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Cigarette Smoking |
Diseases of the blood vessels leading out from the heart, the so-called
peripheral blood vessels, comprise one of the most common diseases afflicting
Americans today. The same process involves these vessels that also
involves the coronary arteries leading to heart attacks, or the cerebral
arteries leading to strokes; the process known as "atherosclerosis".
We have already talked about atherosclerosis, or hardening of the arteries,
and how it is closely related to smoking.
The most common arteries involved are those leading to the legs,
although sometimes the arms can also be diseased. When the leg arteries
become involved with this disease, blood supply to the muscles in the legs
gradually becomes compromised. This disease can be particularly insidious,
and tends to progress rather slowly. The patient gradually begins
to feel calf pain when walking, running, or anything requiring strenuous
legwork. At first, the person does not even realize that there is
anything wrong because there are no symptoms; the arteries are diseased
but the patient feels no symptoms. This is the so-called sub-clinical
asymptomatic phase of the disease. As the disease progresses, the
patient may notice pain when walking up stairs or doing something else
which requires particular leg exertion. At first, this may be only
a nagging discomfort; later, the pain can become severe and disabling.
Eventually, the patient develops pain at rest while not even performing
any work. This pain can be very disabling to the patient's lifestyle
as it will severely restrict his activity, can frequently wake him up out
of a sound sleep at night, and generally make his life miserable.
Poorly healing ulcerations can develop on the legs, which can become severely infected, maybe even life-threatening. This infection may eventually lead to blood poisoning (sepsis) that can cause rapid cardiovascular collapse and death. Additionally, the ulcerations are often particularly painful and disfiguring, and are notoriously difficult to heal, even with the best of care. Antibiotics are not very useful if the reason the ulcerations appeared in the first place, reduction in blood flow due to atherosclerosis, is not reversed. For similar reasons, other conservative treatment usually fail. Eventually, the disease process can progress to the point where the parts of the patient's leg develop gangrene, making amputation a necessity in order to save the patient's life. The arterial system is a group of vessels which carry blood from the heart to the rest of the body. The main artery, the aorta, leaves the heart and travels down the body near the spin, then splits off into smaller and smaller branches. Branches off of the aortic arch under the breast bone travel to the head (carotid arteries) and to the arms (subclavian arteries) among other places. The aorta itself branches into the common iliac artery, which branches into the internal and external iliac arteries. The external iliac artery branches into the femoral artery which then goes into the legs and breaks up into yet smaller and smaller arteries. The arteries eventually break up into arterioles and then capillaries. It is at the capillary level that nutrients pass from the blood and go into tissues, and where metabolic waste products leave the tissues and pass into the blood stream. Obviously, the arterial system is very important because it acts like a messenger bringing food to the rest of the body. If the blood supply to a tissue area decreases below a critical level, then the nutrient supply will simply not be sufficient to keep tissues alive and they will die. There is a gray zone in between abundance of blood supply and critical blood flow; in this gray zone, there is enough blood to keep things going, but only at a sub-optimal level. Perhaps there is enough blood supply to keep the muscles well supplied when they are resting, but simply not enough blood supply to muscles when they are working and require more oxygen. When this happens, the patient may have no muscle pain or discomfort whatsoever while resting, but minimal activity causes additional oxygen needs from the muscles; if these needs are not met perhaps due to an obstruction in one of its blood supplying arteries, then a crampy pain called "claudication" will result. Most commonly, claudication occurs in the legs; the patient will find that walking or other leg exertion activities produces pain. The diagnosis of peripheral vascular disease can usually be easily made by a physician on the basis of history and physical examination. The examination may show reduced arterial pulses in the legs, reduced leg hair, ulcerations, different coloration between the two legs, and other changes. Also, there are non-invasive tests that the physician can have performed using high-frequency sound waves (Doppler study or Ultrasound), or impedence plethysmography (IPG's). If the symptoms become so severe that surgery on the artery is indicated, then it becomes necessary to know precisely where the obstruction is and not just that it is there. Arteriography is an invasive and risky test where dye is placed into an artery and X-ray pictures are taken as the dye passes through the arterial system. When an obstruction is present, the