CAD in Indians by Dr Sarma

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CAD in Indians by Dr Sarma

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Title: CAD in Indians by Dr Sarma

1
Welcome
2
CD ROM Available

The contents of my todays presentations
are made available in a CD-ROM format
This CD, in addition, contains my talks on
Asthma, COPD, Hypertension, ECG, CAD
Dyslipidemias, Diabetes, Osteoporosis

3
Knowledge that isnt implemented never works
4
Coronary Artery Disease in Indians (C A D I)
5
Coronary Heart Disease in IndiansIs it different
from CAD elsewhere ?Should we test it
differently ?What should be our strategy ?

Dr. Sarma V.S.N. Rachakonda
M.D., (Med) M.Sc., (Canada)
Consultant Physician Chest Specialist
visit us at www.drsarma.in

6
http//www.ispub.com/ijc/vol1n2/cadi.xml
7
A must read book
8
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

We have glorious culture, traditions and values
Excellent present prosperity
Enviable future projections too
Innumerable great achievements in all fields
In spite of our three Ps (population, poverty,
politicians)
We are proud to be the children of our mother
land
For a glimpse of the glory of our Bhaarat please
visit
http//chyk.net/Indian_culture.power.asp for a
slide show
With highest reverence and salutations to Mother
India.

11
With Great Reverence

Saare jehan se achchaa .Hindustan hamara
Saare jehan se oonchaa .T2DM hamara hamara
Saare jehan se oonchaa .CADI hamara hamara
2 to 6 fold higher CAD than people of other
ethnicity
Indians have the highest among the highest CAD
rates
Irrespective of gender, region, religion, SES
Same is true of immigrant Indians all over the
globe
CAD risk is considerable even in vegetarian
Indians
Indian CAD is 10 years younger, Often silent MI
Triple vessel disease, SD, MACE are more in
Indians

12
(No Transcript)
13
CADI is Malignant

CADI strikes early !
CADI strikes hard !!
CADI strikes almost any one !!!
CADI strikes unexpectedly !!!!
Conventional RF cant explain it away
CADI is malignant in its onslaught.

14
CAD Mortality
Age Adjusted mortality for 100,000 population per
year in 35-74 age.
15
CAD in Indians
16
CAD in Asian Indians
17
MI in Singapore - Ethnicity
18
CAD in California - Ethnicity
19
CAD Deaths 7 Countries study
20
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

We are in the middle of the wave of CAD epidemic
This CADI epidemic will peak by 2015
50 deaths in India will be CVD deaths.
CADI will overtake Infectious diseases.
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
curable

23
The Quotes

Genetics loads the gun, environment pulls the
trigger. Even if you have a loaded gun, you dont
pull the trigger, no harm is done."
Dr.Enas A Enas
Director, CADI Research Foundation
Just being an Indian places you at higher risk
for heart disease than having high cholesterol
being a smoker
Dr. H. Robert Superko
Director, Berkeley Heart Lab
A lot of people, they just look healthy, they
feel healthy, they dont get tested for heart
disease. By the time some of them find out they
have CAD, theyre either in an ambulance or a
hospital bed
Dr.A.K. Rao
National Asian Indian Heart Disease Program

24
The Berkeley Study

25 of the MIs occur below 40 yrs, unheard of
any where
In the young Indians (lt 30 yrs), CAD mortality is
three fold higher than Whites in UK and ten fold
higher than Chinese.
Sadly many of the Indians are dying young !!
Indians have higher prevalence of thrombotic risk
factors
The conventional risk factors become doubly
dangerous
Even pre-menopausal women showed multi vessel CADI

