1
Welcome
www.drsarma.in
2
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
www.drsarma.in
3
Coronary Heart Disease
(CHD) - Risk Approach
Dr.R.V.S.N.Sarma., M.D.
www.drsarma.in
4
Over view of this CME
Session One
• CHD Prevention is the Mantra
• Over view of atherosclerosis
• Risk Factors in detail
Session Two
• Patient evaluation - what tests to do
• Risk scoring tools
• Management of risk factors
• Take home messages
www.drsarma.in
5
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 !
www.drsarma.in
6
Coronary Artery Disease - CAD
At the end of the show
Cerebro Vascular Disease – CVD
there are only two exits
Peripheral Vascular Disease – PVD
Reno Vascular Disease - MRD
Cardio Vascular
Diseases - CVD
All Other
Causes of Death
Exit 1
Exit 2
50%
50%
www.drsarma.in
7
CHD – THE VOLCANO
www.drsarma.in
8
Treatment Advances in CAD
• Thrombolysis – Rx. Algorithms
•1. Benefit
ICU carethe
– Defibrillators,
Ventilators,
IABP
lucky few patients who
• survived
Coronary Angiogram,
CT Angio,
STS
until the hospital
door
• Primary PTCA – Stents, Elective PTCA
2. They are at best palliative; not curative
• 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
www.drsarma.in
9
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
very
sacred souls
!! we are
So,
oncemortality
we are– a
patient
of MI,
Remaining
– 6/20 (1/3)
– die in+/spite
of us
permanent
patients
invalidity
!!!
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
www.drsarma.in
10
How foolish we are all !!
Samudrae saanta kallole
When the waves stop, then
Snatum itcchati mooda dhi
Shall I bathe, thinks the fool
www.drsarma.in
11
How foolish we are all !!
Samudrae saanta kallole
When the waves stop, then
Snatum itcchati mooda dhi
Shall I bathe, thinks the fool
Samsaare saanta kallole
Sans turbulance I am when,
Jnanam icchati durmati
Then shall I strive for wisdom
www.drsarma.in
12
How foolish we are all !!
Samudrae saanta kallole
When the waves stop, then
Snatum itcchati mooda dhi
Shall I bathe, thinks the fool
Samsaare saanta kallole
Sans turbulance I am when,
Jnanam icchati durmati
Then shall I strive for wisdom
Sareerae hrid rogapeeditae
The CAD strikes my heart when
Roginah kaankshati rakshati
Then, shall I crave for prevention
www.drsarma.in
13
How to win the battle of CHD
• Coronary care units cannot answer all callers
• PTCA
and CABG
not best
always
feasible
Prevention
is theare
only
weapon
• Are
affordable
by and
available
to only
some
Need
to identify
those
at greater
risk
Target
them
early attempt
to forestall
damage
• Why
make
a valiant
to save
the
myocardium after all the damage is done
• Why not protect our tiny blood pipes by
adopting preventive strategies at low cost !
www.drsarma.in
14
Prevention is the key
1.
2.
3.
4.
5.
6.
7.
8.
CVD - Is it preventable ?? - Very much Yes.
The risk assessment must start very early
At the age of 20 years itself
Healthy life style and hearty eating habits
Regular physical exercise from young age
Maintaining ideal weight and hour glass waist
Avoiding tobacco and reducing alcohol
There are enough guidelines – Implementation ?
www.drsarma.in
The Progressive Development of
Cardiovascular Disease
Intervene here
Risk Factors
Endothelial Dysfunction
Atherosclerosis
CAD
Myocardial Ischemia
Coronary Thrombosis
Myocardial Infarction
Arrhythmia & Muscle Loss
Remodeling
Ventricular Dilation
Congestive Heart Failure
End stage Heart Disease
www.drsarma.in
15
16
Continuum Risk for a CHD Event
Secondary
Prevention
Post MI/Angina
Other Atherosclerotic
Manifestations
Primary
Prevention
Subclinical
Atherosclerosis
Multiple Risk Factors
Low Risk
www.drsarma.in
Courtesy of CD Furberg.
17
Note the individual Endothelial Cells
www.drsarma.in
18
www.drsarma.in
19
Endothelial Apoptosis
Normal
www.drsarma.in
Apoptosed
20
The Universal Damage
The Essential Components
Genes
Coronary
Risk Factors
Endothelial
Dysfunction
 NO
↑ Inflammation
↑ Thrombosis
Coronary
Heart
Disease
The Nature (Genetic) conspires with the Nurture (Acquired)
www.drsarma.in
21
www.drsarma.in
(L-NMMA) = N(G)-mono-methyl-L-arginine
Regulatory Functions of the Endothelium
Normal
www.drsarma.in
Dysfunction
Vasodilation
NO, PGI2, EDHF,
BK, C-NP
Vasoconstriction
ROS, ET-1, TxA2,
A-II, PGH2
Thrombolysis
Thrombosis
PAI-1, TF-α, Tx-A2
tPA, Protein C, TF-I, vWF
22
Platelet Disaggregation
Adhesion Molecules
NO, PGI2
CAMs, P,E Selectins
Antiproliferation
Growth Factors
NO, PGI2, TGF-, Hep
ET-1, A-II, PDGF, ILGF, ILs
Lipolysis
LPL
Inflammation
ROS, NF-B
Vogel R
23
Progression of Atherosclerosis
www.drsarma.in
24
Role of LDL in Inflammation
LDL readily enter the artery wall where they may be modified
Vessel Lumen
LDL
Nitric Oxide (NO)
Policing the Endothelium
Endothelium
Oxidation of Lipids
and ApoB
Aggregation
LDL
Hydrolysis of Phosphatidylcholine
to Lysophosphatidylcholine
Other Chemical Modifications
Modified LDL
Modified LDL is Proinflammatory
Steinberg D et al. N Engl J Med 1989;320:915-924.
Intima
Modified LDL Stimulate Expression
of MCP-1 in Endothelial Cells
Vessel Lumen
Monocyte
LDL
MCP-1 LDL
Monocyte Chemotactic
Protein 1 – MCP 1
Endothelium
Modified LDL
Intima
Navab M et al. J Clin Invest 1991;88:2039-2046.
25
26
Differentiation of
Monocytes into Macrophages
Vessel Lumen
Monocyte
LDL
MCP-1
Endothelium
LDL
Intima
Monocyte Chemotactic
Protein 1 – MCP 1
Modified LDL
Macrophage
Steinberg D et al. N Engl J Med 1989;320:915-924.
