1. Role of Anaemia – from CRS to CRAS
CRAS definition and epidemiology 1

2. The First Definition of CRAS
Silverberg proposed the term Cardio-Renal Anaemia Syndrome (CRAS) 10 years ago to reflect that there is an interaction between renal failure, heart failure and anaemia
Anaemia
Renal failure
Heart failure
Silverberg D et al. Eur J Heart Fail 2002;4(6):681–686

3. The Definition of CRAS Differs Depending on your Viewpoint (1)
Nephrologists
CKD
Anaemia
CHF
CKD
Any degree of
anaemia
Any degree of heart failure
CKD
Severe anaemia
Severe heart failure
Renal failure
Severe anaemia
Cardiovascular events
Renal failure
Anaemia
Cardiovascular disease 3

4. The Definition of CRAS Differs Depending on your Viewpoint (2)
Cardiologists
CHF
Anaemia
CKD
CHF
Any degree of
anaemia
Any degree of renal insufficiency
CHF
Severe anaemia
Renal failure
Cardiovascular disease
Severe anaemia
Renal failure
Cardiovascular disease
Anaemia
Renal insufficiency 4

5. A Definition of CRAS for 2010
CRAS is a pathophysiological process involving the progressive deterioration of heart and kidney function linked with worsening anaemia
CRAS is a vicious cycle where worsening of one factor negatively impacts on the other two conditions and itself, resulting in progressive deterioration
CRAS is a combination of heart failure, kidney failure and anaemia
Any degree of heart failure
Any degree of anaemia
Any degree of kidney failure
What defines the above factors? 5

6. The Prevalence of CRAS is Dependant upon your Definition of CKD, CHF and of Anaemia
CHF + CKD
Anaemia
CRAS
Anaemia + CHF
Anaemia + CKD 6

7. Hb levels in the EuroHeart Failure Survey Programme
500
400
N=5249 men
33% with Hb <12 g/dL
300
Number of patients
200
100
4–4.4
5–5.4
6–6.4
7–7.4
8–8.4
9–9.4
10–10.4
11–11.4
12–12.4
13–13.4
14–14.4
15–15.4
16–16.4
17–17.4
18–18.4
19–19.4
20–20.4
Hb (g/dL)
A total of 9,971 patients had a value for Hb reported that was ≤11 g/dL in 18% of men and 23% of women
Cleland JG et al. Eur Heart J 2003;24:442–463 7

8. CRAS in US and European HF Surveys60 50 40
Patients (%) 30 20 10
ADHERE 105,000 patients
EuroHF Survey II
Renal failure
Anaemia
Galvao M et al. J Card Fail 2006;12:100–107; Nieminen MS et al. Eur J Heart Fail 2008;10:140–148 8

9. Prevalence Data for CRAS are Varied
Anaemia is common in patients with heart failure (HF) –prevalence ranges from 4–55%1
In patients with CHF NYHA functional class IV, the prevalence of anaemia when defined as <12g/dL and ≤11g/dL was 79.1%3 and 14.4%, respectively4
The prevalence of renal impairment plus anaemia (≤11g/dL) in New York heart association (NYHA) functional class IV HF patients is 6.3%4
The prevalence of chronic renal insufficiency (CRI) in new onset HF patients is 8.8%2 and the prevalence of renal insufficiency in acutely decompensated HF patients is 30%5
The prevalence of CHF in endstage renal disease is 63.7%6
1. Lang C & Mancini D. Heart 2007;93:665–671; 2. Ezekowitz J et al. Circulation 2003;107:223–225; 3. Silverberg D et al. J Am Coll Cardiol 2000;35:1737–1744; 4. Cromie N et al. Heart 2002;87:377–378; 5. Fonarow G et al. JAMA 2005;293:572–580; 6. Avorn J et al. Arch Intern Med 2002;162:2002–2006 9

10. New-onset HF Patients with both CKD and Anaemia
14% 3% 6%
77%
Population-based cohort of 12,065 patients with new-onset CHF
Database analysis from 138 acute- care Canadian hospitals
April 1993–March 2001
Analysis of prevalence and cause of anaemia
CHF + anaemia alone (n=1,696)
CHF + anaemia + CKD (n=387)
CHF + CKD alone (n=674)
CHF alone (n=9,308)
Adapted from Ezekowitz J et al. Circulation 2003;107:223–225 10

11. HF, CKD and Anaemia Occur Frequently in the Same Patient
Multivariable analysis of data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program
2,653 patients with NYHA class II–IV
Prospective, single-centre, observational study2
955 consecutive patients with HF (LVEF <45%)
Median follow-up 531 days
Investigation of the presence of anaemia, and its cause
10%
22%
32%
36%
14%
11.5%
22%
52.5%
CHF + anaemia* alone (n=304)
CHF + anaemia* + CKD** (n=373)
CHF + CKD** alone (n=583)
CHF alone (n=1393)
CHF + anaemia* alone (n=94)
CHF + anaemia* + CKD** (n=211)
CHF + CKD** alone (n=307)
CHF alone (n=343)
LVEF, left ventricular ejection fraction
*Hb <12 g/dL in women, <13 g/dL in men;
**eGFR <60 mL/min/1.73 m2
Adapted from de Silva R et al. Am J Cardiol 2006;98:391–398 11

12. Prevalence of CRAS may be Greater than Current Estimates
“…about half the patients admitted to hospital with a primary diagnosis of CHF…have anaemia…and the great majority will also have CKI (chronic kidney insufficiency)”1
Silverberg et al. noted the majority of CKI patients with anaemia also had CHF2
1. Silverberg DS et al. Semin Nephrol 2006;26:296; 2. Silverberg D et al. Nephrol Dial Transplant 2003;18(suppl 8):viii7–viii12 12

13. Prevalence Data for CRAS are Limited
Very few studies have specifically assessed the prevalence of CRAS within the CKD and CHF populations
Exclusion criteria for clinical trials often remove patients with CRAS and so a true prevalence of the disorder is unknown 13