Download cabahug - Philippine Heart Association

A clinical conversation on…
Managing the CVD
patient with
multi-organ dysfunction
Panel
Dr. Raffy Castillo ( Chair )
Dr. Albert Chua
Dr. Oscar Cabahug
The cardiovascular patient with multiorgan dysfunction
Myocardial infarction
and stroke
Atherosclerosi
s and
left ventricular
hypertrophy
Risk factors
Remodelling
Ventricular dilation/
cognitive dysfunction
CV High-Risk
Congestive heart failure/
secondary stroke
Hypertension
Angiotensin II
HF
Death
Adapted from
Dzau VJ, et al. Circulation 2006;114:2850–2870; Figure adapted from Dzau V, Braunwald E.
Am Heart J 1991;121:1244–1263; Yusuf S, et al. Lancet 2004;364:937–952
Image reproduced with kind permission of Professor Böhm
Death
Case
 For the first time, you see a 55 year old, male,
smoker for 30 pack years, non-alcoholic,
with hypertension for 20 yrs and
abnormal renal function for the past 2 years .
He was prescribed medications which he
erratically took.
 Patient complains of episodes of dizziness,
easy fatigue, orthopnea and bipedal edema for
the past 2 weeks.
3
Physical exam
 BP = 150/100, HR = 95/min, RR = 25,
Wt = 90kg, obese, WC = 43 inches
 Awake, coherent, oriented
 Positive bilateral carotid bruit, distended
neck veins with bibasal crackles.
 Apex beat 6th ICS LMCL, irregularly
irregular rhythm, no murmurs
 Liver span is 12 cm, no fluid wave noted
 Grade 2 bipedal edema
This patient likely has a:
A. Primary cardiac problem
B. Primary kidney problem
C. Primary liver problem
5
Cardiorenal interaction may include:
A. Acute decompensated heart failure leading
to acute kidney injury
B. Chronic CHF leading to CKD
C. Combined heart and kidney dysfunction
due to a systemic cause
D. All of the above
JACC 2008 52 (19)
6
Question
Which of the following statements regarding CVD risk in
CKD patients is correct:
A. CKD is a risk factor for CVD
B. Urine albumin level does not predict CV events
C. CVD risk starts to increase with CKD stage 3
D. CV mortality is the # 3 cause of death among
dialysis patients
In healthy individuals –
risk of CV death starts to rise at GFR 90 ml/min
8913 randomly selected apparently healthy individuals,
10 year follow-up
(
eGFR
ml/min/1.73m2)
CV mortality
standardized rate/
1000 person years
Hazard Ratio
adjusted
(95%CI)
< 75.6
2.57
2.46
(1.27-4.78)
75.6 - 89.4
2.61
2.62
(1.34-5.14)
89.4 -104.3
1.9
1.9
(0.93-3.86)
> 104.3
0.99
1
van Biesen, Europ.Heart J.(2007) 28:478
Prevalence of Cardiovascular Diseases in Renal Patients
CAD
General Population
5 – 12 %
Chronic Kidney Disease 16 - 35 %
Dialysis Patients
50 %
LVH (Echo)
20 %
25 – 50 %
75 %
At start of HD, only about 16 % have normal 2DEcho
Heart failure seen in about 40 % of Dialysis Patients
Presence of HF associated with increase risk of death by 93 %
CV Mortality accounts for about 50 % of deaths in
dialysis patients ( ranks # 1 )
AHA Statement 2003:
Kidney Disease is a Risk Factor for CVD
Cardiovascular Risk Factors in CKD
Traditional Risk Factors
 Age
 Gender
 Hypertension
 Diabetes mellitus
 Hyperlipidemia
 LVH
 Physical inactivity
 Smoking
Nephr Dial Trans 2000
Kidney Disease related risk factors
 Albuminuria
 Dyslipidemia
 Ca x P product 
 PTH 
 Vascular calcification
 Fibrinogen 
 Homocysteine 
 CRP 
 Increased oxidative stress
 Volume overload
 Hyperuricemia
 Insulin resistance
 Anemia
What work-up will you request to evaluate renal
function:
A. Urinalysis and Urine Albumin/Creatinine ratio
B. Serum creatinine
C. Kidney ultrasound
D. All of the above
15
Cockcroft-Gault Formula
eGFR =
(140 – Age ) X Wt in kgs
______________________
72 X Serum Cr in mgs/dl
* Multiply result by 0.85 for female
Case:
55 y/o male, Wt= 90Kg, Creat = 3 mg/d
eGFR = 35.4 ml/min
CKD Stage 3b A3
Revised CKD Classification KDIGO 2009
What work-up will you request for the
hepatomegaly?
A. Liver enzymes (ALP, AST, ALT)
B. Protime
C. Liver ultrasound
D. All of the above
18
Lab results of the patient:





Hgb = 10 gm/dl
FBS = 105 mg/dl
Na = 138 meq/L
Cholesterol = 240 mg/dl
HDL 35mg/dl
 ALT = 80 U/L
 ALP = 110 U/L
 Albumin = 3.1 gm/dl
Uric Acid = 8 mg/dl
Creatinine = 3 mg/dl
K = 4.8 meq/L
LDL = 155 mg/dl
Triglycerides = 190 mg/dl
AST = 100 U/L
INR = 1.1
 Urinalysis: +2 protein
 Urine Protein/Creatinine = 1800 mg/gm
19
Lab results of the patient:
 Ultrasound = Hepatomegaly with fatty infiltration,

Normal gallbladder, biliary tree and spleen,

Bilateral diffuse renal parenchymal disease
 ECG: Atrial fibrillation with moderate ventricular
response, IVCD, Non-specific ST TWC
 Chest x-ray: Cardiomegaly (CTr = 0.6) with
pulmonary congestion
 2D Echo: Eccentric LVH with diffuse hypokinesia;
EF= 34 % ; mild mitral / tricuspid regurgitation
20
Will you refer this patient for coronary
angiogram?
A. Yes
B. No
21
Contrast-Induced Nephropathy Risk Score
Mehran R, Nikolsky E, et al
Kidney Int 2006;69
You’d preferably prescribe this patient for his
cardiovascular problem the following drugs
EXCEPT?
A. RAAS blocker
B. Beta-blocker once Heart Failure is stabilized
C. Loop diuretics
D. Verapamil or Diltiazem for rate control
23
Impact of RAAS Blockade on
Progression of CKD
Normal
Micro
albuminuria
Ravid 1998
BENEDICT 2004
ROADMAP 2011
Overt
Proteinuria
Ravid 1993
UKPDS 1998
CALM 2000
MICRO-HOPE 2000
MARVAL 2001
IRMA 2001
DETAIL 2004
ADVANCE 2010
ESRD
RENAAL 2001
IDNT 2001
ADVANCE 2010
CV event
Death
FOSIDIAL 2006
Cooperative CV
Project 2003
Candesartan 2006
Prevention of Chronic Kidney Disease Progression in
the Candesartan Antihypertensive Survival
Evaluation in Japan (Case-J) Trial
T Saruta, et al Hypertens Res 2009 Jun
Subgroup analysis of CASE-J trial showed that in
Hypertensives with CKD, Candesartan, and Amlodipine,
are equally effective in controlling blood pressure and
reducing the incidence of cardiovascular events, but
Candesartan is more effective in preventing deterioration
of renal function
Events Candesartan Amlodipine
CV
61 (7.3%)
74 (9.3%)
Renal
10 (1.2%)
22 (2.8%)
HR
0.780
0.430
P value
0.140
0.022
Question
What is the target Blood Pressure level for this patient ?
A. < 140 / 90
B. < 130 / 80
C. < 120 / 75
D. < 110 / 70
Case:
CKD stage 3b A3
UK National Institute for Health and Clinical Excellence
(NICE) 2008 CKD Guidelines
What is the risk of this patient to develop
ischemic stroke?
A. Low risk
B. Intermediate risk
C. High-risk
30
Risk of stroke according to CHADS2
CHADS2 criteria
0
Congestive heart failure
1
Hypertension
1
Age ≥75 years
1
2
Diabetes mellitus
1
3
Stroke/transient ischaemic
attack
2
1
CHADS2 total score
Score
4
5
6
0
5
10
15
20
Risk of stroke, %/year*
25
30
Error bars = 95% confidence intervals; *Theoretical rates without therapy
ACC/AHA/ESC guidelines: Fuster V et al. Circulation 2006;114:e257–354 & Eur Heart J 2006;27:1979–2030;
Gage BF et al. JAMA 2001;285:2864–70
31
To prevent cardioembolic problems, what would
you prescribe this patient?
A. Aspirin
B. Clopidogrel
C. Anticoagulant
32
AF-RELATED STROKE IS PREVENTABLE
 Effective stroke prevention is a priority for patients with AF1
 Two-thirds of strokes due to AF are preventable with appropriate
anticoagulant therapy2
 A meta-analysis of 29 trials in 28,044 patients showed that the vitamin
K antagonist (VKA) warfarin reduces the risk of stroke and allcause mortality2
64% reduction in stroke and 24% reduction in all-cause mortality compared with placebo
 Aspirin also reduced the risk of stroke, but less effectively than warfarin (19% reduction
compared with placebo)