dye flow will stop if the obstruction is total, or be diminished if the obstruction is partial. However, since arteriography is an invasive procedure with certain very significant potential risks, admission to a hospital is usually required so that the patient can be carefully watched. Because of the potential for complications, arteriography is only performed when there the patient is very symptomatic and when there is a very real chance that surgery will have to be performed to ease these symptoms and to prevent the occurrence of gangrene. Non-Surgical Treatment for Peripheral Vascular Disease There are other measures that can be used besides surgery for the patient with peripheral vascular disease. These measures are less sure of an effect, but they may work in some individuals and are certainly worth a try. Naturally, the sooner in the progression of the disease these less invasive measures are performed, the greater the chance of avoiding surgery altogether. Smoking Cessation and Peripheral Vascular Disease Smoking cessation is the most important step that anyone with this disease must do if any therapy is to be successful. As we will see later in greater detail, smoking does many bad things to the vessels which makes them more susceptible to disease. For now, let's just say that smoking does many bad things to the blood making it more likely to cause disease. For example, smoking makes platelets (the cellular element in blood that is extremely important in clot formation) more likely to clump together; when platelets are activated and clump together, the entire atherosclerotic process is encouraged. Additionally, the lipoprotein make-up of blood is changed in a way that encourages fat deposition on the arterial wall; this also encourages the atherosclerotic process. Finally, smoking causes the arteries to constrict and become narrower, thereby reducing the amount of bloodflow and oxygen the artery carries to already starved tissues. Patients with peripheral vascular disease who continue to smoke cigarettes simply will not get better, even if they do everything else correctly. Additionally, when they smoke after surgery is performed on their arteries to try to open them up, the entire process may start all over again in another location or recur at the graft site. Therefore, out of all of the possible preventative or treatment modalities possible, smoking cessation is without a doubt the most important. Diabetic Control and Peripheral Vascular Disease Other important measures can be taken in addition to smoking cessation to treat peripheral vascular disease. If the subject has diabetes (which is frequently present in those who develop peripheral vascular disease - but not always) then aggressive control of blood glucose (sugar) becomes necessary. Elevation of blood glucose will accelerate the entire process and encourage its development. The subject should lose weight if obese, and hypertension should be controlled if present. The subject should try to prevent injury to the endangered tissues, usually the feet, as any injury will heal more slowly and have a much greater chance of getting infected. These conservative measures will help prevent progression of peripheral vascular disease in the majority of subjects. Some patients are not so lucky, however. Some may not be able to follow the advice of their physician (especially with regards to smoking cessation) or their disease progresses despite all attempts at therapy. Nonetheless, all of these patients do not necessarily have to have surgery performed, for recently a new therapeutic technique has been developed which may help selected patients. Those who have a single well defined atherosclerotic narrowing in one of their arteries may be able to have that narrowing opened through the use of a technique called percutaneous balloon angioplasty. This technique involves a tiny catheter (or hose) that is placed by a physician into a large artery, and fed down the artery toward the narrowing. This is done with a low energy X-ray machine so that the position of the catheter tip can be brought right up to the narrowed artery. At the end of the catheter tip is a tiny balloon which is collapsed until the physician puts air into it. To open the narrowing, the catheter tip with the balloon is placed into the narrowing and the balloon is expanded hopefully opening up the vessel. This technique is often helpful in those who have a single narrowing, or only a few discrete narrowings, but is not applicable to patients who have diffuse disease. If the symptoms are significant, then surgery may be indicated. Surgery is not always indicated for those with peripheral vascular
disease, however. Most patients will have significant relief of their
symptoms with conservative therapy or possibly with percutaneous angioplasty
balloon dilitation; only about 10 percent of patients with arterial occlusive
disease will require surgery. Surgery for peripheral vascular disease
generally means either taking out the narrowed diseased arterial segment
and placing in a plastic artificial graft, or bypassing the obstruction
with another vessel. Both of these procedures are associated
with complications of their own, can become infected, and may not always
work; especially if there are many obstructive lesions.
