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Global burden of cardiovascular disease
1
Fortis Escorts Hospital, Jaipur,
India; 2 Government Medical
College, Akola, India; 3 Madras
Diabetes Research Foundation,
Chennai, India; 4 Public Health
Foundation of India, New Delhi,
India; 5 Population Health
Research Institute, McMaster
University, Hamilton, Canada
Correspondence to:
Dr R Gupta, Fortis Escorts
Hospital, JLN Marg, Malviya
Nagar, Jaipur 302017, India;
rajeevg@satyam.net.in
Accepted 4 September 2007
16
Epidemiology and causation of coronary heart
disease and stroke in India
R Gupta,1 P Joshi,2 V Mohan,3 K S Reddy,4 S Yusuf5
ABSTRACT
Cardiovascular diseases are major causes of mortality and
disease in the Indian subcontinent, causing more than
25% of deaths. It has been predicted that these diseases
will increase rapidly in India and this country will be host
to more than half the cases of heart disease in the world
within the next 15 years. Coronary heart disease and
stroke have increased in both urban and rural areas.
Case–control studies indicate that tobacco use, obesity
with high waist:hip ratio, high blood pressure, high LDL
cholesterol, low HDL cholesterol, abnormal apolipoprotein
A-1:B ratio, diabetes, low consumption of fruits and
vegetables, sedentary lifestyles and psychosocial stress
are important determinants of cardiovascular diseases in
India. These risk factors have increased substantially over
the past 50 years and to control further escalation it is
important to prevent them. National interventions such as
increasing tobacco taxes, labelling unhealthy foods and
trans fats, reduction of salt in processed foods and better
urban design to promote physical activity may have a
wide short-term impact.
The World Health Organisation (WHO) reports
that in the year 2005 cardiovascular diseases caused
17.5 million (30%) of the 58 million deaths that
occurred world wide.1 Cardiovascular diseases such
as coronary heart disease (CHD) and strokes are
the largest causes of death in developing countries
and are one of the main contributors to disease
burden.2 Between 1990 and 2020 these diseases are
expected to increase by 120% for women and 137%
for men in developing countries as compared with
30–60% in developed countries.3 It has been
projected that by the year 2010 60% of the world’s
patients with heart disease will be in India.2 Age-
standardised cardiovascular disease death rates (per
100 000) in middle-aged subjects (30–69 years) are
low in developed countries such as Canada (120)
and Britain (180) and high in developing countries
Brazil (320), China (280), Pakistan (400), Nigeria
(410), Russia (680) and India (405).1 Moreover, in
India about 50% of CHD-related deaths occur in
people younger than 70 years compared with only
22% in the West.2 In developing countries 94% of
deaths from stroke occur in people aged ,70 years
in contrast to 6% in developed countries.2 This
article summarises the evidence which shows that in
India there is a fully developed epidemic of cardio-
vascular diseases such as CHD and stroke. Several
studies from India show that the disease burden
estimated by disease prevalence studies is increasing
in both urban and rural populations, the risk factors
for this epidemic are similar to those elsewhere in the
world, and there has been a substantial increase in
these risk factors in India in recent years.
CORONARY HEART DISEASE AND STROKE
MORTALITY
According to the Global Burden of Diseases Study
in India, in the year 1990 CHD caused 0.62 million
deaths in men and 0.56 million deaths in women
(total 1.18 million) and strokes were responsible for
0.23 million deaths in men and 0.22 million deaths
in women (total 0.45 million).3 By the year 2000
CHD had led to 1.59 million deaths and stroke to
0.60 million deaths.3 Mortality from these condi-
tions is predicted to increase rapidly and the
absolute numbers of CHD cases in India to
overtake those of the established market econo-
mies and China while stroke mortality would also
increase (table 1).
Leading major cause groups of deaths during
1984 to 1998 have been reported by the Registrar
General of India.4 Trends show that there has been
a significant decline in the proportion of deaths
from infectious diseases from 22% to 16%, whereas
mortality from cardiovascular diseases has
increased from 21% to 25%. The reliability of
mortality data has been questioned on issues of
medical classification of deaths as a large number
of deaths are recorded as senility or old age and a
major cause in this group is cardiovascular disease,
hence the current sources may underestimate the
deaths due to cardiovascular diseases.
Gajalakshmi et al evaluated the causes of deaths
in subjects aged 25–69 years using a verbal autopsy
in urban Chennai.5 From 1995 to 1997 there were
72 165 deaths in Chennai, of which 5388 (7%)
were due to suicides, violence and accidents. Verbal
autopsy to identify clearly the cause of death was
performed in 48 357 of the remaining 66 777
(72.4%). Cardiovascular diseases were the largest
group with 18 680 deaths (38.6%) followed by
cancer (8.7%), tuberculosis (5.8%) and respiratory
causes (3.5%). Unspecified medical causes
accounted for 19 825 (41.0%) deaths.
Joshi et al reported mortality statistics from the
Andhra Pradesh Rural Health Initiative.6 The study
prospectively evaluated causes of death in a
population cluster of about 150 000 subjects, and
it was reported that in both men and women
cardiovascular diseases were the major causes of
deaths. In this study there were 1354 deaths in the
first year of follow-up and analysis using a
validated verbal autopsy instrument showed that
diseases of the circulatory system caused 34% of
male and 30% of female deaths.
Mohan et al reported that in urban south
Indians, mortality rates are twofold higher in
people with diabetes than in non-diabetic subjects,
and among diabetic subjects, cardiovascular
(52.9%) and renal diseases (23.5%) were the
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Table 1 Cardiovascular deaths in India, China and developed countries in millions (Global Burden of Diseases Study)10
1990 2000
India China EME India China
Cardiovascular diseases 2.26 2.57 3.18 3.01 3.30
Coronary/ischaemic heart 1.18 0.76 1.67 1.59 0.99
disease
Cerebrovascular diseases 0.45 1.27 0.79 0.60 1.65
EME, established market economies.
commonest causes of death.7 These studies show that these
diseases are a major cause of death in Indian urban and rural
locations. The continuing prospective Sample Registration
System Verbal Autopsy (SRS-VA) Million Deaths Study in
India8 and the Prospective Urban Rural Epidemiology (PURE)
Study9 should provide more definitive answers.
CORONARY HEART DISEASE BURDEN AND PREVALENCE
STUDIES
The Global Burden of Diseases Studies reported the disability-
adjusted life years (DALYs) lost by CHD in India in years 1990
and 2000. In 1990 CHD was responsible for 5.6 million DALYs
in men and 4.5 million in women.10 This was projected to
increase in years 2000, 2010 and 2020 among men to 7.67, 10.46
and 14.36 and in women to 5.55, 6.55 and 7.66 million,
respectively. Data from the World Health Report (2002)11 shows
that in South East Asia, a region that also includes other
countries with high childhood and high adult mortality
(Bangladesh, Bhutan, Maldives, Myanmar, Nepal and North
Korea), cardiovascular diseases caused a loss of 35.4 million
DALYs, CHD 17.99 million, rheumatic heart disease 2.34
million and cerebrovascular diseases 7.98 million. India com-
prises 81.2% of population in this region and therefore the
DALYs lost in India owing to CHD according to this report
would be 14.61 million which is much more than the earlier
projections.
In the absence of reliable nationwide prospectively collected
morbidity data, estimates of the burden of CHD have been
based on indicators from population-based, cross-sectional
surveys. Multiple epidemiological studies have been performed
in urban and rural populations in India over the past 60 years.12
Table 2 shows the prevalence of CHD in various studies.
Limitations of these studies include small and variable sample
Figure 1 Coronary heart disease (CHD) prevalence (%) in Indian urban
and rural subjects aged .30 years as reported in epidemiological
studies. The diagnostic criteria used were either known CHD, or angina
on the Rose questionnaire or electrocardiographic Q/ST/T wave changes.
There is a significantly increasing trend of CHD in both urban and rural
populations.
Heart 2008;94:16–26. doi:10.1136/hrt.2007.132951
Global burden of cardiovascular disease
2010 2020
EME India China EME India China EME
3.49 3.80 3.81 3.53 4.77 4.53 3.66
1.84 2.03 1.15 1.87 2.58 1.37 1.95
0.87 0.75 1.91 0.88 0.95 2.29 0.91
size, variable and, at times, low response rates, inappropriate
diagnostic criteria such as history, non-specific electrocardio-
graphic changes—for example, abnormal ST-T waves, lack of
age standardisation, and incomplete reporting of results.12 13 On
the other hand most of these studies used similar population-
based recruitments, methodology and diagnostic criteria
(known CHD, Rose questionnaire angina and/or electrocardio-
graphic Q-ST-T changes) as shown in table 2.
The age groups evaluated in these studies are variable and
therefore we compared studies that included subjects aged >25–
30 years to determine secular trends. A high prevalence is
consistently seen in studies at urban locations (Chandigarh
6.6%,16 Rohtak 3.6%,17 Delhi 9.7%,18 Varanasi 6.5%,19 Jaipur
9.2%,20 Trivandrum 12.7%,21 Chennai 11.0%,22 Jaipur 9.1%,23 and
Goa 12.5%24) as compared with the rural (Haryana 2.1%,26
Haryana 2.7%,28 Punjab 3.1%30 and Rajasthan 4.3%31). There are
significantly increasing trends in urban (r2 = 0.60) as well as
rural (r2 = 0.31) populations (fig 1). Analyses of prevalence
studies in various decades in India also provide significant
information about the absolute number of CHD cases.12
Decadal variations indicate that the adult prevalence has
increased in urban areas from about 6.5% in the mid-1960s to
7.0% in 1980, 9.5% in 1990 and 10.5% in 2000, while in rural
areas it increased from 2% in 1970s to 2.5% in 1980, 4% in 1990
and 4.5% in 2000. This would translate into 4.5 million urban
subjects in 1970, 5.6 million in 1980, 9.7 million in 1990 and 14.1
million in the year 2000, and in rural populations into 4.1
million in 1970, 6.4 million in 1980, 11.8 million in 1990 and
15.7 million in 2000.12 Thus, epidemiological studies show that
there are at present 29.8 million patients with CHD in this
country, which is similar to the numbers obtained by the
National Commission on Macroeconomics and Health.35 As
epidemiological studies do not identify patients with silent and
asymptomatic CHD the actual number of cases may be much
greater.
STROKE PREVALENCE STUDIES
According to recent WHO estimates, developing countries
account for 85% of deaths from stroke world wide.1 Stroke
death rates per 100 000 in selected countries among people aged
30–69 years is high in developing countries (Nigeria 122,
Tanzania 118, India 100, China 96, Pakistan 84 and Brazil 82)
as compared with ,20 in UK and Canada.36 Disability due to
strokes in these countries is almost seven times that in
developed countries.36 The Global Burden of Diseases Study
reports that stroke is common in India, although stroke
mortality is currently lower than in China (table 1).10
Prevalence data for stroke in India are scanty and the available
studies suffer from multiple biases that are similar to those for
CHD.13 A low prevalence in community studies might also be
due to low survival after an acute event, and many cases of
transient ischaemic attacks and complete recovery from strokes
may be missed on inquiry hence these prevalence rates might be
underestimates. Table 3 shows the major epidemiological
17
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Global burden of cardiovascular disease

