip service but instituted withadequate behavioral and expert support and


41/98

Lifestyle Changes

The lifestyle measures that are widely recognized

to lower BP or cardiovascular risk and that shouldbe 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 anddecrease in saturated and total fat intake

Because long-term compliance with lifestylemeasures is low and the BP response highlyvariable, patients under non pharmacological

treatment should be followed-up closely to start


42/98

Choice of AntihypertensiveDrugs

The choice of a:

specific drugor a

drugcombinationand

the avoidance

of othersshould takeinto accountthe following:

The previous favorable or

unfavourable experience ofthe individual patient

the cardiovascular risk profileof the individual patient

The presence ofsubclinicalorgan damage, clinicalcardiovascular disease, renaldisease or diabetes

The possibilities ofinteractionswith drugs used for otherconditions

The presence of other

coexisting disorders that maylimit the use of articular (Cont)


43/98

The initiation and maintenance ofantihypertensive treatment, alone or in

combination The main benefits ofantihypertensivetherapy are due tolowering of BPper se

Five major classes ofantihypertensive agents:

thiazide diuretics, calcium antagonists,

ACE inhibitors,

angiotensin receptor

antagonists and -

-blockers,especially incombination with a

thiazide diuretic,should not be usedin patients with themetabolicsyndrome or at highrisk of incidentdiabetes

(Cont)


44/98

Choice of AntihypertensiveDrugs

Continuing attention should be given toside effects of drugs, because they are themost important cause of non-compliance.Drugs are not equal in terms ofadverse

effects, particularly in individual patientsThe BP lowering effect should last 24

hours. This can be checked by office orhome BP measurements at trough or by

ambulatory BP monitoring Drugs which exert their antihypertensive

effect over 24 hours with a once-a-dayadministration should be preferredbecause a sim le treatment schedule

(Cont)


45/98

Antihypertensive Treatment:Preferred Drugs

General rules: lower SBP and DBP to goal. Use any effective agent at adequate doses, ifuseful in combination. Use long acting agents to lower BP throughout 24 hours. Avoid or

minimize adverse effects.

Subclinical organ damageLeft ventricular hypertrophy ACE inhibitors, calcium antagonists,

angiotensin receptor antagonistsAsymptomatic atherosclerosis Calcium antagonists, ACE inhibitorsMicroalbuminuria ACE inhibitors, angiotensin receptor antagonistsRenal dysfunction ACE inhibitors, angiotensin receptor antagonists

Clinical eventPrevious stroke Any BP lowering agentPrevious MI -blockers, ACE inhibitors, angiotensin receptorantagonists Angina pectoris -blockers, calcium antagonistsHeart failure diuretics, -blockers, ACE inhibitors, angiotensinreceptor antagonists, antialdosteroneagentsAtrial fibrillation

Recurrent ACE inhibitors, angiotensin receptor

antagonistsContinuous -blockers, non-dihydropiridine calcium

antagonistsRenal failure/proteinuria ACE inhibitors, angiotensin receptor antagonists,loop diuretics Peripheral artery disease Calcium antagonists

ConditionIsolated systolic hypertension (elderly)Duretics, calcium antagonistsMetabolic syndrome ACE inhibitors, angiotensin receptor

antagonists, calcium antagonistsDiabetes mellitus ACE inhibitors, angiotensin receptor antagonists

(Cont)


46/98

Antihypertensive Treatment:Preferred Drugs

General rules:

lower SBP and DBP to goal. Use any effective agent at adequatedoses, if useful in combination.

Use long acting agents to lower BPthroughout 24 hours.

Avoid or minimize adverse effects(Cont)


47/98

Antihypertensive Treatment:Preferred Drugs 1. Subclinical

organ damageLeft ventricularhypertrophy

Asymptomatic

atherosclerosis

Microalbuminuria

Renal dysfunction

ACE inhibitors, calciumantagonists, Angiotensin receptor

antagonists

Calcium antagonists,

ACE inhibitors

ACE inhibitors, angiotensin receptor

antagonists

ACE inhibitors, angiotensin receptor

antagonists(cont)

