ABPM-AMBULATORY BP MONITORING
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Transcript of ABPM-AMBULATORY BP MONITORING
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