INTRODUCTION

Mortality data from Global Burden of Diseases Studies has revealed that cardiovascular diseases such as coronary heart disease are important causes of death in low and middle income countries.1 The World Health Organization (WHO) has summarized burden of chronic diseases in low and middle income countries and reports that shows ischemic heart disease and cerebrovascular diseases are major causes of death (Table 1).2 It was subsequently reported that of the 35 million deaths from chronic diseases in the year 2005 cardiovascular diseases caused 17.5 million deaths. Other major causes of deaths were cancer (7.6 million), chronic respiratory diseases (4.1 million), HIV/AIDS (2.8 million), tuberculosis (1.6 million), diabetes (1.1 million) and malaria (0.9 million). Of the chronic disease deaths, 20% were in high income countries, 8% in upper-middle income countries, 37% in lower-middle income countries and 35% in low income countries.2 Age-standardized cardiovascular diseases death rates (per 100,000) demonstrate low rates in developed countries such as Canada (120) and Britain (180)  and high rates in Brazil (320), China (280), India (405), Pakistan (400), Nigeria (410) and Russia (680)2 showing that In middle aged subjects (30-69 years) the death rates are inappropriately high in developing countries. This is a see change from the middle years of the last century when communicable diseases, under nutrition-related diseases and perinatal causes were major causes of mortality in these countries.3 This article summarizes the epidemiological transition occurring in the low income countries such as India which now has a fully developed epidemic of non-communicable diseases. As compared to previous years, there has been a reversal of socioeconomic differentials in prevalence of coronary risk factors and cardiovascular diseases, especially coronary heart disease, in this country and these can no longer be considered diseases of affluence.

CORONARY HEART DISEASE IN INDIA
In the absence of reliable mortality data in India, estimates of the burden of coronary heart disease have mostly been based on morbidity indicators from population based cross-sectional surveys.4 Morbidity surveys involve problems of sample design, sample size, standardization, and measurement errors but are useful to assess the disease burden.4 In the urban population the prevalence has increased from 1.05% (Agra, 1962)5 and 1.04% (Delhi, 1962)6 to 6.60% (Chandigarh, 1968)7. In recent years a consistent high prevalence of coronary heart disease has been reported from Delhi (9.67%, 1990)8, Jaipur (7.8%, 1995)9, Chennai (9.0%, 2001)10, Jaipur (8.1%, 2002)11, and Chandigarh (13.2%, 2004)12. In semi-urban populations of Haryana and Kerala the prevalence has increased from 3.6% (1975)13 to 7.4% (1993)14. In rural populations the prevalence increased from 2.06% (Haryana, 1974)15 and 1.69% (Vidarbha, 1988)16 to 2.71% (Haryana, 1989)17, 3.09% (Punjab, 1994)18, 3.46% (Rajasthan, 1997)19, and 5.00% (Himachal, 2002)20. Rural-urban comparison shows that while prevalence has increased two-fold in rural areas (2.06% in the 1970s to 4.14% in the 1990s) the prevalence in urban areas has increased nine-fold (1.04% in the early 1960s to 9.45% in the mid 1990s).4 There is evidence of increase in coronary heart disease as subjects migrate from rural to semi-urban to urban areas with the highest prevalence reported from metropolises.4
Analyses of prevalence studies in various decades in India provide significant information regarding the absolute number of coronary heart disease cases. Decadal variations indicate that the prevalence has increased in urban areas from about 2% in 1960 to 6.5% in 1970, 7.0% in 1980, 9.7% in 1990 and 10.5% in 2000 while in rural areas it increased from 2% in 1970 to 2.5% in 1980, 4% in 1990 and 4.5% in 2000. In urban populations, the calculated numbers have increased from 0.5 million in 1960 to 4.5 million in 1970, 5.6 million in 1980, 9.7 million in 1990 and 14.1 million in the year 2000. In rural populations the numbers have increased from 4.1 million in 1970 to 6.4 million in 1980, 11.8 million in 1990 and 15.7 million in 2000. Thus epidemiological studies show that there were 29.8 million coronary heart disease patients in the year 20004 that are projected to increase to 46.9 million in 2010 and 61.5 million in 2015 according to the Indian National Commission on Macroeconomics and Health.21 This number is similar to derived from Global Burden of Diseases Studies.3 As epidemiological studies exclude many patients with silent and asymptomatic disease the actual numbers may be much greater. Another major concern is occurrence of first event at younger age in Indians and presence of diffuse coronary artery disease at presentation.4 Appropriate preventive measures can substantially delay the onset of the disease.22

SOCIOECONOMIC STATUS AND CORONARY HEART DISEASE IN INDIA
            In Europe and North America, till middle of last century it was reported that cardiovascular diseases were more in persons of higher socioeconomic strata. In 1930’s when the coronary epidemic was on the rise in developed countries it was noted in Britain that the disease was more common in social classes I and II as compared to semi-skilled and unskilled classes IV and V.22 This changed in mid 1960’s in Britain and many West European and North American countries.23 The Whitehall Study in British civil servants initially reported that coronary heart disease mortality was more than twice in persons in lower civil service grades as compared to administrative groups.22 In India and other developing countries it is well known that the least privileged groups are more prone to suffer from acute and chronic infections and poverty is a major determinant of mortality.24 Major infectious causes of mortality among adults in developing countries include chest infections, tuberculosis and HIV/AIDS.3,25 All these are more prevalent among the lower socioeconomic status subjects. Non-communicable diseases such as ischemic heart disease, cerebrovascular diseases, chronic obstructive lung disease, cancer, and road traffic accidents are also major problems among adult populations.25 There is some evidence that these diseases are now equal or more common in the low socioeconomic status subjects in India.26
Mortality statistics:
Reliable cardiovascular mortality statistics based on socioeconomic stratifications are not available from India. Data from the Registrar General of India and National Family Health Surveys have provided some estimates of cardiovascular mortality.27 At a macro-level, evaluation of within-country variations in cardiovascular disease mortality reveals wide disparity and more affluent states such as Punjab, Tamilnadu and Andhra Pradesh having higher mortality rates as compared to the poorer central and eastern Indian states.27 There is a significant positive correlation of cardiovascular mortality with obesity, visible fat intake, and sugar/jaggery intake and negative correlation with fruit and vegetable consumption. On the other hand no correlation of various indices of poverty such as illiteracy, infant mortality rate and fertility rates with cardiovascular mortality is observed.27 In a recent study in rural Andhra Pradesh which prospectively evaluated causes of death in a population-cluster of more than 150,000 subjects it was reported that in both males and females cardiovascular diseases were the major causes of deaths.28 In this study there were 1354 deaths in the first year of follow-up and analysis using a validated verbal autopsy instrument revealed that

diseases of circulatory system caused 34% of male and 30% of female deaths.28 This study clearly shows that cardiovascular disease especially coronary heart disease are major cause of death even among the poor subjects in Indian rural locations. The ongoing prospective Million Deaths Study in India29 and the Prospective Urban Rural Epidemiology (PURE) Study30 would be able to provide more clear answers.