Antihypertensive Treatment: Preferred Drugs


48/98

yp g

2. Clinical event Previous stroke

Previous MI

Angina pectoris

Heart failure

Atrial fibrillationRecurrent

Continuous

Renalfailure/proteinuria

Peripheral arterydisease

Any BP lowering agent

-blockers, ACE inhibitors,angiotensin receptor antagonists -blockers, calcium antagonists

diuretics, -blockers, ACE inhibitors,angiotensin receptor antagonists,antialdosterone agents

ACE inhibitors, angiotensin receptorantagonists

-blockers, non-dihydropiridinecalcium antagonists

ACE inhibitors, angiotensin receptorantagonists, loop diuretics

Calcium antagonists

(cont)

ih i f d


49/98

Antihypertensive Treatment: Preferred Drugs

3. Condition

Isolated systolichypertension (elderly)

Metabolic syndrome

Diabetes mellitus

Pregnancy

Blacks

Duretics, calciumantagonists

ACE inhibitors,

angiotensin receptorantagonists, calciumantagonists

ACE inhibitors,angiotensin receptorantagonists

Calcium antagonists,methyldopa, -

blockers (cont)

Conditions favoring use of some


50/98

Conditions favoring use of someantihypertensive drugs versus

others

Hypertension inblacks

Pregnancy

PregnancyGlaucoma

Carotid/ CoronaryAtherosclerosis

Tachyarrhythmias

Supraventriculartachycardia

LV hypertrophyHeart failureHypertension inblacks

Carotidatherosclerosis

Angina pectorisPost-myocardialinfarction

Heart failure

Angina pectorisIsolated systolichypertension(elderly)

Anginapectoris

Isolated systolichypertension(elderly)

Calcium

antagonists(verapamil/diltiazem)

Calcium

antagonists(dihydropyridines)

Beta-

blockers

Thiaside

diuretics

(cont)

Conditions favoring use of some


51/98

Conditions favoring use of someantihypertensive drugs versus

others

Metabolic

syndrome

Atrial fibrillation

ACEI - inducedcough

Proteinuria/Microalbuminuria

Metabolicsyndrome

Carotidatherosclerosis

Atrial fibrillationLV hypertrophy

LV hypertrophyNon-diabeticnephropathy

Proteinuria/Microalbuminuria

Diabeticnephropathy

Diabeticnephropathy

Post-myocardialinfarction

Heart failurePost-myocardialinfarction

Post-myocardialinfarction

LV dysfunction

End stage renaldisease

Heart failureHeart failureHeart failure

Loop

diuretics

Diuretics

antialdosterone

Angiotensin

receptorantagonists

ACE

Inhibitors

Compelling and possible


52/98

Compelling and possiblecontraindications to use of

antihypertensive drugs

Renal failure

Hyperkalaemia

PregnancyHyperkalaemiaBilateral renal arterystenosis

Pregnancy

Angioneurotic oedemaHyperkalaemiaBilateral renal arterystenosis

A-V block (grade 2 or 3)Heart failure

TachyarrhythmiasHeart failure

Peripheral artery diseaseMetabolic syndromeGlucose intoleranceAthletes and physically active

patientsChronic obstructive pulmonarydisease

Asthma

A-V block (grade 2 or 3)

Metabolic syndromeGlucose intolerancePregnancy

Gout

Diuretics(antialdosterone)

AT1 blockers

ACE inhibitors

Calcium antagonists(verapamil,dilitazem)

Calcium antagonists(dihydropiridines)

Beta-blockers

Thiazide diuretics

PossibleCompelling

h


53/98

Monotherapy versusCombination Therapy

Regardless of the drug employed, monotherapy

allows to achieve BP target in only a limitednumber of hypertensive patients

Use of more than one agent is necessary toachieve target BP in the majority of patients. A

vast array of effective and well toleratedcombinations is available

Initial treatment can make use ofmonotherapy orcombination of two drugs at low doses with asubsequent increase in drug doses or number, if

needed Monotherapy could be the initial treatment for a

mild BP elevation with a low or moderate totalcardiovascular risk. A combination of two drugs atlow doses should be preferred as first steptreatment when initial BP is in the grade 2 or 3


54/98

Monotherapy versusCombination Therapy

Fixed combination of two drugs can simplifytreatment schedule and favour compliance

In several patients BP control is not achieved by

two drugs and a combination of three of moredrugs is required

In uncomplicated hypertensives and in the

elderly, antihypertensive therapy should normallybe initiated gradually. In high risk hypertensives,goal blood pressure should be achieved morepromptly, which favours initial combinationtherapy and quicker adjustment of doses