Modified LDL Promote
Differentiation of
Monocytes into
Macrophages
Modified LDL Induces Macrophages to Release
Cytokines - Stimulate Adhesion Molecule
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
MCP-1
Cytokines
Endothelium
LDL
Modified LDL
Macrophage
Nathan CF. J Clin Invest 1987;79:319-326.
Intima
27
Recruitment of Blood Monocytes by
Endothelial Cell Adhesion Molecules
Monocyte
Rolling
Sticking
Vessel Lumen
Transmigration
E-Selectin
VCAM-1
ICAM-1
Endothelium
MCP-1
Intima
Charo IF. Curr Opin Lipidol 1992;3:335-343.
28
Macrophages Express Receptors
that take up Modified LDL
29
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
MCP-1
Endothelium
LDL
Modified LDL
Taken up by
Macrophage
Foam Cell
Macrophage
Steinberg D et al. N Engl J Med 1989;320:915-924.
Intima
Macrophages and Foam Cells Express
Growth Factors and Proteinases
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
Cytokines
Macrophage
MCP-1
LDL
Modified
LDL
Foam Cell
Ross R. N Engl J Med 1999;340:115-126.
Endothelium
Intima
Growth Factors
Metalloproteinases
Cell Proliferation
Matrix Degradation
30
The Remnants of VLDL and
Chylomicrons are also Proinflammatory
Vessel Lumen
Monocyte
Remnant Lipoproteins
Adhesion
Molecules
Cytokines
Macrophage
Endothelium
MCP-1
Remnants
Modified
Remnants
Foam Cell
Doi H et al. Circulation 2000;102:670-676.
Intima
Growth Factors
Metalloproteinases
Cell Proliferation
Matrix Degradation
31
32
33
Pathogenesis of ACS
Non-Vulnerable
Atherosclerotic
Plaque
www.drsarma.in
Vulnerable
Atherosclerotic
Plaque
34
Atherosclerosis
A Progressive Process
Normal
Fatty
Streak
Fibrous
Plaque
Occlusive
Atherosclerotic
Plaque
Plaque
Rupture/
Fissure &
Thrombosis
Unstable
Angina
MI
Coronary
Death
Stroke
Clinically Silent
Effort Angina
Claudication
Critical Leg
Ischemia
Increasing Age
www.drsarma.in
Courtesy of P Ganz.
The Anatomy of
Atherosclerotic Plaque
35
Intima
Fibrous
cap
Lipid
core
Lumen
Media
–T lymphocyte
– Macrophage
foam cell (tissue factor+)
– “Activated” intimal SMC
(HLA-DR+)
–Normal medial SMC
www.drsarma.in
Libby P. Lancet. 1996;348:S4-S7.
The Matrix Skeleton of Unstable
Coronary Artery Plaque
36
Fissures in
the fibrous
cap
www.drsarma.in
Davies MJ. Circulation. 1996;94:2013-2020.
37
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
www.drsarma.in
38
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
www.drsarma.in
39
CHD Risk Factors - Makers
• If non modifiable – why study them ?
• Non Modifiable – The Tough Six
–
–
–
–
–
–
www.drsarma.in
Age
Gender
Ethnicity
Family H/o of premature CHD
Phenotype B
Type A personality (partly modifiable)
40
CHD Risk Factors - Makers
• If modifiable – why not control them ?
• Modifiable – The Conventional Six
–
–
–
–
–
–
www.drsarma.in
Diabetes Mellitus
Dyslipidemia
Hypertension
Smoking / tobacco
Over weight and Obesity
Physical inactivity
41
CHD Risk Factors - Makers
• Modifiable – The contributing six
–
–
–
–
–
–
www.drsarma.in
hs-CRP
Lp(a)
sLDL
Endothelial dysfunction
Apo B / Apo A1 ratio
Homocysteine
42
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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
43
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
www.drsarma.in
44
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
www.drsarma.in
45
CHD Risk Equivalents
1.
2.
3.
4.
Diabetes Mellitus
Peripheral Vascular Disease (PVD)
Framingham risk score of > 20%
Carotid artery disease –
•
•
Stroke, TIA
> 50% Narrowing, Carotid Bruit
5. Abdominal Aortic Aneurysm (AAA)
Adult Treatment Panel III. NIH publication 01-3095.
www.drsarma.in
46
Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
www.drsarma.in
47
Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
www.drsarma.in
48
Age and CAD
•
•
•
•
•
•
•
•
www.drsarma.in
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
49
Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
www.drsarma.in
50
Gender and CAD
•
•
•
•
•
•
•
•
www.drsarma.in
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
51
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)
www.drsarma.in
52
Deaths in Thousands
CVD Mortality Trends (1979-1999)
www.drsarma.in
American Heart Association. 2002 Heart and Stroke Statistical Update. 2001
53
Death From Breast Cancer or
Heart Disease in Women
www.drsarma.in
US Vital Statistics, 1990
WISE Study - Review of
Ischemic Heart Disease in Women
Percent With
Obstructive CAD
100
54
Typical angina
90
Atypical angina
80
Non-angina chest pain
70
60
60
50
30
20
36 34
36
40
21
11 12 12
17
21
25
21
10
0
www.drsarma.in
35-45 y
45-55 y
55-65 y
Age (years)
65-75 y
Shaw LJ et al. J Am Coll Cardiol. 2006;47(suppl 3):S4-S20.
55
Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
www.drsarma.in
56
Ethnic Differences
•
•
•
•
•
Japanese and Chinese lowest rates
Whites or Caucasians lower rates
Hispanics intermediate rates
Asian Indian higher rates
Afro-Caribbeans (negroid) highest
rates
www.drsarma.in
57
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.
www.drsarma.in
58
CAD Mortality
INDIA
Age Adjusted mortality
for 100,000 population
per year in 35-74 age.
www.drsarma.in
59
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
www.drsarma.in
The CADI study
60
Only 14% of Asian Indian males &
5% of females have Optimal HDL
Journal, Ind. Acad. clin. med vol 2 Jul-Sept 2001
120
100
80
60
40
20
0
86
95
14
5
Asian Indian
females
Asian Indian
males
% 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.
Prevalence of coronary heart disease and its risk factors in Asian Indians
Atherosclerosis , Rosemount , IL Oct 6-11 , 1991
www.drsarma.in
61
Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
www.drsarma.in
62
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
www.drsarma.in
63
Age-adjusted prevalence (%) of
moderate calcification
(CAC Score >100)
Coronary Artery Calcification
(CAC) and CHD Family History
59 56
60
No family history
Parental family history
Sibling family history
Both
50
40
47
44
41
33
32 30
30
23 22
23
35
24
17
16
20
11
10
0
No risk
factors
1 risk factor
2 risk
factors
 3 risk
factors
P<0.001 across categories.
www.drsarma.in
Nasir K et al. Circulation. 2004;110:2150-2156.
