Arterial Stiffness: pathophysiology and clinical impact. Gérard M. LONDON Manhès Hospital Fleury-Mérogis/Paris, France

Transcription

1 Arterial Stiffness: pathophysiology and clinical impact Gérard M. LONDON Manhès Hospital Fleury-Mérogis/Paris, France

2 Determinants of vascular overload (afterload) on the heart Peripheral Resistance Arterial Stiffness Wave reflection Inertance

3 Arterial Impedance as a determinant of afterloadgradients Zc P f Z P R P t b PWV= Zc Aorta Z R Resistance vessels STIFFNESS RESISTANCE REFLECTION Reflection Coefficient = Zr -Zc- Zr - Zc + Zc-characteristic impedance Zr-peripheral resistance

4 mm Hg 140 Systolic pressure Mean BP Pulse pressure 80 Mean BP: Cardiac output peripheral resistance Diastolic pressure Pulse pressure: ventricular ejection arterial stiffness wave reflection

5 Pressure Flow-Pressure relationship - influence of the fraquency (Resistance = slope of the relationship) Steady -mean flow Pulsatile flow 1 Hz Pulsatile flow 2 Hz Pulsatile flow 3 Hz Flow R=8. L/r 4 (-viscosity; L length; r= radius - number of vessels) R= Mean Blood Pressure/Cardiac output

6 Flow (ml/min) Pressure-flow relationship - influence of the fraquency (Resistance = slope of the relationship) Ringer Blood Blood + Noradrenaline Autogegulation Perfusion pressure (mm Hg)

7 VOLUME Diagrammatic representation of volume-pressure relationship P V Transition zone V/P=Compliance P/V=Elastance (Stiffness) PRESSURE

8 Volume Pressure Diagrammatic representation of volume-pressure relationship V/P=Compliance P/V=Elastance (Stiffness) P P V Transition zone V P V Pressure Volume

9 The arterial wall is a heterogeneous material Distensible balloon (rubber=elastin) Rigid/stiff net (steel=collagen) A.Tedgui and B. Levy, 1994

10 The arterial wall is a heterogeneous material A.Tedgui and B. Levy, 1994

11 Pressure Diagrammatic representation of pressure-volume relationships Einc=2 Einc=1 dp/dv Volume

12 Blood pressure Blood pressure Arterial function and blood pressure Pure Conduit Function Conduit and Cushioning Function Mean pressure Mean pressure Systole Diastole Systole Diastole

13 Blood pressure Relationship of Resistance (R) and Compliance (C) with diastolic pressure decay 140 = R.C =1/ = 1/R.C * log scale -time constant of diastolic decay 80 -slope of diastolic decay Adapted from Simon et al. Am J Physiol 1979 Blood pressure * Time (sec)

14 The diameter-pressure curve 7.3 diameter (mm) Diameter (mm) 7.30 Local pressure Time (sec) High-definition echotracking devices Wall Track system NIUS system Time (sec) Aplanation Tonometry Millar Instruments

15 Arterial Diameter (mm) Pressure-diameter relationship : a thermodynamic analysis 2.8 Viscosity = Dissipated energy Distensibility = Exchanged energy Arterial Pressure (mm Hg)

16 Pressure/arterial luminal cross-sectional area and hysteresis loop in vivo before and after desendothelisation Desendothelisation Intact endothekium Boutouyrie P et al. Arterioscler Thromb Vasc Biol 1997;17:

17 Carotid-femoral pulse wave velocity PWV=L/t t L PWV²=Einc*IMTh/D

18 Aortic PWV (cm/s) Correlation between common carotid artery (CCA) distensibility and aortic pulse wave velocity (PWV)in human population r= p< CCA distensibility (kpa )

19 W W Nichols & M O Rourke, Mc Donald s blood flow in

20 Pressure wave analysis measured pressure wave forward/incident pressure wave reflected pressure wave pulse wave velocity

21 Effect of arterial stiffness on timing of forward and reflected Waves PWV 8 m/sec PWV 12 m/sec Negative Aix Positive Aix Systolic Augmentation Pressure (Aix). T T Forward-traveling wave Backward-traveling reflected wave Actual (composite) wave T - traveling time of pressure wave to reflecting sites and back

22 Aortic versus Peripheral pulse pressure Aorta amplification Peripheral Artery Energy dissipation. T Forward-traveling wave Backward-traveling reflected wave Actual (composite) wave T - traveling time of pressure wave to reflecting sites and back

23 (mm Hg) (mm Hg) (mm Hg) Pressure Waves Recorded Along the Arterial Tree Maximum Early Wave Reflection Age 68 years Age 54 years Maximum Amplification Renal artery Age 24 years Femoral artery Thoracic aorta Abdominal aorta Iliac artery Ascending aorta Nichols WW, et al. Arterial Vasodilation. Philadelphia,1993;32.

