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Cardiovascular Risk In Chronic Kidney Disease

Cardiovascular Risk In Chronic Kidney Disease

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Cardiovascular Risk In Chronic Kidney Disease

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  1. Cardiovascular Risk In Chronic Kidney Disease Dr Ginny Quan

  2. Who Shall Live ? NBC documentary screened in the 70’s, USA

  3. Cardiovascular Risk In Chronic Kidney Disease Chronic Kidney Disease • Persistent Renal Damage on Biopsy or Imaging • Persistant abnormal urinalysis • Glomerular Filtration Rate <60mL/min/1.73m2

  4. CHRONIC KIDNEY DISEASE Increased risk of Increased Risk of CARDIOVASCULAR DISEASE

  5. Cardiovascular Risk In CKD 1.Is it important? 2.What factors are responsible? 3.What can be done about them?

  6. Patients with End Stage Renal Disease Die Young Data from USRDS 2002 and USA National Vital Statistics Report 1999

  7. What Do Patients with Renal Disease Die Of ? UK renal registry 2002

  8. What Do People With ERF Die Of ? • Cardiac death slightly increased compared to the general population BUT • Age related risk for Cardiac death is very different x200 age 25-29 x5 age 80-84

  9. Early CKD Predicts Risk of Cardiovascular Disease HOORN Study: • Population based cohort, n=631 • Age 50-75 yrs • Followed 10.2 yrs • 5ml/min drop in GFR increased risk of CV death by 26%

  10. Early CKD Predicts Risk of Cardiovascular Disease P<0.001 P<0.001 22.1% 15.1% 11.4% 6.6% HOPE study : Patients at high risk of cardiovascular events. Mann JF Ann Intern Med 2001 134:629-36

  11. Early CKD Predicts Risk Of Cardiovascular Disease The hazard ratio for renal dysfunction in the HOPE study was as high as that conferred by diabetes

  12. Microalbuminuria/Proteinuria Predicts Risk of Cardiovascular Disease • Predicts CV risk in DM • Predicts CV mortality in general population • PREVEND increase in cardiovascular mortality of 1.35 for each doubling of urinary albumin excretion • Predicts CV risk in patients with other high risk factors • HOPE, Linear association between microalbuminuria and an increased risk of endpoint

  13. Cardiovascular Risk In CKD • Cardiovascular risk increases as soon as chronic kidney disease can be measured • As renal function deteriorates risk of cardiovascular disease increases proportionally • In ESRD cardiovascular risk up to 200 times the general population • CKD associated with poorer outcome post cardiovascular events

  14. Is It Important ? • Prevalence diagnosed CKD estimated at 5554 pmp (0.5%) • >80% will not develop ESRD • Majority of these will die of CVD • Population screening studies estimate up to 10% population with CKD

  15. Cardiovascular Risk In CKD 1.Is it important? 2.What factors are responsible? 3.What can be done about them?

  16. What factors are responsible? 1. Increased Prevalence of Conventional Risk Factors Longenecker JC :The CHOICE study J Am Soc Nephrol 2002 ;13;1918

  17. What factors are responsible? 2. Non-conventional risk factors • Cardiac disease is atypical in CKD • CKD is a risk factor for Cardiovascular disease independent of known risk factors

  18. General population: Cardiac death mostly due to Coronary Heart Disease 5% Have LVH on Echo Coronary artery calcification unusual ESRD: Cardiac death often due to Cardiomyopathy /arrhythmia/CHF 75% Have LVH on Echo High incidence of coronary artery calcification Cardiac Disease is Atypical in Renal Disease

  19. What factors are responsible? 3.Lack of risk factor modification • Failure to recognise early CKD as a risk factor for cardiovascular disease • Lack of trials in CKD patients • Fear of polypharmacy and side effects in patients with severe renal disease

  20. Conventional Hypertension Dyslipidaemia Smoking Diabetes ?Under treatment Kidney related Anaemia Calcium metabolism Vascular compliance Fluid shifts Homocysteine levels Inflammation (CRP) ?Under treatment Risk Factors for Cardiac Disease In CKD LVH

  21. Cardiovascular Risk In CKD 1.Is it important? 2.What factors are responsible? 3.What can be done about them?

  22. What should go in a cardiovascular polypill for renal patients ?

  23. Conventional Hypertension Dyslipidaemia Smoking Diabetes Kidney related Anaemia Calcium metabolism Vascular compliance Fluid shifts Homocysteine levels Inflammation (CRP) Risk Factors for Cardiac Disease In CKD LVH

  24. LVH An independent risk factor for CHD in the general population and in renal disease. CONCENTRIC LVH

  25. Prevalence of LVH in HD patients Foley et al, KI 1995;47:186-192

  26. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Normal Survival Concentric LVH Eccentric LVH Systolic dysfunction 0 6 12 18 24 30 36 42 48 54 60 66 72 Months Echo findings predict survival in HD patients Parfrey P et al. NDT. 1996;11:1277-85

  27. LVH Develops Early in Renal Disease LVH on echo found in: • 30% with creatinine clearance 50-75ml/min • 50% with creatinine clearance <25ml/min Levin A Am J Kidney Disease 1999 34 125-34

  28. LVH and Myocardial Dysfunction Risk factors for LVH: • Hypertension is treatable • Anaemia is preventable and treatable • >95% of patients will respond to Epo

  29. Treatment of Hypertension leads to LVH regression in the General Population Regression of LVH in hypertension- meta analysis of 39 trials

  30. Treatment of Hypertension leads to regression of LVH in ESRD • LVH shown to regress with: • Treatment of hypertension in ESRD • Treatment of hypertension in Chronic renal failure • Treatment of anaemia in ESRD • Regression of LVH in one study associated with improved cardiac outcomeFoley RN; J Am Soc Nephrol 2000

  31. Conventional Hypertension Dyslipidaemia Smoking Diabetes ?Under treatment Kidney related Anaemia Calcium metabolism Vascular compliance Fluid shifts Homocysteine levels Inflammation (CRP) ?Under treatment Risk Factors for Cardiac Disease In CKD LVH

  32. Cardiovascular Disease and Hypertension in the general population • Cardiovascular risk increases progressively as blood pressure increases • ? Threshold: relationship holds for blood pressures above 110/75 • Treating blood pressure <140/90 or lower reduces cardiovascular mortality and morbidity .

