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Using exercise to reduce risk†
Journal of Clinical Lipidology (2009) 3, 360–367
Clinical Lipidology Roundtable Discussion
Using exercise to reduce risk† W. Virgil Brown, MD*, Gerald F. Fletcher, MD, Peter W. Wilson, MD Editor–in–Chief, The Journal of Clinical Lipidology, Professor Emeritus, Emory University School of Medicine, Atlanta, GA 30033, USA (Dr. Brown); Professor of Medicine, Mayo Clinic College of Medicine, Rochester, MN (Dr. Fletcher) and Professor of Medicine, Emory University School of Medicine, Atlanta, GA (Dr. Wilson)
Acknowledgment This roundtable discussion was supported by the National Lipid Association.
Disclosure Dr. W. Virgil Brown is an advisor to AstraZeneca, Wilmington, Delaware; Amgen, Thousand Oaks, California; Bristol-Myers Squibb, New York, New York; Eli Lilly, Indianapolis, Indiana; Genzyme Therapeutics, Cambridge, Massachusetts; Liposcience, Raliegh, North Carolina; Merck, Whitehouse Station, New Jersey; Merck/SheringPlough, Whitehouse Station, New Jersey; Pfizer, New York, New York; Roche, Basel, Switzerland; and Unilever, Englewood Cliffs, New Jersey. Dr. W. Virgil Brown has received education or research grants from Abbott Laboratories, Abbott Park, Illinois; AstraZeneca; Eli Lilly; Pfizer and Solvay Pharmaceuticals, Basel, Switzerland; Dr. W. Virgil Brown is a member of the speakers’ bureaus of Merck and Merck Schering-Plough. Dr. Gerald Fletcher has no financial disclosures. Dr. Peter W. Wilson is an advisor to Liposcience, Raleigh, North Carolina. Dr. Peter W. Wilson has received grants from Liposcience.
Discussion Dr. Brown: One of the strong beliefs that we all hold is that lack of exercise is a major problem for modern humans. * Corresponding author. E-mail address: [email protected] Submitted October 18, 2009. Accepted for publication October 19, 2009. † This discussion took place at the Westin Savannah Hotel, Savannah, GA, on August 15, 2009.
We blame our cardiovascular disease, obesity, and type 2 diabetes in part on this deficiency in our daily habits. However, scientific studies of exercise as an intervention to change the incidence of these and other related diseases has been difficult to acquire. Even the epidemiology of exercise has suffered from problems with methods of assessment and multiple confounding issues that accompany sedentary lifestyle such as affluence and diet. Dr. Gerald Fletcher has been a strong proponent of exercise as an intervention for prevention and treatment of cardiovascular disease and has been a major contributor to research and guidance for our current exercise recommendations in this context. Dr. Peter Wilson has a long career in the study of risk factors for cardiovascular disease development and has published extensively on the multiple issues that blend with sedentary lifestyle in attempting to improve our ability to predict and intervene on risk. They are with me to discuss the current status of our recommendations and to bring us up to date on the science that underlies these guidelines. Let’s start with the epidemiologic background. What can we say about cross-population comparisons? Are there any studies that have sufficient controls in them to be able to focus on exercise as a principle component of a healthy lifestyle in different populations? Has it been possible to do that? Dr. Fletcher: There are no randomized controlled trials on the benefits of exercise, nor have there been any on obesity or smoking, which we know have negative effects on health. The available data, as with obesity and smoking, support the negative effect of a sedentary lifestyle. Dr. Brown: But I’m speaking of it in an epidemiologic sense and just comparing one population with another as we’ve done with diet; for example, in Ancel Keys studies. Are there any studies that have measured daily exercise
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in a valid scientific way or is our community data mainly from anecdotal studies, such as the Tarahumara Indians kicking balls through the forest and that sort of thing. Dr. Wilson: Most studies that have focused on reported physical activity and heart disease have used questionnaire data. The survey instruments were rather rudimentary up until the 1970s. A classic group of studies were based on Harvard alumni and reported that increased leisure activity in men in their post-college years was especially predictive of people who were going to experience fewer cardiovascular events. These studies largely focused on the experience and habits of men 40 to 60 years of age. The information was self-reported, and fitness was not measured. The investigations lacked a good gauge for intensity of the activity. Investigators subsequently developed ways to assess kilocalorie expenditure by using crude scoring systems and showed that greater caloric expenditure was generally cardioprotective. One of the best-studied groups in more recent times has been the studies from the Cooper Center in Dallas, Texas. These studies included both men and women, and they collected additional information beyond reported physical activity. Approximately 10,000 men and 3,000 women underwent treadmill testing and were followed for the development of cardiovascular disease. These studies categorized the participants according to their level of fitness and showed that the lowest quintile of cardiovascular fitness on the treadmill was associated with greater vascular disease risk. One of these reports was affectionately called the ‘‘Couch Potato Study.’’ The greatest benefit is achieved by getting off the couch. Dr. Fletcher: Peter is right about the study by Blair et al. in men. Also the St. James study (Martha Gulati and others) compared treadmill data in women at a certain point in time (exercise capacity on a treadmill) with a 5-year follow-up for end points. Those who had the better treadmill time—greater exercise capacity—subsequently had less cardiovascular death, overall mortality, and morbidity. Both studies reflect the importance of the exercise capacity. Dr. Wilson: Another one that comes to mind was done within the Lipid Research Clinics study: they did formal treadmill testing looking for angina symptoms and ischemic changes by electrocardiogram (ECG). They found that assessing this at a standard pulse rate was difficult because exercise is not only limited by cardiovascular conditioning but in those who have arthritis or other lower-extremity complaints. Some get short of breath and stop, and they don’t get to their capacity. They revised the question in some respects and looked at the 6-minute performance level, which has become a very interesting assessment of fitness. The blood pressure and pulse responses at 6 minutes were a better indicator of outcome. Lower blood pressure – pulse product was indicative of lower event rates. It is it’s very difficult to interpret symptom-limited (total aerobic capacity), to do that, you’re talking about going up to stage 4, stage 5. So this has been one of the big barriers of assessing fitness
361 and it’s why many of the studies have gone back to looking at reported physical activity. Dr. Brown: So we have data that have been carefully collected—as I remember the longshoreman studies of Paffenbarger were linked ultimately to outcome data. Do you believe that we have adequate data that links a given level of exercise capacity to actual events? And at what level could you say average daily energy expenditure shows a significant reduction in events? For example, does walking 30 minutes a day show a significant reduction in events? Is there well documented reduction in cardiovascular events with more exercise than that? Dr. Fletcher: One thing we can say: certain people have a basic exercise capacity no matter what they do. Anyone that goes 10 minutes on the Bruce protocol, which is 1 MET/min (whether or not measured by oxygen consumption), has a very good prognosis for overall mortality, morbidity, and cardiovascular disease. If they only go 3 minutes, their outlook is less optimistic. If one can do the work capacity with an oxygen-consumption study, that’s even more accurate. Dr. Wilson: Many of the research projects have been very simple surveys undertaken by nonhealth professionals. These studies may gain some popularity in the lay press, but most of the modern questionnaires such as the SevenDay Recall and the Minnesota Leisure Time Questionnaire that have been used in population studies have also shown pretty good correlations with many of the cardiovascular risk factors. Are leaner individuals protected against heart disease? The answer is yes. Are more physically active and/or more physically fit people protected against heart disease? And the answer again is yes. But then people will say but you don’t show strong associations between being thin or being very active and heart disease risk, and that’s because the cardioprotection translates through the usual risk factors. It’s worth taking some time to discuss exactly what the key determinants for cardiovascular risk factors are for the person who is more physically active. Dr. Brown: I don’t think one can really get at the issue of whether having risk factors and developing a compromised cardiovascular system leads to reduced exercise or whether the person’s exercise habits have indeed led to reduced cardiovascular risk factors from epidemiological studies. So we don’t know which is the cart and which is the horse. Although there have been significant studies in which the authors assessed populations and showed that exercise levels—exercise capacity—clearly does predict outcome and relates to risk factors, interventional studies are necessary to prove that one can change the current status of individual risk. Tell me about interventional studies that you think are important and should provide conformation to the clinician that an effort towards having his patient exercise is truly worthwhile. Dr. Wilson: The person who is put into an exercise intervention program, if he truly follows the intervention, is likely to lose weight. If he’s a smoker, he is likely to reduce his smoking habit. Insulin resistance is likely to improve with physical activity, and so he would typically have a better
