Cardiovascular effects of nicotine

INTRODUCTION — Nicotine is a naturally occurring alkaloid found primarily in tobacco. It is most commonly absorbed from cigarette smoke but is also available from smokeless tobacco (snuff, chewing tobacco), pipe and cigar tobacco, waterpipe tobacco, electronic cigarettes (e-cigarettes), heated tobacco products, and a variety of smoking cessation medications. Nicotine is also present in some insecticides, which may be a source of accidental or intentional poisoning.

This topic will review the cardiovascular effects of nicotine. The cardiovascular effects of secondhand smoke are reviewed elsewhere. (See "Secondhand smoke exposure: Effects in adults", section on 'Cardiovascular disease and stroke' and "Secondhand smoke exposure: Effects in children", section on 'Cardiovascular disease'.)

PHARMACOKINETICS — The peak plasma nicotine concentration during smoking is 10 to 50 ng/mL with about 5 percent being protein-bound. The half-life averages two hours. Approximately 80 to 90 percent of nicotine is metabolized by lung, liver, and kidney; the principal metabolite is cotinine, which has a plasma concentration that is 10-fold higher than nicotine. Cotinine has a half-life of 15 to 20 hours and is used as a biomarker of nicotine exposure [1].

Approximately 17 percent of nicotine is excreted unchanged in the urine. The rate of urinary excretion is pH-dependent, decreasing in an alkaline urine. Nicotine is found in the milk of lactating women with concentrations that parallel those of plasma.

GENETIC CONSIDERATIONS

Cytochrome P450 2A6 gene — Interindividual variability in the plasma concentrations of nicotine and cotinine is considerable among individuals taking in similar doses of nicotine. Nicotine is metabolized primarily by the liver enzyme cytochrome P450 2A6 (CYP2A6). A number of CYP2A6 gene variants have been described, several of which are associated with slower metabolism of nicotine. Some individuals have been described with CYP2A6 gene deletions who metabolize nicotine unusually slowly and generate little cotinine. Genetically slow metabolizers tend to smoke fewer cigarettes per day and are able to quit smoking more easily than fast metabolizers [2].

Nicotinic receptor genes — Nicotine acts on nicotinic cholinergic receptors, which are comprised of five subunits. The receptors containing alpha 4 and beta 2 subunits mediate nicotine addiction. The alpha 3 beta 4 containing receptors mediate cardiovascular effects of nicotine. Specific cholinergic nicotinic receptor subunit (CHRN) genes, which encode the nicotinic acetylcholine receptor subunits, that are associated with an increased risk for nicotine dependence, heaviness of smoking, and smoking-related diseases such as lung cancer, peripheral vascular disease, and chronic obstructive pulmonary disease have been identified [3,4]. Single nucleotide polymorphisms covering the complete family of 16 CHRN genes have been assessed in nicotine-dependent cases and non-dependent controls [4]. A significant association between gene loci and nicotine dependence (two distinct loci in the CHRNA5-CHRNA3-CHRNB4 gene cluster, one locus in the CHRNB3-CHRNA6 gene cluster, and a fourth in the CHRND-CHRNG gene cluster) have been described. Each of these appears to influence the transition from smoking to nicotine dependence.

DRUG INTERACTIONS — Cigarette smoking interacts with a number of drugs. Most interactions are caused by the effects of combustion products (such as polycyclic aromatic hydrocarbons) that induce drug metabolism. Although some are mediated by actions of nicotine, the latter are primarily related to sympathetic nervous stimulation and catecholamine release. The following effects may occur with the cessation of smoking [5]:

●There is de-induction of hepatic enzymes which may require a reduction in dose of certain drugs including caffeine, clozapine, erlotinib, flecainide, fluvoxamine, imipramine, irinotecan, olanzapine, pentazocine, propranolol, tacrine, and theophylline [5,6].

●There is an increase in absorption of subcutaneous insulin which may require a decrease in dose.