25
UK Indian Study
Age-specific death rates form CAD in UK Indians
and general population per 100,000/yr
Balrajan et al, I Heart J 1999
26
CADI Strikes the Young
Enas A Enas et al, I Heart J 2001
27
We have worsened !!
Prevalence of CAD in India from 1960 - 2001
12
11
9.7
10.9
10
8
5.5
Prevalence
6
6.5
4
4
2
0
(1) 1960 30-
(2) 1962 30-
(3) 1968 gt30
(4) 1990 25-
(5) 1994 35-
(6) 2001
70 years
70 years
years
64 years
64 years
gt20 years
Year
Indian Heart J 2002 54 103
1. Agra 3. N India 4. Delhi 6. Chennai
28
CADI Research Foundation
Enas A Enas et al A Heart J 2001
(www.cadiresearch.com) (www.southasianheartcenter.
org) Erectile Dysfunction A Warning Sign for
Heart Disease
29
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

There is a CAD tsunami in India
The immediate step is awareness of CADI
Awareness among doctors is crucial
Then, we need to educate the population at large
Second step is employing preventive strategies
The key to tackling this Tsunami lies in
prevention
PadmaShri Prof. Ashok Seth
Intervention Cardiologist, AIIMS

32
Key Points

Risk for CAD begins in early childhood
Plaque build up develops later in life due to RF
CAD is not an unavoidable consequence for all
Risky blood paves the way for plaque build up
Small, soft, inflamed, lipid rich plaque ruptures
75 of MI occur in people with lt 25 stenosis
Only 1/3 have advanced warning as chest pain
Half of SDs occur in so called Healthy persons
2/3 of these SDs occur before they reach hospital
Dont wait. Begin heart healthy life style now!

33
SHARE and CUPS

The Chennai Urban Population Study (CUPS)
Prevalence of CAD to be 11
10 folds increase in the last 40 years
The Study of Health Assessment and Risk in Ethnic
groups (SHARE) in Canada
CAD prevalence in migrant Indians to be 10.7 ,
in Europeans 4.9 and in Chinese 1.9 .
Analysis of 1.2 m deaths from 1979 to 1993, in
Canada
Mortality in Canadian SA men women 42 and 29
In European men and women 29 and 18
In Chinese men and women 18 and 11

34
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

9. Good, Bad, Ugly Deadly 10. Why not count
the boats ? 11. How to count the risks ? 12. The
Missing Links !! 13. Our Women are Men 14. Our
Novelty of risk factors 15. Fuel on Fire / Fire
on Fuel? 16. Is it the End of the Road?
35
The Progressive Development of Cardiovascular
Disease
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
36
Mirrors of CV Health

Diabetes Mellitus (DM CAD)
Hypertension, Isolated Systolic Hypertension
Pulse Pressure, Mean Arterial Pressure (MAP)
Metabolic syndrome
Left Ventricular Hypertrophy
ABI (Ankle Brachial Index)
Micro albuminuria (MAU)
Intermittent claudication
Erectile Dysfunction (ED)
Retinopathy

37
Dushta Chatushtayam
SMOKING
Only 35- 50 of the angiographically proved CADI
is accounted for by these BIG FOUR
HEART ATTACK
DIABETES
HYPERTENSION
? CHOLESTEROL
38
HT CV Mortality
The Framingham Heart Study
Risk Ratio
2.2
2.5
Kannel WB Euro Heart J 199213(Suppl G)34-42.
39
Treatment of HT CV Mortality
5 Randomized Trials in 12,483 Elderly
Hypertensives
494
438
438
383
346
Total Number of Individuals Affected
288
Overall BP Difference Systolic 15 mm
Hg Diastolic 6 mm Hg
Reduction in odds
19 plt0.05
34 plt0.001
23 plt0.001
Adapted from MacMahon S, Rodgers A. Clin Exper
Hypertension 199315(6)967-978.
40
CVE and LVH
The Framingham Heart Study
CHD
Stroke
Risk Ratio
3.2
5.3
3.7
3.0
Cupples LA, DAgostino RB. NIH Publication No
87-2703, Feb 1987.
41
DM and CVE LIFE study
Increased Risk of Primary Endpoint
(n7998)
(n7867)
(n1195)
(n1326)
Relative Risk 2.0
1.2

42
DM and CAD - CUPS
Mohan V et al CUPS
(www.cadiresearch.com) (www.southasianheartcenter.
org) Erectile Dysfunction A Warning Sign for
Heart Disease
43
HT and CAD in CUPS
Mohan V et al CUPS
44
How important is the CAG ?