64
Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
www.drsarma.in
65
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
www.drsarma.in
66
Nature conspires with Nurture
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
www.drsarma.in
67
Phenotype B or ALP
• 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
www.drsarma.in
Characteristics 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
www.drsarma.in
68
69
Cumulative Distribution of TG
Levels Phenotypes A and B
100
90
80
70
% Cumulative60
frequency 50
40
Phenotype A
Phenotype B
30
20
10
0
20 40 60 80 100 120 140 160 180 200 220 240 260 280 300
500
TG (mg/dL)
Austin M et al. Circulation. 1990;82:495-506.
www.drsarma.in
70
Cumulative Distribution of HDL
Levels Phenotypes A and B
100
90
80
70
% Cumulative60
frequency 50
Phenotype A
Phenotype B
40
30
20
20
25
30
35
40
45
50
55
60
65
70
75
80
HDL-C (mg/dL)
Austin M et al. Circulation. 1990;82:495-506.
www.drsarma.in
71
Non Modifiable Risk factors
1. Age
2. Gender
3. Ethnicity
4. Family H/o of premature CHD
5. Phenotype B
6. Type A personality
www.drsarma.in
72
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
www.drsarma.in
73
Personality
Type B Person
Type A Person
www.drsarma.in
74
Modifiable Risk factors – BIG 6
1.
2.
3.
4.
5.
6.
www.drsarma.in
Diabetes Mellitus
Dyslipidemia
Hypertension
Smoking
Over weight and Obesity
Physical inactivity
Relative risk of CHD
Additive Effect
Smoking
4.5
16
1.6
3
SBP >160
5
6
4
Dyslipidemia
With DM all risks are doubled
www.drsarma.in
75
76
CHD Risk Factors - PROCAM Study
Risk factor
Smoking
LDL cholesterol (mg%)
> 100 but < 160
> 160
Hypertension (SBP > 140; DBP > 90)
HDL cholesterol (mg%)
40 to 55
< 40
Triglycerides (mg%)
105- 167
>167
Fasting blood glucose (mg%)
110 - 126
> 126
Family history of MI
www.drsarma.in
Relative risk
P Value
2.3
0.001
1.9
4.3
1.8
0.01
0.001
0.001
1.7
2.7
0.01
0.001
1.6
2.6
0.01
0.001
1.4
1.9
1.4
0.05
0.01
0.05
77
www.drsarma.in
Multiple Risk Factors: ‘Gang Up’
Mean cumulative risk %
The total severity of multiple low-level risk factors often
exceeds that of a single severely elevated risk factor.
27%
30
25
19%
20
15
10
13%
8%
5
0
BP 165/95 mm Hg BP 165/95 mm Hg
Age 56 years
BP 165/95 mm
BP 165/95 mm
HgAge 56 years
HgAge 56 years
LDL-C 155 mg/dL LDL-C 155 mg/dL
Smoker
Grundy SM et al. J Am Coll Cardiol 1999;34:1348-1359.
78
79
Modifiable Risk factors – BIG 6
1.
2.
3.
4.
5.
6.
www.drsarma.in
Diabetes Mellitus
Dyslipidemia
Hypertension
Smoking
Over weight and Obesity
Physical inactivity
80
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
www.drsarma.in
81
Public 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
www.drsarma.in
2
82
Diabetes – 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.
www.drsarma.in
3
83
Diabetes – 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
www.drsarma.in
4
84
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
www.drsarma.in
5
85
Atherosclerosis and IR and DM
Hypertension
Obesity
Hyperinsulinemia
Insulin
Resistance
Diabetes
Hypertriglyceridemia
Small, dense LDL
Low HDL
Hypercoagulability
www.drsarma.in
Atherosclerosis
CHD Mortality and Hyperinsulinemia
Paris Prospective Study (n=943)
86
3
P<0.01
CHD
mortality
(per 1,000)
2
1
0
29
30-50
51-72
73-114
115
Quintiles (pmol) of fasting
plasma insulin
www.drsarma.in
Fontbonne AM et al. Diabetes Care. 1991;14:461-469.
Progression to atherosclerotic clinical
events in patients with Diabetes
Hyperglycemia
Inflammation
Infection
 Defense
mechanisms
 Pathogen burden
Insulin Resistance
Dyslipidemia
 AGE
 Oxidative
stress
 IL-6
 CRP
 SAA
87
HTN
Endothelial
dysfunction
Subclinical Atherosclerosis
 LDL
 TG
 HDL
Thrombosis
 PAI-1
 TF
 tPA
Disease Progression
Atherosclerotic Clinical Events
Biondi-Zoccai GGL et al. J Am Coll Cardiol. 2003;41:1071-1077.
88
DM and CAD - CUPS
www.drsarma.in
Mohan V et al CUPS…
89
DM and CVE : LIFE study
60
Non-Diabetic (n=7998)
(n=1195)
Diabetic
46
50
40
30
23
20
10
0
Primary Endpoint
Relative Risk:
2.0
Rate per 1000 Patient-Years
Rate per 1000 Patient-Years
Increased Risk of Primary Endpoint
60
Non-ISH (n=7867)
ISH
(n=1326)
50
40
30
25
30
20
10
0
Primary Endpoint
1.2
Finnish Diabetes Prevention Study
Reduction in Risk for Diabetes
90
23%
25
(n=257)
20
Diabetes
(%)
15
10
11%
(n=265)
5
0
*P<0.001;
Intervention
Control
4-year results
Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
91
Dyslipidemia in IR and DM
• Elevated TG
• Elevated VLDL
All• Diabetics
Reduced must
HDL be given STATIN
• Increase in SD-LDL
• Decrease in Apo A I
• Increase in Apo B
• Ratio of Apo B /Apo A 1 > 1.5
92
Modifiable Risk factors – BIG 6
1.
2.
3.
4.
5.
6.
www.drsarma.in
Diabetes Mellitus
Dyslipidemia
Hypertension
Smoking
Over weight and Obesity
Physical inactivity
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
www.drsarma.in
94
Dyslipidemia and CAD
•
•
•
•
•
www.drsarma.in
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
Structure of LDL
95
Surface
Monolayer of
Phospholipids
and Free
Cholesterol
apoB
Hydrophobic Core
of Triglyceride
and Cholesteryl
Esters
Murphy HC et al. Biochemistry 2000;39:9763-970.
Structure of HDL
apoA-I
apoA-II
Rye KA et al. Atherosclerosis 1999;145:227-238.