CARDIOVASCULAR EFFECTS — Nicotine is a ganglionic and central nervous system stimulant, the actions of which are mediated via nicotinic cholinergic receptors. Nicotine binds to nicotinic cholinergic receptors that are located in the brain, autonomic ganglia, the adrenal glands, and at neuromuscular junctions [5]. These receptors, which demonstrate diversity in subunit structure, function, and distribution within the nervous system, presumably mediate the complex actions of nicotine described in tobacco users.

The major cardiovascular effect of nicotine is sympathetic neural stimulation [7,8]. Central nervous system-mediated sympathetic stimulation can occur through activation of peripheral chemoreceptors, a direct effect on the brainstem, and effects on caudal portions of the spinal cord. The site that appears to be most sensitive to low levels of nicotine is the carotid chemoreceptor. Peripheral mechanisms include catecholamine release from the adrenal and direct release or enhancement of release of catecholamines from vascular nerve endings.

Nicotine also enhances the release of various neurotransmitters, including epinephrine, norepinephrine, dopamine, acetylcholine, serotonin, vasopressin, glutamate, nitric oxide, calcitonin growth-related peptide, and beta-endorphin [9]. Some of these may contribute to the effects of nicotine on blood vessels.

Biphasic actions are observed depending upon the dose administered. The main effect of nicotine in small doses is stimulation of all autonomic ganglia; with larger doses, initial stimulation is followed by blockade of transmission. Biphasic effects are also evident in the adrenal medulla; discharge of catecholamines occurs with small doses, whereas prevention of catecholamines release is seen with higher doses as a response to splanchnic nerve stimulation.

SMOKING AND CARDIOVASCULAR RISK — Smoking is an important and established risk for myocardial infarction and other coronary events, including angina pectoris, as well as sudden cardiac death, restenosis after coronary artery stenting or bypass surgery, stroke, aortic aneurysm, peripheral vascular disease, heart failure, and atrial fibrillation [10-12]. The mechanisms by which cigarette smoking accelerates atherosclerosis and precipitates acute coronary events are complex. The main responsible constituents are combustion products, including oxidizing chemicals, acrolein, butadiene, metals (such as cadmium), polycyclic aromatic hydrocarbons, particulates, and carbon monoxide. Oxidizing chemicals increase free radicals, increase lipid peroxidation, and contribute to several potential mechanisms of cardiovascular disease, including inflammation, endothelial dysfunction, oxidation of low-density lipoprotein (LDL), and platelet activation.

Nicotine may also contribute to acute coronary events. There are a number of ways in which nicotine can affect the cardiovascular system to increase the risk of atherosclerosis and cardiovascular events such as myocardial infarction.

Increased myocardial work — Smoking produces a transient rise in blood pressure of approximately 5 to 10 mmHg [13-15]. This effect is most prominent with the first cigarette of the day in habitual smokers. The hemodynamic effects of cigarette smoking are mediated by nicotine which also increases heart rate up to 10 to 20 beats per minute after an individual cigarette and on average seven beats per minute throughout the day [15] (see "Smoking and hypertension"). As a result of the increased myocardial work, myocardial oxygen demands and coronary artery blood flow increase. However, myocardial ischemia may ensue in patients with coronary disease, particularly in the presence of underlying coronary vascular disease when the coronary vasoconstrictive effect of smoking is superimposed. (See 'Coronary vasoconstriction' below.)

Despite these acute effects, habitual smokers generally have lower blood pressures than nonsmokers [16,17]. This is seen when blood pressure is measured after a period of nonsmoking, as is usually the case when a smoker is seen in the office or hospital. Ambulatory blood pressure recording shows that smoking increases blood pressure. The mild reduction in blood pressure in smokers may be related to reduced blood volume that is seen as a consequence of nicotine-mediated vasoconstriction and possibly decreased body weight, which reflects a nicotine-induced stimulation of energy expenditure [18]. In addition, a vasodilator effect of cotinine, the major metabolite of nicotine, also may contribute to the hypotensive response [19].

