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Welcome
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Please Note• Only SMS will be sent in future for CMEs• Postal / courier invitation will not be sent• Make sure you give us your Mobile No.• Confirm your participation by SMS• Reply to our SMS – To know you received• Make sure to send your name in your reply• Mark this No. as Dr Sarma 98940 60593• Bring along any other interested doctors• Give your e-mail ID. Create one, if not having
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Coronary Heart Disease (CHD) - Risk ApproachCoronary Heart Disease (CHD) - Risk ApproachDr.R.V.S.N.Sarma.
, M.D.
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Over view of this CMESession One• CHD Prevention is the Mantra • Over view of atherosclerosis• Risk Factors in detailSession Two• Patient evaluation - what tests to do• Risk scoring tools• Management of risk factors• Take home messages
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Very Alarming Indeed !!
• India is the Diabetic capital of the world
• Indians have one of highest rates of CAD
• Indian CAD is malignant in its onslaught
• Obesity in India is 3 fold compared to 1970
It is high time, all of us collectively do what
ever best is possible to prevent worsening !
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Exit 1
Exit 2
Cardio Vascular Diseases - CVD
All Other Causes of Death
At the end of the show
there are only two exits
50% 50%
Coronary Artery Disease - CAD
Cerebro Vascular Disease – CVD
Peripheral Vascular Disease – PVD
Reno Vascular Disease - MRD
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CHD – THE VOLCANO
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Treatment Advances in CAD
• Thrombolysis – Rx. Algorithms• ICU care – Defibrillators, Ventilators, IABP• Coronary Angiogram, CT Angio, STS• Primary PTCA – Stents, Elective PTCA• Rescue Angioplasty – Drug Eluted Stents• CABG – Beating Heart Surgery• MRV, Angiogenesis - Stem Cell Research• Remember, all the above are prohibitively
expensive and not accessible to all
1.Benefit the lucky few patients who survived until the hospital door
2.They are at best palliative; not curative
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CAD Scenario• Out 100 cases of MI
– 20 persons die – what ever we do or not ! - blessed ones !
– Of these – 14/20 (2/3) die even before they see us – lucky
– Pre hospital mortality – very sacred souls !!
– Remaining – 6/20 (1/3) – die in spite of us
– Some more may perish – because of us – iatrogenic causes
– 2 – 3% SCD – Sudden Cardiac deaths – exemplary !!!
– 1/3 cases of MI are silent MIs – ↑ Risk of death
– Among the 80 survivors – Reinfarction rates of > 30%
– Re-stenosis and failure of PTCA around 25%
– 10% of survivors – LVDF and CHF – chronic invalids
So, once we are a patient of MI, we are permanent patients +/- invalidity !!!
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How foolish we are all !!
Samudrae saanta kallole
Snatum itcchati mooda dhi
When the waves stop, then
Shall I bathe, thinks the fool
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How foolish we are all !!
Samudrae saanta kallole
Snatum itcchati mooda dhi
Samsaare saanta kallole
Jnanam icchati durmati
When the waves stop, then
Shall I bathe, thinks the fool
Sans turbulance I am when,
Then shall I strive for wisdom
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How foolish we are all !!
Samudrae saanta kallole
Snatum itcchati mooda dhi
Samsaare saanta kallole
Jnanam icchati durmati
Sareerae hrid rogapeeditae
Roginah kaankshati rakshati
When the waves stop, then
Shall I bathe, thinks the fool
Sans turbulance I am when,
Then shall I strive for wisdom
The CAD strikes my heart when
Then, shall I crave for prevention
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How to win the battle of CHD
• Coronary care units cannot answer all callers
• PTCA and CABG are not always feasible
• Are affordable by and available to only some
• Why make a valiant attempt to save the
myocardium after all the damage is done
• Why not protect our tiny blood pipes by
adopting preventive strategies at low cost !
Prevention is the only best weapon
Need to identify those at greater risk
Target them early to forestall damage
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Prevention is the key
1. CVD - Is it preventable ?? - Very much Yes.
2. The risk assessment must start very early
3. At the age of 20 years itself
4. Healthy life style and hearty eating habits
5. Regular physical exercise from young age
6. Maintaining ideal weight and hour glass waist
7. Avoiding tobacco and reducing alcohol
8. There are enough guidelines – Implementation ?
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15The Progressive Development of Cardiovascular Disease
End stage Heart DiseaseEnd stage Heart Disease
Congestive Heart FailureCongestive Heart Failure
Ventricular DilationVentricular Dilation
RemodelingRemodeling
Arrhythmia & Muscle LossArrhythmia & Muscle Loss
Myocardial InfarctionMyocardial Infarction
Myocardial IschemiaMyocardial Ischemia
CADCAD
AtherosclerosisAtherosclerosis
Endothelial DysfunctionEndothelial Dysfunction
Risk FactorsRisk Factors
Coronary ThrombosisCoronary Thrombosis
Intervene here}
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Post MI/Angina
Other Atherosclerotic Manifestations
Subclinical Atherosclerosis
Multiple Risk Factors
Low Risk
Secondary
Prevention
PrimaryPrevention
Courtesy of CD Furberg.
Continuum Risk for a CHD Event
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Note the individual Endothelial Cells
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Endothelial Apoptosis
Normal Apoptosed
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Coronary Coronary Heart Heart
DiseaseDisease
Endothelial Endothelial DysfunctionDysfunction
NO NO ↑ ↑ Inflammation Inflammation ↑ Thrombosis↑ Thrombosis
The Universal Damage
GenesGenes
Coronary Risk Factors
The Essential Components
The Nature (Genetic) conspires with the Nurture (Acquired)
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(L-NMMA) = N(G)-mono-methyl-L-arginine
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22Regulatory Functions of the EndotheliumNormal Dysfunction
Vasodilation VasoconstrictionNO, PGI2, EDHF,
BK, C-NPROS, ET-1, TxA2,
A-II, PGH2
Thrombolysis Thrombosis
Platelet Disaggregation
NO, PGI2
Adhesion Molecules
CAMs, P,E Selectins
Antiproliferation
NO, PGI2, TGF-, Hep
Growth Factors
ET-1, A-II, PDGF, ILGF, ILs
Lipolysis Inflammation
ROS, NF-B
PAI-1, TF-α, Tx-A2tPA, Protein C, TF-I, vWF
LPLVogel R
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Progression of Atherosclerosis
24Role of LDL in InflammationRole of LDL in Inflammation
Steinberg D et al. N Engl J Med 1989;320:915-924.
Endothelium
Vessel LumenLDL
LDL readily enter the artery wall where they may be modified
LDL
Intima
Modified LDL
Modified LDL is Proinflammatory
Hydrolysis of Phosphatidylcholineto Lysophosphatidylcholine
Other Chemical Modifications
Oxidation of Lipidsand ApoB
Aggregation
Nitric Oxide (NO) Policing the Endothelium
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LDL
LDL
Modified LDL Stimulate Expression Modified LDL Stimulate Expression of MCP-1 in Endothelial Cellsof MCP-1 in Endothelial Cells
Navab M et al. J Clin Invest 1991;88:2039-2046.
Endothelium
Vessel Lumen
Intima
Monocyte
Modified LDL
MCP-1
Monocyte Chemotactic Protein 1 – MCP 1
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LDL
LDL
Differentiation of Differentiation of Monocytes into MacrophagesMonocytes into Macrophages
Steinberg D et al. N Engl J Med 1989;320:915-924.
Endothelium
Vessel Lumen
Intima
Monocyte
Modified LDL
Modified LDL PromoteDifferentiation ofMonocytes intoMacrophages
MCP-1
Macrophage
Monocyte Chemotactic Protein 1 – MCP 1
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LDL
LDL
Modified LDL Induces Macrophages to Release Modified LDL Induces Macrophages to Release Cytokines - Stimulate Adhesion MoleculeCytokines - Stimulate Adhesion Molecule
Nathan CF. J Clin Invest 1987;79:319-326.
Endothelium
Vessel LumenMonocyte
Modified LDL
Macrophage
MCP-1
AdhesionMolecules
Cytokines
Intima
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Endothelium
Vessel Lumen
MCP-1
E-Selectin
Charo IF. Curr Opin Lipidol 1992;3:335-343.
Recruitment of Blood Monocytes by Recruitment of Blood Monocytes by Endothelial Cell Adhesion MoleculesEndothelial Cell Adhesion Molecules
Intima
VCAM-1ICAM-1
StickingMonocyte Rolling
Transmigration
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LDL
LDLEndothelium
Vessel LumenMonocyte
Macrophage
MCP-1
AdhesionMolecules
Steinberg D et al. N Engl J Med 1989;320:915-924.
Macrophages Express Receptors Macrophages Express Receptors that take up Modified LDLthat take up Modified LDL
Foam Cell
Modified LDL Taken up by Macrophage
Intima
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LDL
LDLEndothelium
Vessel LumenMonocyte
Macrophage
AdhesionMolecules
Macrophages and Foam Cells Express Macrophages and Foam Cells Express Growth Factors and ProteinasesGrowth Factors and Proteinases
Foam Cell
IntimaModified
LDLCytokines
Cell ProliferationMatrix Degradation
Growth FactorsMetalloproteinases
Ross R. N Engl J Med 1999;340:115-126.