Epidemiological studies:
Epidemiological studies from India are few and mainly cross-sectional.4 There is very little information on influence of socioeconomic status on prevalence of coronary heart disease. Initial studies in urban populations reported that the disease was more among the upper social classes. Representative studies from Chandigarh (1968)7 and Delhi (1990)8 observed that the disease as diagnosed by known disease or presence of electrocardiographic changes was more in the upper socioeconomic status subjects as compared to the poor.             A study in western Indian rural area, where the problem of illiteracy is high, reported in mid 1990’s that the disease was more among the illiterate subjects as compared to the more literate.31 Age adjusted prevalence of coronary heart disease diagnosed using history and electrocardiographic Q, ST and T wave changes among men was reported as 4.7%, 2.3%, 2.4%, 3.6% in illiterate, and those with primary, secondary, and higher education respectively (Table 2). Among urban populations it is now being reported that the disease diagnosed according to the educational status is equally prevalent in all groups.32 Serial epidemiological studies in India among urban populations have reported that the disease is increasing more among the illiterate and low educational classes as compared to the highly literate and higher socioeconomic subjects.33 All these data portend a widely prevalent coronary heart disease epidemic among the low socioeconomic status subjects in India. However, more data needs to be accumulated to clearly define the burden of coronary heart disease among the urban poor and the rural subjects in India.

Table 2: Coronary Heart Disease Prevalence (%) and Literacy Levels in a Rural Indian Population31

Educational Status	Men (n=1982)				Women (n=1166)
	Numbers	Clinical and ECG changes	ST, T and Q	Q waves only	Numbers	Clinical and ECG changes	ST, T and Q	Q waves only
Illiterate	765	4.7	4.1	2.0	608	5.3	4.9	1.6
1-5 years	350	2.3	2.3	0.6	304	2.0	1.3	-
6-10 years	591	2.4	1.5	1.0	254	2.0	1.6	0.4
>10 years	276	3.6	2.5	1.1	-	-	-	-

Case-Control Studies:
Sanjivi in South India in early 1960’s reported from hospital case-series data that cases of acute myocardial infarction were more common from the low

socioeconomic status subjects as compared to the higher.34 He ascribed this finding to possible hospital-case selection bias although a possibility of risk factors other than dietary fat was considered. However, many subsequent hospital-based case-control studies from different regions of India continued to report that the disease was more among the affluent as compared to the poor classes.35

Recent case-control studies in India have revealed that persons with low socioeconomic status as identified by low educational status have greater incidence of acute myocardial infarction. Pais et al36 from Bangalore reported that low socioeconomic status as determined by low income was a risk factor for acute myocardial infarction (multivariate odds ratio 2.67, 95% confidence intervals, CI, 1.20-5.94) and higher socioeconomic status appeared to be protective (odds ratio 0.32 highest vs. lowest, and 0.75 middle vs. lowest, p<0.01). Similar results have been reported from a case-control study in Delhi where low literacy levels were observed to be an independent risk factor for acute myocardial infarction (odds ratio 2.1, CI 1.1-4.1, p<0.01).37 On the other hand a study among predominantly rural subjects reported that there was no significant correlation of socioeconomic status with incident infarction (odds ratio 1.55, CI 0.85-2.82).38 The INTERHEART study has reported correlation of socioeconomic status with incident acute myocardial infarction in South Asians. Joshi et al39 have reported that high socioeconomic status as determined by income as well as educational level was protective on univariate as well as multivariate analysis. As compared to highest vs. lowest income quartiles the odds were 0.86 (CI 0.73-1.01). Odds ratios for <8 years vs. 9-12 years vs. <8 years of education were 0.60 (CI 0.51-0.71) and for college education vs. <8 years were 0.73 (CI 0.61-0.87) (p<00.01). These studies show that the socioeconomic distribution of acute myocardial is changing in India and poor urban Indians and those with low literacy levels are more prone to acute coronary events.

SOCIOECONOMIC STATUS AND RISK FACTORS

The coronary heart disease epidemic is driven by demographic and socioeconomic changes that influence the living and working habits of populations. The changes in low-income countries are increasing life expectancy associated with a shift in eating habits and adoption of sedentary lifestyle. These changes result in population-wide escalation in major cardiovascular risk factors- obesity, hypertension, lipid concentrations, and dysglycemia. The levels of these risk factors have increased steeply in all the developing countries in the last two decades.25,26 Although there is some evidence of a gene-environment interaction it is now clear that major acquired cardiovascular risk factors are relevant in all ethnic groups and all populations worldwide.40 As the epidemic matures the coronary risk factors shift from affluent classes to low socioeconomic status subjects. In many of the middle-income countries in South America and Eastern Europe such a scenario already exists and the risk factors are more prevalent in poor classes. In India and some other low-income countries emerging evidence suggests that such a change is occurring rapidly.4,26 Major risk factors dependent on socioeconomic levels are physical activity, dietary intake, smoking and tobacco use, overweight and obesity, high blood pressure, diabetes, cholesterol levels, the metabolic syndrome and psychosocial stress. Socioeconomic differentials in major cardiovascular risk factors in India have not been well studied.

Physical activity:

Scientific data on physical activity among the population in developing countries is sparse. There is a lack of proper assessment tool that can capture long term work-related and discretionary physical activity in both men and particularly women.41 A substantial amount of energy expenditure is in work-related and household chores and most of the physical activity questionnaires fail to capture these activities.41 Contrary to the common belief that physical activity is common in developing countries it has been observed that at best the physical activity among the large rural population groups is intermittent and non-sustained.31 The only group where activity is performed on a continuous basis is the farm labour in rural areas and construction-site labour in urban settings. The low prevalence of obesity in rural areas of developing countries may be more due to calorie deprivation than to high levels of physical activity. Epidemiological studies in India show that leisure-time physical activity is much more among the higher socioeconomic classes in both urban and rural areas.33 However, work related physical activity contributes to major calories losses and these activities are much more in the lower socioeconomic classes. More studies are needed in this direction after development of culturally appropriate assessment tools such as in the ongoing PURE Study.30

Dietary Fat Intake:

Comparison of dietary patterns in rural and urban north Indian population reveals that the poorer rural subjects consume lower calories and have higher intakes of carbohydrates as compared to urban subjects.37,42 The major fat intake in rural populations is monounsaturated varieties and there is a lower consumption of fruits and vegetables.42 In urban subjects it has been reported that when stratified according to educational level, subjects with highest levels of education consumed more calories, saturated fats and green vegetables while with lowest level consumed more monounsaturated and hydrogenated fats.43 In a study at Jaipur urban subjects were classified according to household income and other ownership variables into five socioeconomic groups (Table 3). It was observed that the subjects in the most affluent class were consuming more calories as compared to the low socioeconomic status. However, the total as well as saturated fat consumption was not significantly different among various groups and consumption of cardiovascular friendly monounsaturated fats and omega-3 fats was higher among the upper classes as compared to poorer men and women. More studies in India are required to clarify the diet related issues and socioeconomic differentials.