Coronary vasoconstriction — In subjects with coronary disease, Doppler measurements of coronary blood flow demonstrate that cigarette smoking constricts epicardial arteries, increases total coronary vascular resistance, and reduces coronary blood flow [20-23]. (See "Clinical use of coronary artery pressure flow measurements".) Smoking also reduces coronary vasodilatory flow reserve.

Smoking has also been associated with an increased risk of vasospastic angina and poorer response of recurrent coronary spasm to vasodilator medication. Smoking can produce acute vasospasm during angiography [22,24]. These effects appear to be mediated by increased catecholamines since the acute increase in coronary vascular resistance can be minimized by alpha-adrenergic blockers [23]. (See "Vasospastic angina".)

Cerebral circulation — The effects of acute smoking and nicotine on the cerebral circulation are controversial. In an animal model, smoking a single cigarette produced a biphasic effect on cerebral arteriolar tone, resulting in both constriction and dilation; repeated smoking attenuated vasodilation [25]. Vasodilatation is most likely an effect of nicotine, mediated, in part, by sympathetic activation, nitric oxide production, and potassium channel activation. Vasoconstriction is partially due to release of thromboxane A2 induced by cigarette smoke.

Secondary erythrocytosis is a recognized consequence of smoking that contributes to increased venous and arterial thrombosis [26,27]. Carbon monoxide exposure from cigar and cigarette smoke can result in elevated red-cell volume or a reduced plasma volume (or both) [28]. These may impact the risk of stroke, although data are lacking.

Hypercoagulable state — Cigarette smoking produces a hypercoagulable state associated with platelet activation, increased red blood cell mass, and increased fibrinogen levels [29-32]. Individuals who smoke have increased platelet aggregation, primarily induced by oxidants in smoke and possibly also promoted by elevated catecholamine levels [32]. Fibrinogen, identified in the Framingham study as a predictor of coronary events, is increased and, in association with elevated red blood cell mass (a consequence of carbon monoxide-mediated functional hypoxemia), will increase blood viscosity [29]. Upon smoking cessation, plasma fibrinogen levels decrease; however, the full normalization may take several years.

Thrombosis is a major factor in acute vascular events in smokers [33,34]. Cigarette smoking increases the risk of acute myocardial infarction and sudden death much to a greater extent than it increases the risk of angina pectoris. Support for a role for thrombosis comes from studies showing that smokers who died with acute myocardial infarction were more likely to have thrombotic occlusion at autopsy, and smokers with acute myocardial infarction have more extensive thrombosis and less severe underlying coronary artery disease compared with non-smokers. While oxidant chemicals are thought to be most responsible for smoking-induced thrombosis [35,36], nicotine has been shown to increase the endothelial cell production of plasminogen activator inhibitor-1, which is a major regulator of fibrinolysis [37].

Further supporting the role of thrombosis are observations from several studies that smokers who receive a thrombolytic agent for an acute myocardial infarction have a better outcome than nonsmokers [35,38-41].

●In the Thrombolysis in Myocardial Infarction (TIMI) II trial, the mortality at 42 days was lower in current and ex-smokers compared with nonsmokers (3.6 and 4.8 versus 8.0 percent, p<0.001) [39].

●The largest trial to evaluate the impact of cigarette smoking on outcome was the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) I trial, which included 11,975 nonsmokers, 11,117 ex-smokers, and 17,507 current smokers [35]. Non-smokers had a significantly higher 30-day mortality than smokers (10.3 versus 4.0 percent). The lower mortality in smokers could be explained by younger age and less severe underlying coronary artery disease, both consistent with thrombosis playing a major role in acute myocardial infarction. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)

Also supporting the hypothesis that thrombosis is a major mechanism of smoking-related coronary events is the observation that smokers who continue to smoke after thrombolysis or angioplasty have a substantially increased risk of reinfarction or reocclusion [42,43].

Inflammation — Cigarette smoking results in a chronic inflammatory state and evidence of increased leukocyte count, C-reactive protein, and acute phase reactants such as fibrinogen. Smoking also activates monocytes and enhances recruitment and adhesion of leukocytes to blood vessel walls, an integral step in vascular inflammation.