MCP-1MCP-1
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Endothelium
Vessel LumenMonocyte
Macrophage
MCP-1MCP-1AdhesionMolecules
The Remnants of VLDL and The Remnants of VLDL and Chylomicrons are also ProinflammatoryChylomicrons are also Proinflammatory
Foam Cell
IntimaModifiedRemnantsCytokines
Cell ProliferationMatrix Degradation
Doi H et al. Circulation 2000;102:670-676.
Growth FactorsMetalloproteinases
Remnant Lipoproteins
Remnants
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Pathogenesis of ACS
Non-Vulnerable Atherosclerotic
Plaque
Non-Vulnerable Atherosclerotic
Plaque
Vulnerable Atherosclerotic
Plaque
Vulnerable Atherosclerotic
Plaque
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Normal
FattyStreak
Fibrous
Plaque
Occlusive Atherosclerot
icPlaque
PlaqueRupture/Fissure &
Thrombosis
MI
Stroke
Critical Leg Ischemia
Clinically Silent
Coronary
Death
Increasing Age
Effort AnginaClaudication
Unstable
Angina
Courtesy of P Ganz.
Atherosclerosis A Progressive Process
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Libby P. Lancet. 1996;348:S4-S7.
Media
–T lymphocyte
– Macrophagefoam cell (tissue factor+)– “Activated” intimal SMC (HLA-DR+)–Normal medial SMC
Fibrouscap
Intima
Lipidcore
Lumen
The Anatomy of Atherosclerotic Plaque
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Davies MJ. Circulation. 1996;94:2013-2020.
Fissures inthe fibrous cap
The Matrix Skeleton of UnstableCoronary Artery Plaque
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CHD Risk Factors – So Many ?
• Malaria – One causative parasite• Tuberculosis – One definite bacterium • HIV and AIDS – One deadly virus• But for CHD – No one specific cause
– It is a non communicable disease
– It is multi factorial in its causation
– The more ignorant we are about the causation,
the more risk factors we seek and try to explain
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CHD – Makers and Markers
The Makers – Risk Factors– Non Modifiable – The tough six– Modifiable – The conventional six– Modifiable – The contributing six
The Markers – Surrogate tests– We rarely care – The simple six – We barely know – The complex six– We hardly need – The experimental six
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CHD Risk Factors - Makers
• If non modifiable – why study them ?
• Non Modifiable – The Tough Six– Age– Gender– Ethnicity– Family H/o of premature CHD– Phenotype B– Type A personality (partly modifiable)
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CHD Risk Factors - Makers
• If modifiable – why not control them ?
• Modifiable – The Conventional Six– Diabetes Mellitus– Dyslipidemia– Hypertension– Smoking / tobacco– Over weight and Obesity– Physical inactivity
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CHD Risk Factors - Makers
• Modifiable – The contributing six– hs-CRP– Lp(a)– sLDL– Endothelial dysfunction– Apo B / Apo A1 ratio– Homocysteine
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CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Dip stick test– LVH – By Echocardiography, ECG, CXR
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CHD Risk Factors - Markers
• We barely know & test – The complex six– ABPM – Dippers & Non Dippers– FMD – Brachial Flow Mediated Dilatation– PCOS – Polycystic Ovarian Syndrome - USG– CIMT – Carotid Intima Media Thickness– FFAG – Florescence Fundus Angiography– STS – Stress Thallium Scan – for perfusion study
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CHD Risk Factors - Markers
• We hardly need to test – The experimental six– C Peptide – Measure of Insulin Resistance– Uric Acid – Surrogate for Inflammation– Fibrinogen – Surrogate for coagulability– PAI 1 – Plasminogen Activator Inhibitor 1– Inflam. markers – sICAM, ICAM. SAA, IL-6, MMP
– Sub fractions – of LDL and HDL, IVUS
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1. Diabetes Mellitus2. Peripheral Vascular Disease (PVD)3. Framingham risk score of > 20%
4. Carotid artery disease – • Stroke, TIA• > 50% Narrowing, Carotid Bruit
5. Abdominal Aortic Aneurysm (AAA)
CHD Risk Equivalents
Adult Treatment Panel III. NIH publication 01-3095.
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Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
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Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
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Age and CAD
• CHD risk increases as age advances
• Men > 45 and women > 55 – high risk
• CAD-I is 10 years younger
• Men suffer CAD 10 years early
• Increased longevity – Aging population
• Increased duration of risk exposure
• Multiplicity of risk factors occurs
• Treatment responses are blunted
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Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
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Gender and CAD
• CAD is ‘Disease of the Men’ – a myth
• Women CAD presents atypically
• Silent MI more common; 10 yrs later
• First attack mortality more common
• CAD deaths are twice those from all Ca
• DM is a more powerful risk factor for ♀
• ↑ TG, LDL and ↓ HDL are common in ♀
• Physical inactivity, Abd. obesity is more
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Indian Women are Men !!
• Indian women compete with men in CAD rates• Women CADI is one of the highest on the globe• Pre-menopausal women enjoy protection, but• This estrogen related protection is annulled
• If the women has Lp(a) > 30 mg%• If she has developed T2DM, IGT, IFG, PCOS, GDM• If she has central adiposity (who is non cylindrical?)• If she is a smoker (in rural India women smoke)
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CVD Mortality Trends (1979-1999)
American Heart Association. 2002 Heart and Stroke Statistical Update. 2001
Dea
ths
in T
ho
usa
nd
s
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Death From Breast Cancer or Heart Disease in Women
US Vital Statistics, 1990
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WISE Study - Review of Ischemic Heart Disease in Women
Shaw LJ et al. J Am Coll Cardiol. 2006;47(suppl 3):S4-S20.
Perc
en
t W
ith
O
bstr
ucti
ve C
AD
Age (years)
11 12 12
2117
21
36
2521
60
36 34
0
10
20
30
40
50
60
70
80
90
100
35-45 y 45-55 y 55-65 y 65-75 y
Typical angina
Atypical angina
Non-angina chest pain
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Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
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Ethnic Differences
• Japanese and Chinese lowest rates
• Whites or Caucasians lower rates
• Hispanics intermediate rates
• Asian Indian higher rates
• Afro-Caribbeans (negroid) highest rates
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Coronary Artery Disease in Indians
• CADI strikes early !
• CADI strikes hard !!
• CADI strikes almost any one !!!
• CADI strikes unexpectedly !!!!
• Conventional RF can’t explain it away
• CADI is malignant in its onslaught.
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CAD Mortality
Age Adjusted mortality for 100,000 population per year in 35-74 age.
INDIA
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The CADI Volcano• We are in the middle of the wave of CAD epidemic
• This CADI epidemic will peak by 2015
• 50% deaths in India are CVD deaths.
• CADI will overtake Infectious diseases in morbidity too
• By 2015 CADI will be six times more than the West
• CADI will be 20 times more than the Chinese, although
• Our culture shuns smoking, 50% are vegetarians and
• We lack many of the classic risk factors for CAD
• Remember CADI is preventable & predictable
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The CADI studyOnly 14% of Asian Indian males & 5% of females have Optimal HDL
Prevalence of coronary heart disease and its risk factors in Asian Indians
Atherosclerosis , Rosemount , IL Oct 6-11 , 1991
120
86
100
80604020
0 14
95
5
Asian Indian males
Asian Indian females
% with < optimal level of HDL-C
% with an optimal HDL-C levels
In Indian patients with CAD, High TG levels are
found more often than high cholesterol levels.
Journal, Ind. Acad. clin. med vol 2 Jul-Sept 2001
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Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
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Family Hx. of premature CAD
• H/o CAD in the first degree relatives
• CAD in male relative before the age 55
• CAD in female relative before the age 65
• Aggressive approach to Rx. of risk factors
• Look for non-conventional risk factors
• Lp(a), sLDL, ↓ HDL the main culprits
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Nasir K et al. Circulation. 2004;110:2150-2156.
Ag
e-ad
just
ed p
reva
len
ce (
%)
of
mo
der
ate
calc
ific
atio
n(C
AC
Sco
re >
100)
P<0.001 across categories.
Coronary Artery Calcification(CAC) and CHD Family History
1116
23 22 17
23
32 30
24
33
4441
35
47
59 5660
50
40
30
20
10
0
No riskfactors
1 risk factor 2 risk factors
3 risk factors
No family history
Parental family history
Sibling family history
Both
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Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
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Phenotype B and CAD
• There are 2 phenotypes of lipoproteins
• Phenotype A and Phenotype B
• Phenotype A is atheroprotective
• They have high HDL and low TG
• Atherogenic lipoprotein Phenotype B - ALP
• They have low HDL and high LDL, TG
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The interaction between our current genotype
and our present day life style and eating habits
places us at very high risk of having this
phenotype B that makes us highly susceptible
to atherosclerosis.
Journal of Internal Medicine 2003:254(2):114-25
Nature conspires with Nurture
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• This ALP or phenotype B is present and seen most often in• Insulin resistant individuals• Diabetics• Obese persons• Sedentary life style
• More prevalent in India (40% of Indians)• Apo B ÷ Apo A1 will be > 1.5
Phenotype B or ALP
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68Characteristics of LDL
Phenotype B
• Common heritable trait
• Frequency: 25%–30% of population
• Autosomal dominant inheritance
• Reduced penetrance in males 20 yr and in premenopausal females
• Associated with
• Increased TG, VLDL, and IDL and ↓ HDL2
• Threefold increase in MI risk
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0
10
20
30
40
50
60
70
80
90
100
20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 500
Phenotype A
Phenotype B
% Cumulativefrequency
TG (mg/dL)
Cumulative Distribution of TG Levels Phenotypes A and B
Austin M et al. Circulation. 1990;82:495-506.