Table 3: Socioeconomic Status and Dietary Fat Intake in an Indian Urban Population44   Upper Upper-middle Middle Lower-middle Lower Men (n=360) Calories (per day) 2268+216 2217+148 2184+144 1928+167 1879+53 Fat (g/day) 98+16 79+9 72+4 74+8 72+4 Fat energy % 38.7+3.9 32.4+2.6 29.7+2.3 34.9+4.6 34.5+1.8 SFA energy% 17.1+6.7 15.2+4.5 14.7+5.2 15.4+4.7 14.3+2.6 MUFA energy% 9.9+3.6 8.5+2.4 8.1+2.4 9.2+1.7 9.0+1.4 PUFA energy% 11.7+2.3 9.5+1.7 9.1+1.6 11.6+1.6 9.6+1.2 n-3 fat energy% 0.4+0.2 0.6+0.2 0.6+0.1 0.6+0.1 0.6+0.1 Women (n=402) Calories (per day) 1934+205 2012+366 1804+366 1734+168 1758+342 Fat (g/day) 71+4 70+11 72+5 75+9 68+14 Fat energy % 33.6+5.0 31.3+5.0 36.1+3.5 39.4+6.4 35.0+5.4 SFA energy% 16.5+3.3 14.5+7.8 16.2+1.1 17.9+5.0 15.6+8.4 MUFA energy% 9.8+2.7 8.8+4.3 9.3+2.0 9.0+1.8 9.6+6.0 PUFA energy% 9.0+1.7 8.7+2.2 10.1+1.3 13.4+1.6 11.0+3.4 n-3 fat energy% 0.6+1.1 0.6+0.2 0.6+0.1 0.7+0.1 0.5+0.3

Smoking and tobacco use:
A major risk factor for cardiovascular diseases especially coronary heart disease is smoking and tobacco use. It is well known in the developed countries that smoking is most prevalent among the least privileged groups.45 We observed an inverse association of educational status with tobacco use (smoking and other forms) in studies in western Indian state of Rajasthan.46 In successive cross-sectional epidemiological studies- the Jaipur Heart Watch (JHW)- in rural (JHW-R; n=3148, men=1982), and urban subjects: JHW-1 (n=2212, men=1415), JHW-2 (n=1123, men=550) and JHW-3 (n=456, men=226), we evaluated various cardiovascular risk factors. The greatest tobacco consumption was observed among the illiterate and low educational status subjects as compared to more literate in both men (JHW-R 60%, 51%, 46% and 36%; JHW-1 44%, 52%, 30%,19%; JHW-2 54%, 43%, 29% and 24%; and JHW-3 50%, 27%, 25%, 25%) as well as women (Figure 1, p for trend <0.05). In the illiterate subjects the odds ratios (OR) and 95% confidence intervals (CI) for smoking or tobacco use as compared to the highest educational groups in rural (men OR 2.68, CI 2.02, 3.57; women OR 3.13, CI 1.22, 8.08) as well as larger urban studies- JHW-1 (men OR 2.47, CI 1.70, 3.60; women OR 13.78, CI 3.35, 56.75) and JHW-2 (men OR 3.81; CI 1.90, 7.66; women OR 13.73, CI 1.84, 102.45) were significantly greater (p<0.01). Similar trends have been reported from other studies in India.47 These studies indicate that smoking and tobacco use which is a major cardiovascular risk factor in South Asians48 is highly prevalent among the low socioeconomic status subjects in India.

Figure 1: Educational status and prevalence of tobacco use (smoking and other forms) in various study cohorts. Tobacco use is the highest among the rural subjects as well as the illiterate subjects and decline with increasing levels of education. There is a significant inverse correlation of educational level with tobacco use in both men and women in the rural cohort as well as urban Jaipur cohorts in the first Jaipur Heart Watch (JHW-1), second (JHW-2) and the third (JHW-3) studies (p for trend <0.05).42 Light bars indicate men and dark bars women.

Obesity:             Dietary inadequacy has been a major issue in all the developing country populations, more in the poor class. However, with the currently expanding habit of consumerism in these countries there has been a large-scale change in eating habits especially in the urban populations.49 Traditional high-fibre low-fat diet in these populations has been replaced with calorie-dense high-fat food stuffs (Table 3). In countries that went through the epidemiological transition earlier such as Russia and Brazil the problem of overweight and obesity is a problem of the low socioeconomic status50 while in countries currently undergoing this transition such as India the obesity problem is seen in the upper socioeconomic strata subjects.33 The second National Family Health Survey in India has reported a low prevalence of obesity in Indian rural and urban women and has not reported on socioeconomic differences.51 The Jaipur Heart Watch studies, on the other hand, report significantly escalating trends in both obesity and truncal obesity in low socioeconomic status urban subjects.33 In certain urban areas of India overweight is present in significant numbers among the urban poor.52 Causes of this problem include easy availability and low cost of calorie-dense foods and rapidly spreading sedentary lifestyles among children. It has been argued that obesity epidemic is similar to the tobacco epidemic and both are driven by industry interests, especially in countries in the middle income category.53

Table 4: Educational Status and Changing Total Cholesterol Levels (mg/dl, mean+SD) in Urban Subjects in India33

Educational Group	Men			Women
	JHW-1 (n=199)	JHW-2 (n=532)	Absolute Change	JHW-1 (n=98)	JHW-2 (n=550)	Absolute Change
Illiterate	166.4+35	205.7+39	39.3 (27.5 to 51.1)*	176.1+55	209.8+46	33.7 (20.1 to 47.3)*
1-10 years	164.9+38	195.8+46	30.9 (15.7 to 46.1)*	168.3+37	185.7+52	17.4 (-1.1 to 35.9)
11-15 years	173.4+44	187.8+40	14.4 (1.5 to 27.4)*	155.0+0	177.9+51	22.9
>16 years	178.6+45	193.8+44	15.2 (-2.5 to 32.9)	-	177.6+61	-
JHW Jaipur Heart Watch; JHW-1 conducted in years 1993-1995; JHW-2 in 1999-2001. * significant

