indian heart journal 65 (2013) 369e377

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Original Article Smokeless and cardiovascular disease in low and middle income countries

Rajeev Gupta a,*, Nishant Gupta b, R.S. Khedar a a Department of Medicine, Fortis Escorts Hospital, JLN Marg, Jaipur 302017, India b Department of Oral Surgery, Fortis Escorts Hospital, JLN Marg, Jaipur 302017, India article info abstract

Article history: Smoking is an important cardiovascular risk factor, however, use of has Received 14 January 2013 not been well studied. Smokeless tobacco use is high in countries of South and Southeast Accepted 19 June 2013 Asia, Africa and Northern Europe. Meta-analyses of prospective studies of smokeless to- Available online 16 July 2013 bacco users in Europe reported a relative risk for fatal coronary heart disease of 1.13 (confidence intervals 1.06e1.21) and fatal stroke of 1.40 (1.28e1.54) while in Asian countries Keywords: it was 1.26 (1.12e1.40). Case-control studies reported significantly greater risk for acute Tobacco coronary events in smokeless tobacco users (odds ratio 2.23, 1.41e3.52), which was lower Smoking: coronary heart disease than smokers (2.89, 2.11e3.96), and subjects who both chewed and smoked, had the Cardiovascular disease greatest risk (4.09, 2.98e5.61). There is a greater prevalence of hypertension and metabolic Smokeless tobacco syndrome in users of smokeless tobacco. Smokeless tobacco use leads to accelerated atherothrombosis similar to smoking. There is an urgent need for public health and clinical interventions to reduce smokeless tobacco addiction. Copyright ª 2013, Cardiological Society of India. All rights reserved.

1. Introduction we describe the epidemiology of smokeless tobacco use with focus on low and middle income countries and its association Smoking is the most reliably documented cardiovascular risk with CVD and CVD risk factors. factor.1 Historical trends in cardiovascular disease (CVD) mortality and smoking in the United States from 1900 to 1990 closely mirror each other, with both rates increasing through 2. Epidemiology of smokeless tobacco use the 1950s, followed by a precipitous fall beginning in the 2 1960s. There is a strong epidemiological, experimental, clin- Smoking and tobacco use is a worldwide health problem ical and randomized controlled trial evidence of support for (Fig. 1).1,6 Use of smokeless tobacco predates smoking. Initial 3 smoking as important CVD risk factor. Prevalence of smoking descriptions are available from the American continents in 4 has declined in most high income countries. On the other middle of second millennium.7 Native Americans in North hand, in many middle and low income countries, especially in and South America chewed the leaves of the plant, frequently South and Southeast Asia, smoking as well as use of smoke- mixed with the mineral lime. was the most 5 less tobacco is increasing. CVD risks associated with prevalent form of tobacco use in the United States until it was smokeless tobacco use are not well described. In this review, overtaken by cigarette smoking in the early 20th century.7

* Corresponding author. Fax: þ91 1414008151. E-mail addresses: [email protected], [email protected] (R. Gupta). 0019-4832/$ e see front matter Copyright ª 2013, Cardiological Society of India. All rights reserved. http://dx.doi.org/10.1016/j.ihj.2013.06.005 370 indian heart journal 65 (2013) 369e377

Fig. 1 e Smoking and tobacco use among adults in different regions of the world. Adopted from WHO.1