Lipid metabolism — Cigarette smoking has an adverse effect on the lipid profile (see "Secondary causes of dyslipidemia"). While the mechanisms of this effect are not fully understood, catecholamine-mediated increases in adipocyte lipolysis and increased re-esterification of free fatty acids by the liver are thought to contribute. Compared with nonsmokers, smokers have higher serum levels of triglycerides and lower levels of high-density lipoprotein (HDL) cholesterol [44]. In the screening phase of the Bezafibrate Infarction Prevention Study Group, for example, the mean serum HDL-cholesterol level was 39.6 mg/dL (1.03 mmol/L) in nonsmokers, 37.2 mg/dL (0.97 mmol/L) in former smokers, and 35 mg/dL (0.91 mmol/L) in current smokers of two packs per day or more [45].

Smokers may also have higher levels of oxidized LDL, which are believed to promote atherogenesis [46,47]. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)

The lipid changes induced by smoking are fully reversible within one to two months after smoking cessation [48,49]. It remains unclear, however, whether these changes contribute to the increased risk of coronary disease. Data from the Lipid Research Clinics trial in which almost 7500 adults in 10 North American populations were followed for an average of 8.5 years, show the adverse effect of smoking on coronary disease appeared to be independent of LDL and HDL cholesterol [50].

Smoking and secondhand smoke exposure also causes an increase in arterial lipid lesions [51].

Endothelial dysfunction — Cigarette smoking produces endothelial damage and impairs flow-mediated, endothelium-dependent arterial vasodilation both in coronary and peripheral arteries [52], an effect that is partly reversible after smoking cessation [53]. By contrast, endothelium-independent vasodilation is preserved [54] (see "Coronary endothelial dysfunction: Clinical aspects"). Oxidizing chemicals and nicotine appear to be responsible for endothelial dysfunction.

Smokers, particularly those with coronary atherosclerosis, have a paradoxical response to acetylcholine in which vasoconstriction rather than normal vasodilation is seen [55]. This abnormality appears to result from impaired release of endothelium-derived relaxing factor, nitric oxide [56].

Nitric oxide release has potentially beneficial cardiovascular effects including vasodilation and reductions in platelet aggregation, smooth muscle cell proliferation, and adhesion of monocytes to the endothelium. Cigarette smoking impairs release of nitric oxide, which could contribute to both acute cardiovascular events and accelerated atherogenesis.

Carotid artery intimal-medial thickness and cigarette smoking — The Atherosclerosis Risk in Communities Study (ARIC) evaluated the association between carotid artery wall thickness and active and passive cigarette smoking in 12,953 adults, aged 45 to 65 years [57]. Increased carotid intimal-media thickness (C-IMT) was noted with a progressive increase in frequency in each of the following groups: never smokers reporting no exposure to environmental tobacco smoke (ETS), never smokers reporting weekly exposure to ETS or "passive smoking" of at least one hour, past smokers, and current smokers.

Similar findings were noted in an observational study of nearly 1800 patients attending a lipid clinic [58].

OTHER NICOTINE PRODUCTS AND CARDIOVASCULAR RISK — Various other forms of nicotine, including smokeless tobacco (eg, oral snuff or chewing tobacco) and electronic cigarettes (e-cigarettes) are used widely [59-62]. Nicotine is the principal alkaloid absorbed through the mucosa from smokeless tobacco products [63,64]. The amount of total and free nicotine varies substantially among products [65]. (See "Patterns of tobacco use", section on 'Smokeless tobacco' and "Vaping and e-cigarettes", section on 'Prevalence'.)

Smokeless tobacco

Hypertension — Data from the majority of smokeless tobacco studies do not support an increase in the incidence or prevalence of hypertension [66-68].

The proposed mechanisms by which smokeless tobacco might increase blood pressure are as follows. Some smokeless tobacco products, such as loose snuff and chewing tobacco, contain large amounts of sodium, part of the sodium bicarbonate alkaline buffer, enhancing nicotine absorption. The sodium load (30 to 40 excess mEq per day) could potentially aggravate hypertension and heart failure [69]. Some smokeless tobacco products contain significant amounts of licorice. Glycyrrhizinic acid, an active chemical in licorice, has mineralocorticoid activity, which may potentiate hypertension and potassium wasting [70].