 However, VKAs are associated with complications, such as increased
bleeding risk
 Guidelines for antithrombotic therapy in AF recommend Aspirin or
VKA depending on the presence of risk factors for stroke1
1. Fuster V, et al. Circulation 2006;114:e257–354. 2. Hart RG, et al. Ann Intern Med 2007;146:857-867.
What will be your management of choice to
lower the cholesterol level?
A. Low cholesterol diet initially
B. Lowest possible dose of statin
C. Ezetimibe plus statin
D. Gemfibrozil plus statin
34
Ezetimibe 10 mg
SHARP TRIAL: Study of Heart and Renal Protection
Lancet June 2011
RCT, 9438 CKD patients, 1/3 on dialysis, ffup 4.9 yrs
There was no difference in the progression to ESRD
between treated grp (33.9%) and placebo (34.6%)
CLINICAL GUIDELINES: CVD in CKD
UK Renal Association 2011
 Guideline 1.6 - Statins
Statins should be considered for primary prevention in
all CKD Stages 1-4 and transplant patients
 Guideline 1.7 – Target Lipid level
Total cholesterol of <4 mmol/l or 25% reduction from
baseline or fasting LDL of <2 mmol/l
 Guideline 1.8 – Statins in dialysis patients
Statins should not be withdrawn from patients in whom
they were previously indicated and should continue
when such patients start renal replacement therapy
CLINICAL GUIDELINES: CVD in CKD
UK Renal Association 2011
Guideline on Secondary prevention of CV risk
CKD patients with a history of chronic stable
angina, acute coronary syndrome, myocardial
infarction, stroke, peripheral vascular disease, or
who undergo surgical or angiographic coronary
revascularisation, should receive:
Aspirin, ACE-inhibitor, Beta-blocker
and Statins unless contraindicated
What would be your next step in the management
of the fatty liver of this patient?
A. Observe liver transaminases with the cholesterol
lowering agents
B. Initiate therapy with essential phospholipids /
silymarin
C. Check for hepatitis B or C for possible interferon
therapy
D. Check serum insulin level for possible
metformin therapy
39
Therapy for NAFLD
 Anti-oxidants
- vitamin E – based on 2 small open label
studies but refuted by an RCT
 Ursodeoxycholic acid
- initial results also refuted by an RCT
Therapy for NAFLD
 Insulin sensitizer
- use of metformin proved improvement of the
liver enzymes and amount of steatosis but
improvement of inflammation is equivocal
- pioglitazone and rosiglitazone shows promise
in terms of improvement of inflammation but some
patients develop greater elevation of transaminase
levels
Therapy for NAFLD
 Lipid lowering drugs
- gemfibrozil and statin show promise but no
RCTs yet
 TNF- blockade
- TNF- contributes to insulin resistance
- use of pentoxifylline and adiponectin and its
effect on TNF- should be investigated
 Liver transplantation
- 60 – 100% recurrence of steatosis
Renoprotective strategies in this patient
includes use of:
A. RAAS blocker
B. Oral Bicarbonate
C. Allopurinol
D. All of the above
43
Measures to Prevent Progression of CKD
•
•
•
•
•
•
•
•
•
Lifestyle modification
Glycemic control
Blood pressure control
Renin Angiotensin Aldosterone System blockade
Reduction of proteinuria
Protein restriction – LPD, VLPD+KAA
Lipid lowering
Correct hyperuricemia, acidosis, anemia
Avoid nephrotoxic agents, infections, etc
- Tao-Li. Kidney International, April 2005
Correction of Acidosis
 JASN 2009 – De Brito et al
 RCT of oral sodium bicarbonate in 134 adults with CKD Stage 4 and
serum bicarbonate 16 -20 mmol / l.
 2 years ff-up, 22 patients in control group vs 4 in bicarbonate group
progressed to dialysis (33% vs 6.5%)
 Bicarbonate group less likely to experience rapid progression
 Kidney International 2010 - Mahajan et al
 5-year, RCT on oral sodium bicarbonate vs NaCl vs placebo
 120 patients with early CKD w/o acidosis
 GFR at the end of the study was significantly higher in the
bicarbonate-treated group, by about 5 ml /min.
 Urine albumin excretion and NAG excretion were both
significantly reduced.
Hyperuricemia in CKD
 Hyperuricemia is an independent risk factor
for renal and CV disease
 Goicoechea, M. et al. Effect of Allopurinol in
CKD progression and cardiovascular risk.
 Clin. J. Am. Soc. Nephrol. 2010
 showed that Allopurinol slowed progression of
renal disease and reduced the risk of CV events
in patients with CKD.
June 24, 2011
Bardoxolone grp have mean increase in eGFR of 10 mL/min.
73% of Bardoxolone grp have improvement in eGFR vs 2% of
placebo grp (P<.001)
What should we advise for the diet in this
patient?
A. High protein diet to prevent muscle atrophy
B. Liberal sodium to prevent hyponatremia
C. Force oral fluids to reduce azotemia
D. Restrict potassium and phosphorus sources
48
Fouque D et al,:. 2006. Low protein diets for chronic
renal failure in nondiabetic adults
Cochrane Database Syst. Rev. CD001892
Favors LPD
Courtesy Professor Anders Alvestrand 2009
facebook.com/LriTherapharma
To GOD be the glory