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20 25 30 35 40 45 50 55 60 65 70 75 80
Phenotype A
Phenotype B
% Cumulativefrequency
HDL-C (mg/dL)
100
90
80
70
60
50
40
30
20
Cumulative Distribution of HDL Levels Phenotypes A and B
Austin M et al. Circulation. 1990;82:495-506.
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Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
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Type A Personality and CAD
• TABP – Type A behaviour pattern
• Impatience and time urgency
• Strong desire to achieve more in less time
• Free floating hostility – Ever irritated
• Unwarranted anger, Unable to relax
• Have many ‘to do lists’ that never end
• Highly competitive, Very ambitious
• Grinding their teeth, clinching the fists
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Personality
Type B Person
Type A Person
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Modifiable Risk factors – BIG 6
1. Diabetes Mellitus
2. Dyslipidemia
3. Hypertension
4. Smoking
5. Over weight and Obesity
6. Physical inactivity
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Additive Effect
SBP >160
Dyslipidemia
Smoking
4
3
5
4.5
16
With DM all risks are doubledWith DM all risks are doubled
Relative risk of CHD
1.6
6
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76CHD Risk Factors - PROCAM Study
Risk factor Relative risk P ValueRisk factor Relative risk P Value
Smoking 2.3 0.001LDL cholesterol (mg%)
> 100 but < 160 1.9 0.01> 160 4.3 0.001
Hypertension (SBP > 140; DBP > 90) 1.8 0.001HDL cholesterol (mg%)
40 to 55 1.7 0.01< 40 2.7 0.001
Triglycerides (mg%)105- 167 1.6 0.01>167 2.6 0.001
Fasting blood glucose (mg%)110 - 126 1.4 0.05> 126 1.9 0.01
Family history of MI 1.4 0.05
Smoking 2.3 0.001LDL cholesterol (mg%)
> 100 but < 160 1.9 0.01> 160 4.3 0.001
Hypertension (SBP > 140; DBP > 90) 1.8 0.001HDL cholesterol (mg%)
40 to 55 1.7 0.01< 40 2.7 0.001
Triglycerides (mg%)105- 167 1.6 0.01>167 2.6 0.001
Fasting blood glucose (mg%)110 - 126 1.4 0.05> 126 1.9 0.01
Family history of MI 1.4 0.05
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Multiple Risk Factors: ‘Gang Up’The total severity of multiple low-level risk factors often exceeds that of a single severely elevated risk factor.
8%
Grundy SM et al. J Am Coll Cardiol 1999;34:1348-1359.
BP 165/95 mm Hg BP 165/95 mm Hg Age 56 years
BP 165/95 mm HgAge 56 years
LDL-C 155 mg/dL
BP 165/95 mm HgAge 56 years
LDL-C 155 mg/dL Smoker
13%
19%
27%
0
5
10
15
20
25
30
Mean c
um
ula
tive r
isk
%
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Modifiable Risk factors – BIG 6
1. Diabetes Mellitus
2. Dyslipidemia
3. Hypertension
4. Smoking
5. Over weight and Obesity
6. Physical inactivity
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DM and CAD
• Normal values - FBG 100; PPBG 140• Only oral Fasting and Post Glucose test• No half hourly blood sampling• Nothing as full GTT etc. Measure HbA1c• Pre Diabetes
• IFG – FBG > 100 to 125 • IGT – PPBG > 140 to 199
• Diabetes• FBG 126 or more; PPBG 200 or more
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Public AwarenessPublic Awareness
A survey of people with Diabetes Findings
68% do not consider cardiovascular disease to be complication of diabetes
50%+ don’t feel risk for heart condition or stroke
60% don’t feel at risk for high blood pressure or cholesterol
Awareness lowest among elderly, minorities
A survey of people with Diabetes Findings
68% do not consider cardiovascular disease to be complication of diabetes
50%+ don’t feel risk for heart condition or stroke
60% don’t feel at risk for high blood pressure or cholesterol
Awareness lowest among elderly, minorities
2
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Diabetes – CAD FactsDiabetes – CAD Facts
More than 65% of all deaths in people with diabetes are caused by cardiovascular disease.
Heart attacks occur at an earlier age in people with diabetes and often result in premature death.
More than 65% of all deaths in people with diabetes are caused by cardiovascular disease.
Heart attacks occur at an earlier age in people with diabetes and often result in premature death.
3
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Diabetes – CAD FactsDiabetes – CAD Facts
Up to 60% of adults with diabetes have high blood pressure.
Nearly all adults with diabetes have one or more cholesterol problems, such as:
high triglycerides
low HDL (“good”) cholesterol
high LDL (“bad”) cholesterol
Up to 60% of adults with diabetes have high blood pressure.
Nearly all adults with diabetes have one or more cholesterol problems, such as:
high triglycerides
low HDL (“good”) cholesterol
high LDL (“bad”) cholesterol
4
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The Good News… The Good News…
By managing the ABCs of diabetes, people with diabetes can reduce their risk for heart disease and stroke.
A stands for A1C
B stands for Blood pressure
C stands for Cholesterol
By managing the ABCs of diabetes, people with diabetes can reduce their risk for heart disease and stroke.
A stands for A1C
B stands for Blood pressure
C stands for Cholesterol
5
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Atherosclerosis and IR and DM
HypertensionHypertension
ObesityObesity
HyperinsulinemiaHyperinsulinemia
DiabetesDiabetes
HypertriglyceridemiaHypertriglyceridemia
Small, dense LDLSmall, dense LDL
Low HDLLow HDL
HypercoagulabilityHypercoagulability
InsulinInsulinResistanceResistance
InsulinInsulinResistanceResistance AtherosclerosisAtherosclerosisAtherosclerosisAtherosclerosis
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0
1
2
3
CHD mortality
(per 1,000)
Fontbonne AM et al. Diabetes Care. 1991;14:461-469.
29 30-50 51-72 73-114 115
Quintiles (pmol) of fasting plasma insulin
P<0.01
CHD Mortality and Hyperinsulinemia
Paris Prospective Study (n=943)
87
Subclinical Atherosclerosis
Atherosclerotic Clinical Events
Hyperglycemia
AGE Oxidative
stress
Inflammation
IL-6 CRP SAA
Infection
Defensemechanisms
Pathogen burden
Insulin Resistance
HTN Endothelial dysfunction
Dyslipidemia
LDL TG HDL
Thrombosis
PAI-1 TF tPA
Disease Progression
Biondi-Zoccai GGL et al. J Am Coll Cardiol. 2003;41:1071-1077.
Progression to atherosclerotic clinicalevents in patients with Diabetes
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88
DM and CAD - CUPS
Mohan V et al CUPS…
89
DM and CVE : LIFE study
Increased Risk of Primary Endpoint
23
46
0
10
20
30
40
50
60
Primary EndpointRat
e pe
r 10
00 P
atie
nt-Y
ears
Non-DiabeticDiabetic
2530
0
10
20
30
40
50
60
Primary EndpointRat
e pe
r 10
00 P
atie
nt-Y
ears
Non-ISHISH(n=1195)
(n=7998)
(n=1326)
(n=7867)
Relative Risk: 2.0 1.2
90
Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
*P<0.001; 4-year results
11%
23%
0
5
10
15
20
25
Intervention Control
(n=265)
(n=257)
Diabetes (%)
Finnish Diabetes Prevention StudyReduction in Risk for Diabetes
91
• Elevated TG
• Elevated VLDL
• Reduced HDL
• Increase in SD-LDL
• Decrease in Apo A I
• Increase in Apo B
• Ratio of Apo B /Apo A 1 > 1.5
Dyslipidemia in IR and DM
All Diabetics must be given STATIN
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92
Modifiable Risk factors – BIG 6
1. Diabetes Mellitus
2. Dyslipidemia
3. Hypertension
4. Smoking
5. Over weight and Obesity
6. Physical inactivity
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93
Dyslipidemia and CAD
• ‘Good’, ‘Bad’, ‘Ugly’ and ‘Deadly”• Total Cholesterol – TC 200 mg• Triglycerides – TG 150 mg• Low density lipoprotein LDL 100 mg• High density lipoprotein HDL 50 mg (40 ♂)• Lipoprotein (a) or Lp(a) 25 mg• Apo B ÷ Apo A 1 (Normal) < 1.5
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94
Dyslipidemia and CAD
• Non HDL = TC – HDL = 200 – 50 = 150• TC ÷ HDL = 200 ÷ 50 = 4 (Often used)• TG ÷ HDL = 150 ÷ 50 = 3 (Imp. Indians)• LDL ÷ HDL = 100 ÷ 50 = 2 (Often used)• LTI – Lipid Tetrad Index (New one 2005)
[TC x TG x Lp(a) ] 200 x 150 x 25
HDL 50
= 15000; Normal is up to 10 K
10 K to 20 K is boarder line
More than 20 K is abnormal
=
95Structure of LDLStructure of LDL
Murphy HC et al. Biochemistry 2000;39:9763-970.
