Arterial Pressure in CKD5 - ESRD Population Gérard M. London

Transcription

1 Arterial Pressure in CKD5 - ESRD Population Gérard M. London INSERM U970 Paris

2 150 SBP & DBP by Age, Ethnicity &Gender (US Population Age 18 Years, NHANES III) 150 SBP (mm Hg) Non-Hispanic Black Non-Hispanic White Mexican American SBP (mm Hg) DBP (mm Hg) 70 DBP (mm Hg) SBP (mm Hg) 130 SBP (mm Hg) Pulse pressure 110 Pulse pressure DBP (mm Hg) 70 DBP (mm Hg) 70 Burt VI, et al. Hypertension. 1995;25: Men, Age (y) Women, Age (y)

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

4 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) 100 } Diastolic Hypertension 17% 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:

5 Difference Between SBP and DBP in CHD Prediction, as a Function of Age* 1.0 *Ages 20 to 79 Adjusted for age, sex, & other risk factors + β(sbp) - β(dbp) β(sbp) - β(dbp) = * age (P=0.008) Favor SBP Favor DBP Age (years) Franklin et al. Circulation 2001;103:

6 Hypertension Control by Age Group % Controlled Age <=60 (n=295) Age (n=533) Age >75 (n=361) 20 0 DBP Goal SBP Goal Cross-sectional analysis among 1189 treated hypertensive subjects from Framingham Lloyd-Jones Hypertension 2000;36:594

7 Steep Rise in Pulse Pressure With Increasing Age Data From the Framingham Study Pulse Pressure (mm Hg) Group Data Pulse Pressure (mm Hg) Individual Data <120 Age (y) Age (y) Franklin SS et al. Circulation 1997;96: n=2036

8 Relationship of SBP and DBP to risk for CHD in a dual component model: The Framingham Heart Study CHD hazard ratio SBP 150 mm Hg (P = 0.02) SBP 130 mm Hg (P = 0.06) SBP 110 mm Hg (P = 0.03) Adjusted for age, sex, and other risk factors P = probability for β coefficients DBP (mm Hg) Franklin SS, et al. Circ. 1999;100:354. Mean age = 61 years (range: 50-79), n = 1924

9 Cardiovascular Risk Associated with Increasing SBP at Fixed Values of DBP 2-year risk of endpoint 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 Staessen, et al. Lancet. 2000;355: Cox regression.

10 Blood Pressure and CHD Risk Dual BP Component Models Chi Sq. Hazard Ratio P Value Model 1 SBP ( ) <0.001 DBP ( ) <0.05 Model 2 DBP ( ) NS PP ( ) <0.001 Hazards per 10 mm Hg increment Adjusted for age, sex, smoking, ECG-LVH, BMI, glucose intolerance, total/hdl cholesterol Franklin et al. Circulation 1999;100:354

11 Blood Pressure and Risk for CHD by Age Groups: Results of a Single BP Component Model CHD Hazard Ratio/10 mm Hg (CI) *** SBP (10 mm Hg) DBP (10 mm Hg) *** PP (10 mm Hg) * * *** ** < *** Age (y) Adjusted for age, sex, and other risk factors *P<0.1, **P<0.01, ***P<0.001 Franklin SS, et al. Circulation 2001;103:

12 Evolution of Systolic and Diastolic BP in CKD patients Rohrscheib MP et al CJASN 2008;3:1407

13 Rohrscheib MP et al CJASN 2008;3:1407

14 Klassen PS et a l. JAMA 2002;287: n=37069

15 Liu M et al. NDT 2003; 18:563

16 One Year Mortality for Patients on Hemodialysis predicted by pulse pressure Adjusted for level of systolic blood pressure Hazard Ratio for Death n = 37,069 Predialysis PP Postdialysis PP 4 2 Ref >110 Categories of Pulse Pressure (mmhg) Klassen et al. JAMA 2002;287:

17 Brachial Pulse Pressure and Cardiovascular mortality in ESRD patients Cardiovascular free events Cox model: P=0.033 adjusted for age and mean BP Follow-up (months) PPbr 55 mm Hg P<0.001 PPbr 75 mm Hg NS PPbr 75 mm Hg Safar ME et al Hypertension 2002

18 Common Carotid Pulse Pressure and Cardiovascular mortality in ESRD patients 1.00 Cardiovascular free events PPcc <50 mm Hg PPcc 75 mm Hg PPcc 70 mm Hg Cox model: P= adjusted for age and mean BP P<0.05 P<0.001 P< Follow-up (months) Safar ME et al Hypertension 2002

19 1-year Mortality predicted by SBP Experience at 782 US dialysis facilities n = 37,069 Hazard Ratio for Death Ref Predialysis SBP Postdialysis SBP < > 175 Categories of SBP (mmhg) Klassen et al. JAMA 2002;287:

20 1-year Mortality predicted by DBP Experience at 782 US dialysis facilities Hazard Ratio For Death n = 37,069 Predialysis Postdialysis Adjusted for level of systolic blood pressure > 110 DBP (mmhg) Klassen et al. JAMA 2002;287:

21 Survival curves in hemodialysis patients for each baseline level of diastolic BP 1.0 Baseline d BP (mm Hg) 100+ Proportion surviving Duration of observation, months ISEKI K. et al. Kidney Int 1997

22 Hypertension 2005;45:811

23 All cause mortality according Systolic blood pressure (PAS) N = 5692 P<0.01 Adjusted Cox Z-value 2.23; p= ( ) for 1 mmhg increase Fouque D et al Observatoire National

24 All cause mortality according Diastolic blood pressure (PAd) N = 5692 P<0.01 Adjusted Cox: Z-value = 6.73; p< ( ) for 1 mmhg increase Fouque D. et al Observatoire National

25 Systolic pressure 140 mm Hg Mean BP Pulse pressure 80 Diastolic pressure Mean BP: Cardiac output peripheral resistance Systolic pressure: ventricular ejection (stroke volume and ejection time) arterial stiffness wave reflection Diastolic pressure: arterial resistance arterial Stiffness Diastolic decay time

26 Correlation between arterial pulse pressure, wave reflexion (Augmentation index) aortic pulse wave velocity and stroke volume (n=230) Systolic Pressure (mm Hg) R=0.47 p< Systolice Pressure (mm Hg) R=0.60 p< Augmentation Index (%) Aortic pulse wave velocity (cm/s) Systolic Pressure (mm Hg) R=0.17 P <0.05 London et al KI Stroke volume (ml)

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

28 Systolic pressure (mm Hg) r = 0.21 P = NS-PWV and SV adjusted Interdialysis body weight changes (kg) Aortic pulse wave velocity-pwv (cm/s) r = 0517 P < Adjust for Systolic BP Age and SV Interdialysis body weight changes (kg) Stroke volume - SV (ml) r = P < 0.01 Adjust. For Systolic BP and PWV Interdialysis body weight changes (kg) London et al Kidney Int 1989

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

30 ROC Curves of CVdeath Sensitivity Pulse Pressure AUC 72.7±3.2 Aortic PWV AUC 83.4±2.7 Brachial PWV AUC 58.9±3.9 Femoral PWV AUC 56.2± Specificity Pannier B et al Hypertension 2005

31 Correlation between Age and Aortic Pulse Wave Velocity in General population ( ) and ESRD patients ( ) Aortic PWV (m/s) r=0.625 p< Age (years) r=0.719 p< Characteristic impedance (dynes.s.cm-5) r=0.525 P< r=0.340 P< Age (years) Pannier et al Artery 2007;1:78-89

32 Age related changes in arterial internal diameters Carotid artery diameter (mm) Age (years) Brachial artery diameter (mm) Age (years) Controls (r = 0.400; P < 0.01) Controls (r = 0.525;P < 0.01) ESRD (r = 0.438; P < ) ESRD (r = 0.277;P = 0.065) Controls ESRD patients

33 Age related changes in Carotid IMTh Common carotid artery IMTh(mm) Age (years) Controls ESRD patients Pannier et al Hypertension 2005

