Coronary Artery Disease in Indians:

Glimpses from Indian DataDr. Prafulla Kerkar

KEM Hospital and Asian HeartMumbai

New York Times: 4th Dec 2014Chronic 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

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

Acknowledgments

Alwan A. Global Status Report on Non communicable Diseases 2010. Geneva:

World Health Organisation; 2011

Age-standardized IHD mortality- GBD 2010

Premature CVD Burden in South AsiaDALYs at Age <50y in Men and Women

5.8

3.9

2.8

1.8 1.9

0.61.1

2.21.7

1.1

0.4 0.5 0.3 0.4

Men Women

Moran et al. Glob Heart. 2014;9:91-9

DALYs in Millions

Increase in Absolute DALYs and YLDs for IHD In South Asia: GBD Study 1990-2010

1990 1995 2000 2005 2010-5

0

5

10

15

20

25

30

35

17.9

22.5

26.228.7

31.1

0.64 0.76 0.91 1.09 1.26

DALYYLD

11Moran et al. Circulation. 2014; 129:1483-92

Mill

ions

Cardiovascular COPD Diarrhea Perinatal Chest infections TB Cancers0

5

10

15

20

25

20.3

9.3

6.7 6.45.4

7.1

5.4

16.9

89.9

6.2 7.14.7

6

Male Female

CVDs are Largest Causes of Death in IndiaMillion Death Study

Registrar General of India. 2009Gupta 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 StatesDeaths in India annually: n= 10,500,000

%

Cardiovascular diseases 1.8-2.0 million/yr

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

490525

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 61.791.3

141

201.2239.6 255.5

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

High Premature CVD Mortality in India

25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70+0

100

200

300

400

500

600

700

800

22 33.7 42.6 61.791.3

141201.2

239.6 255.5

775.2

Men Women Total

Age Groups

Nu

mb

ers

‘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

Premature Cardiovascular Deaths in MDSProportional mortality from CVD at various age-groups

30-44 45-59 60-69 70+0

5

10

15

20

25

30

35

17.3

29.231.8

27.2

12.3

24.9

28.5

25.1

30-44 45-59 60-690

5

10

15

20

25

30

35

12.6

20 19.2

6.6

13.9 14.1

30-44 45-59 60-690

5

10

15

20

25

30

35

3.3

7.710.8

3.5

8.912.3

30-44 45-59 60-69

0

1

2

0.30.1 0.1

0.8

0.20.1

CVD IHD

Stroke RHD

Million Death Study Report Submitted to GOI-MOH. 2012

Prof. Prasanna Nyayadhish RIP

Premature Acute Coronary Syndromes in South Asians: Younger Age of Onset

iNTERHEART NEW YORK

52

5858

61

SOUTH ASIANS CAUCASIANS

1990’s 2010’s

Yusuf et al, Lancet, 2004 Silbiger et al, Ethn Dis, 2013

Premature Atherosclerosis in Coronary Artery and Aorta in India: Autopsy Study

10-34y n=52 35-85y n=610

10

20

30

40

50

60

16

30

18

48

Coronary Aorta

Thej MJ, et al. J Cardiovas Dis Res. 2012

Coronary Angiographic Findings in South Asians vs Caucasians in UK and US

pLAD0

10

20

30

40

50

60

50

37

South Asians n=41Caucasians n=42

Tillin et al. Int J Cardiol. 2008;129:406-13

DVD TVD0

5

10

15

20

25

30

25

19

3 3

South Asians n=63Caucasians n=61

Hasan et al. Am J Cardiovasc Dis. 2011;1:31-7

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

• 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

Risk Factors for CAD in the Young

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

Risk Factors for Acute MI in South AsiansINTERHEART 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

South Asians

Others

Joshi PP, et al. JAMA 2007; 297:286-94

Premature Occurrence of AMI in South AsiansBefore and After Adjustment for 9 Risk Factors

INTERHEART Study

Joshi PP, et al. JAMA. 2007:297:284-292

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

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

Cholesterol

High fat

Low fruit/veg

Diabetes

LDL

Fibrinogen

Triglycerides

Hypertension

Low HDL

Homocysteine

Smoking

1.4

1.7

1.9

1.9

2.5

2.9

3.6

8.9

10.3

10.5

19.4

Age-adjusted Odds Ratios

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

Risk Factor Burden by Country Income: PURE Study

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

PURE Study: Event & Case-Fatality Rates for Major CVD’s

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

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.

Challenges for CVD Care in IndiaFocus 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

Thank you

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

CVD Control Policies/Programs in IndiaFocus 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 medicineGupta R, et al. Health Syst Pol Res. 2011; 9:e10

CVD Prevention Pyramid

Gupta R, Deedwania PC. Cardiol Clin. 2011; 29:15-34

Evidence Based Acute and ChronicCVD Management

Clinic based risk factors control.Smoking cessation, BP control

Lipid and Diabetes management

Improving medical education

Healthcare FinancingPolicies for smoking, diet and physical

activity modulation

Tackling Social Determinants of Health

Primordial Prevention

Primary Prevention

SecondaryPrevention

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

Genetics of CAD: Indian Studies