Transcript CAD in Indians by Dr Sarma

www.drsarma.in
Welcome
1
2
CD ROM Available
The contents of my today’s 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…
Dr.Sarma@works
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Knowledge that isn’t
implemented never works
Dr.Sarma@works
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Coronary Artery
Disease in Indians
(C A D I)
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Coronary Heart Disease in Indians
Is 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
5
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http://www.ispub.com/ijc/vol1n2/cadi.xml
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A must read book
7
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
8
www.drsarma.in
Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
9
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Meraa Bhaarat Mahaan
• 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….
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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
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CADI is ‘Malignant’
• 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.
13
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CAD Mortality
INDIA
Age Adjusted mortality
for 100,000 population
per year in 35-74 age.
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CAD in Indians
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CAD in Asian Indians
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MI in Singapore - Ethnicity
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CAD in California - Ethnicity
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CAD Deaths – 7 Countries study
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
20
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21
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The Volcano
• 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
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The Quotes
• “Genetics loads the gun, environment pulls the trigger. Even if you
have a loaded gun, you don’t 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 don’t
get tested for heart disease. By the time some of them find out
they have CAD, they’re either in an ambulance or a hospital bed”
Dr.A.K. Rao
National Asian Indian Heart Disease Program
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The Berkeley Study
• 25 % of the MIs occur below 40 yrs, unheard of any where
• In the young Indians (< 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
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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
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CADI Strikes the Young
Enas A Enas et al, I Heart J 2001
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We have worsened !!
Prevalence %
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Prevalence of CAD in India from 1960 - 2001
9.7
10
10.9
11
8
5.5
6
6.5
4
4
2
0
(1) 1960; 30- (2) 1962; 30- (3) 1968; >30 (4) 1990; 25- (5) 1994; 3570 years
70 years
years
64 years
64 years
(6) 2001
>20 years
Year
1. Agra; 3. N India; 4. Delhi; 6. Chennai
Indian Heart J 2002; 54: 103
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CADI Research Foundation
Enas A Enas et al A Heart J 2001
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
29
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CAD Tsunami in India
•
“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
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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 < 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
Don’t wait. Begin heart healthy life style now!
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SHARE and CUPS
1.
The Chennai Urban Population Study (CUPS)
•
Prevalence of CAD to be 11%
•
10 folds increase in the last 40 years
2.
The Study of Health Assessment and Risk in Ethnic
groups (SHARE) in Canada
•
3.
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%
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
34
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
Dr.Sarma@works
End stage Heart Disease
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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
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Dushta Chatushtayam
DIABETES
HYPERTENSION
SMOKING
Only 35%- 50% of the angiographically proved
HEART
CADI is accounted for by these BIG FOUR
ATTACK
↑ CHOLESTEROL
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HT – CV Mortality
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.
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Treatment of HT – CV Mortality
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.
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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
10
Women
3.7
8
Men
Women
Stroke
3.2
5.3
Cupples LA, D’Agostino RB. NIH Publication No 87-2703, Feb
1987.
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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
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DM and CAD - CUPS
Mohan V et al CUPS…
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HT and CAD in CUPS
Mohan V et al CUPS…
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How important is the CAG ?
•
2/3 of ACS result from CA stenosis of < 50%
•
< 15% MI result from CA stenosis of < 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
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
45
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Who Loads the Gun ?
•
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)
46
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
47
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CAD Prediction in 21st Century
Cardiovascular Risk
Lipids
HTN
Diabetes
Behavioral
Hemostatic
Inflammatory Genetic
Thrombotic
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What Pulls the Trigger ?
•
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
49
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. Who pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
50
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Intra abdominal fat
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The Treasure in Tummy
Normal
CourtesyofofWilfred
Wilfred
Y. Fujimoto,
Courtesy
Y. Fujimoto,
MD. MD.
Central Adiposity
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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 > 30%
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Our cut off values !
For Indians
• BMI < 23
• BMI of 23 to 24.9
• BMI of > 25
1.
2.
3.
4.
Normal
Over weight
Obesity
BMI < 23, WC Normal BMI > 23, WC Normal BMI < 23, WC Increased BMI > 23, WC Increased -
Good
Bad
Worse
Worst
Central adiposity causes ↑IL6, which ↑hepatic hs-CRP
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Metabolic Syndrome
Hypertension
Microalbuminuria
Central
obesity
200% CVD Risk
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.
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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
NCEP guidelines 2001 (WHO Modified for Indians)
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Acanthosis Nigricans
