Curs Hta 2014 Final Revazutt

HIPERTENSIUNEA
ARTERIALA
Prof univ dr Ion C.intoiu

Univ Titu Maiorescu
Clinica medicina interna
CURS NR 1
HIPERTENSIUNEA ARTERIALA
HYPERTENSION
HYPERTENSON
HYPERTENSION
SUMARY
-CLINICAL REALITY
-MEASUREMENT AND ABPM
-PHYSIOPATHOLOGY
-CLASIFICATION AND STADIALIZATION
-SPECIAL CONDITION :ACUTE ,ISOLATED AND FAMILIAL
-DIAGNOSTIC
-TREATMENT
.Circulaia sngelui
Sngele efectueaz n orgnanism. un dublu circuit: de la inim
diversele organe, i, napoi, de. la acestea la inim.
Acest dublu circuit este prezentat n figura de mai jos.
Hipertensiunea arterial
prevalen crescut n populaia general, la nivel
mondial (30%);
13% din totalul deceselor de pe glob sunt datorate HTA
i complicaiilor acesteia.
Problem major de sntate public
HTA: principalul factor de risc

cardiovascular
13% din total decese pe glob
50% din povara BCV TA suboptimala
HTA = cel mai puternic factor de risc cv.
Cu cat TA e mai mare, cu atat riscul e mai mare
TAs mai bine corelata cu riscul
Mensah. Cardiol Clin. 2002;20:181-185;
World Health Organization. World Health Report 2002. Geneva, Switzerland
Global Hypertension
Control
Percentages
of Patients
whose
Hypertension is Controlled
< 140/90 mmHg
USA
Canada
27
England
6
13
France
24
< 160/95 mmHg

Finland
Spain
Australia
20.5
20
Germany Scotland
22.5
17.5
19
India
9
> 65 years
USA: JNC VI. Arch Intern Med 1997
Canada: Joffres et al. Am J Hypertens 2001
England: Colhoun et al. J Hypertens 1998
France: Chamontin et al. Am J Hypertens
1998
Dr.Sarma@works
MarquesMarques-Vidal P et al. J Hum Hypertens 1997
Adapted from G. Mancia / L.

Ruilope 17
Procentul pacientilor tratati
EHS iunie 2007
Hypertension Prevalence and

Treatment: North America and Europe
Prevalence of Hypertension
Patients on Therapy
55
50
100
45
40
90
80
US
Canada
Italy
Sweden
England
Spain
Finland
Germany
70
35
% 60
50
30
25
40
30
20
15
20
10
10
5
0
Country
Wolf-Maier K et al. JAMA. 2003;289:2363-2369.
SEPHAR
SEPHAR
Country
6.5 milioane
hipertensivi n Romania
2.4 mil
3.7 mil
2.8 mil
0.4 mil
Frecvena subtipurilor de hipertensiune

la toi subiecii fr tratament (%)
Distribuia n funcie de vrst a subtipurilor de

hipertensiune la persoanele fr tratament
Distribuia procentului global de

hipertensiune netratat n respectiva
categorie de vrst
Vrsta (ani)
Hipertensiune sistolic izolat ( 140 / <90 mm Hg)
Hipertensiune sistolic i diastolic ( 140 / 90 mm Hg)
Hipertensiune diastolic izolat ( 90 mm Hg)
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure (JNC VII).
Disponibil la: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Beneficiile scaderii TA
Reducere % medie RR
AVC
3540%
IM
2025%
IC
50%
JNC 7 JAMA 21.05.2003
Scderea TAS cu doar 2 mm Hg scade riscul de evenimente

CV cu 7-10%
Meta-analiz a 61 de studii prospective,

observaionale
1 milion aduli
12.7 milioane pacienti-an
2 mm Hg scdere
n TAS medie
7% reducere a
riscului de
mortalitate prin
cardiopatie
ischemic
10% reducere n
riscul de mortalitate
prin accident
vascular cerebral
Lewington S et al. Lancet 2002;360:1903-1913.
THE VITAL SIGNS

BLOOD PRESSURE
PULSE
RESPIRATORY RATE
TEMPERATURE
WHY DO WE MONITOR THE BLOOD

PRESSURE?
NORMOTENSION
HYPERTENSION
HYPOTENSION
HOW DO WE MEASURE BLOOD

PRESURE?
DIRECTLY - CATHETER IN THE
ARTERY the best
INDIRECTLY AUSCULTATORY OR
PALPATORY
WHAT IS THE EFFECT OF EXERCISE

ON THE BP?
SYSTOLIC BP WILL INCREASE.
DIASTOLIC BP CHANGES MINIMALLY.
THEREFORE, IF BP LEVELS RETURN TO
NORMAL AFTER EXERCISE THE PATIENT IS
NOT HYPERTENSIVE.
DLIN RA ET AL. AM HEART J. 106:316-320;1983
HERE IS HYPERTENSION ????

-CONTRACTIA CARDIACA
-DEBITUL CARDIAC
-REZISTENTA SISTEMICA
-STRUCTURA VASCULARA
Physiologic Components of BP
Heart
HR
Veins
Stroke
Volume
Arteries
SVR
Algebra of Blood Pressure

BP = Cardiac Output x SVR
CO = HR x Stroke Volume
BP
HR
Stroke Volume
SVR
Identifiable
Causes of Hypertension
PRIMARY or SECUNDARY
Sleep apnea
Drug-induced or related causes
Chronic kidney disease
Primary aldosteronism
Renovascular disease
Chronic steroid therapy and Cushings syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease
32
HYPERTENSION- ICEBERG
www.drsarma.in
HYPERTENSION
What we record as B.P.

It is only a marker of the bigger problem
The Truth is
Hypertension is a multi-organ systemic disease

The Problem is
Hypertension is asymptomatic in 85% of cases
33
How many are really Dx. and Rx.ed ??
Under control (40%)

Diagnosed
HT
37%
Hypertensives
(22%)
Normotensives (78%)
63%
Under
Un Rx. treatment
HT
(50%)
(7.5% of the total

hypertensives)
Uncontrolled
hypertension (60%)
Undiagnosed
HT
A study from Europe on 23,339 patients

34
BP Measurement Techniques
Method
Brief Description
In-office
Two readings, 5 minutes apart. Sitting in chair, not on exam

table. Confirm elevated reading in contralateral arm.
Self-measurement
Provides information on response to therapy. May help

improve adherence to therapy and evaluate white-coat
HTN.
Ambulatory BP
monitoring
Indicated for evaluation of white-coat HTN. Can be used to

confirm self-measurement when inconsistent with in-office
measurement. Reimbursable.
http://hin.nhlbi.nih.gov/nhbpep_slds/menu.htm; Accessed October 20, 2003; 8:15AM
Examples of recommended BP monitors.
Mercury sphygmomanometers (gold

standard).
(details available BHS website)
Simptome si semne
Maj. nu au semne specifice.

Sunt identif. in timpul exam. fizic
Simptomele :
1. TA crescute insasi
2. bolii vasculare hipertensive
3. bolii de fond (HTA sec)
Cefaleea (z. occipitala) dimineata (la trezire) si dispare spontan dupa
catava ore HTA severa
Vertij
Palpitatii
Oboseala acc.
Impotenta (la barbati)
HTA sec: poliurie, polidipsie, slabiciune musc. sec hipokaliemiei (in
hiperaldosteronism primar sau obezi), labilitate emotionala (in sindr.
Cushing)
Anamneza
Istoric familial de HTA

intermitente de val. ale TA in antecedente
HTA sec dupa trat. cu corticosteroizi sau estrogeni
Istoric de: angina pectorala, insuf. cerebrala, insuf. cardiaca congestiva,

insuf. vasc. periferica.
Factori de risc: fumatul, diabet zaharat, dislipidemia, decese premature in

familie datorate bolilor cardiovasc.
Stil de viata: dieta, activitatea fizica, statutul familial, profesia, nivelul de

educatie.
Examen fizic
aspectul general (fata rotunda, obezitatea tronculara sindr Cushing?)
Compararea TA si pulsului la cele 2 membre sup. in ortostatism si

clinostatism
Inaltimea si greutatea pacientului
Examenul fundului de ochi
Examinarea inimii si plamanilor
Teste de baza pt evaluarea initiala a HTA
A. Intotdeauna incluse:
Glucoza, sangele, proteinele urinare

Hematocrit
Potasemia
Creatinina serica si/sau ureea sanguina
EKG
De obicei incluse, in fctie de cost si alti factori:

Examen microscopic al urinii
Leucocitemia
Glucoza plasmatica sanguina, colesterol, colesterol HDL, TG
plasmatice/sanguine
Acid uric, fosfati si calciu serice
Radiografie toracica, ecocardiografia.
Teste speciale pt evaluarea HTA sec
Boala renovasculara: renograma cu IEC, examinarea ambilor rinichi cu

ultrasunete
Feocromocitom: det. creatininei, metanefrinelor si catecolaminelor in
urina/24h sau a catecolaminelor plasmatice.
Sindrom Cushing: testul de supresie nocturna cu dexametazona sau det.
cortizolului in urina/24h.
AFECT. CARDIOVASCULARE
HTA
Tratament nefarmacologic - combaterea factorilor de risc:

Reducerea aportului de sare la 5-6 g/zi
Renuntarea la alim. bogate in colesterol si grasimi saturate
Alimentatie hipolipidica si hipocalorica
Dieta bogata in legume, fructe si lactate (aport optim de K, Na, Ca)
Renuntarea la tutun si cafea
Reducerea consumului de alcool: < 30g etanol/zi barbati, < 15g/zi femei
Combaterea sedentarismului si obezitatii
Evitarea stresului
Tratamentul farmacologic:
Este permanent in HTA esentiala
Adaptat la gradul, grupul de risc, stadiul de HTA si evolutia bolii.
Med. CI in HTA:
Excitantele SNC (cafeina, anorexigenele amfetaminice)
Forme farm. eff.
Mercury Myth
Mercury sphygmomanometers have been banned?
Not True!
Fact
You can still use mercury!
It will eventually be phased out, but not yet,
no date set
Advantages of Self-Measurement
Identifies white-coat hypertension

Assesses response to medication
Improves adherence to treatment
Potentially reduces costs
Usually provides lower readings than
those recorded in clinic (hypertension is
defined as SBP > 135 or DBP > 85 mm
Hg)
ABMP IS BETTER !
Ambulatory Blood Pressure Monitoring - ABPM

1. 24 hour B.P monitoring (every 15
minutes)
2. Today - 24 hour B.P. control is essential
3. Identifies dippers and non-dippers
4. Excludes white coat hypertension
5. Treatement solution and control
46
Dippers & Non Dippers
What is this pattern in HT Dippers and Non-dippers ?

What is its significance and clinical relevance ?
47
Systolic Blood Pressure (mm Hg)
Systolic Blood Pressure

160
150
140
Non - dippers
130
Dippers
120
110
6
10
12
14
16
18
20
22
24
24 hours clock time

Yonsei, Med J, Vol 43, No 3: 2002
48
1. Less than 10% circadian variation in SBP and DBP

2. Essential hypertension patients are usually
Dippers
3. Non dippers are Dx. by ABPM They are usually
1. Secondary HT cases
2. More end organ damage
3. More LVH
4. More responsive to salt restriction
5. Diabetics are non dippers
6. Diuretics convert a non dipper to dipper
49
Valori normale ale TA evaluata prin MAATA (ABPM)

(studiu) pe 10 ani
24 ore
Ziua
Noaptea
TA optima
<115/75
<120/80
<100/65
TA normala
<125/75
<130/85
<110/70
Hipertensiune
130/80
140/85
120/70
N.B.=5682 p Olanda, Belgia, Japonia, Suedia )10 ani)

377 p- AVC
435 p evenimente cardiovasculare
(dupa Kikuva M, Journ of Hipertension 2007, 25-S136)
HYPERTENSOIN
PHYSIOPATHLOGY
HYPERTENSION
CLASIFICATION AND STADIALIZATTION
Globally Renowned HT Societies

1. JNC VII Joint National Committee on HT, USA
2. ISH WHO International Society on HT
3. AHA American Heart Association, USA
4. ACC American College of Cardiologist
5. BHS British Hypertension Society
6. NIHLB National Inst. Heart Lung & Blood vessels
7. EHS European Hypertension Society
8. CHS Canadian Hypertension Society
9. NKF National Kidney Foundation, USA
10.AKA American Kidney Association, USA
57
U.S. Department of
Health and Human
Services
National Institutes
of Health
National Heart, Lung,

and Blood Institute
National Heart, Lung, and Blood

Institute
National High Blood Pressure
Education Program
The Seventh Report of the

Joint National Committee
(JNC)
on
Prevention, Detection,
Evaluation, and Treatment
of High Blood Pressure
(JNC 7-8)
Hypertension:
Focus on JNC VIII
Partners in Healthcare Education, LLC 2009
59
JNC 7 Classification of Blood Pressure
STAGE 1
STAGE 2
SBP 160 mm Hg or
DBP 100 mm Hg
SBP 140-159 mm Hg or
DBP 90-99 mm Hg
PREHYPERTENSION
SBP 120-139 mm Hg or
DBP 80-89 mm Hg
NORMAL
SBP <120 mm Hg and
Treatment
recommended
Consider treatment in
those with diabetes or
renal disease who fail
lifestyle modification
DBP <80 mm Hg
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230. Available at:
www.nhlbi.nih.gov/guidelines/hypertension/jnc7full..
JNC-7
HT-EMERGENCY >180/120 +TOD

HT-URGENCY
>180/120 -TOD
JNC VIII:
Messages to Clinicians
JAMA. 2003:289:2560-2577.
62
e
s
J
N
C
VThe risk of CVD, beginning at

I 115/75mm Hg, doubles with each
increment of 20/10 mm Hg
I
I
JAMA. 2003:289:2560-2577.
63
Why Prehypertension?
Patients normotensive at age 55 have a 90% lifetime risk
to develop HTN
Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure
Prehypertensive: 120139 / 8089 mmHg
HT-135-85mmHg- (JNC 8)
Require health-promoting lifestyle modifications to
prevent CVD
Public health goal: Prevent hypertension and
cardiovascular disease before it happens
True or False
NormalbloodpressureisdefinedasSBP<
135andDBP<90.
False
120andDBP<80.PeoplewithSBP120
139orDBP8089shouldbeconsidered
prehypertensive.
Classification of Blood Pressure for

Adults (IHS)
Category
SBP
(mm Hg)
DBP
(mm Hg)
Optimal
< 120
and
< 80
Normal
< 130
and
< 85
High-normal
130-139
or
85-89
Hypertension
Stage 1
Stage 2
Stage 3
140-159
160-179
180
or
or
or
90-99
100-109
110
When SBP and DBP fall into different categories, use the higher category.
Ghidul HTA ESH/ESC 2007

Definiii ale TA i variantelor de HTA
TA sistolic
(mm Hg)
TA diastolic
(mm Hg)
< 120
< 80
TA normal
120-129
80-84
TA normal nalt
130-139
85-89
HTA gradul 1 (uoar)
140-159
90-99
HTA gradul 2 (moderat)
160-179
100-109
HTA gradul 3 (sever)
> 180
> 110
HTA sistolic izolat
> 140
< 90
Categorie
TA optim
Mancia G, De Baker D et al., 2007 Guidelines for the Management of AHT. J Hypertens 2007; 25: 1105-1187
Isolated Systolic Hypertension
1. What is ISH ?
SBP 140+ , DBP < 90
2. What percentage of 65+ aged have ISH ?

