HTA ET DIALYSE DR ALAIN GUERIN

Transcription

1 HTA ET DIALYSE DR ALAIN GUERIN

2 Cardiovascular Disease Mortality General Population vs ESRD Dialysis Patients 100 Annual CVD Mortality (%) >85 Age (years) GP Male GP Female GP Black GP White Dialysis Male Dialysis Female Dialysis Black Dialysis White GP: General Population. Foley RN, et al. Am J Kidney Dis. 1998;32:S112-S119.

3 Survival rate (%) 100 Impact of LVH on survival rates g/m n=91 >125 g/m Time (years) Silberberg et al. J Kidney Int, 1989

4 LVMI (g/m 2 ) Correlation in ESRD patients between the stroke work index and LVMI 410 r = 0.62 p < Stroke work index (g.m/m 2 ) 170 London et al. Seminar Dial 1999

5 Predicting LVH (baseline) Odds ratio CI Age (1 year) Sex (female) Hb (0.1 g/dl) SBP (1 mm/hg) Levin et al. AJKD, 1999

6 Predicting LV growth Odds ratio CI Change in Hb (0.5 g/dl) Change in SBP (5 mm/hg) Baseline LVMI Levin et al. AJKD, 1999

7 Echocardiographic measurements Measurement ESRD Controls (n=210) (n=150) LV end-diastolic diameter (mm) 54 ± 4 50 ± 3 ** Posterior wall thickness (mm) 11 ± ± 1.6 ** Interventricular septal thickness (mm) 12.5 ± ± 1.8 ** LV mass index (g/m 2 ) 197 ± ± 30 ** ** p < London et al. Advances in Nephrol 1991; 20:

8 Hemodynamic characteristics of controls and ESRD patients on hemodialysis Controls (n=76) ESRD (n=115) Systolic BP (mmhg) * Diastolic BP (mmhg) Mean BP (mmhg) Pulse pressure (mmhg) *** Heart period (ms) ** Cardiac index (ml/min/m 2 ) *** Peripheral resistance (dynes sec cm -5 m 2 ) *** LV outflow velocity integral (cm/beat) *** Mean + SD; LV - left ventricle; *p<0.05; **p<0.01; ***p<0.001

9 Determinants of vascular overload (afterload) on the heart Peripheral Resistance Complianc e Pulse wave reflection Inertance

10 Determinants of pulse pressure Timing of reflected wave Body size Tappering Reflection sites Pulse pressure Arterial stiffness Heart rate Stroke volume Peripheral resistance CO MAP Age, genetics, smoking, diabetes, cholesterol...

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

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

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

14 Reflected Wave SPTI DPTI SPTI DPTI

15 Principal determinants of systolic BP and their respective weight (multivariate analysis) A B Stroke volume Arterial distensibility Dependent variable: carotid art. systolic BP Independent variables r 2 p value % RMSE Carotid distensibility 0.70 < Stroke volume RMSE: Root Mean Square Error n = 230 subjects

16 One Year Mortality for Patients on Hemodialysis with Compromised Cardiac Function 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 Relative risk of mortality among 5433 hemodialysis patients 3.5 By pre-and postdialysis systolic blood pressure adjusted for age, race, gender, cause of end-stage renal disease, Kt/V, serum, and antihypertensive medications all modeled as time-dependent covariates in a Cox proportional hasards regression model. Relative risk < > 180 Pre-Dialysis Post-Dialysis Systolic Blood Pressure (mm Hg) From ZAGER et al., Kidney Int 54 : , 1998

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

19 Maximal vasodilation Coronary reserve with LVhypertrophy Coronary flow ml/m Normal condition (Autoregulation) Perfusion pressure mm Hg

20 Pathogenesis of vascular diseases in renal failure altered tensile stress (hypertension) altered shear stress (change in blood flow) age gender homocysteine antiatherogenic factors AGE Arteriosclerosis vs Atherosclerosis in CRF local growth factors / inhibitors Ca, P, Vit D, PTH lipoprotein changes AOPP Lp(a)