Smokeless tobacco is consumed in un-burnt forms through 2.1. Middle and low income countries chewing or sniffing and contains several carcinogenic com- pounds.1 Smokeless tobacco has been associated with oral In contrast to the United States and Western European cancer, hypertension, heart disease and other conditions.1 countries, smokeless tobacco use is high in Northern Euro- Smokeless tobacco may also refer to tobacco dipping, , pean and African countries and in Asia.1,11 In India, 22% of , creamy snuff or tobacco toothpaste, tobacco gum, men and 17% of women use smokeless tobacco, in Sudan 40% dissolvable tobacco, topical tobacco paste, tobacco water, of men and 10% women use toombak, a locally brewed herbal smokeless tobacco, etc. Smokeless tobacco use is more smokeless tobacco, and in Sweden among those >16 years of prevalent in countries of Asia, Africa and the Middle East than age 21.2% of men and 3.9% women use snus.1,11 in Europe and the Americas.7 Data on these forms of tobacco The WHO Southeast Asian Region is the hub of smokeless use are not readily available for most parts of the world. tobacco users.12 It has a history of people using different Prevalence of smokeless tobacco use has been studied in smokeless tobacco products for centuries. Decades ago, high income countries and reports a low prevalence. Behav- people used only locally made smokeless tobacco products iour Risk Surveillance System Study reported smokeless to- such as betel quid with tobacco. However, in recent times with bacco use in USA.8 The use ranged from 1-9% in different large-scale production of tobacco, varieties of manufactured states and was more in younger men with low educational products have become widely available to the people in this status, and in states with high smoking prevalence. The US region. It is home to nearly 250 million smokeless tobacco Current Population Survey9 reported a significant decline in users.12,13 Chewing, sucking and applying tobacco prepara- smokeless tobacco use from 1992 to 2002. The US National tions are common ways of using tobacco orally. The simplest Health Interview Surveys (1991e2003)10 also reported decline form of smokeless tobacco product is a betel quid, where to- in smokeless tobacco use. Prevalence of smokeless tobacco bacco is added to the betel leaf and areca nut with some slaked use has also been reported from European countries. It is lime. It is commonly available and has been in use for many almost similar to USA with rates ranging from 1-9% in years in Bangladesh, India, Myanmar and Nepal. Prevalence of different countries.1 The Global Adult Tobacco Survey, 2009 smokeless tobacco among men in the Southeastern countries reported that in Russian Federation, 0.6% (0.7 million) of adult ranges from 1.3% in Thailand to 51% in Myanmar.12 Among population used smokeless tobacco. Prevalence was more women, it ranges from 4.6% in Nepal to 27.9% in Bangladesh.12 among males (1.0%) than among females (0.2%) and higher in Use of smokeless tobacco products among male students in urban areas (0.7%) as compared to rural areas (0.3%).1 this region aged 13e15 years ranged from 3.3% in Indonesia to indian heart journal 65 (2013) 369e377 371