More than 90%
3. Which is more harmful SBP or DBP ?

Of course SBP
4. Why is ISH important ?

Because of CVA and CHD mortality
69
HYPERTENSION EVALUATION
CLINIC
PHISICAL EXAMINATION
LABORATORY TESTS
ELECTROCARDIOGRAPHY
CHEST X RAY
ECHOCARDIOGRAPHY
SPECIFIC TEST FOR TOD
Evaluation Components in HT
Medical history
Physical examination
Routine laboratory tests
Optional tests
Classification
Treatment
Medical History
Duration and classification of hypertension
Patient history of cardiovascular disease
Family history
Symptoms suggesting causes of
hypertension
Lifestyle factors
Current and previous medications
Physical Examination
Blood pressure readings (2 or more)-ABPM Verification in contralateral arm
Height, weight, and waist circumference
Funduscopic examination
Examination of the neck, heart, lungs, abdomen,
and extremities
Neurological assessment
Clinical Signs of LV Dysfunction
Hypotension
Pulsus alternans
Trigeminy, Bigeminy
Reduced volume of carotid
LV apical
Enlargement/displacement
Sustained heave of apex
Change in heart sounds
Soft S1
Paradoxically split S2
S3 gallop
S4 impaired LV compliance)
Mitral regurgitation
Pulmonary congestion rales
74
HYPERTENSION
PARACLINIC EVALUATION
Laboratory Tests and Other Diagnostic

Procedures
Determine presence of target organ

damage and other risk factors
Seek specific causes of hypertension
Tests Recommended Before Initiating

Therapy
Urinalysis
Complete blood count
Blood chemistry (potassium, sodium, creatinine, and fasting
glucose)
Lipid profile (total cholesterol and HDL cholesterol)
12-lead electrocardiogram
Chest x ray
Echocardiography
Specific for target organs (CT,MRI,ANGIOGRAPHY etc)
Optional Tests and Procedures
Creatinine clearance
Microalbuminuria
24-hour urinary protein
Serum calcium
Serum uric acid
Fasting triglycerides
LDL cholesterol
Glycosolated hemoglobin
Thyroid-stimulating hormone
Plasma renin activity/ urinary
sodium determination
Limited echocardiography
Ultrasonography
Measurement of ankle/arm
index
HYPERTENSION
ACUTE HYPERTENSIVE SYNDROMES
HYPERTENSION
RISC FACTOR
CVD Risk Factors

Hypertension
Cigarette smoking
Obesity* (BMI >30 kg/m2)
Physical inactivity
Dyslipidemia
Diabetes mellitus
Microalbuminuria or estimated GFR <60 ml/min
Age (older than 55 for men, 65 for women)
Family history of premature CVD
(men under age 55 or women under age 65)
*Components of the metabolic syndrome.
HYPERTENSION
TARGET ORGAN DAMAGE (TOD)
Diseases Attributable to Hypertension
Coronaryheartdisease
Stroke
Heartfailure
Cerebralhemorrhage
Myocardialinfarction
Leftventricular
hypertrophy
Hypertension
Aorticaneurysm
Retinopathy
Peripheralvasculardisease
Chronickidneyfailure
Hypertensive
encephalopathy
All
Vascular
85
Adaptedfrom:ArchInternMed1996;156:19261935.
Target Organ Damage (TOD)

Heart
Left ventricular hypertrophy (LVH)
Angina or prior myocardial infarction (CHD)
Prior Coronary revascularization PTCA or CABG
Heart failure (Systolic / Diastolic dysfunction)
Brain
CVA Stroke or Transient Ischemic Attack (TIA)
Kidney : Chronic kidney disease and CRF
Vessels : Peripheral arterial disease PVD
Eyes : Hypertensive Retinopathy
86
Target Organ Damage - Assessment

Routine Tests
Electrocardiogram, Echocardiography (desirable)
Urinalysis for proteinuria, Microalbuminuria
Blood glucose (F and PP), and Hematocrit
Serum Na and K, Creatinine or GFR, Calcium
Lipid Profile complete, Eye examination, ABI
Optional tests
X-Ray Chest PA
24 hr. urine albumin excretion or ACR
More extensive testing is not generally indicated
87
Normal weight 350 to 450 g

88
Transverse Section of HEART - LVH
10 mm
Dr.Sarma@works
25 mm
89
Echocardiography of Heart - LVH
Dr.Sarma@works
90
ECG and Left Ventricular Hypertrophy
91
Chest PA view of Heart - LVH
C/T ratio > 50%

92
RELATIA DINTRE HTA SI HVS

HTA
ALTI FACTORI:
Genetici, varsta,
sex, etnie
Obezitate
DZ
Aport de sodiu
HVS
CRESTERE CELULARA, FIBROZA, APOPTOZA
mediate de SRAA, SNS, INSULINA etc.
ISCHEMIE
BOALA DE
A. CORONARE
EPICARDICE
ARITMII
BOALA
MICROVASCULARA
FORME CLINICE
DE BOALA ISCHEMICA
DISFUNCTIE DE VS
DIASTOLICA
MS
SISTOLICA
ICC
Neuroretinitis in Optic Fundi of Subject with

Malignant Hypertension
1
4
HYPERTENSION
MORBIDITY and MORTALITY
Morbidity and Mortality in HT

Most of the morbidity and mortality of HT is due to
LVH LV diastolic and systolic dysfunction
Increased risk of Coronary Artery Disease
Increased risk of Cerebral Vascular Disease
Hypertensive heart failure
Chronic Renal Disease of hypertension
Hypertensive vascular damage
96
Hypertension: A Significant CV and Renal

Disease Risk Factor
CAD
Stroke
CHF
LVH
Hypertension
Morbidity
Renal
disease
Peripheral
vascular disease
Disability
National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186208.
Protectie de
organe
AVC
23%
P=0,0003
EVENIMENTE
CORONARIENE
13%
P=0,007
EVENIMENTE
RENALE
15%
P=0,0187
ASCOT investigators. The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure

Lowering Arm (ASCOT-BPLA). Lancet. 2005; 366: 895-906.
S
HYPERTENSION MORBIDITY AND MORTALITY
99
CURS NR 2
HIPERTENSIUNEA ARTERIALA
MECANISMELE HIPERTENSIUNII ARTERIALE

Sindrom hiperkinetic, inotropism ,
volum circulant
CRESTEREA REZISTENTEI
VASCULARE PERIFERICE
CRESTEREA DEBITULUI
CARDIAC
SISTEME PRESOARE
RAA
SISTEME DEPRESOARE
RETENTIE
SNS SI ENDOTELINA
HIDROSALINA SI
ANOMALII DE
TULBURARI IONICE
BAROREFELEXE
TRANSMEMBRANARE
RIGIDIZAREA AORTEI
DISFUNCTIA
ENDOTELIALA - NO
Angiotensinogen
RENINA
Angiotensina I
ENZIMA DE
CONVERSIE
ANGIOTENSINA II
BRADIKININA
AT1
Vasoconstictie
Hipertrofie, fibroza,apoptoza
Retentie hidrosalina Actiuni in SNC
Stimulare simpatica Prooxidant si proinflamator
AT2
Vasodilatatie
Efect antiproliferativ
Natriureza
Produ
si
inactiv
i
Angiotensinogen
RENINA
IEC
Angiotensina I
ENZIMA DE
CONVERSIE
ANGOTENSINA II
-
AT1
Vasoconstictie
BRADIKININA
AT2
Vasodilatatie
Prod.
inactiv
i
Angiotensinogen
RENINA
Angiotensina I
ENZIMA DE
CONVERSIE
CHIMAZE
ANGOTENSINA II
BRADIKININA
AT1
Vasoconstictie
AT2
Vasodilatatie
Natriureza
Produ
si
inactiv
i
Angiotensinogen
RENINA
Angiotensina I
ENZIMA DE
CONVERSIE
CHIMAZE
ANGOTENSINA II
BLOCANTI
R-AT1
AT1
Vasoconstictie
Prod.
BRADIKININA
AT2
Vasodilatatie
Natriureza
inactiv
i
SISTEMUL NERVOS SIMPATIC SI HTA
HTA =
UCIGASUL
SECRET/
CLANDESTIN
Hypertension and Management:

Old School
Hypertension = Systemic disease
Hemodynamics altered
Treat the blood pressure
Therapeutic options
Beta
Blockers
ACE
ARB
Diuretics
CCB
Adapted from Vascular Biology Working Group, University of Florida

College of Medicine, Carl Pepine, MD, Director
Others
110
Hypertension and Management: New School

Hypertension =
Disease of the blood vessels
Vascular biology altered
Treat the vasculature
Therapeutic options
Beta
Blockers
ACE
ARB
Diuretics
CCB
Adapted from Vascular Biology Working Group, University of Florida

College of Medicine, Carl Pepine, MD, Director
Others
111
Ce ne dorim de la o medicatie
antihipertensiva?
Sa scada eficient TA si sa asigure

atingerea si mentinerea tintelor TA la un
procent cat mai mare de pacienti
Sa fie bine tolerata / sa asigure

persistenta superioara pe tratament
Sa ofere protectie de organ-tinta,

dincolo de scaderea TA
Pharmacotherapy of Hypertension
Alpha Blocker
AT1Antagonist
- agonists
ACE
Dr. Rx
Ganglionic
Rationa
Inhibitor
l
blockers
Vasodilators Drug of choice Beta Blocker
Ca++ Antagonist
Diuretic
Pharmacologic Sites of Action

Veins
Thiazides
Loops
Aldosterone Ant.
Nitrates
ACEI
ARB
Heart
Beta Blockers
Diltiazem
Verapamil
Via Central
Mechanism:
Clonidine
Arteries
Dihydropyridine
CCBs
Hydralazine
Minoxidil
Alpha1 Blockers
ACEI
ARB
The Many Faces of HT Therapy Today
CCBs
Centrally acting agents

ics
t
e
r
u
Di
a
Bet
rs
e
k
c
blo
ARBs
ACE in
hibitors
Hypertension
115
Algorithm for Treatment of

Hypertension
Begin or Continue Lifestyle Modifications

Lose weight
Limit alcohol
Increase physical
activity
Reduce Sodium
Maintain potassium
Maintain calcium and
magnesium
Stop smoking
Reduce saturated fat,
cholesterol
Not at Goal Blood Pressure
Lifestyle Modification
Modification
Weight reduction
Approximate BP reduction
(range)
520 mm/10 kg wt loss
Adopt DASH eating plan
814 mmHg
Dietary sodium reduction
28 mmHg
Physical activity
49 mmHg
Abstinence from alcohol
24 mmHg
All put together reduce BP by 20 to 55 mmHg
117
Which drug in each class
www.drsarma.in
118
DIURETIX reduces the number

of sacks on the wagon
1.Diuretics
1.Thiazides
hydrochlorothiazide(HydroDIURIL,Esidrix);
chlorthalidone(Hygroton)
2.Loopdiuretics
furosemide(Lasix);bumetadine(Burmex);
ethacrynicacid(Edecrin)
3.K+Sparing
amiloride(Midamor);spironolactone(Aldactone);
triamterene(Dyrenium)
4.Osmotic
mannitol(Osmitrol);urea(Ureaphil)
5.Other
CombinationHCTH+triamterene(Dyazide)
acetazolamide(Diamox)
Diuretics(cont)
1.SiteofAction
RenalNephron
2.MechanismofAction
UrinaryNa+excretion
Urinarywaterexcretion
ExtracellularFluid
and/orPlasmaVolume
3.EffectonCardiovascularSystem
AcutedecreaseinCO
ChronicdecreaseinTPR,normalCO
Mechanism(s)unknown
Diuretics(cont)
4.AdverseReactions
dizziness,
electrolyteimbalance/depletion,
hypokalemia,
hyperlipidemia,
hyperglycemia(Thiazides)
gout
5.Contraindications
hypersensitivity,
compromisedkidneyfunction
cardiacglycosides(K+effects)
hypovolemia,
hyponatremia
QuickTmeand
TIF(Uncompresd)ecompreso
aren d tosethispcture.
Diuretics(cont)
6.TherapeuticConsiderations
Thiazides(mostcommondiureticsforHTN)
Generallystartwithlowerpotencydiuretics
GenerallyusedtotreatmildtomoderateHTN
UsewithlowerdietaryNa+intake,
andK+supplementorhighK+food
K+Sparing(combinationwithotheragent)
Loopdiuretics(severeHTN,orwithCHF)
Osmotic(HTNemergencies)
Maximumantihypertensiveeffectreached
beforemaximumdiuresis2ndagentindicated
QuickTmeand
TIF (Uncompres d)ecompreso
aren de tose thispcture.
ACEI reduces the number of sacks

on the wagon
ACEi
1-126
A-
AA
ACEi-ARB--MECHANISM
Renin Inhibitors
127
127
ARB
AntiAngiotensinIIFormation
AngiotensinIIFormation
1. AngiotensinConvertingEnzyme
Inhibitors
enalopril(Vasotec);
quinapril(Accupril);
fosinopril(Monopril);
moexipril(Univasc);
lisinopril(Zestril,Prinivil);
benazepril(Lotensin);
captopril(Capoten)
2.AngIIReceptorAntagonists
losartan(Cozaar);
candesartan(Atacand);
valsartan(Diovan)
Angiotensinogen
ACE
AngI
Renin
Lung
VSM
Brain
Kidney
AdrGland
AngI
AT1
Ang II
ACE
AT2
AngII
AntiAngiotensinIIDrugs,cont
QuickTime and a
GIF decompressor
are needed to see this picture.
Volume
Aldosterone
Vasopressin
CO
HR/SV
AngiotensinII
Norepinephrine
SymNS
CO
AngiotensinII
Vasoconstriction
SymNS
TPR
AntiAngiotensinIIDrugs,cont
4.AdverseEffects
hyperkalemia
angiogenicedema(ACEinhib);cough(ACEinhib);
rash;itching;
5.Contraindications
pregnancy;hypersensitivity;bilateralrenalstenosis
6.TherapeuticConsiderations:
usewithdiabetesorrenalinsufficiency;
adjunctivetherapyinheartfailure;
oftenusedwithdiuretic;
Enalapril,ivforhypertensiveemergency
BB
BBBB
Beta- Blocker Therapy
-Blockers
Limit the donkeys speed, thus saving energy
Adrenoceptor
ADRENALINE
Adrenoceptor
Betablockers
A. Classification and
1. Receptor
selectivity
Mechanisms
-selective: Betaloc Zok, atenolol

