Relationship between smoking and coronary heart disease

relationship between smoking and coronary heart disease

Quitting smoking is probably the most important step you can take to decrease your chance of coronary artery disease Click here to see more. Secondhand smoke can cause heart disease and lung cancer in people who don 't Call your local chapter of the American Lung Association. Objective To use the relation between cigarette consumption and cardiovascular disease to quantify the risk of coronary heart disease and.

Careful evaluation of the available data is obviously desirable, but all studies have defects and the relative merits of one over another is subjectively assessed and the assessment is subject to imponderable biases of the evaluation. In a general way, a number of criteria for the evaluation of the causal significance of an association can be stated.

The strength of the association. There can be little doubt that the importance of an association increases as its strength increases. Exceptions can be noted without detracting from the general applicability of this rule. The specificity of the association. This rule cannot be applied blindly, either, but together with the first rule determine the precision with which one component of an associated pair can be used to predict the occurrence of the other.

This is most important in judging the causal significance of the relation between them. In this connection, prediction of an unlikely event is of greater significance than prediction of a common occurrence.

The consistency of the association. This concept is related to the prior ones, but includes the notion that different studies, using different methods, done in different populations should yield similar conclusions. The precedence of the causal component of the association. Within the limitations of methods of measurement the component of the association which is presumed to be causal must precede the other.

The coherence of association. Along with all the other requirements, an association of a factor with a disease process should be coherent with the known facts of the biology of that disease.

This may be impaired by insufficient or incorrect concepts of pathogenesis but eventually all the information must fit into an ordered structure. The application of these rules may be modified by knowledge of the precision with which the variables may be measured and by whether a factor is considered to be necessary or contributory and sufficient or insufficient.

All of these considerations must be involved in the judgement of the importance of smoking as a causative factor in the etiology of coronary heart disease. The Nature of the Association A. Indirect Measures of the Association Observations of different aspects of the co-variation of smoking and CHD are commonplace and, while they testify to the presence of an association between the two, are often couched in such broad generalities that they do not generate much confidence in their reliability.

These observations have been summarised in Smoking and Health 1 and by Bronte-Stewart. During the last half-century both cigarette smoking and CHD have been increasing in a generally similar fashion, at least in Great Britain and in the United States.

Risks are not reduced by smoking cigarettes with lower machine-measured yields of tar and nicotine. Smokers of only pipes or cigars seem to have lower risks of CVD than do cigarette smokers. However, cigarette smokers who switch to pipes or cigars often inhale the tobacco smoke and may not experience the lower CVD risk of persons who primarily smoke a pipe or cigar.

Stopping cigarette smoking and eliminating exposure to secondhand smoke rapidly and substantially reduce risks of various CVDs.

They found a causal relationship among both men and women between exposure to secondhand smoke and increased risks of CHD morbidity and mortality.

Pooled RRs from meta-analyses indicated a to percent increase in risk of CHD from exposure to secondhand smoke. The study by Whincup and associateswhich was based on blood levels of cotinine in men, suggested a to percent increase in risk of CHD from exposure to secondhand smoke. The risk of acute MI appeared to decline rapidly after cessation of exposure to secondhand smoke, as evidenced by a decline in hospital admissions for MI after smoke-free laws were put in place Dinno and Glantz ; Lightwood and Glantz ; Meyers et al.

As for stroke, the evidence was insufficient to infer a causal relationship between increased risk of CHD morbidity and mortality and exposure to secondhand smoke. Studies of the effects of secondhand smoke on subclinical vascular disease, particularly thickening of the walls of the carotid arteries, also suggest a causal relationship between exposure to secondhand smoke and atherosclerosis.

As mentioned previously, the substantial CVD risk associated with involuntary exposure to cigarette smoke indicates that the risks estimated in most studies of active smoking are biased downward because the control groups generally included large numbers of persons with exposure to secondhand smoke. Pathophysiology This section on pathophysiology focuses primarily on mechanisms by which cigarette smoking may increase risk of CVD. Cigarette Smoke Constituents and Cardiovascular Disease Three constituents of cigarette smoke have received the greatest attention as potential contributors to CVD: Some research also investigated the contributions of polycyclic aromatic hydrocarbons PAHsparticulate matter, and other constituents of tobacco smoke to the pathophysiology of CVD including atherogenesis Brook et al.