24 Aortic (carotid) pressure waveforme P= augmented pressure P PP=pulse pressure Augmentation index=p/ PP Tsh= time to shoulder LVET=left ventricular ejection time PP Tsh. Tsh LVET Forward- wave Reflected wave Actual wave

25 Time to shoulder (TSh ms) Relationship between the time of appearance of reflected wave on the pressure wave in central artery (time to shoulder - TSh) and aortic pulse wave velocity (PWV) R= p< aortic PWV (cm/s)

26 Time to shoulder (TSh ms) Relationship between the time of appearance of reflected wave on the pressure wave in central artery (time to shoulder - TSh) and body height R=0.585 p< Body height (cm)

27 Arterial Impedance Gradients Zc-characteristic impedance; Zr-peripheral resistance Reflection Coefficient ( ) = Z Z R R - Z + Z C C = P P b f Zc P b P f Z R P t PWV=6 m/s PWV=10 m/s Pb P f P t PWV=12 m/s PWV=11 m/s Aorta Muscular arteries Resistance vessels

28 Fourier series - the mean terma and first 6 harmonics of a presure wave from ascending aorta (Westerhof et al 1979) Pressure = 0+P1+P2+P3 = a1 cos(t+1) + a2 cos(t+2)+ a3 cos(t+3)...

29 Pressure and flow waves broken down into mean term and Fourier series Modulus is the amplitude of pressure harmonic divided by the amplitude of corresponding flow harmonic, and phase as the delay between corresponding harmonics

30 Modulus and phase of impedance in the ascending aorta McDonald blood flow in the arteries 1994

31 Schematic representation of vascular impedance (Modulus= Pressure/flow) Peripheral resistance (Zr) Modulus (dynes sec cm-5) First minimum of impedance modulus - f min (lowest pressure for a given flow) Characteristic impedance Zc (Heart rate) Frequency (Hertz)

32 Pressure and flow waves along the tubular model completely occluded. At the closed end the pressure is maximal and flow zero. The best coupling minimal pressure for maximal flow is at 1/4 of the wavelength ( =PWV/frequency ) equal to the distance L to site of reflection Flow Pressure L=/4 Best coupling L=/4=PWV/4f fmin=1/2 tp T L = PWV* tp/2 Exemple: tp = 0.125s, 2 tp=0.25s, fmin=1/0.25=4hz

33 First minimum of impedance (Hz) Relationship between the first minimum of impedance modulus and body height r= P< Body height (cm) London GM personal data

34 First minimum of impedance (Hz) Relationship between the first minimum of impedance modulus and aortic PWV r=0.495 P< London GM personal data Aortic PWV (cm/s)

35 Schematic representation of vascular impedance (Modulus= Pressure/flow) 2000 Zr=Zr Control ESRD Modulus (dynes sec cm-5) f min f min Zc Zc (Heart rate) Frequency (Hertz)

36 Representation of the impedance modulus and amplitude (power) of flow harmonics Modulus (dynes sec cm-5) First minimum of impedance modulus Flow (ml/m) for different frequencies Cycles (multiples of 1st in Hertz) (1st = Heart rate)

37 Impedance modulus and flow harmonics during exercise (shift of flow harmonics with increased heart frequency) Modulus (dynes sec cm-5) Flow (ml/m) 0 (Heart rate) Cycles (Hertz)

38 Heart rate (3.3Hz) 1st minimum of impedance is close to heart rate (i.e. frequency of the highest flow harmonic for lowest pressure harmonic) Heart rate 60 (1Hz) heart rate is far from 1st min. of impedance (flow develops a high pressure)

39 First minimum of impedance (Hz) Relationship between the first minimum of impedance modulus and heart period R= p= Hz London GM personal data Hz Hz Hz Heart Period (ms) Hz

40 Fmin/Heart frequency (ratio) Relationship between the ratio of the first minimum of impedance modulus and heart period and body height (better coupling between heart rate and arterial properties in tall subjects R= P< London GM personal data Body Height (cm)

41 LV velocity of fiber shortening (c/s) Correlation between Fmin/heart frequency and Left Ventricular velocity of fiber shortening r= P< London GM personal data Fmin/heart frequency (ratio)

42 Reflected Wave SPTI DPTI SPTI DPTI

43 CBF (ml/min) BP (mmhg) Superimposed simultaneous phasic recording of aortic (Ao), left ventricular (LV) pressures and coronary blood flow (CBF) (Buckeberg et al. Circ Res. 1972) 100 Ao Ao DPTI DPTI 0 STTI LV STTI LA or PA Wedge 100