2/3 of ACS result from CA stenosis of lt 50
lt 15 MI result from CA stenosis of lt 75
CAG may give a false sense of security
In asymptomatic subjects CAG not indicated
Instead focus on conventional and novel RF
In ACS, CAG is a must to plan Rx. strategy
The nature of the plaque determines occlusion
Lipid rich, soft plaques are rupture vulnerable

45
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

Genetics loads the gun
Indian CAD Gun is heavily loaded
CADI is a combination of Nature and Nurture
Genetically high Lp(a) levels
Genetic predisposition to DM, IRS, TNFr2
Atherogenic Lipoprotein Phenotype (ALP)
Genetically low HDL 2b sub fraction
Genetically more of LDL Phenotype B
Elevated Homocysteine in Indians (tHCy)

47
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

CADI is a combination of Nature and Nurture
Sedentary life style, Affluence, Urbanization
?CHO, Crunchy, munchy, fatty food habits
Minimal or non eating of fruits, nuts, vegetables
?Fiber, Over boiling, Reuse of oil, ?Fast foods
Central adiposity, Visceral fat, IRS
Carelessness about risk assessment
Emphasis on treatment rather than prevention
Device ridden, Intervention oriented approach
Extremely important, often forgotten factor -
Stress

50
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
Who pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

9. Good, Bad, Ugly Deadly 10. Why not count
the boats ? 11. How to count the risks ? 12. The
Missing Links !! 13. Our Women are Men 14. Our
Novelty of risk factors 15. Fuel on Fire / Fire
on Fuel? 16. Is it the End of the Road?
51
Intra abdominal fat
52
The Treasure in Tummy
Normal
Central Adiposity
Courtesy of Wilfred Y. Fujimoto, MD.
Courtesy of Wilfred Y. Fujimoto, MD.
53
Metabolic Syndrome

Insulin resistance Hyperinsulinemia
Hyperglycemia IFG, IGT, DMII
Pro-inflammatory state (?CRP)
Pro-coagulant changes (?PAI-1, ?Fibrinogen)
Dyslipidemia (?TG, ?HDL)
Premature atherosclerosis, IHD, CAD
Type 2 diabetes
Hypertension, ED
Prevalence of 17 to 25 in Indians gt 30

54
Our cut off values !

For Indians
BMI lt 23 Normal
BMI of 23 to 24.9 Over weight
BMI of gt 25 Obesity

BMI lt 23, WC Normal - Good
BMI gt 23, WC Normal - Bad
BMI lt 23, WC Increased - Worse
BMI gt 23, WC Increased - Worst

Central adiposity causes ?IL6, which ?hepatic
hs-CRP
55
Metabolic Syndrome
200 CVD Risk
Diabetes Care 199821(2)310314. Williams G,
Pickup JC. Handbook of Diabetes. 2nd Edition,
Blackwell Science. 1999.
56
Metabolic Syndrome, Syndrome X, Deadly Quartet,
Reavens Syndrome

Risk Factor Defining Level
Abdominal Obesity Waist Circumference
Men gt90 cm (gt36 in)
Women gt80 cm (gt32 in)
Triglycerides gt150 mg/dl
HDL cholesterol
Men lt40 mg/dl
Women lt50 mg/dl
Blood pressure gt130/gt85 mmHg
Fasting glucose gt110 mg/dl

NCEP guidelines 2001 (WHO Modified for Indians)
57
Acanthosis Nigricans
58
Acanthosis Nigricans
59
Acanthosis Nigricans
60
Plasma Insulin Levels in Asian Indians
Europeans Mohan et al 1986