21 Large artery characteristics in controls and ESRD patients on hemodialysis Controls (n=76) HD (n=115) CCA diameter (mm) *** CCA intima-media thickness (µm) *** CCA wall-to-lumen ratio CCA - common carotid artery *** p < 0.001

22 Correlation Between LV Outflow Velocity and CCA Diameter in ESRD Patients 9 r = 0.50 P < Diameter (mm) CCA = common carotid artery LV outflow velocity integral (cm/beat) London GM et al. Kidney Int 1996;50:

23 Ventricular-vascular interactions in ESRD Primary flow overload (anemia, fistula, hydration) Cardiac output Arterial diameter Left ventricular volume Uremia Arterial thickness Left ventricular mass Left ventricular Stiffness Arterial stiffness Pressure load Primary pressure overload London et al. NDT 1998

24 Correlations between CCA and LV dimensions Interventricular septal thickness (cm) 1.90 r = 0.59 p < LV diastolic diameter (cm) 7 r = 0.39 p < CCA intima media cross-sectional area (mm 2 ) CCA diameter (mm) London, Parfrey. Adv Ren Replace Ther 1997

25 Characteristics of arterial system Functional characteristics of arterial system in control subjects and ESRD patients on hemodialysis Controls (n=76) ESRD (n=115) Common carotid artery distensibility (kpa ) 19.3 ± ± 8.8** Common carotid artery elastic modulus (kpa.10 3 ) ± ± 0.46*** Aortic pulse wave velocity (cm/s) 1020 ± ± 309** Radial artery elastic modulus (kpa.10 3 ) 3.3 ± ± 4* Brachial pulse wave velocity (cm/s) 1117 ± ± 170* Mean ± SD; *p<0.05; **p<0.01; ***p<0.001 / + (controls n=20; ESRD n=20)

26 Correlation between morphologic and functional cardiovascular parameters in HD patients 20 0 Left ventricular mass (g/m 2 ) r = 0.52 p < Aortic pulse wave velocity (cm/sec)

27 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

28 Proportional Hazard Regression of cardiovascular mortality in ESRD VARIABLE Z Value P value Age (years) PWV (m/s) Hemoglobin (mmol/l) Diastolic BP (mmhg) ²=68.91; p< Blacher et al Circulation 1999

29 Impact of aortic stiffness attenuation on survival in ESRD (Guérin et al Circulation 2001) 150 patients were included from september 1988 until april % male ; 8% diabetes mellitus ; age 52 ± 16 y The mean follow up was 51 ± 38 months Aortic stiffness estimated as pulse wave velocity determined at baseline and quarterly Therapeutical intervention - decrease in blood pressure -arterial stiffness is pressure dependent and should decrease in parallel with blood pressure Guérin et al Circulation 2001

30 Approach to reduction of aortic stiffness with antihypertensive treatment Control of overhydration BP>160/90 perindopril nitrendipine BP>160/90 Perindopril + atenolol Nitrendipine + atenolol BP>160/90 Perindopril-atenolol-nitrendipine Nitrendipine-atenolol-perindopril Guérin et al Circulation 2001

31 Change in blood pressure from inclusion until the end of the follow-up in the entire cohort Parameter Inclusion (1) Target BP (2) End of follow-up (3) Systolic BP (mmhg) 169 ± ± 25* 148 ± 24* Diastolic BP (mmhg) 90 ± ± 13* 79 ± 14* Heart rate (beats/min) 75 ± ± ± 11 Values are means SD. Abbreviations used : BP : blood pressure ; PWV : pulse ware velocity * P< and 3 vs 1 P< vs 1 Guérin et al. Circulation 2001

32 All cause survival according to changes in aortic pulse wave velocity ( PWV) in response to BP decrease Survival rate Negative PWV 2 = P< Duration of follow-up (months) Positive PWV Guérin et al. Circulation

33 Cox regression- cardiovascular mortality VARIABLE RR (95% CI) P value CVD (yes-1/no-0) 4.72 ( ) LV mass.i (+10g)) 1.11 ( ) PWV (+=1/ neg= 0) 2.35 ( ) ACE inhibitor (1yes/0 no) 0.18 ( ) ²=59.54 ; p< Guerin et al Circulation 2001