M th


55/98

Monotherapy versuscombination strategies

Choose between

If goal BP not achieved

If goal BP not achieved

Previousagent at full

dose

Switch todifferent agent

at low dose

Previouscombination at

full dose

Add a thirddrug at low

dose

Two-to three-drugcombination at full

dose

Full dosemonotherap

y

Two-three drugcombination at full

doses

Mild BP elevation

Low/moderate CV riskConventional BPtarget

Marked BP elevation

High/very CV high riskLower BP target

Single agent at

low dose

Two-drug combination at

low dose

P ibl bi ti b t


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Possible combinations betweensome classes of antihypertensive

drugsThiazidediuretics

ACEinhibitors

-blocker

s

Angiotensinreceptor

antagonists

Calciumantagonists

-

blockers

The preferred combinations in the general hypertensive population arerepresented as thick lines.

A tih t i T t t i


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Antihypertensive Treatment inthe Elderly

Randomized trials in patients with systolic-

diastolic or isolated systolic hypertension aged60 years have shown that a marked reduction incardiovascular morbidity and mortality can beachieved with antihypertensive treatment

Drug treatment can be initiated with thiazidediuretics, calcium antagonists, angiotensinreceptor antagonists, ACE inhibitors and -blockers, in line with general guidelines. Trialsspecifically addressing treatment of isolated

systolic hypertension have shown the benefit ofthiazide and calcium antagonists but subanalysisof other trials also show efficacy ofangiotensinreceptor antagonists

Initial doses and subsequent dose titration should

be more gradual because of a greater chance of

A tih t i T t t i


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Antihypertensive Treatment inthe Elderly

BP goal is the same as in younger patients, i.e.


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Antihypertensive Treatment inDiabetics

Where applicable, intense non-pharmacologicalmeasures should be encouraged in all diabeticpatients, with particular attention to weight loss andreduction of salt intake in type 2 diabetes

Goal BP should be


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Antihypertensive Treatment inDiabetics

A blocker of the renin-angiotensin system shouldbe a regular component ofcombination treatmentand the one preferred when monotherapy issufficient

Microalbuminuria should prompt the use of

antihypertensive drug treatment also when initialBP is in the high normal range. Blockers of therenin-angiotensin system have a pronouncedantiproteinuric effect and their use should bepreferred

Treatment strategies should consider anintervention against all cardiovascular riskfactors, including a statin

Because of the greater change ofpostural

hypotension, BP should also be measured in the

A tih t i Th i


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Antihypertensive Therapy inpatients

with Renal Dysfunction Renal dysfunction and failure are associatedwith a very high risk of cardiovascular events

Protection against progression of renaldysfunction has two main requirements: a)strict blood pressure control(1 g/day); b)lowering proteinuria to values as near tonormal as possible

To achieve the blood pressure goal,combination therapy of severalantihypertensive agents(including loopdiuretics) is usually required

(cont)

A tih t i Th i


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Antihypertensive Therapy inpatients

with Renal Dysfunction To reduce proteinuria, an angiotensin receptorblocker, an ACE inhibitor or a combination of bothare required

There is a controversial evidence as to whether

blockage of the renin-angiotensin system has aspecific beneficial role in preventing or retardingnephrosclerosis in non-diabetic non-proteinurichypertensives, except perhaps in Afro-Americanindividuals. However, inclusion of one of these

agents in the combination therapy required bythese patients appears well founded

An integrated therapeutic intervention(antihypertensive, statin and antiplatelet therapy)has to be frequently considered in patients withrenal damage because under these

A tih t i t t t


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Antihypertensive treatmentin patients with

Cerebrovascular Disease In patients with a history of stroke or transientischemic attacks, antihypertensive treatmentmarkedly reduces the incidence of stroke recurrenceand also lowers the associated high risk of cardiacevents

Antihypertensive treatment is beneficial inhypertensive patients as well as in subjects with BPin the high normal range. BP goal should be


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Antihypertensive treatment inpatients with Cerebrovascular