Peripheral vascular disease can be terribly demoralizing to the patient, and may produce severe illness, cost, and reduction in standard of living. However, the disease is generally preventable - it does not have to happen. Recently, medicine has begun to concentrate on preventing serious disease rather than curing it. It is always easier and less expensive to prevent disease from happening in the first place rather than valiantly trying to battle it after it occurs. Unfortunately, disease prevention is less glamorless and it is always difficult to ascertain improvement of health in the community through quantifying the disease that never happened. The most important risk factor for the development of peripheral vascular disease is smoking (1), and the disease is rather rare in those who have never smoked (2). High fat levels have also been appreciated in those with peripheral vascular disease. Smoking does not produce increased amounts of total lipoprotein (hyperlipidemia) but increases peripheral disease through other mechanisms (3). There is an abnormal distribution of lipoprotein pattern with 43 percent of males showing high triglyceride levels (Type IV hyperlipoproteinemia) (4). Greenhelgh (5) reported elevations of lipoprotein levels in 44 percent of consecutive patients with peripheral vascular disease; in 30 percent the serum triglyceride level was elevated while in 15 percent the serum cholesterol was increased. While these studies have demonstrated an increased incidence of abnormal lipoprotein patterns with peripheral vascular disease, further evidence was necessary to show a causal relationship between the two. Naturally, causal relationships are difficult to establish in human diseases since most people will not submit themselves to the rigorous testing methods necessary to prove causality. while it is possible to even show a direct relationship between the degree of elevation of lipoproteins (6), this still is not sufficient to prove causality. For example, high lipoprotein levels may be produced through a third factor which is the real cause of peripheral vascular disease. Additionally, the risk of peripheral vascular disease is so strongly associated with cigarette smoking that the risk associated with hyperliproteinemia is small in comparison. Hypertension is another independent risk factor for peripheral vascular disease (in addition to coronary heart disease and cerebrovascular disease) (7). Hypertension probably promoted peripheral vascular disease by sheering forces, especially in the larger arteries (8). Hypertension has been shown to accelerate development of peripheral vascular disease associated with high serum cholesterol in dogs, and that the effect is multiplicative rather than merely additive (9). Clearly, the risk of peripheral vascular disease increases markedly when several risk factors are present simultaneously. Multiple risk factor analysis was performed by Rosen (10) in 109 patients with peripheral vascular disease. The site of disease was established by angiography and classified into three anatomic regions; aortoileal, combined aortoileal and femoropopliteal, and femoropopliteal. These three anatomic regions are of progressively smaller (although still rather large) arteries. Cigarette smoking was the most common risk factor in all three groups, being present in 90 percent of aortoileal and combined disease, and in 75 percent of those with femoropopliteal involvement. Also, those who smoked cigarettes have onset of their disease approximately ten years before non-smokers. On the other hand, high triglyceride levels and diabetes are more common in subjects with femoropopliteal disease. We have so far discussed the strong relationship between smoking cigarettes and the development of peripheral vascular disease. The evidence supporting this notion is quite strong, although not as overwhelming as the evidence for the association between smoking and coronary heart disease. This is because peripheral vascular disease, while very common and potentially very disabling, is not the death risk as is coronary heart disease. However, the basic underlying process behind the two diseases - atherosclerosis - is the same. Many studies have been performed, however, which show the relationship between smoking and peripheral vascular disease. Approximately 90 percent of those subjects with peripheral vascular disease are smokers in the studies of Juergens et al. (11), Begg (12), Schwartz et al. (13), and Widium et al. (14). Additionally, those with peripheral vascular disease will suffer more symptoms of claudication when they smoke more than 15 cigarettes per day (15). Interestingly, the development of claudication does not seem to depend upon the number of cigarettes smoked per year or the number of years of smoking, but simply rather a person smoked or not! We have shown that patients with peripheral vascular disease tend to be smokers - but if you are a smoker, what are your chances of getting peripheral vascular disease? The Framingham Heart Study (1) investigates this question and determined that heavy smokers have a threefold greater risk than non-smokers, and that cigarette smoking was as strong a risk factor for women