2. • Cardiovascular disease (CVD) is very common
in patients with chronic kidney disease (CKD)
and is by far the leading cause of morbidity
and mortality in dialysis patients (USRDS,
2008).
3. • The majority of patients, particularly those
with an estimated glomerular filtration rate
(eGFR) of <60 ml/min, usually die from heart
disease before they reach ESRD
4. Cardiovascular Mortality in the General Population and
in ESRD Treated by Dialysis
0.01
100
10
1
0.1
Annual mortality (%)
25–34 45–54 65–74 8535–44 55–64 75–84
Male
Female
Black
White
Dialysis
General population
Age (years)
5. Go AS, Chertow GM, Fan D, McCulloch CE,
Hsu C-Y. N Engl J Med. 2004;351:1296-1305.
6. Risk Factors Contributing to CVD in CKD
Microalbuminuria/Proteinuria
Hypertension
Diabetes
Dyslipidemia
Smoking
8. Microalbuminuria/Proteinuria
• indicator of kidney damage and a risk factor
for progression of kidney disease
• associated with an increased risk of CVD
events in the general population and in
patients with hypertension diabetes and
established atherosclerotic disease
9. Hypertension
• left ventricular hypertrophy, MI, angina, heart
failure, stroke, and peripheral arterial disease
• According to 2008 data from the US Renal
Data System (USRDS), hypertension was
present in 91.4% of patients with advanced
CKD, and was more common in African
Americans (96%) than in Caucasians (90.7%)
10. • A post hoc analysis of the Heart Outcomes
and Prevention Evaluation (HOPE) trial
evaluated cardiovascular outcomes according
to baseline serum creatinine value and
presence or absence of hypertension
11. • Compared with hypertensive individuals
having a serum creatinine value less than 1.4
mg/dL, hypertensive patients with a serum
creatinine value of at least 1.4 mg/dL had
higher primary cardiovascular end point rates
(approximately 45 events per 1000 person-
years vs 65 events per 1000 person-years)
12. Diabetes
• According to USRDS 2008 data, diabetes
mellitus is prevalent in patients with CKD,
occurring in 48.2% of patients with stage 1 or
2 and in 49.4% of those with stage 3 to 5
13. • A study involving a 5% sample (N = 1,091,201)
of the US Medicare population evaluated the
impact of diabetes in CKD on CVD and death,
by comparing patients with and without CKD
and diabetes over 2 years
14. • The CVD outcomes included congestive heart
failure, acute MI (AMI), cerebrovascular
accident/ transient ischemic attack (stroke),
peripheral vascular disease (PVD), death, and
atherosclerotic vascular disease, which was a
combined end point of AMI, stroke, and PVD.
15. • Patients without CKD and diabetes had the
lowest incidence per 100 patient-years for all
events. Diabetics without CKD had numerically
higher rates of the events, but rates were less
than those found in nondiabetics with CKD.
16. • The highest rates of all events were observed
in patients with CKD and diabetes
17. • The third report of the National Cholesterol
Education Program (NCEP) considers diabetes
a CHD equivalent, so it is interesting that CKD
had a higher impact than diabetes on CVD in
the Medicare population study
21. • Data from the placebo group of the
Justification for the Use of statins in
Prevention, an Intervention Trial Evaluating
Rosuvastatin (JUPITER)
22. • The NKF and NCEP recommend aggressive
treatment and maintaining a goal low-density
lipoprotein (LDL) cholesterol level of 100
mg/dL or less.
23. Smoking
• Tobacco smoking in patients with CKD without
established CVD is associated with a 59%
increase in heart failure and 68% increase in
PVD compared with nonsmokers over 2.2
years
25. Anemia
low hemoglobin versus
a hemoglobin target of
11 to 12 g/dL (with ESA
use) resulted in a 1.14-
fold increase in the OR
of death.
26. hemoglobin target of
greater than 12 g/dL in
patients with CKD or
ESRD was associated
with a 1.12-fold increase
in the OR of death
27. Calcium and phosphate metabolism
• Analysis from two large national databases
from the United States revealed that
hyperphoshatemia, elevated
calcium*phosphorus product and elevated
parathyroid hormone were specifically
associated with death from coronary artery
disease and sudden cardiac death in ESRD
29. • Vascular calcification that develops secondary
to hyperphosphatemia classically occurs in the
media and is also known as the 'Monckeberg's
calcinosis'.