Table 2 Coronary heart disease prevalence studies in India

Crude prevalence
First author Year reported Location Sample size Age group Diagnostic criteria (%)

Urban
Mathur KS14 1960 Agra 1046 30–70 K+H+ECG-Q-ST-T 1.05
Padmavati S15 1962 Delhi 1642 30–70 K+H+ECG-Q-ST-T 1.04
Sarvotham SG16 1968 Chandigarh 2030 30–70 K+H+ECG-Q-ST-T 6.60
Gupta SP17 1975 Rohtak 1407 30–70 K+H+ECG-Q-ST-T 3.63
Chadha SL18 1990 Delhi 13 723 25–65 K+H+ECG-Q-ST-T in 9.67
random sample
Sinha PR19 1990 Varanasi 648 30–70 K+H+ECG-Q-ST-T 6.48
Gupta R20 1995 Jaipur 2212 20–80 K+H+ECG-Q-ST-T 7.59
Begom R21 1995 Trivandrum 506 30–80 K+H+ECG-Q-ST-T 12.65
Mohan V22 2001 Chennai 1150 20–70 K+H+ECG-Q-ST-T 11.00
Gupta R23 2002 Jaipur 1123 20–80 K+H+ECG-Q-ST-T 8.12
Pinto VG24 2004 Panjim 371 35–64 K+H+ECG-Q-ST-T 13.21
Kumar R33 2006 Chandigarh 1012 35–80 K+H+ECG-Q 7.21
Kamili MA25 2007 Srinagar 1576 40–80 K+H+ECG-Q-ST-T 8.37

Rural
Dewan BD26 1974 Haryana 1506 30–70 K+H+ECG-Q-ST-T 2.06
Jajoo UN27 1988 Vidarbha 2433 30–70 K+H+ECG-Q-ST-T 1.69
Chadha SL28 1989 Haryana 1732 35–65 K+H+ECG-Q-ST-T in 2.71
random sample
Kutty VR29 1993 Kerala 1130 25–65 K+H+ECG-Q-ST-T 7.43
Wander GS30 1994 Punjab 1100 30–70 K+H+ECG-Q-ST-T 3.09
Gupta R31 1994 Rajasthan 3148 20–80 K+H+ECG-Q-ST-T 3.53
Gupta AK32 2002 Himachal 1160 20–80 K+H+ECG-Q-ST-T 5.00
Kumar R33 2006 Haryana 1188 35–80 K+H+ECG-Q 1.60
Kumar R33 2006 Punjab (semiurban) 1685 35–80 K+H+ECG-Q 2.91
Chow C34 2007 Andhra 345 20–90 K+H+ECG-Q 3.60
Kamili MA25 2007 Kashmir 1552 40–80 K+H+ECG-Q-ST-T 6.70
K, known coronary heart disease; H, history of angina as assessed by WHO questionnaire; ECG, electrocardiogram; Q-ST-T,
electrocardiographic waves.

studies in India that determined the community stroke
prevalence. The crude prevalence rates of stroke appear to be
higher in urban populations than in rural subjects, but there are
location-based differences as seen by a very high prevalence
among Parsis in Mumbai (842/100 000)46 as compared with the
Mumbai general population (220/100 000)38 Evaluation of
secular trends in stroke in India is not possible owing to the
small numbers of studies.
The incidence of stroke has been reported by a study from
West Bengal in India and was significantly greater in rural
subjects than in the urban population.47 In a 5-year prospective
study among 20 842 rural subjects the age-adjusted incidence
rate was 262/100 000 a year,48 while in a study among 50 291
urban subjects the incidence was 105/100 000.39 These studies
have excluded deaths from stroke and the data are likely to be
underestimates. The Global Burden of Diseases Study reported
an estimated population-based annual stroke incidence in India
of 89/100 000 in 2005, which is projected to increase in 2015 to
91/100 000 and in 2030 to 98/100 000.10 This is compounded by
high stroke mortality in India. In hospital-based studies 30-day

Table 3 Stroke prevalence studies in India

Age-adjusted
Crude prevalence prevalence per
First author Year reported Location Sample size per 100 000 100 000

Urban
Bansal BC37 1973 Rohtak 79 046 44 –
Bharucha NE46 1988 Mumbai Parsi 14 010 842 424
Dalal PM38 1997 Mumbai 145 456 220 –
Banerjee TK39 2001 Kolkata 50 291 147 334
Gourie-Devi M40 2004 Bangalore 51 502 136 –

Rural
Abraham J41 1970 Tamilnadu 258 576 57 84
Gourie-Devi M42 1987 Karnataka 57 660 52 –
Razdan S43 1989 Kashmir 63 645 143 244
Das SK44 1996 West Bengal 37 286 126 –
Saha SP45 2003 West Bengal 20 842 147 –
Gourie-Devi M40 2004 Kanataka 51 055 165 262

