Guidelines and recommendations for conventional

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1 42 PREVENTIVE CARDIOLOGY WINTER 2007 PERSPECTIVES CME Fitness: The Ultimate Marker for Risk Stratification and Health Outcomes? Barry A. Franklin, PhD Guidelines and recommendations for conventional coronary risk factors are widely available, as are clinically relevant threshold values for hypertension, cholesterol and its subfractions, overweight/obesity, and impaired fasting glucose. 1,2 In a widely-cited meta-analysis, Williams 3 reported that increasing levels of physical activity and cardiorespiratory fitness had significantly different relationships to cardiovascular disease. There was a 64% decline in the risk of heart disease from the least to the most fit, with a precipitous drop in risk when comparing the lowest (0) to the next lowest fitness category (ie, 25th percentile), but only a 30% decline from the least to the most physically active (Figure 1). It was concluded that being unfit warrants consideration as an independent risk factor, and that a low cardiorespiratory fitness or aerobic capacity increases the risk of cardiovascular disease to a greater extent than merely being physically inactive. Moreover, Blair et al. 4 demonstrated that the risk of cardiovascular disease and all-cause mortality in men and women was the highest for low fitness (least fit, 20%) vs other conventional risk factors. oxygen content per deciliter of blood. Thus, it is apparent that both central and peripheral regulatory mechanisms affect the magnitude of somatic oxygen consumption. The most widely recognized measure of cardiorespiratory fitness is the aerobic capacity or maximal oxygen consumption (VO 2 max). This variable is defined physiologically as the maximum rate of oxygen transport and utilization, as verified by a leveling off of oxygen consumption with increasing workloads. Because most healthy sedentary adults and cardiac patients reach a level of volitional fatigue and discomfort that is below their physiologic maximum, precluding attainment of their true VO 2 max, the preferred terminology for the highest rate of oxygen consumption achieved is the VO 2 peak. Although the VO 2 max or VO 2 peak may be expressed on an absolute basis in L/min, reflecting total body energy output and caloric expenditure (1 L of oxygen consumed is equivalent to 5 kcal [21 kj]), large persons usually have a large absolute oxygen consumption simply by virtue of their AEROBIC CAPACITY Somatic oxygen consumption may be expressed mathematically by a rearrangement of the Fick equation: VO 2 = HR SV (CaO 2 CvO 2 ) where VO 2 is oxygen consumption in ml/min, HR is heart rate in bpm, SV is stroke volume in milliliters per beat; and CaO 2 CvO 2 is the arterial venous oxygen difference in milliliters of From the Division of Cardiology, Cardiac Rehabilitation and Exercise Laboratories, William Beaumont Hospital, Royal Oak, MI Address for correspondence: Barry A. Franklin, PhD, William Beaumont Hospital, Beaumont Health Center, Preventive Cardiology/Cardiac Rehabilitation, 4949 Coolidge Highway, Royal Oak, MI bfranklin@beaumont.edu ID: 5759 Figure 1. The risks of coronary heart disease and cardiovascular disease decrease linearly in association with increasing percentiles of physical activity. In contrast, there is a precipitous drop in risk when comparing the lowest to the next-lowest category for aerobic capacity. Beyond this demarcation, the reductions in risk parallel those observed with increasing physical activity, but are essentially twice as great for aerobic capacity. Adapted from Williams. 3

2 WINTER 2007 PREVENTIVE CARDIOLOGY 43 large muscle mass. Consequently, the value is usually divided by body weight (in kilograms) so that people of various sizes may be compared. This variable, when expressed as milliliters of oxygen per kilogram body weight/minute (ml/kg/min), or as metabolic equivalents (METs; 1 MET = 3.5 ml/kg/ min), is considered the single best index of physical work capacity or cardiorespiratory fitness. 5 Because it is inconvenient to measure oxygen consumption directly, requiring sophisticated equipment, technical expertise, and frequent calibration, and collection of expired air inhibits verbal communication by the subject, clinicians have increasingly sought to predict or estimate VO 2 max from the treadmill speed and percent grade (Figure 2), or the cycle ergometer workload, expressed as kg m/min. 2 The conventional Bruce treadmill protocol is perhaps the most widely used, because it offers a rapid and safe progression for which estimated values for oxygen uptake have been established. 