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fasting glucose and fasting insulin. Mild improvements in high-density lipoprotein (HDL) cholesterol often occur with physical activity. Running approximately 10 miles a week might typically lead to a 10-percent change in HDL cholesterol in the favorable direction. And similar, maybe even larger changes in the favorable direction for fasting triglycerides and not much change for LDL cholesterol. These risk factors have been documented to change with increased and consistent exercise programs. Dr. Fletcher: I would expand a bit on that. The triglycerides, absolutely. This can be changed in as short as 3 weeks. The HDL cholesterol takes sometimes 6 months or more to change. It’s a slow process but it can happen. The LDL can if there’s associated weight loss but not with exercise alone. Some have done small studies on vascular intimal medial thickness to look at the difference in those changes in people who exercise and who don’t. The endothelial function has been measured, and there’s good data to show that people who exercise with and without coronary artery disease do have improved endothelial function. A classic interventional study was reported by Hambrecht and Schuler some years ago. They evaluated coronary intimal lesions by coronary angiography in patients and controls before and after exercise. The exercise group did vigorous exercise for several months—6 days weekly at home plus once weekly in their clinic. The control group remained sedentary. There were no adverse events. In the exercise group repeat coronary studies revealed regression or lack of progression of the coronary lesions compared with the control patients, in whom there was no change. In this study the exercise was the only intervention. These data were published in well-reviewed journals and provides interesting data with interventional (anatomical) measurements to support the concept that post diagnosis exercise is beneficial. Our guidelines for rehabilitation would now prevent us from doing such a study in this country. One can no longer assign a post event patient to ‘‘no exercise.’’ Dr. Brown: I would like for you to expand a little more on lipoprotein changes. As you said, the change in the HDL takes a while and the LDL may not change at all. Is there a relationship with the level of exercise achieved or is it adipose tissue change that is the real operative measure here in terms of changing lipoproteins? We did a study in San Diego from the Lipid Research Clinic Cohort in men who were screened for the Coronary Primary Prevention Trial, had high cholesterol, and were without coronary disease but who didn’t actually participate in the trial. Their LDL cholesterol had fallen below the 175 mg/dL threshold for inclusion after they were given diet instruction. We put them on a supervised exercise program of increasing running to 4 miles per day, 3 days per week. We asked them maintain total body weight during the program. And they succeeded in doing that. At 6 months, there was a tremendous variability in adipose tissue mass measured at the beginning and the end of the
study. An increase in HDL cholesterol correlated beautifully with a decrease in adipose tissue mass. The mean HDL actually didn’t change significantly, but the correlation coefficient with change in adipose tissue mass was quite striking. LDL didn’t change just as you said. Triglycerides decreased dramatically. HDL often takes a while and doesn’t appear until well after loss of adipose tissue. It then increases to a greater level later after weight has been stabilized. This is true with calorie restriction as well. So the response of HDL concentrations is quite interesting and unexplained in terms of these weight changes. Is this a consistent finding, that the HDL is more strongly associated with adiposity rather than specifically with the level of exercise accomplished by a patient? Dr. Wilson: I don’t have an answer to that, but I think for the clinician who is wondering about average levels among people who are heavy exercisers that there are reasonable rules of thumb. The average HDL cholesterol for a middle-aged man is around 45 mg/dL. A male weekend jogger’s HDL-C is 55 mg/dL on average, and average levels in male marathoners are 65 mg/dL. HDL-C levels are generally greater for the women. For a typical sedentary woman the average HDL-C would be 55 mg/dL, and the woman who is very active you may see greater than that. You don’t tend to see very many women marathoners, but you do see women who will be taking some estrogen and a little bit of alcohol. So HDL-C levels in 55 to 70 mg/dL range are common. When I see an HDL of 70 mg/dL in a woman, I expect to find that she goes to the health club and she’s thin and she may be taking estrogens as well. Dr. Brown: There’s an interesting study of these marathoners done at Baylor. These people had in the 60 mg/dL plus range. They were asked to stop exercising for 4 weeks or so—about a month—and the HDL fell like a shot. By the end of that time it had dropped 15 to 20 points. They then they put them back on the exercise program and it took months to rebuild to that 60 to 65 HDL level. I find it intriguing again that HDL has these peculiar response times that don’t seem to fit nicely with our concepts of what exercise might do. Dr. Fletcher: That goes in concert with other training effects. If you ‘‘de-train’’ somebody for 3 weeks you lose a lot of their training achievements. It takes 6 weeks or more for them to ‘‘re-train.’’ This has been shown with people who go on lengthy and inactive vacations. Dr. Wilson: What about the different types of exercise? The groups that tend to get the most emphasis is what we would call endurance exercise and for men that’s often walking, jogging, and running, and swimming. Does the type of activity affect the physiologic and metabolic changes? What about strength training? Dr. Fletcher: Exercise needs to be done frequently. Those who exercise almost every day seem to have a better benefit, and we’re trying to recommend this to most. Aerobic exercises—running, biking, et cetera—are the ones that usually change the risk factors. You need some resistance exercise 2 or 3 times a week with the aerobics. But we’re
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looking more and more on a regular basis at not missing a day doing something. You may be physically active walking or in whatever you’re doing—even your yard work— but you should do physical activity every day. About 130 to 150 minutes per week is recommended exercise, and that’s not a lot of time if you consider how many minutes are in the week. Dr. Wilson: Some individuals gauge their activity with their achieved heart rate and it is important to realize that the responses depend on conditioning and age. A 75-yearold man who is walking at a fast clip is typically getting his heart rate up to over 100 and it is having an exercise effect. Do you agree with that? Dr. Fletcher: Surely I agree. It’s the perceived exertion that is better than heart rate or blood pressure. How hard are you working? If you can work until you’re very tired, that’s a good level of exercise—be it walking, bicycling, swimming, or running. Dr. Wilson: Please make a comment on weight lifting and its cardiovascular effects. Dr. Fletcher: For weight lifting, there are some data that it has an aerobic effect, but we’re really careful not to make that the only type of exercise people use. Adding some resistance exercise is important when you’re older because if you are stronger, you’re less likely to fall and there’s less frailty. So this is important as part of your exercise regimen. Dr. Brown: It’s interesting that professional athletes who require a lot of muscle strength but not necessarily a great amount of aerobic exercise don’t do well later. Weightlifters, for example, championship weightlifters often are quite heavy and quite obese actually. Sometimes football players can have both a lot of muscle and a lot of adipose tissue—and we know that the history there is not good either. Dr. Fletcher: There are some studies in the football players—the NFL players. The linemen (defensive, offensive)—their prognosis is not good when they retire unless they continue to exercise and control their weight. Dr. Brown: Are there good data on blood pressure control through exercise regimens? We know the lipid changes and we’ve discussed those, but what about other risk factors—diabetes control and blood pressure control? Dr. Fletcher: We looked at a large number of studies and the systolic blood pressure can be reduced by as much as 5 to 6 points and the diastolic as much as 3 to 4 points. This is just with exercise alone—no change in diet, no change in salt, and no change in anything else. But those are modest changes, and when you measure blood pressure these may be difficult to measure. Dr. Brown: But on a population basis, a 4-mm drop is quite significant. That predicts the prevention of a lot of strokes. Dr. Fletcher: Right. It’s hard to measure that difference at times when you’re taking blood pressure, but this is what we reported. Dr. Brown: There may be even more data on the question of diabetes control and exercise?