Hydrophobic CoreHydrophobic Core of Triglyceride of Triglyceride and Cholesteryl and Cholesteryl EstersEsters
apoBapoB
Surface Surface Monolayer of Monolayer of Phospholipids Phospholipids and Free and Free CholesterolCholesterol
96Structure of HDLStructure of HDL
Rye KA et al. Atherosclerosis 1999;145:227-238.
Hydrophobic CoreHydrophobic Core of Triglyceride of Triglyceride and Cholesteryl and Cholesteryl EstersEsters
apoA-IIapoA-II
Surface Surface Monolayer of Monolayer of Phospholipids Phospholipids and Free and Free CholesterolCholesterolapoA-IapoA-I
97Risk Factors for Future Cardiovascular Risk Factors for Future Cardiovascular Events: WHSEvents: WHS
Relative Risk of Future Cardiovascular Events0
Ridker PM et al. N Engl J Med 2000;342:836-843.
Lipoprotein(a)
Homocysteine
IL-6
TC
LDL-C
sICAM-1
SAA
Apo B
TC:HDL-C
hs-CRP
hs-CRP + TC:HDL-C1.0 2.0 4.0 6.0
98
Lipid Profile in Young Indian Patients with Angiographically Proven CHD
Parameter % Patients
Total cholesterol >200 mg/dl 54.3
Triglyceride >200 mg/dl 56.1
HDL <35 mg/dl 59.6
Lp(a) >30 mg/dl 61.4
n=57; age <40 yrsMishra et al (Cuttack)
Indian Heart J 2001; 53: Abst 60
99
Trends in Total Cholesterol* for US Adults, 1960-1962 to 1999-2002
200
210
220
230
240
250
260
270
1960-1962 1971-1974 1976-1980 1988-1994 1999-2002
Men (aged 60-74)
Women (aged 50-59)
Women (aged 60-74)
†
†
†
*Mean values. †P<0.001 for difference between NHANES III (1988-1994) and NHANES 1999-2002.
Carroll MD et al. JAMA. 2005;294:1773-1781.
TC
(m
g/d
L)
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100
RF in CAD – PROCAM Study
Odds Ratio for CAD when LP(a) > 20 mg
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101
0
2
4
6
Mean annual CHD
mortality rate/1,000
Adapted from Fontbonne A et al. Diabetologia. 1989;32:300-304.
Cholesterol (mg/dL)
220 >220 220 >220
TG 123 mg/dL TG 123 mg/dL
Fasting TG and Risk for CHDDeath: Paris Prospective Study
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102
Indian Dyslipidemia
A. Isolated High Lp(a) 32.90%B. Isolated low HDL 21.35%C. Isolated high TG 10.45%
IHJ, 2000, 52: 173-177Am J Med, 1998, vol 105(1A), 48S-56S
↑ Lp(a)
↓HDL
↑TG
The Triad
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103
Diabetic Dyslipidemia
IHJ, 2000, 52: 173-177Am J Med, 1998, vol 105(1A), 48S-56S
↑sLDL
↓HDL
↑TG
The Triad
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104
Atherogenic lipid profile
IHJ, 2000, 52: 173-177Am J Med, 1998, vol 105(1A), 48S-56S
↑sLDL
↓HDL
↑Lp(a)
The Triad
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105
LIVER
Reverse Cholesterol Transport
MF in Vascular Endothelium
Free Chol.
L CAT Enzyme
UECEC
HDL
HDL scavenges LDL out from EM
HDL Prevents LDL oxidation in EM
HDL is anti-inflammatory at EM
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106TGs Predict CAD Risk
Independent of TC and HDL
0 1 2 3 4 5 6 7 8 9 10
Definite Type III (P<0.0001)
TG 800+, any HDL (P=0.16)
TG 200-799, HDL <40 (P<0.0001)
TG <200, HDL <40 (P<0.0001)
TG 200-799, HDL 40+ (P<0.000)
TG <200, HDL 40+
Odds Ratio
Hopkins PN et al. J Am Coll Cardiol. 2005;45:1003-1012.
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107How does ↑ ↑ TGincrease CHD Risk ?
• Accumulation of chylomicron remnants• Accumulation of VLDL remnants• Generation of small, dense LDL-C• Association with low HDL-C• Increased coagulability
plasminogen activator inhibitor (PAI-1) factor VIIc• activation of prothrombin to thrombin
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108
Modifiable Risk factors – BIG 6
1. Diabetes Mellitus
2. Dyslipidemia
3. Hypertension
4. Smoking
5. Over weight and Obesity
6. Physical inactivity
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109
Hypertension and CAD
• Normal BP is < 120/80• Pre hypertension – SBP 120 to 139
DBP 80 to 89• ISH – DBP normal, SBP > 160• Pulse Pressure is more predictive CVD• 90 % have ISH by 60 years of age• HT is strong risk factor for CVA• 90% of HT is primary or essential
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110
0
5
10
15
20
00 100100 200200 300300
5 Y
ea
r R
isk
(%
)
Stroke
Myocardial Infarction
Systolic Blood Pressure (mmHg)
HT- RR of stroke and MIHT- RR of stroke and MI
Brown, M.J. Lancet 2000; 355: 659 - 660
20 40 60 80 120 140140 160 180 220 240 260 280
Normotensives Hypertensives
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111
Is SBP more dangerous or DBP ?
112HT – CV Mortality
Kannel WB Euro Heart J 1992;13(Suppl G):34-42.
29
14
65
35
0
10
20
30
40
50
60
70
Men Women
Age
-Adj
uste
d R
ate/
1000
NormotensiveHypertensive
The Framingham Heart Study
Risk Ratio 2.2 2.5
113
Adapted from MacMahon S, Rodgers A. Clin Exper Hypertension 1993;15(6):967-978.
0
100
200
300
400
500
600
Stroke CHD VascularDeaths
Treatment of HT – CV Mortality
5 Randomized Trials in 12,483 Elderly Hypertensives
% Reduction in odds: 19%p<0.05
34%p<0.001
23%p<0.001
346383
288
438 Treatment
Control
Tot
al N
umbe
r of
In
divi
dual
s A
ffec
ted
438494
Overall BP DifferenceSystolic: 15 mm HgDiastolic: 6 mm Hg
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114
Modifiable Risk factors – BIG 6
1. Diabetes Mellitus
2. Dyslipidemia
3. Hypertension
4. Smoking
5. Over weight and Obesity
6. Physical inactivity
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115
Smoking – The Devil
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116
THE DEADLIEST DEVILTHE DEADLIEST DEVIL
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117
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118
WOMEN SMOKERS
PASSIVE SMOKERS
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119
TENDER AGE GROUPS
COLLEGE STUDENTS
Intense cause for concern
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120
AND HONESTLYAND HONESTLY
Tell me what harm smoking
does not cause ??
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121
Ezzati M et al. Circulation. 2005;112:489-497.
Smoking-RelatedCV Mortality in Year 2000
Million
s o
f A
du
lts A
ged
>30 Y
ears
Total Men Women
World Industrialized
Countries
Developing
Countries
Total Men Women Total Men Women
1.62
1.17
0.45
0
0.5
1
1.5
2
0.96
0.65
0.3
0
0.5
1
1.5
2
0.67
0.52
0.15
0
0.5
1
1.5
2
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Tobacco Smoke and Metabolic Syndrome in Adolescents
ETS = environmental tobacco smoke.Weitzman M et al. Circulation. 2005;112:862-869.
Perc
en
t W
ith
MetS
1.2%
5.4%
8.7%
0
1
2
3
4
5
6
7
8
9
Nonexposed ETS Exposed Active Smokers
P<0.001n=2,273
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123
Modifiable Risk factors – BIG 6
1. Diabetes Mellitus
2. Dyslipidemia
3. Hypertension
4. Smoking
5. Over weight and Obesity
6. Physical inactivity
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124
Obesity and Sedentary Life
• Two important culprits• Physical inactivity• Heart unhealthy dietary habits
• These give rise to over weight & obesity• This causes insulin resistance• Lipid and other metabolic abnormalities• Metabolic syndrome sets in
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125
Our cut off values !
For Indians• BMI < 23 Normal• BMI of 23 to 24.9 Over weight• BMI of > 25 Obesity
• WC for ♂ Normal 90 cm (36”)• WC for ♀ Normal 80 cm (32”)
Central adiposity causes ↑IL6, which ↑hepatic hs-CRP
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126
Television watching became even more convenient with Sony’s introduction of a new remote controlled remote control – Tokyo News line
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127
This is how we walk the dog !
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128
With in no time !!
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129
Metabolic Syndrome - Characteristics
HypertriglyceridemiaLow HDL-cholesterolElevated apolipoprote in BSmall, dense LDL particlesInflammatory profile
Insulin resistanceHyperinsulinem iaGlucose intoleranceImpaired fibrino lysisEndothelial dysfunction
These features can lead to type 2 diabetes,
hypertension and cardiovascular disease
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130
Metabolic Syndrome
InsulinInsulin
ResistanceResistance
Hyper-Hyper-
insulinaemiainsulinaemia
HypertensionMicroalbuminuria
Centralobesity
Triglycerides
HDLcholesterol
Small dense LDL
Hyperuricemia
Prothrombotic state (fibrinogen,Factor VIIa,
fibrinolytic activity)
Impaired Glucose Tolerance
Type 2 DiabetesDiabetes Care 1998;21(2):310–314.
