MONITORIZAREA AMBULATORIE A TENSIUNII ARTERIALE

DE LA CERCETARE LA APLICABILITATEA CLINICA

Alexandru AndritoiuAlexandru AndritoiuSp. Clinic de Urgenta Militar Craiova

Sectia Medicina Interna

Moto:

,, Blood pressure is a quantity with a very large range…hypertension is a quantitative disease,,

Sir George White Pickering

(1904-1980)

1968

1961

Office BP vs. Out-of-Office BPOffice BP vs. Out-of-Office BP

• Office BPOffice BP TA de cabinet

• Out-of-Office BPOut-of-Office BPABPM Auto-masurarea TA la domiciliu

ESH/ESC 2013

TEHNICI DE MONITORIZARE TATEHNICI DE MONITORIZARE TA

Non-invaziveNon-invazive• ABPM ambulatory

blood pressure monitoring

• HBPM home blood pressure monitoring

InvaziveInvazive• Manometrie I.A.

Metode ABPMMetode ABPM

• Metoda oscilometrica

• Metoda auscultatorie

• Metoda pletismografica

Protocoale de validare AAMI (1990) si BHS (1993)

SpaceLabOMRONTakedaT2420

Home BP monitoringHome BP monitoring

IndicatiiIndicatii

FARA TRATAMENT• HTHA (WCH)• HTA borderline• HTA refractara• HTA secundara• HTA sarcina• hipoTA ortostatica• HTA episodica• Disf. autonoma

CU TRATAMENT• Eficienta terapeutica• HTA rezistenta

Giusepe Mancia

Parametrii ABPMParametrii ABPM

TA -24 h (h 7.00-7.00)TA diurna (h 7.00-22.00)TA nocturna (h 22.00-7.00)TA trezire (h 5.00-8.00)TA maxTA minTAMPPIDFCBP load Index hiperbarDS

COMPONENTA TONICA

TAS, TAD, TAM, BPload

COMPONENTA PULSATILA

PP

COMPONENTA FAZICA

ID, SD-TA 24h

FC -24 ore

ESH/ESC 2013

FORME CLINICE DE HTA (ABPM)FORME CLINICE DE HTA (ABPM)

• HTA de halat alb (WC-HT)

• HTA diurna

• HTA nocturna

• HTA sustinuta

• HTA episodica

• Masked hypertension

Traseu ABPM normalTraseu ABPM normal

HTA de halat alb (WC-HT)HTA de halat alb (WC-HT)

Andritoiu A. Hipertensiunea de halat alb-intre normal si patologic. Infomedica, 2001:10:12-16

PREVALENTA WC-HTPREVALENTA WC-HT

Bangash F- CJASN 2009;4:656-664

HTA diurnaHTA diurna

HTA episodicaHTA episodica

HTA sustinutaHTA sustinuta

HTA nocturnaHTA nocturna

HTA matinalaHTA matinala

Morning surgeMorning surge

Morning BP surgeMorning BP surge: TAS medie in timpul celor 2 ore dupa trezire-TAS medie din timpul de 1 ora ce include cea mai scazuta TAS din timpul somnului (Kario K 2003)

Cresterea TAS>50 mmHg si/sau TAD>20 mmHg in intervalul 6.00-10.00a.m. (Marfella R 2003)

HTA sistolica (izolata)HTA sistolica (izolata)

Masket hypertension Masket hypertension

PREVALENTA HTA MASCATA PREVALENTA HTA MASCATA

Bangash F - CJASN 2009;4:656-664

Masket HT-subtipuriMasket HT-subtipuri

• HTA matinala

• HTA diurna

• HTA nocturna

Kawano Y et al- Clin Exp Hypertens 2008;30(3):289-96

CaCaracteristicracteristicileile pts cu Masket HTpts cu Masket HT

• Varsta tanara• Sex M, • Stress cotidian• Fumatori • Consumatori de alcool (seara)• Obezitate centrala• HTA ocazionala• Prehipertensivi• Pacienti cu scor mare de risc CV• Semne de afectare organe tinta cu TA normala la

cabinet• Pacienti hipertensivi sub tratament

Poate precede HTA sustinutaPoate precede HTA sustinuta

Lot - 46 adulti cu HTA la cabinet

40%

25%

15%

20%

WCH episodica diurna sustinuta

Andritoiu A, 2000

HTA LA TINERIHTA LA TINERI

Andritoiu AAndritoiu A si colab. The significance of high blood pressure in cardiovascular pathology of young adults. The 4th Cong BMMC 1999, Bucuresti

Andritoiu AAndritoiu A. Monitorizarea ambulatorie a tensiunii arteriale-aplicabilitate diagnostica si prognostica. Rev Med Mil 1999;1107-126.

