Hypertension epidemiology in the 21 century India

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1 Rajeev Gupta, MD, PhD*; Nishant Gupta, MDS * Department of Medicine; Department of Oral Surgery Fortis Escorts Hospital, Jaipur, India Abstract South Asian Indians have one of the highest cardiovascular morbidity and mortality in the world. Studies have identified that multiple risk factors, such as hypertension, high low density lipoprotein cholesterol, low high density lipoprotein cholesterol, diabetes, smoking and tobacco use, and abnormal lifestyles are important causes of premature occurrence of cardiovascular diseases. Hypertension is the main cause contributing for 57% stroke deaths and 24% coronary heart disease deaths in India. High prevalence of hypertension is reported from various regions of India and among the emigrant populations. Recent studies have reported that hypertension is present in 25 30% urban and 10 15% rural subjects in India and more than 40% adults among migrant Indians. Approximately, 70% of these are Stage I hypertension (systolic BP and/or diastolic BP mm Hg). There is low awareness, treatment and control status among urban and rural Indian populations. There are limited mechanistic studies for identification of unique genetic or pathophysiological pathways of hypertension in this group. Population based cost-effective hypertension control strategies should be developed. Salt intake is high in India and moderation of its intake is a contentious public health issue. Pharmacodynamic and pharmacokinetic studies of various antihypertensive drugs are also not available. Clinical trials have reported that there are no significant differences in efficacy of various drugs in Indians/South Asians as compared to Caucasians. Identification of high risk individuals is important and aggressive risk factor control is required to achieve universal cardiovascular risk reduction. Key Words Cardiovascular disease Hypertension Risk factors Prevention Introduction Cardiovascular diseases (CVD) account for a large proportion of all deaths and disability worldwide. South Asian region (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) is the most populous in the world and emerging burden of CVD in countries of this region is alarming. In , CVD accounted for 20% of all deaths in this region. Coronary heart disease (CHD) was responsible for 60% of these and 40% attributed to stroke. This proportion has increased to 30%, and currently almost 3 million deaths are 2 annually caused by CVD in this region. Age-adjusted annual mortality from CVD in rural area varies from /100,000 and in urban area from in males and in females. These rates are much more than comparable rates in high income countries where these are /100,000 in men and /100,000 per year in 2 women. Escalating cardiovascular risk factors, such as smoking, high blood pressure (BP), high low density lipoprotein (LDL) cholesterol, low high density lipoprotein (HDL) cholesterol, metabolic syndrome and diabetes are 3 associated with the increasing CVD in India. Populationbased epidemiological studies have reported that all these risk factors have increased by 2 5 times in urban and rural regions, over the last 50 years. Downward revision of the predicted increase in cardiovascular disease will require modification of risk factors with two characteristics 1. The risk factors must have high attributable risk, high prevalence, or both 2. Reversal of most or all of the risks must be costeffective. Received: ; Revised: ; Accepted: Disclosures: This article has not received any funding and has no vested commercial interest Acknowledgements: None BP is a major risk factor for several types of cardiovascular disease, and the association of BP with cardiovascular risk 350

2 is continuous. Large proportions of most populations have 4 non-optimal BP values. Moreover, most or all BP related risk can be significantly reduced within a few years using relatively inexpensive interventions. The Global Burden of Diseases study has reported that hypertension is the most important cardiovascular risk factor in this region and 5 responsible for the largest burden of disease and mortality. 21st century estimates are that if a 2 mmhg populationwide decrease in systolic BP is achieved, more than 151,000 stroke and 153,000 coronary heart disease deaths 4 could be prevented in India. st Hypertension in India in 21 century Both urban and rural areas in India have been surveyed to 6,7 estimate the prevalence of hypertension. In the mid- 1950s, Indian urban population studies used older World Health Organization (WHO) criteria for diagnosis (known hypertension or BP >160 mmhg systolic and/or 95 mmhg diastolic) reported hypertension prevalence of % in 1950s. Since then prevalence of hypertension in Indian cities has been steadily increasing from 3 4.5% in early 1960 s to % in mid 1990s. Although rural populations in India generally have lower prevalence of hypertension there has been a significant increase in these populations from less than 1% in early 1960s to 5 7% in late 1990s. Systolic BP >140 mmhg and/or diastolic BP >90 mmhg is the currently accepted diagnostic threshold for hypertension. No prospective epidemiological studies exist among Indians; therefore, the level of BP at which the risk of cardiovascular events begins to increase is not well defined. Most studies from developing countries show a lower mean population BP as compared to developed 8 10 countries. Therefore, the values above which high BP increases cardiovascular risk could be lower in these coun tries. However, in the absence of prospective data and also because of the current recommendations of the WHO and many Indian Consensus Groups, the criteria of Table 1: Recent Indian hypertension prevalence studies (BP >140/>90 mmhg) First author Year reported Place Age group Sample size Prevalence (%) Urban Populations Gupta R 1995 Jaipur Anand MP 2000 Mumbai Gupta R 2002 Jaipur Shanthirani CS 2003 Chennai Gupta PC Prabhakaran D Mumbai Delhi Reddy KS Mohan V National Chennai Kaur P 2007 Chennai Yadav S 2008 Lucknow Rural Populations Gupta R 1994 Rajasthan Kusuma 2004 Andhra Hazarika NC 2004 Assam Krishnan 2008 Haryana Todkar SS 2009 Maharashtra Bhardwaj R 2010 Himachal By Y 2010 Karnataka Kinra S 2010 National