Williams G, Pickup JC. Handbook of Diabetes. 2nd Edition, Blackwell Science. 1999.
200% CVD Risk
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131
Risk Factor Defining Level
Abdominal Obesity Waist Circumference
Men >90 cm (>36 in)
Women >80 cm (>32 in)
Triglycerides >150 mg/dl
HDL cholesterol
Men <40 mg/dl
Women <50 mg/dl
Blood pressure >130/>85 mmHg
Fasting glucose >110 mg/dl
Metabolic Syndrome, Syndrome X, Deadly Quartet, Reaven’s Syndrome
NCEP guidelines 2001 (WHO Modified for Indians)
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132
Accelerated atherosclerosis
Clinical diabetes
Hyperinsulinemia Impairedglucose
tolerance
HypertriglyceridemiaDecreased HDL-C
Essentialhypertension
Insulin resistance
Insulin Resistance and Atherosclerosis relationship
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133
Hypertension Obesity Hyper-insulinemia Diabetes
Hypertri-glyceridemia
Small,dense LDL
Low HDL Hypercoagu-lability
Atherosclerosis
Insulin Resistance
Interrelation between Atherosclerosisand Insulin Resistance
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134
Acanthosis Nigricans
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135
Acanthosis Nigricans
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136
Acanthosis Nigricans
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Composite CIMT With Metabolic Syndrome in Young Adults
*National Cholesterol Education Program definition. Tzou WS et al. J Am Coll Cardiol. 2005;46:457-463.
Com
posit
e U
ltra
sou
nd
Caro
tid
Inti
ma-M
ed
ia T
hic
kn
ess,
mm
0.64
0.66
0.68
0.70
0.72
0.74
0.76
0.78
0.80
0 1 2 3 4
Number of Metabolic Syndrome Components*
r=0.997, Ptrend <0.001
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138
Metabolic Syndrome and10-Year CVD Risk
*National Cholesterol Education Program definition.Dekker JM et al. Circulation. 2005;112:666-673.
1.98
1.18
2.25
0.76
1.882.05
1.91
1.68
0
0.5
1
1.5
2
2.5
Mortality Fatal CVD Nonfatal CVD Fatal +Nonfatal CVD
MenWomen
Ag
e-A
dju
ste
d H
aza
rd R
ati
o*
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139
CHD Risk Factors - Makers
• Modifiable – The New Six– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
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140
CHD Risk Factors - Makers
• Modifiable – The New Six– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
141
142
143
144
145
146
147
148
149
150
151
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152
0
5
10
15
20
25
Elevated CRP Levels in Obesity Elevated CRP Levels in Obesity NHANES 1988-1994NHANES 1988-1994
Visser M et al. JAMA 1999;282:2131-2135.
Normal
Perc
en
t w
ith
CR
P
0.2
2 m
g/d
L
Overweight Obese
153
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154
CHD Risk Factors - Makers
• Modifiable – The New Six– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
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155
Lp(a) or Little‘a’
• Similar to LDL molecule• Apo B + additional Apo ‘a’ attached by S=S bond• Primary determinant is genetic• Normal value 20 mg %, > 30 high risk• It competes with plasminogen because of its
structural similarity and so interferes with plasmin synthesis and thrombolytic pathway
• Nicotinic acid, Estrogens ↓it
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156
Look at the risks
• Low HDL + High LDL +• LP(a) excess > 30 mg% + • LP(a) excess > 30 mg% + LDL high ++• LP(a) excess > 30 mg% + low HDL +++• LP(a) excess > 30 mg% + Incr. tHCy ++++• LP(a) excess + Incr. tHCy + low HDL ++++
+• Circulating lipids are one aspects• Tissue lipid content is more important
J. Atherosclerosis : Hopkins PN, 1997 – 17, 2792
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157
CHD Risk Factors - Makers
• Modifiable – The New Six– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
158
www.drsarma.in
Atherogenic Particles
Apolipoprotein BApolipoprotein BNon-HDL-CNon-HDL-CMeasurementsMeasurements
TG-rich lipoproteinsTG-rich lipoproteins
VLDLVLDL VLDLRVLDLR IDLIDL LDLLDL SDLSDL
Cholesterol lipoproteinsCholesterol lipoproteins
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159
Feingold KR et al. Arterioscler Thromb. 1992;12:1496-1502.Lamarche B et al. Circulation. 1997;95:69-75.
Significance of Small, Dense LDL
• Low cholesterol content of LDL particles particle number for given LDL-C level
• Associated with levels of TG and LDL-C, and levels of HDL2
• Marker for common genetic trait associated with risk of coronary disease (LDL subclass pattern B)
• Possible mechanisms of atherogenicity– Greater arterial uptake uptake by macrophages oxidation susceptibility
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160
Odds ratio=3.0; P<0.01.95% CI=1.7-5.2.
Adapted from Austin M et al. JAMA. 1988;260:1917-1921.
Association of Small, Dense LDLwith Myocardial Infarction
LDL pattern (size) Cases Controls
N (%)
A (LDL 1,2) 54 (37) 90 (63)
B (sLDL 4,5) 55 (64) 31 (36)
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161
CHD Risk Factors - Makers
• Modifiable – The New Six– hs-CRP
– Lp(a)
– sLDL
– Endothelial Dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
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162
O2 Endothelial Cells and
H2O2 Vascular Smooth Muscle
Oxidative Stress: Endothelial Dysfunction and CAD
Endothelial Dysfunction
Apoptosis
VasoconstrictionLeukocyteadhesion
Lipiddeposition
ThrombosisVSMCgrowth
HypertensionSmokingDiabetes LDL Homocysteine Estrogen
deficiency
163
Prediction future CVE by Endothelial Dysfunction
164
• Control of all the known CV risk factors
• Main focus on the big six – DM, HTN, Lipids, Obesity, Smoking, Sedentary life style
• Diet and physical activity are vital in Rx of ED
• Statins are the first line treatment for ED
• Glitazones have proven value to improve ED
• Insulin and Rx. Insulin resistance improves ED
What is the Rx. for Endothelial Dysfunction?
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165
CHD Risk Factors - Makers
• Modifiable – The New Six– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
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166
Inter Heart Study
Apo B / Apo A1 Ratio No evidence of threshold
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167
CHD Risk Factors - Makers
• Modifiable – The New Six– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
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168
Homocysti(e)ne
• Normal value is up to 10 μ mols/L
• Folic acid, Vitamin B6 and B12 are essential for the normal transulfuration and remethylation cycles
• Excess of homocystine generates oxidative stress on the cell membranes. DNA and protein denaturation through ROS formation
• Folic acid 5 mg/ day + Vit. B6 and B12 are to be given on regular basis
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169
Hyper-homocyst(e)inemia
Blood Homocyst(e)ine Levels
Classification Values in mmol/LNormalModerateIntermediateSevere
05 – 1011 – 30
31 – 100 > 100
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170
CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Prognostic Index– LVH – By Echocardiography, ECG, CXR
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171
CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Dip stick test– LVH – By Echocardiography, ECG, CXR
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172
Intra abdominal fat
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173
Treasure in our Tummy
RISK LEVEL BMI < 23 BMI > 23
WC < 90 cm ♂
WC < 80 cm ♀
GOOD
1
BAD
4
WC > 90 cm ♂
WC > 80 cm ♀
WORSE
8
WORST
16
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174
CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Dip stick test– LVH – By Echocardiography, ECG, CXR
175
Erectile Dysfunction – Today’s concept
Penis is the barometer of Endothelial Health
Erectile Dysfunction is amirror of Cardiovascular Risk
ED = ED
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176
ED = ED
• Erectile Dysfunction = Endothelial Dysfunction
• Marker of CV Health and CVD
• Due poor NO balance at the endothelium
• Penis is the barometer of cardiovascular health
• Close questioning is essential to uncover it
• Data suggests that is more so in South Asians
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177
CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Dip stick test– LVH – By Echocardiography, ECG, CXR
178
Ankle-Brachial Index (ABI)
Resting and post exercise SBP in ankle & arm
• Normal ABI is 1 to 0.90
• ABI < 0.9 has 95% specificity for angiographic early PVD
• ABI of 0.6- 0.84 correlates with claudication
• ABI < 0.6 advanced ischemic limb
• Always check pedal pulses
• Question for intermittent claudication
179
ABI Population Study
ABI < 0.9 Sensitivity Specificity
CHD 16.5 (12.8–20.2) 92.7 (92.1–93.3)
Stroke 16.0 (12.9–19.1) 92.2 (91.9–92.5)
All-cause mortality 31.2 (27.8–34.6) 88.9 (88.2–89.6)
CV mortality 41.0 (33.8–48.2) 87.9 (87.2–88.6)
180Edinburgh Artery Study on ABIEdinburgh Artery Study on ABI Ankle/brachial blood pressure index (ABI) in randomly
selected population, 5-year follow-up 1592 men and women, 614 with CHD, aged 55–74 137 fatal and nonfatal CHD events during follow-up
>1.1 1.1–1.01 1.0–0.91 0.9–0.71 <0.7
ABI
CH
D E
ven
t O
utc
om
es
per
Year
(%)
Leng GC et al. BMJ 1996;313:1440-1444.
