Air Pollution and Cardiovascular Disease in India

D Prabhakaran DM, FRCP, FNAScDirector, 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

Cardiovascular Disease…………

Hypertension and Diabetes

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

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

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, 2011,2013,20155

* 2040

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

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

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

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

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

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 factorso Prenatal/early childhood exposureso Neurodevelopmental effects

• Most studies either time-series or cross-sectionalo Long-term exposure?

• Microenvironment profileso E.g. in-transit/in-vehicle exposures

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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

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GEOHealth Hub

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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

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About CARRS

• 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

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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

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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

•

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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

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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.

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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

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