as for men. Age was also found to be a significant risk factor in the prevalence of peripheral vascular disease, with almost half of the cases occurring in subjects over the age of 70 years (16). In this study, a higher percentage of males than females have peripheral vascular disease. The greater incidence of intermittent claudication with age has also been reported by DeBacker et al. (17), but also found a significant correlation with serum cholesterol, hypertension, diabetes, and cigarette smoking. Not only has arterial disease of the lower extremity been associated with cigarette smoking, but also disease of the arteries leading from the aorta to the kidneys, the renal arteries. Meakay et al. (18) demonstrated that renal artery narrowing or "stenosis" is almost twice as common as in those who do not smoke. Renal artery stenosis can lead to severe forms of hypertension, and may be one of the reasons why people who smoke have more severe forms of hypertension than those who do not. Passive smoking, or the exposure to cigarette smoke a non-smoker inhales while in the presence of smokers, has been shown to decrease exercise tolerance in those with claudication. This may be due to the increased carbon monoxide levels passive smokers achieve which then binds to hemoglobin causing it to bind less oxygen and to release less to the tissues. It is, however, too early to determine the precise relationship cigarette smoking has in the cause of atherosclerosis in the non-smoker, although it is certainly reasonable to assert that any lesions which are already present will have a greater chance of becoming symptomatic in smokers than in non-smokers Relationship between Smoking and Peripheral Vascular Disease Thus far, we have established a relationship between smoking and peripheral vascular disease. In other words, we have noticed a connection between the two in that they tend to occur together. However, this does not prove a causal relationship, or that smoking actually causes peripheral vascular disease. To prove causal relationships in humans is very difficult since we just simply cannot ethically do the types of experimentation required. However, if we can show that, in addition to the temporal relationship between smoking and peripheral vascular disease that we have already established, we can also show scientific evidence as to how smoking could cause peripheral vascular disease, then our strong case becomes even stronger. This is what we will now attempt to show in clinical studies which have investigated the relationship between cigarette smoke and its constituents on the peripheral vascular system. Cryer et al. (19) in 1976 examined the effects of smoking upon the heart and circulatory system. They demonstrated a significant increase in adrenaline (epinephrine) levels, and an increase in heart rate, blood pressure, blood glycerol and blood lactate/pyruvate ratio. These changes may make the heart work harder or may promote the development of atherosclerosis. Many of these effects could be blocked by medication (propranolol) which is used by physicians to treat hypertension among other things. There is apparently an association between cigarette smoking and circulating hemoglobin. While it may seem a good thing to have more hemoglobin (the molecule that transports oxygen in the red blood cell), it turns out that as might be expected, too much can instead be a bad thing. Then there is too much hemoglobin, the blood can become too thick and actually make the heart work harder. This may be especially true in smokers as a considerable portion of their hemoglobin may be poisoned by the carbon monoxide found abundantly in cigarette smoke. Because this poisoned hemoglobin is unable to carry oxygen, the concentration of oxygen in blood decreases and, through as yet rather poorly understood mechanisms, the bone marrow is stimulated to produce more blood. Thus, the heart of a cigarette smoker has to pump more blood, although the blood may be unable to carry more oxygen. Platelets are also affected by smoking. Platelets are the smaller cellular components in blood which clump together and form a plug when a blood vessel is broken. Platelets are one of the body's first line of defense when cut. As such, they serve a very useful purpose - without them all of us would stand a much greater chance of bleeding to death. However, platelets also have been implicated as part of the very complex chain of events leading to the development of atherosclerosis. When they aggregate along a vessel wall, they may initiate the complex chain of events in that area that eventually leads to atherosclerosis. Davis and Davis (20) studied the effects of smoking on 18 volunteers. They noted that platelets tend to clump much more after smoking only two unfiltered cigarettes over a 20 minute period. The fatty acid concentration remained the same, but aspirin could inhibit the platelet aggregation (21). Experimental studies in animals have helped to further investigate
the mechanisms whereby cigarette smoking influences the development of
atherosclerosis. Birnstingl et al. (22) evaluated the effect of carbon
monoxide at a concentration of 400 ppm on platelet aggregation in rabbits.