6 Aerobic capacity can be estimated from the treadmill time in men, women, and patients with heart disease (Table I). 7 HIGH RISK AND CARDIOPROTECTIVE FITNESS LEVELS Numerous epidemiologic studies in apparently healthy men and women, 4,8 those with comorbid conditions (eg, overweight/obesity, 9,10 hypertension, 11 type 2 diabetes 12 ), and those with suspected 13 or known 14,15 coronary artery disease, have now identified a low level of aerobic fitness as an independent risk factor for all-cause and cardiovascular mortality. Low-fit subjects were approximately 2 5 times more likely to die during the follow-up as compared with their more fit counterparts. Collectively, these findings and other recent reports 16 support the hypothesis that cardiorespiratory fitness provides a strong, graded inverse association with cardiovascular and all-cause mortality in healthy and unhealthy populations, irrespective of gender and/or existing comorbid conditions. The Aerobics Center Longitudinal Study (ACLS) represents the most comprehensive database regarding fitness and mortality. Table II illustrates low, moderate, and high fitness levels (in METs) for men and women, expressed as a function of age. The low-fitness groups are at increased mortality risk, whereas the high-fitness groups generally have an excellent prognosis, regardless of existing comorbidities or underlying coronary disease. These data should also be helpful in counseling patients regarding their current aerobic fitness and long-term fitness goals. Specifically, patients should be encouraged to improve their cardiorespiratory fitness through participation in a structured exercise program, increased lifestyle physical activity, 17 or both, to move them out of the least fit, high-risk cohort. For example, a 53-year-old man who achieves only 6 minutes on the conventional Bruce treadmill Figure 2. Metabolic cost of 3 common treadmill protocols. One metabolic equivalent (MET) signifies resting energy expenditure, equivalent to approximately 3.5 ml/ kg/min. Unlabeled numbers refer to the treadmill grade, expressed as percent. The patient s clinical status and functional class (I-IV) for the peak attained workload are also shown. mph indicates miles per hour. Table I. Conventional Bruce Treadmill Protocol With Metabolic Equivalent (MET) Values for Each Minute Interval Completed STAGE: MPH, MET REQUIREMENT* GRADE, % MIN MEN WOMEN CARDIAC I: 1.7, II: 2.5, III: 3.4, IV: 4.2, V: 5.0, *Note that women and cardiac patients achieve lower VO 2 for equivalent workload. Holding on to the front rail will increase the apparent MET capacity. mph indicates miles per hour. Adapted from American College of Sports Medicine. 7 protocol, corresponding to an estimated aerobic capacity of 7.4 METs (Table I), would be classified in the low fitness category (Table II), which is associated with an increased mortality rate. An initial goal would be to increase his fitness to the moderate category ( METs) and higher (>10.9 METs), if possible, in the future. On the other hand, a 64-year old woman who achieves 5 minutes on the conventional Bruce treadmill protocol,

3 44 PREVENTIVE CARDIOLOGY WINTER 2007 Table II. Aerobics Center Longitudinal Study Fitness Categories in Men and Women, by Age* SEX/ AGE GROUP, Y FITNESS GROUP Men Low Moderate High >12.7 >12.1 >10.9 >9.7 Women Low Moderate High >10.5 >9.5 >8.3 >7.5 *Table values are maximal metabolic equivalents attained during treadmill exercise testing. Adapted with permission from the Cooper Institute for Aerobics Research, Dallas, TX. would have an estimated aerobic capacity of 6.2 METs (Table I), corresponding to the moderate or average fitness category (Table II). A goal for her would be to achieve high fitness, or >7.5 METs. CONCLUSIONS Although the inverse relationship between fitness and cardiovascular and all-cause mortality has been widely promulgated among physiologists and epidemiologists, the medical community has, to a lesser extent, embraced aerobic capacity as one of the strongest and most consistent prognostic markers in persons with and without heart disease. It appears that low-fit individuals may especially benefit from exercise counseling to improve survival. 