96
Surface
Monolayer of
Phospholipids
and Free
Cholesterol
Hydrophobic Core
of Triglyceride
and Cholesteryl
Esters
Risk Factors for Future Cardiovascular
Events: WHS
Lipoprotein(a)
Homocysteine
IL-6
TC
LDL-C
sICAM-1
SAA
Apo B
TC:HDL-C
hs-CRP
hs-CRP + TC:HDL-C
0
1.0
2.0
4.0
6.0
Relative Risk of Future Cardiovascular Events
Ridker PM et al. N Engl J Med 2000;342:836-843.
97
Lipid Profile in Young Indian Patients
Angiographically Proven CHD
Parameter
with
% 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 yrs
Mishra et al (Cuttack)
Indian Heart J 2001; 53: Abst 60
98
99
TC (mg/dL)
Trends in Total Cholesterol* for US
Adults, 1960-1962 to 1999-2002
270
Men (aged 60-74)
260
Women (aged 50-59)
Women (aged 60-74)
250
240
230
†
220
†
210
200
1960-1962
†
1971-1974
1976-1980
1988-1994
1999-2002
*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.
100
RF in CAD – PROCAM Study
Odds Ratio for CAD
when LP(a) > 20 mg
www.drsarma.in
Fasting TG and Risk for CHD
Death: Paris Prospective Study
6
Mean
annual CHD
mortality
rate/1,000
TG 123 mg/dL
101
TG 123 mg/dL
4
2
0
220
>220
220
>220
Cholesterol
(mg/dL)
www.drsarma.in
Adapted from Fontbonne A et al. Diabetologia. 1989;32:300-304.
102
Indian Dyslipidemia
A. Isolated High Lp(a)
B. Isolated low HDL
C. Isolated high TG
32.90%
21.35%
10.45%
↑TG
↑ Lp(a)
The Triad
IHJ, 2000, 52: 173-177
Am J Med, 1998, vol 105(1A), 48S-56S
www.drsarma.in
↓HDL
103
Diabetic Dyslipidemia
↑TG
↑sLDL
The Triad
↓HDL
IHJ, 2000, 52: 173-177
Am J Med, 1998, vol 105(1A), 48S-56S
www.drsarma.in
104
Atherogenic lipid profile
↑Lp(a)
↑sLDL
The Triad
↓HDL
IHJ, 2000, 52: 173-177
Am J Med, 1998, vol 105(1A), 48S-56S
www.drsarma.in
105
Reverse Cholesterol Transport
MF in Vascular
Endothelium
LIVER
EC
Free Chol.
UEC
HDL
HDL scavenges LDL out from EM
L CAT
Enzyme
HDL Prevents LDL oxidation in EM
HDL is anti-inflammatory at EM
www.drsarma.in
106
TGs Predict CAD Risk
Independent of TC and HDL
TG <200, HDL 40+
TG 200-799,
HDL 40+ (P<0.000)
TG <200,
HDL <40 (P<0.0001)
TG 200-799,
HDL <40 (P<0.0001)
TG 800+,
any HDL (P=0.16)
Definite Type III
(P<0.0001)
0
1
2
3
4
5
6
7
8
9
10
Odds Ratio
www.drsarma.in
Hopkins PN et al. J Am Coll Cardiol. 2005;45:1003-1012.
How does ↑ ↑ TG
increase 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
www.drsarma.in
107
108
Modifiable Risk factors – BIG 6
1.
2.
3.
4.
5.
6.
www.drsarma.in
Diabetes Mellitus
Dyslipidemia
Hypertension
Smoking
Over weight and Obesity
Physical inactivity
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
www.drsarma.in
110
HT- RR of stroke and MI
20
5 Year Risk (%)
Normotensives
Hypertensives
15
10
Stroke
Myocardial
Infarction
5
0
0
20
40
60
80
100
120
140
160
180
200
220
240
260
280
300
Systolic Blood Pressure (mmHg)
www.drsarma.in
Brown, M.J. Lancet 2000; 355: 659 - 660
Is SBP more dangerous or DBP ?
www.drsarma.in
111
HT – CV Mortality
112
The Framingham Heart Study
Age-Adjusted Rate/1000
70
65
Normotensive
Hypertensive
60
50
35
40
30
29
20
14
10
0
Risk Ratio
Men
2.2
Women
2.5
Kannel WB Euro Heart J 1992;13(Suppl G):34-42.
Treatment of HT – CV Mortality
113
5 Randomized Trials in 12,483 Elderly
Hypertensives
Total Number of
Individuals Affected
600
494
500
400
300
438
438
346
383
Treatment
Control
288
Overall BP Difference
Systolic: 15 mm Hg
Diastolic: 6 mm Hg
200
100
0
Stroke
34%
p<0.001
CHD
19%
p<0.05
Vascular
Deaths
23%
p<0.001
% Reduction in odds:
Adapted from MacMahon S, Rodgers A. Clin Exper Hypertension 1993;15(6):967-978.
114
Modifiable Risk factors – BIG 6
1.
2.
3.
4.
5.
6.
www.drsarma.in
Diabetes Mellitus
Dyslipidemia
Hypertension
Smoking
Over weight and Obesity
Physical inactivity
115
Smoking – The Devil
www.drsarma.in
THE DEADLIEST DEVIL
www.drsarma.in
116
117
www.drsarma.in
118
WOMEN SMOKERS
PASSIVE SMOKERS
www.drsarma.in
119
Intense cause for concern
COLLEGE STUDENTS
TENDER AGE GROUPS
www.drsarma.in
120
AND HONESTLY
Tell me what harm smoking
does not cause ??
www.drsarma.in
Millions of Adults Aged >30 Years
121
Smoking-Related
CV Mortality in Year 2000
World
Industrialized
2
2
Countries
Developing
2
Countries
1.62
1.5
1.5
1.5
1.17
1
1
0.96
1
0.67
0.65
0.45
0.5
0.5
0.3
0.5
0.52
0.15
0
Total Men Women
www.drsarma.in
0
Total Men Women
0
Total Men Women
Ezzati M et al. Circulation. 2005;112:489-497.
122
Tobacco Smoke and Metabolic
Syndrome in Adolescents
9
Percent With MetS
8
8.7%
P<0.001
n=2,273
7
6
5.4%
5
4
3
2
1.2%
1
0
www.drsarma.in
Nonexposed
ETS Exposed
Active Smokers
ETS = environmental tobacco smoke.
Weitzman M et al. Circulation. 2005;112:862-869.
123
Modifiable Risk factors – BIG 6
1.
2.
3.
4.
5.
6.
www.drsarma.in
Diabetes Mellitus
Dyslipidemia
Hypertension
Smoking
Over weight and Obesity
Physical inactivity
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
www.drsarma.in
125
Our cut off values !