Basal Insulin
Levels (Micro u/ml)
Indians Europeans P value

Non diabetics 16.7 3.0 6.9 0.9 lt
0.01 Diabetics 18.0 5.0 11.5 0.9 lt 0.05
61
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

9. Good, Bad, Ugly Deadly 10. Why not count
the boats ? 11. How to count the risks ? 12. The
Missing Links !! 13. Our Women are Men 14. Our
Novelty of risk factors 15. Fuel on Fire / Fire
on Fuel? 16. Is it the End of the Road?
62
The Thrifty Genes
The human race adapted over millions of years to
living in a world of scarcity, where it paid to
eat everything good tasting in sight when you
could find it.
63
Evolution ?
64
Is this the way ?
Fast and Fatty Foods
Urban Children on an average watch TV for 2-2.5
hrs. in a day
65
Childhood Obesity
Fat pre-teens have arteries of middle-aged
smoker Sharon Kirkey CanWest Med University
66
Television watching became even more convenient
with Sonys introduction of a new remote
controlled remote control Tokyo News line
67
This how we walk the dog !
68
Influence of Affluence

Rapid Urbanization
Rural to Urban Migration
Brain drain to affluent countries
Mechanization and lack of hard physical work
Poor physical activity and sedentary life style
Couch potatoes and Mouse potatoes !!
Increase in calorific and fatty food
Psychological stress of the affluent way of life
Childhood and Adolescent Obesity

69
With in no time !!
70
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

9. Good, Bad, Ugly Deadly 10. Why not count
the boats ? 11. How to count the risks ? 12. The
Missing Links !! 13. Our Women are Men 14. Our
Novelty of risk factors 15. Fuel on Fire / Fire
on Fuel? 16. Is it the End of the Road?
71
Lipoproteins - Boats
Apo A I and A II for HDL Apo B100 for LDL Apo
B100CE VLDL, IDL Apo B100Apo(a) Lp(a)
72
Good, Bad, Ugly Deadly
LDL
GOOD
BAD
VLDL
Lp(a)
UGLY
DEADLY
TG
73
Apolipoprotein B
All are the terrorists
74
Apolipoproteins A1, A2
The soldier-like
The soldiers
75
Blood Lipids

Total Cholesterol lt 200
Good Cholesterol
HDL 1, HDL 2, HDL 3 gt 50
Bad Cholesterols (Non HDLc) lt 150
LDLc, IDLc, SDL lt 100
VLDLc, VLDLr lt 30
Lp(a) lt 20

HDL 1 and HDL 2 are protective HDL 3 Neutral
76
Typical Lipid Profile in Rural China

Total Cholesterol 127
Good Cholesterol
HDL 1, HDL 2, HDL 3 44
Bad Cholesterols (Non HDLc) 83
LDLc, IDLc, SDL 53
VLDLc, VLDLr 20
Lp(a) 10

Highly anti atherogenic lipid profile In some
communities with TC of 80 mg CAD is virtually nil
77
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

Instead of measuring Good, Bad, Ugly Deadly
Better count Apo B boats carrying the terrorists
Count Apo A1 boats carrying the soldiers
Apo A2 carries soldier-like (scouts) people
Express the ratio of Apo B Apo A1
It indicates the ratio of terrorists to soldiers
Apo B includes LDL, VLDL (TG), sLDL, Lp(a)
Apo A1 includes only HDL1 and HDL2
This is the approach used in Interheart study
It is available, not very expensive, ratio lt 2
good

79
Inter Heart Study
Apo B / Apo A1 Ratio No evidence of threshold
80
The Interheart Study

Dyslipidemia
Current smoking
Diabetes
Hypertension
Abdominal obesity (waist circumference)
Psychosocial (stress, depression)
Lack of daily fruit and vegetables in diet
Lack of exercise
Alcohol

81
Inter Heart Study

Nine simple and modifiable risk factors are
strongly associated with acute MI worldwide.
These 9 risk factors account for gt90 of the
PAR globally and in most regions.
Abnormal ApoB-ApoA1 ratio and smoking are the
2 most important risk factors and account for
over two thirds of the PAR.
Implementing preventive strategies would prevent
the majority of premature CHD worldwide.