-selective: butoxamine (research
only)
Nonselective: propranolol
Combined beta- and alpha-blocking:
labetalol
drenergicAntagonists,cont.
3.EffectsonCardiovascularSystem
a.CardiacHR,SVCO
b.RenalReninAngiotensinIITPR
4.AdverseEffects
impotence;bradycardia;
fatigue;exerciseintolerance;
5.Contraindications
asthma;diabetes;bradycardia;
hypersensitivity
drenergicAntagonists,cont.
Selectivity
nadolol(Corgard)nonselective,but20hr1/2life
metoprol(Lopresor)selective,34hr1/2life
Riskyinpulmonarydiseaseevenselective,
Availableasmixedblockeravailablelabetalol
(Trandate,Normodyne)
Usepostmyocardialinfarctionprotective
Usewithdiureticpreventreflextachycardia
BCC
Ca++Channel
Blockers
CC
Drugs:verapamil(Calan);nifedipine(Procardia);
diltiazem(Cardizem);amlodipine(Norvasc)
1.SiteofAction
Vascularsmoothmuscle
2.MechanismofAction
BlocksCa++channel
decreases/preventscontraction
3.EffectonCardiovascularsystem
Vascularrelaxation
DecreasedTPR
Na+ Ca++
K+
BCC: Mecanism de aciune
BCC-
inhib intrarea transmembranar a ionilor de Ca++ n

celulele musculare netede vasculare i n cardiomiocite
inhibiia este selectiv cu efect comparativ mult mai important
asupra celulelor musculare netede vasculare dect asupra
miocardului
efectul vascular vasodilatator determin scderea rezistenei
vasculare periferice i scderea TA
Norvasc - Rezumatul Caracteristicilor Produsului - noiembrie 2010
Ca++ChannelBlockers,cont.
4.AdverseEffects
nifedipineIncreaseSymNSactivity;
headache;dizziness;peripheraledema
5.Contraindications
Congestiveheartfailure;pregnancyandlactation;
Postmyocardialinfarction
verapamilmainlycardiac;interactionsw/cardiac
glycosides
nifedipinemainlyarterioles
diltiazembothcardiacandarterioles
athighdoses,AVnodeblockmayoccur;
nifedipinemayincreaseheartrate(reflex)
Anti Hypertensive drug classes
The A, B, C, D -Good and bad

aspects
143
The A B C D classes
D
Diuretics
ACEI, ARB
Ca
channelBlockers
DIURETICS
ACEI
and ARB
Blockers
D
A
Fourth Choice, Useful
First
Best
Choice
Second
Best
Choice
Goodand
third
Choice
Can
be
combined
with
D, B,
A C
Can
be
combined
with
A,
Can
Canbe
becombined
combinedwith
withD,
A, B,
DC
B C
-Blockers
Ca-Blockers
144
DIURETIC
I am D for DIURETIC
KNOW ME WELL
My Good aspects
Fluid depletion, Na washout, Low cost
Improve CHF, Systolic function, Ca saving
Reduce LVH, Morbidity & Mortality
My Bad aspects
Potassium washout, in Uric acid, Ca
Adverse on Lipids, Glucose control
Dont use me in
Gout, Hypokalaemia
Dyslipedemia, Uncontrolled DM
www.drsarma.in
145
ACEI, ARB
I am A for ACEI and ARB

KNOW ME WELL
My Good aspects
Improve Diastolic function, Systolic function
Control Proteinuria, Very favourable in DM
Improve Coronary Ischemia, Good on Lipids
Reduce LVH, Morbidity & Mortality
My Bad aspects
Bradykinin accumulation, Angio-edema
Serum K , GFR
Dont use me in
Pregnancy, Creatinine is > 3 mg%, K 5.0 meq
www.drsarma.in
Bilateral Renal Artery Stenosis, Angio-edema

146
Blocker
I am B for Blocker
KNOW ME WELL
My Good aspects
Heart rate, Forceof contraction, Conduction
Myocardial O2 demand, Improve Ischemia
Improve QUALY in CHD, Useful in CHF, Migraine
My Bad aspects
Constrict peripheral vessels, Bradycardia
Unfavourable on Lipids, Glucose
Dont use me in
Bradycardia, Conduction defects, Caution in CHF
Prinzmetal Angina, MSD, PVD, BA, COPD, Dys lipid
www.drsarma.in
Pheochromocytoma, Chronic smokers

147
I am C for Ca channel Blocker

Ca+ Blockers
KNOW ME WELL
My Good aspects
Vasodilatory, Suitable in elderly, Low cost
Anti arrhythmic (Verapamil), Coronary BF (Diltz)
Neutral on lipidemia, Vasospastic Angina
My Bad aspects
Fluid retention, Impair failing heart
Adverse on Glucose control , Pedal edema ? Rx.
Dont use me in
Tachycardia, arrhythmias, CHF,
Uncontrolled DM, Volume overload
www.drsarma.in
148
DUAL-THERAPY
149
Hypertension Rational Drug Combinations
ACEI and ARB = A
Diuretics = D Rank 1
Beta Blockers = B
ACEI and ARB = A Rank 2
Calcium Channel (CCB) = C
Beta Blockers = B Rank 3
Diuretics Drugs= D
CCB = C Rank 4
D and A combination is excellent -
Ramace H, Losar H, Enace D
D and B combination next -
Betaloc H, Atecard D, Tenoric
D and C combination sixth -
Amlogaurd H, Stamlo D
A and B combination Third -
Losar A, Cardif Beta
A and C combination fourth -
Amlopres L, Hipril A, Amlo LS
B and C combination fifth -
Amlo AT, Amlobet, Beta Nicardia
www.drsarma.in
150
Some Irrational Combinations
Beta blockers + Beta1 stimulants -
Rebound HT, Paradoxical BP
Beta blockers + Vepapamil -
Extreme bradycardia, HB, CHF
Thiazide + Furesemide
Potential volume and K
CCB + Thiazide
No RCTs to support the additive
Prazocin + Beta blocker -
They nullify the effects of each other
Verapamil / Dilzem + Nefidepine -
No rationale (cardiac actions contridic)
Beta blocker + ACEI
Not for HT alone, Good for CHF, MI, IHD
Sub clinical doses of two drugs
Try one drug in good dosage, then add
Two drugs of same class -
No rationale (like Enalapril + Ramipril)

(Atenelol + Metoprolol, Nefidepine + Amlo)
www.drsarma.in
151
Hypertension Treatment by Drug Class

Diuretics
-Blocker
ACE Inhibitors
CCBs
ARBs
IMS Health NDTI, 1978-2002
JNC 7 algoritmul pentru tratamentul HTA

Modificri ale stilului de via
TA int (<140/90 mmHg sau <130/80 mmHg pentru cei cu diabet sau boal renal cronic)
neatinsa
Alegerea tratamentului iniial
Tratament antihipertensiv fara o
recomandare stricta a ghidurilor
Tratament antihipertensiv cu o
recomandare stricta a ghidurilor
HTA stadiul 1
HTA stadiul 2
(TAS 140-159 sau TAD 90-99

mmHg)
(TAS 160 mmHg sau TAD 100

mmHg)
Diuretic tiazidic pentru majoritatea
Combinaie de 2 medicamente pentru

majoritatea (de obicei diuretic tiazidic
i IECA sau sartan sau -blocant sau
CCB)
Putei considera IECA, sartan, blocant, CCB, sau combinaii
Medicamente pentru
indicaii obligatorii
Alte medicamente
antihipertensive (diuretic,
IECA, sartan, -blocant, CCB)
n funcie de necesar
TA int neatins
Adaptat dup JNC 7 VII, Hypertens.
2003;42:1206-1252.
Optimizai dozele sau adugai medicamente pn cnd TA int

este atins
Considerai consultarea unui expert n tratamentul HTA
ANOTHER ANTI- HYPERTENSION DRUGS
ADRENERGICAL ANTAGONIST
CENTRAL SYMPATHOLYTICS
NITRATES
PeripheralAdrenergicAntagonists
Drugs:prazosin(Minipres);terazosin(Hytrin)
1.SiteofActionperipheralarterioles,smoothmuscle
QuickTime and a
Photo - JPEG decompressor
CRITICALPOINT!
Majormechanism/siteofSymNScontrolofbloodpressure.
CentralSympatholytics(2Agonists)
Drugs:clonidine(Catapres),methyldopa(Aldomet)
1.SiteofAction
CNSmedullary
cardiovascularcenters
clonidine;direct2agonist
methyldopa:falseneurotrans.
2.MechanismofAction
CNSadrenergicstimulation
Peripheralsympathoinhibition
Decreasednorepinephrinerelease
3.EffectsonCardiovascularSystem
DecreasedNE>vasodilation>DecreasedTPR
CRITICALPOINT!
Stimulationofreceptorsinthemedulladecreasesperipheral
sympatheticactivity,reducestone,vasodilationanddecreasesTPR.
Nitrates
Veins
Mechanism: Direct venodilation by

release of nitric oxide
Examples:
Thiazides
Loops
Aldosterone Ant.
Nitrates
Isosorbide dinitrate 10 mg TID

IMDUR 30 mg daily
In renal patients with resistant

hypertension addition to 3-4 drug
regimen may help get patient to
goal
Provide 8h nitrate free interval daily
Compelling indications: Angina
HT -TREATMENT
SOME COMMON C0-EXISTING
CONDITION
Hypertensiontreatmentwith
somecommoncoexistingconditions
HeartFailure
ACEinhibitors
Diuretics
MyocardialInfarction
blockers
ACEinhibitors
Diabetes
ACEInhibitors
AVOIDblockers
Isolatedsystolichypertension(Olderpersons)
Diureticspreferred
calciumchannelantagonist
TreatmentStrategywith
SomeCommoncoexistingConditions,cont
RenalInsufficiency
ACEInhibitors
Angina
blocker
Calciumchannelantagonists
Asthma
Ca++channelblockers
WHAT IS NEW IN HYPERTENSION
161
Ce putem face pentru

pacientul
cu HTA necontrolata
(rezistenta la >4
antihipertensive)?
New drugs
SOLUTII PENTRU HTA REZISTENTA

LA >4 ANTIHIPERTENSIVE
Darusentan
2. Rheosistem device implantabil in sinus carotidian

Studiu si influenta receptorilor barometrici prin algoritm
programabil
3. ALISKIREN+IEC+ARB+IEC+HCTZ etc
4. Vaccin antiangiotensina II (ANGQB-CYT006)
Aliskiren Binds to the Active Site of Renin
Renin
Aliskiren
Angiotensinogen
Angiotensin I
Adapted from Wood JM, et al. 2003
Aliskiren binds to a
pocket in the renin
molecule, blocking
cleavage of
angiotensinogen to
angiotensin I
ENDOTHELIN ANTAGONISTS.
Endothelin (ET-1) is one of the most potent

vasoconstrictors known. ET-1
Tezosentan (an endothelin receptor blocker), would

reduce LV filling
pressures, decrease afterload, increase cardiac output
Vaccin antiAngiotensina II
(rezultate)
N.B. = procent non dipper diminuat (p<0,05)

(dupa TISSOT A.C. Journ of Hypert. 2007,25. S 139)
SOLUTII PENTRU HTA REZISTENTA

LA >4 ANTIHIPERTENSIVE
CONCLUSION
What we record as B.P.

