Smoking Cessation in the Cardiac Patient
Mary O’Sullivan
For patients with cardiac heart disease, quitting smoking is associated with a 36% reduction in all-cause mortality.1 For patients with left ventricular (LV) dysfunction after myocardial infarction (MI), smoking cessation is associated with a 40% lower hazard of all-cause mortality over a median follow-up of 42 months.2 Current smoking is a powerful independent risk factor for sudden cardiac death among patients with a previous MI or stable angina. Those who quit have the same risk of sudden death as those who have never smoked.3 The impact of smoking cessation in this population is therefore of at least the same magnitude as that of angiotensin-converting enzyme (ACE) inhibitors (19% relative risk decrease), β-blockers (23% relative risk decrease), and aldosterone antagonists (15% relative risk decrease).4,5 and 6
The effects of smoking on heart rate, blood pressure, cardiovascular blood flow, myocardial oxygen demand, and thrombosis are largely reversible. Because the benefit is of immediate onset, and as there are effective tools available, smoking cessation for the cardiac patient is an essential component of care.7 In this chapter we will review how cigarettes induce cardiac disease, the role of nicotine in this process, the pharmacologic tools available, their safety profile in the cardiac patient, and the basics of behavioral modification for the smoking addiction. Helping patients to quit smoking is certainly more challenging than simply ordering a medication. Understanding the biology involved assists us in helping our patients break this notoriously severe addiction.
HOW DOES SMOKING CAUSE HEART DISEASE?
Although the entry portal for cigarette smoke is the lung, where the chemicals present in the smoke are quickly and easily absorbed, the resulting inflammatory cascade has a profound effect well beyond the confines of the lung. The systemic effects of cigarette smoking include a variety of complicated processes that induce, in the genetically susceptible individual, vascular and hematologic abnormalities that can result in accelerated atherosclerosis as well as the acute events of MI and sudden death. The chemicals that are inhaled induce oxidative stress, systemic inflammation with activation and release of both inflammatory cells and inflammatory mediators, endothelial dysfunction, and abnormalities of coagulation and hemostasis8:
Oxidative stress. The particulate (tar) phase of cigarette smoke contains >1017 free radicals per gram, and the gas phase contains >1015 free radicals per puff. Many of the damaging effects of smoking are induced by these molecules. The sustained release of reactive free radicals from the tar and gas phases of smoke imposes an oxidant stress, inducing a variety of chemical injuries including the promotion of lipid peroxidation. Also, the inhaled oxidant molecules significantly deplete the body’s antioxidant defense system.8,9
Systemic inflammation. Long-term cigarette smoking increases total WBC counts. There is an increased early bone marrow release of polymorphonuclear leukocytes (PMNs) and platelets into the circulation. These activated inflammatory cells then produce a variety of inflammatory mediators, acute phase proteins, and cytokines, among them C-reactive protein (CRP), fibrinogen, IL-6, and tumor necrosis factor. Some of the inflammatory mediators and hematologic effects of smoking decline rapidly after smoking cessation. However, CRP can remain elevated for 10 to 19 years.10 These mediators may not be just markers of disease but may be actively involved in the proinflammatory and proatherogenic effects of chronic smoke exposure.
Endothelial dysfunction. Smoking-induced endothelial dysfunction is mainly caused by decreased production or availability of nitric oxide (NO) resulting in impaired vasodilatory function at the macrovascular level (e.g., coronary arteries) as well as at the microvascular level.11,12 NO is also affected by cigarette smoke through the changes induced on low-density lipoprotein (LDL). In cigarette smokers, LDL gets oxidatively modified by the inhaled oxidant molecules. The modified LDL then interferes with the protective effect of NO on the arterial wall. The result is increased inflammatory cell entry into the arterial wall. The oxidatively modified LDL is taken up by the macrophages that enter the arterial wall; cholesterol esters are deposited and foam cells form.
Abnormalities of coagulation and hemostasis. Smoking cigarettes induces a hypercoaguable state that is the predominant cause of acute cardiovascular events induced by smoking. Viscosity is increased, with increased levels of fibrinogen, lipoproteins, and hematocrit. Antithrombotic, prothrombotic factors, and platelet function are affected. There is impaired release of the t-PA, the main fibrinolytic activator resulting in impaired fibrinolysis. Hypercoaguability is responsible for 25% to 50% of the link between smoking and coronary artery disease (CAD)3 and is especially involved in acute cardiac events. This is borne out in multiple clinical situations:
Smoking increases the risk of MI and sudden death much more than it increases the risk of angina, reflecting the importance of acute thrombus formation.13
Similarly, the prognosis after thrombolysis is better in smokers than in nonsmokers. This reflects the greater part that clot plays in the disease process.14
Sudden cardiac death is correlated with the presence of acute thrombosis and not the level of plaque burden.13
Smokers who continue to smoke after thrombolysis or angioplasty have a substantially increased risk of reinfarction or reocclusion.15,16
At least a part of the thrombotic effects of smoking are induced by even passive smoke.17,18 The remarkable sensitivity of the coagulation system to the effect of cigarette smoke19 mandates that the cardiac patient must cease all smoking, not just cut down their habit, to achieve reversal of these effects. Patients should be taught the seriousness of this issue.