Disease There is at present no evidence that BP loweringhas a beneficial effect in acute stroke but moreresearch is under way. Until more evidence isobtained antihypertensive treatment should start

when post-stroke clinical conditions are stable,usually several days after the event. Additionalresearch in this are is necessary becausecognitive dysfunction is present in about 15% and

dementia in 5% of subjects aged 65 years In observational studies, cognitive decline andincidence of dementia have a positiverelationship with BP values. There is someevidence that both can be somewhat delayed by

antihypertensive treatment

Antihypertensive treatment in


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Antihypertensive treatment inpatients with Coronary Heart

Disease and Heart Failure In patients surviving a myocardial infarction, earlyadministration of-blockers, ACE inhibitors orangiotensin receptor antagonists reduces theincidence of recurrent myocardial infraction and

death. These beneficial effects can be ascribed tothe specific protective properties of these drugsbut possibly also to the associated small BPreduction

Antihypertensive treatment is also beneficial in

hypertensive patients with chronic coronary heartdisease. The benefit can be obtained withdifferent drugs and drug combinations (includingcalcium antagonists) and appears to be related to

the degree of BP reduction. A beneficial effect has

Antihypertensive treatment in


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Antihypertensive treatment inpatients with Coronary Heart

Disease and Heart Failure A history of hypertension is also beneficial inhypertensive patients with chronic coronary heartdisease. In these patients, treatment can makeuse ofthiazide and loop diuretics, as well as

of-blockers, ACE inhibitors, angiotensinreceptor antagonists and antialdosteronedrugs on top ofdiuretics. Calciumantagonists 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 adverseprognosis. There is at present no evidence on thesuperiority of specific antihypertensive drugs

Hypertension in women


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Treatment of Hypertension in women

Response to antihypertensive agents andbeneficial effects of BP lowering appear to besimilar in women and in men. However, ACEinhibitors and angiotensin receptor antagonists

should be avoidedin pregnant and pregnancyplanning women because ofpotential teratogeniceffects during pregnancy !

Oral Contraceptives

Even oral contraceptives with low oestrogencontent are associated with an increased risk ofhypertension, stroke and myocardial infarction.

The progestogen-only pill is a contraceptiveoption for women with high BP, but their

influence on cardiovascular outcomes has been(cont.)



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Hypertension in women (cont.)

1. Hypertension in pregnancy

Hypertensive disorders in pregnancy,

particularly pregnancy induced

hypertension with proteinuria (pre eclampsia),

may adversely affect neonatal and

maternal outcomes

(cont.)

Hypertension in pregnancy (cont)


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Non- pharmacologicalmanagement

for pregnant womenwith

SBP 140-149 mmHg or

DBP 90-95 mmHg.

Pharmacological

managementIn non-severe

hypertension,

including :

close supervision and

restriction ofactivities.

oral methyldopa, labetalol, calcium antagonists

and (lessfrequently)

-blockers(cont.)



70/98


In the presence ofgestationalhypertension (withor withoutproteinuria)

but in the case ofpre existinghypertensionwithout organdamage

drug treatment isindicated atBP levels 140/90

mmHg,

threshold fordrug treatment may be

150/95 mmHg.

SBP levels 170 or DBP 110 mmHgshould be considered an

emergency requiring hospitalisation (cont.



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Hypertension in pregnancy (cont.)

Under emergency circumstances:- intravenous labetalol,

- oral methyldopa and

- oral nifedipine are indicated.

Intravenoushydralazine is no longer the drug ofchoice because of an excess of perinatal adverseeffects. Intravenous infusion ofsodiumnitroprusside is useful in hypertensive crises, butprolonged administration should be avoided (fetal

cyanide poisoning) Calcium supplementation, fish oil and low doseaspirin have failed to consistently preventgestational hypertension, especially pre-eclampsia, and are thus not recommended.

However, low dose aspirin may be used (cont.)

Hypertension in pregnancy


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Hypertension in pregnancy(cont.)

In pre-eclampsiawith pulmonaryoedema,

Diuretic therapy isinappropriate becauseplasma volume isreduced in pre-

eclampsia. !

in the treatment ofseizures

nitroglycerine isthe drug of choice.

Magnesiumsulphate

The Metabolic Syndrome


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The metabolic syndrome is characterized by the

variable combination ofvisceral obesity andalterations in glucose metabolism, lipidmetabolism and BP. It has a high prevalence inthe middle age and elderly population

Subjects with the metabolic syndrome also havea higher prevalence ofmicroalbuminuria, leftventricular hypertrophy and arterialstiffness than those without the metabolicsyndrome. Their cardiovascular risk is high and

the chance of developing diabetes markedlyincreased

In patients with a metabolic syndrome diagnosticprocedures should include a more in-depth

assessment ofsubclinical organ damage.