1.4%
3.8%
0
1
2
3
4
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181
CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Prognostic index– LVH – By Echocardiography, ECG, CXR
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182
Which is important ? SBP or DBP
183
184
185
PulseMetricPulseMetric
Brachial Artery Distensibility, SVR, CO, LV dP/dtUses Oscillometric BP cuff
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186
CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Prognostic index– LVH – By Echocardiography, ECG, CXR
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187
Micro Albuminuria (MAU)
• MAU: 30-300mg albumin in urine over 24 hrs
• Occurs in DM and HT
• Detected by new dipstick tests for MAU
• Most accurate assessment is 24hr collection
• Screening by ACR on spot urine (first morning)
• MAU is a marker of early stage renal damage
• Regression of MAU decreases risk
• A marker of generalized CVD risk
188
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Definitions of abnormalities in albuminuria
Category24 hour collection(mg/24h)
Timed collection(g/min)
Spot collection(g/mg Creatine)
Normal < 30 < 20 < 30
Microalbuminuria 30-299 20-199 30-299
Clinical (macro) albuminuria
300 200 300
Because of variability in urinary albumin excretion, 2 of 3 specimens over3-6 should be abnormal before considering diagnostic threshold positive
False positive: exercise < 24 hours, fever, CHF, marked hyperglycemia, marked HTN, pyuria and hematuria.
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189
Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.
Microalbuminuria
10
8
6
4
2
0
10.02
Smoking Hypertension
CHD Odds Ratio
6.52
Cholesterol
2.323.20
Relative Importance of MAU
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CHD Risk Factors - Markers
• We rarely care to identify – The simple six– WC – Waist Circumference – Are we tailors?– ED – Erectile Dysfunction; ED = ED – ABI – Ankle Brachial Index, IC, Pedal pulse– PP – Pulse Pressure – Importance of ISH– MAU – Micro Albuminuria – Dip stick test– LVH – By Echocardiography, ECG, CXR
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TS OF HEART - LVH
Normal < 10 mm
This case 26 mm
192
CVE and LVH
The Framingham Heart Study
Cupples LA, D’Agostino RB. NIH Publication No 87-2703, Feb 1987.
2315
10 8
69
55
32
42
0
10
20
30
40
50
60
70
80
Men Women Men Women
Age
-Adj
uste
d R
ate/
1000
No LVHLVH
Risk Ratio 3.2 5.33.73.0CHD Stroke
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CHD Risk Factors - Markers
• We barely know & test – The complex six– ABPM – Dippers & Non Dippers– FMD – Brachial Flow Mediated Dilatation– PCOS – Polycystic Ovarian Syndrome - USG– CIMT – Carotid Intima Media Thickness– FFAG – Florescence Fundus Angiography– STS – Stress Thallium Scan – for perfusion study
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CHD Risk Factors - Markers
• We barely know & test – The complex six– ABPM – Dippers & Non Dippers– FMD – Brachial Flow Mediated Dilatation– PCOS – Polycystic Ovarian Syndrome - USG– CIMT – Carotid Intima Media Thickness– FFAG – Florescence Fundus Angiography– STS – Stress Thallium Scan – for perfusion study
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Yonsei, Med J, Vol 43, No 3: 2002
Dippers & Non Dippers
Non - dippers
Dippers
24 hours clock time
Sys
toli
c B
loo
d P
ress
ure
(m
m H
g)
110
120
130
140
150
160
6 8 10 12 14 16 18 20 22 24 2 4
Systolic Blood Pressure
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Yonsei, Med J, Vol 43, No 3: 2002
Dippers & Non Dippers
Non - dippers
Dippers
24 hours clock time
Dia
sto
lic
Blo
od
Pre
ssu
re (
mm
Hg
)
70
80
90
100
6 8 10 12 14 16 18 20 22 24 2 4
Diastolic Blood Pressure
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CHD Risk Factors - Markers
• We barely know & test – The complex six– ABPM – Dippers & Non Dippers– FMD – Brachial Flow Mediated Dilatation– PCOS – Polycystic Ovarian Syndrome - USG– CIMT – Carotid Intima Media Thickness– FFAG – Florescence Fundus Angiography– STS – Stress Thallium Scan – for perfusion study
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Brachial Artery Flow-Mediated Vasodilation
Baseline 5 Minutes Post-OcclusionBlood Pressure CuffOcclusion – 1 Minute Release
3.1 mm 3.6 mm
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Management of CHD
Risk
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What Evaluations We Need ?
• Age, Sex, Tobacco, Family Hx. premature CAD
• Nature of occupation and level of physical activity
• Height, Weight, BMI, Waist Circumference
• Blood pressure, pulse pressure, peripheral pulses
• Clinical LVH, ECG, CXR for LVH, Echo better
• FBG, PPBG, Hb A1c for DM and Pre Diabetes
• Fasting Lipid profile, Lp(a) once, hs-CRP once
• Urine albumin, MAU, ABI, Questing for ED, IC
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CHD Risk Scoring
• Framingham Risk Score
• UKPDS Risk Engine
• PROCAM Risk Calculator
• Diabetes PHD (ADA)
325 fatal and nonfatal myocardial infarctions in 4,818 men aged 35-65 years
Independent variables were: age, systolic blood pressure, LDL-C, HDL-C, triglycerides, diabetes mellitus, smoking, family history of MI
I II III IV V
The PROCAM Algorithm
MI´s (%) in 10 Years
0.6 2.1 2.8
7.6
21.4
Quintile of point Score
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T2DM Risk Estimation
• HOMA Calculator
• Indian Diabetic Risk Score
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CHD Prevention Total Life Style Change (TLC)
Medical Nutrition Therapy (MNT)Physical Activity (PA)
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Physical Activity
• What type of activity? Walking/Jogging
• How much? At least 45 min/day
• How often? On ever day almost
• At what intensity? HR of 120 –130/mt
The answer is
The health benefits of physical activity are
proportionately related to ‘Exercise Volume’
Exercise Volume = Duration x Frequency x Intensity
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Intervention Goals• Dietary/weight
counseling
Diabetes management
• Achieve optimal BMI saturated fats; fruits,
vegetables, fiber
• Achieve HbA1c <7%
• Exercise
• Education of patients and families
• Improve physical fitness (aim for 30 min/d on most days per week)
• Optimize awareness of CAD risk factors
Braunstein JB et al. Cardiol Rev. 2001;9:96-105.
CVD Risk Management
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General Principles
• Sugar and CHO to be replaced by complex CHO
• Fiber should be integral part – What foods ?
• Saturated fat to be avoided totally
• Do not reuse boiled oil – It is saturated fat
• Grill, Broil, Bake, Cook in water or Microwave
• Don’t eat deep fat fried items – very tasty !
• Use non stick cook ware. Reduce portion sizes
• Fresh fruits and raw vegetables - must every day
• Don’t eat fried snacks – chips, savories, sweets
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Foods - Glycemic IndexFoods - Glycemic Index
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DASH DIET
Type of Food Servings (1600 K cal)
Grains (whole grains) 6 per day
Vegetables 3 per day
Fruits (not tinned juices) 4 per day
Low fat milk 2 per day
Lean meat, poultry 3 per day
Nuts, seeds (dry roast, soak) 3 per week
Fats and oils 2 per day
Sweets and pastries 0 per day
Salt at table and salted foods None
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211Alternative Food Plans Alternative Food Plans Healthy Eating PyramidHealthy Eating Pyramid
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212Vegetarian Food PyramidVegetarian Food Pyramid
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213
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214 Fruits and vegetablesFruits and vegetables Fruit sugars are safeFruit sugars are safe Fruit pulp is to be eatenFruit pulp is to be eaten Not canned fruits, juicesNot canned fruits, juices Avoid coffee, chocolateAvoid coffee, chocolate Gift fruits - not sweetsGift fruits - not sweets Offer fruits as courtesyOffer fruits as courtesy Eat fresh cut vegetablesEat fresh cut vegetables Snack on fruits, nutsSnack on fruits, nuts Don’t over cook veg.Don’t over cook veg. Reduce simple CHOReduce simple CHO Fruits give us KFruits give us K++
Use soups, butter milkUse soups, butter milk
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Type Fats in our food
• Saturated Fatty acids – SAFA - ↑ LDL ↑ TG, ↑ LDL-R • Butter, Ghee, Palm oil, Beef oil, Coconut oil
• Unsaturated Fatty acids - UFA– Mono unsatur. fatty acids – MUFA ↓ LDL ↓ TG, HDL, AA
• Olive oil, Safflower oil, Canola oil, Groundnut oil
– Poly unsatur. fatty acids – FUFA ↓ LDL , ↓ Pl Agg, ↓Inflam.
• Corn oil, Sunflower oil, Cotton seed oil – N3 and N6 FAs
– Trans unsatur. fatty acids – TRUFA ↑LDL ↑SDL, ↓HDL, A • Dalda, Vanaspati, Margarine, processed fried foods
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Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
*Trans fatty acids also raise LDL-C and should be kept at a low intake.Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight.
