Κεντρικές ή περιφερικές πιέσεις;
ΧαράλαµποςΧαράλαµπος ΒλαχόπουλοςΒλαχόπουλοςΕπίκουροςΕπίκουρος ΚαθηγητήςΚαθηγητής ΚαρδιολογίαςΚαρδιολογίας
ΑΑ’’ ΠανεπιστηµιακήΠανεπιστηµιακή ΚαρδιολογικήΚαρδιολογική
ΚλινικήΚλινική
IIπποκράτειοπποκράτειο ΓΓ..ΝΝ..ΑΑ..
ΔομικοίΔομικοίΔομικοίΔομικοίΔομικοίΔομικοίΔομικοίΔομικοίΛειτουργικοίΛειτουργικοίΛειτουργικοίΛειτουργικοίΛειτουργικοίΛειτουργικοίΛειτουργικοίΛειτουργικοί
Καρωτιδική βλάβη
Σφυροβραχιόνιος
δείκτης
Αρτηριακή
σκληρία
Ανακλώµενα
σφυγµικά
κύµατα – κεντρικές πιέσεις
Ενδοθηλιακή
δυσλειτουργία
Αρτηριακοί βιοδείκτες
Αµφιβληστροειδοπάθεια
Biomarker overload
Criteria of a BiomarkerCriteria of a Biomarker
A theoretical basis
High reproducibility
Ease of use
Incremental value
Ability to monitor and guide therapy
R Vasan 2006
Criteria of a BiomarkerCriteria of a Biomarker
A theoretical basis
High reproducibility
Ease of use
Incremental value
Ability to monitor and guide therapy
R Vasan 2006
• διαστολικής πιέσεως
• στεφανιαίας πίεσης
άρδευσης
• µεταφόρτιου ΑΚ
•συστολικού έργου της AK
•MVΟ2
στεφανιαίας πίεσης άρδευσης
Αρτηριακή σκληρία και ανακλώµενα κύµατα
Αρτηρίες διατάσιµες: φυσιολογικό PWV
Αρτηρίες µε αυξηµένη σκληρία: αυξηµένο PWV
Peripheral and central pressures
Are they the same?
ΤΤhe two Fridas, he two Fridas, 19391939
� amplification
CBPs: theoretical basisCBPs: theoretical basis
� peripheral BP may overestimate central SP and PP, especially in young subjects
CBPs: theoretical basisCBPs: theoretical basis
July 2007
Criteria of a BiomarkerCriteria of a Biomarker
A theoretical basis
High reproducibility
Ease of use
Incremental value
Ability to monitor and guide therapy
R Vasan 2006
Arterial TonometryArterial Tonometry ::
an an Avatar Avatar for central pressuresfor central pressures
Arterial TonometryArterial Tonometry ::
an an Avatar Avatar for central pressuresfor central pressures
CBPs: Reproducibility/RepeatabilityCBPs: Reproducibility/Repeatability
First author Year, country Population Variables - repro ducibility
Wilkinson 1998, UK Healthy, hypertensives,
diabetics
Aortic AIx: intraobserver difference 0.49±5.37%interobserver difference 0.23±3.80%
Liang 1998, Australia Healthy Carotid AIx: coefficient of variation 1.3%
Siebenhoffer 1999, UK Healthy Derived aortic SBP: interobserver difference 0.1±1.7 mmHg Derived aortic DBP: interobserver difference 0.1±0.7 mmHg Aortic AIx: interobserver difference 0.4±6.4%
Filipovsky 2000, Czech Republic
Healthy Aortic AIx: intraobserver variability 7.7% Aortic SBP: intraobserver variability 6.3%
Savage 2002, UK Chronic renal failure
Aortic AIx: intraobserver difference 0±4% interobserver difference 0±3%
Aortic MAP: intraobserver difference 0±3 mmHg interobserver difference 1±9 mmHg
Matsui 2004, Japan Hypertensives Carotid AIx: intraobserver difference 0.5±5.9%
Papaioannou 2004, Greece Cardiogenic shock
Aortic AIx: intraobserver difference 0.10±5.82%
Williams (CAFÉ)
2006, UK-Sweden
Hypertensives Aortic SBP: interobserver difference 0.3±2.9 mmHgAortic AIx: interobserver difference 1.5±5.9%
Roman (Strong Hear
Study)
2007, USA High-risk subjects
Carotid SBP: interobserver CC: 0.99intraobserver CC: 0.99
Carotid DBP: interobserver CC: 0.99 intraobserver CC: 0.99
CBPs: Accuracy/ValidityCBPs: Accuracy/Validity
First author Year, country Population Variables - repro ducibility
Pauca (radial) 2001, Australia Cardiac surgery (mostly CABG)
Resting conditions: SBP 0.0±4.4 mmHg; DBP 0.6±1.7 mmHg; PP-0.7±4.2 mmHg; MAP -0.5±2.0 mmHgNitroglycerin infusion: SBP -0.2±4.3 mmHg; DBP 0.6±1.7 mmHg; PP -0.8±4.1 mmHg; MAP -0.4±1.8 mmHg.
