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CARDIOVASCULAR DISEASE AND CHRONIC KIDNEY DISEASE

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Title: CARDIOVASCULAR DISEASE AND CHRONIC KIDNEY DISEASE


1
CARDIOVASCULAR DISEASE AND CHRONIC KIDNEY
DISEASE
  • BY
  • CHRISTINA AMIRA MB.BS, M.Sc, FWACP, FISN
  • NEPHROLOGY UNIT LUTH

2
OUTLINE
  • Introduction
  • Epidemiology of CVD in CKD
  • Spectrum of CVD in CKD
  • Why is CKD a risk factor for CVD
  • Therapeutic options
  • Conclusion

3
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.

4
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

5
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

6
Approximate Prevalence of CVD
7
CARDIOVASCULAR MORTALITY IN THE GENERAL
POPULATION (NCHS) AND IN KIDNEY FAILURE PATIENTS
TREATED BY DIALYSIS OR TRANSPLANT (USRDS)
8
SURVIVAL RATE IN ESRD AND GENERAL POPULATION
9
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

10
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11
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

12
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

13
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14
PREVALENCE OF CARDIAC DISEASE IN DIALYSIS PATIENTS
15
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

16
INVESTIGATIONS OF ATHEROSCLEROSIS
  • Carotid intima-media thickness measured by B-mode
    ultrasonography
  • Coronary stress tests
  • Stress echocardiography
  • Radionuclear stress tests
  • Coronary angiographic

17
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

18
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

19
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

20
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

21
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.

22
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

23
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

24
TRADITIONAL RISK FACTORS
25
CARDIOVASCULAR RISK FACTORS UNIQUE TO CKD
26
ANAEMIA
  • Anaemia is associated with CVD in kidney disease
  • Increases CO
  • Limited myocardial O2 supply
  • Decreases PR
  • Volume overload
  • LV dysfunction
  • CHF

27
CARDIORENAL ANAEMIA SYNDROME
  • CKD

A vicious cycle
Anaemia
CHF
Each of the entities of CKD, CHF, and anaemia
precipitates the others
28
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

29
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

30
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

31
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

32
DEFINITIONS OF PROTEINURIA
33
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.

34
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

35
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

36
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

37
CKD AND CVD OUTCOMES
38
CKD AND CVD OUTCOMES
39
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

40
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41
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

42
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

43
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

44
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).

45
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.

46
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).

47
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

48
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

49
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

50
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.

51
THERAPEUTIC GOAL
  • The goal of patient management is to reduce CV
    risk and slow down the progression of renal
    disease.

52
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

53
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
54
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

55
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

56
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.

57
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

58
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.

59
THANK YOU FOR YOUR ATTENTION
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