43.2% in Timor-Leste, and among females from 2.3% in across 110 sites reported a substantial variation in non- Indonesia to 40.7% in Timor-Leste.1 Some sub-national sur- cigarette forms of tobacco use, which include smokeless to- veys show that working children and street children are far bacco from a low of 1.0% in China to 43.7% in Northwest more likely to use tobacco than students.1 Namibia.18 Global Tobacco Surveillance System reported pat- In India, tobacco consumption is mainly in two forms: terns of tobacco use among nearly 750,000 youth, aged 13e15 smoked tobacco products and smokeless tobacco.13 Most years at more than 10,000 schools and 395 sites in 131 coun- commonly used smokeless tobacco products include e to- tries.19 The use of non-cigarette forms of tobacco use, which bacco pan masala, tobacco with lime, tobacco with pan and include smokeless tobacco (11.2%), was more than smoking betel quid. According to a recent report, the prevalence of (8.9%). The rates were the highest in Southeast Asia (13.3%) smokeless tobacco consumption in India is 20%.12 It is and the Eastern Mediterranean region (12.9%) and were less significantly higher in males than in females (28% in males than 10% in the Western Pacific and European regions.19 and 12% in females), and in rural population as compared to Anecdotal evidence suggests that smokeless tobacco use, urban population.13 Third National Family Health Survey in among the youth has increased exponentially in India India (2005e2006) reported 34% prevalence of chewable (Table 2).20 Project MYTRI, a cross-sectional study conducted smokeless tobacco use in men 15e54 years.14,15 Easy afford- in India (Delhi and Chennai), reported higher levels of ability, lesser cost and misconceptions regarding its useful smokeless tobacco use among 6th grade students than 8th health effects are important contributory factors for increased graders. This suggested increased tobacco use among younger smokeless tobacco consumption. Tobacco consumption is children in India.21 higher among poor, less educated, scheduled castes and Trends in prevalence of smokeless tobacco use have not scheduled tribes. Global Adult Tobacco Survey e India report been well studied in low income countries. In India, the Na- mentions a high use of smokeless tobacco among men and tional Family Health Surveys from 1992 to 2006 did not report women aged >15 years in India.1 A sample of almost 800,000 significant changes in smoking or smokeless tobacco use.22 A men and women was evaluated for habit of tobacco use and study among urban subjects in Northwest India reported data showed that almost a quarter (26%) of all adults in India declining trends in smoking among men and women over a use smokeless tobacco either by chewing, sniffing or applying 20-year-period (1991e2010) but trends in smokeless tobacco to teeth or gums. Use of smokeless tobacco was more preva- use were not reported.23 lent than smoking and was more in men (33%) than in women (18%).1 WHO Global Health Observatory Data Repository has reported prevalence of smokeless tobacco use among adults 3. Smokeless tobacco and cardiovascular in 2008 (Table 1).16 The use is significantly greater among men disease than in women in almost all the countries. Prevalence is greater in low income countries. There are limited studies in There are several adverse health effects attributable to e Africa. A study in Nigeria reported 7.5% prevalence of smokeless tobacco.24 26 Similar to smoked tobacco, the smokeless tobacco use with the most common form being smokeless tobacco also contains , a chemical with snuff.17 addicting properties. Unfortunately, people are not aware of Smokeless tobacco use is an important health issue among the addiction potential of smokeless and other forms of to- children and youth in low income countries. Global school bacco.24 They are also unable to stop its use once addicted based health surveys in the year 2006 among 44 countries because of unpleasant withdrawal symptoms. Smokeless and other tobacco products are known to cause oral, pancre- atic, pharyngeal, esophageal and stomach cancers.26 Some studies also show that smokeless tobacco users die of CVD and other circulatory diseases.24 Low birthweight and still- Table 1 e Smokeless tobacco use among adults in births are two major adverse reproductive outcomes found in selected countries according to WHO Global Health association with its use in pregnancy.27 Observatory Data Repository (2008) and Global Adult Association of smokeless tobacco consumption with Tobacco Survey India (2010).21,22 occurrence of adverse cardiovascular events like myocardial Country Men Women Total infarction, stroke, and ischemic heart disease has been stud- (%) (%) (%) ied in detail in western population.24 Results from these High income countries studies paint a mixed picture with some showing increased Denmark 1.9 0.5 1.2 incidence of these events while others showing no such as- e Sweden 7.0 3.0 sociation. Similarly, contradictory results have been seen in Middle income countries studies evaluating increased risk factors for CVD in smokeless Malaysia 0.5 3.1 0.6 Uzbekistan 22.5 0.4 11.3 tobacco consuming population. South Africa 2.4 10.9 e Yemen 15.1 6.2 10.7 3.1. Prospective studies Low-middle/low income countries Bangladesh 14.8 24.4 19.7 There are limited prospective studies that assessed role of Cambodia 17.0 1.0 10.1 smokeless tobacco on CVD outcomes or mortality.24 Most of India 32.9 18.4 25.8 these studies have been performed in Northern Europe. Re- Nepal 31.2 4.6 18.6 sults on the risk for myocardial infarction or stroke have 372 indian heart journal 65 (2013) 369e377

Table 2 e Non-cigarette forms of tobacco use which include smokeless tobacco among adolescents in Global Youth Tobacco Survey e 1999e2005 (Percent, 95% confidence intervals).25 Region Total Boys Girls

