CHAPTER 30: EPIDEMIOLOGY OF SMOKING AND PATHOPHYSIOLOGY OF CARDIOVASCULAR DAMAGE

This chapter provides an epidemiological overview of cigarette smoking and its impact on health, with a focus on cardiovascular diseases. Although smoking-related pathophysiological changes are discussed in all relevant chapters, this chapter aims to provide a synopsis of smoking-related pathological changes in the cardiovascular system. As health care providers striving to improve cardiovascular health, we are uniquely positioned to promote smoking cessation through counseling and clinical support for both primary and secondary prevention. Chapter 31 discusses the clinical management of patients to prevent and mitigate the adverse effects of smoking. The seriousness, resources, and political will to counterbalance the strong interest and position of the smoking industry may be catching up after a lag of almost half a century. There are growing concerns about (1) an increase in the total number of smokers worldwide with population growth despite a reduction in smoking rates, (2) an increasing prevalence of smoking among young adults and in developing countries, and (3) an increasing uptake of electronic cigarettes (e-cigarettes) ahead of research examining its health effects.

Tobacco Control: A Long and Arduous Journey

Although the Surgeon General’s report in 1957 concluded that cigarette smoking is associated with an increased risk of lung cancer, it was not until publication of the landmark 1964 Surgeon General’s report that the adverse relationship between cigarette smoking and cardiovascular disease was seriously recognized. The Surgeon General’s report concluded that cigarette smoking is strongly associated with myocardial infarction and coronary heart disease deaths, and it laid the foundation for tobacco control.¹ Unfortunately, health care providers, professional societies, civic bodies, and governments have also played negative or timid roles, largely attributed to the smoking industry’s exploitation of the natural skepticism and probabilistic nature inherent in scientific evidence, serious conflicts of interest, and lack of a strong public will. Smoking has claimed more than 20 million lives with premature deaths in the United States alone since the publication of the 1964 report.

The annual per capita cigarette consumption in the United States was at its peak in early 1960s, with a prevalence of about 45% in 1965. Through concerted efforts over more than half a century, the cigarette consumption in the United States has declined to half of its peak prevalence rates—to about 18% in 2012.² Multiple factors, including an improved understanding of the adverse effects of secondhand smoke, and policy measures, such as ban of broadcast advertising, increased public awareness, and the increase in taxes on cigarettes, have played an important role in this epidemiological transition (Fig. 30–1). Despite years of progress, cigarette smoking still remains the leading cause of preventable cardiovascular morbidity and mortality across the globe.

Global Burden of Cigarette Smoking

Globally, about one billion individuals smoke (Fig. 30–2B). The majority (about 800 million) are males. Although the prevalence of smoking has declined over the past few decades, the total number of smokers has increased globally, owing to population growth (Fig. 30–2A).

The worldwide prevalence of smoking is highly variable by country and region, suggesting a heavy influence of socioeconomic and cultural currents as well as national policies. In 2012, the prevalence of smoking among adults was 49% in eastern Europe; 45% in China; 36% in Japan; 28% in western Europe; 23% in India; and about 18% in Australia, the United States, and Canada³ (Fig. 30–3). In China, an increase in cigarette use from 1.5 trillion cigarettes in 1998 to 2.5 trillion in 2016 is disturbing. Tobacco control in China is complex: the state acts as a regulator but also simultaneously owns the Chinese National Tobacco Company, the world’s largest tobacco company by volume.⁴ Strong surveillance systems reporting trends at frequent regular intervals will be necessary on a global platform to inform policy and decision making. For instance, a rapid rise in smoking is predicted among men in Africa and among both genders in the eastern Mediterranean, based on recent surveillance data calling for action.⁵

The prevalence of smoking had decreased by about 1% to 2% annually from 1980 through 2005. Unfortunately, after many years of steady decline, the annualized rate of decline has plateaued; it didn’t change for males for the year 2012.³

When considering differences by age groups, the highest prevalence of smoking worldwide in the year 2012 was seen in males aged 44- to 49-year (41% prevalence), and females aged 50- to 54-year (8.7% prevalence) (Fig. 30–4). There is a disproportionately high burden of smoking among males compared to females in countries such as China and India. This is also reflected in the recent estimates of deaths attributable to smoking in China; of the nearly 1 million deaths in 2010, 840,000 were among males in contrast to 130,000 among females.⁶ A high burden of smoking among adolescents and young adults (more than 150 million smokers were 25 years or younger) remains a major concern and challenge.³ During 2012, the prevalence of smoking among 20- to 24-year-old males was above 50% in eastern Europe, Russia, Indonesia, 41% in China, 37% in Japan, 28% in Latin America, 24% in Pakistan, 21% in Australia, 19% in Canada and the United States, and 13% in India.