363 Dr. Fletcher: Especially with adult-onset diabetes— absolutely. But diabetics need to be careful if they have end organ problems, foot problems, et cetera, where they might have problems with the disease process itself being exacerbated by their exercise. We prescribe low-impact exercises that are carefully done in proper shoes. Dr. Brown: I think we’ve built a pretty good case for the clinician to recommend exercise as a beneficial intervention for our patients. Let me turn to the case of a young man who comes in at age 40, who may have a history of heart disease and a few risk factors—let’s say LDL of 160 and HDL of 35, triglycerides of 150. What would you tell him to do, Jere? Dr. Fletcher: He has risk factors and he’s 40 years old and he has had no type of cardiovascular event—no symptoms? Dr. Brown: Correct. Dr. Fletcher: I believe this type of person should start with a moderate level of exercise, nothing vigorous. He could start walking or maybe slow jogging, done most days of the week. If there is any question about significant coronary disease, a very simple exercise test on the treadmill should be performed, especially with those risk factors. But again, if it’s a low-level program then I believe it would be safe to do some regular aerobic exercise after review of the medical history and physical examination. Dr. Brown: You mentioned earlier that the duration of time on the tread mill probably tells you as much as anything in the asymptomatic person. Dr. Fletcher: On a treadmill—with the standard Bruce protocol, yes. Dr. Brown: And so is it possible to use that measure— duration with a Bruce protocol—to help you guide to the appropriate starting point with your exercise regimen? Dr. Fletcher: If you had a negative test in this 40-yearold man, absolutely. If he went 8 or 9 or 10 minutes and did a little running on the treadmill, then he would be free to go on if it’s a totally negative test—ECG, blood pressure, and all the other end points. I believe he could begin slow jogging program, carefully building up over a period of three to four weeks, not overdoing it but maintaining it. Dr. Brown: Would you give him a distance to run or a time to run? How would you tell him to do that? Dr. Fletcher: We’re recommending 30 to 60 minutes most days of the week, defined as 6 days a week (preferably most or all days of the week), and you can divide this up. We found it’s better—particularly for women—to do some activity in the morning and some in the afternoon. When you stop, there’s some training effect for a few minutes while you cool down. If one can’t go out and do 30 or 40 minutes at one time, then do some in the morning and some in the afternoon. Maybe a stationary bike in the morning and then go out for a jog in the afternoon after work. The quantity of exercise is important—how much you do per week and the long-term adherence. Dr. Brown: What about the use of these pedometers that have been very popular? Have those actually proven to be useful in your experience?
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Dr. Fletcher: I believe so. Certain people love little machines or devices. These often give them motivation and a means to measure what they are doing daily. Yes, they’re fine, and most of them now are very affordable. Dr. Brown: And have you ever built that into your regimen? Let’s say I know that 10,000 steps has been a number that’s often quoted as an appropriate amount of walking to keep you in a fairly good condition as part of an exercise program. And if you’ve done your 10,000 steps, you’ve really paid your debt in terms of exercise. Dr. Fletcher: Sometimes 10,000 steps can be done very slowly. People walk slowly at times and the 10,000 steps may not require much aerobic expenditure. If someone wants a good exercise program, make sure they’re doing moderate aerobic expenditure doing those steps to make sure that they achieve some training effect. Dr. Brown: Okay. Well now what about the person who is 70 and asymptomatic and comes to you? Do you deal with that person differently? Dr. Fletcher: A little, yes. These people, as we all know, have more heart disease and stroke risk when they’re older. So they probably need to start out more slowly. There are often musculoskeletal and arthritis problems. Low-impact exercise is very important in these people. Dr. Wilson: What about exercise in the person who is taking statins? Should we alter the exercise prescription? The patient may already be on a statin and wants to start an exercise program. Should he avoid certain types of aerobic exercise? Should he go a lot more gradually into a heavier program because he’s a statin user? Do we have firm recommendations? Dr. Fletcher: I don’t know of any data to support that current statin use makes a difference. We would of course make note that they’re on a statin, but we still recommend aerobic exercise. The American Heart Association’s statement on statin drugs some years ago did not reflect concern. Dr. Wilson: Some individuals are very heavy weekend exercisers and are taking statins. They may have very elevated creatine phosphokinase (CPK) levels. They may even be moderately high at baseline but then they come in to Monday morning clinic extremely high. What do you recommend concerning heavy-duty aerobic activity for these patients? Dr. Fletcher: In many clinical trials we’ve seen very high CPKs in patients who have done exercise but that has not correlated with statin use. So it may be more of a ‘‘property’’ of the individual rather than of the statin use. Dr. Brown: Let’s continue this discussion regarding the fitting of the exercise program to the patient at hand. What about the patient who has had an acute coronary event? Now I guess we think of this as a rehab operation. How is that different from the 70-year-old patient who comes in with the idea of maintaining a longer period of health in his life rather than the one who is now trying to recover from an acute coronary event—where we know we’ve got vascular disease present?
Dr. Fletcher: After acute infarction, it is best management for most to join a cardiac rehabilitation program for a designated period of time to begin exercise. Dr. Brown: This is to provide supervision of their exercise? Dr. Fletcher: To teach them how to exercise, and to provide appropriate monitoring. The ideal is a cardiac rehabilitation program and an exercise test before they are allowed to exercise at home. But if they wish to do only low-level activity and they’re absolutely asymptomatic and clinically stable, many can safely do such on their own and be checked periodically by a health professional. Dr. Wilson: The typical patient after experiencing a myocardial infarction (MI) will enter a 12-week cardiac rehab program? Let’s say he’s got a body mass index of 25 to 30 kg/m2 and he’s been relatively inactive. What level of fitness might he expect to achieve during rehabilitation? Dr. Fletcher: I would hope after cardiac rehabilitation that he could to do about 7 to 8 minutes on the Bruce protocol. This would be a modest level of intensity. This patient could include brisk walking, biking and recreational sports. Through the cardiac rehab we can usually determine limitations, and prescribe for them at home. They need to understand what they can do within boundaries, but intermittently. They should have an exercise test evaluation after a few weeks—especially those who have had some type of complication. Dr. Wilson: There are devices available that will monitor activity and caloric expenditure. Should patients use these devices? How should they monitor their symptoms? Dr. Fletcher: Many of them are on beta blockers. These affect the heart rate end point. Again the perceived exertion is important—seeing what they did on their discharge treadmill test—what the symptom level was on testing. They should do that level of exercise or less than that on their own at home. Monitoring the heart rate is difficult sometimes because of the inability to accurately do it and also because of beta blockers and other drugs that might affect heart rate. Dr. Brown: One of the problems with the older patient is that they often are restricted by other issues, arthritis, for example—osteoarthritis involving the lower extremities or back. What do you do with a patient where you believe exercise is an important component of their prevention where their mobility is really restricted? Dr. Fletcher: For many of these patients, aerobic water sports can be very good. Sometimes pools are not available, but the machines we have today—the low-impact elliptical trainers, the leg and arm/leg bikes, and other machines are very desirable and very good for training effects. Walking is very good for elderly people because there is less impact to the feet, ankles, knees, and hips. Dr. Wilson: Does that mean that older patients who are post-MI and who have gone through rehab need to go get a good pair of walking shoes? Dr. Fletcher: It is so important to have shoes that properly fit and with special foot problems as in diabetics, professional advice from a podiatrist or orthopedic service is wise.
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Dr. Wilson: It behooves the physician to help him find them—perhaps to identify a store that has the correct shoes and good counsel. Dr. Fletcher: Yes, that’s right. There are stores that do this. They may cost a little more, but the elderly should not chance ankle or foot injury by using improper shoes. Dr. Brown: How do you tell that you’ve been successful with an exercise program? What are the measures that you use to say that this person has really achieved what they should have achieved and that more exercise is not needed for this person? Dr. Fletcher: One thing that usually improves (and can be measured) is the quality of life. Those who have an exercise program really enjoy life. But we can also measure by follow-up exercise tests, the ECG, heart rate, rhythm, and evidence for control of weight, blood pressure and lipids. Dr. Wilson: The public health or population exercise prescription is in the range of 150 minutes a week of activity. What about exercising more than that? Is it only for personal satisfaction? Dr. Fletcher: That’s the main reason. If people have time and wish to do more activity, of course they may do their regular aerobic exercise and in addition go bowling, play tennis, do recreational sports—something they enjoy doing. Physical activity over and above 150 minutes adds even more to the health benefits. Dr. Brown: But a recommendation to the public and in general is very different from monitoring a patient. Dr. Fletcher: Yes. Dr. Brown: I would think a patient attempting to manage risk should have the goals that you as a physician can use in assessing success and so are there clues? Are there specific measures? For example, the Bruce protocol—is that ever used to find out if the patient truly has achieved a reasonable level of exercise? And are there other measures that you can use to make a judgment about whether you push the patient to do more, or recommend that they do less? Dr. Fletcher: The exercise test is always good and we’ve talked about those levels. But the 6-minute walk is also of benefit. Measuring the 6-minute walk distance and comparing it at 1 month, 3 months, and at 6 months is another way to assess the success of an exercise program. Dr. Wilson: What is the utility of a 6-minute walk? Should a patient go to the local high school track and see how far he can go in 6 minutes? Would you advise that as a reasonable way to assess their fitness, or should evaluations be done in a doctor’s office? What is your recommendation? Dr. Fletcher: If they are patients who have had coronary artery disease, they should probably do that in the hallway of the hospital where we do some of our studies, or in the physician’s office. Dr. Brown: I would suspect there’s a risk of walking with an 18-year-old by you and being challenged by that, too. Dr. Fletcher: Yes.