The typical dose of nicotine systematically absorbed from each cigarette is 1 to 2 milligrams mg.

relationship between smoking and coronary heart disease

Although plasma nicotine levels peaked sharply after each cigarette, trough values also rose during the first six to eight hours of regular smoking during the day Benowitz et al.

This accumulation pattern was consistent with an elimination half-life for nicotine of two hours Benowitz et al. In persons who smoke regularly, venous plasma levels of nicotine reached a plateau in early afternoon and remained at that level until bedtime Figure 6. Thus, these findings indicate that the regular smoker is exposed to significant levels of nicotine 24 hours per day. Adapted from Benowitz et al. Nicotine is a sympathomimetic drug that releases catecholamines both locally from neurons and systemically from the adrenal gland.

In studies of the pharmacodynamics of nicotine, the intensity of its maximal effect was greater with more rapid delivery Porchet et al.

relationship between smoking and coronary heart disease

Pharmacodynamic studies also indicated that although tolerance to the effects of nicotine developed rapidly, tolerance was incomplete Porchet et al. In one study, a constant intravenous infusion of nicotine increased the heart rate even though nicotine levels in the blood were relatively low.

As the infusion continued, the heart rate reached a plateau despite a progressive rise in blood levels of nicotine Benowitz et al. The same phenomenon was observed in comparisons of acceleration of heart rate with level of blood nicotine during regular cigarette smoking throughout the day Benowitz et al.

relationship between smoking and coronary heart disease

In another study, heart rate measured by ambulatory monitoring was higher throughout the day when persons were smoking than when they were not smoking Benowitz et al. The extent of elevation was independent of the blood level of nicotine absorbed from the cigarettes. The researchers concluded that the elevated heart rate reflected persistent stimulation of the sympathetic nervous system, a possible contributing factor to CVD. Nicotine may also contribute to endothelial dysfunction, lipid abnormalities, and insulin resistance Benowitz CO is a major constituent of cigarette smoke.

In regular smokers, carboxyhemoglobin levels average about 5 percent, compared with 10 percent or higher in heavy smokers Benowitz et al. These values compare with levels of 0. Like nicotine levels, elevated carboxyhemoglobin levels persist for 24 hours a day in smokers Figure 6.

CO exposure can aggravate ischemia and worsen symptoms in persons with vascular disease, although it is not clear that CO contributes directly to atherosclerosis Benowitz CO binds avidly to hemoglobin, reducing the amount of hemoglobin available to carry oxygen and impeding release of oxygen by hemoglobin. In some studies, inhalation of CO at levels comparable to those in cigarette smokers reduced exercise tolerance in patients with angina pectoris, intermittent claudication, or COPD Calverley et al.

Another study reported that CO exposure in persons with obstructive coronary disease resulted in a greater degree of exercise-induced ventricular dysfunction and an increase in the number and complexity of ventricular arrhythmias during exercise Sheps et al. Inhaling CO reduced the threshold for ventricular fibrillation in animals DeBias et al. Long-term CO exposure in smokers resulted in greater red blood cell mass and reduced the oxygen- carrying capacity of red blood cells, resulting in relative hypoxemia Benowitz In response to hypoxemia, red blood cell masses increased to maintain the amount of oxygen needed by organs in the body.

The increase in red blood cell mass increased blood viscosity and may contribute to hypercoagulation in smokers. Cigarette smoke delivers a high level of oxidizing chemicals to smokers, including oxides of nitrogen and many free radicals from both the gas and tar phases of cigarette smoke Church and Pryor Exposure to oxidant chemicals in smoke was associated with depletion of endogenous levels of antioxidants, manifested as lower blood levels of vitamin C in smokers than in nonsmokers Lykkesfeldt et al.

Cigarette smoking also was reported to increase levels of lipid peroxidation products in the plasma and urine of smokers Morrow et al. Study results also indicated that oxidant stress contributes to several potential mechanisms of CVDincluding inflammation, endothelial dysfunction, lipid abnormalities such as oxidation of low-density lipoprotein LDLand platelet activation Burke and FitzGerald Acrolein, a reactive aldehyde produced by endogenous lipid peroxidation, is present at high levels in cigarette smoke.

Acrolein binds covalently to form protein adducts, and acrolein-induced modification of proteins has been implicated in atherogenesis. HDL protects against atherosclerosis.