US Smoking Prevalence and Trends

According to the Behavioral Risk Factor Surveillance System (BRFSS) survey, the prevalence of smoking among United States adults has declined by 25%, with only 17.9% smokers in 2013 as compared to 24.1% smokers in 1998.⁷ There are important differences in the smoking prevalence by states/regions in the United States. Similarly, US population-based survey data (National Health and Nutrition Examination Survey [NHANES]) for 2011-2012 showed a much higher smoking prevalence among people 20 to 49 years of age (23.1%) compared to those 50 years of age and older (16.3%).⁷

There is significant heterogeneity in smoking prevalence by race/ethnicity and gender. Although smoking rates did not differ by gender among Asians residing in the United States; they were slightly different among non-Hispanic white men and women. Furthermore, the smoking rate among Hispanic men (16%) is almost two times higher than it is among Hispanic women (8.3%) (Fig 30–5).

Among various cardiovascular risk factors, however, there has been progress toward reducing smoking rates. Cigarette smoking prevalence is still high and seems to have stagnated recently around 18%. A larger change in smoking prevalence has been seen among US high school students: 15.7% in 2013 compared to 36.4% in 1997.

Health Effects of Smoking

About 5 to 6 million deaths worldwide and about 0.5 million in the United States are attributable to cigarette smoking each year. This estimate is projected to increase to more than 10 million in a few decades.^8,9 In countries such as China, noncommunicable diseases account for 84% of all deaths in 2010 compared to 74% in 1990; sadly, 16.5% of these deaths are attributable to smoking.¹⁰ About one in ten cardiovascular deaths worldwide is still attributed to smoking.¹¹

In 1990, smoking was the third-ranked risk factor after childhood malnutrition and indoor pollution from biofuels for loss of disability-adjusted life years (ie, sum of years of life lost and years lived with disability [DALY]). With improvement in nutrition and clean fuel availability, in 2010 it has become the second most common contributor to loss of DALYs (6.3%; 95% confidence interval, 6.2-7.7).¹² Smoking is the highest contributor to loss of DALYs in males worldwide and both males and females in many developing countries.

A loss of about a decade of life expectancy is estimated because of smoking throughout adulthood among both men and women in various countries, including the United Kingdom, the United States, Japan, and India (Fig. 30–6).⁸ Importantly, people who have smoked cigarettes since early adulthood but stopped at 30, 40, or 50 years of age gain back 10, 9, and 6 years of life expectancy, respectively.⁸ The US societal costs of cigarette smoking per year are around $289 billion; this includes about $151 billion in lost productivity caused by premature deaths and remaining as direct health care costs.⁷

Smoking has been associated with increased and accelerated atherosclerosis and acute plaque rupture and all cardiovascular end points, including myocardial infarction, stroke, and peripheral arterial disease.¹³ While smoking causes incremental and independent risk with other risk factors, such as hypertension and diabetes, on coronary and cerebral vasculature, its prominent role in peripheral vasculature and small-vessel disease has been appreciated: fivefold increased risk of peripheral arterial disease and abdominal aortic aneurysm compared to a 1.5- to 2-fold increased risk of ischemic heart disease and stroke.¹⁴ A linear and independent relationship of smoking duration and intensity has been reported, with an increase in arterial stiffness measured using brachial-ankle pulse wave velocity.¹⁵

The availability of low-cost and high-fidelity genetic analysis has opened new vistas of expansion to our understanding of the genetic basis of smoking behavior, such as finding a few genes localized to the substantia nigra, the brain area associated with reward and addiction, as well as end-organ damage.¹⁶