Total 11.2 (9.7e12.7) 13.8 (11.7e15.9) 7.8 (6.0e9.6) African region 10.5 (8.3e12.7) 10.9 (8.0e13.8) 9.9 (7.3e12.5) Americas region 11.3 (9.8e12.8) 14.8 (12.6e17.0) 7.8 (6.2e9.4) Eastern Mediterranean region 12.9 (10.6e15.2) 15.6 (12.4e18.8) 9.9 (7.3e12.5) European region 8.1 (5.8e10.4) 10.0 (6.7e13.3) 6.0 (4.0e8.0) Southeastern Asian region 13.3 (12.3e14.3) 16.4 (15.0e17.8) 8.4 (6.8e10.0) Western Pacific region 6.4 (5.2e7.6) 7.7 (6.1e9.3) 5.4 (3.9e6.9)

provided conflicting evidence.28,29 Critchley and Unal per- 3.2. Association studies formed a meta-analysis of studies of association of smoke- less tobacco use and CVD.28 Very few studies were identified; There are limited case-control studies that evaluated cardio- only three from Sweden considered CVD outcomes and the vascular risks in smokeless tobacco users as compared to non- results were discrepant. There was a modest association users. Two case-control studies from Sweden showed the between the use of Swedish snuff (snus) and CVD (relative same cardiovascular risks among smokeless tobacco users as risk 1.4, 95% confidence interval 1.2e1.6 in one prospective in non-tobacco users.33,34 The odds ratios for all and fatal cohort study). Several other studies have considered associ- myocardial infarction remained non-significant after adjust- ations between smokeless tobacco use and intermediate ments for various potential confounders. outcomes (CVD risk factors).24 It was concluded that there INTERHEART study evaluated 27,089 participants for as- may be an association between smokeless tobacco use and sociation of cardiovascular risk factors with acute myocar- CVD, however, further rigorous studies with adequate sam- dial infarction in 52 countries (12,461 cases, 14,637 ple sizes were required. controls).35 Relationship between risk of myocardial infarc- Boffetta and Straif also performed a meta-analysis of these tion with current or former smoking, type of tobacco, studies.29 In all, eight studies that evaluated risk of fatal smokeless tobacco use and exposure to second hand tobacco myocardial infarction and five studies that evaluated fatal smoke was determined. Current smoking was associated stroke were analyzed. Three studies showed increased risk for with a greater risk of non-fatal myocardial infarction (OR cardiovascular deaths (fatal myocardial infarction and stroke) 2.95, 95% CI 2.77e3.14) compared with never smoking. when compared to non-smokers, while others did not show Smoking beedies alone (indigenous to South Asia) was any significant difference in outcomes (Fig. 2). The summary associated with increased risk (OR 2.89, 95% CI 2.11e3.96) odds ratio (OR) statistic and 95% confidence intervals (CI) show similar to that associated with cigarette smoking. Chewing greater risk of fatal myocardial infarction (OR 1.13, 95% CI tobacco alone was associated with OR 2.23 (95% CI 1.41e3.52), 1.06e1.21) and fatal stroke (OR 1.40, 95% CI 1.28e1.54). A and smokers who also chewed tobacco had the highest risk population based prospective study in Sweden reported that (OR 4.09, 95% CI 2.98e5.61) of acute myocardial infarction. among snuff users the risk of myocardial infarction (OR 0.82, Similar results have been reported by smaller case-control 95% CI 0.46e1.43) or sudden cardiac death (OR 1.18, 95% CI studies.24 0.38e3.70) was not significant.30 Studies in low and middle income countries of Asia and Africa have been few. Gupta et al performed a prospective study involving about 100,000 men and women in Mumbai, 4. Smokeless tobacco and cardiovascular India.31 At follow-up of five years, relative risk of fatal car- risk factors diovascular event among male users of smokeless tobacco was not significantly different from non-tobacco users. In In high income countries, there have been studies to deter- women, smokeless tobacco use was associated with signifi- mine association of smokeless tobacco use and cardiovascular cantly greater risk of cardiovascular mortality (Fig. 3). Zhang risk factors.24 Older studies among young Swedish snuff- et al performed a meta-analysis of studies on association of using subjects36 or US professional baseball players37 did not smokeless tobacco use and cardiovascular outcomes in report any significant association. A study among 58-year old Asia.32 Studies from China, Taiwan and India were included men reported significantly greater waist-size, triglycerides (Fig. 4). The study reported insignificant association of to- and other manifestation of dysmetabolic syndrome in bacco use and cardiovascular mortality in India but the smokeless tobacco users.38 This was confirmed in a prospec- relationship was significant in studies in China and tive Swedish study, which showed that over a period of 10 Taiwan.32 The summary odds ratio was 1.26 (95% CI years, high dose consumption of snus was associated 1.12e1.40), which indicated moderate risk of cardiovascular with development of metabolic syndrome (OR 1.6, 95% CI death with smokeless tobacco use. Thus, use of smokeless 1.26e2.15).39 tobacco (with snuff being the most studied variant) involves Prospective studies that evaluated development of other a much lower risk for adverse cardiovascular effects than cardiovascular risk factors have also been performed. Hergens smoking. et al performed a cohort study with 15 year follow-up of a indian heart journal 65 (2013) 369e377 373