High blood pressure:

            Hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases. The prevalence of hypertension has been exponentially increasing in India and many developing countries whereas the rates of awareness, treatment and control remain dismally low.54, A review of hypertension epidemiology in India reported a high prevalence of hyper­tension in both urban and rural areas.55 Hypertension defined by recent WHO crite­ria (>140/>90) is prevalent in 30-40% adults in larger Indian cities and 10-20% in rural populations. These findings are consistent with other regions of Asia and elsewhere where it has been reported that at a given time about half of all individuals have high blood pressure.        Studies that evaluate effect of socioeconomic status on hypertension are very sparse in developing countries. In an Indian rural population with very high illiteracy, it was reported that hypertension was more common in the illiterate as compared to the most educated.31 Reddy et al56 reported that in an urban Indian population prevalence of hypertension was similar among all the socioeconomic groups defined by educational classes (Figure 2). Similar observations from urban subjects have been reported from Jaipur33 and Delhi52.

Figure 2: Educational class and prevalence of risk factors in urban Indian population. While there is a clear gradient in prevalence of smoking (p<0.001), prevalence of other risk factors are not different in subjects among various educational classes. Class IV= illiterate; Class III less than high school; Class II high school; and Class I graduate or more education (Adapted from Reddy et al56).

Awareness status of hypertension in India is poor. In middle and low socioeconomic urban subjects in Mumbai there was a very low awareness of hypertension and only 6% males and 10% females were aware of the high blood pressure.57 In Jaipur it has been reported that only 11% of male and 16% of female hypertensives were aware of their condition.58 Higher awareness of hypertension has been reported from more educated populations in Kerala59  and Parsi subjects in Mumbai.60 In community dwelling elderly individuals in Kerala hypertension was present in 52% subjects and 45% of these individuals were aware of their condition.59

Among highly literate Parsis in Mumbai it was reported that 53% of men and 44% of women were unaware of their hypertensive status although 90% had had their blood pressure measured in the past.60 This level of awareness is similar to reported from many developed countries and shows that within India there is a wide variation in hypertension awareness status depending on the socioeconomic status of the population. Clearly more affluent are more aware of the blood pressure problem and control it better. This leads to lower deaths due to hypertension generated diseases as reported from USA where it has been observed that despite a high hypertension prevalence the mortality due to hypertension is lower that many European countries due to higher treatment and control rates.61

Diabetes:

            Type-2 diabetes mellitus is a new epidemic in developing world62 and is a result of societal influences and changing lifestyles. Epidemiological studies in India reveal that this condition has increased remarkably in urban populations and presently even the underprivileged are not exempt.63 Epidemiological studies in late 1980’s and later reported prevalence rates that vary from 5-15% among urban populations, 4-6% in semi-urban populations and 2-5% in rural populations. There is a significantly increasing trend in urban populations while among rural populations the prevalence is increasing at a slower rate. The diabetes scenario is similar to other South Asian countries and evolving populations in East Asia, Middle-East, the Americas, Australasia and Pacific Islands and gene-environment interactions appear to be responsible for this rapid increase among these newly acculturated populations.64  Socioeconomic differential in prevalence of diabetes in developing countries has not been well studied. Low prevalence of diabetes has been reported from tribal and rural populations of India63 but a recent study in rural Andhra Pradesh reported a high diabetes prevalence in adults >30 years at 13.2% of which 48% were known diabetics and 52% were previously undiagnosed.65 It has also been reported that diabetes complications are much more among the illiterate and low socioeconomic status subjects.66

Cholesterol levels:

            In developed countries there has been a significant decline in population cholesterol levels.  In the US the mean cholesterol levels declined from 220+1.5 mg/dl in years 1960-62 to 203+1.2 mg/dl in 1999-2002.67 On the other hand the population cholesterol levels are escalating in developing countries and in Indian urban populations mean cholesterol increased from 160 mg/dl in 1981 to 191 mg/dl in

1995.68 There are substantial area based differences in cholesterol levels in India and mean cholesterol levels are lower in rural populations as compared to the urban. Within the urban populations cholesterol levels are higher in areas with middle socioeconomic status families as compared to low socioeconomic status individuals.33,56 Serial epidemiological studies from western India reported that prevalence of dyslipidemias is increasing more among the low socioeconomic subjects as compared to the upper classes.33 In successive studies among urban populations the mean cholesterol levels in men increased from 175.8+43 mg/dl in 1995 to 194.4+43 mg/dl in 2002. While the total cholesterol levels among the most literate men increased by 15.2 mg/dl, among the illiterate subjects the levels increased by 39.3 mg/dl (Table 5). Role of dietary and lifestyle factors in escalation of cholesterol and atherogenic dyslipidemia among developing countries need further studies.

The metabolic syndrome:

            Presence of the metabolic syndrome indicates a conglomeration of cardiovascular risk factors and is a useful marker of future coronary heart disease risk. Only a few studies are available of population prevalence of metabolic syndrome in India and report a medium to high prevalence. In Indian urban populations in north and south India prevalence varies from 20-30% in men and 25-35% in women.69,70 In Brazil and Russia the metabolic syndrome is present in greater numbers among the low socioeconomic status subjects.71 A study from urban industrial population has reported that individual components (abdominal obesity, hypertension, diabetes, dyslipidemia), as well as the syndrome are equally prevalent among the rich and the poor (Figure 2).56

Psychosocial stress:

            One of the more important but neglected risk factor in pathogenesis of coronary heart disease is psychosocial stress.72 Migration from the rural to an urban residence is not only associated with change in physical parameters such as increasing sedentariness, obesity, truncal obesity, hypertension, dyslipidemias and the metabolic syndrome but also involves a large burden of social and psychological stress.73 Chronic stress such as that of living in urban environment, work-related stress and chronic deprivation can lead to both unhealthy behaviors (e.g., smoking, high fat intake) as well as biological changes that include homeostatic and allostatic changes, neuroendocrine changes and alteration in autonomic functions, development of the metabolic syndrome and insulin resistance, disturbances of coagulation, and heightened inflammatory and immune responses.72 All these factors are important in pathogenesis of coronary atherosclerosis and it is not surprising that stress among the low social classes associated with a poor coping mechanisms are leading to the epidemic among the deprived individuals in the developing world.74