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stroke mortality in Mumbai was 32% in 1963–8, which declined
to 12% in 1978–82,49 but still remains significantly greater than
in the developed countries where short-term mortality rates
vary from 5% to 10%.36
In most parts of the world about 70% of strokes are due to
ischaemia, of which 25% are cardioembolic, 27% are haemor-
rhagic and 3% are of unknown cause.36 An important difference
in stroke epidemiology in developing countries is the greater
occurrence of haemorrhagic strokes. In China 17.1–39.4%
strokes are due to intracerebral haemorrhage. In other low-
and middle-income countries the incidence of haemorrhagic
stroke varies from 29% to 57% in Africa, 19% to 46% in Asia and
19% to 43% in South America compared with 10% to 20% in
North America and Western Europe.49 Only a few studies in
India have reported statistics such as these. A population-based
study reported ischaemic stroke in 68% and haemorrhagic in
32%.50 This is consistent with data in other developing
countries, although more and larger studies are needed to
determine trends in stroke subtypes in India.
WHY THE INCREASE?
There have been multiple hypotheses to explain the increase in
cardiovascular diseases in India. Studies in emigrants indicated
that South Asians had higher rates of CHD, but no higher rates
of risk factors than the local population.51 Genetic factors were
implicated. These studies suffered from multiple biases, the
major being the ‘‘healthy survivor’’ bias, as survivors of acute
coronary event that reached these hospitals were younger, more
educated, affluent and had risk factors that were not considered
significant with the available knowledge, thus perpetuating the
allegory that there was something unique among the Indians.
Most important was that these studies did not study the
relationship between the risk factors and CHD and, moreover,
did not measure several of the risk factors.
Epidemiological studies and risk factors
There is a strong correlation between urbanisation and increase
in the risk of cardiovascular disease in Indian subjects. Coronary
risk factors that are more prevalent in Indian urban subjects
may explain their excess cardiovascular disease.12 Padmavati
reported that the prevalence of CHD was significantly greater in
urban subjects in Delhi than in rural subjects around Delhi.15
They also reported that coronary risk factors such as hyperten-
sion and high cholesterol levels were more prevalent in the
urban subjects. Similar urban–rural differences were reported by
Gupta and Malhotra,17 Chadha et al18 and the Indian Council of
Medical Research studies52 who evaluated urban–rural risk
factor differences. All these studies reported that multiple
lifestyle factors (sedentariness, dietary calorie and fat intake) as
well as physiological factors (weight, body mass index (BMI),
waist–hip ratio (WHR), blood pressure, high total and low-
density lipoprotein (LDL) cholesterol, low high-density lipopro-
tein (HDL) cholesterol, total/HDL cholesterol ratio, triglycerides
and diabetes) were significantly more prevalent in the urban
populations. These studies also noted that smoking, which is an
established cardiovascular risk factor, was more common in
rural subjects and therefore could not provide conclusive
guidance.
In the mid-1990s we systematically compared the prevalence
of multiple coronary risk factors in rural and urban subjects in
Rajasthan and also correlated these risk factors with the
prevalence of CHD.23 31 We found that the prevalence of risk
factors was similar to those found in the studies reported above.
Heart 2008;94:16–26. doi:10.1136/hrt.2007.132951
Global burden of cardiovascular disease
We then determined the importance of various risk factors in
CHD using logistic regression and reported that smoking was an
independent risk factor in both rural and urban subjects. Other
major risk factors were obesity, high WHR, hypertension and
lipid abnormalities. This showed that standard cardiovascular
risk factors were important in Indians. Emigrant versus native
South Asian case–control studies have reported a greater
prevalence of risk factors such as diabetes, impaired glucose
tolerance and other lipid abnormalities to explain the greater
prevalence of CHD in emigrant South Asians.53–55
The prevalence of stroke seems to be similar in urban and
rural populations, but only a limited number of comparable
studies exist. Smoking and hypertension are well-known stroke
risk factors and explain the greater stroke incidence among the
Chinese population.36 It is well known that smoking and
tobacco use is greater among the rural populations in India.56
Recent studies have reported a high prevalence of hypertension
in rural subjects in different parts of the country.57 Thus, stroke
in rural populations may be explained by these standard risk
factors, although results of continuing studies using either a
cross-sectional design (eg, INTERSTROKE Study)50 or a
prospective design (namely, PURE Study)9 are awaited to
evaluate accurately stroke determinants in India.
CHD risk factors in case–control studies
Hospital-based case–control studies in the 1960s and 1970s
reported that smoking or tobacco use, hypertension, diabetes
and cholesterol levels were significantly greater in subjects with
CHD.58 Subsequent case–control studies reported that other
lipid abnormalities such as high LDL cholesterol and triglycer-
ides, and low HDL cholesterol were also important.59–63
Abnormalities of the apolipoprotein system, including high
apolipoprotein B100, high lipoprotein(a) and low apolipoprotein
A-1 levels, in patients with CHD as compared with controls
have also been reported.62 63 A high prevalence of abnormalities
of coagulation and platelet functions has also been reported.64
Ethnic susceptibility to CHD among South Asians was initially
observed among people who had emigrated to the West Indies,
East Indies and Britain.65 McKeigue et al reported that an
increased WHR and abnormalities of glucose and lipid
metabolisms were major coronary risk factors in South Asians
in Britain.53 It was reported that these subjects had a greater
WHR and this was associated with a conglomeration of
metabolic risk factors—peripheral insulin resistance and hyper-
insulinaemia, hypertriglyceridaemia, low HDL cholesterol,
borderline raised LDL cholesterol and type 2 diabetes.53 65–67
Pais et al studied 200 cases of first myocardial infarction in
Bangalore and compared the risk factor profile with that of 200
age-matched controls.68 The most important predictor of acute
myocardial infarction was current smoking of both cigarettes
and bidis, followed by a history of hypertension and diabetes.
Other important risk factors were increased fasting glucose and
a high WHR.69 Rastogi et al performed a multicentre case–
control study in Delhi and Bangalore to identify important
coronary risk factors and reported similar findings.70 71 Cigarette
or bidi smoking, BMI .25 kg/m2, WHR .1.0, and a history of
hypertension, high cholesterol and diabetes were important risk
factors. An inverse association of CHD risk with dietary intake