<200 mg/dCholesterol
~15% of total caloriesProtein
30–40 g/dFiber
50%–60% of total caloriesCarbohydrate (esp. complex carbs)
25%–35% of total caloriesTotal fat
Up to 20% of total caloriesMonounsaturated fat
Up to 10% of total caloriesPolyunsaturated fat
<7% of total caloriesSaturated fat*
Recommended IntakeNutrient
ATP III: NutritionalComponents of the TLC Diet
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217Chemical Structure of FatsChemical Structure of Fats
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Comparison of Dietary Fats
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219Reduced Intake of Trans-Fatty Acids: Estimated Effects on CHD*
Mozaffarian D et al. N Engl J Med. 2006;354:1601-1613.
*Nonfatal myocardial infarction or death†Population attributable riskCHD=coronary heart disease
Reduction by half Near-elimination
Population Change inTrans-Fatty Acid IntakeP
rop
ort
ion
of
CH
D E
ven
ts P
reven
tab
le
in t
he U
nit
ed
Sta
tes (
%)
†
-25
-20
-15
-10
-5
0
Based on change in total: HDL-C (dietary trials)
Based on replacement with carbohydrates (prospective studies)
Based on additional benefits of replacement with cis unsaturated fats(prospective studies)
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220Fruit/Vegetable Consumption: Effects on Stroke Risk Reduction
0.5 1.0 1.5
Pooled Relative Risk (95% CI)
>5 vs <3 servings
3-5 vs <3 servings 0.89(0.83-0.97)
Meta-Analysis of 8 Studies (N=257,551)
0.74(0.69-0.79)
He FJ et al. Lancet. 2006;367:320-326.
P<0.0001
P=0.005
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Approximate Mortality Reduction: Pharmacotherapy* and Lifestyle/Diet†
Potential lifestyle/diet range(approx.)
Perc
en
t M
ort
ality
Red
ucti
on
Adapted from Iestra JA et al. Circulation. 2005;112:924-934.
*In coronary artery disease patients. †After myocardial infarction.
1821
2326
0
5
10
15
20
25
30
35
40
45
Low-doseAspirin
Statins Beta-blockers
ACEIs
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Study N Patient type Therapy
Duration
(yr)
% (Control-Treatment)
Progression Regression
Lifestyle 28 CAD Diet, exercise,meditation
1 35 -40
STARS 90 CAD, high TC Diet (including fiber)
3.2 35 -38
Heidelberg 113 CAD Diet + exercise 1 25 -15
Superko HR, Krauss RM. Circulation. 1994;90:1056-1069.
Effect of Lifestyle Changeson Angiographic CAD
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Obesity – Treatment Issues
• Goal – Reduction of 5 to 10% of existing weight
• Time frame – 6 months to 1 year
• No quick fixes; Crash weight reduction harmful
• Sibutramine – Leptos, Obirax, Slenfig
• Orlistat – Xenical, Obestat
• Rimonabant – ECB1antagonist. New- for obesity
• Gastric banding
• GI plasty, Liposuction
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CHD Prevention Smoking Cessation
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SURE TO GRAVESURE TO GRAVE
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Five steps in quitting
Onus is on the Doctor
One success is great !
• ASK
• ADVISE
• ASSESS
• ASSIST
• ARRANGE
How to Quit Smoking ? • Ask all patients about
• personal history of smoking• exposure to passive smoke inhalation• Ask at each visit to check smoking status
• Advice to quit must be clear and unambiguous
• Be supportive and nonjudgmental !• Remember, you aren’t the one quitting !• Offer resources and support consistent
with individual’s needs readiness to quit• Follow-up at each visit !
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Smoking Cessation
5. Withdrawal
4. Boredom
3. Sense of deprivation
or depression
2. Emotional upset and stress
1. Alcohol abuse !
one devil replaced by another devil
5. Withdrawal
4. Boredom
3. Sense of deprivation
or depression
2. Emotional upset and stress
1. Alcohol abuse !
one devil replaced by another devil
• Reduction of total personal exposure to tobacco smoke,
• Smoking cessation is the single most effective - and cost effective - intervention to ↓ the risk of COPD
• It is crucial for CAD prevention
• It is the corner stone in PAD
• Reduction of total personal exposure to tobacco smoke,
• Smoking cessation is the single most effective - and cost effective - intervention to ↓ the risk of COPD
• It is crucial for CAD prevention
• It is the corner stone in PAD
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Smoking Cessation
1. Bupropion Smoquit-SR, Nicotex
2. In psychological dependence on nicotine
3. Useful in individuals with or at risk for depression–
4. Contraindicated in drug interactions or seizure disorder
1. Bupropion Smoquit-SR, Nicotex
2. In psychological dependence on nicotine
3. Useful in individuals with or at risk for depression–
4. Contraindicated in drug interactions or seizure disorder
• Helpful for physical withdrawal symptoms
• Can be dosed according to degree of use
• Costs the same as daily smoking habit
• Most products of NRT - cautious use in cardiac patients
• Bupropion may be alternative to NRT
• Dosage form depends on need
• Patch is more constant level, sprays & inhaler a more rapid effect
• Helpful for physical withdrawal symptoms
• Can be dosed according to degree of use
• Costs the same as daily smoking habit
• Most products of NRT - cautious use in cardiac patients
• Bupropion may be alternative to NRT
• Dosage form depends on need
• Patch is more constant level, sprays & inhaler a more rapid effect
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CHD Prevention Medications
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Expert Panel/Writing Group. Circulation. 2004;109:672-693.
Key Strategies for High-Risk Patients
(10-year CHD risk >20%)• Physical activity/cardiac rehabilitation• Smoking cessation• Diet tx; weight maintenance/reduction• BP, lipid control (statin tx)• Aspirin, ß-blocker tx• ACE inhibitor tx (ARBs if contraindicated)• Glycemic control in diabetes• No routine HRT in PM women
AHA Evidence-Based Guidelines For CVD Prevention
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CHD PreventionStrategies
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Primary Prevention of CHD
• Hypertension control A, B, D
• Aspirin 100 to 150 mg
• Exercise, Weight Reduction
• Smoking cessation
• Statin therapy to lower cholesterol levels
• Estrogen replacement therapy no benefit
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Secondary Prevention of CHD
• Hypertension control
• Beta blockers
• Aspirin 150 to 300 mg
• ACEi or ARB
• Aggressive Statin therapy
• PTCA; CABG
• Smoking cessation
• Exercise rehabilitation
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234Lowest Effective Aspirin Dose for MI and Stroke Reduction
• Primary Prevention (mg/d)– MI in men ≥50 160– MI in women ≥50 100– Stroke in men ≥50 160– Stroke in women ≥50 100– Stroke in men/women with AF 325
• Secondary Prevention (in men/women) (mg/d)– MI with HX stable CAD 75– MI with HX AMI 160– Stroke with HG stroke/TIA 50– Stroke without HG acute stroke 160
Dalen JE. Am J Med. 2006;119:198-202.
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Secondary Prevention of CAD
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Control of Diabetes
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Control of DM
• T2DM is CAD Equivalent, PVD more common
• It equalizes gender difference before 50 years
• FBG & PPBG control – diet, exercise, medicines
• HbA1c must be kept below 7 – preferably 6.5
• B.P. target 130/80 – 10 mm less than non DM
• Must get statin even if lipids are normal
• Aggressive control of Dyslipidemia
• ACEi are a must. B blockers if there is no PVD
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Control of DM• Oral Agents
1. Metformin
2. Sulfonylureas – New Generation
3. Thiazolidines – Pioglitazone, Rosiglitazone
4. Repaglinide and Metaglinide
5. AGIs – Acarbose, Meglitol
• Insulins– Conventional, Pens, Analog insulins, Aerosol, Pump
• Latest developments – Exenitide, GLP-1 analogs, Dual PPARs, Amylin
239
*Cases per 100 person-years; †vs placebo.RRR=relative risk reduction.
58 (48–66)31 (17–43)RRR (%, 95% CI)†
4.87.811Diabetes incidence*
Results
164 ± 17165 ± 17165 ± 17Plasma glucose 2 hours postchallenge (mg/dL)
106 ± 8107 ± 9107 ± 8Fasting plasma glucose (mg/dL)
51 ± 1151 ± 1050 ± 10Age (y)
32/6834/6631/69Male/Female (%)
Baseline Characteristics
Lifestyle(n=1,079)
Metformin(n=1,073)
Placebo(n=1,082)
DPP Research Group. N Engl J Med. 2002;346:393-403.
Diabetes Prevention Program
240
Pyörälä K et al. Diabetes Care. 1997;20:614-620.
Total mortality 2321672415
CHD mortality 172991712
Major CHD event 5784074424
Any CHD event 8716675641
CABG or PTCA 3632382015
Cerebrovascular event 9070125
Any atherosclerotic event 9617506146
NondiabeticDiabetic
P S
0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
RR with 95% CIs
No. patients Simvastatin Placebowith events better better
Secondary Prevention: CHD Risk Reduction in the 4S Subgroup of Patients With Diabetes
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Control of Hypertension
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Control of HT
• HT is a strong risk factor for CHD and CVD
• ISH is more important than ↑ DBP alone
• Salt restriction – daily 2 g/day of Na
• Diet low in saturated fats. Rx. Of dyslipidemia
• Goal B.P. is 140/90 – 10 mm less for Diabetic HT
• ACEIs / ARBs, BB, Thiazides - at least 2 drugs
• ISH – CCBs and BBs; Indapamide useful
• TOD – LVH, ABI, Pulse pressure, Brachial FMD
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Control of Dyslipidemia
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Gould AL et al. Circulation. 1998;97:946-952.
