CARDIOVASCULAR DISEASE AND CHRONIC KIDNEY DISEASE

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CARDIOVASCULAR DISEASE AND CHRONIC KIDNEY
DISEASE

• BY
• CHRISTINA AMIRA MB.BS, M.Sc, FWACP, FISN
• NEPHROLOGY UNIT LUTH

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OUTLINE

• Introduction
• Epidemiology of CVD in CKD
• Spectrum of CVD in CKD
• Why is CKD a risk factor for CVD
• Therapeutic options
• Conclusion

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INTRODUCTION

• The initial enthusiasm for dialysis as a survival
  measure for patients with chronic renal failure
  (CRF) was tempered in 1974 when Linder and
  colleagues noted the extraordinarily high
  frequency of coronary heart disease and cardiac
  death in the first patients who underwent
  dialysis in Seattle at that time
• This observation lead to the hypothesis of
  accelerated atherosclerosis in CRF which has
  remained to date.

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INTRODUCTION

• CKD is a world wide public health problem
• Incidence and prevalence is rising worldwide with
  poor outcomes and high cost
• NKF KDOQI new classification describes 5 stages
  of kidney disease and the complications
  associated with CKD particularly CV risk factors

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EPIDEMIOLOGY OF CVD

• Cardiovascular disease (CVD) is the leading cause
  of morbidity and mortality among patients with
  chronic kidney disease accounts for 40-50 of
  deaths in dialysis pts
• CVD is defined as presence of CHF,CHD,CVD,PVD
• 40-75 of pts starting dialysis already have CVD
• CVD mortality in dialysis pts is 10-20 times
  higher than in general population
• High CVD mortality is due to high prevalence of
  CVD and high case fatality

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Approximate Prevalence of CVD
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CARDIOVASCULAR MORTALITY IN THE GENERAL
POPULATION (NCHS) AND IN KIDNEY FAILURE PATIENTS
TREATED BY DIALYSIS OR TRANSPLANT (USRDS)
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SURVIVAL RATE IN ESRD AND GENERAL POPULATION
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EPIDEMIOLOGY

• Mortality after MI in 34, 189 long term dialysis
  pts (1977 1995) was 73 and 90 at 2yrs 5yrs
  respectively Cf 25 at 2yrs in Diabetic men and
  34 in diabetic women in the Worcester Heart
  Attack study
• Pts with earlier stages of CKD also die from CVD.
• Recently CKD is now considered to be a risk
  factor for CVD
• The NKF task force on CVD in CRD issued report
  that CKD pts are in the highest risk for CVD

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SPECTRUM OF CVD IN CKD

• Alteration in cardiac geometry (Cardiomyopathy)
• LVH - Eccentric and Concentric
• Atherosclerosis is an intimal disease
  characterized by the presence of plaques and
  occlusive lesions
• Ischemia is due to large coronary artery
  disease and may also result from small vessel
  disease or assoc with severe LVH and fluid
  overload
• Arteriosclerosis
• Remodeling of large arteries with
  calcification
• Reduction in arterial wall compliance

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CARDIOMYOPATHY- LVH

• Concentric LVH is associated with pressure
  overload e.g. HTN, arteriosclerosis. Causes
  diastolic dysfunction.
• Eccentric LVH is associated with anaemia, volume
  overload. It leads to systolic dysfunction
• Prevalence of LVH increases with declining renal
  function

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PREVALENCE OF CARDIAC DISEASE IN DIALYSIS PATIENTS
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CLINICAL PRESENTATION OF ATHEROSCLEROSIS IN CKD

• Ischaemic heart disease which could present as
  angina, myocardial infarction and sudden death
• Cerebrovascular disease
• Peripheral vascular disease
• Heart failure

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INVESTIGATIONS OF ATHEROSCLEROSIS

• Carotid intima-media thickness measured by B-mode
  ultrasonography
• Coronary stress tests
• Stress echocardiography
• Radionuclear stress tests
• Coronary angiographic

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ARTERIOSCLEROSIS

• Disease of large vessels such as the carotids and
  aorta
• Diffuse media involvement resulting in increased
  arterial stiffness and decreased distensibility
  or compliance
• Increased stiffness results in increased pulse
  pressure, causing increased LV afterload and
  concentric LVH

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ARTERIOSCLEROSIS

• Arteriosclerosis predisposes to IHD by decreasing
  sub-endocardial coronary perfusion
• High SBP, wide pulse pressure, LVH are
  independent risk factors for CV morbidity
  mortality in ESRD
• Arterial stiffness is measured by aortic pulse
  wave velocity