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Acanthosis Nigricans
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Acanthosis Nigricans
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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 < 0.01
Diabetics
18.0 ± 5.0
11.5 ± 0.9 < 0.05
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
61
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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.
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Evolution ?
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Is this the way ?
Fast and Fatty Foods
Urban Children on an average
watch TV for 2-2.5 hrs. in a day
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Childhood Obesity
“Fat pre-teens have
arteries of middleaged smoker”
Sharon Kirkey
CanWest Med University
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Television watching became
even more convenient with
Sony’s introduction of a new
remote controlled remote control
– Tokyo News line
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This how we walk the dog !
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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
68
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With in no time !!
69
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
70
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Lipoproteins - Boats
TG
EC
Apoprotein boat
Apo A I and A II for HDL
Apo B100+C+E – VLDL, IDL
Apo B100 for LDL
Apo B100+Apo(a) – Lp(a)
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Good, Bad, Ugly & Deadly
HDL
GOOD
LDL
C
TG
T
G
A I, A II
VLDL
TG
BAD
B 100
UGLY
Lp(a)
DEADLY
TG
C
B 100 + E +C
C
TG
C
B 100+ (a)
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Apolipoprotein B
Measurements
VLDL
VLDLR
TG-rich lipoproteins
Apolipoprotein B
Non-HDL-C
IDL
LDL
SDL
All are the terrorists
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Apolipoproteins A1, A2
A-I
A-I
CE
CE
The soldiers
HDL 1
The soldier-like
CE
A-II
HDL 2
APO A I
Atheroprotective
A-II
HDL 3
Alcohol increases
Athero-neutral
74
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Blood Lipids
• Total Cholesterol
• ‘Good’ Cholesterol
– HDL 1, HDL 2, HDL 3
• ‘Bad’ Cholesterols (Non HDLc)
– LDLc, IDLc, SDL
– VLDLc, VLDLr
– Lp(a)
< 200
> 50
< 150
< 100
< 30
< 20
HDL 1 and HDL 2 are protective HDL 3 Neutral
75
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Typical Lipid Profile in Rural China
• Total Cholesterol
• ‘Good’ Cholesterol
– HDL 1, HDL 2, HDL 3
• ‘Bad’ Cholesterols (Non HDLc)
– LDLc, IDLc, SDL
– VLDLc, VLDLr
– Lp(a)
127
44
83
53
20
10
Highly anti atherogenic lipid profile
In some communities with TC of 80 mg CAD is virtually nil
76
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
77
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Better Count the Boats
•
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 < 2 good
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Inter Heart Study
Apo B / Apo A1 Ratio
evidence of threshold
No
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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
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Inter Heart Study
•
Nine simple and modifiable risk factors are
strongly associated with acute MI worldwide.
•
These 9 risk factors account for >90% 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. 2004;364:937-52.
81
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Inter Heart Study
Multiplicative effect of risk
82
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
83
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CAD in Asian Indians - RF
84
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Total Cholesterol and CAD
Framingham Heart Study—26-Year Follow-up
No CHD
35% of CHD
Occurs in
People with
TC<200 mg/dL
150
CHD
200
250
300
Total Cholesterol (mg/dL)
Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.
1996 Reprinted with permission from Elsevier Science.
85
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CADI Urban v/s Rural
Risk Factor
Smoking
BMI >25 Kg/m2
“Apple” shape obesity
Hypertension
Diabetes
Cholesterol >200*
HDL Cholesterol <40*
Triglycerides >150*
*mg/dl
Urban Delhi
Female
Male
n=1594
n=1456
2.6
48.6
39.1
29.0
11.2
39.7
59.9
39.7
28.7
35.5
70.9
25.5
10.9
36.8
38.7
45.2
Rural Haryana
Female
Male
n=1417
n=1070
25.3
11.4
22.1
10.8
2.6
16.3
55.9
29.9
54.7
7.9
42.3
14.0
2.9
16.3
45.6
33.0
Sethi K.K. Coronary Artery Disease in Indians, 1998
86
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Lp(a) in Young Indian Patients with
Angiographically Proven CHD
Parameter
% Patients
Total cholesterol >200 mg/dl
54.3
Triglyceride >200 mg/dl
56.1
HDL <35 mg/dl
59.6
Lp(a) >30 mg/dl
61.4
n=57; age <40 yrs
Mishra et al (Cuttack)
Indian Heart J 2001; 53: Abst 60
87
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CAD Deaths - Cholesterol
88
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CADI v/s FHS study
89
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RF in CAD – PROCAM Study
Odds Ratio for CAD
when LP(a) > 20 mg
90
Coronary heart disease and HDL-C
Framingham Heart Study
200
Rate/1000
150
100
Women
50
Men
0
<25
25–34
35–44
45–54
55–64
65–74
75+
HDL-C (mg/dl)
Gordon, Castelli et al. Am J Med 1977; 62: 707–
714
Relative risks of MI
The Physicians Health Study
3.78
3.21
2.41
1.00
Low total cholesterol
<212 mg/dl
Low HDL cholesterol
<47 mg/dl
High HDL cholesterol
47 mg/dl
High total cholesterol
212 mg/dl
Stampfer, Sacks et al. N Engl J Med 1991; 325: 373–381
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
2
HDL-C
1.5
25 mg/dl
45 mg/dl
65 mg/dl
85 mg/dl
1
0.5
0
100 mg/dl
160 mg/dl
220 mg/dl
LDL-C
*Men aged 50–70
Gordon, Castelli et al. Am J Med 1977; 62:
707–714
HDL-C is strongly predictive
despite desirable TC
Developing
subsequent CAD
events (%)
80
70
Percentage
60
50
75%
<35 mg/dl
40
30
45%
>35 mg/dl
20
10
0
HDL-C levels
Miller, Circulation 1992; 86: 1165–1170
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RF for CV Events
Lipoprotein(a)
Homocysteine
IL-6
TC
LDLC
sICAM-1
SAA
Apo B
TC: HDLC
hs-CRP
hs-CRP + TC: HDLC
0
1.0
2.0
4.0
6.0
Relative Risk of Future Cardiovascular Events
Ridker et al, N Engl J Med. 2000;342:836-43
95
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
96
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Indian Dyslipidemia
•
•
•
•
•
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 2002:15-18
Lipid Disorders:Implications & Management Ed. Tripathy & Das, 2002
Sethi K.K. Coronary Artery Disease in Indians, 1998
97
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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)
98
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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 %, > 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)
99
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
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Multiplicative with Lp(a)
•
•
•
•
•
•
•
•
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
101
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CAD & Lp(a) – PROCAM Study
Odds Ratio for CAD
LP(a) levels, TC/HDL
102
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, 56:110-118