of vegetables, green leafy vegetables, cereals and mustard oil was
noted. Patil et al performed a case–control study to identify risk
factors for acute myocardial infarction in a rural population of
Central India.72 One hundred and eleven consecutive cases of
acute myocardial infarction were recruited and compared with
222 controls matched for age and sex. Important risk factors
19
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Global burden of cardiovascular disease
Figure 2 Proportionate probability of acute myocardial infarction in
South Asian (SA) subjects as compared with subjects from rest of the
world (ROW). There is greater probability of acute myocardial infarction
in young South Asian subjects as compared with people from other
countries (p = 0.001). However, the difference disappears when the
probability is adjusted for the nine INTERHEART risk factors (p = 0.27).
Adapted from Joshi et al.74
were smoking, raised fasting glucose and a high WHR. Smoking
has been identified as the most important risk factor among the
young survivors of myocardial infarction in many studies.58
The INTERHEART study was a large case–control study
performed in 52 countries of the world with 15 152 cases of first
myocardial infarction and 14 820 controls.73 This study identi-
fied nine well-known coronary risk factors—abnormal lipids,
smoking, hypertension, diabetes, a high WHR, psychosocial
factors, low fruit and vegetable consumption, low alcohol
consumption, and lack of physical activity—as accounting for
more that 90% cases of acute myocardial infarction world wide.
An important finding of this study was a younger age of
occurrence of acute myocardial infarction in South Asians.74 The
mean (SD) age of occurrence of a first myocardial infarction
among 1732 participants from South Asia was 53.0 (11.4) years
as against 58.8 (12.2) years in other countries. Although the
mean age of myocardial infarction was lower in South Asians
than in subjects from other countries, the risk factors were
similar. Before adjustment for the nine INTERHEART risk
factors there was a higher probability of patients who were
younger than 40 years in the South Asian group (p = 0.001), but
after adjustment for these risk factors the difference was
attenuated and not significant (p = 0.27) (fig 2).
The risk factors that were found to be important in the
overall INTERHEART cohort were also important in the South
Asian cohorts (table 4).74 Some harmful risk factors were more
common in South Asians (raised Apo B/Apo A-1 ratio and
diabetes) and all the risk factors occurred at a younger age in
this group. Bidi smoking as well as use of non-smoked tobacco,
which is peculiar to the Indian subcontinent, also emerged as an
important risk factor.74 In the INTERHEART Study bidi
smoking was associated with age and sex adjusted odds ratio
(OR) of 2.89 (95% confidence interval (CI) 2.11 to 3.96) in the
overall cohort and was same in South Asians (OR = 2.73, 95%
CI 1.90 to 3.92).75 Participants who were current smokers of
cigarettes or bidis and who chewed tobacco had an OR of 4.09
(95% CI 2.98 to 5.61) while those who chewed tobacco were
also at increased risk (OR = 2.23, 95% CI 1.41 to 3,52). These
data are especially relevant for India where tobacco smoking
and chewing are widely prevalent both in men and women.76
20
These case–control studies have potential biases, but appear
plausible given that their findings are consistent among
themselves and also with the findings of cohort studies
conducted in Western populations. Prospective cohort studies
in South Asian populations are highly desirable. Cohort studies
also have their limitations—for example, they are not good
methods for studying acute precipitators such as stress and
variations in environment due to air pollution or temperature.
On the other hand, cohort studies are useful in studying the
effects of chronic exposures, assuming that one or a few
measures accurately characterise the exposure. We believe that a
carefully conducted case–control study is just as valuable as a
cohort study. The population attributable risk calculated in a
case–control study is an estimate of the proportion of cases that
would be avoided if the exposure is removed. This statistic (as in
the INTERHEART Study) combines information about the
strength of association of the relative risk with information
about the prevalence of exposure, and is important to estimate
modifiable environmental exposures. Additionally, it is difficult
to include enough cases of young patients with a myocardial
infarction in a cohort study or in other populations where the
incidence of the event is low. Continuing prospective studies
such as the PURE Study9 involving 28 500 people from five
locations in India and an additional 4000 subjects from Pakistan
and Bangladesh (n = 32 500) is likely to provide more important
information.
Stroke risk factors
Stroke is a non-homogeneous condition caused by either
extracranial/intracranial vascular atherothrombotic disease or
intracranial haemorrhagic lesions.77 Differences in cardiovascular
risk factors can partly influence the pathological types of stroke
as well as subtypes of ischaemic stroke across populations. Risk
factors for each type of stroke differ—atherosclerosis risk factors
(as in CHD) predominate in the former, whereas hypertension
and smoking are the known leading causes of the latter. Leading
stroke risk factors are raised blood pressure, smoking, high
cholesterol, low fruit and vegetable intake, physical inactivity
and alcohol excess.78 However, there is evidence that these risk
factors are associated with differing attributable risks for stroke
as compared with CHD, and some established CHD risk factors
such as high cholesterol are of uncertain importance for stroke.50
Hypertension is an important and consistent conventional
risk factor for stroke. The Prospective Studies Collaboration
meta-analysis of over one million subjects79 reported a log-linear
relationship of blood pressure and stroke. An Asia-Pacific
regional systematic review on blood pressure and stroke
correlation also reported similar results.80 Correlation of
hypercholesterolaemia with stroke is not clear and a meta-
analysis of 45 prospective cohort studies reported no significant
association between total cholesterol and ischaemic stroke,
although a trend was evident.81 Trials of LDL cholesterol
lowering with statins report a 20% relative risk reduction for
stroke, which is much less than for CHD (.50%). Diabetes has
been reported to be an independent risk factor for ischaemic
stroke.
Lifestyle factors such as smoking and tobacco use have been
reported to be important for both ischaemic and haemorrhagic
strokes.50 The relationship between excessive salt intake and
hypertension was established by the INTERSALT Study, but
relationship between salt intake and stroke is variable.82 In
countries with a high salt intake there is a clear association,
whereas in countries with a low sodium intake it is variable.50
Other dietary factors, such as fruit and vegetable consumption,
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Global burden of cardiovascular disease