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WHY IS CKD A RISK FACTOR FOR CVD

• Increased Prevalence of CVD risk factors
• Shared risk factors for dev of CVD and CKD
• HTN, DM
• CKD causes CVD risk factors levels to rise
• Reverse causation CVD causing CKD e.g. renal
  arterial disease, Heart failure
• CKD is an independent risk factor for CVD
• Proteinuria and decreased GFR

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INCREASED PREVALENCE OF CV RISK FACTORS

• Traditional risk factors as defined in the
  General population in the Framingham Study. These
  are highly prevalent in CKD
• Non-traditional risk factors
• a.? Prevalence as kidney function
  declines
• i.- Same found to be risk factors for
  general population
• Homocysteine, LP(a), Lip remnants
• b.Unique to CKD
• i. - Anaemia
• ii - Increased PTH
• iii - Increased Ca and Phosphate

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INCREASED PREVALENCE OF CV RISK FACTORS

• MDRD STUDY
• A cross sectional study with 1795 Patients with
  CRI
• Looked at traditional risk factors. They
  computed
• the Coronary Point Score (CPS) which
  predicts the probability of developing CAD over
  5-10yrs in individuals free from CVD
• The results showed that the coronary point score
  in patients with CKD was no different from those
  in the general population thus suggesting that
  the traditional risk factors could not
  sufficiently account for the burden of CVD in
  CKD.

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CVD RISK FACTORS

• TRADITIONAL
• Older age gt 55yrs for men 65yrs for women
• Male sex
• HTN
• Higher LDL cholesterol
• Lower HDL cholesterol
• DM
• Smoking
• Physical inactivity
• Menopause
• F History of CVD
• LVH

• NONTRADITIONAL
• Albuminuria
• Homocysteine
• LP(a) and apo (a) isoforms
• Lp remnants
• Anaemia
• Abnormal Ca/PO4 metabolism
• ECF overload
• Oxidative stress
• Inflammation (CRP)
• Malnutrition
• Thrombogenic factors
• Endothelial dysfunction

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INCREASED PREVALENCE OF CV RISK FACTORS

• Traditional risk factors
• ? HTN, DM , Smoking, Dyslipidemia
• HTN 90 in dialysis pts
• Cholesterol not as high as in general
  population
• In our centre mean total cholesterol was3.56
• HDL 1.24
• LDL 1.85
• TG 1.05
• DM most common cause of ESRD in US

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TRADITIONAL RISK FACTORS
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CARDIOVASCULAR RISK FACTORS UNIQUE TO CKD
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ANAEMIA

• Anaemia is associated with CVD in kidney disease
• Increases CO
• Limited myocardial O2 supply
• Decreases PR
• Volume overload
• LV dysfunction
• CHF

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CARDIORENAL ANAEMIA SYNDROME

• CKD

A vicious cycle
Anaemia
CHF
Each of the entities of CKD, CHF, and anaemia
precipitates the others
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ANAEMIA

• Hastens progression to ESRD
• Increases CV risks
• Increases the risks for retinopathy and blindness
• Increases the risk of death
• Increases the risk of developing renal failure
• Decreases quality of life

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ANAEMIA

• The bulk of the evidence supports the treatment
  of anaemia in patients with kidney disease.
• Nevertheless, research has demonstrated that
  anaemia is not adequately treated in CKD patients
  who are starting dialysis

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CALCIUM/PHOSPHATE

• Elevated Ca/ PO4 product has been associated with
  ? mortality
• ? vessel calcification
• PTH is a growth factor for SM cells ?sclerosis of
  major arteries ?LV dysfunction
• Endothelial Dysfunction in CKD caused by
  increased levels of ADMA, NOS inhibitor
• Increased oxidative stress- injure epithelium,
• Accumulation of oxLDL

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REVERSE CAUSATION

• Levin et al in Canada
• Multicentre observational study involving 313pts
• Mean GFR 36ml/min
• 46 had CVD to start
• Looked at probability of reaching RRT
• Pts with CVD ended up on dialysis more frequently
  RR 1.58

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DEFINITIONS OF PROTEINURIA
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CKD IS AN INDEPENDENT RISK FACTOR FOR CVD -
MICROALBUMINURIA

• Microalbuminuria is assoc. with a ? prevalence of
  traditional CVD risk factors in both DM non DM
  ?BP, dyslipidaemia, obesity, insulin resistance
• Microalbuminuria is assoc. with surrogates of
  CVD like ? CIMT in HTN pts, LVH ECG
  abnormalities in cross-sectional analysis.
• Microalbuminuria is assoc with a higher
  prevalence of
• clinical CVD
• Microalbuminuria was independently assoc. with
  
• increased risk for CVD in longitudinal
  studies.