Cigarette smoking is intimately (Fig. 30–7) involved in development and progression of cardiovascular disease. Cigarette smoke is a mixture of more than 5000 toxic chemicals¹⁷ and 10¹⁵ to 10¹⁷ free radicals.^18,19 It is conventionally divided in two chemically different phases: a tar phase and a gas phase.²⁰ The tar or particulate phase is material that is trapped when the smoke steam is passed through the glass-fiber (cigarette) filter. The cigarette filter retains 99.9% of all particles of greater than 0.1 μm. Nicotine is a major chemical component of the particulate phase of cigarette smoke.²¹ The gas (or vapor) phase consists of the material that passes through the cigarette filter.²¹ The common chemical components of the gas phase include carbon monoxide (CO), acetaldehyde, formaldehyde, acrolein, nitrogen oxides, and carbon dioxide. Both phases are high in reactive oxygen species (ROS).²² Despite the presence of multitude of constituents in both phases, only three constituents (ie, nicotine, CO, and ROS) have been shown to play a role in the initiation and progression of cardiovascular disease.²³

Cigarette smoke affects various cell lines and acts through several pathophysiological mechanisms.^{24,25,26,27,28,29} These mechanisms include, but are not limited to, hemodynamic changes, cardiac remodeling, inflammation, endothelial dysfunction, thrombosis, and changes in glucose and lipid metabolism. The central role in the cigarette smoking–related cardiovascular pathogenesis belongs to oxidative stress. Most of the molecular changes associated with cigarette smoking are triggered by high concentration of oxidizing chemicals inhaled by smokers with the cigarette smoke.

The net effect of various endogenous chemicals from cigarette smoke, such as oxidative free radicals and nicotine, together with inflammatory molecules and endogenous-produced ROS released by activated inflammatory cells, is disruption of cardiovascular homeostasis leading to hemodynamic changes, endothelial dysfunction, inflammation, thrombosis and plaque progression, and abnormalities in lipid and glucose metabolism.¹⁹

Hemodynamics

Nicotine from cigarette smoke is the major culprit for hemodynamic changes caused by cigarette smoking. It is a strong sympathomimetic drug that stimulates release of catecholamines from the adrenal medulla and local sympathetic neurons.²⁵ Via sympathetic stimulation, nicotine leads to an increase in cardiac contractility, acute and chronic increase in heart rate up to 7 to 10 beats per minute,²⁵ and elevation in systolic blood pressure up to 5 to 10 mm Hg from baseline.²³ Interestingly, a large study using mendelian randomization selecting genes associated with smoking heaviness to overcome the observational nature of studies did not find any relationship with hypertension, and it hypothesized that a lower body mass index among smokers may be nullifying adverse effects of smoking on blood pressure.³⁰ The study did find an important relationship between smoking and higher heart rate.

The net result is increased myocardial oxygen demand that can predispose individuals to myocardial ischemia. In long-term smokers with coronary artery disease, cigarette smoking causes coronary vasoconstriction. Smoking-induced coronary vasoconstriction can be prevented with the α-adrenergic blocker phentolamine and potentiated with the β-blocker propranolol, suggesting that the α-adrenergic pathway is the main mechanism of smoke-related cardiac hemodynamic changes.²⁴ CO is another component of cigarette smoke that has been implicated in cigarette smoke–induced hemodynamic changes. By binding to hemoglobin, CO reduces the oxygen-carrying capacity of hemoglobin, resulting in relative hypoxemia and subsequent dilation of coronary arteries.³¹ However, this increase in coronary blood flow is lower than required to keep up with nicotine-mediated increased sympathetic drive toward the heart. A combination of nicotine-induced increased oxygen demands on one side, and CO-associated reduced oxygen availability on the other side, may lower the threshold for angina onset in smokers.³²