Van Bortel (carotid)
2001, Belgium, Netherlands
Coronary angiography
PP -10.2±14.3 mmHg
Smulyan(radial)
2003, USA-France
Coronary angiography
SBP 1.5±11.3 mmHg; DBP -10.4±12.7 mmHg; PP 11.5±13.6 mmHg
Hope (radial) 2004, Australia Cardiac catheterization
SBP (invasive calibration) -1±8 mmHgSBP (non-invasive calibration) 7±12 mmHg
Sharman (radial)
2006, Australia Coronary angiography
Rest SBP -1.3±3.2 mmHgExercise SBP -4.7±3.3 mmHg
Criteria of a BiomarkerCriteria of a Biomarker
A theoretical basis
High reproducibility
Ease of use
Incremental value
Ability to monitor and guide therapy
R Vasan 2006
CBPs/indices as markers of disease and predictors of CBPs/indices as markers of disease and predictors of surrogate endsurrogate end--pointspoints
Cross-sectional and longitudinal studiesFirst author Year, country Population Design Parameter End-point
Saba*† 1993, USA Normotensives Cross-sectional Carotid AIx LVMI, carotid thickness
Boutouyrie*† 1999, France Hypertensives Cross-sectional Carotid PP Carotid thickness
Boutouyrie*† 2000, France Hypertensives Longitudinal (9-month FU)
Carotid PP Carotid IMT reduction with treatment
Roman 2000, USA Normotensives, Hypertensives
Cross-sectional Carotid systolic BP Relative LV wall thickness
Waddell*† 2001, Australia CAD Cross-sectional Carotid BP Extent of CAD
Nishijima* 2001, Japan Suspected CAD Cross-sectional Aortic fractional PP Incident CAD
Nurnberger 2002, Germany Healthy + CVD Cross-sectional Carotid AIx CV risk scores
Philippe* 2002, France CAD Cross-sectional Aortic PP Extent of CAD
Hayashi* 2002, Japan Suspected CAD Cross-sectional Aortic AIx Incident CAD
De Luca † 2004, REASON study Hypertensives Longitudinal (1-year FU) Carotid PP LVMI reduction
Weber 2004, Austria Suspected CAD Cross-sectional Aortic AP, AIx Incident CAD
Jankowski* 2004, Poland CAD Cross-sectional Aortic BP Extent of CAD
Danchin* 2004, France Suspected CAD Cross-sectional Aortic PP Incidence and extent of CAD
Booth 2004, UK Systemic vasculitis
Cross-sectional Aortic AIx Disease activity
Roman 2007, USA High-risk pts Cross-sectional Aortic PP Carotid IMT and mass
Hashimoto † 2007, Japan Hypertensives Longitudinal (1-year FU) Aortic AIx LVMI reduction with treatment
Dart 2007, Australia Eledrly hypertensives
Longitudinal (4-year FU) Carotid/Brachial BP BP with treatment
Jiang 2007, China Hypertensives Longitudinal (2-mo FU) Central SP BP with treatment
* Measured invasively Incremental value
CBPs/indices as a predictors of eventsCBPs/indices as a predictors of events
* Measured invasively
Longitudinal studies
Incremental value
First author Year, country
Population Design Parameter End-point
Nakayama * 2000, Japan CAD-PTCA Longitudinal (3-month FU) Aortic fractional PP restenosis
Lu * 2001, China CAD-PTCA Longitudinal (6-month FU) Aortic PP restenosis
London † 2001, France
ESRD Longitudinal (52-month FU) Carotid AIx CV mortality
Safar † 2002, France
ESRD Longitudinal (52-month FU) Carotid PP, PP amplification
All-cause and CV mortality
Ueda* 2004, Japan CAD-PTCA Longitudinal (6-month FU) Aortic AIx restenosis
Chirinos *† 2005, USA CAD Longitudinal (3.2-year FU) Aortic AP CV mortality and events
Weber † 2005, Austria
CAD-PTCA Longitudinal (2-year FU) Aortic AIx CV mortality and events
Dart 2006, Australia
Elderly female hypertensives
Longitudinal (4.1-year FU) Carotid AIx, Brachial BP CV mortality and events