Although some of the effects of smoking on inflammatory markers may persist for years, a great portion of these effects are reversible by stopping smoking.
WHAT IS THE ROLE OF CARBON MONOXIDE IN THIS PROCESS?
CO acutely poisons the oxygen delivery system, placing the patient at risk for arrhythmia and MI.13
HOW DOES NICOTINE PARTICIPATE IN THIS PROCESS?
Although much of the toxic effects of cigarette smoke are due to the other chemicals present, nicotine is the chemical that is responsible for the addiction. It is inhaled in cigarette smoke and rapidly reaches the nicotinic cholinergic receptors, found both in the peripheral and central nervous system, resulting in the release of a variety of neurotransmitters including dopamine, glutamate, γ-aminobutyric acid, norepinephrine, acetylcholine, serotonin, and endorphins, which are important in the development of addiction in the susceptible individual. The pleasure derived from the dopamine release contributes to the addictive process.
Nicotine dependence is highly heritable. It is determined by a number of genes that are receptors for the drug, and they determine its rate of metabolism, its pleasurable effects as well as its withdrawal syndrome. One of the primary genes involved is the CYP2A gene that is a controller of the rate of metabolism of nicotine, the vulnerability to tobacco dependence, the response to smoking treatment, and is involved with lung cancer risk. The α3β4 nicotinic acetyl choline receptor is believed to mediate the cardiovascular effects of nicotine.20
With repeated exposure, nicotine tolerance develops through a desensitization of the receptors to the effect of nicotine and an increase in the number of nicotine receptors. Nicotine withdrawal is a complex process—not unlike that of withdrawal from alcohol, cocaine, opiates, and cannabinoids—that results in a state of anxiety, stress, generalized discomfort, inability to concentrate, and depressed mood.20
Thus smokers learn to use the cigarette’s nicotine as a modulator of anxiety, concentration, depressive symptoms, and pleasure; a major tool for handling life’s stresses. At the same time, those who are genetically susceptible to the addiction, after a relatively short period of use, become trapped by an inability to function without the satisfaction of the increased number of less-responsive nicotine receptors. By smoking, not only does the intense discomfort of withdrawal get relieved within 10 seconds, but the relief is accompanied by significant pleasure.
With time the smoker associates certain situations with smoking: after a meal, drinks with friends, coffee, stress, and so on. This association is learned and contributes significantly to the activity of the nicotine receptors and the expectation of immediate relief. These conditioned responses play a significant role in maintaining the addiction and become a significant impediment to the process of quitting. Understanding the biology makes clear the importance of the behavioral component of smoking cessation.20 As we will see from the studies on smoking cessation in the cardiac patient, the behavioral component of therapy is as important as the pharmacologic component. The permanence of the receptors and the persistence of the learned behavior make the incidence of relapse very high; thus the importance of “learning” new sources of pleasure, stress management, concentration, and mood regulation.
WHAT IS THE ROLE OF NICOTINE IN THE DEVELOPMENT OF CARDIOVASCULAR DISEASE?
Sympathetic overactivity is a significant factor by which smoking, and at least in part nicotine, induces cardiovascular disease.13 Nicotine releases catecholamines, increases heart rate and cardiac contractility, constricts cutaneous and coronary blood vessels, and transiently increases blood pressure.21 There is an increase of myocardial work and oxygen consumption through an increase of blood pressure, heart rate, and myocardial contractility.22 Nicotine also reduces sensitivity to insulin and may contribute to endothelial dysfunction.23,24 How much of the sympathetic overactivity induced by smoking results from the effect of nicotine in the cigarette is unclear, but this is of obvious concern when we are considering using nicotine replacement therapy (NRT) in the cardiac patient.
IS THE USE OF NICOTINE REPLACEMENT THERAPY SAFE?
In a 2010 meta-analysis of adverse events associated with the use of NRT among 177,390 participants, Mills et al.25
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