Importanta metodei in expertiza medico-militaraImportanta metodei in expertiza medico-militara

BP loadBP load

Definitie:

In 1988, the Mayo ClinicMayo Clinic suggested the use of a BP loadBP load,defined as the percentage of BP values exceeding a given constant threshold,usually 140/90mm Hg for systolic/diastolic BP during activity and   120/80mm Hg during resting hours.

The hyperbaric index (HBI),hyperbaric index (HBI), as a determinant of BP excess, can be calculated as the total area of any given patient’s BPabove the threshold. 

Stadializarea HTA dupa BP loadStadializarea HTA dupa BP load

BP LOAD (%) STADIU % BP LOAD (%) STADIU %

0 - 5 normal 15

5 - 15 borderline 35

15 - 25 usoara 20

25 - 75 moderata 25

75 -100 severa 5Andritoiu A. Semnificatia parametrului BP load in evaluarea severitatii hipertensiunii.

Al 38-lea Cong Nat Cardiol 1999, Sinaia

Stadializarea HTA dupa BP loadStadializarea HTA dupa BP load

BP load(%)BP load(%) GradGrad N=45N=45 %%

0-5 normal 10 22

6-15 borderline 12 27

16-25 usoara 5 11

26-75 moderata 10 22

76-100 severa 8 18

Andritoiu A, 2000

Valorile BP load fct tipul HTA (ABPM)Valorile BP load fct tipul HTA (ABPM)

WC-HTWC-HT 6.42+/-6.43

HTA episodicaHTA episodica 10.76+/-9.85

HTA diurnaHTA diurna 43.67+/-20.46

HTA sustinutaHTA sustinuta 77.64+/-22.79

Andritoiu A, 2000

N = 45 pacienti

Blood Pressure LoadBlood Pressure Load

2,1 +/- 3,3

27,2 +/- 25,8

0 5 10 15 20 25 30

n -TA

HTA

HTA

n -TA

Andritoiu A, 2000

Presiunea Pulsului (PP)Presiunea Pulsului (PP)

Definitie:

diferenta dintre presiunea sistolica si presiunea diastolica: forta generata de cord la fiecare contractie

TAS = 120 mmHg; TAD=80 mmHg; PP=40 mmHG

PP: predictor de evenimente CV mai bun decat TAS si/sau TAD izolate

Componenta fazica - pulsatila (PP)Componenta fazica - pulsatila (PP)

LOT I LOT II p< (hipertensivi) (normali)

PP - 24 h 50,7 +/- 6,3 50,8 +/- 4,7 NS

PP - day 51,5 +/- 6,4 51,1 +/- 5,3 NS

PP - night 45,1 +/- 9,6 48,9 +/- 4,0 NS

Andritoiu A, 2000

Creste semnificativ in HTA sistolica (ateromatoza Ao)

Variabilitatea TA in 24 hVariabilitatea TA in 24 h

• variabilitatea beat-to-beat

• variabilitatea measure-to-measure

Parametrul:

SD (TAS, TAD, TAM, PP)

Variabilitatea circadianaVariabilitatea circadiana

• Definitie (ID index diurn):

Dipper vs. non-Dipper

ESH/ESC 2013

Forme de dippingForme de dipping

Dipping absent

(HTA nocturna)

ratio>1.0

Dipping moderat 0.9<ratio<1.0

Dipping 0.8<ratio<0.9

Dipping extrem ratio<0.8

ESH/ESC 2013

Normotensiv-DipperNormotensiv-Dipper

Normotensiv non-DipperNormotensiv non-Dipper

Hermida et al. Chronobiol Int 2013

Non-DipperNon-Dipper

Non-DippingNon-Dipping

• Salt sensitive hypertension• HTA secundara• Disfunctie autonoma• Diabet zaharat• Sdr. de apnee in som• Sdr. Cushing• Feocromocitom• Hiperaldosteronismul primar• Virsta avansata (HT sistolica severa)• Etnicitate (rasa Afro-Americana)• Medicamente (ciclosporina, corticosteroizi)• Insuf. renala (dializati)• Insuf. cardiaca congestiva

LOT I LOT II p<

(hipertensivi) (normali)

ID - TAM 15,5 +/- 8,5 13,8 +/- 6,4 ns

DS .TAS-24h 15,4 +/- 3,8 11,3 +/- 2,8 0,05

Andritoiu A, 2000

VARIABILITATEAVARIABILITATEA CIRCADIANACIRCADIANA

RELATIA CU TOD

VALOAREA PROGNOSTICAVALOAREA PROGNOSTICA

Cresterea TAS-24h cu 1 mmHg este asociata unei cresteri a riscului de mortalitate cardiovasculara de 4.7% !