Williams † 2006 CAFE study
Hypertensives Longitudinal (up to 4-year FU) Aortic PP CV mortality and events during
treatment
Roman † 2005 and 2007, USA
High-risk pts Longitudinal (4.8-year FU) Aortic PP CV mortality and events
Negative value
Central Hemodynamics
† equal contribution
Vlachopoulos C / Aznaouridis K, et al. Eur Heart J 2010
5,648 pts / mean FU 45 months
For 10% increase in AIx increase in RR: 32% and 38% respectively
Central Hemodynamics
Central vs. Peripheral Pressures
Central Hemodynamics
Vlachopoulos C / Aznaouridis K, et al. Eur Heart J 2010
Reference values
Reference Values for Central Pressures Collaboratio n Project
UNDER CONSTRUCTION
Criteria of a BiomarkerCriteria of a Biomarker
A theoretical basis
High reproducibility
Ease of use
Incremental value
Ability to monitor and guide therapy
R Vasan 2006
Vlachopoulos C et al. Am J Hypertens 2005
no consumption
low consumption
high consumption
no consumption
low consumption
high consumption
no consumption
low consumption
high consumption
Vlachopoulos C, et al. Am J Cardiol 2007
Dark Chocolate and Arterial StiffnessDark Chocolate and Arterial Stiffness
ARTERIAL STIFFNESS AND
PSYCHOLOGICAL FACTORS
∆ράµα
0 min 15 min 30 minBaseline
0.4
0
0.2
dPWV
2009
2009
0 min 15 min 30 minBaseline
-0.4
0
-0.2
dPWV
ARTERIAL STIFFNESS AND
PSYCHOLOGICAL FACTORS
Pharmacological Interventions
Protogerou et al. Curr Pharm Des 2009
Lowering central pressures:not all drugs are created equal
Boutouyrie et al, Hypertension 2010
The EXPLOR study
Amlodipine+valsartan
Amlodipine+atenolol
Lowering central pressures:not all drugs are created equal
The J-CORE study
ASCOT endpointsASCOT endpoints
The area of the yellow square is proportional to the amount of statistical information
Amlodipine ± perindopril better Atenolol ± thiazide better0.50 0.70 1.00 1.45
PrimaryPrimaryNon-fatal MI (incl silent) + fatal CHD
SecondaryNon-fatal MI (exc. Silent) +fatal CHDTotal coronary end pointTotal CV event and proceduresAll-cause mortalityCardiovascular mortalityFatal and non-fatal strokeFatal and non-fatal heart failure
TertiarySilent MIUnstable anginaChronic stable anginaPeripheral arterial diseaseLife-threatening arrhythmiasNew-onset diabetes mellitusNew-onset renal impairment
Post hocPrimary end point+coronary revasc procsCV death + MI + stroke
2.00
ΣΚ (95% CI)0.90 (0.79-1.02)
0.87 (0.76-1.00)0.87 (0.79-0.96)0.84 (0.78-0.90)0.89 (0.81-0.99)0.76 (0.65-0.90)0.77 (0.66-0.89)0.84 (0.66-1.05)
1.27 (0.80-2.00)0.68 (0.51-0.92)0.98 (0.81-1.19)0.65 (0.52-0.81)1.07 (0.62-1.85)0.70 (0.63-.078)0.85 (0.75-0.97)
0.86 (0.77-0.96)0.84 (0.76-0.92)
CAFÉ Study
CBPs: Ability to monitor and guide therapyCBPs: Ability to monitor and guide therapy
Williams B, et al. Circulation 2006
CBPs, therapy and CBPs, therapy and prognosisprognosis
CAFÉ Study
Peripheral
Central
Williams B, et al. Circulation 2006
Amlodipine ± perindopril
Atenolol ± thiazide
CBPs: Where do we stand today?CBPs: Where do we stand today?
“ Though a wider use of PWV and AIx measurements may add further precision to the assessment of arterial damage, the availability of these techniques is largely limited to research centres.”
CBPs: Where do we stand today?CBPs: Where do we stand today?
July 2007
Robert Doisneau, Paris 1948Robert Doisneau, Paris 1948
Biomarkers: Biomarkers: Seeing what is importantSeeing what is important