Overview and Rationale for the PURE Study

Dubai, UAE

January 6, 7 2006

Life Enhancing: Average Life Expectancy at Birth

Economist, Nov 2001

EPIDEMIOLOGIC TRANSITION OF CARDIOVASCULAR DISEASES

Stages of Development

% of total deaths

from CVD

Predominant CVDs Regions

1. Age of pestilence & famine

5 to 10 Rheum. HD, infections, nutritional cardiomyopathies

Sub-Saharan, Africa, rural India, S.Amer

2. Age of receding pandemics

10-35 As above + hyperten HD, and hem strokes

China

3. Age of degen & man-made dis

35-55 All strokes, IHD at young ages, obesity & diabetes

Urban India, former socialist econ, aboriginals

4. Age of delayed degenerative dis

< 50 Stroke and IHD at old age W. Eur, N. America, Austral, N-Zealand

5. Age of Health Regression & Social Upheaval

35-55 Re-emerg of rheumatic HD, infections, IHD & hypertens dis in the young

Russia

Contribution of NCD to the Global Mortality and GBD in 1998, in LIC & MIC Countries

Disease Category

Contrib of NCD’s to

total global mortality

(%)

LIC + MIC Contrib to

global NCD mortality

(%)

Contrib of NCD’s to

total burden of disease

(%)

LIC + MIC Contrib to

NCD burden of disease

(%)

Total NCD 58.8 77 43.0 85

CVD 30.9 78 10.3 86.3

Cancers 13.4 72 5.8 79

Diabetes 1.1 73 0.8 73

COPD 4.1 87.5 2.0 91.4

Schema of Relative CVD Rates in Different Societies Based on Early vs Late Industrialization

0

1

2

3

4

5

1900 1950 2000 2050

Sta

ge o

f EP

I Tra

nsiti

on

India/China

N.Am/W. Eur

REASONS FOR THE GLOBAL INCREASE IN CVD

1. Decrease in childhood and infectious diseases more middle age & older people

2. Increased tobacco used3. Urbanization:

a) phys activity during daily life (e.g. automation, cars, etc.)b) energy consumptionc) fat consumptiond) psychosocial stress

Increase in Wt/Obesity

Dyslipidemia, Dysglycemia, BP

Percent of Population Living in Urban Settings 1970-2025

Region 1970 1994 2025

World 36.6 44.8 61.1

Developed Countries

67.5 74.4 84.0

Economies in Transition

25.1 37.0 57.0

Developing Countries

12.6 21.9 43.5

Risk of AMI associated with Risk Factors in the Overall Population

Risk factor % Cont % Cases PAR 1 (99% CI) PAR 2 (99% CI)ApoB/ApoA-1(5 v 1) 20.0 33.5 54.1 (49.6, 58.6) 49.2 (43.8, 54.5)

Curr smoking 26.8 45.2 36.4(33.9,39.0) 35.7,(32.5,39.1)Diabetes 7.5 18.5 12.3 (11.2, 13.5) 9.9 (8.5, 11.5)Hypertension 21.9 39.0 23.4 (21.7, 25.1) 17.9 (15.7, 20.4)

Abd Obesity (3 v 1) 33.3 46.3 33.7 (30.2, 37.4) 20.1 (15.3, 26.0)Psychosocial - - 28.8 (22.6, 35.8) 32.5 (25.1, 40.8)Veg & fruits daily 42.4 35.8 12.9 (10.0, 16.6) 13.7 (9.9, 18.6)Exercise 19.3 14.3 25.5 (20.1, 31.8) 12.2 (5.5, 25.1)Alcohol 24.5 24.0 13.9 (9.3, 20.2) 6.7 (2.0, 20.2)Combined - - 90.4 (88.1, 92.4) 90.4 (88.1, 92.4)

Population Attributable Risk by Region and Overall

LIFESTYLE FACTORS

Region Smoke % Fr/vg % Exer % Alc % All LS

W. Europe 28.9 12.9 38.8 18.9 67.8E/C Europe 30.2 10.2 11.3 12.9 49.6Middle East 44.8 8.1 4.0 -4.4 45.5Africa 38.0 3.8 11.1 27.3 63.2S. Asia 37.5 18.4 24.3 -5.3 55.2China 35.8 17.8 21.1 5.3 62.4S.E. Asia 36.2 11.2 31.4 27.9 69.9Australia/NZ 44.7 10.7 23.8 18.5 65.8S. America 38.5 6.7 27.2 -3.1 56.9N. America 26.3 19.8 25.3 25.3 59.8Overall 1 36.2 12.9 25.5 13.9 62.8Overall 2 35.7 13.7 12.2 6.7 54.6

Population Attributable Risk by Region and Overall

NON-LIFESTYLE RISK FACTORS

Region HTN % Diab % Abd Obes % All PS% Lipids % All 9 RF

W. Europe 22.0 14.9 63.6 38.9 44.6 94.0E/C Europe 24.5 9.1 28.0 4.9 35.0 72.5Middle East 9.7 15.5 26.7 41.6 70.5 95.0Africa 29.9 17.1 58.3 40.0 74.1 97.4S. Asia 19.4 12.1 37.0 15.9 58.7 89.4China 22.1 10.0 5.5 35.6 43.8 89.9S.E. Asia 38.4 21.0 58.0 26.7 67.7 93.7Australia/NZ 22.8 7.2 61.6 28.9 43.4 89.5S. America 32.8 12.8 45.4 35.6 47.6 89.4N. America 18.9 7.9 59.6 51.4 50.5 98.7Overall 1 23.4 12.4 33.7 28.8 53.8 90.4Overall 2 17.9 9.9 20.1 32.5 49.2 90.4

A Societal Pathophysiologic Pathway for COR HT DIS

RURAL LIFESTYLE

Proximal Determinants of Behaviour• urban structure & mechanization•Food & Tobacco policy•Cultural attitudes•Social/Education•Global influences

URBAN LIFESTYLE

•Consumption of energy rich food•Sedentarines

s (in usual daily activities)•Psychosocial

factors

Obesity and other risk factors

Modifying influences:•Healthcare•Genes•Knowledge & Attitudes

Clinical Events

++

- -

Yusuf et al. Circ 2001

What is a normal BMI?