This ALP is present and seen in

Insulin resistant individuals

Diabetics
More prevalent in India
Cumulative Distribution of Adjusted Plasma
TG Levels – LDL 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.
Cumulative Distribution of Adjusted
HDL – LDL 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.




When Tg >200 mg/dl, LDL particles will be
small and dense in 90% patients
When Tg <90 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
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
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
109
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Indian Women are Men !!
•
•
•
•
•
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) > 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)
110
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
111
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Novel independent CHD risk factors
1. Micro Albuminuria - MAU
2. hs-CRP
3. Homocysteine (tHCy)
4. Fibrinogen
5. Erectile Dysfunction (ED)
CADI risk Low intake of Zinc
enhancers Low intake of Potassium
112
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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
113
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MAU – CVD risk factors
Gender
Smoking
6
5.6
5.1
5
4
2
1.4
3
2
1
0
Relative risk of
CHD
2.5
Microalbuminuria
Normoalbuminuria
2.1
1
1
F
M
-
SBP (mmHg)
+
Total Cholesterol (mmol/L)
12
10.5
10
8
6
4
5.3
2.2
2
0
4.9
3.3
1
1.5
< 140
140-160
Borch-Johnson K et al. 1999 (MONICA Study)
2.2
2.5
> 160
1
< 5.2
4.8
Micro
2.2
5.2-7.0
>7.0
114
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115
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hs-CRP and CAD
P Trend <0.001
P<0.001
3
Relative Risk of MI
P<0.001
2
P=0.03
1
0
1
2
3
4
Quartile of hs-CRP
Ridker et al, N Engl J Med. 1997;336:973–979.
116
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RR of CAD - hs-CRP+TC:HDL
Relative Risk
5.0
4.0
3.0
2.0
1.0
0.0
High
Medium
High
Medium
Low
Low
Total Cholesterol:HDL Ratio
Ridker et al, Circulation. 1998;97:2007–2011.
117
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hs-CRP interpretation
1 mg/L
Low
Risk
3 mg/L
Moderate
Risk
10 mg/L
High
Risk
>100 mg/L
Acute Phase Response
Ignore Value, Repeat Test in 3 weeks
118
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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
119
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Hyper-homocyst(e)inemia
Blood Homocyst(e)ine Levels
Classification
Normal
Moderate
Intermediate
Severe
Values in mmol/L
05 – 10
11 – 30
31 – 100
> 100
120
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
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
198
172
25
26
Tg mg/dl
144
129
Fibrinogen mg/dl
420
305
Tc mg/dl
HDL mg/dl
IHJ, 1999, 51, 499-502
Hypertriglyceridemia and CHD Risk
Associated Abnormalities