3 Gupta R, et al Table 2: 20 trends in age and sex-adjusted prevalence of selected cardiometabolic risk factors in 30 urban subjects in India (JHW Jaipur Heart Watch studies) First author JHW-1 (n = 712) JHW-2 (n = 558) JHW-3 (n = 374) JHW-4 (n = 887) JHW-5 (n = 537) X2 test for trend p value Overweight (BMI 25.0 kg/m2) 145 (20.4) 287 (51.4) 166 (44.5) 460 (53.0) 248 (46.8) <0.001 Hypertension (history/awareness) 39 (5.5) 103 (18.5) 64 (17.2) 161 (18.2) 105 (19.5) <0.001 Hypertension 212 (29.9) 197 (35.3) 133 (35.8) 286 (39.4) 150 (28.1) Cholesterol 0 mg/dl 136 (25.2) 95 (25.6) 129 (25.9) 164 (30.5) Diabetes mellitus 44 (8.1) 28 (7.5) 59 (10.7) 42 (8.8) systolic >140 mmhg and/or diastolic >90 mmhg is accepted as the cut-off level for the diagnosis of hypertension. Many prevalence studies of hypertension defined by current crite ria have been performed in the late 20th and early 21st century has been performed among urban and rural Indian populations in the country (Table 1). These studies reveal high prevalence of hypertension in Indian urban populations and escalating hypertension in Indian rural populations. It is now obvious that almost a third of adult Indian population has high BP. This is similar to other parts of the developing world and slightly lower than the developed countries where high BP is present in 40 50% of 29 adults. Serial hypertension surveys over a period of 20-years in urban Indian populations among the middleclass subjects have reported persistent high prevalence 30 (Table 2). According to the WHO, in adults aged years, BP levels were the highest among Indian men, as compared to 31 those of 20 other developing countries. Population-based studies of hypertension prevalence among other South Asian countries are also emerging. A study in Nepal in the early 1980s, reported hypertension to be present in 10% of 32 urban subjects. In Bangladesh hypertension was reported 33,34 in less than 5% of rural subjects. High prevalence of hypertension has been reported from urban as well as rural populations in Pakistan. However, there are large regional differences in hypertension prevalence in India and other large countries of the South Asian region, and large trans-national studies are needed. Also required are population based prospective studies to identify causes, and consequences of hypertension in this population which has a high prevalence of multiple cardiovascular risk factors. In India, an estimate regarding the absolute number of patients with hypertension that would be eligible for treatment can be made from epidemiological studies. 352 Current studies have shown that hypertension is present in 38 25% of urban and 10% of rural subjects in India. Because of a difference in the number of BP measurements (typically 1 in epidemiological studies and 2 3 over a timeperiod in clinical studies), it has been estimated that epidemiological studies over-diagnose hypertension by %. If we discount this proportion, currently 19% adults in the urban and 7.5% in the rural areas of India would be eligible for antihypertensive therapies. Translating these proportions into numbers reveals a massive burden of this disease in India. According to the 2011 census, there are 700 million adults in India, of whom 500 million are in rural and 200 million in urban areas. The absolute number of hypertensive patients in India in the early 21st century would therefore be 38 million among rural and a similar number in urban subjects, for a total of million subjects with hypertension. Hypertension risk factors Although the precise reasons for the increase in hypertension prevalence among Indians have not been established, several possibilities exist. BP in unacculturated societies is generally lower and do not 40 increase with age. In non-westernized Indian rural populations, there is only a small increase in the prevalence in hyper tension as the population ages. On the other hand, in urban populations exposed to the stress of acculturation and modernization, hyperten sion prevalence rates have more than doubled in the last 30-years. There is epidemiological evidence that population demographic changes in India have increased 41 environmental risk factors for hypertension. There is increasing life expectancy, urbanization, development, and affluence in India. In 1901, only 11% of the population lived in an urban area; this proportion grew over time to 17% in 1951, 20% in 1971, 26% in 1991, 28% in 2001 and 42 is likely to increase to 40% by year There is a strong correlation between urbanization and the increase in