Other risk factors:
            Maternal malnutrition associated with fetal stunting leads to long-term pathophysiological changes in endocrine and biochemical milieu.75 These changes are postulated as important mechanisms for adult onset diabetes and cardiovascular diseases. If true, this theory forecasts a massive burden of cardiovascular diseases in India and other developing countries as these nations join the economic prosperity bandwagon.76 Prospective studies within developing countries are required to test this hypothesis.
CASE-FATALITY AND SECONDARY PREVENTION
            An important issue in coronary heart disease in developing countries is a high case-fatality rate following an acute myocardial infarction. The MONICA study has reported variable case-fatalities in different countries in Europe.77 Combined out-of-hospital and in-hospital case fatality rates at 28 days were high in the overall cohort and varied from 35-50% in men and 25-60% in women. Low case fatality was reported from cohorts in more affluent countries such as Switzerland, Austria, Sweden and Canada and very high rates in some cohorts in middle income countries such as Poland, Russia and Yugoslavia.
            The CREATE Registry of acute coronary syndromes in India78 reported mortality in acute coronary syndromes according to socioeconomic status. In this study of 20937 patients with acute coronary syndromes, it was observed that 30-day unadjusted mortality in rich, upper middle class, lower middle class and poor subjects classified using multiple socioeconomic variables was 5.5%, 5.9%, 6.5% and 8.2% respectively (p<0.0001). The gradient remained after adjustment for multiple risk factors (p=0.0093) as well as location of infarct (0.04). The differences disappeared when adjusted for acute treatments including use of anti-thrombotic agents, anti-platelet drugs, ACE inhibitors, beta-blockers and lipid lowering therapies suggesting that use of evidence based therapies is lower than optimum among low socioeconomic subjects in India.
The WHO-PREMISE study79 reported use of standard secondary prevention treatments in ten countries in Asia, Europe, South America and Africa. Use of expensive secondary preventive therapies such as ACE inhibitors and statins was lower in illiterate and poor subjects. Clearly, the poor are disadvantaged in terms of appropriate treatment for acute myocardial infarction as well as secondary prevention therapies after an acute event. Whether these differences translate into long term cardiovascular mortality remain to be studied.
EPIDEMIOLOGICAL TRANSITION: OMRAN, GILLUM, YUSUF, AND OLSHANSKY

            Various non-communicable diseases such as joint diseases, diabetes, cancer, cardiovascular diseases and coronary heart disease were traditionally known as diseases of the affluent. Omran described a state of epidemiological transition wherein he examined the trends in evolution of communicable diseases in populations and hypothesized that the non-communicable disease epidemic also follows a similar trend.80 He postulated that the disease epidemic changes as populations age and move from poverty to affluence. In the initial phases characterized by poverty the diseases are related mainly to undernutrition and infection and death occurs at younger ages. With socioeconomic progress the diseases patterns change and infections are replaced with degenerative diseases (Figure 3a). Gillum in early 1990’s modified this schema after study

of hypertension and stroke among the blacks in USA.81 He postulated that in a population initial lifestyle changes associated with affluence led to increase in salt and fat intake leading to epidemic of hypertension, hypercholesterolemia and later to cardiovascular diseases. More socioeconomic evolution leads to positive changes in lifestyle with control of smoking, high blood pressure and cholesterol levels. This is associated with decline in cardiovascular diseases (Figure 3b). Yusuf et al added another dimension to this graph wherein the impact of socioeconomic disturbances was included.82 This hypothesis explained the increased cardiovascular mortality after the breakdown of communism in Eastern Europe and Russia (Figure 3c). The present phase in developed countries is characterized by massive increases in obesity and the metabolic syndrome that is poised to lead to a second wave of cardiovascular diseases epidemic83 in such countries (Figure 3d). Recent studies have shown that despite increasing obesity, the metabolic syndrome and diabetes in developed countries the cardiovascular mortality has continued to decline showing importance of risk factor control.84

Figure 3: Stages of epidemiological transition. The initial model of Omran80 considered the epidemic of chronic degenerative diseases as a linear model with constant increase as population gets morer affluent and evolves from the stage of infections and under-nutrition. Subsequent modifications to this model show that the chronic diseases can be controlled and decreased by changes in lifestyle (Gillum)81. On the other hand socioeconomic upheavals, e.g., in Russia in early 1990’s, can reverse the gains causing a rebound in chronic diseases (Yusuf)82 . The second wave hypothesis83 is based on the resurgence of the cardiovascular diseases associated with the current epidemic of obesity and metabolic syndrome.

The changes of epidemiological evolution are predominantly driven by socioeconomic progress. In India a whole spectrum of socioeconomic situations exists in different locations. Among the poor tribal and rural subjects, which form 35-40% of the India’s billion plus population, the scenario is of Omran’s80,82 initial two stages I and II of epidemiological transition and cardiovascular diseases as well as infections are predominant causes of disability and death. Even 30% of deaths due to cardiovascular diseases in this group as reported from Andhra Pradesh, 28 would translate into huge numbers. With socioeconomic progress the middle class urban and rural Indians have reached the stage III of transition and there is an epidemic of coronary heart disease in this population. This group comprises of ~30% of the Indian population and is facing the full impact of premature coronary heart disease. More data are needed and ongoing prospective studies should provide more definitive answers regarding socioeconomic differences in mortality in the rural29 as well as urban30 socioeconomic subgroups in India.  
THE WAY AHEAD
            The incidence of cardiovascular diseases in any population is associated with positive shifts (rightward skew) in distribution of its biological characteristics -serum lipids, blood pressure, blood glucose, insulin, thrombogenic factors, and others.22 Population wide negative shifts are possible by suitable interventions. The low and middle income countries where more than two-thirds of the world population live have much to gain from prevention efforts. Ezzati et al estimated global and regional potential health gains from reducing multiple risk factors.85 An estimated 47% of premature deaths and 39% of total disease burden in the year 2000 was due to joint effects of twenty selected leading risk factors. These risk factors caused 83-89% of ischemic heart disease and 70-76% of strokes and removal of these risk factors was postulated to increase global healthy life expectancy by a mean of 9.3 years (17%) ranging from 4.4 years (6%) in developed countries to 16.1 years (43%) in parts of Sub-Saharan Africa. Control of risk factors is therefore crucial to prevent the early onset of the disease in India.
Primary prevention:
The epidemic of coronary heart disease in India warrants an urgent action in terms of expanding public education, control of primordial and primary risk factors by population-based and high-risk interventions and other effective preventive strategies.25 Influence of societal affluence levels on cardiovascular diseases suggest that global solution that shall have the greatest impact on slowing or stopping this epidemic is not with the individuals but with the policy-makers and governments. Although the current Millennium Development Goals are not focused on chronic diseases,86 goals that deal with improving socioeconomic structures of the population, increasing education and improving maternal nutrition are important pathways to chronic disease prevention in poor countries.
There is a need to change the economic and environmental structure of rapidly westernizing societies in urban areas of India so that physical activity and healthy dietary choices are available. Population wide shifts-to-right in physical inactivity level, calorie intake, body-mass index, waist-size and waist-hip ratio should be arrested. Lifestyle management is crucial for adiposity control that is the major precursor of cardiovascular diseases. It is suggested that a comprehensive approach consisting of weight reduction, regular physical exercise and smoking cessation is widely adopted.87