Among “one-time” users of snuff or chewing tobacco, transient (30 to 60 minutes) increases in blood pressure and heart rate have been observed due to effects of nicotine [71]. Moreover, in data from studies in subjects with a history of tobacco use, the acute effects of smokeless tobacco products include an increase in heart rate and no change or transient increases in blood pressure. A crossover study examined circadian blood pressure and heart rate among cigarette smokers, users of oral snuff, users of chewing tobacco, and nicotine non-users [71]. The nicotine-containing products (cigarettes, oral snuff, and chewing tobacco) were associated with significant increases in heart rate but no change in blood pressure.

Mortality and myocardial infarction — Population-based studies have reached differing conclusions about whether smokeless tobacco use is associated with increased risks for nonfatal and fatal coronary heart disease [72]. The first National Health and Nutrition Examination Survey (NHANES) Epidemiological Follow-up Study found no association between smokeless tobacco products and all-cause or cardiovascular mortality [73]. On the other hand, in two other United States studies, Cancer Prevention Study I (CPS-I) and the CPS-II, current smokeless tobacco use was associated with an increased hazard ratio (HR) for all-cause mortality as well as mortality related to coronary and cerebrovascular disease [74]. Some have minimized findings related to CPS-I because the data were collected between 1959 and 1972 when there was a greater prevalence of cardiovascular disease [75].

The overall estimated risk of cardiovascular disease in smokeless tobacco users also differs in two meta-analyses that include reports from Sweden and the United States [76,77]. One report found that smokeless tobacco use was not associated with a significantly increased risk of heart disease (RR 1.12, 95% CI: 0.99 to 1.27) [76]. However, in the other report, ever-use of smokeless tobacco products was associated with an increased risk of fatal myocardial infarction (RR of 1.13, 95% CI: 1.06 to 1.21) and fatal stroke (RR of 1.4, 95% CI: 1.28 to 1.54) [77]. The increased risk was attributed to the inclusion of the United States studies, which found an increased HR for all-cause coronary and cerebrovascular disease.

Data derived from the INTERHEART study, a 52 country international study, showed that chewing tobacco alone was associated with significantly increased risk for myocardial infarction (OR 2.23; 95% CI: 1.41 to 3.52) compared with those who never used tobacco [78]. Furthermore, smokers who also used chewing tobacco had the highest risk for acute myocardial infarction. Differences in cardiovascular events in different countries is most likely due to difference in the smokeless tobacco products.

Stroke — Data from two studies (one from the United States and one from Sweden) suggest that smokeless tobacco product use is associated with a slight increase in the risk of stroke mortality [74,79]. The report from Sweden is supported by two meta-analyses that found smokeless tobacco products were associated with an increased risk of fatal stroke [76,77]. The methodology of these reports has been scrutinized since the smokeless tobacco product users had poorer lifestyle characteristics (eg, tended to be older, less educated, and consumed more dietary fat and fewer vegetables than nonusers), suggesting the potential for other unidentified confounding factors. Additional research is needed regarding smokeless tobacco products to assess the potential relationship between smokeless tobacco use and stroke risk in the United States population.

Electronic cigarettes — There are little empirical data on cardiovascular events in e-cigarette users. With the exception of nicotine, potentially toxic compounds are present in lower concentrations in e-cigarette aerosol compared with cigarette smoke, and most cardiovascular effects are consistent with sympathomimetic effects of nicotine. (See "Vaping and e-cigarettes", section on 'Adverse health effects'.)

A small trial investigating efficacy of e-cigarettes as a tobacco-cessation tool found similar rates of adverse events at six months in 289 e-cigarette users compared with 73 placebo e-cigarette users (47 versus 49 percent) [80]. However, a small cross-sectional case-control study showed that e-cigarette users had heart rate variability findings and plasma findings that may be associated with cardiovascular risk [81].