Studii:• Perloff et al.- JAMA 1983:249:2792-2798.• Perloff D, Sokolow M, Cowan R, Juster RP – J Hypertens 1989;7(suppl):S3-S10.• Perloff D Sokolow M – J Hypertens 1990 (suppl):S105-S111.• Perloff D, Sokolow M, Cowan R – J Hypertens 1991 ;9 (suppl):S33-S39.

,, Average ambulatory BP was better correlated than office BP with the degree of ,, Average ambulatory BP was better correlated than office BP with the degree of target-organ damage and the presence of cardiovascular complications”.target-organ damage and the presence of cardiovascular complications”.

,,The patients with a low ambulatory BP, in relation to the level to the level ,,The patients with a low ambulatory BP, in relation to the level to the level predicted from the office blood pressure, had a better prognostic, and were less predicted from the office blood pressure, had a better prognostic, and were less likely to develop clinical events over a 10-year period, than patients with higher likely to develop clinical events over a 10-year period, than patients with higher BP levels”BP levels”

VALOAREA PROGNOSTICA A DATELOR ABPM

Studiu pe 3 ani

899 pts cu HTA esentiala vs 176 normotensivi

WCH ……………0,45 evenimente / 100pts / an

HTA ……………2,59 evenimente / 100 pts / an

Normo-TA………0,56 evenimente / 100 pts / an

• Un traseu anormal de monitorizare TA ambulatorie a identificat 95% dintre subiectii care aveau sa sufere un eveniment cardiovascular in urmatorii 3,3 ani!

• Valoarea predictiva negativa a ABPM = 98% !

Verdecchia P. Al XII-lea Cong Cardiol;10-14 sept 1994, Berlin

Organele tinta in HTAOrganele tinta in HTA

HTA

Presiunile monitorizate pe 24h se coreleaza cu o varietate de leziuni de organ

• scorul global al afectarii organelor tintascorul global al afectarii organelor tinta• masa VS (gradul HVS)• afectarea functiei VS• nivelul microalbuminuriei• hipertrofia peretelui arterial• distensibilitatea arterelor elastice• deteriorarea creierului (dementa vasculara)• retinopatie

Evaluarea afectarii unor tinte in HTA (lot 800 pts)

78%

43%

22%

14%

FO I / I I Placa ASC HVS Mi Alb

Cuspidi C, 2001

AF. ORG. TINTA (TOD) AF. ORG. TINTA (TOD) (ABPM - 45 hipertensivi)(ABPM - 45 hipertensivi)

0

2

4

6

8

10

12

14

FO HVS E/A<1 CAR AB ALB

Andritoiu A, 2000

Ochiul in HTAOchiul in HTA

• Retina (exudate, hemoragii)• Artere/vene (Sallus)• Tromboza VCR• Ocluzia ACR

Ocluzia ACR

Relatia ABPM – FO la un lot de 45 pacienti cu HTA

Hipertensiune BP load Grad 0/I Grad II/III

WC-HT 6.42+/-6.43 12 0

Episodica 10.76+/-9.85 12 0

Diurna 43.67+/-20.46 2 4

Sustinuta 77.64+/-22.79 3 11

Andritoiu A, 2000

Relatia cu HVS (Eco)Relatia cu HVS (Eco)

TAS-24h si TAD 24h se coreleaza cu:

• SIV+PPVS• PPVS• SIV+PPVS/DTDVS• h/r (HVS concentrica)• Masa VS• AS – cu TAD-24h

Prisant LM, Carr AA. 1990

Corelatia dintre masa VS (Eco) si TAS-24h vs TAS determinata ocazional (cabinet)

Studiu n TAS -24h TAS-cab Rowlands 50 0,60 0,51

Devereux 100 0,50 0,24

Drayer 12 0,81 0,55

Kleinert 93 0,26 0,22

Prisant 55 0,50 0,33

Verdecchia 253 0,48 0,38

Principalii determinanti directi ai HVSPrincipalii determinanti directi ai HVS

• TA medie -24 h• TAS diurna• TAS la trezire• BP load• Var. presionala

• Stresul de forfecare • Stresul parietal• IMC• Virsta• Sexul• Aportul de sodiu in dieta• Factori genetici• Viscozitatea singelui• Rezistenta la insulina• Ingestia cronica de alcool• Factori neuro-hormonali (catecolamine, angiotensina, renina)