Table 4 Risk factors for acute myocardial infarction in South Asians in the INTERHEART Study74
Prevalent Prevalent Population attributable
cases controls Odds ratio risk
Risk factor (%) (%) (95% CI) % (95%CI)

Apolipoprotein B/A-1 ratio (highest vs lowest quartile)

Other countries 48.3 31.8 3.01 (2.77 to 3.26) 45.9 (43.0 to 48.7)
South Asia 61.5 43.8 2.57 (2.03 to 3.26) 46.8 (36.7 to 57.0)

Current and former smoking

Other countries 65.7 49.4 2.22 (2.09 to 2.36) 36.2 (34.1 to 38.3)
South Asia 61.6 40.8 2.57 (2.22 to 2.96) 37.5 (33.1 to 42.1)

Hypertension
Other countries 40.5 23.6 2.44 (2.30 to 2.60) 23.9 (22.5 to 25.4)
South Asia 29.6 12.7 2.92 (2.46 to 3.48) 19.3 (16.6 to 22.4)

Diabetes
Other countries 18.2 7.2 3.20 (2.93 to 3.50) 12.5 (11.6 to 13.4)
South Asia 20.2 9.5 2.52 (2.07 to 3.07) 11.8 (9.6 to 14.5)

High waist:hip ratio

Other countries 46.7 34.0 2.21 (2.06 to 2.38) 33.3 (30.3 to 36.3)
South Asia 44.0 29.6 2.44 (2.05 to 2.91) 37.7 (30.9 to 45.2)

Psychosocial factors
Other countries 84.2 82.0 1.83 (1.58 to 2.13) 19.6 (15.4 to 23.7)
South Asia 86.0 82.6 2.62 (1.76 to 3.90) 16.1 (4.1 to 28.2)

Moderate to intense exercise

Other countries 15.8 21.6 0.70 (0.65 to 0.76) 25.2 (20.7 to 29.7)
South Asia 4.6 6.1 0.72 (0.53 to 0.97) 27.4 (11.7 to 51.8)