They noted a highly significant increase in platelet aggregation followed
the next day by a marked reduction in platelet aggregation. Marshall
et al. (23) also studied the effects of cigarette smoke with varying concentrations
of carbon monoxide and found an increased adherence of platelets to the
vessel wall. Interestingly, it was possible after long exposures,
to demonstrate actual microscopic clots on the vessel wall and degeneration
of those cells lining the vessel wall. These two studies strongly
suggest that carbon monoxide may influence platelet aggregation, damage
vessel walls, and initiate the process of atherosclerosis.
So far, we have discussed the harmful effects of smoking on the peripheral vascular system and investigated potentially important reasons why cigarette smoke is so harmful. The critical question is whether smoking cessation can influence the progression of peripheral vascular disease once it has already begun. The practical difficulty with these studies is, of course, that most people simply do not stop smoking until it is too late - until they already have significant disease, or until after they have had a limb amputated. Thiryvengadam et al. (24) evaluated whether cigarette smokers would stop smoking once they had gotten their disease (since they seem to so rarely stop beforehand). A significant reduction in cigarette smoking was seen in patients with cardiovascular, pulmonary, gastrointestinal disease, cirrhosis of the liver, cancer or diabetes. However, those subjects with peripheral vascular disease or psychiatric illness showed no reduction in smoking compared to controls. Therefore, the occurrence of peripheral vascular disease does not seem to encourage the patient to stop smoking! What is even more difficult to understand is that twelve out of 89 subjects with peripheral vascular disease actually increased their smoking! Another very interesting study by Birkenstock (25) studied what happened to those subjects with peripheral vascular disease who were able to discontinue smoking compared to those treated with conventional medical therapy but continued to smoke. Those subjects were either unwilling or unable to undergo operative treatment for their disease. Medical therapy consisted of foot hygiene, walking exercises, smoking cessation, a low cholesterol diet and Vitamin E therapy. Out of 277 patients who were smokers, 164 were able to stop. Of those who were able to stop smoking, 85 percent showed improvement in their peripheral vascular disease compared to only 20 percent who showed improvement who continued to smoke but were treated with conventional medical therapy. Also, those who stopped smoking showed greater improvement in their symptoms compared to those who improved while smoking. However, no patients with diabetes improved while smoking. As we discussed previously, some patients may fail conservative medical and reconstructive surgical therapy, and end up requiring an amputation. Naturally, both the patient and the surgeon want to leave as much leg behind to improve chances for a successful rehabilitation. For instance, it is much easier to learn to walk again when a leg amputation is performed below the knee rather than above. The surgeon will try to preserve as much leg as possible and may preserve tissue whose blood supply is marginal. Now, this is important because too little blood will produce a poorly healing wound that may even become infected, and require further surgery. The question has arisen as to whether smoking can make the difference between well healing or poorly healing tissue whose blood supply is marginal. This was investigated by Burgess et al. (26) in 1982 who studied the rates of healing in below the knee amputation. He ascertained that 85 percent of those whose amputation failed to heal were smokers, while only 50 percent of those whose amputations healed were smokers. Not all bypass grafts are successful. When a surgeon tries to help a patient with peripheral vascular disease by placing an artificial vessel in place of the diseased one, it is only inevitable that a certain percentage of the artificial grafts will fail and simply clot off. The chances of this occurring are related to underlying diseases, such as diabetes or hypertension, but is also strongly influenced by smoking. Just as smoking contributes substantially to the development of peripheral vascular disease in the first place, so does smoking increase the incidence of disease within the graft and induces graft failure. Importantly, it has also been well shown that smokers who develop peripheral vascular disease and require surgery will have a lower incidence of graft failure if they can only stop smoking. Wray et al. (27) in 1971 showed there was substantially fewer graft occlusion rates when the smoker stops the habit. Of 30 patients who continued to smoke after surgery, 9 late occlusions occurred, while no occlusions occurred in the 16 patients who were able to stop. Myers et al. (28) in 1978 reported upon a series of patients with vascular surgery for arterial occlusion. This study investigated 217 