Stroke in HTAStroke in HTA

• DipperDipper• Non-DipperNon-Dipper• Dipper extremDipper extrem• Dipper inversatDipper inversat

Kario K et al. - Hypertension 2001

Arterele in HTAArterele in HTA

Ax carotidian Artera brahiala

Modificarile carotidiene in HTAModificarile carotidiene in HTA

• Cresterea diametruluiCresterea diametrului• Ingrosarea CIMTIngrosarea CIMT• Placi stenoticePlaci stenotice

Alterarea complianteiAlterarea compliantei

Imbatrinire accelerata a axului carotidian !

100 pts hipertensivi

•

GROUP I GROUP II GROUP III

R-CCA L-CCA R-CCA L-CCA R-CCA L-CCA

Dd 5,8+/-0.8 5,6+/-0.7 6,5+/-0.7 6.7+/-0,9 8,3+/-0.3 7.7+/-0,2

(mm)

IMTh 0,45+/-0,2 0,44+/-0,2 0,67+/-0,2 0,65+/-0,3 0,89+/-0,3 0,93+/-0.2

(mm)

% Plaques 28,5% 80%

% Segnif.stenosis 22 % 14%

Mean stenosis(%) 45+/-10,7 % 38+/-9,7%

Andritoiu Al. Modificari morfologice si functionale ale arterelor carotide comune in hipertensiune comparativ cu imbatrinirea-studiu Eco-Doppler. A II-a Conf Nat Ultrasonografie , Craiova, 1999.

GROUP II GROUP III

CCA-middle 3 5

CCA-bulb 4 10

ICA 5 11

ECA 2 6

TOTAL 12 32

Distributia topografia a placilor ATS-CAR

Andritoiu Al. Modificari morfologice si functionale ale arterelor carotide comune in hipertensiune

comparativ cu imbatrinirea-studiu Eco-Doppler. A II-a Conf Nat Ultrasonografie , Craiova, 1999.

Modificarile a. brahiale in HTAModificarile a. brahiale in HTA

• Cresterea in diametru/arie• Modificarea profilului spectral• Alterarea vasodilatatiei - dependenta de endoteliu (Ach) - independenta de endoteliu (NTG)

Se coreleaza cu parametrii ABPM-24h si la trezire !

Andritoiu A, 2000

Profil spectral – a. brahiala (largire spectrala)

Rinichiul in HTARinichiul in HTA

• Microalbuminurie (30-300 mg/24 h) • microalbuminurie de efort• proteinurievaloare predictiva poz. ptr evenimente CV subsecvente Metode de determinare RIA/nefelometrie laser Dipstick +2

CONSECINTE• Nefroangioscleroza• Insuficienta renala cr. Cr. ser > 1,5 mg/dl Cl. Cr < 60 ml/min

SCORUL AFECTARII ORGANELOR TINTASCORUL AFECTARII ORGANELOR TINTA

• Ex. FO: Std I ……………………………………. 1p. Std.II……………………………………. 2p. Std. III……………………………………3p.• Prezenta HVS…………………………………..3p.• Disfunctia VS diastolica (E/A <1) …………..2p.• Ecografia carotidiana: Diametrul >6.5 mm……………………….1p. CIMT > 1mm………………..…………….1p. Placi ……………………………………….2p.• A. Brahiala (largire spectrala)…………………1p.• Ex urina (albuminurie)………………………….2p. SCOR Max. = 15p.

Andritoiu A, 2000

TOD - SCOR MEDIUDIURNA vs SUSTINUTA vs WC-HT

0

1

2

3

4

5

6

DIURNA SUSTINUTA WCH

3.71p

6p

1.33p

Andritoiu A, 2000

CORELATII Scor TOD vs…

TASTAS R= 0.87

TADTAD R= 0.72

TAMTAM R= 0.80

SBP loadSBP load R= 0.74

DBP loadDBP load R= 0.61

FC R= 0.23

PARAMETRII MONITORIZARII TENSIONALE LA TREZIRE SI

AFECTAREA ORGANELOR TINTA IN HTA

Andritoiu A. Al 41 Cong Nat Cardiol 2002, Sinaia

Relatia scor-TOD si parametrii ABPM la trezire (lot 45 pacienti HT)