For Indians
• BMI < 23
• BMI of 23 to 24.9
• BMI of > 25
Normal
Over weight
Obesity
WC for ♂ Normal
WC for ♀ Normal
90 cm (36”)
80 cm (32”)
•
•
Central adiposity causes ↑IL6, which ↑hepatic hs-CRP
www.drsarma.in
126
Television watching became
even more convenient with
Sony’s introduction of a new
remote controlled remote control
– Tokyo News line
www.drsarma.in
This is how we walk the dog !
www.drsarma.in
127
With in no time !!
www.drsarma.in
128
129
Metabolic Syndrome - Characteristics





Hypertriglyceridemia
Low HDL-cholesterol
Elevated apolipoprotein B
Small, dense LDL particles
Inflammatory profile





Insulin resistance
Hyperinsulinemia
Glucose intolerance
Impaired fibrinolysis
Endothelial dysfunction
These features can lead to
type 2 diabetes,
hypertension and
cardiovascular disease
www.drsarma.in
130
Metabolic Syndrome
Hypertension
Microalbuminuria
Central
obesity
200% CVD Risk
www.drsarma.in
Insulin
Resistance
Hyperinsulinaemia



Hyperuricemia
 Triglycerides

Prothrombotic state
(fibrinogen,
Factor VIIa,
fibrinolytic activity)
 Small dense
LDL
 HDL
cholesterol
Impaired Glucose Tolerance

Type 2 Diabetes
Diabetes Care 1998;21(2):310–314.
Williams G, Pickup JC. Handbook of Diabetes. 2nd Edition, Blackwell Science. 1999.
Metabolic Syndrome, Syndrome X,
Deadly Quartet, Reaven’s Syndrome
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
www.drsarma.in
NCEP guidelines 2001 (WHO Modified for Indians)
131
Insulin Resistance and
Atherosclerosis relationship
132
Insulin resistance
Hyperinsulinemia
Impaired
glucose
tolerance
Hypertriglyceridemia
Decreased HDL-C
Clinical diabetes
Accelerated atherosclerosis
www.drsarma.in
Essential
hypertension
Interrelation between Atherosclerosis
and Insulin Resistance
133
Insulin Resistance
Hypertension Obesity
HyperHypertriSmall,
Low HDL HypercoaguDiabetes
insulinemia
glyceridemia dense LDL
lability
Atherosclerosis
www.drsarma.in
134
Acanthosis Nigricans
www.drsarma.in
135
Acanthosis Nigricans
www.drsarma.in
136
Acanthosis Nigricans
www.drsarma.in
137
Composite Ultrasound Carotid
Intima-Media Thickness, mm
Composite CIMT With Metabolic
Syndrome in Young Adults
0.80
r=0.997, Ptrend <0.001
0.78
0.76
0.74
0.72
0.70
0.68
0.66
0.64
0
1
2
3
4
Number of Metabolic Syndrome Components*
www.drsarma.in
*National Cholesterol Education Program definition.
Tzou WS et al. J Am Coll Cardiol. 2005;46:457-463.
138
Age-Adjusted Hazard Ratio*
Metabolic Syndrome and
10-Year CVD Risk
2.5
2
Men
Women
2.25
1.98
1.88
2.05
1.91
1.68
1.5
1.18
1
0.76
0.5
www.drsarma.in
0
Mortality
Fatal CVD
Nonfatal CVD
Fatal +
Nonfatal CVD
*National Cholesterol Education Program definition.
Dekker JM et al. Circulation. 2005;112:666-673.
139
CHD Risk Factors - Makers
• Modifiable – The New Six
– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
www.drsarma.in
140
CHD Risk Factors - Makers
• Modifiable – The New Six
– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
www.drsarma.in
141
142
143
144
145
146
147
148
149
150
151
Percent with CRP 0.22 mg/dL
Elevated CRP Levels in Obesity
NHANES 1988-1994
152
25
20
15
10
5
0
www.drsarma.in
Normal
Overweight
Obese
Visser M et al. JAMA 1999;282:2131-2135.
153
154
CHD Risk Factors - Makers
• Modifiable – The New Six
– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
www.drsarma.in
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
www.drsarma.in
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
www.drsarma.in
157
CHD Risk Factors - Makers
• Modifiable – The New Six
– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
www.drsarma.in
158
Atherogenic Particles
Apolipoprotein B
Non-HDL-C
Measurements
VLDL
VLDLR
TG-rich lipoproteins
www.drsarma.in
IDL
LDL
SDL
Cholesterol lipoproteins
159
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
www.drsarma.in
Feingold KR et al. Arterioscler Thromb. 1992;12:1496-1502.
Lamarche B et al. Circulation. 1997;95:69-75.
160
Association of Small, Dense LDL
with Myocardial Infarction
N (%)
LDL pattern (size)
Cases
Controls
A (LDL 1,2)
54 (37)
90 (63)
B (sLDL 4,5)
55 (64)
31 (36)
Odds ratio=3.0; P<0.01.
95% CI=1.7-5.2.
www.drsarma.in
Adapted from Austin M et al. JAMA. 1988;260:1917-1921.
161
CHD Risk Factors - Makers
• Modifiable – The New Six
– hs-CRP
– Lp(a)
– sLDL
– Endothelial Dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
www.drsarma.in
162
Oxidative Stress: Endothelial
Dysfunction and CAD
Hypertension
Diabetes
Smoking
LDL
Homocysteine
Estrogen
deficiency
 O2
Endothelial Cells and
 H2O2 Vascular Smooth Muscle
Endothelial Dysfunction
Apoptosis
Leukocyte
adhesion
www.drsarma.in
Lipid
deposition
Vasoconstriction
VSMC
growth
Thrombosis
Prediction future CVE by
Endothelial Dysfunction
163
What is the Rx. for
Endothelial Dysfunction?
• 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
164
165
CHD Risk Factors - Makers
• Modifiable – The New Six
– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
www.drsarma.in
166
Inter Heart Study
Apo B / Apo A1 Ratio
evidence of threshold
www.drsarma.in
No
167
CHD Risk Factors - Makers
• Modifiable – The New Six
– hs-CRP
– Lp(a)
– sLDL
– Endothelial dysfunction
– Apo B / Apo A1 ratio
– Homocysteine
www.drsarma.in
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
www.drsarma.in
169
Hyper-homocyst(e)inemia
Blood Homocyst(e)ine Levels
Classification
Normal
Moderate
Intermediate
Severe
www.drsarma.in
Values in mmol/L
05 – 10
11 – 30
31 – 100
> 100
170
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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
171
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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
Intra abdominal fat
www.drsarma.in
172
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
www.drsarma.in
174
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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 a
mirror of Cardiovascular Risk
ED = ED
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
www.drsarma.in
177
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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)
Edinburgh 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
CHD Event Outcomes
per Year (%)
 137 fatal and nonfatal CHD events during follow-up
3.8%
4
3
2
1.4%
1
0
>1.1
1.1–1.01 1.0–0.91 0.9–0.71
ABI
Leng GC et al. BMJ 1996;313:1440-1444.