PAR population attributable risk Apo
apolipoprotein
YusufS et al. Lancet. 2004364937-52.
82
Inter Heart Study
Multiplicative effect of risk
83
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

9. Good, Bad, Ugly Deadly 10. Why not count
the boats ? 11. How to count the risks ? 12. The
Missing Links !! 13. Our Women are Men 14. Our
Novelty of risk factors 15. Fuel on Fire / Fire
on Fuel? 16. Is it the End of the Road?
84
CAD in Asian Indians - RF
85
Total Cholesterol and CAD
Castelli WP. Atherosclerosis. 1996124(suppl)S1-S
9. ?1996 Reprinted with permission from Elsevier
Science.
86
CADI Urban v/s Rural

Urban Delhi Rural
Haryana
Risk Factor Female Male Female Male n1594 n1456
n1417 n1070
Smoking 2.6 28.7 25.3 54.7
BMI gt25 Kg/m2 48.6 35.5 11.4 7.9
Apple shape obesity 39.1 70.9 22.1 42.3
Hypertension 29.0 25.5 10.8 14.0
Diabetes 11.2 10.9 2.6 2.9
Cholesterol gt200 39.7 36.8 16.3 16.3
HDL Cholesterol lt40 59.9 38.7 55.9 45.6
Triglycerides gt150 39.7 45.2 29.9 33.0
mg/dl

Sethi K.K. Coronary Artery Disease in Indians,
1998
87
Lp(a) in Young Indian Patients with
Angiographically Proven CHD

Parameter Patients
Total cholesterol gt200 mg/dl 54.3
Triglyceride gt200 mg/dl 56.1
HDL lt35 mg/dl 59.6
Lp(a) gt30 mg/dl 61.4

n57 age lt40 yrs Mishra et al (Cuttack) Indian
Heart J 2001 53 Abst 60
88
CAD Deaths - Cholesterol
89
CADI v/s FHS study
90
RF in CAD PROCAM Study
Odds Ratio for CAD when LP(a) gt 20 mg
91
Coronary heart disease and HDL-CFramingham Heart
Study
200
150
Rate/1000
100
Women
50
Men
0
lt25
2534
3544
4554
5564
6574
75
HDL-C (mg/dl)
Gordon, Castelli et al. Am J Med 1977 62 707714
92
Relative risks of MI
The Physicians Health Study
3.78
3.21
Low HDL cholesterol lt47 mg/dl
2.41
1.00
High HDL cholesterol ?47 mg/dl
Low total cholesterol lt212 mg/dl
High total cholesterol ?212 mg/dl
Stampfer, Sacks et al. N Engl J Med 1991 325
373381
93
HDL-C vs LDL-C as a predictor of CHD risk
CHD RR
Risk of CAD over 4 years of follow-up
3
2.5
HDL-C
2
1.5
25 mg/dl
45 mg/dl
1
65 mg/dl
0.5
85 mg/dl
0
100 mg/dl
160 mg/dl
220 mg/dl
LDL-C
Men aged 5070
Gordon, Castelli et al. Am J Med 1977 62 707714
94
HDL-C is strongly predictive despite desirable
TC
Developing subsequent CAD events ()
80
70
75 lt35 mg/dl
60
50
Percentage
40
45 gt35 mg/dl
30
20
10
0
HDL-C levels
Miller, Circulation 1992 86 11651170
95
RF for CV Events
Ridker et al, N Engl J Med. 2000342836-43
96
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

High Triglyceride levels
Low levels of HDL
High levels of small dense LDL
Atherogenic lipoprotein phenotype (ALP)
Moderately increase in LDL levels