365 Dr. Wilson: For people without any symptoms do you believe that self-evaluation at the high school track is appropriate? Dr. Fletcher: Yes, and the 6-minute walk is probably fine if there are no symptoms and no known risks or disease. Dr. Brown: What if the 40-inch waist that you’re trying to reduce remains at 40 inches even though the patient’s exercise capacity increases and they now reach 8 minutes on the Bruce protocol? Would you believe that that is still a problem? Dr. Fletcher: It’s a 40-inch waist in a man or a woman? Dr. Brown: In a man. Dr. Fletcher: In a man, that’s borderline increased. There’s not much more you can do with exercise. Proper diet is in order to achieve weight loss. Dr. Brown: Among exercise activists who are also overweight, might make the point that being in condition really pretty much cancels out being obese and I think that there is evidence to the contrary, so I would like to hear your opinion—both of you—as to whether you think exercise completely abolishes the problem of having a fat pad around your middle. Dr. Wilson: About 20 years ago it was believed that running a marathon provided firm cardio protection. Unfortunately this is not true, and Jim Fixx’s death reminds us of the fact. He was a marathoner who had hyperlipidemia that was being treated. It’s also been more recently disproven even with moderate degrees of activity in those who don’t mind their lipids. The first unhealthy activity to limit is cigarette smoking. Heavy smokers in those who exercise can be a lethal combination. The person who smokes a pack a day and then says I’m going to go out and run fast can experience a sudden cardiac death. Reduction or total elimination of cigarette smoking is important and should be emphasized when talking with patients. The second major goal is to have lipids controlled. There certainly are some persons who say, ‘‘Today I’m going to become a moderately active walker, runner, jogger, eventually a marathoner,’’ and they follow on that path and their life is changed. The number of people who actually undertake such a program leading to a marathon is pretty small. Dr. Brown: Well it sounds like you’re also making a plea for building the exercise program into your lifestyle as demanded by your occupation or other issues, do you want to comment on that? Dr. Fletcher: It has to be part of your life—something you enjoy doing: Some hate exercising. Once they have a [cardiac] event or someone gets their attention in the workplace or in the physician or nurse’s office, they may become motivated. But for the long term, they need to find something they enjoy doing—maybe something they did in their school years. Such could be tennis, biking or swimming. Dr. Brown: Exercise has its place, we all agree. But I think there are people who have adopted exercise or
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devotees to exercise who seem to believe that exercise takes care of all of the risk factors. A major point that Peter was developing is that other risk factors may not be dealt with by the best exercise regimen, blood pressure that falls from 165 to 160 is not cured. LDL cholesterol that falls from 165 to 160 with exercise is not without risk. An HDL rise of a few points with exercise does not take away the risk of heart disease. As much as exercise may help, we must manage aggressively the total package of risk factors in a patient if we want to prevent coronary disease. Is that a fair statement? Dr. Fletcher: Absolutely. There’s no doubt about it, especially the lipids. All of these risks should be monitored and managed appropriately. Dr. Wilson: The lifestyle prescription needs to be different and much more gradual for the obese smoker. And the smoking program probably comes first. The obesity is always going to be a problem, and then I think you probably have to go much more gradually with the exercise program in the obese patient. Can you be fat, fit, and free of heart disease? We have colleagues who have touted this over the years, and I think the evidence is now leaning towards ‘‘no.’’ Individuals need get their risk factors in control to assure a lower risk of heart disease. Dr. Brown: I had the experience of hearing a lecture from one who believes very strongly about exercise and who made that point to a national medical meeting. About 3 months later we learned that symptoms appeared and a coronary bypass grafting procedure was being done. So I felt very badly for him, but on the other hand it was a lesson for an audience of medical people who heard and saw the story. Dr. Wilson: It is important to consider safety of the exercise. Jogging and bicycling on busy roadways can be a dangerous activity. Training at safe outdoor venues, health clubs, and gyms is important. Dr. Brown: In addition to the accidents, the fumes and so forth from cars and buses are harmful. This has been shown in a number of populations. Dr. Fletcher: Yes. There are good data to support harmful cardiac and pulmonary effects of exhaust fumes. Dr. Wilson: Should there be a different prescription for the man versus the woman? Let’s say they’re post-MI, 60 years old, relatively inactive. Do you say anything different to the man versus the woman in that situation? Dr. Fletcher: Not really. It’s individualized but of course a woman’s physical ‘‘makeup’’ can be a factor. There’s some difference in a woman’s cardiac output. For example, in women the left ventricular ejection plateaus with maximal exercise, while in men in continues to increase. But this doesn’t really affect the exercise prescription. Dr. Brown: There’s one group that we haven’t talked about that needs some special considerations and that is the person with peripheral vascular disease. How do you approach it when they get leg pain from ischemia when they move?
Dr. Fletcher: Bill Hiatt knows and has studied this quite well. There have been some good studies to show that longterm walking exercise to the point of slight discomfort can improve symptoms in these patients. With an exercise program, they can experience better exercise capacity and possibly improvement in the disease itself. Dr. Brown: Are there additional points that we haven’t covered and that either of you would like to see made? Dr. Fletcher: To emphasize the point that Peter made: The 3 biggest health problems in this country—smoking, sedentary lifestyle, and obesity are well known. These are lifestyle issues. The American public needs to be responsible, to have their own exercise program, to have eating habits to control body weight, and to refrain from smoking. This must be an individual responsibility. Physicians, health officials can of course nurture it along but this has to be an individual’s decision and commitment. Dr. Wilson: A special group is the diabetic population. Peripheral vascular disease is more common and may limit exercise opportunities for these individuals. Dr. Fletcher: Absolutely. Dr. Wilson: Peripheral neurological problems are more common in persons with diabetes mellitus. They often do not have good sensation in their feet and they may even have a greater need for specially fitted shoes. Another special consideration, especially for the insulin user or for the sulfonylurea user is the risk of hypoglycemia during exercise. Insulin users should be instructed on how to titrate their insulin according to carbohydrate intake and caloric expenditure. Extra visits to diabetes educators may help these patients. Dr. Fletcher: I would just echo that low-impact exercise is probably better for these types of patients because of what Peter mentioned. I recommend using elliptical machines or arm/leg and leg bikes; rather than running and other high-impact activities. Dr. Brown: Some of the diabetics I’ve taken care of have had a good habit: they either eat an apple before they exercise or they take something that’s going to have a longer, flatter glycemic index but that will maintain blood glucose. And they worked this out themselves because they determine from experience what food and the amount that will not throw their glucose out of control but will in fact sustain them through an exercise program. Dr. Wilson: Diabetic patients and those with coronary disease usually benefit by having an exercise buddy, somebody watching out for you, and that know how to treat hypoglycemia. They don’t have to be an expert, but their first reaction is to know that you may have some extra sugar in your purse or wallet and some appropriate responses. Dr. Fletcher: Having an exercise buddy is important. In post-cardiacs and not just diabetics. It is usually not wise to exercise alone. Dr. Wilson: One of the powers and strengths of the cardiac rehab programs is that people start to identify with individuals who are at the facilities when they go on a regular basis. Unfortunately, these are only 12-week programs. And just as the person is starting to change their lifestyle, our health
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system no longer continues funded support. This weakens the probability that this person’s new activity and new social network will be sustained. I believe that there are bikers or joggers who are not going to continue long term by themselves but might continue when involved in group activities. Dr. Brown: Are there organizations like Weight Watchers that might be exercise promoters, groups that can provide support and motivational interaction? I know there are health clubs like LA Fitness and so forth, but what about those that are actually more group oriented?
367 Dr. Fletcher: I don’t know of any Weight Watcher type programs that use exercise. It might be a great combination. Dr. Brown: Well, this has been a rich discussion that should be of substantial interest to our readers. Lipidologists should view advice regarding exercise regimens as one of the therapeutic maneuvers that offers real efficacy when adopted and sustained by our patients. Thank you very much for participating and our thanks to Daniel Sosnoski of the National Lipid Association for assisting with the preparation of this discussion.