Risk Factor and Disease Surveillance:

                Cardiovascular mortality and risk factor surveillance in India is very primitive and no organized system exists in rural as well as urban populations. Screening could act as a tool to increasing awareness by identification of cardiovascular risk factors such as tobacco use, obesity, central obesity, high blood pressure, blood glucose and cholesterol levels.88 It also creates awareness and is a form of subtle intervention. It has been discussed that there are benefits and harms of screening and value based principles are important in implementation of screening processes. We and others believe that given the massive prevalence of cardiovascular risk factors in India it is mandatory for the government and non-government agencies to perform large scale screening and take appropriate action for control of these factors.88,89

Secondary prevention:

            Improved surveillance mechanisms mandate an appropriate therapeutic strategy that should be available at the grass roots level. Apart from focus on lifestyle measures such as smoking and tobacco control, dietary intervention and enhanced physical activity, there is an urgent need for low-cost blood pressure, lipid and glycemia control strategies. An important issue is to transfer the available knowledge regarding appropriate evidence-based therapies to the basic healthcare professional.90 It is very common to observe inappropriate prescribing of useless multivitamins and antioxidants to patients with established coronary heart disease in lieu of lifesaving statins, aspirin, ACE inhibitors or beta-blockers.91 Continuing medical education programs coupled with incentive driven healthcare is needed. Some components of the British National Health Service could be useful to emulate.88,92

            In conclusion, coronary heart disease epidemic has taken wide roots in India. The disease is highly prevalent in urban and rural Indian populations and is increasing rapidly among the low socioeconomic subjects. This is driven by escalating major cardiovascular risk factors among these groups. Smoking which is responsible for ~40% coronary risk40 is highly prevalent among the rural as well as urban poor while other risk factors such as hypertension, hypercholesterolemia, diabetes and metabolic syndrome are equally prevalent among all socioeconomic classes in urban locations and are increasing rapidly among the lower socioeconomic groups. The overall cardiovascular risk as determined by Framingham risk score is more among the low socioeconomic subjects.93 The answer to coronary epidemic in the low socioeconomic status subjects in India is of population and patient empowerment and availability of healthy choices. While communicable disease epidemic are failure of the healthcare system the non-communicable diseases epidemic currently sweeping India is a failure of individuals due to lack of information and proper choices. 94 Population based prevention policies coupled with high-risk population based and individual based strategies are urgently needed to stem the inexorable drive of the cardiovascular disease epidemic especially among the poor in India.

REFERENCES

1. Leeder S, Raymond S, Greenberg H, Liu H, Esson K. A race against time: the challenge of cardiovascular disease in developing economies. New York. Columbia University. 2004.
2. World Health Organization. Preventing chronic diseases: a vital investment. Geneva. World Health Organization 2005.
3. Murray CJL, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global burden of disease study. Lancet 1997; 349:1498-1504.
4. Gupta R, Joshi P, Mohan V, Reddy KS, Yusuf S. Epidemiology and causation of coronary heart disease and stroke in India. Heart 2008; 94:16-26.
5. Mathur KS. Environmental factors in coronary heart disease. An epidemiological survey at Agra (India). Circulation 1960; 21:684-689.
6. Padmavati S. Epidemiology of cardiovascular disease in India. II. Ischemic heart disease. Circulation 1962; 25:711-717.
7. Sarvotham SG, Berry JN. Prevalence of coronary heart disease in an urban population in northern India. Circulation 1968; 37:939-952.
8. Chadha SL, Radhakrishnan S, Ramachandran K, Kaul U, Gopinath N. Epidemiological study of coronary heart disease in an urban population of Delhi. Indian J Med Res 1990; 92:424-430.
9. Gupta R, Prakash H, Majumdar S, Sharma SC, Gupta VP. Prevalence of coronary heart disease and coronary risk factors in an urban population of Rajasthan. Indian Heart J 1995; 47:331-338.
10. Mohan V, Deepa R, Rani SS, Premalatha G. Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India. J Am Coll Cardiol. 2001; 38:682-687.
11. Gupta R, Gupta VP, Sarna M, Bhatnagar S, Thanvi J, Sharma V, et al. Prevalence of coronary heart disease and risk factors in an urban Indian population: Jaipur Heart Watch-2. Indian Heart J. 2002: 54:59-66.
12. Kumar R, Singh MC, Ahlawat SK, Thakur JS, Srivastava A, Sharma MK, et al. Urbanization and coronary heart disease: a study of urban-rural differences in northern India. Indian Heart J 2006; 58:126-130.
13. Gupta SP, Malhotra KC. Urban-rural trends in epidemiology of coronary heart disease. J Assoc Phys India 1975; 23:885-892.
14. Kutty VR, Balakrishnan KG, Jayasree AK, Thomas J. Prevalence of coronary heart disease in the rural population of Thiruvananthapuram district, Kerala, India. Int J Cardiol 1993; 39:59-70.
15. Dewan BD, Malhotra KC, Gupta SP. Epidemiological study of coronary heart disease in rural commuity of Haryana. Indian Heart J 1974; 26:68-78.
16. Jajoo UN, Kalantri SP, Gupta OP, Jain AP, Gupta K. The prevalence of coronary heart disease in the rural population from central India. J Assoc Phys Ind 1988; 36:689-693.
17. Chadha SL, Gopinath N, Radhakrishnan S, Ramachandran K, Kaul U, Tandon R. Prevalence of coronary heart disease and its risk factors in a rural community in Haryana. Indian J Comm Med 1989; 14:141-147.
18. Wander GS, Khurana SB, Gulati R, Sachar RK, Gupta RK, Khurana S, et al. Epidemiology of coronary heart disease in a rural Punjab population: prevalence and correlation with various risk factors. Indian Heart J 1994; 46:319-323.
19. Gupta R, Prakash H, Gupta VP, Gupta KD. Prevalence and determinants of coronary heart disease in a rural population of India. J Clin Epidemiol. 1997; 50:203-209.
20. Gupta AK, Bharadwaj A, Ashotra S, Gupta BP. Feasibility and training of multipurpose workers in detection, prevention and control of coronary artery disease in apple-belt of Shimla hills. South Asian J Prev Cardiol 2002; 6:17-22.