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CKD IS AN INDEPENDENT RISK FACTOR FOR CVD

• In the HOPE Study, microalbuminuria
• Was assoc with 1.97-fold ?in CVD outcomes and
  2.15-fold ?in CVD death in diabetics
• Microalbuminuria in non diabetics was assoc. with
  a 61 increased risk of Stroke, MI and CVD deaths
  and 2 fold increased risk for all cause mortality
• Framingham study, there was significant
  independent assoc btw proteinuria and CVD death
  in women but not in men

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CKD IS AN INDEPENDENT RISK FACTOR FOR CVD

• Prevention of Renal and Vascular End Stage
  Disease (PREVEND) Study
• Community study in Netherlands
• Doubling of urine albumin concentration was
  assoc. with a 29 increase in RR for CVD
  mortality

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REASONS WHY ALBUMINURIA IS RISK FACTOR FOR CVD

• Is assoc with high prevalence of traditional risk
  factors
• May reflect generalised endothelial dysfunction,
  increased vascular permeability and abnormal of
  coagulation system
• May be assoc with markers of inflammation
• May indicate the severity of end organ damage

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CKD AND CVD OUTCOMES
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CKD AND CVD OUTCOMES
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MINOR RI OR ?GFR AS RISK FACTOR FOR CVD

• Studies across diff population show that CKD is
  an independent risk factor for CVD
• Framingham Heart Study
• 6233 adults mean age 54yrs
• CRI defined as Scr 136-265µmol/L in men 120-265
  µmol/L in women
• Follow up 15yrs.
• Mild RI was assoc with increase in all cause
  mortality in men but not in women

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REDUCED GFR OR MILD RENAL DYSFUNCTION

• Reduced GFR is associated with high prevalence of
  CVD risk factors, CVD surrogates, and Clinical
  CVD
• Reduced GFR is associated with CVD outcomes in
  several prospective studies, HOPE study, WISE,
  BARI study

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MINOR RI OR ?GFR AS RISK FACTOR FOR CVD

• ARIC Study
• 15 350
• Age 45-64
• Data stratified according to GFR
• In multivariate analysis minor renal dysfunction
  was risk factor for CV events and death
• 10ml/min /1.73m2 lower GFR was assoc with 5
  higher adjusted CV risk

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REASONS FOR THE ASSOCIATION OF ?GFR WITH CVD
OUTCOMES

• ? GFR is associated with ? level of
  non-traditional risk factors
• May be a marker of vascular disease
• May be a measure of residual confounding from
  traditional risk factors (HPT, dyslipidaemia)
• Subjects are less likely to receive medications
  or therapies such as ACEI, ASA,ß blockers,
  thrombolytics, PCI

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THERAPEUTIC OPTIONS

• Although many identifiable risk factors and
  therapeutic strategies exist for treatment of
  CVD, most of them are underused in the care of
  patients who have kidney disease.
• Early recognition of both CKD and attendant CVD
  is becoming the responsibility of the primary
  care physicians in conjunction with members of
  subspecialty teams (Nephrologists
  Cardiologists).

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THERAPEUTIC OPTIONS

• Data from the general population show the
  efficacy of treatment of traditional CVD risk
  factors, but few such data are available in
  kidney disease populations.
• Unfortunately, the lack of data may have
  contributed to less intensive treatment of risk
  factors in CKD patients.
• Despite the well-known protective effects of
  angiotensin-converting enzyme (ACE) inhibitors,
  lipid-lowering agents, and aspirin, their use is
  less than optimal in patients with CKD who have a
  high CVD risk.

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THERAPEUTIC OPTIONS

• Reports suggest that only 22 of dyslipidemic
  patients with CKD are taking lipid-lowering
  agents, 60 are using ACE inhibitors, and few are
  taking aspirin
• Similarly, blood pressure control, well known to
  both delay the progression of kidney disease and
  attenuate overall cardiovascular risk, is rarely
  achieved to within recommended target guidelines
  (lt130/80 mm Hg).