Clinical Lipidology Roundtable Discussion
Using exercise to reduce risk† W. Virgil Brown, MD*, Gerald F. Fletcher, MD, Peter W. Wilson, MD Editor–in–Chief, The Journal of Clinical Lipidology, Professor Emeritus, Emory University School of Medicine, Atlanta, GA 30033, USA (Dr. Brown); Professor of Medicine, Mayo Clinic College of Medicine, Rochester, MN (Dr. Fletcher) and Professor of Medicine, Emory University School of Medicine, Atlanta, GA (Dr. Wilson)
Acknowledgment This roundtable discussion was supported by the National Lipid Association.
Disclosure Dr. W. Virgil Brown is an advisor to AstraZeneca, Wilmington, Delaware; Amgen, Thousand Oaks, California; Bristol-Myers Squibb, New York, New York; Eli Lilly, Indianapolis, Indiana; Genzyme Therapeutics, Cambridge, Massachusetts; Liposcience, Raliegh, North Carolina; Merck, Whitehouse Station, New Jersey; Merck/SheringPlough, Whitehouse Station, New Jersey; Pfizer, New York, New York; Roche, Basel, Switzerland; and Unilever, Englewood Cliffs, New Jersey. Dr. W. Virgil Brown has received education or research grants from Abbott Laboratories, Abbott Park, Illinois; AstraZeneca; Eli Lilly; Pfizer and Solvay Pharmaceuticals, Basel, Switzerland; Dr. W. Virgil Brown is a member of the speakers’ bureaus of Merck and Merck Schering-Plough. Dr. Gerald Fletcher has no financial disclosures. Dr. Peter W. Wilson is an advisor to Liposcience, Raleigh, North Carolina. Dr. Peter W. Wilson has received grants from Liposcience.
Discussion Dr. Brown: One of the strong beliefs that we all hold is that lack of exercise is a major problem for modern humans. * Corresponding author. E-mail address: [email protected] Submitted October 18, 2009. Accepted for publication October 19, 2009. † This discussion took place at the Westin Savannah Hotel, Savannah, GA, on August 15, 2009.
We blame our cardiovascular disease, obesity, and type 2 diabetes in part on this deficiency in our daily habits. However, scientific studies of exercise as an intervention to change the incidence of these and other related diseases has been difficult to acquire. Even the epidemiology of exercise has suffered from problems with methods of assessment and multiple confounding issues that accompany sedentary lifestyle such as affluence and diet. Dr. Gerald Fletcher has been a strong proponent of exercise as an intervention for prevention and treatment of cardiovascular disease and has been a major contributor to research and guidance for our current exercise recommendations in this context. Dr. Peter Wilson has a long career in the study of risk factors for cardiovascular disease development and has published extensively on the multiple issues that blend with sedentary lifestyle in attempting to improve our ability to predict and intervene on risk. They are with me to discuss the current status of our recommendations and to bring us up to date on the science that underlies these guidelines. Let’s start with the epidemiologic background. What can we say about cross-population comparisons? Are there any studies that have sufficient controls in them to be able to focus on exercise as a principle component of a healthy lifestyle in different populations? Has it been possible to do that? Dr. Fletcher: There are no randomized controlled trials on the benefits of exercise, nor have there been any on obesity or smoking, which we know have negative effects on health. The available data, as with obesity and smoking, support the negative effect of a sedentary lifestyle. Dr. Brown: But I’m speaking of it in an epidemiologic sense and just comparing one population with another as we’ve done with diet; for example, in Ancel Keys studies. Are there any studies that have measured daily exercise
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in a valid scientific way or is our community data mainly from anecdotal studies, such as the Tarahumara Indians kicking balls through the forest and that sort of thing. Dr. Wilson: Most studies that have focused on reported physical activity and heart disease have used questionnaire data. The survey instruments were rather rudimentary up until the 1970s. A classic group of studies were based on Harvard alumni and reported that increased leisure activity in men in their post-college years was especially predictive of people who were going to experience fewer cardiovascular events. These studies largely focused on the experience and habits of men 40 to 60 years of age. The information was self-reported, and fitness was not measured. The investigations lacked a good gauge for intensity of the activity. Investigators subsequently developed ways to assess kilocalorie expenditure by using crude scoring systems and showed that greater caloric expenditure was generally cardioprotective. One of the best-studied groups in more recent times has been the studies from the Cooper Center in Dallas, Texas. These studies included both men and women, and they collected additional information beyond reported physical activity. Approximately 10,000 men and 3,000 women underwent treadmill testing and were followed for the development of cardiovascular disease. These studies categorized the participants according to their level of fitness and showed that the lowest quintile of cardiovascular fitness on the treadmill was associated with greater vascular disease risk. One of these reports was affectionately called the ‘‘Couch Potato Study.’’ The greatest benefit is achieved by getting off the couch. Dr. Fletcher: Peter is right about the study by Blair et al. in men. Also the St. James study (Martha Gulati and others) compared treadmill data in women at a certain point in time (exercise capacity on a treadmill) with a 5-year follow-up for end points. Those who had the better treadmill time—greater exercise capacity—subsequently had less cardiovascular death, overall mortality, and morbidity. Both studies reflect the importance of the exercise capacity. Dr. Wilson: Another one that comes to mind was done within the Lipid Research Clinics study: they did formal treadmill testing looking for angina symptoms and ischemic changes by electrocardiogram (ECG). They found that assessing this at a standard pulse rate was difficult because exercise is not only limited by cardiovascular conditioning but in those who have arthritis or other lower-extremity complaints. Some get short of breath and stop, and they don’t get to their capacity. They revised the question in some respects and looked at the 6-minute performance level, which has become a very interesting assessment of fitness. The blood pressure and pulse responses at 6 minutes were a better indicator of outcome. Lower blood pressure – pulse product was indicative of lower event rates. It is it’s very difficult to interpret symptom-limited (total aerobic capacity), to do that, you’re talking about going up to stage 4, stage 5. So this has been one of the big barriers of assessing fitness
361 and it’s why many of the studies have gone back to looking at reported physical activity. Dr. Brown: So we have data that have been carefully collected—as I remember the longshoreman studies of Paffenbarger were linked ultimately to outcome data. Do you believe that we have adequate data that links a given level of exercise capacity to actual events? And at what level could you say average daily energy expenditure shows a significant reduction in events? For example, does walking 30 minutes a day show a significant reduction in events? Is there well documented reduction in cardiovascular events with more exercise than that? Dr. Fletcher: One thing we can say: certain people have a basic exercise capacity no matter what they do. Anyone that goes 10 minutes on the Bruce protocol, which is 1 MET/min (whether or not measured by oxygen consumption), has a very good prognosis for overall mortality, morbidity, and cardiovascular disease. If they only go 3 minutes, their outlook is less optimistic. If one can do the work capacity with an oxygen-consumption study, that’s even more accurate. Dr. Wilson: Many of the research projects have been very simple surveys undertaken by nonhealth professionals. These studies may gain some popularity in the lay press, but most of the modern questionnaires such as the SevenDay Recall and the Minnesota Leisure Time Questionnaire that have been used in population studies have also shown pretty good correlations with many of the cardiovascular risk factors. Are leaner individuals protected against heart disease? The answer is yes. Are more physically active and/or more physically fit people protected against heart disease? And the answer again is yes. But then people will say but you don’t show strong associations between being thin or being very active and heart disease risk, and that’s because the cardioprotection translates through the usual risk factors. It’s worth taking some time to discuss exactly what the key determinants for cardiovascular risk factors are for the person who is more physically active. Dr. Brown: I don’t think one can really get at the issue of whether having risk factors and developing a compromised cardiovascular system leads to reduced exercise or whether the person’s exercise habits have indeed led to reduced cardiovascular risk factors from epidemiological studies. So we don’t know which is the cart and which is the horse. Although there have been significant studies in which the authors assessed populations and showed that exercise levels—exercise capacity—clearly does predict outcome and relates to risk factors, interventional studies are necessary to prove that one can change the current status of individual risk. Tell me about interventional studies that you think are important and should provide conformation to the clinician that an effort towards having his patient exercise is truly worthwhile. Dr. Wilson: The person who is put into an exercise intervention program, if he truly follows the intervention, is likely to lose weight. If he’s a smoker, he is likely to reduce his smoking habit. Insulin resistance is likely to improve with physical activity, and so he would typically have a better