TASTAS R= 0.87

TADTAD R= 0.72

TAMTAM R= 0.80

SBP loadSBP load R= 0.74

DBP loadDBP load R= 0.61

FC FC R= 0.23

Andritoiu A, 2002

MONITORIZAREA TA IN SARCINA

Hypertension in pregnancy, as diagnosed by ABPM, is superior to the office measurement of BP in predicting outcomes

ABPM in sarcina

Recomandata deRecomandata de:

Soc. Elvetiana de Hipertensiune

Soc. Franceza de Hipertensiune

Nerecomandata deNerecomandata de:

Marea Britanie, SUA, Germania, Brazilia

Valorile normale (ABPM) in sarcina

Sapt. 9-17 18-22 26-30 >30

TA diurna 130/77 132/79 133/81 135/86

(Brown MA et colab. 1998)

Trim I Trim II Trim III

TA-24h 110/70 116/74 125/80

TA diurna 113/69 119/78 126/83

TA nocturna 100/71 113/73 111/78

(Gheorman V, Andritoiu A, Raca N 2002)

Profilul circadian al TAS, TAD, TAM, FC in sarcina

Hermida RC, Hypertension 2001;38:746

Valorile medii pe fiecare trimestru de sarcina

ParametruParametruABPMABPM TRIM ITRIM I TRIM IITRIM II TRIM IIITRIM III

TAS 24 h 99.5+/-5.5 104.1+/-6 108.7+/-8.2

TAD 24 h 66.3+/-2.2 67.8+/-3 70.3+/-5.3

TAM 24 ore 77.8+/-9.7 79.6+/-10.2 86.8+/-12.4

TAS diurna 101.3+/-5.8 106.3+/-6 111.7+/-7.2

TAD diurna 66.8+/-1.2 69.3+/-4 72+/-5.6

TAM diurna 79.6+/-5.6 82.6+/-6.6 88.4+/-6.7

TAS nocturna 95.3+/-2.3 99+/-6.8 100.5+/-5.5

TAD nocturna 62.8+/-3.9 65.3+/-4 66.7+/-5.4

TAM nocturna 76.8+/-5.2 77.3+/-4.5 79.2+/-5.6

Andritoiu A, Raca N, Gheorman V.- Metode noi in predictia preeclampsiei. Ed. Info, Craiova, 2007.

Limita cut-off

Parametru ABPM

TRIM I TRIM II TRIM III

TA – 24 h 110.5/70 116/74 125/80

TA diurna 113/69 119/78 126/83

TA nocturna 100/71 113/73 111/78

110.5116

125

70 7480

0

20

40

60

80

100

120

140

TRIM I TRIM II TRIM III

TAS TAD

Andritoiu A, 2006

PP – presiunea pulsuluiPP – presiunea pulsului(TAS-TAD)(TAS-TAD)

ParametruABPM

TRIM I TRIM II TRIM III

PP 24 ore 33.5+/-5.5 36.1+/-6 38.5+/-8.2

PP diurn 33.3+/-5.8 36.3+/-6 40.2+/-7.2

PP nocturn 33.3+/-2.3 34.2+/-6 33.5+/-5.533.5

36.1

38.5

30

32

34

36

38

40

42

TRIM. I TRIM. II TRIM. III

virsta sarcinii

PP

-24

ore

Andritoiu A, 2006

Sarcina de presiune(BP load)

ParametrulABPM

TRIM I TRIM II TRIM III

SBP load 3.2+/-0.05 6.2+/-0.05 7.5+/-0.02

DBP load 3.3+/-0.08 4.6.+/-0.06 5.5+/-0.03

Andritoiu A, 2006

Frequency distribution of maximum BP load from normotensive pregnant women (top) and women with a final diagnosis of gestational hypertension or preeclampsia (bottom)

sampled in different trimesters of pregnancy.