It is only a marker of the bigger problem
The Truth is
Hypertension is a multi-organ systemic disease

The Problem is
Hypertension is asymptomatic in 85% of cases
169
Nu tot ce conteaza
poate fi masurat
si nu tot
ce poate fi masurat
conteaza
ALBERT EINSTEIN
THE END???
DEFINITIE
Se consider HIPERTENSIUNE ACEL

NIVEL AL PRESIUNILOR DE LA CARE RISCUL
CARDIOVASCULAR SE DUBLEAZ PE TERMEN LUNG:
140/90 mmHg
IMPACT
1. EFECTELE ASUPRA RISCULUI CARDIOVASCULAR:
Meta-analiza efectuata de Prospective Studies

Collaboration riscul de atac de cord sau de stroke
este dublat atunci cand TAs cu 20 mmHg sau cand
TAd cu 10 mmHg.
LEWINGTON S. si colab., Lancet, 2002; 360: 1903-1913
HTA FACTOR
CARDIOVASCULAR
DE
RISC
Studiul MRFIT: TA are o relaie continu cu

riscul cardiovascular
Arch. Intern. Med., 1993; 153:186
HTA
FACTOR
CARDIOVASCULAR
DE
MacMahon S. i colab., Lancet, 1990; 335: 765
RISC
IMPACT
2. PREVALENTA FOARTE MARE cel mai raspandit factor

de risc CV:
1/4 din populatia globului are HTA
- 1,56 miliarde de oameni vor avea HTA in 2025
45% din populatia adulta a Romaniei are HTA
75% din cei in varsta > 65 ani au HTA
KERNEY P.M. si colab., Lancet, 2005; 365: 217-233
DOROBANTU M si colab., Rev. Rom. Cardiol., 2006; Vol XXI, 3
CLASIFICARE
1. IN FUNCTIE DE VALORI:
Gr. 1
TA sistolica
sau
TA diastolica
140-159
90 99
Gr.2
160-179
100-109
Gr.3
180
110
CLASIFICARE
2. SISTOLICA IZOLATA/DIASTOLICA/SISTOLO-DIASTOLICA
3. IN FUNCTIE DE ETIOLOGIE
- Esentiala/primara/idiopatica
- Secundara
ETIOPATOGENIE
BOALA CU DETERMINISM POLIGENIC PUTERNIC

INFLUENTATA DE FACTORI DOBANDITI de exemplu
obezitatea, consumul excesiv de sare etc
MECANISMELE HIPERTENSIUNII ARTERIALE

Sindrom hiperkinetic, inotropism ,
volum circulant
CRESTEREA REZISTENTEI
VASCULARE PERIFERICE
CRESTEREA DEBITULUI
CARDIAC
SISTEME PRESOARE
RAA
SISTEME DEPRESOARE
RETENTIE
SNS SI ENDOTELINA
HIDROSALINA SI
ANOMALII DE
TULBURARI IONICE
BAROREFELEXE
TRANSMEMBRANARE
RIGIDIZAREA AORTEI
DISFUNCTIA
ENDOTELIALA - NO
Angiotensinogen
RENINA
Angiotensina I
ENZIMA DE
CONVERSIE
ANGIOTENSINA II
BRADIKININA
AT1
Vasoconstictie
AT2
Vasodilatatie
Natriureza
Produ
si
inactiv
i
Angiotensinogen
RENINA
IEC
Angiotensina I
ENZIMA DE
CONVERSIE
ANGOTENSINA II
-
AT1
Vasoconstictie
BRADIKININA
AT2
Vasodilatatie
Prod.
inactiv
i
Angiotensinogen
RENINA
Angiotensina I
ENZIMA DE
CONVERSIE
CHIMAZE
ANGOTENSINA II
BRADIKININA
AT1
Vasoconstictie
AT2
Vasodilatatie
Natriureza
Produ
si
inactiv
i
Angiotensinogen
RENINA
Angiotensina I
ENZIMA DE
CONVERSIE
CHIMAZE
ANGOTENSINA II
BLOCANTI
R-AT1
AT1
Vasoconstictie
Prod.
BRADIKININA
AT2
Vasodilatatie
Natriureza
inactiv
i
HTA =
UCIGASUL
SECRET/
CLANDESTIN
COMPLICATIILE HTA
1. AVC
Risc X 7
2. SINDROAME
CORONARIENE
ACUTE
Risc X 3
3. INSUFICIENTA
CARDIACA
Risc X 2-3
COMPLICATIILE HTA
1. VASE CAPILARE
Rarefactie capilara
si disfunctie
endoteliala
2. VASE DE
REZISTENTA SI
ARTERIOLE
Remodelare
eutrofica si aterogeneza
3. VASE MARI
Rigidizare si
aterogeneeza
HTA FACTOR DE RISC

CARDIOVASCULAR
VASELE MARI: RIGIDIZAREA AORTEI; ANEVRISM

I DISECIE DE AORT
VASELE MEDII I MICI: REMODELARE
VASCULAR SISTEMIC; EFECTE PARTICULARE
N ARTERELE RETINEI I AA. CEREBRALE
HTA FACTOR DE RISC

CARDIOVASCULAR
COMPLICAIILE CARDIACE ALE HTA: HIPERTROFIA

VENTRICULAR STNG; INSUFICIENA CARDIAC;
BOALA CORONARIAN
TIME; dec. 13, 2004
HTA FACTOR DE RISC

CARDIOVASCULAR
COMPLICAII RENALE: NEFROANGIOSCLEROZA

HIPERTENSIV
TIME; dec.13,2004
Dupa Dzau si Braunwald, J. Hypertens., 2008; 26 (Suppl. 4)
Remodelarea arterelor
mici si a arteriolelor
in HTA
HTA
induce
postsarcina crescuta si
favorizeaza HVS de tip
concentric.
Prevalenta HVS la
hipertensivi variaza in
functie de metoda de
evaluare: 20-50% in HTA
moderata si severa.
Devereux R.B. si colab.,
Circulation, 1977; 55: 613-618
Dupa Lancet, 1982; 1: 1165-1168

HTA
ALTI FACTORI:
Genetici, varsta,
sex, etnie
Obezitate
DZ
Aport de sodiu
HVS
CRESTERE CELULARA, FIBROZA, APOPTOZA
mediate de SRAA, SNS, INSULINA etc.
ISCHEMIE
BOALA DE
A. CORONARE
EPICARDICE
ARITMII
BOALA
MICROVASCULARA
FORME CLINICE
DE BOALA ISCHEMICA
DISFUNCTIE DE VS
DIASTOLICA
MS
SISTOLICA
ICC
EVALUAREA HVS
ECG
Indicele Sokolow-Lyon (SV1 +
RV5-6 > 38 mm)
Produs Cornell = Voltaj Cornell
(RaVL+SV3)
x
durataQRS
>
2240mmxmsec
Pattern de strain indicator de
risc
+
Tulburari de ritm
Modificari ischemice
EVALUAREA HVS
ECOGRAFIE CARDIACA MASA VS
IMVS > 110 g/m2 femei;
IMVS > 125 g/m2 barbati
Perete VS raportat la
raza (wall to radius ratio)
0.42-0.45
HVS concentrica = IMVS
+ perete raportat la raza
Mai sensibila decat ECG in detectarea HVS
Levy D si colab., Ann. Intern.Med., 1990; 108:7; Reichek N. si colab.,
Circulation, 1981; 63: 1391-1398
EVALUAREA HVS
ECOGRAFIE CARDIACA
FUNCTIA DIASTOLICA SI SISTOLICA
Fluxul
transmitral E/A
Fluxul in venele
pulmonare
Fluxul
transmitral Vp
Expansiunea inelului
mitral in TDI
Volumul indexat al
AS
FE a VS
EVALUAREA HVS
RMN
RMN
cardiac
realizeaza
evaluarea cu cea mai mare
acuratete
si
reproductibilitate
a
dimensiunilor si structurii
cardiace.
Artham S. M. si colab., Prog. Cardiovasc.

Dis., 2009; 52: 153-167
SEMNIFICATIA PROGNOSTICA A HVS

Studiul Framingham a evidentiat ca la pacientii cu
semne ECG de HVS riscul de mortalitate
cardiovasculara creste de 8x similar cu al
pacientilor dupa un infarct miocardic, iar la cei cu
dovezi ecocardiografice de HVS riscul de deces sau
de complicatii non-fatale este multiplicat de 2-4x.
Kannel W.B. si colab., Ann. Intern. Med., 1970; 72: 813-822; Levy D. si
colab., N.Engl.J.Med., 1990; 322: 1561-1566
Relatia dintre masa

VS si riscul CV este
continua
si
se
manifesta de la valori
aflate sub criteriile de
HVS.
Schillaci G. si colab.,
Hypertension, 2000; 35: 580-586
Prognosticul HVS
depinde de geometria
VS. Varianta cea mai
severa este hipertrofia
concentrica.
Patel D. si colab., Circulation,
2008; 118: S602
Din: Ann.Intern.Med., 1991; 114: 345352

HVS si INSUFICIENTA CARDIACA
HVS mareste riscul de aparitie a insuficientei
cardiace congestive si de deces prin insuficienta
cardiaca.
Drazner M.H. si colab., J.Am.Coll.Cardiol., 2004; 43: 2207-2215; Okin P. M. si
colab., Circulation, 2006; 113: 67-73
Din: Okin P. M. si colab., Circulation, 2006; 113: 67-73

(LIFE Study)
PARTEA A 2-A
DIAGNOSICUL HTA
1896
Scipione Riva-Rocci inventeaz

sfigmomanometrul cu mercur
pentru msurarea tensiunii
arteriale la om
DIAGNOSICUL HTA
1. MASURAREA TA IN CABINET MEDICAL efectul de halat alb

2. MASURAREA AMBULATORIE AUTOMATIZATA A TA
3. AUTOMASURARE
DIAGNOSICUL HTA
TAs
CLASIC
TAd
< 140
< 90
MATA
Media 24h
<125-130
Media diurna
< 80
<130-135
Media nocturna
< 120
AUTOMASURARE
< 130-135
< 85
< 70
< 85
EVALUAREA HTA
1. EVALUAREA CLINICA
2. EVALUAREA FACTORILOR DE RISC CV SI A
COMPLICATIILOR
3. EVALUAREA SIGURANTEI TRATAMENTULUI
4. EVALUAREA FORMELOR SECUNDARE DE HTA
EVALUAREA PACIENTULUI HIPERTENSIV IN

NOILE GHIDURI HTA ESH/ESC 2007
EVALUAREA PACIENTULUI HIPERTENSIV IN

NOILE GHIDURI HTA ESH/ESC 2007
NOU INTRODUS IN GHID
!!!
NOU INTRODUS
IN GHID
!!!
CLASIFICARE
GHIDUL HTA ESC/ESH 2007, Journal of Hypertension, 2007;

25: 1105-1187
SCADEREA HTA REDUCE RISCUL

CARDIOVASCULAR DOVEZILE TRIAL-URILOR
Tratamentul antihipertensiv se asociaza cu o

reducere de:
35-40% - a riscului de accident vascular cerebral
20-25% - a riscului de infarct de miocard
50% - a riscului de insuficienta cardiaca
21% - a riscului de mortalitate CV
NEAL B. si colab., Lancet, 2000; 356: 1955-1964
VALORILE-TINTA ALE TRATAMENTULUI IN

HTA
TAs < 140 i/sau TAd < 90mmHg

TAs < 135 i/sau TAd < 85mmHg, nu < 120 mmHg
TAs DIABET ZAHARAT
TAs < 125 i/sau TAd < 75mmHg PROTEINURIE
1g/24h
GREU DE ATINS!
TRATAMENTUL NON-FARMACOLOGIC
Corectarea stilului de via ar trebui instituit de cte ori este
posibil, la toi pacienii n etapa de temporizare a tratamentului
farmacologic sau n paralel cu acesta, dac a fost iniiat.
TRATAMENTUL FARMACOLOGIC
1. CU CE CLASE DE MEDICAMENTE INITIEM TRATAMENTUL?
2. MONOTERAPIE vs TERAPIE ASOCIATA
DIURETICE
DIURETICE TIAZIDICE
COMPUSI: Hidroclorotiazida (12,5 25 mg/zi), Indapamida (6,25-1,5mg/zi) in
priza unica
MECANISM DE ACTIUNE: inhiba reabsorbtia de Na si Cl in tubul contort
distal
INDICATII:
in asociere cu IEC/sartani/blocante ale canalelor de calciu efect sinergic
sunt folosite in combinatii fixe
HTA la varstnici
EFECTE SECUNDARE: hipopotasemie, hiperuricemie, hipercolesterolemie,
hipercalcemie, hiperglicemie
CI/PRECAUTII: DZ, guta, insuficienta renala (Clcr<20 ml/min)
DIURETICE
DIURETICE DE ANSA
COMPUSI: furosemid (20-80mg/zi) in 2-3 prize/zi, bumetanid, torasemid,
acid etacrinic
MECANISM DE ACTIUNE: inhiba Na/K/Cl co-transporter-ul din portinea
ascendenta a ansei Henle
INDICATII:
HTA asociata cu patologie de retentie hidrosalina si alternativa la diuretic
tiazidic in insuficienta renala severA
EFECTE SECUNDARE: hipovolemie, hipopotasemie, hiperuricemie,
hipercalcemie, alcaloza metabolica
CI/PRECAUTII: hiperaldosteronism primar, hiperuricemie
DIURETICE
DIURETICE ECONOMISITOARE DE POTASIU
COMPUSI: spironolactona (25-50 mg/zi), eplerenona/ triamteren, amilorid
MECANISM DE ACTIUNE: antagonisti de receptori de aldosteron/inhiba
pompa Na-H+ in TCD
INDICATII:
HTA din hiperaldosteronism-ul primar
In asociere cu tiazidice in HTA reziztenta la tratament
EFECTE SECUNDARE: hiperpotasemia, mai ales in asociere cu IEC sau
sartani
CI/PRECAUTII: insuficienta renala, hiperpotasemia
IEC
COMPUSI: captopril, enalapril (5-20 mg/zi 2 prize), ramipril (5-10 mg/zi priza
unica), perindopril (5-10 mg/zi priza unica), lisinopril (5-20 mg/zi priza unica),
fosinopril, zofenopril, etc
MECANISM DE ACTIUNE: vezi patogenie
INDICATII:
HTA in general
HTA cu IC, HTA si boala coronariana
EFECTE SECUNDARE: hiperpotasemie, tuse (10-15%), induce insuficienta
renala in conditii de hipoperfuzie renala, efecte alergice,
CI/PRECAUTII: insuficienta renala, stenoza de artera renala bilaterala, sarcina
SARTANI
COMPUSI: losartan (50-100 mg/zi), telmisartan (40-80 mg/zi), valsartan (80160/zi), candesartan (8-16mg/zi), irbesartan (150-300mg/zi)
MECANISM DE ACTIUNE: vezi patogenie
INDICATII:
HTA in general
HTA cu IC, HTA si boala coronariana, indicatii specifice de nefroprotectie
la pacientii cu DZ
EFECTE SECUNDARE: IRA, hiperpotasemie
CI/PRECAUTII: sarcina, stenoza de artera renala bilaterala, conditii de
hipoperfuzie renala
BLOCANTE ALE CANALELEOR DE CALCIU

COMPUSI: Nifedipina retard (20-40 mg/zi), amlodipina (5-10 mg/zi),
lercanidipina (10-20 mg/zi), felodipina/ verapamil (80-240 mg/zi)
MECANISM DE ACTIUNE: blocarea canalelor de calciu si relaxarea
musculaturii netede vasculare
INDICATII:
HTA in general
HTA la varstnic
HTA cu insuficienta renala
EFECTE SECUNDARE: tahicardie, eritem facial, tulburari GI, edeme,
cefalee/BAV (diltiazem, verapamil),
CI/PRECAUTII: ICC, BAV grad II-III
BETA-BLOCANTE:
COMPUSI:
Beta blocante: propranolol, atenolol (50-100mg/zi), metoprolol (50-200mg/zi),
bisoprolol (5-10 mg/zi),),
Beta-blocante cu actiune asociata alfa-litica: labetolol (20mg/zi), carvedilol (2550 mg/zi)
Beta-blocante cu vasodilatatie mediata de NO: nebivolol
Mecanism de actiune: efect central + scaderea debitului cardiac
BETA-BLOCANTE:
INDICATII:
HTA cu boala coronariana
HTA cu IC
HTA cu FA
HTA cu hiperstimulare adrenergica/anxietate
EFECTE SECUNDARE: tulburari metabolice la cele neselective sau putin
selective
CI/PRECAUTII: bradiaritmii
INHIBITORII ADRENERGICI PERIFERICI