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fasting glucose and fasting insulin. Mild improvements in high-density lipoprotein (HDL) cholesterol often occur with physical activity. Running approximately 10 miles a week might typically lead to a 10-percent change in HDL cholesterol in the favorable direction. And similar, maybe even larger changes in the favorable direction for fasting triglycerides and not much change for LDL cholesterol. These risk factors have been documented to change with increased and consistent exercise programs. Dr. Fletcher: I would expand a bit on that. The triglycerides, absolutely. This can be changed in as short as 3 weeks. The HDL cholesterol takes sometimes 6 months or more to change. It’s a slow process but it can happen. The LDL can if there’s associated weight loss but not with exercise alone. Some have done small studies on vascular intimal medial thickness to look at the difference in those changes in people who exercise and who don’t. The endothelial function has been measured, and there’s good data to show that people who exercise with and without coronary artery disease do have improved endothelial function. A classic interventional study was reported by Hambrecht and Schuler some years ago. They evaluated coronary intimal lesions by coronary angiography in patients and controls before and after exercise. The exercise group did vigorous exercise for several months—6 days weekly at home plus once weekly in their clinic. The control group remained sedentary. There were no adverse events. In the exercise group repeat coronary studies revealed regression or lack of progression of the coronary lesions compared with the control patients, in whom there was no change. In this study the exercise was the only intervention. These data were published in well-reviewed journals and provides interesting data with interventional (anatomical) measurements to support the concept that post diagnosis exercise is beneficial. Our guidelines for rehabilitation would now prevent us from doing such a study in this country. One can no longer assign a post event patient to ‘‘no exercise.’’ Dr. Brown: I would like for you to expand a little more on lipoprotein changes. As you said, the change in the HDL takes a while and the LDL may not change at all. Is there a relationship with the level of exercise achieved or is it adipose tissue change that is the real operative measure here in terms of changing lipoproteins? We did a study in San Diego from the Lipid Research Clinic Cohort in men who were screened for the Coronary Primary Prevention Trial, had high cholesterol, and were without coronary disease but who didn’t actually participate in the trial. Their LDL cholesterol had fallen below the 175 mg/dL threshold for inclusion after they were given diet instruction. We put them on a supervised exercise program of increasing running to 4 miles per day, 3 days per week. We asked them maintain total body weight during the program. And they succeeded in doing that. At 6 months, there was a tremendous variability in adipose tissue mass measured at the beginning and the end of the
study. An increase in HDL cholesterol correlated beautifully with a decrease in adipose tissue mass. The mean HDL actually didn’t change significantly, but the correlation coefficient with change in adipose tissue mass was quite striking. LDL didn’t change just as you said. Triglycerides decreased dramatically. HDL often takes a while and doesn’t appear until well after loss of adipose tissue. It then increases to a greater level later after weight has been stabilized. This is true with calorie restriction as well. So the response of HDL concentrations is quite interesting and unexplained in terms of these weight changes. Is this a consistent finding, that the HDL is more strongly associated with adiposity rather than specifically with the level of exercise accomplished by a patient? Dr. Wilson: I don’t have an answer to that, but I think for the clinician who is wondering about average levels among people who are heavy exercisers that there are reasonable rules of thumb. The average HDL cholesterol for a middle-aged man is around 45 mg/dL. A male weekend jogger’s HDL-C is 55 mg/dL on average, and average levels in male marathoners are 65 mg/dL. HDL-C levels are generally greater for the women. For a typical sedentary woman the average HDL-C would be 55 mg/dL, and the woman who is very active you may see greater than that. You don’t tend to see very many women marathoners, but you do see women who will be taking some estrogen and a little bit of alcohol. So HDL-C levels in 55 to 70 mg/dL range are common. When I see an HDL of 70 mg/dL in a woman, I expect to find that she goes to the health club and she’s thin and she may be taking estrogens as well. Dr. Brown: There’s an interesting study of these marathoners done at Baylor. These people had in the 60 mg/dL plus range. They were asked to stop exercising for 4 weeks or so—about a month—and the HDL fell like a shot. By the end of that time it had dropped 15 to 20 points. They then they put them back on the exercise program and it took months to rebuild to that 60 to 65 HDL level. I find it intriguing again that HDL has these peculiar response times that don’t seem to fit nicely with our concepts of what exercise might do. Dr. Fletcher: That goes in concert with other training effects. If you ‘‘de-train’’ somebody for 3 weeks you lose a lot of their training achievements. It takes 6 weeks or more for them to ‘‘re-train.’’ This has been shown with people who go on lengthy and inactive vacations. Dr. Wilson: What about the different types of exercise? The groups that tend to get the most emphasis is what we would call endurance exercise and for men that’s often walking, jogging, and running, and swimming. Does the type of activity affect the physiologic and metabolic changes? What about strength training? Dr. Fletcher: Exercise needs to be done frequently. Those who exercise almost every day seem to have a better benefit, and we’re trying to recommend this to most. Aerobic exercises—running, biking, et cetera—are the ones that usually change the risk factors. You need some resistance exercise 2 or 3 times a week with the aerobics. But we’re
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looking more and more on a regular basis at not missing a day doing something. You may be physically active walking or in whatever you’re doing—even your yard work— but you should do physical activity every day. About 130 to 150 minutes per week is recommended exercise, and that’s not a lot of time if you consider how many minutes are in the week. Dr. Wilson: Some individuals gauge their activity with their achieved heart rate and it is important to realize that the responses depend on conditioning and age. A 75-yearold man who is walking at a fast clip is typically getting his heart rate up to over 100 and it is having an exercise effect. Do you agree with that? Dr. Fletcher: Surely I agree. It’s the perceived exertion that is better than heart rate or blood pressure. How hard are you working? If you can work until you’re very tired, that’s a good level of exercise—be it walking, bicycling, swimming, or running. Dr. Wilson: Please make a comment on weight lifting and its cardiovascular effects. Dr. Fletcher: For weight lifting, there are some data that it has an aerobic effect, but we’re really careful not to make that the only type of exercise people use. Adding some resistance exercise is important when you’re older because if you are stronger, you’re less likely to fall and there’s less frailty. So this is important as part of your exercise regimen. Dr. Brown: It’s interesting that professional athletes who require a lot of muscle strength but not necessarily a great amount of aerobic exercise don’t do well later. Weightlifters, for example, championship weightlifters often are quite heavy and quite obese actually. Sometimes football players can have both a lot of muscle and a lot of adipose tissue—and we know that the history there is not good either. Dr. Fletcher: There are some studies in the football players—the NFL players. The linemen (defensive, offensive)—their prognosis is not good when they retire unless they continue to exercise and control their weight. Dr. Brown: Are there good data on blood pressure control through exercise regimens? We know the lipid changes and we’ve discussed those, but what about other risk factors—diabetes control and blood pressure control? Dr. Fletcher: We looked at a large number of studies and the systolic blood pressure can be reduced by as much as 5 to 6 points and the diastolic as much as 3 to 4 points. This is just with exercise alone—no change in diet, no change in salt, and no change in anything else. But those are modest changes, and when you measure blood pressure these may be difficult to measure. Dr. Brown: But on a population basis, a 4-mm drop is quite significant. That predicts the prevention of a lot of strokes. Dr. Fletcher: Right. It’s hard to measure that difference at times when you’re taking blood pressure, but this is what we reported. Dr. Brown: There may be even more data on the question of diabetes control and exercise?