Endothelial Dysfunction

Cigarette smoking–induced endothelial dysfunction is an important factor in coronary hemodynamic disturbances and the progression of atherosclerosis. Endothelium is an active regulator of the vascular tone through the release of nitric oxide (NO), prostacyclin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1.²³ Endothelium-dependent vasodilation in coronary and peripheral vessels is diminished in smokers when compared to nonsmokers. The primary mechanism by which smoking leads to vascular and endothelial dysfunction is thought to be suppression of endothelial nitric oxide synthase (eNOS) expression and subsequent decreased bioavailability of NO caused by oxidant chemicals from cigarette smoke.³³ NO is synthesized by eNOS when L-arginine is transformed to L-citrulline in the presence of oxygen, and cofactors such as calmodulin, tetrahydroxybiopterin (BH4), and reduced nicotinamide adenine dinucleotide phosphate.²⁶ The main role of endothelial NO is vasodilation and increased blood flow. However, NO also participates in various vascular functions such as inhibition of platelet aggregation and adhesion, inhibition of leukocyte adhesion, and reduction of smooth muscle proliferation.²⁶ Therefore, deficiency of NO participates in initial phases of plaque formation and atherosclerosis pathogenesis. Biomolecular pathways behind decreased NO production in endothelial cells caused by smoking-related oxidative stress are complex and involve several different components of the cigarette smoke, such as free radicals, ROS, and reactive aldehydes. Free radicals from cigarette smoke oxidize and deplete BH4 in vascular endothelial cells, an important cofactor of eNOS, resulting in uncoupling of eNOS and production of superoxide anions (O₂) instead of NO.²⁶ Another mechanism by which oxidative stress affects endothelium-mediated vasodilation is direct degradation of NO by oxidant chemicals from inhaled cigarette smoke. If vitamin C is administered to smokers, it may reverse endothelial-mediated vasodilation, thus providing additional support that pathogenesis of endothelial dysfunction caused by smoking involves oxygen-derived free radicals from cigarette smoke.³⁴ Chronic application of nicotine decreases the bioavailability of endogenous NO by producing superoxide anions and impairs vasodilation of pial vessels.³⁵

Prothrombotic State

Cigarette smoking has been shown to promote a prothrombotic state through several mechanisms. These mechanisms include alterations in platelet activity as well as alterations in antithrombotic and prothrombotic factors, including fibrinolytic factors and platelet-mediated pathways.^20,36

Once atherosclerotic plaque is formed, its vulnerability for rupture depends on the amount of its lipid content, thickness of the fibrous cap, size of its necrotic core, the rate of plaque progression,³⁷ recruitment of inflammatory cells, and intraplaque hemorrhage.³⁸ Smokers are shown to have higher extracellular content in their plaque³⁹ and lower activity of n-prolyl-4-hydroxylase,⁴⁰ a key enzyme in arterial wall collagen metabolism that could contribute to thinning of the fibrous cap in the atherosclerotic plaque of smokers. Furthermore, cigarette smoking leads to increased activity of matrix metalloproteinases (MMPs) involved in degradation of extracellular matrix proteins within atherosclerotic plaque.⁴¹ Taken together, most of pathologic changes associated with highly vulnerable plaque and plaque rupture³⁷ are potentiated by smoking.³⁸ Moreover, cigarette smoke accelerates biopathological pathways, such as platelet activation and aggregation, that occur after plaque rupture. Platelets isolated from smokers have shown to exhibit an increased spontaneous and stimulated aggregation compared to nonsmokers.⁴² Not only does smoking decrease endothelial NO production, it also leads to diminished bioavailability of platelet-derived NO and decreased platelet sensitivity to NO.^28,29,43 Both mechanisms promote platelet activation and adhesion, making smokers’ platelets more thrombogenic. In addition to impaired NO release from platelets, cigarette smoke also triggers the release of thromboxane A₂, a potent vasoconstrictor, and inhibits coronary endothelial release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation.²⁴ Cigarette smoking exposure has also been related to different clot dynamics that are more resistant to thrombolysis compared with clots of nonsmokers.³⁸ An increased level of circulating von Willebrand factor, an important ligand of platelet binding, has been demonstrated in smokers compared to nonsmokers.^44,45 Furthermore, cigarette smoking is associated with increased concentration of fibrinogen^46,47; increased expression of tissue factor that contributes to thrombosis after plaque rupture⁴⁸; and reduced basal production of tPA,³³ which is an essential regulator of plasminogen-plasmin transformation. Lower level of activated plasmin leads to diminished lysis of fibrin and propagation of thrombus. As previously mentioned, CO from cigarette smoke causes relative hypoxemia, which compensatory leads to increase in the number (and mass) of erythrocytes in the circulation which increases blood viscosity.³¹ An increased blood viscosity may mildly increase predisposition to thrombosis and atherosclerotic plaque formation.