Criteriile NCEP ATP IIIde diagnostic a Sindromului X Metabolic


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de diagnostic a Sindromului X Metabolic

Obezitate abdominal Femei > 88 cm

Circumferina taliei Brbai > 102cm

Trigliceride 150 mg/dL

HDL Colsterol Femei < 40

mg/dL

Brbai


75/98

Definiia OMS a SMet

Glicemie bazal / Toleran la glucozAlterate

Indice talie-old

Trigliceride 150 mg/dL

Tensiune arterial 140/90 mm Hg

Femei> 0.85

Brbai> 0.9

Microalbuminurie rata urinar de excreie 20g/min

HDL-colesterol < 40 mg/dL

Raport albumin/creatinin 30 mg/g

IMC > 30 kg/m2

sau

sau

sau

22dincrietr

ii

dincrietr

ii

Factori geneticiFactori de mediu

si stil de via


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SindromulSindromulmetabolicmetabolic

Inflamaie

TG

HTA HDL-C

Glicemie

Obezitatevisceral

Rspunsvascular

inadecvat

Stareprotrombotic

Evenimente

cardiovasculare Diabet



77/98


In all individuals with metabolic syndrome

individuals intense lifestyle measures should beadopted. When there is hypertension drugtreatment should start with a drug unlikely tofacilitate onset to diabetes. Therefore, a blocker ofthe renin-angiotensin system should be usedfollowed, if needed, by the addition of a calciumantagonist or a low-dose thiazide diuretic. Itappears desirable to bring BP to the normal range

Lack of evidence from specific clinical trialsprevents firm recommendations on use ofantihypertensive drugs in all metabolic syndrome

subjects with a high normal BP. There is someevidence that blocking the renin-angiotensinsystem may also delay incident hypertension

Statins and antidiabetic drugs should be given inthe presence of dyslipidemia and diabetes,

respectively. Insulin sensitizers have been shown

Causes of Resistant


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Causes of ResistantHypertension 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 scarcely reversible organ damage

Volume overload due to: Inadequate diuretic therapy Progressive renal insufficiency High sodium intake

Hyperaldosteronism

Causes of Resistant


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Causes of ResistantHypertension

Causes of spurious resistant hypertension:

Isolated office (white-coat) hypertension

Failure to use large cuff on large arm

Pseudohypertension

Hypertensive Emergencies


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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 cerebrovascularaccident

Crisis associated with phaeochromocytoma Use of recreational drugs such as amphetamines,

LSD, cocaine or ecstasy

Hypertension perioperatively

Severe pre-eclampsia or eclampsia

Treatment of Associated Risk


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Treatment of Associated RiskFactors

Lipid Lowering Agents

All hypertensive patients with establishedcardiovascular disease or with type 2 diabetesshould be considered for statin therapy aiming atserum total and LDL cholesterol levels of,

respectively,


82/98


Antiplatelet Therapy

Antiplatelet therapy, in particular low-doseaspirin, should be prescribed to hypertensivepatients with previous cardiovascular events,provided that there is no excessive risk of

bleeding Low-dose aspirin should also be considered in

hypertensive patients without a history ofcardiovascular disease if older that 50 years, with

a moderate increase in serum creatinine or with ahigh cardiovascular risk. In all these conditions,the benefit-to-risk ratio of this intervention(reduction in myocardial infraction greater thanthe risk of bleeding) has been proven favourable

To minimize the risk of haemorrhagic stroke,

Treatment of Associated Risk


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Glycaemic Control

Effective glycaemic control is of great importancein patients with hypertension and diabetes

In these patients dietary and drug treatment of

diabetes should aim at lowering plasma fastingglucose to values6 mmol/L (108 mg/dL) and at glycatedhaemoglobin of


84/98

Patient s Follow Up

Titration to BP control requires frequent visits in

order to timely modify the treatment regimen inrelation to BP changes and appearance of sideeffects

Once target BP has been obtained, the frequency

of visits can be considerably reduced. However,excessively wide intervals between visits are notadvisable because they interfere with a gooddoctor patient relationship, which is crucial forpatients compliance