2.5

Fatal myocardial infarction 2

1.5

1 Huhtasaari Accortt Henley Henley Hergens Haglund Hergens Wenneberg Overall ) CI 0.5 5% 5% (9 0 2.5

Fatal stroke lative risk lative 2 Re

1.5

1 Accortt Henley Henley Haglund Hergens Overall

0.5

0

Fig. 2 e Smokeless tobacco use and risk of fatal myocardial infarction (upper graph) or fatal stroke (lower graph) in high income countries. Summary meta-analysis odds ratio statistic and 95% confidence intervals (CI) show greater risk of fatal stroke (1.40, CI 1.28e1.54) as compared to fatal myocardial infarction (1.13, CI 1.06e1.21). Data source: Boffetta & Straif. BMJ, 2009.29

Swedish national sample of male construction workers.40 1.7 times (95% CI 1.3e2.1) more likely to have a systolic Blood pressure (BP) was measured at baseline and at follow- BP > 160 mmHg.41 up. As compared to non users (n ¼ 4815), men who used Several studies in Sweden have examined the effect of snuff regularly (n ¼ 1010) had an increased relative risk of smokeless tobacco products on serum lipids.24 No significant hypertension of 1.43 (95% CI 1.12e1.83). In a population based effects were found in levels of total cholesterol and HDL cross-sectional study of >30,000 participants in Sweden, cholesterol among snuff users compared to controls in these smokeless tobacco users were 1.8 times (95% CI 1.5e2.1) more populations. On the other hand, Tucker et al from a large likely to have a diastolic BP reading more than 90 mmHg and population based study reported that subjects who used smokeless tobacco had 2.5 times greater prevalence of

2

2.5

1.5 2

1.5

1 1 Non-smoker Smokeless Smoker Non-smoker Smokeless Smoker Gupta Yen Lin Lan Wen Guh Overall

Relative risk (95% CI) 0.5

0.5 neM nemoW 0

Fig. 3 e Smoking, smokeless tobacco use and Fig. 4 e Smokeless tobacco use and cardiovascular cardiovascular mortality in India: Mumbai Cohort Study. mortality in Asian countries. Studies from China, Taiwan Smokeless tobacco use in women is significantly and India have reported significant association of tobacco associated with cardiovascular mortality (relative risk 1.19, use and cardiovascular mortality in cohort studies. 95% CI 1.02e1.38) while the association is not significant in Summary odds ratio (1.26, CI 1.12e1.40) indicates men (relative risk 0.94, 95% CI 0.82e1.09). Data source: moderate risk. Data source: Zhang, et al. J Zhejiang Univ Gupta, et al. Int J Epidemiol, 2005.31 Sci, 2010.37 374 indian heart journal 65 (2013) 369e377

