CKD and CVD - FOMA District 2 · CKD and CVD • CKD is an independent risk for all types of CVD...
Transcript of CKD and CVD - FOMA District 2 · CKD and CVD • CKD is an independent risk for all types of CVD...
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CKD and CVD
• Jamal Salameh, MD, FACP, FASN
First Coast Nephrology
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An Epidemic of Kidney Disease
Clinical Practice Guidelines for CKD Am J Kidney Dis. 2002;39(suppl 1):S17–S31.
GFR = glomerular filtration rate (mL/min/1.73 m2); *with kidney damage
Stage 1: GFR ≥90*
Stage 3: GFR 30–59
Stage 4: GFR 15–29
Stage 2: GFR 60–89*
Stage 5: GFR <15
n=5,900,000
n=5,300,000
n=7,600,000
n=400,000
n=300,000
Total=23 million USA
Prevalence CKD stages 1- 4
10% 1988-94
13% 1999-2004 Coresh, JAMA 298:2038, 2007
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Scope of Disease: NHANES data
Figure 1.1 (Volume 1)
NHANES participants age 20 & older.
USRDS Annual Data Report 2011 Fig 1.1, Vol 1
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CKD and CVD
• CKD is an independent risk for all types of CVD
• In addition, CKD is associated c adverse outcomes in patients c CVD
• This includes an inc M/M in CAD, PCI, CABG, PTA, CHF, PVD and arrhythmias (not discussed)
• Both a decrease in GFR and Proteinuria independently increase risk of CVD
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KDIGO controversies conference KI 80:17-28, 2011
Albuminuria and GFR affect mortality and CKD outcomes
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CKD predicts CV events: HOPE study
Mann et al. Ann Intern Med 2001;134:629–636
0
10
20
30
40 All patients
Patients taking placebo
Patients taking ramipril
Creatinine
<124 µmol/l Creatinine
≥124 µmol/l
n=8307
n=908 Events per
1000
person
years
HOPE=Heart Outcomes and
Prevention Evaluation study
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Rates of death and cardiovascular events rise
as renal function declines
1.0
8 4.7
6
11
.36
14
.14
21
.8
36
.6
0.7
6
11
.29
3.6
5
2.1
1
0
10
20
30
40
>60 45-59 30-44 15-29 <15
Ag
e-s
tan
dard
ised
rate
per
100 p
ers
on
years
Death from any cause
Cardiovascular events
Go et al et al. NEJM 2004 23: 351(13): 1296-1305
Estimated GFR (ml/min/1.73 m2)
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25-34 35-44 45-54 55-64 65-74 75-84 >85
Age
An
nu
al m
ort
ality
(%
)
Adapted from Levey AS et al. Am J Kidney Dis 1998; 32: 853-906.
Cardiovascular Mortality Rates are Higher among Dialysis Patients
General
population: male
General
population:
female
Dialysis: male
Dialysis: female
10
100
1
0.01
0.1
0.001
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CKD and CVD
• Spectrum of disease:
-CAD (Angina/ACS)
-CHF
-CVA
-PVD
-SCD (Sudden Cardiac Death)
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Prevalence of Co-morbidity and Level of GFR
%
GFR 60 ml/min
GFR <60 ml/min
DM CHF Stroke/
TIA
PVD Any
CVD
IHD
0
5
10
15
20
25
30
35
40
GFR 60
GFR< 60
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CKD and CAD
• Incidence/Severity of CAD inc c dec GFR
• In pts c CAD, CKD worsens prognosis
• Pattern of Diffuse Multivessel dz
• Incidence approaches or > 50% in ESRD pts
• M/M are Inversely assoc c Dec GFR