Proinflammatory Effects

Chronic vascular inflammation mediated by cigarette smoking may play an important role in the progression of atherosclerosis.⁴⁹ The exact molecular-pathogenic mechanisms by which smoking induces vascular inflammation are not completely established. Nonetheless, the role of several proinflammatory cytokines as well as activation and interaction between leukocytes and endothelial cells is well recognized in this process. Smoking increases the peripheral leukocyte count by 20% to 25%⁵⁰ and promotes leukocyte adhesion to endothelial cells within the blood vessel wall, starting an initial inflammatory step in atherosclerosis.⁵¹ One of the proposed biochemical pathways that links cigarette smoking to vascular inflammation is enhanced expression of soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin, which leads to increased leukocyte-endothelial cell interaction.⁵² Increased levels of multiple proinflammatory markers have been associated with smoke exposure; these include C-reactive protein, cytokines such as the interleukins (ILs) IL-1β and IL-6, and tumor necrosis factor-α (TNF-α).²⁷ It has been shown that cigarette smoking induces release of proinflammatory cytokines in macrophages⁵³ and lymphocytes by activation of NF-κB and post-translational modification of histone deacetylase.⁴⁹ Free radicals in cigarette smoke in synergy with inflammatory cytokines (IL-1β and TNF-α), present in the serum of smokers, increase the activity of nicotinamide adenine dinucleotide phosphate oxidase within endothelial cells, leading to generation of superoxide anion and induction of cyclooxygenase-2 (COX-2) expression via the p38 mitogen-activated protein kinase (MAPK)/Akt pathway.²⁷ COX-2 induces production of prostanoids, which diffuse toward endothelial cells and attenuate vasodilation by decreasing the activity of soluble guanylate cyclase and production of cyclic guanosine monophosphate (cGMP).⁵⁴

Cardiac Remodeling

Smoking has been associated with left ventricular hypertrophy and left atrial enlargement in animal models.^55,56 Smokers exhibit higher level of activation of MMPs that degrade elastin and collagen in the extracellular matrix. Within myocardium, increased MMP activity leads to breakdown of the supporting fibrillary collagen and ventricular wall thinning.⁵⁷ Smoke-related ROS stimulate fibroblasts to proliferate and induce myocardial cell apoptosis, leading to cardiac fibrosis and remodeling.⁵⁸ Cigarette smoking–induced cardiac remodeling has also been linked to increased activation of MAPKs by either norepinephrine (NE), which is increased in smokers’ serum, or directly by free radicals from cigarette smoke.⁵⁷ Within the heart, NE can lead to myocyte hypertrophy by binding to α₁-adrenergic receptors or apoptosis by binding to β₁-adrenergic receptors.⁵⁹ Nicotine increases the expression of angiotensin-converting enzyme and production of angiotensin II,⁶⁰ which has an important role in cardiac remodeling through stimulation of hypertrophic gene program within cardiomyocytes as well as through stimulation of fibroblast proliferation within myocardium.

Lipid Metabolism

Multiple studies have demonstrated that cigarette smoking enhances atherosclerosis at least in part by altering the lipid profile. Cigarette smoking lowers serum high-density lipoprotein (HDL), but it increases triglycerides, cholesterol, and low-density lipoprotein (LDL).⁶¹ More importantly, smokers have higher levels of oxidized LDL, which is involved in pathogenesis of atherosclerosis.⁶² Exposure of human plasma to cigarette smoke causes oxidative modification of plasma LDL that is actively taken up by the macrophages and forms foam cells in the culture.⁶² In addition to this, smoking increases hepatic lipase activity, which leads to production of small dense LDLc and small dense HDLc. First, LDLc has toxic effects on endothelium and promotes release of even more ROS. Second, HDLc has no protective antiatherogenic effects, which are normally attributed to HDL.⁶³ A nicotine-induced increase in circulating catecholamines induces lipolysis and release of plasma-free fatty acids.^23,64

Glucose Metabolism

Cigarette smoking increases the risk of development of diabetes mellitus type 2.⁶⁵ A dose-response relationship has been found between the smoking and the incidence of diabetes mellitus in both men and women.⁶⁶ Data from the Cancer Prevention Study have shown that there is a 45% higher diabetes rate among smokers than among men who had never smoked. Higher levels of HbA1C have been found in smokers with diabetes as compared to nonsmokers with diabetes. Smoking also increases requirements for insulin and causes insulin resistance in nondiabetics.⁶⁷ Studies have also shown increased risk of microvascular complications of diabetes such as diabetic neuropathy and faster progression of renal disease.⁶⁸ There has been a debate about whether possible weight gain associated with quitting smoking is associated with increased risk, too.⁶⁹ Although confounding in observational studies makes it difficult to test this relationship further, the increased risk of weight gain after cessation ameliorates with duration of smoking cessation.⁶⁹ The pathogenesis of smoking and glucose metabolism is not well understood, but nicotine appears to have central role in this process.^19,70 Nicotine stimulates cathecholamine release from the adrenal medulla and sympathetic nervous system, which may lead to insulin resistance. It also increases the release of corticosteroids, which are known hyperglycemic hormone.²³