Asian J Diabetol Jan-Mar 200215-18 Lipid
DisordersImplications Management Ed. Tripathy
Das, 2002 Sethi K.K. Coronary Artery Disease in
Indians, 1998
98
Missing Links

35 to 50 of CADI only have the BIG FOUR
Many CADI have no traditional risk factors.
Low HDL by itself is Dyslipidemia in Indians
Many have normal LDL but low HDL
30 to 50 may not have BIG four and ?HDL
High Lp(a), MS, ?TG, tHCy account for most
sLDL, ?Fibrinogen, Inflammation, Infection
Elevated Homocysteine in Indians (tHCy)

99
Lipoprotein(a) or Lp(a)

Similar to LDL molecule
A single apo-A is attached by a disulfide
bond to apo-B 100
Primary determinant is genetic
Normal value 20 mg , gt 30 mg high risk
It competes with plasminogen because of its
structural similarity and so interferes with
plasmin synthesis and thrombolytic pathway
Nicotinic acid, Statins, Fibrate noeffect
TRUFA ?Lp(a) and n-3 fattys (Omega) ?Lp(a)

100
Association of Lp(a) to CAD

Meta analysis of 27 prospective studies, 5436 CHD
cases, F/u of 10 yrs
People with Lp(a) levels in the top third of
baseline measurement are at about 70 increased
risk of CHD compared with those in the bottom
third.
Circulation, 2000, 102 1082-1085
Serum Lp(a) is an independent risk factor for CAD
in NIDDM patients in south India
Diabetes care, 1998, 21, 1819-1823

101
Multiplicative with Lp(a)

Low HDL High LDL
LP(a) excess gt 30 mg
LP(a) excess gt 30 mg LDL high
LP(a) excess gt 30 mg low HDL
LP(a) excess gt 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

102
CAD Lp(a) PROCAM Study
Odds Ratio for CAD LP(a) levels, TC/HDL
103
Hypertriglyceridemia and CHD Risk Associated
Abnormalities

Atherogenic lipoprotein profile or Phenotype B
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
Elevated levels of fibrinogen

The Netherlands J Med , 2000, 56110-118
104

This ALP is present and seen in
Insulin resistant individuals
Diabetics
More prevalent in India

105
Cumulative Distribution of Adjusted Plasma TG
Levels LDL Phenotypes A and B
100
90
80
70
60
Cumulativefrequency
50
40
Phenotype A
30
Phenotype B
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. 199082495-506.
106
Cumulative Distribution of Adjusted HDL LDL
Phenotypes A and B
100
90
80
70
60
Cumulativefrequency
50
Phenotype A
40
Phenotype B
30
20
20
25
30
35
40
45
50
55
60
65
70
75
80
HDL-C (mg/dL)
Austin M et al. Circulation. 199082495-506.
107

When Tg gt200 mg/dl, LDL particles will be small
and dense in 90 patients
When Tg lt90 mg/dl, almost all particles will be
large and fluffy
The frequency of phenotype B is increased 2 fold
in patients with type 2 diabetes
ALP is associated with 3-4 fold increase in the
risk of CAD

Am J Cardiol, 1998, 82 67U-73U
108
Atherogenecity of small and dense LDL

Generates free radicals
Increased trans endothelial filteration
susceptibility to oxidation
Reduced affinity for the LDL receptor
Increased binding to intimal proteoglycan
Formation of proaggregatory /vasoconstrictor
mediators.
Br J Clin Pharmacol, 48 125-133, 1999
Associated with impaired invivo endothelial
function independent of HDL, LDL, Tg.
Circulation, 2000, 102 716-721

109
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

Who said there is gender discrimination in India?
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) gt 30 mg
If she has developed T2DM, IGT, IFG, PCOS
If she has central adiposity (who is non
cylindrical?)
If she is a smoker (in rural India women smoke
more)

111
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

Micro Albuminuria - MAU
hs-CRP
Homocysteine (tHCy)
Fibrinogen
Erectile Dysfunction (ED)