In another trial in which 33 healthy volunteers used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control on different days, cardiac sympathetic nerve activity as measured by heart rate variability was attributed to the inhaled nicotine rather than the non-nicotine constituents [82].

Heated tobacco products — Heat-not-burn products are battery-powered devices that heat disposable tobacco sticks, but at lower temperatures than cigarettes, therefore avoiding generation of most combustion products. There is limited information on the health effects of heated tobacco products. (See "Patterns of tobacco use", section on 'Heat-not-burn tobacco products'.)

In a study of over five million adult males in South Korea, persons who were cigarette smokers had greater risk of a cardiovascular disease event (hospitalization for coronary heart disease or stroke) than those who quit and then switched to a noncombustible nicotine or tobacco product (NNTP; adjusted hazard ratio [HR] 0.81, 95% CI 0.78-0.84) [83]. In this study population, NNTPs were estimated to be largely heated tobacco products rather than nicotine vaping products. Compared with smokers who quit without NNTP use, smokers who quit and then use NNTPs may be at higher future CVD risk.

MECHANISM OF ACTION OF SECONDHAND SMOKE — Secondhand smoke exposure is associated with an increased risk of acute coronary events, including acute myocardial infarction [84]. The effects of secondhand smoke exposure on the number and function of endothelial progenitor cells, plasma vascular endothelial growth factor, circulating endothelial microparticles, and flow-mediated vasodilation were evaluated for 24 hours after brief exposure of real-world levels of smoke to 10 normal volunteers [85]. Brief exposure not only causes acute vascular injury, as indicated by endothelial dysfunction and microparticle generation, but also leads to sustained changes of the vascular repair system with a mobilization of dysfunctional endothelial progenitor cells. Mechanistically, these effects are linked to an impairment in the function of or no production of endothelial progenitor cells. Taken together, these findings provide evidence that even a very short period of passive smoke exposure has strong, persistent vascular consequences.

Secondhand smoke may harm the vasculature not only by directly injuring the vascular endothelium but also by interfering with the vascular repair system, which may lead to chronic damage with recurrent exposures. These results indicate that involuntary secondhand smoke exposure constitutes a risk even at low levels [85]. The cardiovascular effects of secondhand smoke are reviewed in detail elsewhere. (See "Secondhand smoke exposure: Effects in adults", section on 'Cardiovascular disease and stroke' and "Secondhand smoke exposure: Effects in children", section on 'Cardiovascular disease'.)

INSULIN RESISTANCE — Cigarette smoking increases the risk of type 2 diabetes and insulin resistance [86]. Patients with insulin resistance have an increased risk of coronary disease (see "Metabolic syndrome (insulin resistance syndrome or syndrome X)"). Nicotine, most likely mediated via catecholamine release, contributes to the development of insulin resistance. This was illustrated in one study of 40 non-obese middle-aged men which found that the long-term use of nicotine-containing chewing gum was associated with the presence of insulin resistance and hyperinsulinemia [87]. There was a correlation between the extent of nicotine use and the degree of insulin resistance.

SAFETY OF NICOTINE REPLACEMENT THERAPY — The risks associated with nicotine replacement therapy in patients with cardiac disease have been of concern in the past. Smokers and ex-smokers are at increased risk for acute myocardial infarction and other coronary events; however, establishing a causal relation between nicotine replacement and cardiovascular events is problematic since acute cardiovascular events are common in smokers and cardiac risk persists beyond the time of smoking cessation.

Nicotine replacement delivered by any mechanism, including gum, lozenges, nasal spray, and transdermal patches has effects qualitatively comparable to cigarette smoking with respect to increasing myocardial work. However, the risk of smoking while using nicotine replacement therapy appears no greater than the risk of smoking alone [5,88]. The apparent absence of added risk may reflect both the relatively flat dose-response relation for nicotine and the fact that, even with continued smoking during nicotine replacement, the total intake is modest compared with usual smoking because the amount of cigarettes smoked is usually less during nicotine replacement [88].