Increased coagulability




 plasminogen activator inhibitor (PAI-1)
 factor VIIc
activation of prothrombin to thrombin
Elevated levels of fibrinogen
The Netherlands J Med , 2000, 56:110-118
www.drsarma.in
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
124
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. What pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
125
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Atherothrombosis
Vulnerable (high risk) Plaque
+
Vulnerable (high risk) Blood
=
High risk (vulnerable) Patient
126
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“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
127
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Atherothrombosis
Progression of Atherosclerosis
Atherothrombosis
128
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Atherothrombosis
Plaque Erosion
Plaque Rupture
129
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The Vulnerable plaque
A mild to moderate atherosclerotic plaque is more likely to
rupture & trigger thrombosis (MI or Stroke) than a severe plaque.
130
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Atherosclerosis Time Line
Foam
Cells
Fatty
Streak
Intermediate
Atheroma
Lesion
Fibrous
Plaque
Complicated
Lesion/ Rupture
Endothelial Dysfunction
From First
Decade
From Third
Decade
From Fourth
Decade
131
Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104).
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How the Occlusion develops
132
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Acute Coronary Syndrome ACS
Triggering activities
of patients
Acute Risk Factors of an Arterial
Acute Risk Factors of a coagulability
Pressure surge or Vasoconstriction
Increase or Vasoconstriction lead to
lead to Plaque Disruption
complete occlusion by Thrombus
Minor Plaque Non-Occlusive Occlusive
Thrombus
Disruption
Thrombus
Non-Vulnerable Vulnerable
Atherosclerotic Atheroscler
otic Plaque
Plaque
Asymptomatic
MI or Sudden
Unstable Angina or
Cardiac Death
Non-Q-MI
Major Plaque
Occlusive
Disruption
Thrombus
133
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Tissue Factor
Vessel wall TF
Circulating TF
Inflammation
Thrombosis
Juno – the two-faced God
134
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Circulating TF - Cellular Sources
Sambola A. Circulation 2003; 107: 973-979
135
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Circulating TF and Risk Factors
Sambola A. Circulation 2003; 107: 973-979
136
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Inflammation – Thrombosis Link
Sambola A. Circulation 2003; 107: 973-979
137
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Therapeutic Target - TF
Spliced TF
138
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Lets learn what we are !!
1. Meraa Bhaarat Mahaan
9. Good, Bad, Ugly & Deadly
2. The Volcano
10. Why not count the boats ?
3. The Tsunami
11. How to count the risks ?
4. Mirrors of CV Health
12. The Missing Links !!
5. Who loads the Gun ?
13. Our Women are Men
6. Who pulls the triggers ?
14. Our Novelty of risk factors
7. Our Treasure in Tummy
15. Fuel on Fire / Fire on Fuel?
8. Influence of Affluence
16. Is it the End of the Road?
139
www.drsarma.in
Lipid Screening - a must
1. “Screening and aggressiveness of treatment for
Lipid abnormalities lagged behind that for
hyperglycemia and hypertension, despite the
simplicity and demonstrated benefit of lipid control.
2. 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
140
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Moving Beyond LDL
1. 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.
2. Hence, European/ American recommendations
on the use of statins as first-line agents may not
be entirely applicable to all populations.”
3. Normal total cholesterol and normal LDL may
operate as risk factors in the presence of the
above RFs in South Asia populations.
Lancet 2002;360:1015-18 141
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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
142
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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
143
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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 < 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
144
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Recommendations on Testing
Enas A Enas et al, Int J Cardio, 2003
1. Look for Metabolic Syndrome in every one above 20 yrs
2. Waist circumference and not BMI alone is to be recorded
3. Screen FBG and PPBG from age 20 years (earlier if F H+)
4. Lp(a) and tHCy at least once around 20 years or even early
5. If abnormal, follow up after due interventions
6. Full lipid profile at 20 yrs, Repeat every 5 yrs or 5 Kgs
7. 20% lower cut off values LDL than global guide lines
8. 10% lower cut off values for other lipids, higher for HDL
9. BMI cut off 23, IFG cut off 100 mg%, WC 90 ♂ and 85 ♀
10.Heart healthy life style and food habits form childhood itself 145
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Secondary Prevention of CAD
146
Where are we heading ??
20000 B.C.
2006
Paleolithic sup. age
Neolithic age
19th century
21st century
Technology has changed
a lot the way we live
Processed
Hunting-gathering
subsistence
High level of
physical activity
But, we have not
Thrifty genotype
foods
Animal fats
and glucides
¯ Dietary fibre
Sedentary
altered life
our
lifestyle
Susceptibility genotype
Journal of internal medicine 2003:254(2):114-25
We have to pay the very heavy price !!
What could be prevented, we treat or leave
www.drsarma.in
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
149
150
CD ROM Available
The contents of my today’s 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…
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A Place Called Love
Grand Parenthood
151