4 hypertension prevalence. Affluence (as measured by evaluation of per capita net domestic product, growth of production, and human development index) has also increased sharply in India and other countries of this region in recent years and correlates with the increase in the prevalence of hypertension. Per capita fat and oil consumption has also increased during the last 40 years. It was 5.79 kg/person/year in 1961, 5.85 in 1971, 6.48 in 1981 and 6.96 in 1987, and increasing. According to Indian National Nutrition Monitoring Bureau the salt consumption was 10.7 g/person/day in 1971 and increased to 13.0 in 1981, 15.8 in 1991 and 16.9 in 1994 and is 43 maintained at this level over the last 15 years. Summation of these socio demographic and lifestyle factors may be accelerating the hypertension epidemic, currently sweeping India and other countries of this region. High salt intake is possibly the most important reversible 44 hypertension risk factor. Intake is especially high in Indian population as mentioned above. In India, the average intake of salt (sodium chloride) varies from 8 15 g/day, more among the rural populations. This is compounded by false perception among the healthcare professionals of excessive salt loss due to hot weather conditions. Recent meta-analyses have clearly shown harms of excessive salt intake and guidelines recommend 45,46 intake less than 6 g/day among general population. Sub-national and regional epidemiological studies have reported that important correlates of hypertension in Indian populations are increasing socioeconomic status and obesity. In Indian middle socioeconomic status subjects, Jaipur Heart Watch studies reported 20-year trend in hypertension awareness and prevalence (refer Table 2). Increasing awareness of hypertension was noted over this period. Prevalence of hypertension did not increase significantly despite increasing body weight and obesity. Whether a reversal in socioeconomic gradient in prevalence of hypertension, with greater hypertension in poorer subjects as is present in most developed countries, takes place in India and other countries of this region awaits further studies. Specific issues of hypertension management in Indians Treatment of hypertension is associated with reduction in cardiovascular morbidity and mortality, but the number of events prevented is generally related to the absolute risk of the population being treated. Prospective Studies Collaboration has reported that reducing BP can substantially decrease cardiovascular risk and 47 cardiovascular as well as all-cause mortality. This risk reduction is steeper in younger subjects than in the older subjects and is more when baseline BP levels are high. In a meta-analysis of 61 studies involving more than a million patients with hypertension and 12.7 million years of follow-up it was observed that reducing systolic as well as diastolic BP reduced cardiovascular events. At ages years, each difference of 20 mmhg systolic BP or 10 mmhg diastolic BP was associated with more than a twofold difference in the stroke death rate, and with two-fold differences in the death rates from coronary heart disease and other vascular causes. All of these proportional differences in vascular mortality were about half as extreme at ages years as at ages years, but the annual absolute differences in risk were greater in old age. Thus, in high-risk populations (e.g., older individuals, diabetics, or those with very high BP), many events can be prevented with BP control using relatively inexpensive drug treatment, but with lower-risk patients and in the young, lifestyle modifications are sometimes recommended over drug therapy, because they can be implemented in large populations and involve fewer direct 31 costs. In the Treatment of Mild Hyper tension Study 48 (TOMHS) lifestyle modifications plus drug treatment in individuals with only mildly raised BP (Stage I hypertension: systolic mmhg and/or diastolic mmhg; average 142/91 mm Hg) was associated with improved outcomes as compared to those who received placebo plus lifestyle modifications. In 1992, Stamler recommended an average population systolic BP 49 of 110 mmhg as a realistic goal. Reports from the Seven 50 Countries Study and Framingham Heart Study51 showed that what was termed high normal BP (systolic BP mmhg and/or diastolic BP mmhg) and Stage I hypertension carry a significant cardiovascular risk, and there is need to reduce this BP. Pharmacological therapies for these individuals will be expensive, and needs more studies, although TOMHS demonstrated that drug 48 therapy reduces cardiovascular end-points. For BP higher than Stage 1, almost all guidelines recommend pharmacological therapy. This translates into million persons in India, who would require regular antihypertensive medications. This carries a huge economic burden on already over-stressed economies of these poor countries. Studies that examine cost-effective approaches to optimally control BP among these populations are urgently needed. Lifestyle changes that are needed to control high BP include low dietary salt and fat intake, weight control, regular physical activity, moderation of alcohol intake, and 52 yoga exercises. Studies exist from India that have demonstrated usefulness of each of these measures. However, recent studies such as the Dietary Approaches to 353

5 Gupta R, et al Stop Hypertension (DASH) in USA have reported 53 usefulness of comprehensive dietary changes. This approach leads to decrease of high BP along with multifactorial cardiovascular risk factor control. Similar studies are required in this region, although observational studies report benefit of low-fat Indian vegetarian diets in controlling high BP and vascular risk. There are ethnic differences in therapeutic response to 54 antihypertensive drug treatment. The African-Americans respond less well to drugs that suppress the reninangiotensin system (e.g., beta blockers and angiotensinconverting enzyme inhibitors) as compared to other drugs (diuretics and calcium channel blockers). No trials of efficacy of different antihypertensive agents are available in Indians or other South Asian groups. However, as there is a greater prevalence of diabetes, insulin resistance, and 55 metabolic syndrome among this population, drugs that improve insulin sensitivity and provide vasculoprotective effects such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers could be considered first- 56 line options. Prospective studies in India are required that address influence of different anti-hypertensive agents on cardiovascular events and other hard end points. Results st In conclusion, hypertension is highly prevalent in the 21 century India. This is a manifestation of demographic and epidemiological transition, changing lifestyles (increase in dietary fat and salt intake and low physical activity) and increasing obesity and central obesity. There is low awareness, treatment and control status in Indian urban as well as rural populations. Hypertension carries a huge economic burden on already overstressed economy of India. 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