Alcohol consumption .1/week

Other countries 25.7 26.9 0.79 (0.74 to 0.85) 15.8 (11.7 to 19.9)
South Asia 13.3 10.7 1.06 (0.85 to 1.30) 24.6 (22.4 to 14.7)

Fruit and vegetable consumption .1/day

Other countries 38.3 45.2 0.70 (0.65 to 0.76) 12.2 (9.6 to 14.8)
South Asia 20.0 26.5 0.65 (0.53 to 0.81) 21.4 (13.2 to 32.7)

Combined effects
Other countries – – 125.7 (88.5 to 178.4) 88.2 (86.3 to 89.9)
South Asia 123.3 (38.7 to 400.2 85.8 (78.0 to 93.7)

are associated with a reduced risk of stroke and excessive fried
foods and fat intake with an increased risk.77 Excessive alcohol
intake is also a risk factor for stroke. Folate supplementation has
been reported to be associated with a reduced risk of stroke in a
meta-analysis.83 Regular physical activity is also protective. No
population-based prospective studies exist in India, and data on
stroke risk factors still rely on small case–control studies.38 49 In
certain geographical areas socioeconomic factors, ethnicity and
race are important risk factors for stroke.78
It is also important to realise that specific infections common
in India may also contribute to stroke. These infections include
malaria, neurocysticercosis, leptospirosis and viral haemorrhagic
fevers. Conditions such as sickle cell anaemia, and snake bites
are other prevalent disorders that can produce a stroke-like
picture owing to intracerebral haemorrhage.84 Cerebral venous
sinus thrombosis is a common cause of stroke among women in
India, especially during the postpartum period.85
In India only small case–control studies to identify risk factors
have been performed. Dalal reported that diabetes, hypertension,
tobacco use and low haemoglobin levels were important risk
factors in a study in Mumbai.38 A study in urban subjects in
Kolkata reported that hypertension was the most important risk
factor, whereas another study in West Bengal rural subjects
reported that existing heart disease, hypertension and smoking
were important.47 All these studies were small and larger studies
that are currently in progress such as the INTERSTROKE Study50
should be able to identify risk factors more accurately.
RISK FACTOR TRENDS
Major risk factors dependent on the demographic and societal
transition are physical inactivity, excess dietary calories and fat
intake, smoking and tobacco use, being overweight and obesity,
high blood pressure, diabetes, cholesterol levels, the metabolic
syndrome and psychosocial stress. There is epidemiological
evidence that the levels of many of these risk factors are
increasing in India. The rapid urbanisation and globalisation is
increasing mechanisation leading to sedentariness and this,
coupled with recently found affluence, is increasing tobacco,
calorie and fat intake, leading to increases in weight, glucose,
blood pressure and unfavourable lipid profiles.