<0.7
180
181
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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
182
Which is important ? SBP or DBP
www.drsarma.in
183
184
185
PulseMetric
The morphology of the waveform should be considered when interpreting the numbers below.
CARDIAC PARAMETERS
LV Ejection Time (sec)
LV dP/dt Max (mmHg/s)
LV Contractility (1/s)
Cardiac Output (L/min)
Cardiac Index (L/min/m2)
Stroke Volume (mL)
Stroke Vol Index (mL/m2)
0.373
1,200
15.95
4.41
2.47
74.2
41.6
[Normal
Range(Male)*]
[0.207 - 0.388]
[847 - 1506]
[12.39 - 19.08]
[3.59 - 7.9]
[1.95 - 3.74]
[57.7 - 100.7]
[31.8 - 48]
SYSTEMIC VASCULAR PARAMETERS
SV Compliance
1.43
[1.02 - 2]
(mL/mmHg)
SV Resistance
1598
[871 - 1902]
(dynes/sec/cm5)
BRACHIAL ARTERY PARAMETERS
BA Compliance
0.069
[0.056 - 0.132]
(mL/mmHg)
BA Distensibility
5.44
[4.38 - 9.28]
(%/mmHg)
Brachial Artery Distensibility, SVR, CO, LV dP/dt
Uses Oscillometric BP cuff
186
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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
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
www.drsarma.in
188
Definitions of abnormalities in albuminuria
Category
24 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 over
3-6 should be abnormal before considering diagnostic threshold positive
False positive: exercise < 24 hours, fever, CHF, marked hyperglycemia,
marked HTN, pyuria and hematuria.
www.drsarma.in
189
Relative Importance of MAU
10.02
10
8
6.52
6
CHD Odds
Ratio
4
3.20
2.32
2
0
Microalbuminuria
Smoking
Hypertension
Cholesterol
Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.
www.drsarma.in
190
CHD Risk Factors - Markers
• We rarely care to identify – The simple six
–
–
–
–
–
–
www.drsarma.in
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
191
TS OF HEART - LVH
Normal < 10 mm
This case 26 mm
www.drsarma.in
192
CVE and LVH
Age-Adjusted Rate/1000
The Framingham Heart Study
80
70
60
50
40
30
20
10
0
69
55
42
32
23
15
Men
Risk Ratio
No LVH
LVH
3.0
CHD
Women
3.7
10
8
Men
Women
Stroke
3.2
5.3
Cupples LA, D’Agostino RB. NIH Publication No 87-2703, Feb
1987.
193
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
www.drsarma.in
194
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
www.drsarma.in
Dippers & Non Dippers
Systolic Blood Pressure
Systolic Blood Pressure (mm Hg)
160
150
140
Non - dippers
130
Dippers
120
110
6
8
10
12
14
16
18
20
22
24
2
4
24 hours clock time
www.drsarma.in
Yonsei, Med J, Vol 43, No 3: 2002
195
Dippers & Non Dippers
Diastolic Blood Pressure (mm Hg)
Diastolic Blood Pressure
100
90
Non - dippers
80
Dippers
70
6
8
10
12
14
16
18
20
22
24
2
4
24 hours clock time
www.drsarma.in
Yonsei, Med J, Vol 43, No 3: 2002
196
197
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
www.drsarma.in
198
Brachial Artery Flow-Mediated Vasodilation
3.6 mm
3.1 mm
Baseline
www.drsarma.in
5 Minutes
Blood Pressure Cuff
Occlusion – 1 Minute
Release
Post-Occlusion
199
Management
of CHD Risk
www.drsarma.in
200
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
www.drsarma.in
201
CHD Risk Scoring
• Framingham Risk Score
• UKPDS Risk Engine
• PROCAM Risk Calculator
• Diabetes PHD (ADA)
www.drsarma.in
The PROCAM Algorithm
MI´s (%) in 10 Years
25
21.4
20
15
10
5
0
7.6
0.6
I
2.1
2.8
II
III
IV
Quintile of point Score
V
Independent variables were: age, systolic blood pressure, LDL-C,
HDL-C, triglycerides, diabetes mellitus, smoking, family history of MI
325 fatal and nonfatal myocardial infarctions in 4,818 men aged 35-65 years
203
T2DM Risk Estimation
• HOMA Calculator
• Indian Diabetic Risk Score
www.drsarma.in
204
CHD Prevention
Total Life Style Change (TLC)
Medical Nutrition Therapy (MNT)
Physical Activity (PA)
www.drsarma.in
205
www.drsarma.in
206
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
www.drsarma.in
207
CVD Risk Management
Intervention
• Dietary/weight
counseling
Diabetes management
• Exercise
• Education of patients
and families
www.drsarma.in
Goals
• Achieve optimal BMI
•  saturated fats;  fruits,
vegetables, fiber
• Achieve HbA1c <7%
• 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.
208
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
www.drsarma.in
209
Foods - Glycemic Index
www.drsarma.in
DASH DIET
Type of Food
Grains (whole grains)
Vegetables
Fruits (not tinned juices)
Low fat milk
Lean meat, poultry
Nuts, seeds (dry roast, soak)
Fats and oils
Sweets and pastries
Salt at table and salted foods
www.drsarma.in
Servings (1600 K cal)
6 per day
3 per day
4 per day
2 per day
3 per day
3 per week
2 per day
0 per day
None
210
Alternative Food Plans
Healthy Eating Pyramid
www.drsarma.in
211
Vegetarian Food Pyramid
www.drsarma.in
212
213
www.drsarma.in
www.drsarma.in
 Fruits and vegetables 214
 Fruit sugars are safe
 Fruit pulp is to be eaten
 Not canned fruits, juices
 Avoid coffee, chocolate
 Gift fruits - not sweets
 Offer fruits as courtesy
 Eat fresh cut vegetables
 Snack on fruits, nuts
 Don’t over cook veg.