ALFA-BLOCANTE
COMPUSI: prazosin, doxazosin (1-20 mg/zi 2-3 prize)
MECANISM DE ACTIUNE: blocarea alfa1-rceptorilor din perifere
INDICATII:
HTA rezistenta la tratament
HTA din insuficienta renala
EFECTE SECUNDARE: hipotensiune severa la prima doza, hipotensiune
ortostatica
CI/PRECAUTII: boala cardiaca ischemica, insuficienta cardiaca
INHIBITORII ADRENERGICI CENTRALI

COMPUSI: clonidina, metildopa trei prize; rilmenidinum/moxonidinum o
priza pe zi
MECANISM DE ACTIUNE: stimularea alfa2-receptorilor adrenergici centrali
cu inhibarea eferentelor simpatice + stimularea alfa2-receptorilor presinaptici
cu scaderea elib de NA
INDICATII: HTA rezistenta la tratament, HTA din sindromul
metabolic/obezitate; alfa-metildopa are indicatie de electie in HTA din sarcina
EFECTE SECUNDARE: hTA posturala, somnolenta/ metildopa - sd lupus
like, hepatita cr autoimuna, anemie hemolitica
CI/PRECAUTII: foecromocitom
VASODILATATOARE
COMPUSI: hidralazina, minoxidil, nitroprusiat de sodiu
MECANISM DE ACTIUNE: actiune directa de vasodilatatie
INDICATII: restaranse
EFECTE SECUNDARE: hiperstimularea adrenergica refelexa
CI/PRECAUTII: boala cardiaca ischemica
CU CE CLASE DE MEDICAMENTE TREBUIE

SA INITIEM/EFECTUAM TRATAMENTUL HTA?
1
DIURETICE TIAZIDICE
BETA-BLOCANTE
INHIBITORI DE ENZIMA DE CONVERSIE
ANTAGONISTI AI RECEPTORILOR DE A II
BLOCANTE ALE CANALELOR DE CALCIU

ESH-ESC GUIDELINES, J. Hypertens, 2007
Tratamentul hipertensiunii arteriale
Principalele cauze de deces la persoane de orice

vrst din regiunile cu venituri mici i medii
(venit brut/loc < 9200 $)
BCV
Cancer
Traumatisme
Infectii resp.
Boli pulm. cr.
BCV
Tumori maligne Traumatisme
Infecii respiratorii
Boli pulmonare cronice
HIV/SIDA
Total decese (%)
SIDA
Europa
i
Asia Central
Orientul Mijlociu i
Africa de Nord
Asia de Sud
Asia de Est
i
Pacific
America Latin
i
Caraibe
Africa
subsaharian
Gaziano TA. Circulation. 2005;112:35473553.
Ponderea factorilor de risc in

determinarea mortalitatii
Cum se diagnosticheaza HTA

Masuratori ocazionale (cabinet)
Tehnica corecta
Minim 3 masuratori (peste 140/90) in 4 luni
Automasuratoare
Verificare
Monitorizare continua (MATA)
Limite
Generale
Tehnica incorecta
Aparatura neverificata (aparat optim = Hg)
Masuratoare in cabinet
Tensiunea de halat alb
Automasuratoare
Cine masoara
MATA
Hypertension Prevalence and

Treatment: North America and Europe
Prevalence of Hypertension
Patients on Therapy
55
50
100
45
40
90
80
US
Canada
Italy
Sweden
England
Spain
Finland
Germany
70
35
% 60
50
30
25
40
30
20
15
20
10
10
5
0
Country
Wolf-Maier K et al. JAMA. 2003;289:2363-2369.
SEPHAR
SEPHAR
Country
6.5 milioane
hipertensivi n Romania
2.4 mil
3.7 mil
2.8 mil
0.4 mil
Frecvena subtipurilor de hipertensiune

la toi subiecii fr tratament (%)
Distribuia n funcie de vrst a subtipurilor de

hipertensiune la persoanele fr tratament
Distribuia procentului global de

hipertensiune netratat n respectiva
categorie de vrst
Vrsta (ani)
Hipertensiune sistolic izolat ( 140 / <90 mm Hg)
Hipertensiune sistolic i diastolic ( 140 / 90 mm Hg)
Hipertensiune diastolic izolat ( 90 mm Hg)
Hipertensiunea secundara
Renoparenhimatoasa
Renovasculara
Feocromocitom
Hiperaldosteronismul primar
Sindrom Cushing
Apneea obstructiva din (de) somn
Coarctatia de aorta
Secundara medicamentoasa
HT secundara renala
Parenhimatoasa
Cea mai frecventa cauza
Evaluare
Ecografie renala (atentie rinichi polichistic)
Examen de urina: proteine, eritrocite, leucocite
Vasculara
Prevalenta ~ 2 % !! displazii, aterosclerotica
Evaluare: sufluri, hipoK, alterare functionala, dimensiune
renala (>1.5 cm), Doppler
Tratament: angioplastie versus medical
HTA secundare endocrine

Feocromocitom
Prevalenta 0.2 0.4 % (2 8/1 milion loc)

Diagnostic = dozare metanefrine plasmatice sau urinare
Teste de stimulare (glucagon) sau supresie (clonidina)
Imagistica
Hiperaldosteronism primar
Prevalenta 1 11 %
Morfopatologie: ~ 30 % adenoame sr (mai frecv );
% hiperplazie, f.rar carcinoame
Crestere TA rezistenta la tratament hipoK
Diagnostic = testul de supresie cu fludrocortizon;
raportul aldosteron/renina discutabil
S. Cushing
Habitus sau latent
Dozare excretie urinara de cortizol (> 110 mmol sau 40 g) + test de
supresie cu dexametazona
70
Alte HTA secundare

Apneea obstructiva din somn
Situatii clinice
Obezitate cu HTA rezistenta
Non-dipperi
Clinica: somnolenta diurna, tulb concentrare, somn agitat, inec in

somn
Indicele apnee/hipopnee = nr episoade/ora
5 15 = usor, 15 30 = moderat, >30 sever
Coarctatia de aorta
Suflu sist/ continuu
Indusa de medicamente/droguri
Contraceptive orale, steroizi, AINS, cocaina, amfetamine,
eritropoietina, ciclosporine, tacrolimus
Modificri ale clasificrii tensiunii arteriale

CAT. ESC
TAS / TAD
(mm Hg)
Optim
< 120 / 80
Normal
120-129 / 80-84
Normal nalt
130-139 / 85-89
Hipertensiune
140 / 90
Gradul 1
140-159 / 90-99
Gradul 2
160-179 / 100-109
Gradul 3
180 / 110
TAS: tensiune arterial sistolic

TAD: tensiune arterial diastolic
CAT. JNC 7
Normal
Prehipertensiune
Hipertensiune
Stadiul 1
Stadiul 2
Modificri ale clasificrii tensiunii arteriale

CAT. ESC
TAS / TAD
(mm Hg)
Optim
< 120 / 80
Normal
120-129 / 80-84
Normal nalt
130-139 / 85-89
Hipertensiune
140 / 90
Gradul 1
140-159 / 90-99
Gradul 2
160-179 / 100-109
Gradul 3
180 / 110
Hipertensiune sistolica izolata

TAD: tensiune arterial diastolic
140 / < 90
CAT. JNC 7
Normal
Prehipertensiune
Hipertensiune
Stadiul 1
Stadiul 2
Riscul global categorii

TA optima fara alti factori de risc = risc etalon
Risc adaugat
Ev. cardiovasculare Mortalitate cv

la 10 ani
la 10 ani
Mic
< 15 %
< 4%
Moderat
15 20 %
45%
Mare
20 30 %
58%
Foarte mare
> 30 %
>8%
Stratificarea riscului global

Elemente TA
TA normal
de risc
normala inalta
TA grad 1
Risc adaugat Risc ad.

mic
mic
TA grad 2
TA grad 3
Risc ad.
moderat
Risc ad.
mare
Fara FR
Risc
etalon
2 FR
Risc ad. Risc ad. mic

mic
Risc ad.
moderat
Risc ad.
moderat
Risc ad.
mare
> 3 FR
sau LOT
sau DZ
Risc ad. Risc ad.

moderat mare
Risc ad.
mare
Risc ad.
mare
Risc ad.
f. mare
BCA
Risc ad. Risc ad.

mare
f. mare
Risc ad.
f. mare
Risc ad.
f. mare
Risc ad.
f. mare
Riscul de BCI la 10 ani (%)
Riscul de BCI la zece ani n funcie de

tensiunea arterial sistolic i de prez ena
altor factori de risc
60
TAS = 120 mm Hg
TAS= 180 mm Hg
50
40
30
20
10
0
Colesterol
180
240
240
240
240
240
HDL
50
50
35
35
35
35
Fumat
Nu
Nu
Nu
Da
Da
Da
Diabet
Nu
Nu
Nu
Nu
Da
Da
HVS
Nu
Nu
Nu
Nu
Nu
Da
BCI: boal coronarian ischemic

HDL: colesterol din lipoproteine cu densitate mare
HVS: hipertrofie ventricular stng
Beneficiile controlului HTA

Complicatia cardio-vasculara Scadere procentuala
Cardiopatia ischemica
20 25
Accidentul vasculr cerebral
35 40
Insuficienta cardiaca
~ 50
Actualitati 1959 - BBPS

Virsta
(ani)
TA
(mmHg)
35
Speranta de viata (ani)
Reducerea
sperantei de
viata (ani)
120/80
130/90
140/95
150/100
41.5
37.5
32.5
25
4
9
16.5
45
120/80
130/90
140/95
150/100
32
29
26
20.5
3
6
11.5
55
120/80
130/90
140/95
150/100
23.5
22.5
19.5
17.5
1
4
6
Nr. persoane
Riscul in HTA
Valori TA
Evaluarea bolnavului hipertensiv

Leziunea subclinica de organ
Cord: ECG (HVS), Eco (HVS)
Rinichi: Clearence creat, microalbuminurie
Artere: grosime intima-medie
Diabetul zaharat:
Glicemie a jeun > 120 mg/dl
Incarcare la 2 h > 198 mg/dl
Alti factori de risc

Dislipidemie
Disglicemie
Tratamentul HTA
Schimbarea stilului de viata

Medicamentos
Interventional
Tratamentul HTA
Schimbarea stilului de viata
Abandonarea fumatului
Scadere in greutate
Scadere consum alcool
Exercitiu fizic
Reducere consum de sare
Crestere consum fructe si legume
Medicamentos
Interventional
Fumatul
Efect
Imediat creste TA cu 10 15 mm
Pe termen lung - 0
Beneficiu
Nul pe TA, bun pentru riscul cv
Metode
Inlocuitori nicotina
Bupropion
Vareniclina
Scaderea in greutate
Scadere si stabilizare a greutatii
Studii observational: greutatea coreleaza
cu TA
Beneficiu
Pina la 20 mm Hg
Metaanalizao scadere cu 5.1 kg duce la o
scadere a TA cu 4.4 3.6 mm Hg
Scaderea consumului de alcool

Consumul de alcool si curba in J
Consumul mare asociat cu AVC (inclusiv
binge-drinking
Alcoolul atenueaza efectul medicatiei
hipotensive
Beneficiu reducere TA cu pina la 4 mm Hg
Doze limitative:
Barbati = 20 30 g Alcool
Femei = 10 20 g Alcool
Exercitiul fizic
Lipsa de antrenament fizic = predictor independent de
mortalitate cardiovasc.
Exercitiul aerobic scade TA de repaus cu pina la 9 mm Hg
(6.9/4.9 mm Hg)
Beneficii suplimentare: scadere in greutate, creserea
sensibilitatii la insulina, cresterea HDL
Concluzie: se recomanda 30 45 min zilnic

(mers, inot, jogging)
Exercitiul de rezistenta (izometric) NU se recomanda
Examinare inainte de recomandare
Modificarea dietei
Scaderea consumului de sare
Studii epidemiologice coreleaza consumul de sare cu TA
Consumul mediu de sare ~ 10 g/zi; reducerea la ~ 5 g ar
scadea TA cu 5 mm Hg (pina la 8 mm Hg)
Recomandari:
nu alimente sarate,
consum ~ 4 g/zi
Posibila controversa
Problema restrictiei de sare
Studiul belgian al echipei Stolarz-Skrzypek

Populatia 3681 persoane fara boala cardiovasculara (26 % hipertensivi)
Urmarire 8 ani
S-a urmarit excretia urinara de Na
Rezultate:
1. excretia de Na coreleaza invers cu mortalitatea cv (4.1% vs 0.8% in
tertilul minim vs maxim)
2. 2096 normotensivi = nici o asociere excretie Na - aparitie HTA
3. 1499 hipertensivi netratati = excretia mai mare de Na coreleaza cu o
valoare TAs semnificativ, dar modest, mai mare
Stolarz-Skrzypek si colab. JAMA 2011; 305: 1777
Alte recomandari dietetice

Recomandari
Cresterea consumului de K
Cresterea consumului de legume si fructe
Scaderea consumului de grasimi saturate si
colesterol
Suplimentarea cu acizi polinesaturati -3
Beneficiu
Scaderi pina la 8 mm Hg (medie 4)
Tratamentul medicamentos
Tiazidice
-blocante
ARB
-blocante
Antag Ca
IECA
Fiziopatologie esentiala
Continator = tonus vascular
Continut = volemie
TA
Activitate pompa = cord
Medicatia hipotensoare
Continator = tonus vascular
Continut = volemie
Diuretice
Vasodilatatoare directe
Blocanti SRAA
Blocanti simpatici
TA
Activitate pompa = cord
Blocanti SRAA
Blocanti simpatici
Clase medicamente hipotensoare

Blocantii SRAA
IECA
BRA
Antialdosteronice
Blocanti simpatici
-blocanti
-blocanti
Blocanti centrali
Diuretice
Tiazidice si similare
De ansa
Altele
Blocantii canalelor de calciu
Nitrati
Hidrazinoftalazina
Calitatile hipotensorului ideal

Sa scada TA eficient
Administrare orala
Actiune de durata lunga (>24 h)
Fara efecte secundare
Actiuni favorabile pe comorbiditati
Blocantii sistemului renina-angiotensina-aldosteron
Inhibitorii enzimei de conversie