30. • Hyperphosphatemia may also increase cardiac
fibrosis, hypertrophy and aggravate
microvascular disease and predispose to
sudden cardiac death in dialysis patients
31. • ESRD patients frequently exhibit both intimal
and medial type of calcification but the intimal
calcification is usually more extensive and
severe as compared to non-uraemic subjects
32. • Deficiency of vitamin D, associated with
declining kidney function, also contributes to
calcium and phosphate abnormalities,
independently increasing the risk of mortality
33. Inflammation
• one of the major non-traditional risk factors
for accelerated atherosclerosis in dialysis
patients. Using C-reactive protein (CRP) as the
prototype marker of inflammation,
inflammation was detected in 20 - 50% of
ESRD patients
35. Cardiovascular morbidity and mortality
Arrhythmias
Arrhythmias are frequently
observed in patients undergoing
dialysis. These events are a
significant cause of mortality in
the dialysis population.
36. • The incidence of atrial fibrillation (AF) in
patients with ESRD is between 1 and 4.1 per
100 patient– years
37. • Multiple mechanisms have been proposed for
the development of AF in ESRD, but most
appear to be attributable to the atrial stretch
caused by hemodynamic (pressure and
volume) overload.
39. critical ischemia in a previously injured and often scarred myocardium.
Left ventricular hypertrophy
anemia, the rapid fluid
electrolyte shifts during hemodialysis, endothelial dysfunction
myocardial interstitial fibrosis and low myocardial tolerance to ischemia
40. • The risk increases with patient age and
duration of dialysis
41. • Data from USRDS study of all incident US
dialysis patients (1995-1999), the rate of
cardiac arrest progressively increased from 93
events per 1000 patients-years at 2 yrs after
dialysis initiation to 164 events per 1000
patient-years 5 year after dialysis initiation
(USRDS,2008).
42. • On Sunday preceding the dialysis on Monday
(after a weekend without dialysis) the risk of
SCD is three times the average risk. Mondays
for patients who dialyze on Tuesdays hold
similar risk
43. Ischemic heart disease
25% in younger non diabetic
patients with end-stage renal
disease (ESRD) and 85% in older
dialysis patients with a
longstanding history of diabetes
mellitus
44. Uremia-specific risk factors”:
inflammatory markers,
C-reactive protein
hyperphosphatemia
vascular calcification
electrolyte abnormalities
25-hydroxy vitamin D deficiency
anemia
45. • Anemia and left ventricular hypertrophy
which are very prevalent among dialysis
patients can exaggerate the ischemic effects of
obstructive coronary lesion by increasing the
myocardial oxygen demand
46. • KDOQI guideline recommends a baseline
echocardiogram at the initiation of dialysis
and every 3 yrs after
47. evaluation for CAD is recommended
classical angina/ angina equivalent symptoms
recurrent hypotension
CHF unresponsive to dry weight changes or inability to
achieve dry weight because of hypotension,
significant LV dysfunction with EF< 40 %; evaluation for
CAD is recommended
48. Valvular heart disease
• Premature and accelerated calcific
degeneration of the mitral annulus and aortic
valve in ESRD most commonly manifest as
mitral annular calcification and aortic stenosis
49. • 1-year survival being 70% for patients with
valvular calcification as compared with 93%
for those without.
51. the median overall survival of ESRD patients with
CHF is reported to be 36 months compared with
62 months in patients without CHF
52. • Fewer than 15 % of dialysis patients are alive 3
years after hospitalization for CHF
53. Stroke/transient ischemic attack (TIA)
• Stroke is the third leading cause of death in
the United States and other developed
countries
54. Peripheral vascular disease
• Smoking cessation, lipid lowering, glycemic
control, HTN control and use of antiplatelet
agents are important in primary prevention.
The relative role of these risk factor
modifications on the outcome, after PVD has
already set in; is not known