Low intake of Zinc Low intake of Potassium
CADI risk enhancers
113
Micro Albuminuria (MAU)

MAU 30-300mg albumin in urine over 24 hrs
Occurs in DM and HT
Not detected on protein dipstick
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

114
MAU CVD risk factors
115
(No Transcript)
116
hs-CRP and CAD
Ridker et al, N Engl J Med. 1997336973979.
117
RR of CAD - hs-CRPTCHDL
Relative Risk
hs-CRP
Total CholesterolHDL Ratio
Ridker et al, Circulation. 19989720072011.
118
hs-CRP interpretation
119
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

120
Hyper-homocyst(e)inemia
Blood Homocyst(e)ine Levels
Classification Values in mmol/L
Normal Moderate Intermediate Severe 05 10 11 30 31 100 gt 100
121
Fibrinogen as a risk factor

A meta analysis of 12 population based study and
6 studies in patients with pre existing vascular
disease suggest a strong association between
fibrinogen levels and CAD risk as well as the
role for fibrinogen in predicting outcome of
patients with CADI.

IHJ, March-Aapril, 2000, 52 221-225
122
Role of fibrinogen in CAD patients

In Indian population, elevated plasma fibrinogen
levels and abdominal obesity appear to be
significantly associated with CAD

Parameters Cases Controls
Tc mg/dl 198 172 HDL mg/dl 25 26 Tg
mg/dl 144 129 Fibrinogen mg/dl 420 305
IHJ, 1999, 51, 499-502
123
Hypertriglyceridemia and CHD RiskAssociated
Abnormalities

Increased coagulability
? plasminogen activator inhibitor (PAI-1)
? factor VIIc
activation of prothrombin to thrombin
Elevated levels of fibrinogen

The Netherlands J Med , 2000, 56110-118
124
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

125
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
What pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

Vulnerable (high risk) Plaque
Vulnerable (high risk) Blood
High risk (vulnerable) Patient

127
Vulnerable (hyper reactive) Blood

Classic
Diabetes, Smoking, Hyperlipidemia
Inflammation/ Apoptosis/ Infection?
Cathecholamines
Fibrinogen Lp(a) Homocysteinemia
Factor V Leiden, Platelet- Polymorph Shear rate
Genetic Protein deficiencies (AT III, Prot C or
S)
Hypercoagulable state (?FVII, ?F1.2, ?FPA)
Hypofibrinolytic state (?PAI-1, ?t-PA, ?u-PA)
Not so classic
Depression, Circulating TF activity, Stress

128
Atherothrombosis
Progression of Atherosclerosis
Atherothrombosis
129
Atherothrombosis
Plaque Erosion
Plaque Rupture
130
The Vulnerable plaque
A mild to moderate atherosclerotic plaque is
more likely to rupture trigger thrombosis (MI
or Stroke) than a severe plaque.
131
Atherosclerosis Time Line
Atheroma
Intermediate Lesion
Fibrous Plaque
Complicated Lesion/ Rupture
Fatty Streak
Foam Cells
From First Decade
From Third Decade
From Fourth Decade
Adapted from Pepine CJ. Am J Cardiol.
199882(suppl 104).
132
How the Occlusion develops
133
Acute Coronary Syndrome ACS

Triggering activities of patients

Acute Risk Factors of an Arterial Pressure surge
or Vasoconstriction lead to Plaque Disruption
Acute Risk Factors of a coagulability Increase or
Vasoconstriction lead to complete occlusion by
Thrombus
Occlusive Thrombus
Minor Plaque Disruption
Non-Occlusive Thrombus
Vulnerable Atherosclerotic Plaque
Non-Vulnerable Atherosclerotic Plaque
Asymptomatic Unstable Angina or Non-Q-MI
MI or Sudden Cardiac Death
Major Plaque Disruption
Occlusive Thrombus
134
Tissue Factor
Vessel wall TF Inflammation
Circulating TF Thrombosis
Juno the two-faced God
135
Circulating TF - Cellular Sources
Sambola A. Circulation 2003 107 973-979
136
Circulating TF and Risk Factors
Sambola A. Circulation 2003 107 973-979
137
Inflammation Thrombosis Link
Sambola A. Circulation 2003 107 973-979
138
Therapeutic Target - TF
Spliced TF
139
Lets learn what we are !!