Avantaje
Efect protector endotelial

Efect protector renal
Efect util in insuficienta cardiaca
Crestere bradichinina
Limite
Efecte secundare
Tuse
hiperK
Retentia azotata
Efect fetopatic
angioedem
Membrii clasei
Diferente neesentiale de actiune
Diferente de farmacochinetica
Membrii cu dovezi: ramipril, perindopril
Blocantii receptorului de angiotensina II

Avantaje
Blocare mai eficienta a angiotensinei
Efect protector renal
Efect util in insuficienta cardiaca
Limite
Efecte secundare
hiperK
Retentia azotata
Efect fetopatic
Pretul
Membrii clasei
Substanta
T ore
Reducere doza
Losartan
2.5; metab 6 9
Insuf. hepatica
Irbesartan
11 15
Candesartan
Insuf. renala
Valsartan
Insuf. hepatica
Olmesartan
10 15
Telmisartan
24
Insuf. hepatica
Antialdosteronicele
Avantaje
Antifibrozant util in CIC
Diuretice economizatoare de K
Utile in insuficienta cardiaca
Limite
Efecte secundare
Insuficienta renala
hiperK
ginecomastie
Membrii clasei
Aldactona, Eplerenona
Blocantii sistemului simpatic
-blocante
Avantaje
Scad TA la persoanele simpaticotone (unii hipertensivi)
Scad rezistenta periferica
Scad frecventa cardiaca
Limite
Produc spasm bronsic

Scad sensibilitatea la insulina
Scad simptomele si revenirea din hipoglicemie
Scad conducerea a-v
Membrii clasei
Membrii clasei
Proprietati
Selectivitate Stabilizarea
membranei
Act.
Absorbtie
simpaticomim
intrinseca
Biodisp.
T
(ore)
Nadolol
Nu
30 %
30-50 % 24
Propranolol
Nu
++
< 90 %
30 %
3-5
Carvedilol
Nu
++
> 90 %
~ 30 %
7-10
Metoprolol
Nu
~ 100 %
40-50 % 3-7
Atenolol
Da
90 %
50-60 % 6-7
Bisoprolol
Da
90 %
80 %
9-12
Esmolol
Da
0.15
-blocante
Avantaje
Vasodilatatie arteriolara si venoasa
Scad tonusul muscular prostatic si in colul vezical
Limite
Induc tahicardie si retentie hidrosodata
Hipotensiune posturala
Membrii clasei
Neselectivi - fenoxibenzamina, fentolamina
Selectivi 1 prazosin, urapidil, etc
Selectivi 2 (centrali) - yohimbina
Cu actiune centrala
Mecanism actiune
Receptorii - 2 centrali si imidazolinici
Avantaje
Scade eficient TA
Limite
Sedare
Uscaciunea gurii
Hipotensiune ortostatica
Membrii clasei
Clonidina
Rilmenidina
Metildopa
(Guanabenz, Guanetidina)
Rezerpina
Selectivitatea moxonidinei pe receptorii

imidazolinici I1 si pe receptorii 2
Ki = constanta de afinitate
Afinitatea pe I1 versus 2
(log Ki la niv receptorilor I1 / Ki la nivelul receptorilor 2
-5
-4
-3
-2
-1
0
1
2
3
moxonidina
rilmenidina
clonidina
norepinefrina
epinefrina
guanabenz
2 > I1
Ernsberger PR et al. J Cardiovasc Pharmacol 1992;20(suppl 4):S1-S10
I1 > 2
Diuretice
De ansa
Avantaje
Efect rapid, scurt
Limite
Diselectrolitemie
Hipovolemie cu toate consecintele
Ototoxicitate
Membrii clasei
Substanta
Puterea relativa
T ore
Furosemid
~ 1.5
Bumetanid
40
~ 0.8
Ac. etacrinic
0.7
~1
Torasemid
~ 3.5
Diuretice
Tiazidice si similare
Avantaje
Durata mai lunga de actiune
Limite
Diselectrolitemie
Scaderea tolerantei la glucoza
Dislipidemie
Scaderea efectelor anticoagulantelor orale
Interactiune cu antiaritmicele ce gresc QT
Alte rare (digestive, SNC, hemato)
Membrii grupului
Blocantele canalelor de calciu

Avantaje
Scadere eficienta a TA
Neutralitate metabolica
Limite
Produc edeme
Stimulare simpatica
Afectarea conducerii av (nondih)
Membrii clasei
Dihidropiridinici cu actiune lunga
Nondihidropiridinici
Nitrati
Nitroprusiatul de Na
Actiune scurta numai in urgente
Hidralazina
Limite
Stimulare simpatica
Durata de actiune scurta
Furt singe
Sindrom lupic
Minoxidilul
Mecanism actiune deschide canalul K modulat de ATP
Limite
Retentie hidrosalina
Activare simpatica ischemie
Diazoxidul
Strategia tratamentului
farmacologic
Problemele deciziei terapeutice
Cind se incepe tratamentul
Nefarmacologic ?
Medicamentos ?
Cit timp tratam ?

Care sunt tintele cifrice ?
Cu ce tratam ?
Cind se incepe tratamentul ?

Nefarmacologic
Inainte de diagnostic la persoanele cu factori de risc
!! Tratam riscul !!
La diagnostic (probabil inclusiv normalul inalt)
Farmacologic
La cei fara alti FR la valori peste 140/90 care nu
raspund la tratament nefarmacologic
La cei cu alti FR, fara diabet sau atingere subclinica
de organ la valori peste 140/90
La cei cu diabet sau atingere subclinica de organ la
valori peste 130/85
Cit timp tratam ?
Toata viata
Monitorizare permanenta
Tratament ajustat
Care sunt tintele ?
Valorile TA atinse in trialuri de terapie

antihipertensiva
Tintele terapiei antihipertensive

Pe baza datelor actuale poate fi prudenta
recomandarea de a reduce SBP/DBP la
valori in limitele 130-139/80-85 mmHg, si
posibil la valori mai reduse in aceste
limite, la toti hipertensivii
Tintele terapiei antihipertensive

Recomandarea Ghidurilor precedente de a
reduce mai mult TAs (<130 mmHg) la diabetici si
la pacientii cu risc foarte inalt poate fi inteleapta,
dar nu este sustinuta consistent de dovezi din
studii clinice
In nici un trial randomizat la pacienti diabetici nu
s-a demonstrat beneficiu cu reducerea TAS sub
130 mmHg , iar trialurile in care TAS a fost
redusa sub 130 mmHg la pacienti cu boala CV
preexistenta, rezultatele au fost controversate
Tintele terapeutice
Exista dovezi suficiente pentru a
recomanda reducerea TAs sub 140
mmHg si a TAd sub 90 mmHg la toti
hipertensivii, atat la cei cu risc moderat,
cat si cei cu risc inalt.
Dovezile lipsesc la pacientii varstnici la
care beneficiile reducerii TAs sub 140
mmHg nu au fost niciodata testate in
trialuri
Optimal BP values in CKD
Appel JA si colab (AASK Collab Research Group): NEJM, 363:918; 2010
Optimal BP values in CKD
Composite outcome: dubling of SC value, ESRD or death
P=0.01
P=0.16
Appel JA si colab (AASK Collab Research Group): NEJM, 363:918; 2010
Cu ce tratam ?
Exista droguri mai utile in general ?
Ce preferam: un drog sau asocieri ?
Exista asocieri interzise sau preferate ?
Cind se administreaza medicatia ?
Exista medicamente special utile,

de prima intentie ?
Terapia antihipertensiva in
prevenirea bolii CV
Law MR, BMJ 2009
Terapia antihipertensiva in
prevenirea bolii CV
Law MR, BMJ 2009
ALLHAT: Risk of secondary end points with

amlodipine vs chlorthalidone, lisinopril vs
chlorthalidone, and doxazosin vs chlorthalidone
Comparison
CHD
Amlodipine vs chlorthalidone
Lisinopril vs chlorthalidone
Hospitalized fatal heart failure
Doxazosin vs chlorthalidone
Hospitalized fatal stroke
Doxazosin vs chlorthalidone
Hazard 95% CI
ratio
1.00
0.98
0.92 1.08
0.90 1.06
0.95
0.64
1.12
1.00
1.07
1.02 1.22
0.91 1.09
0.98 1.17
0.01
0.94
0.13
0.99
1.04
1.02
0.89 1.09
0.94 - 1.15
0.92 1.12
0.81
0.41
0.72
Cushman WC. American Heart Association 2009 Scientific Sessions; November 18, 2009; Orlando, FL.
Astfel, cea mai mare meta-analiza a studiilor

randomizate de reducere a TA arata ca
scaderea TAS cu 10 mmHg sau a TAd cu 5
mmHg utilizand oricare din clasele majore de
antihipertensive reduce evenimentele
coronariene cu cca 1/4 si AVC cu cca 1/3
independent de prezenta sau absenta bolii CV
in antecedente si de TA initiala.
Insuficienta cardiaca se reduce cu cca 1/4
Law MR, BMJ 2009
Nu exista droguri preferentiale.

Tinta este reducerea valorilor TA.
Alegerea depinde de patologia coexistenta.
Indicatiile claselor de medicamente

in functie de patologia coexistenta
IECA
HVS
BRA
Anti ald
-bloc
+
+
Angor pectoris
+
Fibrilatie Atriala
Tahicardii supraventic
Nefropatii
+
+
Insuf Renala terminala

Sindrom Metabolic
+
+
HTA sistolica izolata

Sarcina
Glaucom
Tuse post IECA
+
+
Aterosc carotidiana
Diur ans
Disfunctie VS
Post infarct miocardic
Bloc Ca Diur tiaz
+
+
--
Contraindicatiile unor clase de medicamente

IECA
BRA Anti ald
-bloc Bloc Ca Tiazidice
++
Bloc av gr II
++
Boala arteriala periferica
Guta
++
++
Sindrom metabolic
Disglicemii
++
Astm bronsic
++
Stenoza bilat artera renala
++
++
Hiperkaliemie
++
++
Insuficinta renala
Sarcina
++
++
++
++
++
Locul asocierilor medicamentoase
Numarul de droguri necesare pentru a atinge

tinta TA
Study
UKPDS1
BP goal
(mm Hg) 1
No. of drugs
2
DBP 85
ABCD2
DBP 75
MDRD3
MBP 92
HOT4
DBP 80
AASK5
MBP 92
IDNT6
SBP135/DBP85
ALLHAT7
SBP140/DBP90
1. UK Prospective Diabetes Study Group. BMJ. 1998;317:703713. 2. Estacio RO, et al. Am J Cardiol. 1998;82:9R14R. 3. Lazarus JM, et al. Hypertension.
1997;29:641650. 4. Hansson L, et al. Lancet. 1998;351:17551762. 5. Kusek JW, et al. Control Clin Trials. 1996;16:40S46S. 6. Lewis EJ, et al. N Engl J Med.
2001;345:851860. 7. ALLHAT. JAMA. 2002;288:29983007
The Am J of Hypertens. 2009; 122:290-300
Schema propusa in Ghidul 2007

Alegeti intre
Crestere usoara TA
Crestere importanta TA
Risc cv mic/moderat
Risc CV mare/f.mare
Tinta conventionala
Tinta TA joasa
Un hipotensor in doza mica
Combinatie a doua hipotensoare

in doza mica
Tinta TA nu este atinsa

Agentul initial
Alt agent
in doza maxima
in doza mica
Combinatia
precedenta in doza max
Adaugati al treilea
in doza mica
Tinta TA nu este atinsa

Combinatie 2 3 in
Acelas doza max
Combinatie 2 3 in
A Simplified Approach to the Treatment of

Uncomplicated Hypertension: A Cluster
Randomized, Controlled Trial
STITCH-care algorithm. Feldman RD et al Hypertension 2009;53:646-653
Terapia combinata
Exista tot mai multe dovezi ca pentru vasta
majoritate de pacienti controlul eficace al TA
poate fi obtinut doar prin combinatia de cel
putin doua medicamente antihipertensive
Adaugarea unui medicament din alta clasa la
cel prescris initial ar trebui sa fie strategia
terapeutica preferata, exceptand necesitatea de
a opri primul medicament (r. adverse,
ineficienta)
Asocieri preferabile
sau
Asocieri ce trebue evitate
Terapia combinata
Combinatia betablocante-diuretice favorizeaza
aparitia diabetului zaharat si ar trebui evitata, cu
exceptia situatiilor in care are alte indicatii decat
HTA
Utilizarea combinatiei ACEI-sartan are avantaje
discutabile si efecte adverse crescute cu exceptia
nefropatiei cu proteinurie, unde exista beneficii
dovedite (efect antiproteinuric marcat)
Cand sunt necesare trei medicamente pentru
controlul HTA, combinatia cea mai rationala este
un blocant al SRA cu calciublocant si cu diuretic la
doze eficiente
Cind se administreaza
tratamentul ?
Evolutia circadiana a TA
16
21
Reducerea scaderii nocturne (prifil nondeeper) se

asociaza cu cresterea riscului cv
Media TA nocturne este un predictor mai bun de risc
decit media diurna
Implicatia terapeutica studiul MAPEC

publicat sept 2010
2156 subiecti (1044 barbati) cu HTA de minim 6 luni, diagnosticati cu MATA

(TA diurna 135/85; nocturna 120/70 mm Hg), virsta media ~ 55 ani
1380 netratati anterior, 776 tratati si rezistenti
Medicatia la latitudinea medicului curant
Randomizati sa ia medicatia dimineata sau seara
Urmarire 5.6 ani
REZULTATE
Evenimente cardiovasculare 187 versus 68
Evenimente majore (moarte cv, IM, AVC) 55 vs 18
CONCLUZII
Cel putin un medicament trebue administrat seara
Complianta si Aderenta
Tratamentul interventional
Metode moderne
Denervarea renala
50 pac. cu TA 160 mm Hg pe trata cu 3 medicamente (inclusiv diuretic)

TA medie sist - 17720 mm Hg , diast 101 15 mm Hg
RFG estimata 81 mL/min/1.73 m
Timp (luni)
Lot tratat 45 pac
Lot martor 5 pac
- 14/-10
+ 3/- 2
- 21/-10
+ 2/+ 3
- 22/-11
+ 14/+ 9
- 24/-11
+ 26/+17
12
-27/- 17
Incidente
1 disectie stentata
Raspuns 83 % (scadere cu 10 mm Hg)
Krum H, Schlaich M, Whitbourn R si colab.:Lancet 2009; DOI:10.1016/S0140-6736(09)60566-3
Denervarea renala
24 centre Europa, Austarlia, Noua Zeelanda