• Typical Risk Factors are common in CKD
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Cardiovascular diseases in CKD
patients
Damage to the heart
(Uremic cardiomyopathy)
Damage to the
arteries
(Uremic arteriopathy)
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CKD and CAD
• Typical Risks include:
-Age (>55 M and >65 F)
-Sex (Male)
-Dyslipidemia (Inc LDL, Low HDL)
-Smoking
-FHx of CAD
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CKD and CAD
• Traditional Risk Factors for CAD
-HTN
-DM
-LVH
-Sedentary Lifestyle
-Menopause
-Obesity
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CKD Screening in the Primary Care Population: Who is “At Risk”
National Kidney Foundation Kidney Disease Outcome Quality Initiative: • NKF KDOQI • Provides evidence-based
clinical practice guidelines
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CKD and CAD
• Non Traditional Risk Factors for CAD:
-Albuminuria
-Hyperhomocysteinemia
-Anemia
-Abnl Ca and PO4 metabolism-Vasc Ca++
-ECF Overload
-Inflammation
-Lipoprotein abnormalities
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Cardiovascular Disease in CKD : Multifactorial Pathogenesis
Cardiovascular
Disease Chronic
inflammation
Exogenous
vitamin
D/deficit
Oxidative
stress
Duration of
dialysis Elevated PTH/
2°HPT
Hypertension
Dyslipidemia
Diabetes
Mellitus
Genetics
Increased homocysteine
levels
Elevated Ca ×
P product
Exogenous Ca
intake
Hyperphos-
phatemia
Smoking
Traditional risk factors
Non Traditional risk factors
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Patients New to Dialysis and Established Patients
Prevalence of Vascular Calcification in CKD
40%
57%
83%
0%
20%
40%
60%
80%
100%
Russo et al RIND TTG
*Russo et al AJKD 2004 (CrCl =33 ml/min) **Spiegel D et al. Hemod Internat 2004: 8:265 ***Chertow et al KI 2002
*
**
***
Stage 3-4 CKD
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Probability of All-Cause Survival According to Calcification Status
*Comparison Between Curves Was Highly Significant (x2=42.66, P<0.0001)
Source: Blacher A, et al. Hypertension:938-942, October 2001
Pro
bab
ilit
y o
f S
urv
ival
0.00
0.25
0.50
0.75
1.00
Duration of Follow-Up (Months)
0 20 40 60 80
Calcification Score: 0
Calcification Score: 1
Calcification Score: 2
Calcification Score: 3
Calcification Score: 4
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Serum Phosphorus and Mortality
in Hemodialysis Patients
1.50
1.00 1.00 1.08
1.25
1.42
1.68
2.03
0
0.5
1
1.5
2
2.5
<3 3-4 4-5 5-6 6-7 7-8 8-9 >9
Serum Phosphorous Concentration (mg/dL)
Rela
tive R
isk o
f D
eath
*
n = 40,538
P < 0.0001
*Multivariable Adjusted Block G, J Am Soc Neph 15: 2208-2218, 2004
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CKD and CAD
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CKD and CAD
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CKD and CAD
• Treatment:
-ASA
-Clopidogrel
-B Blockers
-ACE I/ARB’s
-Statins (not much data in ESRD x SHARP)
-PCI
-CABG (Conflicting data re PCI vs CABG)
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CKD and CHF
• CHF Increases c Declining GFR
• CHF is Leading CV condition in CKD
• Common etiologies are Pressure/Volume XS
• Myocardial Interstitial Fibrosis (RAAS/SNS/Endothelin/ADH/TGF/IL1/TNF..)