 Reduce simple CHO
 Fruits give us K+
 Use soups, butter milk
215
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
www.drsarma.in
ATP III: Nutritional
Components of the TLC Diet
Nutrient
Recommended Intake
Saturated fat*
<7% of total calories
Polyunsaturated fat
Up to 10% of total calories
Monounsaturated fat
Up to 20% of total calories
Total fat
25%–35% of total calories
Carbohydrate (esp. complex carbs)
Fiber
50%–60% of total calories
30–40 g/d
Protein
Cholesterol
216
~15% of total calories
<200 mg/d
*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.
www.drsarma.in
Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
Chemical Structure of Fats
www.drsarma.in
217
Comparison of Dietary Fats
www.drsarma.in
218
Reduced Intake of Trans-Fatty
Acids: Estimated Effects on CHD*
219
Proportion of CHD Events Preventable
in the United States (%)†
Based on change in total: HDL-C (dietary trials)
Based on replacement with carbohydrates (prospective studies)
0
Based on additional benefits of replacement with cis unsaturated fats
(prospective studies)
-5
-10
-15
-20
-25
Reduction by half
*Nonfatal myocardial infarction or death
†Population attributable risk
CHD=coronary heart disease
www.drsarma.in
Near-elimination
Population Change in
Trans-Fatty Acid Intake
Mozaffarian D et al. N Engl J Med. 2006;354:1601-1613.
Fruit/Vegetable Consumption:
Effects on Stroke Risk Reduction
Meta-Analysis of 8 Studies
(N=257,551)
3-5 vs <3 servings
0.89
(0.83-0.97)
P=0.005
>5 vs <3 servings
0.74
(0.69-0.79)
P<0.0001
0.5
1.0
1.5
Pooled Relative Risk
(95% CI)
www.drsarma.in
He FJ et al. Lancet. 2006;367:320-326.
220
Percent Mortality Reduction
Approximate Mortality Reduction:
Pharmacotherapy* and Lifestyle/Diet†
221
45
40
35
30
25
20
18
21
23
26
Potential
lifestyle/
diet range
(approx.)
15
10
5
0
Low-dose
Aspirin
Statins
*In coronary artery disease patients.
†After myocardial infarction.
www.drsarma.in
Betablockers
ACEIs
Adapted from Iestra JA et al. Circulation. 2005;112:924-934.
222
Effect of Lifestyle Changes
on Angiographic CAD
Duration % (Control-Treatment)
Study
N
Lifestyle
28
CAD
Diet, exercise,
meditation
1
35
-40
STARS
90
CAD, high TC
Diet (including
fiber)
3.2
35
-38
CAD
Diet + exercise
1
25
-15
Heidelberg
www.drsarma.in
113
Patient type
Therapy
(yr)
Progression Regression
Superko HR, Krauss RM. Circulation. 1994;90:1056-1069.
223
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
www.drsarma.in
224
CHD Prevention
Smoking Cessation
www.drsarma.in
225
SURE TO GRAVE
www.drsarma.in
226
How to Quit Smoking ?
Five steps in quitting
• Ask all patients about
Onus is on the Doctor
• personal history of smoking
One success is great !
• exposure to passive smoke inhalation
• ASK
• Ask at each visit to check smoking status
• ADVISE
• ASSESS
• Advice to quit must be clear and
unambiguous
• ASSIST
• Be supportive and nonjudgmental !
• ARRANGE
• Remember, you aren’t the one quitting !
• Offer resources and support consistent
with individual’s needs readiness to quit
• Follow-up at each visit !
www.drsarma.in
227
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
www.drsarma.in
• 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
228
Smoking Cessation
1.
2.
3.
4.
Bupropion
Smoquit-SR, Nicotex
•
Helpful for physical withdrawal symptoms
•
Can be dosed according to degree of use
In psychological
•
dependence on nicotine
•
Useful in individuals with
or at risk for depression–
•
Contraindicated in drug
interactions or seizure •
disorder
•
www.drsarma.in
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
229
CHD Prevention
Medications
www.drsarma.in
AHA Evidence-Based Guidelines
For CVD Prevention
230
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
www.drsarma.in
Expert Panel/Writing Group. Circulation. 2004;109:672-693.
231
CHD Prevention
Strategies
www.drsarma.in
232
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
www.drsarma.in
233
Secondary Prevention of CHD
•
•
•
•
•
•
•
•
www.drsarma.in
Hypertension control
Beta blockers
Aspirin 150 to 300 mg
ACEi or ARB
Aggressive Statin therapy
PTCA; CABG
Smoking cessation
Exercise rehabilitation
Lowest Effective Aspirin Dose
for MI and Stroke Reduction
• Primary Prevention
– MI in men ≥50
– MI in women ≥50
– Stroke in men ≥50
– Stroke in women ≥50
– Stroke in men/women with AF
• Secondary Prevention (in men/women)
– MI with HX stable CAD
– MI with HX AMI
– Stroke with HG stroke/TIA
– Stroke without HG acute stroke
www.drsarma.in
234
(mg/d)
160
100
160
100
325
(mg/d)
75
160
50
160
Dalen JE. Am J Med. 2006;119:198-202.
235
Secondary Prevention of CAD
www.drsarma.in
236
Control of Diabetes
www.drsarma.in
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
www.drsarma.in
237
Control of DM
•
Oral Agents
1.
2.
3.
4.
5.
•
Insulins
–
•
Metformin
Sulfonylureas – New Generation
Thiazolidines – Pioglitazone, Rosiglitazone
Repaglinide and Metaglinide
AGIs – Acarbose, Meglitol
Conventional, Pens, Analog insulins, Aerosol, Pump
Latest developments
–
www.drsarma.in
Exenitide, GLP-1 analogs, Dual PPARs, Amylin
238
239
Diabetes Prevention Program
Placebo
(n=1,082)
Metformin
(n=1,073)
Lifestyle
(n=1,079)
31/69
34/66
32/68
Age (y)
50 ± 10
51 ± 10
51 ± 11
Fasting plasma glucose
(mg/dL)
107 ± 8
107 ± 9
106 ± 8
Plasma glucose 2 hours
postchallenge (mg/dL)
165 ± 17
165 ± 17
164 ± 17
11
7.8
31 (17–43)
4.8
58 (48–66)
Baseline Characteristics
Male/Female (%)
Results
Diabetes incidence*
RRR (%, 95% CI)†
*Cases
per 100 person-years; †vs placebo.
RRR=relative risk reduction.
DPP Research Group. N Engl J Med. 2002;346:393-403.
Secondary Prevention: CHD Risk Reduction in
the 4S Subgroup of Patients With Diabetes
No. patients
with events
P
Total mortality
232
24
CHD mortality
172
17
Major CHD event
578
44
Any CHD event
871
56
CABG or PTCA
363
20
Cerebrovascular event
90
12
Any atherosclerotic event 961
61
Nondiabetic
Diabetic
Simvastatin
better
240
Placebo
better
S
167
15
99
12
407
24
667
41
238
15
70
5
750
46
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
RR with 95% CIs
Pyörälä K et al. Diabetes Care. 1997;20:614-620.