21. Indrayan A. Forecasting vascular disease cases and associated mortality in India. In: Burden of Disease in India: Background Papers. New Delhi. National Commission on Macroeconomics and Health. 2005. 197-215.
22. Marmot M, Eliott P. Coronary heart disease epidemiology: from aetiology to public health. In: Marmot M, Elliott P. Eds. Coronary heart disease epidemiology: from etiology to public health. 2nd Ed. Oxford. Oxford University Press. 2005; 3-7.
23. Marmot M, Bartley M. Social class and coronary heart disease. In: Marmot M. Editor. Stress and the Heart. London. BMJ Publishing. 2002; 5-19.
24. Leon DA, Walt G. Poverty inequality and health: an international perspective. Oxford. Oxford University Press. 2001.
25. Reddy KS. Cardiovascular diseases in non-western countries. N Engl J Med 2004; 350:2438-2440.
26. Gaziano TA. Cardiovascular disease in the developing world and its cost-effective management. Circulation 2005; 112:3547-3553.
27. Gupta R, Misra A, Pais P, Rastogi P, Gupta VP. Correlation of regional cardiovascular mortality in India with lifestyle and nutritional factors. Int J Cardiol 2006; 108:291-300.
28. Joshi R, Cardona M, Iyengar S, Sukumar A, Raju CR, Raju KR, et al. Chronic diseases are now a leading cause of death in rural India: mortality data from the Andhra Pradesh Rural Health Initiative. Int J Epidemiol . 2006; 35:1522-1529.
29. Jha P, Gajalakshmi V, Gupta PC, Kumar R, Mony P, Dhingra N, et al, for RGI-CGHR Prospective Study Collaborators. Prospective study of one million deaths in India: rationale, design, and validation results. PLoS Med 2006;3:e18.
30. Yusuf S. Societal and biological determinants of obesity, diabetes and cardiovascular disease: Research proposal. At: www.ccc.mcmaster.ca/lifeheart/downloads/Research_Proposal.pdf. Accessed. 15 September 2006.
31. Gupta R, Gupta VP, Ahluwalia NS. Educational status, coronary heart disease and coronary risk factor prevalence in a rural population of India. BMJ 1994; 309:1332-1336.
32. Gupta R, Gupta VP. Meta-analysis of coronary heart disease prevalence in India. Indian Heart J. 1996; 48:241-245.
33. Gupta R, Gupta VP, Sarna M, Prakash H, Rastogi S, Gupta KD. Serial epidemiological surveys in an urban Indian population demonstrate increasing coronary risk factor among the lower socioeconomic strata. J Assoc Physicians Ind. 2003; 55:470-477
34. Sanjivi KS, Gopalakrishnan S. Coronary artery disease in the low income groups. J Assoc Physicians Ind 1961; 9:407-413.
35. Sapru RP. An overview of cardiovascular diseases in India. In: Wasir HS. Editor. Preventive Cardiology: an introduction. New Delhi. Vikas Publishing House. 1991. 69-86.
36. Pais P, Pogue J, Gerstein H, Zachariah E, Savitha D, Jayaprakash S, et al. Risk factors for acute myocardial infarction in Indians: a case-control study. Lancet 1996; 348:358-363.
37. Rastogi T, Reddy KS, Vaz M, Spiegalman D, Prabhakaran D, Willet WC, et al. Diet and risk of ischemic heart disease in India. Am J Clin Nutr 2004;79:582-592.
38. Patil SS, Joshi R, Gupta G, Reddy MVR, Pai M, Kalantri SP. Risk factors for acute myocardial infarction in a rural population of Central India: hospital based case-control study. Nat Med J Ind 2004; 17:189-194.

39. Joshi PP, Islam S, Pais P, Reddy KS, Prabhakaran D, Kazmi K, et al. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. JAMA 2007; 297:286-294
40. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al, and the INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (The INTERHEART Study): Case control study. Lancet 2004; 364:937-952.
41. Bharathi AV, Sandhya N, Vaz M. The development and characteristics of a physical activity questionnaire for epidemiological studies in urban middle class Indians. Indian J Med Res 2000; 111:95-102..
42. Chadha SL, Gopinath N, Katyal I, Shekhawat S. Dietary profile of adults in an urban and a rural community. Indian J Med Res 1995;101:258-267.
43. Singhal S, Gupta P, Mathur B, Banda S, Dandia R, Gupta R. Educational status and dietary fat and anti-oxidant intake in urban subjects. J Assoc Physicians India. 1998; 46:684-688.
44. Rastogi S. Prevalence of nutritional atherosclerosis risk factors in an urban Indian population. PhD Thesis. University of Rajasthan. 2006.
45. Gajalakshmi CK, Jha P, Ranson K, Nguyen S. Global patterns of smoking and smoking attributable mortality. In: Jha P, Chaloupka F. Editors. Tobacco control in developing countries. Oxford. Oxford University Press. 2000; 11-39.
46. Gupta R. Smoking, educational status, and health inequity in India. Indian J Med Res. 2006; 124:15-22.
47. Subramanian SV, Nandy S, Kelly M, Gordon D, Davey-Smith G. Patterns and distribution of tobacco consumption in India: cross sectional multilevel evidence form the 1998-9 national family health survey. BMJ 2004; 328:801-806.
48. Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet 2006; 368:647-658.
49. Monteiro CA, Moura EC, Conde WL, Popkin BM. Socioeconomic status and obesity in adult populations of developing countries: a review. Bull WHO 2004; 82:940-946.
50. Ezzati M, Hoorn SV, Laws CMM, Leach R, James WPT, Lopez AD, et al. Rethinking the diseases of affluence paradigm: global patterns of nutritional risks in relation to economic development. PLoS Medicine 2005; 2:e133.
51. Mishra V. Effect of obesity on asthma among adult Indin women. Int J Obesity 2004; 28:1048-1058.
52. Misra A, Pandey RM, Devi JR, Sharma R, Vikram NK, Khanna N. High prevalence of diabetes, obesity and dyslipidaemia in urban slum population in northern India. Int J Obes 2001; 25:1722-1729.
53. Chopra M, Darnton-Hill I. Tobacco and obesity epidemics: not so different after all? BMJ 2004; 3328:1558-1560.
54. Kearney P, Whelton M, Reynoldds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365:217-223.
55. Gupta R. Trends in hypertension epidemiology in India. J Hum Hypertens 2004; 18:73-78.
56. Reddy KS, Prabhakaran D, Jeemon P, Thankappan KR, Joshi P, Chaturvedi V, et al. Educational status and cardiovascular disease profile in Indians. Proc Natl Acad Sci USA. 2007; 104:16263-16268.
57. Gupta PC, Gupta R, Pendnekar MS. Hypertension prevalence and blood pressure trends in 88653 subjects in Mumbai, India. J Hum Hypertens 2004; 853-856.
58. Gupta R, Guptha S, Gupta VP, Prakash H. Prevalence and determinants of hypertension in the urban population of Jaipur in Western India. J Hypertens 1995; 13:1193-1200.
59. Joseph A, Kutty VR, Soman CR. High risk for coronary heart disease in Thiruvanthapuram City: a study of serum lipids and other risk factors. Indian Heart J 2000; 52:29-35.
60. Bharucha NE, Kuruvilla T. Hypertension in the Parsi community of Bombay: a study on prevalence, awareness and compliance to treatment. BMC Pub Health 2003; 3:e1
61. Kaplan NM, Opie LH. Controversies in hypertension. Lancet 2006; 367:168-176.
62. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes, estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27:1047-1053.
63. Gupta R, Misra A. Type 2 diabetes in India: regional disparities. Br J Diab Vasc Dis 2007; 7:16-19.
64. Diamond J. The double puzzle of diabetes. Nature 2003; 423:599-602.
65. Chow CK, Raju PK, Raju R, Reddy KS, Cardona M, Celermajer DS, et al. The prevalence and management of diabetes in rural India. Diabetes Care 2006; 29:1717-1718.
66. Ramachandran A, Snehalatha C, Viswanathan V. Burden of type 2 diabetes and its complications: the Indian scenario. Curr Science 2002; 83:1471-1476.