Acrolein-protein adducts co-localize with APO A-I in macrophages in the intima of human atheromatous blood vessels Szadkowski and Myers Acrolein also oxidized thioredoxins 1 and 2 in endothelial cells. Thioredoxins are prominent antioxidant proteins that regulate the oxidation-reduction balance critical for normal cell function.

These results suggest that oxidation of thioredoxins can result in dysfunction and death of endothelial cells, contributing to atherosclerosis. In addition, acrolein induces production of the enzyme cyclooxygenase-2 COX-2 in human endothelial cells in vitro Park et al. This finding is relevant because COX-2 is expressed in atherosclerotic lesions and may participate in atherogenesis.

Acrolein may contribute to thrombogenicity in smokers by inhibiting antithrombin activity Gugliucci Finally, acrolein induces hypercontraction in isolated human arteries and could contribute to smoking-induced coronary vasospasm Conklin et al. Cigarette smoke contains a number of metals, including aluminum, cadmium, copper, lead, mercury, nickel, and zinc. Metals in cigarette smoke catalyze the oxidation of cellular proteins Bernhard et al. This reaction may lead to structural damage, endothelial dysfunction, and detachment of endothelial cells from the walls of blood vessels.

Mixtures of metals and oxidants may be particularly damaging to endothelial cells. Cadmium levels are higher in serum of smokers, and cadmium accumulates in the aortic walls of smokers Abu-Hayyeh et al. Epidemiologic evidence indicates an association between serum levels of cadmium and lead and CVDincluding hypertension and MI Abu-Hayyeh et al.

PAHs found in the tar fraction of cigarette smoke reportedly accelerated atherosclerosis in experimental animals. Weekly injections of benzo[a]pyrene and 7,dimethylbenz[a]anthracene, at doses below those that produce tumors, increased development of atherosclerotic plaque in the aortas of cockerels Penn and Snyder Similarly, inhaled butadiene, a component of the vapor phase of cigarette smoke, increased the amount of atherosclerotic plaque in the same animal model Penn and Snyder The researchers speculated that one mechanism of atherogenesis is a mutation, followed by hyperproliferation of smooth muscle or other cells that may contribute to growth of atherosclerotic plaque.

Studies of the cardiovascular effects of smokeless tobacco may be informative for understanding the pathophysiology of smoking-induced CVD.

Cigarette smoking and coronary heart disease: risks and management.

Traditional smokeless tobacco products vary widely among countries; however, similar to Sweden, forms of oral snuff are the most common types of products used in the United States Substance Abuse and Mental Health Services Administration These products contain a large array of chemicals, including nicotine, nitrosamines, nitrosamine acids, PAHs, aldehydes, and metals IARC A recent systematic review reported that studies from both the United States and Sweden showed an increased risk of death from MI and stroke related to the frequency and duration of use of smokeless tobacco products Boffetta and Straif This review relied heavily 85—89 percent of the weight on results of a large U.

An analysis comparing the effects of using oral snuff with those of smoking cigarettes provided insights into the role of nicotine versus the effects of other toxins from tobacco smoke on CVD and cardiovascular risk factors Benowitz et al. In addition clinical trials of nicotine patches in patients with known CVD have not shown that transdermal nicotine increased cardiovascular risk Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease ; Joseph et al.

In the study of 3, middle-aged smokers with chronic obstructive lung disease, the U. Lung Health Study found no evidence of increased cardiovascular risk in subjects who quit smoking by using nicotine gum versus those who quit without use of nicotine gum Murray et al.

These studies and related evidence suggest that chemicals other than nicotine may contribute to the elevated risk of death from MI and stroke. Smokeless tobacco products have been found to have significant amounts of numerous other toxicants and carcinogens, particularly tobacco-specific nitrosamines as well as volatile aldehydes and PAHs Stepanov et al. Additional research on these and other toxicants in smokeless tobacco, such as heavy metals like cadmium, is needed to understand the observed cardiovascular risks among users of smokeless tobacco products.

Mechanisms Cigarette smoking produces acute myocardial ischemia by adversely affecting the balance of demand for myocardial oxygen and nutrients with myocardial blood supply Figure 6. The increase in demand for oxygen in the myocardium is a consequence of nicotine stimulation of the sympathetic nervous system and the heart.

Cigarette smoking acutely increases levels of plasma norepinephrine and epinephrine and enhanced hour urinary excretion of these catecholamines review by Benowitz and Gourlay Regular smoking increases the heart rate both in the short term up to 20 beats per minute and throughout the day average increase, 7 beats per minuteas measured during ambulatory monitoring.

