Cardiovascular Risk Reduction in Kidney Transplant Recipients

Transcription

1 Cardiovascular Risk Reduction in Kidney Transplant Recipients Rainer Oberbauer R.O. AUG 2010

2 CV Mortality in ESRD compared to the general population R.O.2/32 Modified from Foley et al. AJKD 32 (suppl3): 1998

3 Risk factors for the development of CVD after renal TX R.O.3/32 Shirali AC et Bia MJ. CJASN 2008 Mar;3(2):

4 Agenda Modifyable risk factors & CV outcomes Hemoglobin Lipids Glucose control Blood pressure BMI - Obesity R.O.4/32

5 High prevalence of anemia after renal transplantation (TRESAM, n=4263) 9.6% No anemia 6.8% 11.9% 60.8% Mild anemia Moderate anemia 11.2% 62.4% 17.7% Severe anemia 19.7% Mild: males: Hb >12 g/dl and Hb 13 g/dl Male patients n=2641 females: Hb >11 g/dl and Hb 12 g/dl Moderate: males: Hb >11 g/dl and Hb =12 g/dl females: Hb >10 g/dl and Hb =11 g/dl Female patients n=1622 Severe: males: Hb 11 g/dl, females: Hb 10 g/dl R.O.5/32 Vanrenterghem et al. Am J Transplant 2003;3:835

6 Anemia increase risk of mortality & graft loss (n=938, 118 events) Adjusted for age, gender, egfr, serum albumin, serum CRP, transplantation vintage, pretransplant time on dialysis, number of comorbid conditions, presence of hypertension. Molnar MZ et al. Am J Transplant Apr;7(4):818-24

7 Rate of ESA users after KTX (OEDTR n=1794, 345 events, ) R.O.7/32 Heinze G et al. BMJ 2009;339:b4018

8 Extended KM plot OEDTR n=1794, 345 events, ) R.O.8/32 Heinze G et al. BMJ 2009;339:b4018

9 HR of death depending on Hb levels and ESA use (OEDTR n=1794, 345 events, ) adjusted for: dialysis status, cerebrovascular disease, peripheral vascular disease, coronary heart disease, heart failure, cholesterol level, immunosuppressive regimen, diabetes status, age at transplantation, cold ischemia time Heinze G et al. BMJ 2009;339:b4018 R.O.9/32

10 Hb Variability and Mortality (OEDTR n=1794, 345 events, )) Hb Strata in g/dl: L<10 10<M<12 12<H R.O.10/32 Kainz A J et al. 2010

11 Agenda Modifyable risk factors & CV outcomes Hemoglobin Lipids Glucose control Blood pressure BMI R.O.11/32

12 Statin use and CV Mortality in RTX (OEDTR, N=2041, 223 CV deaths) R.O.12/32 Wiesbauer F et al J Am Soc Nephrol Nov;19(11):2211-8

13 ALERTex Study: Statin use and primary endpoint (MACE) in RTX (N=2102, 192 CV deaths) R.O.13/32 Holdaas H et al. Am J Transplant 2005; 5:

14 Statin use and CV Mortality in RTX (OEDTR, N=2041, 223 CV deaths) R.O.14/32 Wiesbauer F et al J Am Soc Nephrol Nov;19(11):2211-8

15 Crude and adjusted HR of events statin vs no-statin use (OEDTR, N=2041, 223 CV deaths) R.O.15/32 Wiesbauer F et al J Am Soc Nephrol Nov;19(11):2211-8

16 ALERTex Study R.O.16/32 Holdaas H et al. Am J Transplant 2005; 5:

17 Agenda Modifyable risk factors & CV outcomes Hemoglobin Lipids Glucose control Blood pressure BMI R.O.17/32

18 Kaplan-Meier estimates of survival according to quartiles of maximal nonfasting glucose level R.O.18/32 Wiesbauer F et al Transplantation 2010, 89:

19 HR for quartiles of maximal nonfasting glucose levels (adjusted for number of antihypertensive drugs, total cholesterol, type of immunosuppressive therapy, year of transplantation, MAP and donor age) R.O.19/32 Wiesbauer F et al Transplantation 2010, 89:

20 HR for quartiles of HbA1c (adjusted for number of antihypertensive drugs, total cholesterol, type of immunosuppressive therapy, year of transplantation, MAP and donor age) R.O.20/32 Wiesbauer F et al Transplantation 2010, 89:

21 Agenda Modifyable risk factors & CV outcomes Hemoglobin Lipids Glucose control Blood pressure BMI R.O.21/32

22 Effect of ACEI/ARB & hypertension on CV death after RTX (n=2031, 157 CV deaths) R.O.22/32 J Am Soc Nephrol Mar;17(3):889-99

23 Cumulative incidence of patients that received ACEI or ARB during the lifetime of their transplant(s) (n=2246) R.O.23/32 Heinze G et al. 2006J Am Soc Nephrol Feb 15; [Epub ahead of print]

24 ACEI/ARB therapy after renal TX was associated with reduced risk of mortality R.O.24/32 Heinze G et al. 2006J Am Soc Nephrol Feb 15; [Epub ahead of print]

25 Agenda Modifyable risk factors & CV outcomes Hemoglobin Lipids Glucose control Blood pressure BMI R.O.25/32

26 The risk factor paradox General Population Dialysis R.O.26/32 DOPPS 2004

27 Research Design & Methods NHANES I - NHEF linked by SEQN subjects years of age Median 17yr f/u weighted size of 29,807,750 subjects 19.6% high-normal to elevated creatinine (cut-off 1.2 mg/dl) R.O.27/32 Oberbauer R & Ayanian J 2008

28 Results II Crea<1.2, BMI<28 Crea<1.2, BMI>28 Crea >1.2, BMI>28 Crea>1.2, BMI<28 R.O.28/32 Oberbauer R & Ayanian J 2008

29 NHANES I and NHEF - Effect Modification SCr >1.2 x BMI (>28 vs <28) RR 95%CI R.O.29/32 Oberbauer R & Ayanian J 2008

30 Candidate BMI Levels by Year of Listing USRDS n=162, % BMI 35+ Proportion of Wait Listed Candidates (%) 80% 60% 40% 20% BMI 30-<35 BMI 25-<30 BMI 20-<25 0% BMI Year of Wait Listing R.O.30/32 Schold, Oberbauer, Meier-Kriesche. Am J Transplant 2006, 6:1-10.

31 R.O.31/32 Schold, Oberbauer, Meier-Kriesche. Am J Transplant 2006, 6:1-10.

32 Adjusted HR for Overall Graft Loss by Change in BMI from Wait Listing to Transplant USRDS n=162,284 Adjusted Hazard Ratio for Graft Loss * p < 0.05 ** 0-4% represents the reference group * BMI change from wait listing to transplant** >12% increase 8-12% increase 4-8% increase 0-4% increase 0-4% decrease 4-8% decrease 8-12% decrease >12% decrease 0 < BMI level at the time of Transplantation (kg/m 2 ) R.O.32/32 Schold, Oberbauer, Meier-Kriesche. Am J Transplant 2006, 6:1-10.

33 Conclusions Modifyable risk factors & CV outcomes Hemoglobin Lipids Glucose control Blood pressure BMI