Clinical Benefits of Cholesterol Reduction
• A recent meta-analysis of 38 trials demons- trated that for every 10% reduction in TC
•CHD mortality decreased by 15% (P<0.001)•Total mortality decreased by 11% (P<0.001)
• Decreases were similar for all treatment modalities
• Cholesterol reduction did not increase non-CHD mortality
Dr.Sarma@works
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AtorvastatinAtorvastatin211 mg/dl*211 mg/dl*
SimvastatinSimvastatin219 mg/dl*219 mg/dl*
-60%
-50%
-40%
-30%
-20%
-10%
0%
Mea
n %
Cha
nge
from
Bas
e li n
eLDL-C Lowering - Statin Dose
Adapted from Jones P et al. Am J Cardiol 1998;81:582-587.
Daily DoseDaily Dose
10 mg
20 mg
40 mg
80 mg16% with16% with3 Titrations3 Titrations
13%13%
38%
46%
51%54%
28%
35%
41%
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Ezetimibe Efficacy (“10 + 10 = 80”)
Ballantyne CM et al. Circulation 2003;107:2409-2415.
Atorvastatin40 mg(n=66)
20 mg(n=60)
10 mg(n=60)
Me a
n %
Cha
n ge
in L
DL-C
f ro m
Bas
e li n
e
–53%
–37%–42%
–45%
–54%
P < 0.01P < 0.01
80 mg(n=62)
-60%
-50%
-40%
-30%
-20%
-10%
0%
Ezt + Ator10+10 mg
(n=65)
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80
90
100
110
120
130
140
150
160
0 12 24 36 48
Follow-up (mo)
Aggressive Tx (93-96)*
Moderate Tx (134-136)*
6
Post-CABG Trial Investigators. N Engl J Med. 1997;336:153-162.
LDL-C(mg/dL)
* Mean achieved.
Post-CABG Study - Aggressive v/s Moderate Treatment
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248Non-pharmacological Approaches to TG Lowering
Lifestyle Modifications• Diet
– Limit added sugar, carbohydrate (simple sugar)– TG > 500 mg/dL: limit fat intake– TG 150– 500 mg/dL: individualize therapy
• Alcohol– TG >500 mg/dL: no alcohol– TG 200–499 mg/dL: limit alcohol
• Maintain ideal body weight• Exercise• Smoking cessation
Coughlan BJ et al. Postgraduate Med Online. 2000;108(7).Pejic RN, Lee DT. J Am Board Fam Med. 2006;19:310-316.
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New Treatments1. Selective LDL Apopheresis
2. Apo A1 Milano – Recombinant HDL
3. The ECB-1 Receptor antagonist – Rimonabant, weight loss up to 25% – ↑ HDL-C and ↓ TG
4. The Dual α/γ PPAR activator – Muraglitazar – Glycaemic & dyslipidaemia control
5. CETP inhibitors – Torcetrapib ↑ HDL by 50 to 60%
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The Three Canons
↑ LDL - STATIN↑ LDL - STATIN
↑ TG
- FI
BRATE
↑ TG
- FI
BRATE
↓ HDL - NIACIN
↓ HDL - NIACINDYSLIPIDEMIA
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Summary of Drug choice
Lipid abnormality type Choice of Drug
↑ LDL Statin
↑ TG Fibrate
↓ HDL Niacin
↑ LDL + ↑ TG Statin + Fibrate
↑ LDL + ↓ HDL Statin + Niacin
↑ TG + ↓ HDL Fibrate + Niacin
↑ LDL + ↑ TG + ↓ HDL Statin + Fibrate
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Summary of Drug choice
Lipid abnormality type Advised Rx. Remarks
↑ Homocysteine Folic acid B6 + B12 helps
↑ Small dense LDL Statin + Fibrate Aggressive Rx.
↑ Little ‘a’ or LP(a) Niacin Statin no effect
↑ Phenotype B Under research DM, Obesity ↓
↓ in Phenotype A Under research Aerobic exercise
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Some Brand Names
Drug class Brand name
Atorvastatin TG-TOR, Storvas, Avastin, Atcor
Simvastatin Sim, Simvotin, Simcard, Simvas
Atorvastatin + Ezetimibe TG tor Z, Storvas Z,
Ezetimibe Ezedoc, Ezee, Ezet
Fenofibrate Lipicard, Fibrate, Finolip, Stanlip
Niacin Neasyn, Nialip, Nicocin
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Take Home Messages
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CHD – Risk Factors
1. Grundy SM et al. Circulation
1999;100:1481–1492;
2. Haffner SM et al. N Engl J Med
1998;339:229–234
Modifiable6. Physical Inactive
5. Obesity, ↑ WC4. Lipid Abnor
3. Smoking2. Inc.BP
1. DM
Emerging6.Homocysteines5. ApoA1/ ApoB
4. hs- CRP3. ↑SLDL2. Lp(a)
1. ED
CHD RF
Non-Modifiable6. Phenotype B5. Personality 4. F. Hx CVD 3. Ethnicity2. Gender
1. Age
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Sapta Padi – The Seven Steps
1. Screen, define and target high risk patients
2. Modify life style factors – MNT, PA
3. Explain and persuade to quit smoking, ↓ alcohol
4. Aspirin >100 mg in all those with > 1 RF (??)
5. Aggressive control of DM – HBA1c < 7
6. Attain goal B.P of 140/90 in all – DM 10 mm less
7. ACEi and statin for all DM, Statin for ↑ LDL, Address HDL, Lp(a), TG, hs-CRP if abnormal
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Forget not Stress
• TLC is essential to keep ideal weight
• Drugs are inevitable to control risk factors
• Role of Stress and avoidance of it can’t be over emphasized
• Yoga, relaxation, music, family outings, tourism, books, socialization are essential
• Avoiding the Idiot box helps the mind & body
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Shun Negative Behaviour
• Worry, Fault finding
• Anger, Blaming others
• Lust and Greed
• Jealousy and Vengeance
• Anxiety and depression
• All ↑↑ hs-CRP, IL-6, Endothelial dysfunction
• These pave a perfect way for CAD to set in
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Minimum medication needed # Pills Cost/day
Glimiperide 1 + Metformin 500 1 4
Pioglitazone 15 mg 1 2
Nitrate long acting 1 bid 2 6
Aspirin 150 + Clopidogrel 75 1 3
Statin + Ezetemibe 1 9
Fibrate or Niacin 1 6
Ramipril 5 + Hydrochlorthiazide 1 7
Carveidilol or Metoprolol b.i.d 2 8
Other supportive medication 2 5
Total (conservative) 12 50
For each Ill at least one PillOur Cardio-metabolic patient
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At what cost one suffers !!
1. Rs 50 x 30 days = 1500 x 12 months = 18,000/yr
2. Age 45 to 65 – 20 years x 18,000 = 3,60,000
3. Cost of CABG or PTCA + Stent = 2,00,000
4. What about the cost of his consultations, tests etc.
5. What about his co-morbidities like OA, Cataract
6. What about his inter current illnesses and admiss.
7. What about treatment for CHF, RF, PVD, Laser
8. No third party payer – has to spend by himself !!
9. What is value of all this prolonged suffering ? ?
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Hippocrates said ….
Let your FOOD be your Medicine – Lest,
Your Medicines will replace your Food !!
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Where are we heading ? ?
Journal of internal medicine 2003:254(2):114-25
20000 B.C. 2004
Hunting-gatheringsubsistence
High level ofphysical activity
Processedfoods
Animal fatsand glucidesDietary fibre¯
Sedentary life
Paleolithic sup. age Neolithic age 19th century 21st century
Thrifty genotype Susceptibility genotype
Technology has changed a lot in the way we live
But, we have not altered our life style
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We have to pay the very heavy price !!
What could be prevented, we treat or leave
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Think for a moment ….• Should we not address this early from 20s or 30s ?• Should we wait till we all suffer and succumb ?• Is it not cost-effective and safe to take action now ?• What for are we waiting? Whose permission is needed?• Who will bell the cat to motivate for CAD prevention• It will never be a priority for our rulers ! • It is we – the answerable ones for all – should take steps • Take a pledge now to screen all above 30 years• Initiate them into preventive action – persuade – persist
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1
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266
O ! God, I shall blame YOU ?
Maruvanu Ahaarambunu
Maruvanu Paaneeyambunu
Maruvanu naa durgunamulu
I will not refrain from over eating
Neither will part with my drinking
Nor, say good bye to my vices
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O ! God, I shall blame YOU ?
Maruvanu Ahaarambunu
Maruvanu Paaneeyambunu
Maruvanu naa durgunamulu
Maracheda vyaayambunu
Maracheda sat karmabula
Maracheda gurula boodhalu
I will not refrain from over eating
Neither will part with my drinking
Nor, say good bye to my vices
I shall forget my physical exercise
I will not care for healthy life style
I shall forget what all is instructed
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Dear GOD, let a miracle happen !
Please, save my Dad/Mom