Heart 2008;94:16–26. doi:10.1136/hrt.2007.132951 21

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Global burden of cardiovascular disease
Figure 3 Trends in age-adjusted prevalence of various risk factors in Jaipur Heart Watch (JHW) studies among urban subjects aged 20–59 years in
India. These studies were performed in 1992–4 (JHW-1),20 1999–2001 (JHW-2),23 2003–4 (JHW-3)91 and 2005–6 (JHW-4).92 There are significantly
escalating trends in prevalence of obesity (BMI >25 kg/m2), high WHR (.0.95), hypertension and hypercholesterolaemia (cholesterol >5.10 mmol/l)
in both men and women.
Smoking
Smoking and tobacco use became a fashion statement in the
past century in India. This phase was characterised by a large
increase in its consumption driven by prevalent attitudes
and cultural changes. The British studies and US Surgeon
General’s reports on the harm of smoking and tobacco use led to
a gradual decline in smoking in developed countries. On the
other hand, populations of low- and middle-income countries
have been increasing their cigarette consumption since about
1970.86 In these countries the per capita annual consumption of
cigarettes increased from 800/year to more than 1200 from
1970–2 to 1990–2. In India, tobacco use increased by 36% over
the same period.87 According to World Development Report, in
India, the per capita tobacco consumption was 0.7/kg/year in
1974–6 and 0.8/kg/year in 1980 and was projected to increase
to 0.9 kg/year by 2000 in contrast to developed countries where it
was poised to decline from 2.9/kg/year in 1974 to 1.8 in 2000.88
The prevalence of smoking and tobacco use varies in different
regions of India. In the second National Family Health Survey high
smoking and tobacco use was reported among men and women in
northeastern and northern Indian states while a low prevalence
was observed in Punjab and Maharashtra.56 The habit of smoking
is more prevalent in rural subjects (30–60%) than in the urban
population (10–30%).76 Although smoking is low among women,
use of non-smoked tobacco is high.76 There is an urgent need to
curb the tobacco epidemic in India. Important policy steps in this
direction are faithful implementation of the WHO Framework
Convention for Tobacco Control initiative in India and strict
application of the Indian Tobacco Control Act.76 Most of the
recent Indian epidemiological studies have reported an inverse
association between smoking/tobacco use and educational sta-
tus,56 89 and it seems that improving the literacy levels of the
population is an efficient method to decrease tobacco consumption.
Dietary changes and obesity
Per capita consumption of major fats and oils has increased in
India in the past 30 years.90 In 1958 it was 5.62 kg a year which
22
increased to 5.79 in 1961, 5.23 in 1966, 5.85 in 1971, 5.21 in
1976, 6.48 in 1981 and 6.97 in 1986. This consumption is much
lower than in European Union countries (38.98), USA (39.72),
Canada (34.83) and Japan (19.84). Consumption of oils and
hydrogenated oils is increasing similarly. This may be associated
with increasing obesity, although no national data are available.
The Jaipur Heart Watch (JHW) studies reported significantly
escalating trends in obesity and high WHR in an Indian urban
population. These studies were performed in 1992–4 (JHW-1),20
1999–2001 (JHW-2),23 2003–4 (JHW-3)91 and 2005–6 (JHW-4).92
Age-adjusted prevalence in subjects aged 20–59 years shows that
obesity (BMI >25 kg/m2 and high WHR .0.95) has increased
significantly (fig 3). There was a significant correlation of
increasing socioeconomic status (literacy levels) with increasing
obesity and truncal obesity.93 These studies show that in India
increasing socioeconomic status is associated with increasing
obesity in contrast to high- and middle-income countries, where
poverty is associated with greater obesity.94
Hypertension
A review of studies of the prevalence of hypertension in India
has shown a high prevalence in both urban and rural areas.95
Indian urban population-based studies using WHO guidelines
for diagnosis (known hypertension or blood pressure >160 mm
Hg systolic or 95 mm Hg diastolic, or both) have shown
increasing hypertension among adults aged >20 years from
about 5% in the 1960–70s to 11–15% in the late 1990s.57 The
prevalence of hypertension using recent criteria (blood pressure
>140/>90 mm Hg) has been reported among some urban
Indian populations. Gupta et al reported hypertension in Jaipur
in 30% of men and 33% of women,20 Joseph et al reported it in
31% of men and 41% of women in Trivandrum,96 whereas
Mohan et al reported a crude prevalence rate of 21% in
Chennai.97 In Mumbai, Anand reported hypertension in 34%
of middle-class executives,98 whereas Gupta et al reported
hypertension in 44% of men and 45% of women in Mumbai.99
We determined trends in the age-adjusted prevalence of
Heart 2008;94:16–26. doi:10.1136/hrt.2007.132951
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Figure 4 Increasing age-adjusted prevalence (%) of diabetes and
impaired glucose tolerance in Chennai in South India.107
hypertension in JHW studies in subjects aged 20–59 years (fig 3).
A significant escalation of hypertension prevalence was seen in
both men and women. These findings are in accord with those
of many developed countries where it has been reported that, at
any one time, about half of the population have high blood
pressure.100
Lipid levels and dyslipidaemias
The epidemiological studies of cholesterol measurement in India
are hampered by the lack of uniform assay that has resulted in
large variations. However, in recent studies cholesterol levels
measured by enzyme-based assays have shown a progressive
increase. In 1982, Gandhi et al101 estimated cholesterol lipopro-
teins levels in 201 urban Delhi subjects and reported mean (SD)
serum cholesterol of 160 (29) mg/dl (4.10 (0.75) mmol/l) in men
and 150 (25) mg/dl (3.90 (0.65) mmol/l) in women.101 In a more
recent study Reddy et al reported mean (SD) cholesterol levels of
177 (40) mg/dl (4.60 (1.05) mmol/l) in men and 176 (40) mg/dl
(4.55 (1.05) mmol/l) in women in Delhi.102 Pradeepa et al have
demonstrated that even within an urban environment, there
appears to be a significant difference in the lipid levels,
dyslipidaemia being more common and severe in the middle-
income group than in the low-income group.103 High levels of
small dense LDL are more important risk markers, and a study
showed greater levels among emigrant South Asians than in US-
based Caucasians.64 The INTERHEART Study reported that the
ratio of apolipoprotein (apo) B to apo A-1 was an important risk
marker for acute myocardial infarction.73 Higher levels were
seen in South Asian cases (61.5%) than in subjects from other
countries (48.3%).74 Limited information exists about the
changing time trends in prevalence of dyslipidaemia in Indian
subjects from methodologically comparable studies. The Jaipur
Heart Watch studies reported that there is a significant increase
in total cholesterol, LDL cholesterol and triglycerides and a
decline in HDL cholesterol in both men and women at all age
groups.93 Age-adjusted prevalence of high total cholesterol
(>5.17 mmol/l) among subjects aged 20–59 years shows
increasing trends in both men and women (fig 3). The increase
in total cholesterol in urban Indians contrasts with the falling
mean cholesterol level in the USA.2
Diabetes
The first systematic investigation of diabetes in India was
performed by the Indian Council of Medical Research Task
Force on diabetes in the 1970s.104 The population aged
.14 years was screened using a post 50 g glucose load, and
capillary blood glucose .4.40 mmol/l (.170 mg/dl) was taken
Heart 2008;94:16–26. doi:10.1136/hrt.2007.132951
Global burden of cardiovascular disease
to show the presence of diabetes. A total of 34 194 subjects were
screened and the prevalence of diabetes was 2.1% in urban
subjects and 1.5% in rural populations.
Recent studies in large cities in northern and southern India
report that the prevalence of diabetes among adults (>20 years)
ranges from 8% to 15%.105 106 From Chennai a significant
increase in the prevalence of type 2 diabetes among adults has
been reported (fig 4).107 When similar diagnostic criteria (known
diabetes and/or fasting and post-glucose load hyperglycaemia)
were used, the prevalence of age-adjusted diabetes among adults
in urban Chennai increased from 8.3% in 1988–9, to 11.6% in
1994–5, 13.5% in 2000 and 14.3% in 2003–4. An increase in the
prevalence of diabetes has also been reported from rural
Tamilnadu.108 Secular trends in the prevalence of diabetes show
that there is a slow increase in Indian rural subjects as compared
with the urban population.105