Despite early warnings seen in the Surgeon General’s report in 1972, awareness about the adverse health implications of secondhand exposure to cigarette smoke gained significant momentum around early 2000, from multiple epidemiological studies supporting it.⁷¹ Contrary to intuition, the adverse effect of brief secondhand smoke exposure is significant.⁷² A higher coronary calcium score has been reported among never smokers who are exposed to secondhand smoke.⁷³ A higher amount of ammonia, nicotine, and other carcinogens is released in sidestream smoke.⁷⁴ These studies have shaped the policies restricting and banning smoking in public places and gained public support for such efforts. According to NHANES, the secondhand smoke exposure among nonsmoking adults in the United States has decreased from 37.6% in 2005-2008 to 25.5% in 2009-2012.

Exposure to cigarette smoke from parental smoking during childhood was associated with a higher risk of developing carotid atherosclerotic plaques and higher carotid intima media thickness during adulthood, even 25 years after last exposure among Cardiovascular Risk in Young Finns Study participants.^75,76 An improvement in respiratory health, as measured by symptoms, spirometry measures, and markers of inflammation, was seen among bar workers after passage of smoke-free legislation in Scotland.⁷⁷ Importantly, a decrease in cardiovascular morbidity and mortality has been seen immediately following workplace ban of cigarette smoking even among people who never smoked.⁷⁸

Invented in the early 2000s by a Chinese pharmaceutical company and patented in 2004, e-cigarettes deliver a nicotine-containing vapor when a solution of nicotine with humectant solution (glycerol or propylene glycol) and flavoring is heated by a battery-powered atomizer (Fig. 30–8).⁷⁹ Their purported use, also reflected in the US patent application, is to be a substitute for quitting smoking.

Currently, there are no appropriately powered randomized controlled trials with e-cigarettes examining their efficacy on smoking cessation.⁸⁰ Also, studies looking at long-term safety of e-cigarettes are lacking. Among current smokers who are motivated to quit smoking, there was modest success (7.3% abstinence at 6 months) with nicotine e-cigarettes, although this was no different than with using the nicotine patch (5.8% abstinence at 6 months).⁸¹ However, when using the population-based studies in the absence of good randomized controlled trials, e-cigarette users are associated with a 28% lower relative odds of quitting compared to nonusers.⁸² There were no meaningful individual side effects reported with this study with nicotine e-cigarettes over the short duration of follow-up.

There are growing concerns about their use due to absence of studies showing either safety or efficacy. Importantly, e-cigarettes can circumvent the regulations created to control active smoking and second hand smoke exposure, such as taxation, advertisement bans, and ban in smoke-free zones. Their potential for use among adolescents as bait and switch to regular cigarettes, and their continued use among current smokers using them with the intent to quit, remain serious concerns. For instance, among high school students, use of e-cigarettes tripled in 2014 to 2 million (13.4%) from 0.67 million (4.5%) in year 2013.⁸³ Because of a lack of evidence supporting the safety or efficacy of e-cigarettes at this time, e-cigarettes companies cannot advertise them as an alternative for smoking cessation or for therapeutic purposes in the United States. On the one hand, sale of nicotine-containing e-cigarettes is unauthorized in countries such as Canada, and they have been banned in Brazil, Norway, and Singapore.⁸⁰ On the other hand, large tobacco companies have been acquiring and/or launching e-cigarette companies/subsidiaries, and there is growing advertisement and increasing public awareness about their presence.⁸⁰