67. Carroll MD, Lacher DA, Sorlie PD, Cleman JI, Gordon DJ, Wolz M, Grundy SM, Johnson CL. Trends in serum lipids and lipoproteins of adults, 1960-2002. JAMA 2005; 294:1773-1781.
68. Gupta R. Dyslipidaemia and coronary artery disease in the Indian context. In: Dutta AL. Editor. Cardiology Update-2001. Hyderabad. Cardiological Society of India. 2001; 127-139.
69. Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Metabolic syndrome in urban Asian Indians adults: a population study using modiied ATP III criteria. Diab Res Clin Pract 2003; 60:199-204.
70. Gupta R, Deedwania PC, Gupta A, Rastogi S, Panwar RB, Kothari K. Prevalence of metabolic syndrome in an urban Indian population. Int J Cardiol 2004; 97:257-261.
71. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365:1415-1428.
72. Brunner E. Stress mechanisms in coronary heart disease. In: Marmot M. Editor. Stress and the heart. London. BMJ Publishing. 2002; 181-199.
73. Gupta R, Gupta VP. Lessons for prevention from a coronary heart disease epidemiology study in western India. Curr Science 1998; 74:1074-1077.
74. Braveman P, Tarimo E. Social inequalities in health within countries: not only an issue for affluent nations. Soc Sci Med 2002; 54:1621-1635.
75. Barker DJP. Mothers, babies and health in later life. 2nd Ed. Edinburgh. Churchill Livingstone. 1998.
76. Anonymous. Climbing back. The Economist. Jan 21 2006; 69-70.
77. Tunstall-Pedoe for the WHO-MONICA Project. World’s largest study of heart disease, stroke, risk factors, and population trends 1979-2002: Monica Monograph and Multimedia Sourcebook. Geneva. World Health Organization. 2003.
78. Xavier D, Pais P, Devereaux PJ, Xie C, Prabhakaran D, Reddy KS, et al. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet 2008; 371:1435-1442.
79. Mendis S, Abegubde D, Yusuf S, Ebrahim S, Shaper G, Ghannem H, et al. WHO study on prevention of recurrences of myocardial infarction and stroke (WHO-PREMISE). Bull WHO 2005; 83:820-828.
80. Omran AR. The epidemiological transition: a theory of the epidemiology of population change. Milbank Mem Q 1971; 49:509-538.
81. Gillum R. The epidemiology of cardiovascular disease in black Americans. N Engl J Med 1996; 335:1597-1599.
82. Yusuf S, Reddy KS, Ounpuu S, Anand S. Global burden of cardiovascular diseases. Part I: general considerations, the epidemiological transition, risk factors and impact of urbanization. Circulation 2001; 104:2746-2753.
83. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, et al. A potential decline in life expectancy in the Unites States in the 21st century. N Engl J Med 2005; 352:1138-1145.
84. Capewell S, O’Flaherty P. What explains declining coronary mortality? Heart 2008; 94:1105-1108.
85. Ezzati M, Hoorn SV, Rodgers A, Lopez AD, Mathers CD, Murray CJL. Estimates of global and regional potential health gains from reducing multiple risk factors. Lancet 2003; 362:271-280.
86. Fuster V. Cardiovascular disease and the UN millennium development goals: a serious concern. Nat Clin Pract Cardiovasc Med. 2006; 3:401.
87. Deedwania PC, Gupta R. East Asians and South Asians, and Asian and Pacific Islander Americans. In: Wong ND, Black HR, Gardin JM. Editors. Preventive Cardiology. 2nd Edition. New York. McGraw Hill. 2005; 456-472.
88. Shah B, Gupta R, Mathur P, Saxena M, Agrawal RP, Bhardwaj A, et al. An action plan for noncommunicable disease prevention, surveillance, management and control in economically deprived Indian states: Lessons from Rajasthan. South Asian J Prev Cardiol 2006; 10:5-45.
89. Reddy KS, Shah B, Varghese C, Ramadoss A. Responding to the threat of chronic diseases in India. Lancet 2005; 336:1744-1749.
90. Smith S, Jackson R, Pearson TA, Fuster V, Yusuf S, Faergeman O, et al. Principle for national and regional guidelines on cardiovascular disease prevention: a scientific statement from the World Heart and Stroke Forum. Circulation 2004; 109:3112-3121.
91. Sharma KK, Gupta R, Agrawal A, Roy S, Tongia RK. Low use of evidence based secondary prevention therapies in India. Abstract. Indian Heart J 2008; 60:480.
92. Rao M, Nayar KR. Public health in private hands? A note on Public Health Foundation of India. Natl Med J Ind 2006; 19:221-224.
93. Gupta R, Agrawal A, Sarna M, Kaul V, Gupta VP. Framingham risk score shows high cardiovascular risk in low socioeconomic status urban subjects in India. 17th Asia Pacific Congress of Cardiology, Kyoto, Japan. 2009.
94. Goyal A, Yusuf S. The burden of cardiovascular disease in the Indian subcontinent. Indian J Med Res 2006; 124:235-244.