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Synergistic effect of CKD, CHF and Anemia as risk factors for Death
Collins, Adv studies in Med 2003
2 yr mortality (n~ 200,000 5% Medicare sample)
%
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CKD and CHF
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CKD and CHF
• Treatment:
-Na restriction
-Diuretics (usually higher doses) and UF
-ACE I/ARB’s
-BB (Carvedilol, Metoprolol, Bisoprolol)
-Anemia Tx
-Ca and Phos Tx to prevent Calcifications
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CKD and CVA
• Independent risk for ICH and Ischemic-RR=1.4
• ESRD pts have a 5-10 risk of age match population to equal approx 4%/year
• Most CVA ischemic 87% in CHOICE study (enrolled 78% ESRD pts and rest CKD 5)
• Approximately 33% during or just p HD
• Mortality approx 35%, much higher than non
HD population, compared to 12% for CKD only
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CKD and CVA
• Treatment:
-Tx HTN
-Antiplatelets
-Statin rx (controversy in ESRD x SHARP)
-CEA in ipsilateral high grade dz
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CKD and PVD
• CKD independent risk factor for PVD
• NHANES reported prevalence of 24% in CKD
• Other studies report 7% to 48% prevalence
• Worse stage/GFR yields worse dz
• High rate traditional risk factors in CKD pts
• Nontraditional risk factors abound too
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CKD and PVD
• Treatment:
-Antiplatelets
-Smoking cessation
-Plavix not studied in CKD population
-Cilostazol helped in ESRD pts
-Statins (as discussed prior)
-PTA vs Bypass (ESRD pts may?? do better c
PTA)
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CKD and SCD
• SCD defined as sudden death, unexpected
within an hour of Sx onset
• Accounts for 25% of death in ESRD pts
• Annual rate of 5.5% per year
• Survival is quite poor at 3-11% at 6 mos
• SCD incrementally increases c decreasing GFR
• ESRD pts die from SCD > ACS
• CKD pts die from ACS > SCD
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Epidemiology of SCD : CKD populations
• CKD stages 3-5 (not dialysis) SCD risk ↑ by HR of 1.1 for every 10ml/min decline in eGFR
• Event rate 0.8% per yr in non-dialysis CKD
• In non-diabetic dialysis patients, rate is 7% in 1st yr of RRT
• SCD risk is > for HD than PD patients during 1st 6 months of dialysis, but equalizes thereafter
0
10
20
30
40
50
60
70
eventrate per1000 yrs
General
CKD
Dialysis
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Karnik JA et al (Kidney International 2001:60:350-357) : Characteristics associated with arrest on hemodialysis
– Monday or Tuesday (greatest risk last 12 hrs before dialysis)
– Low potassium dialysate – Older age – Diabetic – Catheter for access
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CKD and SCD
• In ESRD pts Inc in SCD p long interHD periods
• Causes (?Hyperkalemia, ?Fluid XS, ?Low K/Ca baths)
• High prevalence of CMO, LVH, Hyperkalemia, Fluid Overlad and Long QT
• Treatment: BB and AICD all not studied well
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0
10
20
30
40
50
60
70
80
50-75 25-50 <25 Dialysis
Creatinine clearance (mL/min)
Pre
vale
nce o
f L
VH
(%
)
p <0.003 (trend
analysis)
Prevalence of Left Ventricular Hypertrophy in Relation to Creatinine Clearance
Patients with diabetes = 24%
Adapted from Levin A et al. Am J Kidney Dis 1999; 34: 125-34.
n = 246
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CKD and CVD
• In Conclusion there is paucity of data here
• ESRD pts are usually excluded from trials
and have a high mortality over a short time
frame complicating our ability to study and
recruit these most vulnerable pts
• Thus the Txs for non ESRD pts should be used
for ESRD pts and further work is needed
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Cumulative probability of a physician visit at month 12 after CKD
diagnosis, by dataset & physician specialty: all CKD Figure 3.5 (Volume 1)
Medicare (age 66 & older)
& MarketScan & Ingenix i3
(age 50–64) patients with
CKD identified in 2007.
CKD patients are receiving most of their care from their PCP
USRDS Annual Data Report 2011
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Timely Referral Leads to Reduced
Mortality
0%
10%
20%
30%
40%
On
e Y
ea
r M
orta
lity
Ra
te
< 1 month 1-4 mos > 4 mosTiming of Referral to
Nephrologist
(Time Prior to Start of
Dialysis)
Impact of Timing of Referral to
Nephrologist on Mortality
Early Referral Late Referral
90 Day Mortality 3 3% 13%
6 Month Mortality 4 13% 31%
1 Year Mortality 5 6% 39%
1 Year Mortality 2 22% 41%
2 Year Mortality 6 56% 69%
2
5
In a Recent Study of 300 Medicare Beneficiaries,
the Risk of Death in the First Year on Dialysis
Was Reduced by 48% For Early Referral
Patients Compared to Late Referral Patients. 2
Several Other Studies Shown Below Confirm
This.