The details of various pharmacological and nonpharmacological options for quitting smoking are discussed in Chapter 31. The majority of the hospitals in the United States have met the Joint Commission of Accreditation of Healthcare Organizations (JCAHO) smoking ban standards.⁸⁴ Although it is pleasing to note that smoking rates among physicians are less than 2%, a high smoking rate of 25% among licensed practical nurses needs action in the health care settings.⁸⁵ Addition of smoking cessation support at the population level has been shown to improve cessation success to 20% per year, compared to 5% in an unaided setting.⁸⁶ In a retrospective analysis of over 2000 patients who underwent percutaneous coronary intervention (PCI) from 1999 to 2009 at Olmsted County, Minnesota, smoking cessation rates at 6 to 12 months were around 50% and did not change over a decade.⁸⁷ The odds of cessation were 2.6 times higher among those who had presented with myocardial infarction and three times among those who participated in cardiac rehabilitation, and cessation was associated with better prognosis.⁸⁷ Similarly, a cessation rate of about 60% was seen in Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial participants and those who continued to smoke had 1.8 times higher risk of death/myocardial infarction/stroke as compared to those who had quit.⁸⁸ It is a big challenge and opportunity for us that less than one in three of the current smokers hospitalized with acute coronary syndrome (ACS) remains abstinent following discharge. Smokers have worse outcomes than nonsmokers after PCI, and those who quit smoking after PCI had less anginal episodes at 1-year follow-up than those who continued.⁸⁹ In a recent study of patients presenting with ACS, varenicline was associated with an abstinence rate of 47.3% versus 32.5% in the placebo group at 6 months.⁹⁰ At the same time, it is sobering to see that in non-ACS patients recruited from community and a long-term cohort in Wisconsin, with lower number of average cigarettes smoked per day than previous studies, there was no difference in smoking cessation with randomization to varenicline versus nicotine patch versus combination nicotine replacement, with a cessation rate at 1 year of about 25%.⁹¹ Not offering smoking cessation counseling to those in need of help may be considered downright unethical and should be the focus of every clinical encounter.⁹² Individualized treatments based on genetics or markers of metabolism may be more effective and safe; further studies are needed in this direction.⁹³ Individual level incentives to quit smoking have been shown to have a higher rate of success than usual care, and should be considered by employers and health insurance companies.⁹⁴ At the level of health care systems, advice from health care workers, use of technology with automated text-based reminders, and individual and group counseling should be strongly considered. The cost-effectiveness of such low-cost interventions needs to be examined.

The Framework Convention on Tobacco Control (FCTC) of the World Health Organization (WHO) created in 2004 has been associated with a steady progress in many countries. However, the goal of a tobacco-free world by the year 2040, with a smoking prevalence rate below 5% without prohibition, requires a turbo-charged approach involving the WHO, United Nations, and national and global investments.⁹⁵

To this effect, the most common and successful step that has been used is tobacco taxes (Fig. 30–9). About 20% decrease in cigarette consumption has been reported with a 50% increase in inflation-adjusted tobacco price⁹⁶ (see Fig. 30–9). Tobacco taxes have proven to be more effective among younger adults, and among poor or less educated groups.⁸ However, a rapid growth in income and purchasing power parity in developing countries and availability of low-priced alternatives, such as “bidis”, is a challenge. The lower excise tax in the low-income countries makes cigarettes cheaper than in developed countries. However, cigarettes may be cheaper in developing countries after due adjustment for purchasing power parity and may replace “bidis” with increase in purchasing power in countries such as India.⁸ Additionally, organized smuggling of cigarettes with a raise in excise remains another challenge that will require stricter tax administration.⁸

Profits from tobacco manufacturing exceeded 50 billion US dollars in 2012,⁹⁷ and beyond industry’s lobbying effort for keeping a check on excise taxes, the major portal for more than half a century has been influence and use of mass media. Although a complete or partial ban on tobacco advertisements remains a strong tool to reduce smoking rates, comprehensive bans may be needed to prevent the industry's use of media for advertisement.⁸

Legislative developments to protect individuals from secondhand smoke, research to continue to study the influence of various interventions in reduction in smoking rates, and understanding the counterforces such as smoking industry and human behavior will be important. Separation and empowerment of regulatory bodies in stages where manufacturing is state-owned-such as in China, the largest cultivator of tobacco in the world with doubling of production since 1978 will remain a difficult and critical task ahead.¹⁰ Large-scale philanthropy and international organizations, such as WHO, have played important critical roles to control/reduce rapid rise in smoking, with programs such as “towards a smoke free China” supported by Bloomberg Initiative and pressures on Chinese delegation by WHO FCTC.¹⁰ Focus on high “growth markets” such as Europe, the Middle East, and Africa will be equally important while focusing on China, where 40% of the world cigarette is consumed. Beyond policy changes, simple low-cost and scalable interventions such as those involving community health care workers, and use of mobile health platforms such as mobile phone texts, need to be examined for efficacy, process evaluation, and cost-effectiveness.⁸⁶