34 Probability of overall survival in hemodialysis patients according to aortic PWV Probability of overall survival Duration of follow-up (months) PWV < 9.4 m/s 9.4 < PWV < 12.0 m/s PWV > 12.0 m/s Blacher et al. Circulation. 1999

35 All cause survival according to changes in aortic pulse wave velocity (Δ PWV) in response to BP decrease Survival rate Decreased PWV χ 2 = P< Unchanged or PWV Duration of follow-up (months) Guérin et al. Circulation

36 Changes of mean blood pressure and aortic PWV MBP (mmhg) PWV (m/s) MBP (mmhg) PWV (m/s) Inclusion At target BP End of follow up Inclusion At target BP End of follow up Survivors Non Survivors Guérin and al. circulation 2001 ; 103 :

37 ROC Curve of CV mortality Sensitivity Criterions Age; AUC 72±5% Pulse Pressure; AUC 72±5% Carotid IMT;AUC 68±6% LVmassix; AUC 72±5% 0.25 Calcification score; AUC 82±4% Aortic PWV; AUC 82±4% Specificity PWV 2 = Einc x arterial IMT/arterial radius wher Einc is incremental elastic modulus London et al. Cur Op hypertens Nephrol 2006

38 Schematic representation of reactive hyperemic response in the human forearm after five minutes of ischemia Forearm blood flow ml/100 ml/min * * * * * * A = Flow debt ml/100 ml Peak flow * * * Flow debt repayment=b/a B = Excess hyperemic flow ml/100ml Duration of hyperemia * * * * * * * * * * * * * * * * baseline occlusion postocclusion Time,min

39 P< P< Flow debt repayment (%) Controls ESRD Time to debt repayment (s) Controls ESRD Pannier B et al. Kidney Int 2001

40 Probability of survival in ESRD patients according to postischemic forearm flow debt repayement (FDR) 1.00 Survivorship χ²=17.9 P< Follow-up (months) FDR>85% FDR<85% London GM et al. Kidney Int 2003

41 Methods of stimulating increased blood flow Mullen, M. J. et al. Circ Res 2001;88:

42 Echotracking is 3 to 10 x more precise than image based techniques Signal averaging RF lines IMT Spatial resolution 2 D TM RF Signal µm µm

43 Graphs show FMD, GTN-induced dilation, and RH in normotensive subjects (white circles and bars) and in patients with essential hypertension (black circles and bars) Ghiadoni, L. et al. Hypertension 2003;41:

44 Traub, O. et al. Arterioscler Thromb Vasc Biol 1998;18: Endothelial cell biology and shear stress

45 Brachial artery characteristics Controls ESRD Baseline BA diameter (mm) 4.12 ± ± 0.11 < 0.01 BA compliance (m 2 1.kPa.10 7 ) 0.45 ± ± 0.02 < BA distensibility (kpa.10 3 ) 3.5 ± ± 0.19 < BA incremental elastic modulus (kpa.10 ) 3.0 ± ± 0.42 < BA circumferential wall stress (kpa) 60 ± ± 1.9 NS Baseline mean flow velocity (cm/s) 4.6 ± ± 0.30 < 0.01 Baseline mean flow (ml/min) 39 ± ± 3.6 NS Baseline mean SR (s- 1 ) 1 Baseline peak SR (s-) 53 ± ± 3.5 < ± ± 26 < 0.05 Whole blood viscosity (cpoise) 3.57 ± ± 0.06 < Baseline mean SS (dynes/cm²) 19 ± ± 1.0 < Baseline peak SS (dynes/cm²) 129 ± 9 83 ± 5 < Verbeke et al JASN 2007

46 Relationship in Controls and ESRD patients between brachial artery (BA) diameter and compliance and BA shear stress Verbeke et al JASN 2007

47 TNT-Δ Brachial artery diameter (%) Controls P < 0.05 ESRD TNT-MD (% from baseline) Brachial artery distensibility (kpa10-3) Verbeke et al. JASN 2007

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