Hermida R C - Hypertension 2001;38:723-729

Parametrii ABPM Parametrii ABPM intervalul de trezire (h 5.00-8.00 am)

Parametru ABPM

TRIM I TRIM II TRIM III

TAS 103.5 +/-12.2 106.6+/-11.3 114.5+/-10.9

TAD 69+/- 11.3 72+/- 13.6 76+/-13.2

TAM 78.6 +/-3.2 83 +/-3.3 88 +/-3.6

FC 72.6+/-8.9 86.6+/-11.2 86.7+/-10.2

Andritoiu A, 2006

Relatia TA clinica -TA ambulatorie

Normal Probability Plot

0.1 1 5 20 50 80 95 99 99.9

percentage

96

116

136

156

176

196 VariablesTAS CAB

TAS DIURNA

Normal Probability Plot

0.1 1 5 20 50 80 95 99 99.9

percentage

64

74

84

94

104

114

124 VariablesTAD DIURNATAD CAB

Andritoiu A, 2006

TAS TAD

Subgrupuri de risc

• WC-HT

• HTG

• PE

• NORM13

35

8 9

0

5

10

15

20

25

30

35

40

NORM WCH HTG PE

Andritoiu A, 2006

Parametrii presionali

TA cabinet @n cele 4 subgrupe

0

20

40

60

80

100

120

140

160

180

NORM WCH HTG PE

subgrup

mm

Hg

TAS cab

TAD cab

TA - 24 ore @n cele 4 subgrupuri

0

20

40

60

80

100

120

140

160

NORM WCH HTG PE

subgrup

mm

Hg

TAS 24 ore

TAD 24 ore

Diferente semnificative statistic s-au observat intre subgrupul PE si subgrupurile NORM si WCH (p <0.001), cit si intre subgrupul PE si subgrupul HTG (p=0.01).

Andritoiu A, 2006

TAM-24 ore

TAM - 24 ore @n cele 4 subgrupuri

0

20

40

60

80

100

120

NORM WCH HTG PE

subgrup

mm

Hg

TAM -24 ore

Diferente s-au inregistrat intre subgrupul PE si subgrupurile NORM si WCH (p<0.001), inclusiv intre PE si HTG (p = 0.004).

Andritoiu A, 2006

TA diurn[ @n cele 4 subgrupuri

0

20

40

60

80

100

120

140

160

NORM WCH HTG PE

subgrup

mm

Hg

TAS diurna

TAD diurna

TA nocturn[ @n cele 4 subgrupuri

0

20

40

60

80

100

120

140

NORM WCH HTG PE

subgrup

mm

Hg

TAS nocturna

TAD nocturna

TA diurna si TA nocturna in cele 4 subgrupuri

Diferente statistice s-au remarcat intre subgrupul PE si NORM, WCH (p<0.001), inclusiv intre PE si HTG (p=0.01).

Diferente statistice s-au remarcat intre subgrupurile PE si NORM si WCH (p<0.001) cit si intre PE si HTG (p =0.01).