Studiu randomizat, deschis
103 pac. TA 160 mm Hg sau 150 mm Hg + DZ 2 luind 3 med.
52 denervare + tratament medical / 51 tratament medical
Lot denervat (52 pac)
Lot martor (51 pac)
Initial
178/96 mm Hg
178/97 mm Hg
6 luni
146/84 mm Hg
177/97 mm Hg
Respondenti
(scadere 10 mm Hg)
84 %
35 %
The Symplicity HTN-2 Trial. Lancet 2010 dec; 376: 1903 - 1906
Substratul fiziologic
Hipertrofie
Aritmii
Consum O2
Eliberare renina
Retentie Na
Flux sangv. renal
Activare SRAA
Cauze de hipertensiune arterial necontrolat

FACTORI CARE IN DE PACIENT:
FACTORI CARE IN DE MEDIC:
Acces limitat la serviciile de sntate
Lipsa de informaii despre

recomandri
Lipsa asigurrii de sntate

Lipsa unui furnizor de servicii medicale
regulat
Susceptibilitate crescut la hipertensiune

Vrst avansat
Obezitate
Lipsa de complian la tratament

Lips de informaii
Costul medicaiei
Scheme de tratament complicate
Efecte nedorite
Comunicare deficitar medic-pacient
Lipsa suportului social
Hipertensiune rezistent (mai puin

frecvent)
Nivele prag ale TA

Hipertensiunea sistolic izolat
Nivele prag la pacienii diabetici
Utilizarea monoterapiei la pacienii la
care TA este greu de controlat
Supraestimarea complianei la
recomandri
Lipsa de consens a recomandrilor
Hipertensiunea sistolic izolat
ngrijorri legate de curba J
ngrijorri legate de efectele nedorite

ale medicaiei
Prerea c TA msurat la cabinet
are tendina s fie mai mare dect TA
msurat la domiciliu
Cauze secundare
Adaptat dup: Wang TJ. Circulation. 2005;112:16511662.
Miliarde de dolari
Costurile directe i indirecte estimate ale principal elor

boli cardiovasculare i accidentului vascular cerebral
n 2006
Heart Disease and Stroke Statistics 2006 Update.

Disponibil la: http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.105.171600v1
Costurile directe i indirecte estimate

ale hipertensiunii n SUA n 2006
Scderea
productivitii/
morbiditate
ngrijiri de
sntate la
domiciliu
Scderea
productivitii/
mortalitate
Miliarde de dolari
Spital
Miliarde de dolari
Costuri directe totale
Costuri indirecte totale
Bunuri
medicale
durabile
Case de
sntate
Medici i ali
profesioniti
Costurile directe
Costurile indirecte
Heart Disease and Stroke Statistics 2006 Update. Circulation. 2006;113:e85-e151.
Costul eecului n atingerea valorilor int

ale tensiunii arteriale n cinci* ri europene
PREVALENA HIPERTENSIUNII *
COSTURILE EVENIMENTELOR CV*
Miliarde de euro
Prevalena* (milioane)
Scdere cu 12,6%
a costului
21%
140/90-160/95
13%
> 160/95
Tensiunea arterial (mm Hg)
*Frana, Germania, Italia, Suedia, i Marea Britanie

CV: cardiovascular
Costurile anuale totale*

pentru evenimente CV
Costurile* pentru
evenimente CV dac
TA cu tratament
atinge valorile int
Hansson L. Blood Pressure. 2002;11:3545.
QUESTIONS
315
Teste de baza pt evaluarea initiala a HTA
A. Intotdeauna incluse:
Glucoza, sangele, proteinele urinare

Hematocrit
Potasemia
Creatinina serica si/sau ureea sanguina
EKG
De obicei incluse, in fctie de cost si alti factori:

Examen microscopic al urinii
Leucocitemia
Glucoza plasmatica sanguina, colesterol, colesterol HDL, TG
plasmatice/sanguine
Acid uric, fosfati si calciu serice
Radiografie toracica, ecocardiografia.
Teste speciale pt evaluarea HTA sec
Boala renovasculara: renograma cu IEC, examinarea ambilor rinichi cu

ultrasunete
Feocromocitom: det. creatininei, metanefrinelor si catecolaminelor in
urina/24h sau a catecolaminelor plasmatice.
Sindrom Cushing: testul de supresie nocturna cu dexametazona sau det.
cortizolului in urina/24h.
AFECT. CARDIOVASCULARE
HTA
Tratament nefarmacologic - combaterea factorilor de risc:

Reducerea aportului de sare la 5-6 g/zi
Renuntarea la alim. bogate in colesterol si grasimi saturate
Alimentatie hipolipidica si hipocalorica
Dieta bogata in legume, fructe si lactate (aport optim de K, Na, Ca)
Renuntarea la tutun si cafea
Reducerea consumului de alcool: < 30g etanol/zi barbati, < 15g/zi femei
Combaterea sedentarismului si obezitatii
Evitarea stresului
Tratamentul farmacologic:
Este permanent in HTA esentiala
Adaptat la gradul, grupul de risc, stadiul de HTA si evolutia bolii.
Med. CI in HTA:
Excitantele SNC (cafeina, anorexigenele amfetaminice)
Forme farm. eff.
Locul act. Med.
Doza
Ind.
Cind.
RA
Caz clinic. Discutii
Pacienta in varsta de 65 ani este externata cu diagnosticul de HTA stadiul II

si dislipidemie.
Tratament:
Monopril 10mg - 1 cp/zi
Betaloc Zok 50mg 2 x 1 cp/zi
Zocor 10mg 1cp/zi
Obiective terapeutice:
Scaderea TA <140/90 mmHg
Reducerea complicatiilor (AVC, insuf. cardiaca, infarct miocardic, insuf.
renala)
Reducerea mortalitatii
Discutii
Monopril (fosinopril) antiHTA, IEC al AT-1 si AT-2
Betaloc Zok (metoprolol) blocant B-adrenergic selectiv, efect antiHTA

moderat
hipercolesterolemiei fact. de risc pt. boli cardiovasc.
Zocor (simvastatina) inhiba HMG-CoA reductaza

Ameliorarea calitatii vietii pacientei
Obs.: Pacienta nu a mai utilizat med. decat in perioada internarii in spital;

necesita consiliere!
Cind:
IEC CI in edem angioneurotic (in antecedente)
B-blocantele de evitat in: astm bronsic, hiperreactivitate bronsica, bloc

atrio-ventricular de grad II sau III, sindrom Raynaud, tulburari circ. periferice.
Inhibitorii HMG-CoA reductazei CI in hepatita cronica, cresteri prelungite

ale transaminazelor serice, miopatie (in antecedente)
Doze. Mod de adm.
Monopril: doza initiala 10mg, o data pe zi, poate fi ajustata in fctie de val. TA
la 20-40mg/zi.
Adm. in priza unica zilnica scade ef antiHTA la sf. intervalului de
dozare !
Se recomanda divizarea dz. zilnice in 2 administrari.
Betaloc Zok: doza initiala metoprolol 100mg/zi, o data/zi sau fractionata in 2

adm.
Contine metoprolol succinat (50, 100, 200 mg) compr. cu elib. controlata.
Se inghit intregi fara a fi zdrobite.
Efectul apare treptat si este max. dupa cca 1 sapt de trat
Doza eficienta 100-450 mg/zi.
Adm. in timpul sau imediat dupa masa.
Zocor: doza initiala 10 20mg/zi.

Ajustarea posologiei la interval de min 4 sapt in fctie de rasp terap
(scaderae LDL-colesterolului)
La varstnici: doza uzuala 5 10 mg/zi
Simvastatina se adm. seara, la culcare,pt un efect maxim al HMG-CoA
reductazei.
Obs: dozele adm. si frecv. adm. sunt corespunzatoare.
RA: usoare, tranzitorii, pot fi prevenite.
RA si precautii la adm. MONOPRILULUI

RA MONOPRIL
hTA ortostatica in primele zile de tratament si la asoc. cu diuretice sau alte
antiHTA
Prevenita prin initierea terapiei cu doze mici, care se cresc treptat si
monitorizarea TA
Hiperpotasemie:
Se evita asoc. cu alte med care pot det. hiperpotasemie (diuretice econ.
de K, saruri de K)
Consum moderat de alim. bogate in K: peste, pasare, lapte, banane, kiwi,
caise, portocale, prune, spanac, cartofi, rosii
Tusea seaca:
Apare dupa cateva sapt. de trat.
Antitusivele sunt ineficace (exceptie: cromoglicat de sodiu)
Se poate inlocui cu un blocant al recept. AT.
RA MONOPRIL
Tulburari de gust
Hipersensibilitate, angioedem
Rash cutanat (tranzitor), edem facial (se intrerupe trat. si se adm.
antihistaminice H1), edem laringian (urgenta: 0.3-0.5 ml adrenalina 1/1000,
s.c.)
Insuf. renala acuta
Se reduce prin doze initiale mici de IECA si monitorizarea fctiei renale.
RA Betaloc Zok
hTA, bradicardie se scad dozele (se monitorizeaza TA, frecv. cardiaca)

hTA ortostatica initierea trat. cu doze mici si cresterea treptata
Insuf. cardiaca dat. deprimarii miocardului
! La cresterea dozelor
Alterarea metab. lipidic

Risc scazut la doza terap. (metoprololul B-blocant cardioselectiv)
! Adm. concomitenta a simvastatinei
Intreruperea brusca a trat.

Angina instabila, infarct miocardic (deces) la pacientii cu antecedente ischemice
Tahicardie, HTA, stare generala de rau efect rebound
Altele: cosmaruri, depresie, tulb. gastro-int.,etc.
RA Zocor
Tulburari hepatice
Cresterea transaminazelor serice (ASAT, ALAT)
Apar la 3-12 luni de la inceperea trat.
Dispare la intreruperea trat. (r. reversibile)
Se evalueaza periodic fctia hepatica
Se intrerupe trat. daca transaminazele cresc de 3X > normal
Miopatii
Dureri musc. inexplicabile, slabiciune musc. (se avertizeaza medicul)
Se monitorizeaza CPK (creatinfosfokinaza serica) de origine musc
Val. CPK > 10X normal miopatie intreruperea trat.!
! La adm. concomitenta de fibrati, acid nicotinic, inhibitoarele metabolizarii
hepatice a simvastatinei (ciclosporina, itraconazol, ketoconazol,
eritromicina, claritromicina)
RA Zocor
Tulb. gastrointest.: constipatie, flatulenta, dispepsie, dureri abdominale,

greata, diaree (tranzitoriu).
Tulb. oculare: agravarea cataractei
Analiza Rp
Nu exista riscul unor interact. M-M pe reteta, eventual
cresterea riscului de hTA ortostatica (metoprololfosinopril)
Interactiuni cu alimentele
Biodisponib. metoprololului creste cu alim. - adm. in timpul sau imediat

dupa masa
Biodisponib. simvastatinei (oral) creste la adm. concomitenta de suc de

grapefruit (creste riscul de miopatii!) CI grapefruit
Schema de adm.
Medicament
Dimineata
(ex. Ora 7)
Monopril 10mg
1 compr.
Betaloc Zok
50mg
1 compr.
2 compr.
(sau 1 comp.
de 100 mg)
Zocor 10mg
Seara
(ex. Ora 19)
La culcare
(ex. Ora 22)
1 compr.
-
Obs.:
Creste
complianta,
dar poate acc.
hTA ortostatica
1 compr.
CONCLUSION
C
WERE IS
HYPERTESSION TREATMENT???
Prof Univ Dr Ion C.Tintoiu FESC

Centrul de Cardiologie al Armatei
Universitatea Titu Maiorescu
Cardiac Resynchronization
Therapy
CONCLUZII
Increase the donkeys (heart) efficiency
PROTECTIE CEREBRALA,CARDIACA,RENALA
Cardiac Resynchronization
Therapy
SARTANII Increase the donkeys (heart) efficiency
-Blockers
Digitalis Compounds
Like the carrot placed in front of the donkey
D-Thiazide Diuretics
D
Veins
Mechanism: inhibit Na/K pumps in

the distal tubule
Examples:
Thiazides
Hydrocholorthiazide 12.5-25 mg daily

Chlorthalidone 12.5-50 mg daily
Effective first line agent and

provides synergistic benefit
As single agent more effective if
CrCl >30 ml/min
Compelling indications: HF, High
CAD risk, Diabetes, Stroke, ISH
D-Loop Diuretics
Veins
Mechanism: Inhibit Na/K/Cl ATPase

in ascending loop of henle
Examples:
Thiazides
Loops
Furosemide 20 mg BID
Typically only beneficial in patients

with resistant HTN and evidence of
fluid; effective if CrCl <30 ml/min
MUST be dosed at least twice daily
(Lasix = Lasts six hours)
Administer AM and lunch time to
avoid nocturia
D-Aldosterone Receptor Antagonists

Veins
Mechanism: inhibit aldosterones

effect at the receptor, reducing Na
and water retention
Examples:
Thiazides
Loops
Aldosterone Ant.
Spironolactone 25 mg daily
Can provide as much as 25 mmHg

BP reduction on top of 4 drug
regimen in resistant hypertension
Monitor SCr and K
Compelling indications: HF
Am J Hypertension. 2003; 16:925-930.
JNC 7: Update on the Management of

Hypertension
New Features and Key Messages
Above 115/75 mmHg, CVD risk

doubles with each BP increase of
20/10 mmHg
Prehypertension
SBP 120139 mmHg
DBP 8089 mmHg
Require health-promoting lifestyle modifications
to prevent CVD
Patient involvement is key
http://hin.nhlbi.nih.gov/nhbpep_slds/menu.htm; Accessed October 20, 2003; 8:15AM
Recommendations: Hypertension/Blood Pressure Control

Treatment (5)
Multiple drug therapy (two or more agents at maximal doses)
Generally required to achieve blood pressure targets (B)
If ACE inhibitors, ARBs, or diuretics are used

Kidney function, serum potassium levels should be monitored (E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Choose between
Mild BP elevation
Low/moderate CV risk
Conventional BP target
Marked BP elevation
High/very high CV risk
Lower BP target
Low-dose single agent
Low-dose 2-drug combination
Not at BP goal
Full dose of
single agent
Switch to
different agent
at low dose
Full dose of
2-drug
combination
Add a
third drug
at low dose
Not at BP goal
23 drug
combination
at full dose
Full-dose
single agent
TOD = target organ damage
Full doses of 23-drug

combination
Task Force for ESHESC. J Hypertens 2007;25:110587
% reduction in incidence of events
Reduction in Incidence of CHD Events and

