Presentation made by Dr. Prafulla Kerkar on the topic- Coronary artery disease in indians: Glimpses from Indian data, at the SIHD conference.

1. Coronary Artery Disease in
Indians:
Glimpses from Indian Data
Dr. Prafulla Kerkar
KEM Hospital and Asian Heart
Mumbai

3. New York Times: 4th Dec 2014
Chronic Diseases are Killing More in Poorer
Countries
• Chronic diseases like heart disease and cancer
are rising fast in low and low-middle income
countries.
• There has been a 50% increase deaths in last 2
decades.
• They strike younger populations in these
countries and have much worse outcomes.
• 80% of deaths and disabilities in Africa and
South Asia are in people <60y age.
Tavernese S. New York Times. 4th Dec 2014

4. • Dr. Rajeev Gupta, Jaipur
• Dr. Ankur Phatarpekar
Acknowledgments

5. Alwan A. Global Status Report on Non communicable Diseases 2010.
Geneva: World Health Organisation; 2011

6. Age-standardized IHD mortality- GBD 2010

7. Premature CVD Burden in South Asia
DALYs at Age <50y in Men and Women
5.8
3.9
2.8
1.8 1.9
0.6
1.1
2.2
1.7
1.1
0.4 0.5 0.3 0.4
SOUTH ASIA EAST ASIA E EUROPE/C
ASIA
HIC MEC LAC SSA
Men Women
Moran et al. Glob Heart. 2014;9:91-9
DALYs in Millions

8. Increase in Absolute DALYs and YLDs for IHD In
South Asia: GBD Study 1990-2010
17.9
22.5
26.2
28.7
31.1
0.64 0.76 0.91 1.09 1.26
-5
0
5
10
15
20
25
30
35
1990 1995 2000 2005 2010
DALY
YLD
11
Moran et al. Circulation. 2014; 129:1483-92
Millions

9. 0
5
10
15
20
25
Cardiovascular COPD Diarrhea Perinatal Chest infections TB Cancers
20.3
9.3
6.7 6.4
5.4
7.1
5.4
16.9
8
9.9
6.2
7.1
4.7
6
Male Female
CVDs are Largest Causes of Death in India
Million Death Study
Registrar General of India. 2009
Gupta R, et al. World J Cardiol. 2012;4:112-120
Analysis of cause of deaths in 1.1 million homes and 113,692 persons in all States
Deaths in India annually: n= 10,500,000
%
Cardiovascular diseases 1.8-2.0 million/yr

10. Unique Features of CVD in India
0
100
200
300
400
500
600
Gujarat 1987
n=750
Andhra 2006
n=180162
Kerala 2010
n=161942
Mumbai 2010
n=148713
USA 2005
246 255
490
525
283
0
225 231
299
145
Men Women
0
100
200
300
400
500
600
700
800
25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70+
22 33.7 42.6 61.7
91.3
141
201.2
239.6 255.5
775.2
Men Women Total
High mortality rates High premature mortality
Increasing burden Regional variation
Gupta et al. Heart 2008 Million Death Study Investigators. 2012
<60 y age: 593K/1882K CVD deaths
Million Death Study Investigators. 2012Gupta et al. Indian Heart J. 2013

11. High Premature CVD Mortality in India
0
100
200
300
400
500
600
700
800
25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70+
22 33.7 42.6
61.7
91.3
141
201.2
239.6 255.5
775.2
Men Women Total
Age Groups
Numbers‘000
Total CVD deaths >15 years in 2010: 1,887 ,000
(M 1,116,000; F 770,000)
Million Death Study Report Submitted to GOI-MOH. 2012
593,500 (31%) CVD deaths <60y

12. Premature Cardiovascular Deaths in MDS
Proportional mortality from CVD at various age-groups
0
5
10
15
20
25
30
35
30-44 45-59 60-69 70+
17.3
29.2
31.8
27.2
12.3
24.9
28.5
25.1
0
5
10
15
20
25
30
35
30-44 45-59 60-69
12.6
20 19.2
6.6
13.9 14.1
0
5
10
15
20
25
30
35
30-44 45-59 60-69
3.3
7.7
10.8
3.5
8.9
12.3
0
1
2
30-44 45-59 60-69
0.3
0.1 0.1
0.8
0.2
0.1
CVD IHD
Stroke RHD
Million Death Study Report Submitted to GOI-MOH. 2012