241
Control of Hypertension
www.drsarma.in
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
www.drsarma.in
242
243
Control of Dyslipidemia
www.drsarma.in
Clinical Benefits of
Cholesterol Reduction
244
• A recent meta-analysis of 38 trials demonstrated 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
www.drsarma.in
Gould AL et al. Circulation. 1998;97:946-952.
245
LDL-C Lowering - Statin Dose
Atorvastatin
211 mg/dl*
Simvastatin
219 mg/dl*
Daily Dose
0%
-10%
-20%
38%
20 mg
-30%
-40%
46%
-50%
51%
54%
-60%
10 mg
28%
35%
41%
16% with
3 Titrations
13
%
40 mg
80 mg
Adapted from Jones P et al. Am J Cardiol 1998;81:582-587.
Dr.Sarma@works
246
Ezetimibe Efficacy (“10 + 10 = 80”)
0%
Ezt + Ator
10+10 mg
(n=65)
Atorvastatin
10 mg
(n=60)
20 mg
(n=60)
40 mg
(n=66)
80 mg
(n=62)
-10%
-20%
-30%
–37%
-40%
-50%
–42%
–53%
–45%
–54%
-60%
P < 0.01
Dr.Sarma@works
Ballantyne CM et al. Circulation 2003;107:2409-2415.
247
Post-CABG Study - Aggressive
v/s Moderate Treatment
160
150
140
Moderate Tx (134-136)*
130
LDL-C 120
(mg/dL)
110
100
90
Aggressive Tx (93-96)*
80
0
6
12
24
36
48
Follow-up (mo)
* Mean achieved.
www.drsarma.in
Post-CABG Trial Investigators. N Engl J Med. 1997;336:153-162.
Non-pharmacological Approaches
to TG Lowering
248
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
www.drsarma.in
Coughlan BJ et al. Postgraduate Med Online. 2000;108(7).
Pejic RN, Lee DT. J Am Board Fam Med. 2006;19:310-316.
New Treatments
1. 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%
www.drsarma.in
249
250
The Three Canons
DYSLIPIDEMIA
↑ LDL - STATIN
www.drsarma.in
251
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
www.drsarma.in
252
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
↑ Phenotype B
Under research DM, Obesity ↓
↓ in Phenotype A
Under research Aerobic exercise
www.drsarma.in
Statin no effect
253
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
www.drsarma.in
254
Take Home Messages
www.drsarma.in
Modifiable
CHD – Risk Factors
Non-Modifiable
6. Phenotype B
5. Personality
4. F. Hx CVD
3. Ethnicity
2. Gender
1. Age
255
6. Physical Inactive
5. Obesity, ↑ WC
4. Lipid Abnor
3. Smoking
2. Inc.BP
1. DM
CHD RF
Emerging
6.Homocysteines
5. ApoA1/ ApoB
4. hs- CRP
3. ↑SLDL
2. Lp(a)
1. ED
www.drsarma.in
1.
Grundy SM et al. Circulation
1999;100:1481–1492;
2.
Haffner SM et al. N Engl J Med
1998;339:229–234
Sapta Padi – The Seven Steps
1.
2.
3.
4.
5.
6.
7.
Screen, define and target high risk patients
Modify life style factors – MNT, PA
Explain and persuade to quit smoking, ↓ alcohol
Aspirin >100 mg in all those with > 1 RF (??)
Aggressive control of DM – HBA1c < 7
Attain goal B.P of 140/90 in all – DM 10 mm less
ACEi and statin for all DM, Statin for ↑ LDL,
Address HDL, Lp(a), TG, hs-CRP if abnormal
www.drsarma.in
256
257
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
www.drsarma.in
258
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
www.drsarma.in
259
Our each
Cardio-metabolic
patient
For
Ill at least one
Pill
Minimum medication needed
# Pills
Glimiperide 1 + Metformin 500
1
Pioglitazone 15 mg
1
Nitrate long acting 1 bid
2
Aspirin 150 + Clopidogrel 75
1
Statin + Ezetemibe
1
Fibrate or Niacin
1
Ramipril 5 + Hydrochlorthiazide
1
Carveidilol or Metoprolol b.i.d
2
Other supportive medication
2
Total (conservative)
12
www.drsarma.in
Cost/day
4
2
6
3
9
6
7
8
5
50
260
At what cost one suffers !!
1.
2.
3.
4.
5.
6.
7.
8.
9.
Rs 50 x 30 days = 1500 x 12 months = 18,000/yr
Age 45 to 65 – 20 years x 18,000 = 3,60,000
Cost of CABG or PTCA + Stent = 2,00,000
What about the cost of his consultations, tests etc.
What about his co-morbidities like OA, Cataract
What about his inter current illnesses and admiss.
What about treatment for CHF, RF, PVD, Laser
No third party payer – has to spend by himself !!
What is value of all this prolonged suffering ? ?
www.drsarma.in
261
Hippocrates said ….
Let your FOOD be your Medicine – Lest,
Your Medicines will replace your Food !!
www.drsarma.in
262
Where are we heading ? ?
20000 B.C.
2004
Paleolithic sup. age
Neolithic age
19th century
21st century
Technology has changedProcessed
a lot in the way we live
Hunting-gathering
subsistence
High level of
physical activity
But, we have not
Thrifty genotype
foods
Animal fats
and glucides
¯ Dietary fibre
Sedentary
altered our
life
life style
Susceptibility genotype
Journal of internal medicine 2003:254(2):114-25
www.drsarma.in
263
We have to pay the very heavy price !!
What could be prevented, we treat or leave
www.drsarma.in
264
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
www.drsarma.in
265
www.drsarma.in
1
266
O ! God, I shall blame YOU ?
Maruvanu Ahaarambunu
I will not refrain from over eating
Maruvanu Paaneeyambunu
Neither will part with my drinking
Maruvanu naa durgunamulu
Nor, say good bye to my vices
www.drsarma.in
267
O ! God, I shall blame YOU ?
Maruvanu Ahaarambunu
I will not refrain from over eating
Maruvanu Paaneeyambunu
Neither will part with my drinking
Maruvanu naa durgunamulu
Nor, say good bye to my vices
Maracheda vyaayambunu
I shall forget my physical exercise
Maracheda sat karmabula
I will not care for healthy life style
Maracheda gurula boodhalu
I shall forget what all is instructed
www.drsarma.in
268
Dear GOD, let a miracle happen !
Please, save my Dad/Mom
www.drsarma.in