“• Median BMI of newborns :13(USA)• Median BMI of 16 yr olds:16(USA)• Median BMI of 20 yr olds:20(USA)• Median BMI of adult males in the 1900:21(USA)• Median BMI of rural B Lore :19.5(India)• Median BMI in Anquing study: 19 (China)

So, why is a BMI of 25 considered to be normal?

Normal” derived from modern day Western countries may not be appropriate .

INTERHEART: Apolipoprotein B/A-1 and MI

Deciles: 1 2 3 4 5 6 7 8 9 10

Cont 1210 1206 1208 1207 1210 1209 1207 1208 1208 1209

Cases 435 496 610 720 790 893 1063 1196 1366 1757

Median 0.43 0.53 0.60 0.66 0.72 0.78 0.85 0.93 1.04 1.28

1

2

4

8

OR

(99

% C

I)

Conceptual issues in examining regional variations in disease

1. State of development of the country or region in relation to the epidemiological transition.

2. Level of urbanization.

3. Variations in ethnicity (cultural and biological)

4. Socioeconomic status, lifestyle (local level variations)

Four major transitions associated with urbanization (1)

1. Mechanization, motorization, energy saving devices

changing economic structure, with increasing importance of non-agricultural sectors

increasing investment in telecommunications, transportation and electrical infrastructure

2. Declining physical activity More sedentary modes of transportation Changing work structure, increased mechanization leads to less

energy expenditure at work and home

Four major transitions associated with urbanization (2)

3. Changing dietary patterns Shift in food production, distribution, availability and costs Higher energy, fat, animal protein, refined and processed food intakes,

lower intake of traditional grains, fruits, vegetables, greater variety

4. Changing stressors, quality of social support Fragmentation of traditional family structure Increased job stress Absence of community support systems (social capacity)

Urban Versus Rural Environments: Not dichotomous or unchanging

• Marked variations within urban and rural environments, but also between urban and rural environments within a region

• Directions of differences in social, cultural and biologic differences between urban and rural environments vary between HIC, MIC and LIC (e.g. CVD less in rural areas of LIC, but more in some urban areas of HIC)

• Urban and rural environments themselves evolve over time– Rural urban through economic developments and expansion of

cities to include neighbouring rural communities– Urban favourable or unfavourable environments

THE ABOVE CHANGES ARE ASSOICATED WITH MARKED SOCIETAL AND LIFESTYLE CHANGES

TWO FUNDAMENTAL TENETS

1. Obesity, Diabetes and CVD are Normal Biologic Responses to Abnormal Environments

2. Biologic factors are generally deterministic (and hence the intervention strategies are more generalizable). Societal factors have a more contextual impact ( and hence the approaches to societal interventions may be more variable.

Basis For PURE

• CVD burden is increasing globally and 80% occurs in L & MIC– Increasing in LMIC– Decreasing in HIC

• Epidemiologic transition has been hypothesized as the cause, but has not been studied

• Key INTERHEART Study Observations– >90% of AMI globally explained by 9 modifiable risk factors– Similarity of impact in all regions and ethnic groups

So, What Causes These Risk Factors?

The Prospective Urban and Rural Epidemiologic (PURE) study

3 interrelated levels of questions:

• Societal influences on health behaviours ,risk factors and chronic diseases.

• Differences in health behaviours, risk factors and disease between urban and rural settings;and their variations in a range of countries at various levels of economic advancement.

• Relationship of societal and individual level factors on disease rates.

Hypothesis:

Maladaptation to urbanization is the proximate cause of obesity, which leads to elevated risk factors (dyslipidemia, dysglycemia, hypertension). The risk factors interact with genetic and psychosocial factors resulting in increased CVD.

Scope

Primary area of interest: • CVD, Diabetes and Obesity

Secondary goals: (high disease burden) • Other chronic disease e.g. common cancers• Infectious diseases e.g. TB • Respiratory diseases e.g. COPD, asthma • Injury and disability• Depression

Objectives - Baseline

To Examine:

1. Urban-rural differences in • Levels of proximal exposures (built

environment,mechanization,activity, community structure, urbanization, diet, food and tobacco policies and prices)

• Prevalence of risk factors (conventional and emerging)• Prevalence of disease.

2. Clustering of the above within households,within communities and within countries

Objectives: Longitudinal study

To determine:

1. whether changes in urbanization are associated with variations in lifestyles and risk factors

2. how changes in individual (lifestyle) are affected by changes in community level factors (eg. mechanization, access to health care) are related to variations in risk factors and disease rates/disability

3. how the above vary in different regions of a country or across countries

4. predictors of disease.5. to track risk factor changes and disease rates over time in the

communities studied.

Current Status of PURE

Countries actively recruiting:India: 22,000 subjects from 5 centresSouth Africa: Over 2000 individuals from one centerChina: 11,000 subjects from 10 locations.

Begun recruiting:Colombia , Sweden and UAE

Ready to start: Brazil, Argentina,Iran,

Sweden,Canada,Chile,Zimbabwe.

Other interested countries: ?Thailand, ?Russia,Tanzania, Poland.