The Lung Health Study cohort of 5887 middle-aged smokers with chronic obstructive pulmonary disease who were followed for five years compared smokers with those who quit with or without nicotine gum [89]. There was no increase in hospital admission for cardiovascular events with nicotine gum treatment, regardless of the dose used. Participants who quit smoking successfully and used nicotine gum had a lower hospital admission rate for cardiovascular disease than subjects who did not quit smoking, regardless of whether or not they used the gum.

The results of two other controlled trials of nicotine replacement and one population-based case-control study of patients with cardiovascular disease also provided no evidence for an increase in coronary events with replacement therapy [90-92]. As an example, a randomized trial of 584 patients (almost all men) with at least one diagnosis of cardiovascular disease found no difference in the incidence of primary cardiovascular end points (death, myocardial infarction, cardiac arrest, and admission to the hospital for cardiovascular disease) at 14 weeks between the nicotine and placebo groups (5.4 versus 7.9 percent with placebo) [90]. Overall, the evidence suggests that chemicals other than nicotine are responsible for the elevated risks of myocardial infarction and stroke in smokers. The risks of nicotine medication in patients with cardiovascular disease, if any, are much lower than those of smoking, and the benefits of nicotine medication far outweigh the risks of continued smoking in such patients.

IMPACT OF A SMOKE-FREE WORKPLACE — Reductions in admissions for myocardial infarction have been reported where smoke-free workplace laws have been implemented. An ordinance implemented in Olmsted County, Minnesota (United States) in 2007 required that all workplaces, including bars, become smoke-free. Comparing the 18 months before implementation of the smoke-free restaurant ordinance with the 18 months after implementation, a 33 percent decline in the incidence of myocardial infarction was observed [93]. (See "Secondhand smoke exposure: Effects in adults".)

SMOKING CESSATION — Smoking cessation reduces cardiovascular morbidity and mortality for smokers with or without cardiovascular disease but is particularly important for patients at high risk for coronary events. (See "Benefits and consequences of smoking cessation" and "Cardiovascular risk of smoking and benefits of smoking cessation".)

Smoking cessation is often difficult for cardiovascular patients, as evidenced by the fact that many are still smoking despite advice that smoking is extremely hazardous to their health. Several characteristics have been identified that distinguish patients who find it difficult to quit smoking after a cardiac event. These include [94]:

●Lower occupational and educational level

●Increasing age

●Higher rates of alcohol consumption or drug abuse

●History of depression and other psychiatric diseases

●A low sense of personal control over the activities of daily life

Despite an understanding of risk, particularly among individuals at risk for recurrent coronary events, there is a high rate of failure in smoking cessation attempts. Smoking cessation strategies are reviewed elsewhere. (See "Pharmacotherapy for smoking cessation in adults", section on 'Cardiovascular disease' and "Pharmacotherapy for smoking cessation in adults", section on 'First-line agents'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Quitting smoking (Beyond the Basics)")

SUMMARY

●The major cardiovascular effect of nicotine is sympathetic neural stimulation. (See 'Cardiovascular effects' above.)

●Nicotine also enhances the release of various neurotransmitters, including epinephrine, norepinephrine, dopamine, acetylcholine, serotonin, vasopressin, glutamate, nitric oxide, calcitonin growth-related peptide, and beta-endorphin. (See 'Cardiovascular effects' above.)

●Nicotine may contribute to the increased risk of cardiovascular events seen with cigarette smoking by transiently increasing blood pressure and heart rate, by causing coronary artery vasoconstriction, and/or by impairing endothelial function. (See 'Smoking and cardiovascular risk' above.)

●Smokeless tobacco contains and delivers levels of nicotine similar to those of smokers and may be associated with an increased risk of myocardial infarction and/or stroke, although the risk is thought to be less than from cigarette smoking. (See 'Smokeless tobacco' above.)

●The risks associated with nicotine replacement therapy in patients with cardiac disease appear to be low and in any case are much less than the risks of continued smoking. The benefits of nicotine medication to promote smoking abstinence or cessation far outweigh the risks in cardiovascular disease patients. (See 'Safety of nicotine replacement therapy' above.)