Patients at low risk or with grade 1 hypertensionmay be seen every months and regular home BPmeasurements 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

Patients Follow-Up


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Patient s Follow Up

Follow-up visits should aim at maintaining control

of all reversible risk factors as well as at checkingthe status of organ damage. Because treatment-induced changes in left ventricular mass andcarotid artery wall thickness are slow, there is no

reason to perform these examinations at lessthan 1 year intervals

Treatment of hypertension should be continuedfor life because in correctlydiagnosed patients

cessation of treatment is usually followed byreturn to the hypertensivestate. Cautiousdownward titration of the existing treatment maybe attempted in low risk patients after long-termBP control, particularly ifnon pharmacologicaltreatment can be successfull im lemented

How to improve compliance to


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How to improve compliance totreatment Inform the patient on the risk of

hypertension and the benefit of effectivetreatment

Provide clear written and oral instructionsabout treatment.

Tailor the treatment regimen to patientslifestyle and needs

Simplifytreatment by reducing, if possible,the number of disease and treatmentplans

Involve patients partner or family in

information on disease and treatment

(Cont)

How to improve compliance to


87/98

How to improve compliance totreatment

Make use ofself measurement of BP at

home and of behavioral strategies such asreminder systems

Pay great attention to side effects (even ifsubtle) and be prepared to timely changedrug doses or types if needed

Dialogue with patient regarding adherenceand be informed of his/her problems

Provide reliable support system andaffordable prices

(Cont)

Total Cardiovascular Risk


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Dysmetabolic risk factors and subclinicalorgan damage are common in hypertensivepatients

All patients should be classified not only inrelation to the grades of hypertension but also in

terms of the total cardiovascular risk resultingfrom the coexistence of different risk-factors, organ damage and disease

Decisions on treatment strategies (initiation

of drug treatment, BP threshold and target fortreatment, use of combination treatment, need ofa statin and other non-antihypertensive drugs) allimportantly depend on the initial level of risk



89/98


There are several methods by which total

cardiovascular risk can be assessed, all withadvantages and limitations. Categorization oftotalrisk as low, moderate, high and very highaddedrisk has the merit of simplicity and can therefore berecommended. 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 cardiovascularevent within 10 years. Because of its heavy

dependence on age, in young patients absolutetotal cardiovascular risk can be low even in thepresence of high BP with additional risk factors. Ifinsufficiently treated, however, this condition maylead to a partly irreversible high risk condition

years later. In younger subjects treatment


90/98

CONCLUZII

Prof. Univ. Dr. Maria Puchi

1 Cu toate dovezile solide


91/98

1. Cu toate dovezile solideexistente pana in prezent:

HTA reprezint unfactor de risccardiovascularmajor

Strategiile dereducere a TA

scad substanialriscul

O mare parte apacienilorhipertensivi nusunt contieni deprezena acesteia,

Sau dac sunt

contieni nu setrateaz

iar

Concluzii 2.


92/98

inteleterapeutice suntrar atinse

Valorile TA sistolicesunt greu decontrolat,excepionalrealizabile

Indiferent dacsunt prescrise deun medic specialistsau de un medic

generalist.

Iar intele de TAsub 130/80 sunt

greu de realizatpentru pacieniidiabetici saupacienii cu risc

nalt!

Concluzii 3


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Aceste evidene explic de cehipertensiunea arterial:

o cauz important de deces imorbiditate cardiovascular n

ntreaga lume, inclusiv n rile bine

dezvoltate

Concluzii 4


94/98

Implementarea:



ar putea duce lacrestereagradului dediagnostic al HTA ,

alprocentului de pacenti tratati

al controlului terapeutic

Concluzii 5


95/98

Ghidul trebuie adaptat pentru fiecareSocietate Nationala

Autorii ghidului 2007 ESH/ESC lrecomand ca pe un material

educational si nu unul prescriptiv,

deoarece ghidul trateaz boala ngeneral, iar situatiile pot fi diferite de

la un subiect la altul.

Concluzii 6


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Judecata clinic este ceacare trebuie s aib

prioritate n practicaclinic zilnic


97/98



Journal of Hypertension2007;25:1105-1187

European Society of HypertensionEuropean Society of Cardiology


98/98

hta,curs 2 med int

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