This document discusses the high burden of cardiovascular disease (CVD) in India and the link between air pollution and increased risk of CVD. It provides the following key points: 1. CVD is the leading cause of death in India, with rates higher than global averages. Major CVDs include IHD, cerebrovascular disease, and hypertension. 2. Risk factors for CVD like hypertension and diabetes are rising dramatically in India and projected to affect hundreds of millions by 2030. 3. Existing evidence suggests air pollution likely increases the risk of CVD and its risk factors through mechanisms like endothelial dysfunction, inflammation, and increased blood pressure. 4. Research aims to better characterize the associations between long-term air

1. Air Pollution and Cardiovascular Disease in
India
D Prabhakaran DM, FRCP, FNASc
Director, Center for Chronic Condition and Injuries and Vice President (
Research and Policy), Public Health Foundation of India, Gurgaon, India
Professor, Department of Epidemiology, London School of Hygiene and
Tropical Medicine, London, UK
Adjunct Professor, Rollins School of Public Health, Emory University, Atlanta ,
GA, USA

2. Cardiovascular Disease…………
Hypertension and Diabetes

3. CVD in India : The High Burden
Diseases Death per 100 000 population
Male Female Total
IHD 178 (128) 112 (85) 144 (106)
Cerebro-vascular 90 (99) 75 (79) 82 (88)
RHD 11 (5) 10 (5) 10 (5)
Hypertensive HD 18 (14) 15 (13) 17 (13)
Total CVD 321 (273) 225 (200) 272 (235)
Prabhakaran D, Jeemon P and Roy A. Circulation 2016;133:1605-1620
Numbers in parenthesis are world average

4. Air Pollution likely increases the risk for both CVD
and risk factors

5. Grim Portends for the future………
Persons with 2000 (Million) 2030 (Million)
Hypertension 118
139 (2008)
214
Diabetes 30 (2000)
61 (2011)
67 (2014)
69 (2015)
79 (2000)
101 (2011)
109 (2014)
124 (2015)*
Persons dying from 2004 (Million) 2030 (Million)
Tobacco 0.9 2 +
CVD 2.7 4
Cancer 0.73 1.5
Reddy K et al. Lancet 2005; 366:1744-49, Patel V et al. Lancet 2011; 377:413-28, IDF Diabetes Atlas, 2011,2013,2015
5
* 2040

6. Top CVD influenced by Air pollution
Cardiovascular Effect Increased Risk (95% CI) Source
Myocardial Infarction RR = 1.16 (1.04-1.29)
RR = 1.025 (1.015-1.036)
OR = 1.022 (1.015–1.030)
(Teng et al., 2014)
Ischaemic heart disease OR = 1.17; (0.98-1.40) (Gardner et al., 2014)
Heart failure RR = 1.21 (1.14–1.28) (Shah et al., 2013)
Stroke RR = 1.011; (1.011-1.012) (Shah et al., 2015) (Tian et al., 2017)
Thrombosis OR = 1.70; (1.30-2.23) (Baccarelli et al., 2008)
Hypertension Adjusted OR of 1.14 for each 10μg/m3
increase in PM2.5
(Lin et al., 2017)
OR = 1.098, (1.015–1.188) for each 10
10μg/m3 increase in PM2.5
(Cai et al., 2016)
Arrhythmias RR = 1.053 (1.012-1.094) for PM2.5 ≥
25µg/m3
(Song et al., 2016)
OR = 1.59 (1.12-2.25) (Folino et al., 2017)
Strongest effect observed for heart failure, thrombosis and arrhythmias

7. Burden of AP-mediated Cardiovascular Diseases (GBD
2015)
832,000 cardiovascular disease deaths
due to air pollution (30% of total) in 2015
~ 1.8 million deaths
(1.1 million Ambient; 700,000
Household)
49 million DALYs (#1 of any risk
factor)
Majority of burden from NCDs
DALY = Years of life lost + years
lived with disability

8. Mechanisms of increased risk for CVD from air pollution : A summary
• Endothelial
dysfunction
• Inflammation/
Lipid peroxidation
• Increased BP
• Abnormalities of
Heart rhythm
• Metabolic
abnormalities
• Atherosclerosis
• Hypertension
• Arrhythmias
• LV dysfunction
• IHD
• PVD
• CHF
• Arrhythmias/
Sudden death
PM2.5 & others

9. Overlapping risk factor attributions from
categories of combustion particles in India
(based on GBD 2010 for the case of Ischemic Heart Disease and Child ALRI)
Smith et al. ARPH, 2014
Burnett et al EHP 2014
PAF for IHD and ALRI remarkably similar
Highly levels of PM2.5 similar to active smoking
Modelled data and needs proof

10. Expanding the Evidence Base
• Review published by the Ministry of Health in
2015
• Documented best available evidence in India
on air pollution exposure and health impacts
• Review acknowledged that while evidence for
policy development was there, further
strengthening of the Indian evidence base was
essential

11. Current the Evidence Base in India
• Most studies deficient in exposure or outcome assessment
• Most studies based on RSPM, SPM, PM10
• Little to no examination of:
o Cardio-metabolic diseases – outcomes and risk factors
o Prenatal/early childhood exposures
o Neurodevelopmental effects
• Most studies either time-series or cross-sectional
o Long-term exposure?
• Microenvironment profiles
o E.g. in-transit/in-vehicle exposures