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THERAPEUTIC OPTIONS

• Tonelli colleagues
• 304 pts with CRI (mean GFR 30ml/min)
• Hyperlipidemia 43
• History of CVD 39
• ASA 27
• HMG Co A 18
• ß blockers 34

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THERAPEUTIC OPTIONS

• Early recognition of both CKD and attendant CVD
• Utilization of therapeutic strategies for
  treatment of CVD in the care of patients who have
  kidney disease.
• ACEI should be part of the BP-lowering regimen
  because their effect on BP, kidney function
  proteinuria
• Combination of ACEI ARBs have synergistic
  effects in the reduction of proteinuria and BP
  control

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THERAPEUTIC OPTIONS

• Control diabetes (Diabetes Control Complication
  Trials, UKPDS)
• Targets FBS 110mg/dl
• Post priandial 140mg/dl
• Statins lower elevated cholesterol TG and also
  have antiproliferative effect on smooth muscle
• AHA ACC recommend measurement of homocysteine
  (HCY) and empirical treatment with folic acid
  vitamin B12 vitamin B6 to achieve target HCY
  levels

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THERAPEUTIC OPTIONS

• Routine use of ACE inhibitors and aspirin is
  encouraged in all patients with CKD, and strict
  glycaemic and blood pressure control is
  recommended for optimal outcomes.
• In addition, patients should be screened and
  treated for risk factors particularly associated
  with kidney disease and CVD morbidity and
  mortality, including anemia, hyperphosphatemia,
  and hyperparathyroidism.

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THERAPEUTIC GOAL

• The goal of patient management is to reduce CV
  risk and slow down the progression of renal
  disease.

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THERAPEUTIC TARGETS

• Target BP lt 130/80 if proteinuria gt 1g lower to
  lt 120/70mmHg
• LDL lt2.5mmol/L
• Proteinurialt 200mg/g
• Stop smoking
• Regular exercise
• Metabolic control in diabetic
• Use of ACEI, ARB
• Statins for dyslipidaemia
• Treat anaemia with erythropoietin
• Treat calcium/ phosphate abnormality

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ALGORITHM FOR SCREENING FOR CKD AND REDUCING CVD
RISK

• One or more risk factors present Agegt60yrs, DM,
  HTN, Family Hx of kidney Dx

Obtain Scr and estimate kidney function using
formulae equations
Perform urinalysis to detect abnormal amounts of
protein
Kidney fxn abnormal (CCr lt 60ml/minor urinalysis
indicates microalbuminuria
Treatment goals Achieve BP control lt 130/80,
Reduce proteinuria, Treat dyslipidaemia, control
blood glucose, treat elevated homocysteine
Additional diagnostic tests Measure PTH, Ca, P,
HB
Abnormal results in diagnostic tests above
CONSULT NEPHROLOGIST
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FORMULAE EQUATIONS

• Cockcroft Gault formula
• Ccr (ml/min) 140 age (yrs) x wt (kg)
• PCr (mg/dl) x 72
• For women multiply by 85 (not 72) cant use in
  obese or oedematous patients
• MDRD equation
• GFR/1.73m2 (170 x (PCr mg/dL) exp -0.999)
  x (Age exp-0.176) x ((SUrea
• mg/dL)exp-0.170) x ((Albumin
  g/dL)exp0.318)
• 3. Abbreviated MDRD GFR, in mL/min per 1.73 m2
• 186.3 x ((serum creatinine) exp -1.154) x (Age
  exp -0.203) x (0.742 if female) x (1.21 if
  African American)
• where exp is the exponential.
• Calculators available on-line

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CONCLUSION

• There is no doubt that CVD and CKD are
  interconnected
• Thus primary care physicians physicians are urged
  to look for evidence of kidney dysfunction in
  patients with CVD and also heart disease or its
  risk factors in patients with kidney disease
• Targets have been clearly defined and are
  achievable for BP control, DM control lipid
  treatment

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CONCLUSION

• CVD accounts for more than 50 of all morbidity
  and mortality in CKD patients who have undergone
  RRT
• CVD is also prevalent in patients with mild and
  moderately severe kidney disease.
• To help address the elevated risks of these
  patients, primary care physicians need to
  maintain vigilance in
• (1) identifying patients who have CKD and
• (2) implementing strategies for reducing the
  prevalence of CVD in this population.

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CONCLUSION

• At each stage of CKD, physicians should evaluate
  for CVD risk factors and severity of CVD, then
  review possibility of reducing progression of
  both CVD and CKD
• Screen patients for mild CKD by measurement of
  Scr and microalbuminuria and calculate GFR using
  equations

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CONCLUSION

• Finally, physicians should be careful to avoid
  therapeutic nihilism in patients with kidney
  disease these patients are at highest risk of
  CVD and are likely to receive the greatest
  benefit from cardiovascular therapies.

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THANK YOU FOR YOUR ATTENTION