13. Prof. Prasanna Nyayadhish
RIP

15. Premature Acute Coronary Syndromes in
South Asians: Younger Age of Onset
52
5858
61
iNTERHEART NEW YORK
SOUTH ASIANS CAUCASIANS
1990’s 2010’s
Yusuf et al, Lancet, 2004 Silbiger et al, Ethn Dis, 2013

16. Premature Atherosclerosis in Coronary
Artery and Aorta in India: Autopsy Study
16
30
18
48
0
10
20
30
40
50
60
10-34y n=52 35-85y n=61
Coronary Aorta
Thej MJ, et al. J Cardiovas Dis Res. 2012

17. Coronary Angiographic Findings in South
Asians vs Caucasians in UK and US
50
37
0
10
20
30
40
50
60
pLAD
South Asians n=41
Caucasians n=42
Tillin et al. Int J Cardiol. 2008;129:406-13
25
19
3 3
0
5
10
15
20
25
30
DVD TVD
South Asians n=63
Caucasians n=61
Hasan et al. Am J Cardiovasc Dis. 2011;1:31-7

18. Phenotypic Uniqueness of South Asian CAD
• Premature atherosclerotic disease
• Small arteries
• Severe atherosclerosis in the young
– More TVD as compared to Caucasians at younger age
– Diffuse and distal disease
• Greater prevalence of LV dysfunction at presentation
• Difficult PCI and complex CABG surgery
– Bifurcation lesions
– Endarterectomy more common
– LV and MV repair
Kaul U, et al. Indian J Med Res. 2010; 132:543-8

19. • Retrospective analysis of 279,256 patients undergoing PCI
from 2004 to 2011 from the British Cardiovascular
Intervention Society national database, of whom 259,318
(92.9%) were Caucasian and 19,938 (7.1%) were South Asian
• South Asians were younger but had more extensive disease
and major risk factors, particularly diabetes.
• However, after correcting for these differences, in-hospital
and medium-term mortality of South Asians was no worse
than that of Caucasians.
• The high prevalence of diabetes exerts an adverse influence
on mortality
• Ethnicity itself is not an independent predictor of outcome.
Mortality in South Asians and
Caucasians after PCI in the UK
Daniel Jones et al J Am Coll Cardiol Intv 2014;7:362-71

20. Risk Factors for CAD in the Young

21. Genetic Risk Factors
Standard CAD/Stroke Genes
• 42 GWAS locations identified for
CAD;
• 15 significant for both stroke and
CAD.
• Most significant were
– 12q24/SH2B3 and ABO
– HDAC9
– 9p21
– RAI1-PEMT-RASD1
– EDNRA
– CYP17A1-CNNM2-NT5C2
• ADAMTS and ABO genes
• Polygenic risk score
Novel Genes in South Asians
• LIPA on 10q23,
• PDGFD on 11q22,
• ADAMTS7-MORF4L1 on
15q25,
• A gene rich locus on 7q22,
• KIAA1462 on 10p11.
C4D Genetics Consortium.
Nat Genetics. 2011; 43, 339-44.
Reilly et al. Lancet. 2011;377:383-92
Dichgans et al. Stroke. 2014;45:24-36

22. Risk Factors for Acute MI in South Asians
INTERHEART Study
Population Attributable Risks %
47
38
19
12
38
16
27
-5
21
46
36
24
13
33
20
25
16
12
-10
0
10
20
30
40
50
SouthAsians
Others
Joshi PP, et al. JAMA 2007; 297:286-94

23. Premature Occurrence of AMI in South Asians
Before and After Adjustment for 9 Risk Factors
INTERHEART Study
Joshi PP, et al. JAMA. 2007:297:284-292