12. 12
Goal: A fully integrated research and training program on air pollution and
cardiometabolic diseases with policy relevance to improve health of Indians
1. Research
• Advancing science of ambient air pollution (AP) epidemiology on cardio-
metabolic (CM) risk factors and outcomes
• Evidence and knowledge to inform development of policy on transportation,
energy, urban planning, etc.
2. Training and Capacity Building
• Developing a cadre of environmental health researchers and faculty in India
• Skill building for effective translation of evidence into policy
12
GEOHealth Hub

13. 13
The CARRS (Centre for cArdiometabolic Risk Reduction in South-asia) Surveillance Study,
• Representative cohort of 12,271 adults (> 20 years old) enrolled between 2010-2011 in
Delhi and Chennai.
• Annual questionnaire follow-up and alternate year biological sample collection
• Participants fully phenotyped for Cardio-Metabolic Diseases
• Households geocoded and integrated into a GIS database
• Cardio-metabolic events and risk factor data collected for 5 years, with a second 5-year
exercise getting underway
Study Partners
13
About CARRS

14. • Potential to provide Framingham like data
• Understand Social determinants
• Bio repositories that can help in understanding mechanisms of disease
600000 aliquots of different components of blood, urine saliva and so on in
long term storage; DNA extracted for nearly 8000 individuals

15. 1515
AIM 1: Developing a model to estimate ambient exposure to air
pollution (AP) in Chennai and Delhi
• Estimate daily average PM2.5 exposure
between 2010-2016 at 1x1 km resolution
in Delhi and Chennai
• This model will be further developed to
cover all of India (Prospective Aim 1)
Partners on the modeling exercise:
• Urban Emissions Pvt. Ltd.
• IIT – Delhi
• IIT –Bombay
• IIT – Kanpur
• CSIR – National Physical Laboratory
• St John’s Medical College, Bangalore

16. 1616
AIM 2: Estimate association between exposure to AP, temperature,
CM risk factors, and CM diseases and characterize susceptibility
• Estimate effects of temperature and long-term exposure to AP on CM risk factors and diseases
• T2DM, HTN , CVD events, dyslipidemia
• blood pressure, fasting glucose, serum total cholesterol
• Identify susceptible populations based on SES, occupation & built environment
• Education, occupation, total household income
• Primary and secondary type of cooking fuel
• Built environment – GEO-coded addresses
• Neighborhood walkability, access to businesses, access to green spaces, access to parks
(satellite green space data), health care access and food access
• Investigate whether SES, occupation or built environment modify effect of AP through
differential exposures & susceptibility to pollution-related health effects
• Generalized linear mixed models adjusted for confounders and multiple pollutants, within-
subject repeated measures, time varying covariates
•

17. 1717
AIM 3: Characterize DNA methylation patterns associated with
CM events & investigate whether they mediate AP effects on CM
events
• Nested case-control design (N~400), CVD events taken place in CARRS cohort in
last 6 years
• Case-control design to maximize power
• ~400 CVD events in CARRS till date
• Age and gender matched controls
• Epigenome-wide data will be generated on ~200 CVD events and controls to
identify the differentially methylated sites associated with CVD outcomes
• Methylation EPICBeadChip: > 850,000 methylation sites
• Secondary purpose to undertake mediation analyses to examine if DNA
methylation mediates the effect of air pollution on cardiovascular events

18. 1818
AIM 4: Estimate the association between AP &
Vitamin D in Chennai & New Delhi (N=1000)
Variation in Vitamin D exposure & up to 6-fold difference in AP levels in Chennai & Delhi
• Composition & distribution of AP between 2 cities:
• Latitude (Chennai 13.1 degrees vs. Delhi at 28.6 degrees)
• Composition (Individual AP pollutants – CO, NO2, SO2, O3)
• Within-city geographic variation (tertiles of AP levels)
• Compare circulating 2-OH-D levels and prevalence of vitamin D deficiency (controlling for season,
matching on sun exposure) in association with AP levels and composition
• Are AP-vitamin D links mediated by differences in CM outcomes (eg, CVD, HTN, T2DB, fasting
glucose levels)?
• Causal mediation analysis – Indirect of AP on CM risk factors mediated by Vitamin D & direct
effect of AP not mediated by vitamin D.

19. 1919
Prospective Aim – Personal Exposure
● Personal exposure to be assessed in a sub-set of
the CARRS cohort as part of 6th follow-up in
2018
● ~250 individuals each in Delhi and Chennai
● Stratified random sampling
● Equipment is currently being finalized
● Protocol being developed with Petros Koutrakis
at HSPH
● Will be one of the first large scale personal
exposure studies for ambient PM2.5 in India
Exposure
Profiles
Personal
Exposure
Monitoring
Cluster-Level
Ambient
Monitoring
Micro
Environment
Monitoring

20. Conclusions
• CVD major cause of death and disability in India
• Exponential increase in CVD and Risk Factors in India
• Putative mechanisms linking Air Pollution with CVD available from small studies
• Air Pollution likely major contributor to CVD in India
• Evidence in India linking AP and CVD is being generated through elegant
research designs addressing both exposure and outcome measurements