Andritoiu A, 2006

WC-HThipertensiunea de halat alb

Parametrii ABPMWCH vs NORM

020406080

100120140160180

TAS

CAB

TAD

CAB

TAS 24

H

TAD 24

H

TAM 24

H

TAS

DIURN

TAD

DIURN

TAS

NOCT

TAD

NOCT

mm

Hg

WCH NORM

AU ACM A OFT

WCH NORM WCH NORM WCH NORM

IP 0.78 0.76 0.88 0.87 1.15 1.18

IR 0.55 0.53 0.58 0.57 0.67 0.66

S/D 2.3 2.2 2.2 2.2 2.8 2.7

76

78

80

82

84

86

88

WCH NORM

bpm

FC - 24 oreWCH vs NORM

Andritoiu A, 2006

HTGhipertensiune gestationala

Parametrii ABPMHTG vs NORM

020406080

100120140160180

TAS

CAB

TAD

CAB

TAS 24

H

TAD 24

H

TAM 24

H

TAS

DIURN

TAD

DIURN

TAS

NOCT

TAD

NOCT

mm

Hg

HTG NORM

0102030405060708090

100

HTG NORM

bpm

FC - 24 oreHTG vs NORM

AU ACM A OFT

HTG NORM HTG NORM HTG NORM

IP 1.11 0.76 0.94 0.87 1.02 1.18

IR 0.63 0.53 0.59 0.57 0.65 0.66

S/D 2.6 2.2 2.4 2.2 2.9 2.7

Andritoiu A, 2006

PE - preeclampsie

Parametrii ABPMPE vs NORM

020406080

100120140160180

TAS

CAB

TAD

CAB

TAS 24

H

TAD 24

H

TAM 24

H

TAS

DIURN

TAD

DIURN

TAS

NOCT

TAD

NOCT

mm

Hg

PE NORM

Distribu\ia valorilor TA @n subgrupul PE

0

20

40

60

80

100

120

140

160

180

1 2 3 4 5 6 7 8 9

nr. paciente

mm

Hg

TAS 24 H

TAD 24 H

0102030405060708090

100

HTG NORM

bpm

FC - 24 orePE vs NORM

AU ACM A OFT

PE NORM PE NORM PE NORM

IP 1.74 0.76 0.83 0.87 1.01 1.18

IR 0.75 0.53 0.58 0.67 0.61 0.66

S/D 3.75 2.2 2.2 2.2 2.5 2.7

Andritoiu A, 2006

Andritoiu A, 2006

NORMNORM

Parametrii presionaliNORM vs REF

0

20

40

60

80

100

120

140

TASCAB

TADCAB

TAS24H

TAD24H

TAM24H

TASDIURN

TADDIURN

TASNOCT

TADNOCT

TAMNOCT

mm

Hg

NORM

REF

FC - 24 oreNORM vs REF

25

35

45

55

65

75

85

95

NORM REF

bp

m

AU ACM A OFT

REF NORM REF NORM REF NORM

IP 0.78 0.76 0.94 0.87 1.24 1.18

IR 0.55 0.53 0.59 0.57 0.72 0.66

S/D 2.3 2.2 2.5 2.2 2.9 2.7

Andritoiu A, 2006

Corelatiile stabilite intre parametrii determinati prin ABPM si PE

in grupul cu risc crescut

Parametru ABPM r = p<

TAS-24 ore 0.68 0.001

TAD-24 ore 0.72 0.001

TAM -24 ore 0.71 0.001

TAS diurna 0.69 0.001

TAD diurna 0.72 0.001

TAS nocturna 0.63 0.001

TAD nocturna 0.70 0.001

FC-24 ore -0.24 NS

Andritoiu A, 2006

TAM-24 ore >100 mmHg

Sb %Sb % 66.66

Sp %Sp % 89.28

VP(+) %VP(+) % 50

VP(-) %VP(-) % 94.33

AC %AC % 86

RRRR 10

Andritoiu A, 2006

PROFILUL CIRCADIAN AL HTA

Corelatia dintre profilul non-dipper si rata aparitiei PE r = 0.71; p<0.001

Sb%Sb% 55.55

Sp%Sp% 96.42

VP(+) %VP(+) % 71.42

VP(-) %VP(-) % 93.1

AC %AC % 90.77

RRRR 10.44

Andritoiu A, 2006

Scorul de risc preeclampticScorul de risc preeclamptic

VariabilaVariabila PunctajPunctaj

ClinicCel pu\in un factor derisc (diabet, primiparitate, varsta =>35 ani, antec. PE sau fat mort)

1 p.

TAD cabinet =>100 mmHg 1p

DopplerIR-a uterina >0.6 1p.

S/D a. uterina >2.4 1p.

Notch grad 1, 2, 3, 1p, 2p, 3p.

Notch bilateral x 2 p.

Notch absent 0p.

IR <0.5 aa. cerebrale materne 1 p.

ABPMTAM-24 ore >100 mmHg 1

TAD nocturna > 75 mmHg 1

Profil non-dipper 1

Scor maxim de risc 14

Andritoiu A, 2006

1.61 1.17

4.87

11.55

0

2

4

6

8

10

12

puncte

NORM WCH HTG PE

SCOR DE RISC PREECLAMPTIC

Plot of Fitted Model

PE = -0.0938699 + 0.0736661*SCOR

0 3 6 9 12 15SCOR

0

0.2

0.4

0.6

0.8

1

PE

Andritoiu A, 2006

CRONOFARMACOLOGIA HIPERTENSIUNII ARTERIALE

Ceasul biologic - master clockCeasul biologic - master clock

• Complex de gene• Arie speciala in

cortex• Nc. suprachiasmatic• Locus ceruleus

Rolul SN autonom - baroreflexe Melatonina-mesager endogen

The cardiovascular system is highly organised in time Lemmer B. - Pharmacol Ther 2006

• TA

• FC

• RVP

• DC

• Hh vasoactivi

CA, SRAA, Et-1, AMPc

DefinitiiDefinitii

• Chronobiologia –stiinta preocupata de mecanismele biologice ale bolilor in relatie cu o structura temporala;

• Chronoterapia (cronofarmacologia): disciplina ce studiaza efectul farmacologic al medicamentelor in relatie cu comportamnetul bolii pe o anume perioada de timp.