Meraa Bhaarat Mahaan
The Volcano
The Tsunami
Mirrors of CV Health
Who loads the Gun ?
Who pulls the triggers ?
Our Treasure in Tummy
Influence of Affluence

Screening and aggressiveness of treatment for
Lipid abnormalities lagged behind that for
hyperglycemia and hypertension, despite the
simplicity and demonstrated benefit of lipid
control.
These disparities may reflect either a
traditional emphasis on glycemic management in
diabetic patients that outweighs emphasis on
other cardiovascular risk factors, or a slow
adoption of lipid management guidelines.

Am J Med, June 1, 2002, Vol. 112 603-609
141
Moving Beyond LDL

Characteristic lipid abnormalities, such as high
triglycerides and low HDL, Lp(a) with normal LDL
values, are common in association with insulin
resistance in South Asians.
Hence, European/ American recommendations on the
use of statins as first-line agents may not be
entirely applicable to all populations.
Normal total cholesterol and normal LDL may
operate as risk factors in the presence of the
above RFs in South Asia populations.

Lancet 20023601015-18
142
Physical Activity

Reduces all-cause mortality
Reduces incidence and fatality of CHD
Reduces risk of NIDDM
Reduces BP, Improves Lipids, CCF
Improves well being, psychological factors
Key component in weight loss regimens
Benefits occur at any age

143
Physical Activity

What type of activity?
How much?
How often?
At what intensity?
The answer is
The health benefits of physical activity are
proportionately related to Exercise Volume

Exercise Volume Duration x Frequency x Intensity
144
Take Home Points on C A D I

High Rates 2 to 4 fold prevalence, Incidence,
Death
Greater prematurity 10 yrs earlier, 5 to 10
fold?in lt 40
Greater severity 3 vessel disease in young ?
and ?
?prevalence of Glucose Intolerance, IRS, DM, abd.
obese
?prevalence of conventional RF, HT, Obesity, LDL,
Smoker
Higher rates of CAD at any given level of the big
four RF
Lower cut off values for intervention (like for
diabetics)
?levels of Lp(a), ApoB, ALP, sLDL, tHCy,
PAI-1,?HDL (2b)
?CVD for lesser degree of atherosclerosis - ?
Inflamation
Higher of unstable or vulnerable plaques - ?
Infections

145
Recommendations on Testing
Enas A Enas et al, Int J Cardio, 2003

Look for Metabolic Syndrome in every one above
20 yrs
Waist circumference and not BMI alone is to be
recorded
Screen FBG and PPBG from age 20 years (earlier
if F H)
Lp(a) and tHCy at least once around 20 years or
even early
If abnormal, follow up after due interventions
Full lipid profile at 20 yrs, Repeat every 5 yrs
or 5 Kgs
20 lower cut off values LDL than global guide
lines
10 lower cut off values for other lipids,
higher for HDL
BMI cut off 23, IFG cut off 100 mg, WC 90 ? and
85 ?
Heart healthy life style and food habits form
childhood itself

146
Secondary Prevention of CAD
147
Where are we heading ??
Technology has changed a lot the way we live
But, we have not altered our lifestyle
Journal of internal medicine 2003254(2)114-25
148
We have to pay the very heavy price !!
What could be prevented, we treat or leave
149
Should we not prevent CADI ?
Superior Doctors Prevent disease Average
Doctors Treat before its evident Inferior
Doctors Wait until its full blown
- Huang Dee Nia-Ching 2600 B.C. 1st Chinese
Medical Text
150
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