Stroke in Relation to Reduction in BP and Age
0
10
CHD
stroke
0
10
20
20
30
30
40
40
50
50
7079yrs
7079yrs
6069yrs
60
6069yrs
60
5059yrs
7079yrs
70
6069yrs
5059yrs
7079yrs
70
6069yrs
Systolic
80
Diastolic
5059yrs
5059yrs
80
0
10
20
30
10
15
Reduction in blood pressure (mmHg) with treatment

Law et al 2009
HYPERTENSION COMPLICATION S
353
Protectie de
organe
AVC
23%
P=0,0003
EVENIMENTE
CORONARIENE
13%
P=0,007
EVENIMENTE
RENALE
15%
P=0,0187
ASCOT investigators. The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure

Lowering Arm (ASCOT-BPLA). Lancet. 2005; 366: 895-906.
UPDATE
2009
GHIDUL ESH DE MANAGEMENT AL HIPERTENSIUNII

ARTERIALE REVIZUIT IN 2009
SUBLINIAZA
NEVOIA COMBINATIILOR DE ANTIHIPERTENSIVE
controlul eficient al tensiunii arteriale poate fi atins numai cu o

combinatie de cel putin 2 antihipertensive.
sal of European guidelines on hypertension management - Journal of Hypertension 2009;27:2121-2158
UPDATE 2009GHIDUL
ESH DE MANAGEMENT AL HIPERTENSIUNII

ARTERIALE REVIZUIT IN 2009
NEVOIA COMBINATIILOR DE ANTIHIPERTENSIVE
ori de cate ori este posibil, utilizarea unei combinatii fixe

ar fi de preferat, deoarece simplificarea tratamentului
aduce avantaje pentru complianta la tratament.
Reappraisal of European guidelines on hypertension management - Journal of Hypertension 2009;27:2121-2158
Cardiovascular disease:
Role of angiotensin II in the CV continuum
Remodelling
Ventricular dilation/
cognitive dysfunction
Myocardial
infarction &
stroke
Atherosclerosis
and LVH
Microalbuminuria
Endothelial
dysfunction
Hypertension risk factors

diabetes, obesity, elderly
Macroproteinuria
Congestive heart failure/

secondary stroke
Nephrotic
proteinuria
End-stage
heart disease,
brain damage
and dementia
End-stage
renal
disease
Cardio/
cerebrovascular
death
Adapted from Dzau V. and Braunwald E., Am Heart J

1991;121:12441263
WERE IS
HYPERTESSION TREATMENT???
Impactul TA asupra mortalitii vasculare este important,

indiferent de vrst
AVC
C a r d io p a t ie is c h e m ic
256
8 0 -8 9
256
8 0 -8 9
128
7 0 -7 9
128
7 0 -7 9
6 0 -6 9
64
6 0 -6 9
5 0 -5 9
32
5 0 -5 9
16
4 0 -4 9
64
32
16
8
1
120
140
160
180
T A S (mm Hg)
120
140
160
180
T A S (mm Hg)
Lewington, et al. Lancet. 2002; 360:1903-1913.
HTA: principalul factor de risc

cardiovascular
13% din total decese pe glob
50% din povara BCV TA suboptimala
HTA = cel mai puternic factor de risc cv.
Cu cat TA e mai mare, cu atat riscul e mai mare
TAs mai bine corelata cu riscul
Mensah. Cardiol Clin. 2002;20:181-185;
World Health Organization. World Health Report 2002. Geneva, Switzerland
Scderea TAS cu doar 2 mm Hg scade riscul de

evenimente CV cu 7-10%
Meta-analiz a 61 de studii prospective, observaionale

1 milion aduli
12.7 milioane pacienti-an
2 mm Hg scdere
n TAS medie
7% reducere a
riscului de
mortalitate prin
cardiopatie
ischemic
10% reducere n
riscul de mortalitate
prin accident
vascular cerebral
Lewington S et al. Lancet 2002;360:1903-1913.
Beneficiile scaderii TA
Reducere % medie RR
AVC
3540%
IM
2025%
IC
50%
JNC 7 JAMA 21.05.2003
How many are really Dx. and

Rx.ed ??
Under control (40%)

Diagnosed
HT
37%
Hypertensives
(22%)
Normotensives (78%)
63%
Under
Un Rx. treatment
HT
(50%)
(7.5% of the total

hypertensives)
Uncontrolled
hypertension (60%)
Undiagnosed
HT
A study from Europe on 23,339 patients

364
Controversies in CV Medicine
Management of Hypertension:
MONO vs DUAL THERAPY
Sever et al. Circulation. 2006;113:2754-2772 (A).
1.Diuretics
1.Thiazides
hydrochlorothiazide(HydroDIURIL,Esidrix);
chlorthalidone(Hygroton)
2.Loopdiuretics
furosemide(Lasix);bumetadine(Burmex);
ethacrynicacid(Edecrin)
3.K+Sparing
amiloride(Midamor);spironolactone(Aldactone);
triamterene(Dyrenium)
4.Osmotic
mannitol(Osmitrol);urea(Ureaphil)
5.Other
CombinationHCTH+triamterene(Dyazide)
acetazolamide(Diamox)
Diuretics(cont)
1.SiteofAction
RenalNephron
2.MechanismofAction
UrinaryNa+excretion
Urinarywaterexcretion
ExtracellularFluid
and/orPlasmaVolume
AcutedecreaseinCO
ChronicdecreaseinTPR,normalCO
Mechanism(s)unknown
Diuretics(cont)
4.AdverseReactions
dizziness,
electrolyteimbalance/depletion,
hypokalemia,
hyperlipidemia,
hyperglycemia(Thiazides)
gout
5.Contraindications
hypersensitivity,
compromisedkidneyfunction
cardiacglycosides(K+effects)
hypovolemia,
hyponatremia
QuickTmeand
TIF(Uncompresd)ecompreso
aren d tosethispcture.
Diuretics(cont)
Thiazides(mostcommondiureticsforHTN)
Generallystartwithlowerpotencydiuretics
GenerallyusedtotreatmildtomoderateHTN
UsewithlowerdietaryNa+intake,
andK+supplementorhighK+food
K+Sparing(combinationwithotheragent)
Loopdiuretics(severeHTN,orwithCHF)
Osmotic(HTNemergencies)
Maximumantihypertensiveeffectreached
beforemaximumdiuresis2ndagentindicated
QuickTmeand
TIF (Uncompres d)ecompreso
aren de tose thispcture.
Vasodilators
Drugs:hydralazine(Apresoline);minoxidil(Loniten);
nitroprusside(Nipride);diazoxide(HyperstatI.V.);
fenoldopam(Corlopam)
1.SiteofActionvascularsmoothmuscle
2.Mechanismofaction
nitroprusside
fenoldopam
NO
DA
Na+
hydralazine
Ca++
Ca++
K+
minoxidil
diazoxide
Vasodilators,
Cont
3.Effectoncardiovascularsystem
vasodilation,decreaseTPR
4.AdverseEffects
reflextachycardia
IncreaseSymNSactivity(hydralazine,minoxidil,diazoxide)
lupus(hydralazine)
hypertrichosis(minoxidil)
cyanidetoxicity(nitroprusside)
5.Contraindications
nitroprussideivonly
hydralazinesafeforpregnancy
diazoxideemergencyuseforseverehypertension
SummaryImportantPoints
HypertensiveAgents
Eachclassofantihypertensiveagent:
1.hasasspecificmechanismofaction,
2.actsatoneormoremajororgansystems,
3.onamajorphysiologicalregulatorofbloodpressure,
4.reducesCOand/orTPRtolowerbloodpressure,
5.hasspecificindications,contraindications,and
therapeuticadvantagesanddisadvantagesassociated
withthemechanismofaction.
Baroreflexes
1) MAP=setpoint
2) Reflexesdefendsetpoint
1) ArterialBaroreflexes
2) Pressure/Natriuresis
3) ChangeinMAPopposedby
reflexresponsetomaintain
setpressure.
4) Hypertensionpressureresets
tohigherleveldefendedby
reflexsystems.
CRITICALPOINT!
**Multipletherapiesoften
neededtoblockreflex
compensation.
QuickTime and a
TIFF (LZW) decompressor
QuickTime and a
QuickTime and a
COXSVR=
MAP
Thiazides
Chlorothiazide
(Diuril)
Chlorthalidone
Hydrochlorthiazide(Microzide,
Hydrodiuril)
Polythiazide (Renese)
Indapamide (Lozol)
Metolazone (Mykrox, Zaroxolyn)
*All trade / brand / generic names are
Benefits of Thiazide Diuretics

Evidence-based support for end points
that matter (prevention of CV and allcause mortality).
Reduced calcium excretion is a potential
benefit for osteoporosis prevention.
Loop Diuretics
Bumetanide (Bumex)
Furosemide (Lasix)
Torsemide (Demadex)
Potassium-sparing Diure
Amiloride (Midamor)
Triamterene
(Dyrenium)
Aldosterone Receptor Blockers

Eplerone (Inspra)
Spironolactone (Aldactone)
Combined alpha- and betablockers

Carvedilol (Coreg)
Labetalol
Trandate)
(Normodyne,
Beta-blockers
Atenolol(Tenormin)
Betaxolol
(Kerlone)
Bisoprolol (Zebeta)
Metoprolol (Lopressor,
Toprol XL)
Nadolol (Corgard)
Propranolol (Inderal/XL)
Timolol (Blocadren)
ACE inhibitors
Benzapril
(Lotensin)
Captopril
(Capoten)
Enalpril
(Vasotec)
Fosinopril
(Monopril)
Lisinopril
(Prinivil, Zestril)
Moexipril
(Univasc)
Perindopril (Aceon)
Quinapril
(Accupril)
Ramipril
(Altace)
Trandolapril (Mavik)
Angiotensin II Receptor Blockers
Candesartan
(Atacand)
Eprosartan (Tevetan)
Irbesartan (Avapro)
Losartan
(Cozaar)
Olmesartan (Benicar)
Telmisartan (Micardis)
Valsartan
(Diovan)
Calcium channel blockers
Dihydropyridines
Amlodipine (Norvasc)
Felodipine (Plendil)
Isradipine (Dynacirc CR)
Nicardipine (Cardene SR)
Nifedipine (Adalat CC,
Procardia XL)
Nisoldipine (Sular)
DHPs can have negative inotropic effects, unlike non-DHPs,

so use with caution in pts with impaired cardiac function
Calcium channel blockers
non-Dihydropyridines:
Diltiazem (Cardizem CD,
Dilacor XR, Tiazac, Cardizem
LA)
Verapamil (Calan SR, Isoptin
SR)

specific to the USA
DHPs can have negative inotropic effects, unlike non-DHPs,

so use with caution in pts with impaired cardiac function
Alpha1 blockers
Doxazosin
Prazosin
Terazosin
(Cardura)
(Minipress)
(Hytrin)
Direct Vasodilators
Hydralazine (Apresoline)
Minoxidil
(Loniten)
Centrally acting drugs
Clonidine
Methyldopa
Reserpine
Guanfacine
(Catapres)
(Aldomet)
(generic)
(generic)
True or False
135andDBP<90.
HYPERTENSION
387
False
120andDBP<80.PeoplewithSBP120
139ORDBP8089shouldbeconsidered
prehypertensive.

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HIPERTENSIUNEA

Prof univ dr Ion C.intoiu

Problem major de sntate public

HTA: principalul factor de risc

< 160/95 mmHg

MarquesMarques-Vidal P et al. J Hum Hypertens 1997

Adapted from G. Mancia / L.

Procentul pacientilor tratati

EHS iunie 2007

Hypertension Prevalence and

Frecvena subtipurilor de hipertensiune

Distribuia n funcie de vrst a subtipurilor de

Distribuia procentului global de

JNC 7 JAMA 21.05.2003

Scderea TAS cu doar 2 mm Hg scade riscul de evenimente

Meta-analiz a 61 de studii prospective,

THE VITAL SIGNS

WHY DO WE MONITOR THE BLOOD

HOW DO WE MEASURE BLOOD

WHAT IS THE EFFECT OF EXERCISE

HERE IS HYPERTENSION ????

Algebra of Blood Pressure

What we record as B.P.

Hypertension is a multi-organ systemic disease

How many are really Dx. and Rx.ed ??

Under control (40%)

(7.5% of the total

A study from Europe on 23,339 patients

Two readings, 5 minutes apart. Sitting in chair, not on exam

Provides information on response to therapy. May help

Indicated for evaluation of white-coat HTN. Can be used to

http://hin.nhlbi.nih.gov/nhbpep_slds/menu.htm; Accessed October 20, 2003; 8:15AM

Examples of recommended BP monitors.

Mercury sphygmomanometers (gold

(details available BHS website)

Maj. nu au semne specifice.

Istoric familial de HTA

Istoric de: angina pectorala, insuf. cerebrala, insuf. cardiaca congestiva,

Factori de risc: fumatul, diabet zaharat, dislipidemia, decese premature in

Stil de viata: dieta, activitatea fizica, statutul familial, profesia, nivelul de

aspectul general (fata rotunda, obezitatea tronculara sindr Cushing?)

Compararea TA si pulsului la cele 2 membre sup. in ortostatism si

Inaltimea si greutatea pacientului

Examenul fundului de ochi

Examinarea inimii si plamanilor

Teste de baza pt evaluarea initiala a HTA

Glucoza, sangele, proteinele urinare

De obicei incluse, in fctie de cost si alti factori:

Teste speciale pt evaluarea HTA sec

Boala renovasculara: renograma cu IEC, examinarea ambilor rinichi cu

Tratament nefarmacologic - combaterea factorilor de risc:

Identifies white-coat hypertension

Ambulatory Blood Pressure Monitoring - ABPM

Dippers & Non Dippers

What is this pattern in HT Dippers and Non-dippers ?

Dippers & Non Dippers

Systolic Blood Pressure (mm Hg)

Systolic Blood Pressure

24 hours clock time

Dippers & Non Dippers

1. Less than 10% circadian variation in SBP and DBP

Valori normale ale TA evaluata prin MAATA (ABPM)

N.B.=5682 p Olanda, Belgia, Japonia, Suedia )10 ani)

CLASIFICATION AND STADIALIZATTION