363 Dr. Fletcher: Especially with adult-onset diabetes— absolutely. But diabetics need to be careful if they have end organ problems, foot problems, et cetera, where they might have problems with the disease process itself being exacerbated by their exercise. We prescribe low-impact exercises that are carefully done in proper shoes. Dr. Brown: I think we’ve built a pretty good case for the clinician to recommend exercise as a beneficial intervention for our patients. Let me turn to the case of a young man who comes in at age 40, who may have a history of heart disease and a few risk factors—let’s say LDL of 160 and HDL of 35, triglycerides of 150. What would you tell him to do, Jere? Dr. Fletcher: He has risk factors and he’s 40 years old and he has had no type of cardiovascular event—no symptoms? Dr. Brown: Correct. Dr. Fletcher: I believe this type of person should start with a moderate level of exercise, nothing vigorous. He could start walking or maybe slow jogging, done most days of the week. If there is any question about significant coronary disease, a very simple exercise test on the treadmill should be performed, especially with those risk factors. But again, if it’s a low-level program then I believe it would be safe to do some regular aerobic exercise after review of the medical history and physical examination. Dr. Brown: You mentioned earlier that the duration of time on the tread mill probably tells you as much as anything in the asymptomatic person. Dr. Fletcher: On a treadmill—with the standard Bruce protocol, yes. Dr. Brown: And so is it possible to use that measure— duration with a Bruce protocol—to help you guide to the appropriate starting point with your exercise regimen? Dr. Fletcher: If you had a negative test in this 40-yearold man, absolutely. If he went 8 or 9 or 10 minutes and did a little running on the treadmill, then he would be free to go on if it’s a totally negative test—ECG, blood pressure, and all the other end points. I believe he could begin slow jogging program, carefully building up over a period of three to four weeks, not overdoing it but maintaining it. Dr. Brown: Would you give him a distance to run or a time to run? How would you tell him to do that? Dr. Fletcher: We’re recommending 30 to 60 minutes most days of the week, defined as 6 days a week (preferably most or all days of the week), and you can divide this up. We found it’s better—particularly for women—to do some activity in the morning and some in the afternoon. When you stop, there’s some training effect for a few minutes while you cool down. If one can’t go out and do 30 or 40 minutes at one time, then do some in the morning and some in the afternoon. Maybe a stationary bike in the morning and then go out for a jog in the afternoon after work. The quantity of exercise is important—how much you do per week and the long-term adherence. Dr. Brown: What about the use of these pedometers that have been very popular? Have those actually proven to be useful in your experience?
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Dr. Fletcher: I believe so. Certain people love little machines or devices. These often give them motivation and a means to measure what they are doing daily. Yes, they’re fine, and most of them now are very affordable. Dr. Brown: And have you ever built that into your regimen? Let’s say I know that 10,000 steps has been a number that’s often quoted as an appropriate amount of walking to keep you in a fairly good condition as part of an exercise program. And if you’ve done your 10,000 steps, you’ve really paid your debt in terms of exercise. Dr. Fletcher: Sometimes 10,000 steps can be done very slowly. People walk slowly at times and the 10,000 steps may not require much aerobic expenditure. If someone wants a good exercise program, make sure they’re doing moderate aerobic expenditure doing those steps to make sure that they achieve some training effect. Dr. Brown: Okay. Well now what about the person who is 70 and asymptomatic and comes to you? Do you deal with that person differently? Dr. Fletcher: A little, yes. These people, as we all know, have more heart disease and stroke risk when they’re older. So they probably need to start out more slowly. There are often musculoskeletal and arthritis problems. Low-impact exercise is very important in these people. Dr. Wilson: What about exercise in the person who is taking statins? Should we alter the exercise prescription? The patient may already be on a statin and wants to start an exercise program. Should he avoid certain types of aerobic exercise? Should he go a lot more gradually into a heavier program because he’s a statin user? Do we have firm recommendations? Dr. Fletcher: I don’t know of any data to support that current statin use makes a difference. We would of course make note that they’re on a statin, but we still recommend aerobic exercise. The American Heart Association’s statement on statin drugs some years ago did not reflect concern. Dr. Wilson: Some individuals are very heavy weekend exercisers and are taking statins. They may have very elevated creatine phosphokinase (CPK) levels. They may even be moderately high at baseline but then they come in to Monday morning clinic extremely high. What do you recommend concerning heavy-duty aerobic activity for these patients? Dr. Fletcher: In many clinical trials we’ve seen very high CPKs in patients who have done exercise but that has not correlated with statin use. So it may be more of a ‘‘property’’ of the individual rather than of the statin use. Dr. Brown: Let’s continue this discussion regarding the fitting of the exercise program to the patient at hand. What about the patient who has had an acute coronary event? Now I guess we think of this as a rehab operation. How is that different from the 70-year-old patient who comes in with the idea of maintaining a longer period of health in his life rather than the one who is now trying to recover from an acute coronary event—where we know we’ve got vascular disease present?
Dr. Fletcher: After acute infarction, it is best management for most to join a cardiac rehabilitation program for a designated period of time to begin exercise. Dr. Brown: This is to provide supervision of their exercise? Dr. Fletcher: To teach them how to exercise, and to provide appropriate monitoring. The ideal is a cardiac rehabilitation program and an exercise test before they are allowed to exercise at home. But if they wish to do only low-level activity and they’re absolutely asymptomatic and clinically stable, many can safely do such on their own and be checked periodically by a health professional. Dr. Wilson: The typical patient after experiencing a myocardial infarction (MI) will enter a 12-week cardiac rehab program? Let’s say he’s got a body mass index of 25 to 30 kg/m2 and he’s been relatively inactive. What level of fitness might he expect to achieve during rehabilitation? Dr. Fletcher: I would hope after cardiac rehabilitation that he could to do about 7 to 8 minutes on the Bruce protocol. This would be a modest level of intensity. This patient could include brisk walking, biking and recreational sports. Through the cardiac rehab we can usually determine limitations, and prescribe for them at home. They need to understand what they can do within boundaries, but intermittently. They should have an exercise test evaluation after a few weeks—especially those who have had some type of complication. Dr. Wilson: There are devices available that will monitor activity and caloric expenditure. Should patients use these devices? How should they monitor their symptoms? Dr. Fletcher: Many of them are on beta blockers. These affect the heart rate end point. Again the perceived exertion is important—seeing what they did on their discharge treadmill test—what the symptom level was on testing. They should do that level of exercise or less than that on their own at home. Monitoring the heart rate is difficult sometimes because of the inability to accurately do it and also because of beta blockers and other drugs that might affect heart rate. Dr. Brown: One of the problems with the older patient is that they often are restricted by other issues, arthritis, for example—osteoarthritis involving the lower extremities or back. What do you do with a patient where you believe exercise is an important component of their prevention where their mobility is really restricted? Dr. Fletcher: For many of these patients, aerobic water sports can be very good. Sometimes pools are not available, but the machines we have today—the low-impact elliptical trainers, the leg and arm/leg bikes, and other machines are very desirable and very good for training effects. Walking is very good for elderly people because there is less impact to the feet, ankles, knees, and hips. Dr. Wilson: Does that mean that older patients who are post-MI and who have gone through rehab need to go get a good pair of walking shoes? Dr. Fletcher: It is so important to have shoes that properly fit and with special foot problems as in diabetics, professional advice from a podiatrist or orthopedic service is wise.
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Dr. Wilson: It behooves the physician to help him find them—perhaps to identify a store that has the correct shoes and good counsel. Dr. Fletcher: Yes, that’s right. There are stores that do this. They may cost a little more, but the elderly should not chance ankle or foot injury by using improper shoes. Dr. Brown: How do you tell that you’ve been successful with an exercise program? What are the measures that you use to say that this person has really achieved what they should have achieved and that more exercise is not needed for this person? Dr. Fletcher: One thing that usually improves (and can be measured) is the quality of life. Those who have an exercise program really enjoy life. But we can also measure by follow-up exercise tests, the ECG, heart rate, rhythm, and evidence for control of weight, blood pressure and lipids. Dr. Wilson: The public health or population exercise prescription is in the range of 150 minutes a week of activity. What about exercising more than that? Is it only for personal satisfaction? Dr. Fletcher: That’s the main reason. If people have time and wish to do more activity, of course they may do their regular aerobic exercise and in addition go bowling, play tennis, do recreational sports—something they enjoy doing. Physical activity over and above 150 minutes adds even more to the health benefits. Dr. Brown: But a recommendation to the public and in general is very different from monitoring a patient. Dr. Fletcher: Yes. Dr. Brown: I would think a patient attempting to manage risk should have the goals that you as a physician can use in assessing success and so are there clues? Are there specific measures? For example, the Bruce protocol—is that ever used to find out if the patient truly has achieved a reasonable level of exercise? And are there other measures that you can use to make a judgment about whether you push the patient to do more, or recommend that they do less? Dr. Fletcher: The exercise test is always good and we’ve talked about those levels. But the 6-minute walk is also of benefit. Measuring the 6-minute walk distance and comparing it at 1 month, 3 months, and at 6 months is another way to assess the success of an exercise program. Dr. Wilson: What is the utility of a 6-minute walk? Should a patient go to the local high school track and see how far he can go in 6 minutes? Would you advise that as a reasonable way to assess their fitness, or should evaluations be done in a doctor’s office? What is your recommendation? Dr. Fletcher: If they are patients who have had coronary artery disease, they should probably do that in the hallway of the hospital where we do some of our studies, or in the physician’s office. Dr. Brown: I would suspect there’s a risk of walking with an 18-year-old by you and being challenged by that, too. Dr. Fletcher: Yes.