patients undergoing aortofemoral or femoropopliteal surgery and noted that patients who had either stopped smoking or smoked 5 cigarettes per day or less, and a patency rate of about 90 percent for aortofemoral surgery and 80 percent for femoropop[liteal surgery. Those who continued to smoke after surgery did much worse, however. they had three times greater complication rates for aortofemoral and four times greater rate for femoropopliteal than did non-smokers or ex-smokers. In fact, there was a good correlation between the number of cigarettes smoked and the complication rate. Thus, we have been able to show some of the latest work regarding cigarette smoking and peripheral vascular disease - and it is not good. Not only are cigarettes bad for arteries, but also they can encourage disease in vessel grafts as well. We still do not have all the answers regarding the precise mechanisms as to how cigarettes encourage arterial disease; there is still much work that needs to be done before all the answers are in. There is no doubt that cigarettes are bad, however, and until a means for reversing the disease is found, there is only one good solution - stop smoking. So far, we have been focusing on the smaller arteries; those within the legs or arms. However, atherosclerosis commonly affects the aorta as well. The aorta is the largest artery in the body. It leaves the heart from the left ventricle and travels near the vertebral column down toward the legs. Near the level of the umbilicus, it divides into the two common iliac arteries which in turn divides and gives off many other branches on the way. Importantly, the aorta is a common site for atherosclerosis just as any other artery; however, its effects are somewhat different. Because of its size, it rarely gets totally blocked off by atherosclerotic plaque, but instead its wall gets weakened. The artery is held together by muscle (smooth muscle), elastic and connective tissue, and when enough lipids gets deposited, the wall weakens. The weakened area in the aorta then sets it up for one of the most feared complications of atherosclerosis, the aortic aneurysm. An aneurysm is a weak spot in the artery where a "bleb" forms due to little support in the wall of the vessel, but with continuous beating from the blood rushing by. Eventually, what will happen is the aneurysm will get larger and larger until it breaks - often leading to an immediate death. Atherosclerosis is the most common cause of aortic aneurysm formation, but there are other causes as well, such as infection, trauma, inherited diseases (such as something called Ehlers-Danlos syndrome) and dissecting aneurysm where the wall just falls apart. The disease may involve only a part of the vessel wall (a saccular aneurysm) or the entire wall (fusiform aneurysm), and usually forms in the abdominal portion of the aorta, generally below the origin of the renal arteries. Most aneurysms are not symptomatic, and are discovered by the
physician on physical examination (when a large pulsatile mass is found
in the abdomen) or on X-ray examination. When symptomatic, they can
produce severe pain as they erode into the vertebral column or the vessel
slowly breaks apart. At this point, the physician may make the diagnosis
using harmless sound waves, or by arteriography where dye is put directly
into a vessel. Surgical repair is usually indicated once the aneurysm
reaches 5-6 cm in diameter because the chances of rupture and sudden death
are so great. The surgeon will generally try to take out the diseased
portion of the vessel and replace it with an artificial graft. This
is often not easy surgery, especially if the patient has other diseased
vessels that can predispose to heart attack or stroke during surgery, or
if there is significant underlying pulmonary disease due to frequent smoking.
The relationship between aortic aneurysm and smoking habits also was investigated by Auerback and Garfinkel in 1980 (30). They reported a direct correlation between the extent of atherosclerotic lesions, age, and smoking history. Additionally, they reported a higher incidence of aortic aneurysms in cigar, pipe smokers, and ex-smokers than in non-smokers. Men over 65 years of age had an aortic aneurysm in 11 percent of cases, with a 16 percent incidence in heavy smokers. Thus, the evidence for aortic aneurysms is clear. Although not as extensive as with peripheral vascular disease or coronary heart disease, there is clear evidence suggesting a direct relationship between smoking history and significant disease of the aorta.
Reference Peripheral Vascular Disease
1. Kannal, W.B. Epidemiology Studies of Smoking in Cerebral and Peripheral
Vascular Disease. In: Wynder, E.L., Hoffman, D., Gori, G.B. (Editors).
Modifying the Risk for the Smoker. volume 1, Proceedings of the Third
World Conference on Smoking and Health, New York, June 2-5, 1978.
U.S. Department of Health, Education, and Welfare, Public Health Services,
National Institutes of Health, National Cancer Institute, DHEW Publication
No (NIH)76-1221, 1976.
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