Nicotine also increases heart rate, blood pressure, and myocardial contractility. These hemodynamic changes result in increases in myocardial work that in turn require increased myocardial blood flow. In healthy persons, cigarette smoking increases coronary blood flow in response to increases in myocardial work. In smokers, the response in coronary blood flow to increased myocardial demand was impaired i.

In addition, oxidant chemicals contribute to platelet activation and thrombogenesis Burke and FitzGerald Exposure to CO may also contribute to the adverse hemodynamic effects of cigarette smoking. By producing functional anemia, CO increases the need for coronary blood flow, especially during physical exertion.

An in-adequate vasodilatory flow reserve produced by cigarette smoking, in the face of need for increased coronary blood flow mediated by carbon dioxide, could contribute to myocardial ischemia with exercise in smokers. In addition to the mechanisms described in Figure 6. In most study participants, both heart rate and blood pressure increased immediately after smoking. Hesse observed a greater response in blood pressure after smoking in persons who smoked than in non-smokers.

The positive chronotropic, inotropic, and blood pressure effects of smoking are explained by nicotine-induced activation of the sympathetic nervous system review by Benowitz Cryer and colleagues elucidated the mechanisms behind observed hemodynamic changes during smoking. These increases were associated with significant increases in heart rate and blood pressure.

This study confirmed that smoking-induced increases in blood pressure and heart rate are attributable to adrenergic mechanisms. The hemodynamic effects of cigarette smoking are mediated primarily by nicotine, although oxidizing chemicals in tobacco smoke also affect vascular function.

Intravenous nicotine, nicotine nasal spray, and nicotine chewing gum all increased the heart rate up to 10 to 15 beats per minute and raised systolic blood pressure by up to 5 to 10 millimeters of mercury mm Hgresponses similar to the effects of cigarette smoking Gourlay and Benowitz Nicotine increased cardiac output by increasing both heart rate and myocardial contractility.

Different vascular beds express different types and ratios of adrenergic receptors. Therefore, not all vascular responses to nicotine or tobacco smoke are the same. For example, nicotine constricts some vascular beds, such as the skin, and cutaneous vasoconstriction explains the reduced temperature of the fingertip observed with administration of nicotine Benowitz et al.

Conversely, nicotine appears to dilate other vascular beds, such as skeletal muscle Diana et al. Vasodilation of skeletal muscle may partly result from the increase in cardiac output, although the release of epinephrine from nerve terminals may also contribute.

The net result of increases in heart rate, blood pressure, and myocardial contractility is an increase in myocardial work, followed by increased myocardial blood flow. Coronary Blood Flow An important hemodynamic consequence of cigarette smoking is its effect on blood flow in the coronary arteries.

Cigarette smoking acutely increased coronary blood flow by up to 40 percent, apparently a response to the increase in myocardial work review by Czernin and Waldherr In anesthetized dogs, coronary blood flow showed a biphasic response to nicotine. Initially, researchers hypothesized that increases in coronary blood flow—in the large coronary vessels as well as the smaller vessels—resulted from an increase in myocardial metabolic demand.

Cigarette smoking impairs the response of coronary blood flow to an increase in myocardial demand for oxygen; that is, it reduces the coronary vasodilatory flow reserve. Thus, the increase in coronary blood flow based on the level of myocardial work is less than would be expected in the absence of exposure to tobacco smoke. Cigarette smoking may also be associated with coronary vasoconstriction. Although cigarette smoking increases coronary blood flow in a person who does not have CHDit may decrease coronary blood flow in the presence of coronary disease.

Regan and colleagues measured coronary sinus blood flow in seven male volunteers with documented CHD before and after they smoked two cigarettes during a period of about 25 minutes; cardiac work increased by about 30 percent during smoking.

Cigarette smoking and coronary heart disease: risks and management.

Even so, in response to smoking, coronary blood flow fell in three patients, did not change in three patients, and increased in one patient. Similar paradoxical responses were observed after long-term smokers were exposed to cold by testing with cold pressors Campisi et al. In the testing, the hand is immersed in ice water for one to two minutes. In healthy volunteers, cold-induced increases of about 30 percent in the product of heart rate and blood pressure were associated with appropriate and similar increases in blood flow.

In contrast, smokers showed no measurable increases in blood flow in response to the cold. Campisi and colleagues ascribed this observation to coronary endothelial dysfunction.