365 Dr. Wilson: For people without any symptoms do you believe that self-evaluation at the high school track is appropriate? Dr. Fletcher: Yes, and the 6-minute walk is probably fine if there are no symptoms and no known risks or disease. Dr. Brown: What if the 40-inch waist that you’re trying to reduce remains at 40 inches even though the patient’s exercise capacity increases and they now reach 8 minutes on the Bruce protocol? Would you believe that that is still a problem? Dr. Fletcher: It’s a 40-inch waist in a man or a woman? Dr. Brown: In a man. Dr. Fletcher: In a man, that’s borderline increased. There’s not much more you can do with exercise. Proper diet is in order to achieve weight loss. Dr. Brown: Among exercise activists who are also overweight, might make the point that being in condition really pretty much cancels out being obese and I think that there is evidence to the contrary, so I would like to hear your opinion—both of you—as to whether you think exercise completely abolishes the problem of having a fat pad around your middle. Dr. Wilson: About 20 years ago it was believed that running a marathon provided firm cardio protection. Unfortunately this is not true, and Jim Fixx’s death reminds us of the fact. He was a marathoner who had hyperlipidemia that was being treated. It’s also been more recently disproven even with moderate degrees of activity in those who don’t mind their lipids. The first unhealthy activity to limit is cigarette smoking. Heavy smokers in those who exercise can be a lethal combination. The person who smokes a pack a day and then says I’m going to go out and run fast can experience a sudden cardiac death. Reduction or total elimination of cigarette smoking is important and should be emphasized when talking with patients. The second major goal is to have lipids controlled. There certainly are some persons who say, ‘‘Today I’m going to become a moderately active walker, runner, jogger, eventually a marathoner,’’ and they follow on that path and their life is changed. The number of people who actually undertake such a program leading to a marathon is pretty small. Dr. Brown: Well it sounds like you’re also making a plea for building the exercise program into your lifestyle as demanded by your occupation or other issues, do you want to comment on that? Dr. Fletcher: It has to be part of your life—something you enjoy doing: Some hate exercising. Once they have a [cardiac] event or someone gets their attention in the workplace or in the physician or nurse’s office, they may become motivated. But for the long term, they need to find something they enjoy doing—maybe something they did in their school years. Such could be tennis, biking or swimming. Dr. Brown: Exercise has its place, we all agree. But I think there are people who have adopted exercise or
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devotees to exercise who seem to believe that exercise takes care of all of the risk factors. A major point that Peter was developing is that other risk factors may not be dealt with by the best exercise regimen, blood pressure that falls from 165 to 160 is not cured. LDL cholesterol that falls from 165 to 160 with exercise is not without risk. An HDL rise of a few points with exercise does not take away the risk of heart disease. As much as exercise may help, we must manage aggressively the total package of risk factors in a patient if we want to prevent coronary disease. Is that a fair statement? Dr. Fletcher: Absolutely. There’s no doubt about it, especially the lipids. All of these risks should be monitored and managed appropriately. Dr. Wilson: The lifestyle prescription needs to be different and much more gradual for the obese smoker. And the smoking program probably comes first. The obesity is always going to be a problem, and then I think you probably have to go much more gradually with the exercise program in the obese patient. Can you be fat, fit, and free of heart disease? We have colleagues who have touted this over the years, and I think the evidence is now leaning towards ‘‘no.’’ Individuals need get their risk factors in control to assure a lower risk of heart disease. Dr. Brown: I had the experience of hearing a lecture from one who believes very strongly about exercise and who made that point to a national medical meeting. About 3 months later we learned that symptoms appeared and a coronary bypass grafting procedure was being done. So I felt very badly for him, but on the other hand it was a lesson for an audience of medical people who heard and saw the story. Dr. Wilson: It is important to consider safety of the exercise. Jogging and bicycling on busy roadways can be a dangerous activity. Training at safe outdoor venues, health clubs, and gyms is important. Dr. Brown: In addition to the accidents, the fumes and so forth from cars and buses are harmful. This has been shown in a number of populations. Dr. Fletcher: Yes. There are good data to support harmful cardiac and pulmonary effects of exhaust fumes. Dr. Wilson: Should there be a different prescription for the man versus the woman? Let’s say they’re post-MI, 60 years old, relatively inactive. Do you say anything different to the man versus the woman in that situation? Dr. Fletcher: Not really. It’s individualized but of course a woman’s physical ‘‘makeup’’ can be a factor. There’s some difference in a woman’s cardiac output. For example, in women the left ventricular ejection plateaus with maximal exercise, while in men in continues to increase. But this doesn’t really affect the exercise prescription. Dr. Brown: There’s one group that we haven’t talked about that needs some special considerations and that is the person with peripheral vascular disease. How do you approach it when they get leg pain from ischemia when they move?
Dr. Fletcher: Bill Hiatt knows and has studied this quite well. There have been some good studies to show that longterm walking exercise to the point of slight discomfort can improve symptoms in these patients. With an exercise program, they can experience better exercise capacity and possibly improvement in the disease itself. Dr. Brown: Are there additional points that we haven’t covered and that either of you would like to see made? Dr. Fletcher: To emphasize the point that Peter made: The 3 biggest health problems in this country—smoking, sedentary lifestyle, and obesity are well known. These are lifestyle issues. The American public needs to be responsible, to have their own exercise program, to have eating habits to control body weight, and to refrain from smoking. This must be an individual responsibility. Physicians, health officials can of course nurture it along but this has to be an individual’s decision and commitment. Dr. Wilson: A special group is the diabetic population. Peripheral vascular disease is more common and may limit exercise opportunities for these individuals. Dr. Fletcher: Absolutely. Dr. Wilson: Peripheral neurological problems are more common in persons with diabetes mellitus. They often do not have good sensation in their feet and they may even have a greater need for specially fitted shoes. Another special consideration, especially for the insulin user or for the sulfonylurea user is the risk of hypoglycemia during exercise. Insulin users should be instructed on how to titrate their insulin according to carbohydrate intake and caloric expenditure. Extra visits to diabetes educators may help these patients. Dr. Fletcher: I would just echo that low-impact exercise is probably better for these types of patients because of what Peter mentioned. I recommend using elliptical machines or arm/leg and leg bikes; rather than running and other high-impact activities. Dr. Brown: Some of the diabetics I’ve taken care of have had a good habit: they either eat an apple before they exercise or they take something that’s going to have a longer, flatter glycemic index but that will maintain blood glucose. And they worked this out themselves because they determine from experience what food and the amount that will not throw their glucose out of control but will in fact sustain them through an exercise program. Dr. Wilson: Diabetic patients and those with coronary disease usually benefit by having an exercise buddy, somebody watching out for you, and that know how to treat hypoglycemia. They don’t have to be an expert, but their first reaction is to know that you may have some extra sugar in your purse or wallet and some appropriate responses. Dr. Fletcher: Having an exercise buddy is important. In post-cardiacs and not just diabetics. It is usually not wise to exercise alone. Dr. Wilson: One of the powers and strengths of the cardiac rehab programs is that people start to identify with individuals who are at the facilities when they go on a regular basis. Unfortunately, these are only 12-week programs. And just as the person is starting to change their lifestyle, our health
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Using exercise to reduce risk
system no longer continues funded support. This weakens the probability that this person’s new activity and new social network will be sustained. I believe that there are bikers or joggers who are not going to continue long term by themselves but might continue when involved in group activities. Dr. Brown: Are there organizations like Weight Watchers that might be exercise promoters, groups that can provide support and motivational interaction? I know there are health clubs like LA Fitness and so forth, but what about those that are actually more group oriented?
367 Dr. Fletcher: I don’t know of any Weight Watcher type programs that use exercise. It might be a great combination. Dr. Brown: Well, this has been a rich discussion that should be of substantial interest to our readers. Lipidologists should view advice regarding exercise regimens as one of the therapeutic maneuvers that offers real efficacy when adopted and sustained by our patients. Thank you very much for participating and our thanks to Daniel Sosnoski of the National Lipid Association for assisting with the preparation of this discussion.