hypercholesterolemia.42 Khurana et al reported significantly the WHO Framework Convention on Tobacco Control (FCTC) lower levels of HDL cholesterol and greater levels of LDL and MPOWER policy package.1 The features include (i) to cholesterol in Asian Indian subjects who chewed tobacco continue working on tobacco control awareness programs regularly.43 In another study of 3128 men, there was higher where all subpopulations have equal access to the activities prevalence of diabetes among long-term users of smokeless and information; (ii) public health policy and interventions tobacco (OR 2.7, 95% CI 1.3e5.5).44 Abnormalities of platelet should cover all types of tobacco products; (iii) periodic function, oxidative stress and coagulation factors have also monitoring of tobacco use through standard surveys should been evaluated among smokeless tobacco users.24 No signifi- be continued and integrated into tobacco control action plans cant differences have been reported as compared to non-users. and existing health systems to implement the concept of To identify cardiovascular risk factors among tobacco chewers, WHO FCTC.1 Government of India and many state govern- Gupta et al performed a population based case-control study in ments have implemented some aspects of FCTC. Tobacco India.45 Tobacco chewers had a significantly greater preva- taxations are being raised regularly.47 A notification of Food lence of resting tachycardia, hypertension, hypercholester- Safety and Standards Authority of India has prohibited the use olemia, low HDL cholesterol, hypertriglyceridemia and of tobacco and nicotine in any food product.48 However, in- diabetes compared to non-smokers/non-tobacco users (Fig. 5). dicators for smokeless tobacco were not included in the The risk factors were similar to smokers (Fig. 5). package. Smokeless tobacco is now exported to many coun- Smoking is a well-established CVD risk factor.24,46 Ciga- tries and available in local brands. With increased availability rette smoking leads to acute coronary thrombosis and of smokeless tobacco products globally, these tobacco control chronically produces endothelial dysfunction, hypercoagula- strategies need to be revisited and regulation and control of bility and inflammation, resulting in accelerated atheroscle- smokeless tobacco products needs to be emphasized. Regional rosis.46 Smoking also leads to a wide variety of mechanistic efforts on curbing smokeless tobacco should be included in disruptions e platelet activation and thrombogenesis, endo- the tobacco control policies. thelial dysfunction, accelerated atherogenesis, inflammation, There is also a need to build capacity for programs among sympathoadrenal activation, arrhythmogenesis, insulin resis- healthcare providers and expand cessation services in the tance and hyperlipidemia e all of which can contribute to national health programs.1 The following action items have CVD. It has been suggested that smokeless tobacco produces been recommended: (i) strengthen the national health system vascular damage through similar biological mechanisms.24,46 to provide smoking and non-smoked tobacco use cessation More studies are required to elicit pathophysiological mech- services in primary healthcare facilities; (ii) introduce anisms of smokeless tobacco on vascular system, thrombosis evidence-based smoking cessation and non-smoked tobacco and atherosclerosis. control approaches and interventions; (iii) formulate a 100% tobacco-free policy for all public places and workplaces to meet the expectations of population; (iv) gradually raise taxes on all types of tobacco products, given the high prevalence of 5. Public health implications non-smoked tobacco use and the low price of smokeless to- bacco products compared to increases in income; (v) expand A concept on implementing state policy on combating tobacco the national tobacco control act to include smokeless tobacco e for 2010 2015 was developed by WHO and approved for use in under the purview of tobacco control at par with all smoking tobacco products with the purpose to prevent the use of smokeless tobacco and any other new tobacco and nicotine 45 45 products; (vi) continue working with mass media on effective 40 40 39 37 anti-smoking and anti-tobacco use media messages that 35 33 target specific demographic groups; (vii) further develop the 30 29 28 health warnings on tobacco products, as health warnings are 25 25 25 22 21 one of the most effective methods for encouraging tobacco 20 20 17 users to quit; (viii) decrease the number and regulate the type 15 15 14 12 of venues where tobacco products can be sold; and (ix) 9 10 8 gradually prohibit tobacco advertising at points of sale, as a 5 high percentage of cigarette smokers and non-smoked to- 0 Obesity Hypertension High Low HDL High TG Diabetes bacco users notice advertisements where they purchase cholesterol them. At the individual level, whether or not the apparent

Non-smoker Smokeless Smoker risk reduction is a useful strategy to help inveterate tobacco users to quit is a matter of debate, as are the public health Fig. 5 e Cardiovascular risk factors in smokers, smokeless effects of a high prevalence of smokeless tobacco use in some tobacco users and non-tobacco users in India. Greater populations. prevalence of hypertension, hypercholesterolemia, low The US National Institutes of Health has also recommended HDL cholesterol, hypertriglyceridemia and diabetes is strategies for tobacco control and focussed on smokeless to- observed among smokeless tobacco users vs non-tobacco bacco use (Table 3).49 The key strategies include population- users (p < 0.05). Prevalence of risk factors is similar to and community-based interventions, increasing consumer smokers. Data source: Gupta, et al. J Assoc Physicians demand for cessation treatments, promoting implementation India, 2007.45 of the existing strategies by healthcare system as well as indian heart journal 65 (2013) 369e377 375