44 LV endo:epi flow ratio DPTI/SPTI plotted against Left Ventricular flow distribution between endocardium and epicardium DPTI/SPTI Adapted from Buckberg et al 1972

45 Correlation between left ventricular mass and aortic pulse wave velocity 200 Left ventricular mass (g/m 2 ) r = 0.52 p < London et al KI Aortic pulse wave velocity (cm/sec)

46 Survival Aortic stiffness and all-cause mortality in general population (Laurent et al Hypertension 2001) Kaplan-Meier P< Low PWV tertile 0.90 Medium PWV tertile 0.80 High PWV tertile Follow-up (years)

47 Cardiovascumar survival Wave reflection (Aix) and cardiovascular survival Log rank test for cardiovascular mortality. Chi square =23.11 ; P< AIX : 1 st quartile 0.75 AIX : 2 nd quartile AIX : 3 rd quartile 0.50 AIX : 4 th quartile Duration of follow-up (months) London et al Hypertension 2001

48 Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by Age ISH (SBP ³140 mm Hg and DBP <90 mm Hg) SDH (SBP ³140 mm Hg and DBP ³90 mm Hg) IDH (SBP <140 mm Hg and DBP ³90 mm Hg) % 16% 16% 20% 20% 11% Frequency of hypertension subtypes in all untreated hypertensives (%) < Age (y) Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37:

49 Evolution of Untreated Systolic and Diastolic BP: The Framingham Heart Study n= <120 Adapted from Franklin et al. Circulation 1997;96:308.

50 2-year risk of endpoint Cardiovascular Risk Associated with Increasing SBP at Fixed Values of DBP EWPHE (n = 840) SYST-EUR (n = 4695) SYST-CHINA (n = 2394) DBP (mm Hg) SBP (mm Hg) Two-year risk adjusted for active treatment, sex, age, previous CV complications, and smoking by multiple Cox regression. Staessen, et al. Lancet. 2000;355:

51 Pulse Pressure (mm Hg) Pulse Pressure (mm Hg) Pulse Pressure (mm Hg) Correlation between arterial pulse pressure, wave reflexion (Augmentation index) aortic pulse wave velocity and stroke volume (n=230) R=0.47 p< R=0.60 p< Augmentation Index (%) Aortic pulse wave velocity (cm/s) 132 R=0.15 p= dapted from London et al KI stroke volume (ml)

52 Pulse wave analysis:

53 Definition of waveform landmarks, AI, and characteristic impedance Mitchell, G. F. et al. Hypertension 2001;38:

54 Arterial Pressure Waves Recorded in Young Subjects Normotensiv e Subjects Pseudo- Hypertensio n Essential Hypertensio n Mahmud A, Feely J. American J Hypertens 2003;16:

55 M O Rourke, Eur Heart J, 1990

56 BRACHIAL BLOOD PRESSURES at 1 year p<0.001 NS p=0.019 p<0.001 SBP DBP MBP PP Per/Ind (n=204) atenolol (n=202) Asmar R, London G, O Rourke M et al. Hypertension 2001;38 : 922-7

57 AORTIC SBP ( At 1 year) 0-4 p< p< SBP (mmhg) p<0.001 Per/Ind (n=65) Aténolol (n=65) Asmar R, London G, O Rourke M et al. Hypertension 2001;38 : 922-7

58 AORTIC PP (At 1 year) p<0.001* PP (mmhg) NS p<0.001 Per/Ind Aténolol (n=65) (n=65) Asmar R, London G, O Rourke M et al. Hypertension 2001;38 : 922-7

59 PWV (carotido-femoral) PWV (m/s) 0-0,5 p<0.001 p< ,5-2 Per/Ind NS* atenolol Asmar R, London G, O Rourke M et al. Hypertension 2001;38 : 922-7

60 AUGMENTATION INDEX (aortic) p<0.001* AIX (%) NS -3-4 p=0.002 Per/Ind atenolol * Asmar R, London G, O Rourke M et al. Hypertension 2001;38 : 922-7

61 LEFT VENTRICULAR HYPERTROPHY LVH (g/m2) 0 p= Per/Ind p<0.001 Aténolol p=0.012 Asmar R, London G, O Rourke M et al. Hypertension 2001;38 : 922-7

62 Arterial Impedance Gradients Zc-characteristic impedance; Zr-peripheral resistance ( ) ReflectionCoefficient = Zr -Zc - Zr - + Zc Zc P b P f Z R P t PWV=6 m/s PWV=10 m/s Pb P f P t PWV=12 m/s PWV=11 m/s Aorta Muscular arteries Resistance vessels