24. Emerging Risk Factors
• Primordial Risk Factors
• Social determinants of health
•Proximate Risk Factors
• Dyslipidemias
• Lipoprotein(a)
• Remnant lipoproteins, triglycerides
• Small dense LDL, oxLDL
• HDL subtypes, dysfunctional HDL
• Vascular risk factors
• Environmental pollution
• Homocysteine
• Infections
• Inflammatory markers and factors

25. Case-Control Study of Risk Factors in
Premature CAD (<50y) in India
Cases 165, Controls 199
Panwar RB, et al. Ind J Med Res. 2011;134:26-32
1.4
1.7
1.9
1.9
2.5
2.9
3.6
8.9
10.3
10.5
19.4
Cholesterol
High fat
Low fruit/veg
Diabetes
LDL
Fibrinogen
Triglycerides
Hypertension
Low HDL
Homocysteine
Smoking
Age-adjusted Odds Ratios

26. Yusuf S, et al. NEJM. 2014; 371:818-27.

27. Risk Factor Burden by Country
Income: PURE Study
Yusuf S, et al. NEJM. 2014; 371:818-27.

28. PURE Study: Event & Case-Fatality Rates for Major CVD’s
Yusuf S, et al. NEJM. 2014; 371:818-27.

29. PURE Study: Implications
• We observed a “Low risk factor-high mortality”
paradox in low-income countries (India/SA).
• This suggests significant gaps in primary prevention
and control of risk factors.
• It also indicates inferior disease management and
poor secondary prevention.
• Implications:
– Focus on early identification and proper management of
CVD risk factors is required.
– Better quality treatment of acute coronary events and
appropriate long-term secondary prevention strategies
(lifestyle, medications, revascularization) is also required.

32. Challenges for CVD Care in India
Focus on Premature CVD
• High burden
• Premature mortality and case fatality
• Regional variations and lack of data
• Health system challenges
• Lack of access and cost of care
• Out of pocket expenditure
• Information asymmetry

33. Thank you

35. 9-P’s of Prevention
• Policy change
• Program
development
• Process
implementation
• Physician education
• Practice paradigm
shift
• Population-wide
interventions
• Primary prevention
• Patient
management
• Patient
empowerment
Gupta R. Ind J Med Res. 2013;138:281-284

36. CVD Control Policies/Programs in India
Focus Needed for Premature CAD Prevention
• Policy initiatives
– Social policies
• Tobacco control, FCTC
• Education act, RTE
• Job guarantee,
MGNREGA
• School mid-day meal
• JSY/JSSY schemes
– Financial policies
• Universal health
insurance
• BPL health care
insurance
– Pharmaceutical
• Essential drug list and
drug price control
• Free medicine supply
• Population based
– School health programs
– Work-site interventions
– Group-based interventions
• High risk approach
– Professional education for
physicians
– Improved acute disease
management
– Task shifting for risk
factor management
– Secondary prevention and
improving adherence
– Use of technology and
personalized medicine
Gupta R, et al. Health Syst Pol Res. 2011; 9:e10

37. CVD Prevention Pyramid
Gupta R, Deedwania PC. Cardiol Clin. 2011; 29:15-34
Evidence Based Acute and Chronic
CVD Management
Clinic based risk factors control.
Smoking cessation, BP control
Lipid and Diabetes management
Improving medical education
Healthcare Financing
Policies for smoking, diet and physical
activity modulation
Tackling Social Determinants of Health
Primordial
Prevention
Primary
Prevention
Secondary
Prevention

38. Conclusion: Why is CAD Premature
and Malignant in South Asians
• Why premature?
– Premature onset of standard risk factors
– Interactions of standard & emerging risk factors
– ? Gene-environment interaction; epigenetics
• Why malignant?
– Disease phenotype
– Social determinants of ill-health
– Gaps in healthcare systems
– Quality of primary prevention and risk factor control
– Acute CAD management
– Poor secondary prevention

39. Genetics of CAD: Indian Studies
Table 6: Indian genetic studies