Table 3 e Strategies for smokeless tobacco control. Strategies Actionable items

Population- and community-based interventions Increased prices through taxation on tobacco products Laws and regulations that prevent young people from gaining access to tobacco products Restrict tobacco advertising Mass media campaigns Increasing consumer demand for proven Proactive telephone tobacco cessation support cessation treatments Healthcare provider advise to stop tobacco use Educational approaches Pharmacological therapies, e.g., bupropion Increase in price of tobacco products Reducing out-of-pocket costs of cessation therapies Culturally tailored, gender-specific, language appropriate programs Promoting implementation of strategies by Healthcare system level interventions for tobacco use cessation healthcare systems and communities Financial incentives Health system level educational and organizational approaches Dedicated staff for tobacco cessation services Control of marketing of smokeless tobacco Control of availability of these products products Inexpensive pharmacological and behavioral cessation therapies Prevention and cessation interventions in Tailored multimodal cessation interventions populations with co-morbidities and risk Proper timing of initiation of interventions behaviors Public health efforts and future research Improve and implement effective interventions Improve and implement effective policies Develop new population- and community-based interventions Smokeless tobacco pathophysiological, behavioral, and intervention research Infrastructure development

communities, control of marketing of smokeless tobacco recommend a worldwide ban on smokeless tobacco products products, and accelerated public health efforts and promotion to attenuate multiple harms, including CVD, associated with of future research. It is essential to integrate worldwide health its use. promotion agencies to support smokeless tobacco control programs. At the population level, tobacco control policies should be integrated into the overall health and development Conflicts of interest agenda.50 This should involve integration of tobacco control into broader health and development agenda such as food and All authors have none to declare. water security, environment, the right to education and human rights. Policy and administrative integration of tobacco and other primordial determinants of cardiovascular health references (physical activity promotion, alcohol control and promotion of healthy diet)51 shall encourage a holistic solution to CVD and non-communicable diseases. 1. World Health Organization. WHO Report on Global Tobacco Epidemic: Warning about Dangers of Tobacco. Geneva: World Health Organization; 2011. 6. Conclusions 2. Nabel EG, Braunwald E. A tale of coronary artery disease and myocardial infarction. N Engl J Med. 2012;366:54e63. This review shows that smokeless tobacco use is an important 3. Gaziano TA, Gaziano JM. Global Burden of Cardiovascular public health problem. Prevalence is high in low income Disease. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald’s Heart Disease. Philadelphia: Saunders; 2012:1e20. countries and the highest in South Asia and Southeastern 4. Fuster V, Kelly BB, Board for Global Health. Promoting Asian regions. Prospective studies have reported a significant Cardiovascular Health in Developing World: A Critical Challenge association of smokeless tobacco use with cardiovascular to Achieve Global Health. Washington: Institute of Medicine; mortality (coronary heart disease and stroke) as well as acute 2010. coronary events. Smokeless tobacco use is associated with 5. Gaziano TA, Bitton A, Anand S, Abrahams-Gessel S, increased cardiovascular risk factors such as the metabolic Murphy A. Growing epidemic of coronary heart disease in Curr Probl Cardiol syndrome and diabetes. Mechanistic issues that lead to an low- and middle-income countries. . 2010;35:72e115. increased cardiovascular risk of smokeless tobacco need more 6. World Health Organization. World Health Statistics, 2008. studies. There is a need for population- and community-wide Geneva: World Health Organization; 2011. policy interventions for smokeless tobacco control. Individual 7. Anonymous. Smokeless Tobacco. Available at: http://en. interventions promoting tobacco cessation are important. We wikipedia.org/wiki/Smokeless_tobacco. Accessed on 21.6.12. 376 indian heart journal 65 (2013) 369e377

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