34 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 et al. Circulation 2001

35 Alterations of LV hypertrophy and outcome of ESRD patients: follow-up interventional study Intervention: parallel treatment of anemia (EPO) and pressure overload (ultrafiltration, antihypertensive drugs) Primary end-point: death (all-cause, cardiovascular) Mean follow-up months London et al J Am Soc Nephrol 2001

36 Left ventricular parameters at baseline and at the end of the follow-up in the overall population Parameters Baseline End of follow-up LV mass (g) P<0.01 LV mass index(g/m 2 ) P<0.001 LV diameter (mm) P<0.001 LV wall thickness (mm) P<0.05 LV relative wall thickness (ratio) London et al. JASN 2001

37 Multiple Regression report for changes of left ventricular mass index (%) as a dependent variable, during follow-up Variable Regression Coefficient T-value P-value Incr R² Sequen r² Partial r² Simple r² PWV (m/s) Hgb (g/dl) ACEi(0;1) DHP(0;1) R²=0.407 F-ratio P-value Abbreviations: PWV-changes of aortic pulse wave velocity; Hgb-changes in hemoglobin; ACEi-perindopril 0-no,1 yes; DHP-nitrendipine 0-no,1-yes.

38 Correlation between changes in aortic pulse wave velocity and changes in left ventricular mass index (g/m²) during the follow-up Changes in left ventricular mass index (g/m²) Changes in aortic pulse wave velocity (m/s) R=0.540 p<0.001

39 Proportional hazards risk ratios (RR) for allcause and cardiovascular mortality for entire population Variable RR (95% CI) z-statistics P-value pseudo- r² All cause Age (year) 1.05 ( ) LV mass (10%decrease) 0.78 ( ) Prior CV disease (0-no;1-yes) 2.42 ( ) ²=65.6; P< ; pseudo r²= Cardiovascular LV mass (10%decrease) 0.72 ( ) Prior CV disease (0-no;1-yes) 3.90 ( ) Age (year) 1.04 ( ) ²=51; P< ; pseudo r²=0.3750

40 Cardiovascular survival in ESRD patients whose left ventricular mass decreased (Responders LVM >10%) and Nonresponders SURVIVORSHIP ²=22.2 ; p< Responders Nonresponders ESRD-end-stage renal disease TIME (months) London et al. JASN 2001

41 Characteristics of responders and non-responders (I) Parameters Responders (n=72) Non-responders (n=81) Baseline (1) Follow-up (2) Baseline (3) Follow-up (4) Systolic BP (mm Hg) *** *** *** Diastolic BP (mm Hg) *** *** Mean BP (mm Hg) *** *** Pulse pressure (mm Hg) *** * *** Hemoglobin (g/100 ml) *** *** ** 1 vs 2; 3 vs 4: * P<0.05; *** P< vs 4: ** P<0.01; *** P<0.001

42 Characteristics of responders and non-responders (II) Parameters Responders (n=72) Non-responders (n=81) Baseline (1) Follow-up (2) Baseline (3) Follow-up (4) Heart rate (beat/min) * ** Stroke volume (ml) *** *** Cardiac output (ml/min) *** * *** TPR (dyne.s.cm -5 ) ** Aortic PWV (m/s) *** *** *** % LV shortening * * 1 vs 2; 3 vs 4: * P<0.05; ** P<0.01; *** P< vs 4: * P<0.05; ** P<0.01; *** P<0.001

43 Characteristics of Responders and Nonresponders Parameters Responders (n = 72) Nonresponders (n = 81) Baseline (1) Follow-up (2) Baseline (3) Follow-up (4) Interdialytic weight gain (kg) Serum albumin (g/l) CRP (mg/l) ** *** Body weight (kg) vs 2; 3 vs 4: ***P < vs 3: **P <0.01

44 Relationship between Left ventricular (LV) mass index (g/m²) during the follow-up and the C-Reactive Protein (Ln CRP) 150 LV mass index (g/m²) r=0.408 p< Serum CRP (Ln mg/l)