• Cronofarmacokinetica• Cronofarmacodinamia

Cronofarmacokinetica• Absorbtia• Distributia• Secretiile gastro-dd• Golirea gastrica • Metabolizarea• Eliminarea renala

Cronofarmacodinamie • Efecte diferite pe

intervalul 24 ore• Momentul

administrarii poate modifica rap. doza/concentratie

Cronotoxicitate

Cronoterapia Cronoterapia hipertensiunii arterialehipertensiunii arteriale

ConcepteConcepte

Homeostazic• Mediul intern ramine

constant Cronobiologic• Variatii (cicluri)

circadieneCum tratam ?

Cand tratam ?

Obiectivele cronoterapiei in HTAObiectivele cronoterapiei in HTA

concentratii mai mari atunci cind este mai multa nevoie (e.x: perioada post-trezire) si mai mici cind nevoile sunt mai reduse (e.g., in intervalul de somn nocturn)

• Normalizarea valorilor TA pe intreg intervalul circadian• Reducerea riscului cardio-vascular• Imbunatatirea/normalizarea profilului circadian al TA (dipper)

Morning versus evening dosing of a once-daily agent !

StudiiStudii

ACE inhibitors• quinapril, enalapril, benazepril, perindopril

BRA• valsartan

Beta-blockers • Atenolol, propranolol MR

Calcium channel blockers • nifedipine-GITS • amlodipine• isradipine• nitrendipine• ditizem• verapamil COER

Morning vs evening dosing

Depinde de formularea farmaceuticaInstant vs ER

• circadian patterns were generally unchanged when comparing morning vs evening administration of a variety of antihypertensive agents

• nocturnal medication dosing generally reduced asleep BP more than morning dosing

Lemmer B. Blood Press Monit 1999;1:161-169.

The impact of dosing time on the response to

antihypertensive therapy

Morning vs Evening dosingMorning vs Evening dosing

Control TA diurn vs. nocturnControl TA diurn vs. nocturn

Prestance (5/5)Prestance (5/5) Non-control

Non-control TA nocturnaNon-control TA nocturna

IECA Non-control

Ce ne rezerva viitorul ....

trialuri clinice comparative ptr. a evalua efectele antihipertensivelor homeostatice vs cronoterapeutice pe end-pointurile clinice ( imbunatatirea controlului TA, QOL, ischemiei miocardice si performantelor miocardice)

PresedintePresedinteConf. Horia Balan

ABPM ACCURACY (1381 readings)

83%

17%

Andritoiu A , 2003

Studii personale

1. Andritoiu A si colab. Monitorizarea automata pe 24 h a tensiunii arteriale. Studiu pe 20 pacienti tineri hipertensivi comparativ cu normalul. Al 37 Cong Nat Cardiol, 1998, Sinaia

2. Andritoiu A si colab. Parametrii de presiune arteriala evaluati prin computerizare automata 24h la un grup de pacienti cu hipertensiune arteriala. Al 37-lea Cong Nat Cardiol 1998, Sinaia

3. Andritoiu A si colab. Monitorizarea automata 24h a tensiunii arteriale (ABPM). A 3-a Conf Nat Semiol Med 1998, Craiova

4. Andritoiu A. Semnificatia diagnostica si prognostica a monitorizarii ambulatorii a tensiunii arteriale. Infomedica 1999;8:2-9.

5. Andritoiu A. Semnificatia parametrului BP load in evaluarea severitatii hipertensiunii. Al 38-lea Cong Nat Cardiol 1999, Sinaia

6. Andritoiu A si colab. The significance of high blood pressure in cardiovascular pathology of young adults. The 4th Cong BMMC 1999, Bucuresti

7. Andritoiu A. Monitorizarea ambulatorie a tensiunii arteriale-aplicabilitate diagnostica si prognostica. Rev Med Mil 1999;1107-126.

8. Andritoiu A. Hipertensiunea de halat alb - intre normal si patologic. Infomedica 2001;10:12-16.

9. Andritoiu A. Complianta terapeutica in managementul hipertensiunii arteriale. Rev Med Mil 2001;2:195-206.

10. Andritoiu A. Parametrii monitorizarii tensionale la trezire si afectarea organelor tinta in HTA. Al 41-lea Cong Nat Cardiol 2002, Sinaia

11. Andritoiu A. Monitorizarea ambulatorie a TA – relatia cu afectarea organelor tinta in HTA. Al 41-lea Cong Nat Cardiol 2002, Sinaia

12. Raca N, Gheorman V, Andritoiu A. Parametrii ABPM in sarcina normala. Al 2-lea Cong Nat Obst-Ginecologie, 2002, Bucuresti

2004