  33. CHD Mortality Related to Blood Pressure Early renal failure estimated to increase diastolic blood pressure 10-20mmHg if untreated Data from prospective studies collabaration Lancet 2002: 360

  34. Cardiovascular Disease and Hypertension in CKD • ESRD • BP>140/90 associated with increased cardiovascular risk • Duration of hypertension prior to dialysis correlates with mortality • CKD • Subgroup analysis hypertension greater cardiovascular risk factor than general population • No major trials looking at reduction cardiovascular risk with BP reduction in renal patients BUT • Biggest reduction in general population is evident in subgroups • Other risk factors/Underlying target organ damage

  35. HOT Study: 51% RR Reduction of CV Events in Diabetics 25 20 Major cardiovascular events/1,000 patient-years 15 p=0.005 for trend 10 5 0 90 85 80 mm Hg Target Diastolic Blood Pressure Hansson L et al. Lancet. 1998;351:1755-1762.

  36. Hypertension in Renal Disease-The size of the problem • CKD • 50-90% hypertensive depending on stage /disease • Around 50% not adequately controlled ie >140/90 • ESRD • 80% of ESRD patients have hypertension • 50%-70% DO NOT achieve BP<130/80

  37. Treating Hypertension in Renal Disease Has Other Massive Advantages • Lowering blood pressure slows progression of renal disease • Bp reduced from 130/80 to 125/75 reduces decline in GFR by 10.2ml/min/yr -6.7ml/min/yr (mdrd trial) • In renal disease aim for • <125/75 with proteinuria • <130/80 without proteinuria

  38. Which Antihypertensive Is Best For Renal Protection? 1993 Lewis EJ

  39. Treatment of Hypertension leads to LVH regression in the General Population Regression of LVH in hypertension- meta analysis of 39 trials

  40. Ramipril reduces cardiovascular endpoints in patients with mild renal impairment Mann JF Ann Intern Med 2001 134:629-36

  41. Summary: Recommendations for BPControl in Renal disease • If target organ damage (Renal+proteinuria) • Aim for BP<125/75 • If possible ACE first line • On haemodialysis renal association standards • pre-dialysis <140/90 • post-dialysis <130/80

  42. Conventional Hypertension Dyslipidaemia Smoking Diabetes ?Under treatment Kidney related Anaemia Calcium metabolism Vascular compliance Fluid shifts Homocysteine levels Inflammation (CRP) ?Under treatment Risk Factors for Cardiac Disease In CKD LVH

  43. Degree of Anaemia predicts survival of patients on dialysis Increased risk of death Ma JZ; J Am Soc Nephrol 1999 Mar;10(3):610-9.

  44. Treatment of anaemia prior to ESRD Evidence now for correcting anaemia prior to dialysis: • Patients feel better • Reduces LVH • Improves survival after starting dialysis • 4800 patients followed prospectively after starting dialysis • EPO given prior to starting improved survival afterwards Fink J Am J Kidney Dis 2001 Feb;37(2):348-55

  45. Summary: Treatment of Anaemia • Treat anaemia with recombinant EPO otherwise Hb stabilises at 7.0g/dl in CRF • £5000 per patient/year • Treat early-Anaemia can first develops at a GFR <30ml/min (creatinine of 200umol/l) • Target Hb >11g/dl

  46. Conventional Hypertension Dyslipidaemia Smoking Diabetes ?Under treatment Kidney related Anaemia Calcium metabolism Vascular compliance Fluid shifts Homocysteine levels Inflammation (CRP) ?Under treatment Risk Factors for Cardiac Disease In CKD LVH

  47. Coronary Artery Disease is Atypical in Renal Disease

  48. Coronary Artery Disease is Atypical in Renal Disease • Dialysis patients age 20-30yrs • 88% of dialysis patients had some coronary artery calcification • 5% of controls • Coronary Artery calcification related to: • Length of time on dialysis • Calcium -phosphate product • Daily dose of calcium Goodman WG Engl J Med 2000 May 18;342(20):1478-83.

  49. Coronary Calcification In Renal Patients In CKD/ESRD AIM TO: • Normalise phosphate • Reduce parathyroid hormone levels • Avoid hypercalcaemia UNTIL RECENTLY OPTIONS LIMITED: • Aluminium binders –long term toxicity • Calcium binders-risk of hypercalcaemia /metastatic calcification • Vitamin D (alphacalcidol)-risk of hypercalcaemia and hyperphosphataemia

  50. Coronary Calcification In Renal Patients New phosphate binder-Sevelamer • Not absorbed • Lowers lipids • May halt progression of coronary calcification • Initial trials suggest mortality benefit (DCOR) New Vit D compounds –Paricalcitol • Reduce PTH levels • Minimal increase in calcium and phosphate Calcimimetics-Cinacalcet • Stimulates calcium receptor • Lowers PTH without increasing calcium and phosphate