Although the prevalence of diabetes is low in rural popula-
tions (2–4%),105 there is evidence of a high burden of impaired
glucose tolerance.106 Studies from rural Tamilnadu in the early
1990s showed a low prevalence of diabetes and a high
prevalence of impaired glucose tolerance.108 Over time, while
the prevalence of diabetes increased that of impaired glucose
tolerance declined associated with increasing obesity. This
study shows that there is a significant pool of potentially
diabetic subjects in rural Indian populations and rapid lifestyle
changes can lead to diabetes. The high prevalence of diabetes
reported from rural Andhra Pradesh in a recent study109 seems to
confirm this observation.
Other factors
Many small studies from India have evaluated unconventional
cardiovascular risk factors, including lipid subfractions, platelet
functional abnormalities, inflammatory markers, homocysteine
and thrombotic factors. Larger studies are needed. Barker’s
hypothesis that focuses on the adverse long-term cardiovascular
impact of fetal undernutrition and low birth weight has been
proposed as a cardiovascular risk factor.110 Studies have reported
that neonates with a low birth weight have higher insulin levels
and insulin resistance than normal weight neonates.111 This
trend persists into early and mid-childhood.112 113 In the UK it
has been observed that South Asian children have a lower birth
weight and greater insulin resistance than Caucasians.114 The
long-term prognostic impact of this finding has been studied in
the New Delhi Birth Cohort Study, which showed that an
increase in birth weight early in life resulted in greater insulin
resistance and more diabetes in low birth weight children at
30 years of age.115 More studies are needed to evaluate the long-
term cardiovascular consequences of this finding.
Cardiovascular risk factor antecedents at childhood and
adolescence have been sparsely studied in India.116 In the
Indian cohort of Global Youth Tobacco Survey a variable
prevalence of tobacco consumption was reported in different
regions, with high use in eastern and central Indian states.117
From Delhi it has been reported that smoking among children is
rapidly increasing, although a study reported that within a
period of 2 years the habit declined.118 This was attributed to
better health awareness and tobacco control initiatives. In
affluent Indian children there seems to be an epidemic of
obesity while among children of low socioeconomic status low
body weight is widely prevalent.119 A high prevalence of high
blood pressure, high cholesterol levels and high glucose levels in
children has been reported from a few centres while many
centres report a low prevalence of these conditions.120 121 The
23
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Global burden of cardiovascular disease
role of genes and gene–environment interactions in the
pathogenesis of cardiovascular diseases also need to be studied.
APPROACHES TO PREVENTION
The increasing burden of coronary heart disease and stroke
emphasises the importance of containing the epidemic of
cardiovascular disease in India as well as combating its impact
and minimising its toll.122 The INTERHEART Study has
conclusively demonstrated that the usual cardiovascular risk
factors are important in Indians.73 Primordial, primary as well as
secondary prevention efforts should be directed towards these
factors. At a macrolevel, better social, economic and cultural
status correlates inversely with lifestyle factors of smoking,
abnormal food patterns and exercise and is recommended for
primordial prevention. Public broadcasting systems, television
and newspapers have an important role in the dissemination of
health-related information among populations. Suitable strate-
gies to impart information to these print and electronic media
should be developed locally. In Indians greater literacy levels and
awareness have led to a decrease in some cardiovascular risk
factors—for example, smoking, in the well educated.89 Public
awareness and demand has led to an increase in the number of
physical activity centres such as parks and walkways in many
urban locations. A new public health education campaign
focusing on lifestyle changes (increased physical activity,
prudent diet and tobacco cessation) has been launched in
Chennai and preliminary results are encouraging.123
The measures that have the greatest impact on population-
based prevention are policy initiatives. The initiatives that
might have an impact even in the short term include an increase
in tobacco taxes, economic and labelling disincentives for
unhealthy foods, removal of trans fats especially in processed
foods, reduction in salt in home-made and processed foods, and
urban design features which promote safe and pleasurable
physical activity. These are more likely to have a much greater
impact than limited community initiatives which will take a
long time to develop and are resource intensive. In India some of
these policy changes are already progressing and tobacco
legislation has been approved by parliament. Some other
national initiatives for prevention and control of cardiovascular
diseases are being planned.122
A high-risk intervention approach is also important. The
effectiveness of this depends directly on practising doctors and
healthcare workers. Doctors and other healthcare providers
serving the populations need to be educated as to the specific
cultural barriers and opportunities that would encourage
implementation of CHD prevention practices. The Indian
Council of Medical Research has developed a chronic diseases
risk factor surveillance programme for India.124 Pilot surveys
have been carried out in various locations in the country using
the WHO-Steps methodology, which outlines the sequential
measurement of behavioural, physical and biochemical risk
factors through its core, expanded and optional modules.125
Preliminary risk factor data in the 15–64-year age group indicate
a high rate of multiple cardiovascular risk factors, with a greater
prevalence of risk factors in respondents residing in urban areas
than in those residing in slum/peri-urban and rural areas.124
Successful adaptation and implementation of the WHO
stepwise approach for non-communicable disease risk factor
surveillance has paved the way for developing a module for risk
factor surveillance in the National Integrated Disease
Surveillance Programme (IDSP).124
A few primary prevention efforts have focused on individual
risk factors. The Indian Diabetes Prevention Programme (IDPP)
24
evaluated increased physical activity versus metformin for
prevention of diabetes in subjects with impaired glucose
tolerance.126 At a median follow-up of 30 months, lifestyle
modification reduced progression to diabetes by 28.5%, which
was same as with metformin (26.4%) and also with combined
metformin and lifestyle changes (28.2%). A yoga-based com-
prehensive lifestyle change has been evaluated in primary and
secondary prevention of CHD risks and preliminary results are
encouraging.127 For comprehensive cardiovascular primary pre-
vention, The Indian Polycap Study (TIPS) is evaluating the
usefulness of various drug combinations for reduction of
cardiovascular risks.128 Secondary prevention practices in
Indian are woefully inadequate both in acute care settings and
in long-tem medical care facilities.129 The influence of the
appropriate use of evidence-based treatments on outcomes in
patients with CHD or stroke is not known in India. The Heart
Outcomes Prevention Evaluation-3 (HOPE-3) Trial will evaluate
the effect of statins and/or angiotensin receptor blockers on
cardiovascular outcomes including a large sample from India.130
Some national initiatives for prevention and control of
cardiovascular diseases in India are being planned.122
In conclusion, cardiovascular diseases, especially CHD and
stroke, are major health problems in India. Risk factors for these
conditions in Indian subjects are similar to those in populations
elsewhere in the world and seem to be escalating. It is
imperative that primordial, primary and secondary prevention
efforts that have been shown to be effective in other regions of
the world131 are translated into active regional and national
initiatives in this country.
Competing interests: None declared.
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26 Heart 2008;94:16–26. doi:10.1136/hrt.2007.132951

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Epidemiology and causation of coronary

heart disease and stroke in India
R Gupta, P Joshi, V Mohan, et al.

Heart 2008 94: 16-26

doi: 10.1136/hrt.2007.132951

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