18 On the other hand, if a high fitness level truly exerts a cardioprotective effect that eliminates or markedly reduces any survival benefit from coronary revascularization, it has enormous implications for risk stratification and cost containment. Our recent preliminary data suggest that exercise capacity more accurately predicts 5-year mortality than does left ventricular ejection fraction in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention. 19 Moreover, there appears to be an inverse relationship between cardiorespiratory fitness and complications after bariatric surgery among morbidly obese adults. 20 Other provocative data support the hypothesis that exercise capacity is inversely associated with health care costs. 21 Collectively, these findings and other recent reports 22 suggest that measurement of exercise capacity can provide independent and additive information to the Framingham risk score. 23 Accordingly, physicians and allied health professionals should expand their medical evaluations and coronary risk factor profiling to include objective data regarding their patients exercise capacity expressed relative to age and gender norms. REFERENCES 1 Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update. Circulation. 2002;106: American College of Sports Medicine. ACSM s Guidelines for Exercise Testing and Prescription. 7th ed. Baltimore, MD: Lippincott Williams & Wilkins; Williams PT. Physical fitness and activity as separate heart disease risk factors: a meta-analysis. Med Sci Sports Exerc. 2001;33: Blair SN, Kampert JB, Kohl HW III, et al. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA. 1996;276: Buskirk E, Taylor HL. Maximal oxygen intake and its relation to body composition, with specific reference to chronic physical activity and obesity. J Appl Physiol. 1957;11: Bruce RA, Kusumi F, Hosmer D. Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J. 1973;85: American College of Sports Medicine. Guidelines for Exercise Testing and Prescription. 4th ed. Philadelphia, PA: Lea & Febiger; 1991:61. 8 Blair SN, Kohl HW III, Paffenbarger RS Jr, et al. Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA. 1989;262: Barlow CE, Kohl HW III, Gibbons LW, et al. Physical fitness, mortality and obesity. Int J Obes Relat Metab Disord. 1995;19(suppl 4):S41 S Wei M, Kampert JB, Barlow CE, et al. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA. 1999;282: Church TS, Kampert JB, Gibbons LW, et al. Usefulness of cardiorespiratory fitness as a predictor of all-cause and cardiovascular disease mortality in men with systemic hypertension. Am J Cardiol. 2001;88: Wei M, Gibbons LW, Kampert JB, et al. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Ann Intern Med. 2000;132: Myers J, Prakash M, Froelicher V, et al. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med. 2002;346: Kavanagh T, Mertens DJ, Hamm LF, et al. Prediction of long-term prognosis in men referred for cardiac rehabilitation. Circulation. 2002;106: Kavanagh T, Mertens DJ, Hamm LF, et al. Peak oxygen intake and cardiac mortality in women referred for cardiac rehabilitation. J Am Coll Cardiol. 2003;42: Laukkanen JA, Lakka TA, Rauramaa R, et al. Cardiovascular fitness as a predictor of mortality in men. Arch Intern Med. 2001;161: Gordon NF, Kohl HW III, Blair SN. Life style exercise: a new strategy to promote physical activity for adults. J Cardiopulm Rehabil. 1993;13: Franklin BA, Gordon NF. Contemporary Diagnosis and Management in Cardiovascular Exercise. Newtown, PA: Handbooks in Health Care Co; Dutcher JR, Kahn JK, Grines CL, et al. Comparison of left

4 WINTER 2007 PREVENTIVE CARDIOLOGY 45 ventricular ejection fraction and exercise capacity as predictors of 2- and 5-year mortality following acute myocardial infarction. Am J Cardiol. In press. 20 McCullough PA, Gallagher MJ, dejong AT, et al. Cardiorespiratory fitness and short-term complications after bariatric surgery. Chest. 2006;130: Weiss JP, Froelicher VF, Myers JN, et al. Health-care costs and exercise capacity. Chest. 2004;126: Gulati M, Pandey DK, Arnsdorf MF, et al. Exercise capacity and the risk of death in women: the St James Women Take Heart Project. Circulation. 2003;108: Wilson PW, D Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:

5 46 PREVENTIVE CARDIOLOGY WINTER 2007 CME QUESTIONS AND ANSWERS Insert your answers on the response page 1. The most widely recognized measure of cardiorespiratory fitness is: A. Peak heart rate B. Daily physical activity level C. Body mass index D. Maximal oxygen consumption 3. A low level of aerobic fitness is a risk factor for: A. Cardiovascular mortality B. All-cause mortality C. Both A and B D. Neither A nor B 2. The estimated peak oxygen consumption of a man who completes stage 3 of the standard Bruce exercise treadmill protocol can be expressed as: A. 10 metabolic equivalents B. 35 ml/kg/min C. Both A and B D. Neither A nor B ACCREDITATION: The University of California, Davis, Health System is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. This activity has been planned and implemented in accordance with the Essential Areas and Policies of the ACCME through the joint sponsorship of Oakstone Medical Publishing and Continuing Medical Education, UC Davis Health System. This CME activity was planned in accordance with the ACCME essentials for enduring materials. Length of time has been determined to be 1 hour. Please read the date of release and date of approval. PHYSICIAN CREDIT: Continuing Medical Education at the University of California, Davis, Health System designates this continuing medical education for 1 hour in Category 1 of the Physician s Recognition Award of the American Medical Association and the Certification Program of the California Medical Association. No partial credit is allowed for this CME activity. FACULTY DISCLOSURE: In accordance with standards of the ACCME and the guidelines of the Association of American Medical Colleges, the authors of this material have been asked to disclose any real or apparent conflicts of interest which may have a direct bearing on the subject matter presented. Authors are expected to disclose: 1) any significant financial interests or other relationships with manufacturers of commercial products and/or providers of commercial services discussed in their presentations; and 2) any off-label uses for pharmaceutical or medical device products discussed in their materials. The intent of this disclosure is not to prevent authors with significant financial or other relationships from making presentations, but rather to provide participants with information with which they can make their own judgments. AUTHOR DISCLOSURE: The author has no relationships to disclose. HOW TO OBTAIN CME CREDIT: To obtain CME credit, the University of California, Davis, Health System, Continuing Medical Education requires that you complete and return the answer sheet and program evaluation form with a check for $25, or you may fax the materials with Visa/MasterCard information for payment. Checks should be made payable to Regents of the University of California and mailed to: Continuing Medical Education, UC Davis Health System, 3560 Business Drive, Suite 130, Sacramento, CA To pay by Visa/Mastercard, please complete the entire application to include credit card number, expiration date and name of cardholder. You may fax this information to (916) Upon completion of the above, your certificate of credit will be mailed to you within 4 weeks. All required information for enduring materials are located at the Office of Continuing Medical Education, UC Davis Health System, 3560 Business Drive, Suite 130, Sacramento, CA Any questions about this process may be directed to Pamela Stotlar-McAuliffe at (916) ; FACULTY ADVISOR: Ezra A. Amsterdam, MD, Professor of Medicine, Division of Cardiovascular Medicine, University of California, Davis, School of Medicine, and Director, Cardiac Care Unit, University of California, Davis, Medical Center, Sacramento, CA OBJECTIVE AND TARGET AUDIENCE: All primary care physicians and cardiologists are eligible to receive credit. At the conclusion of this activity, participants should be able to: (1) summarize the important points discussed in the paper reviewed, (2) identify patients to whom the paper is relevant, (3) modify management practices as new information is learned, and (4) identify deficiencies in their knowledge base. CME answers are available on the Preventive Cardiology page at

6 WINTER 2007 PREVENTIVE CARDIOLOGY 47 INSTRUCTIONS: In order to complete this educational activity successfully, you must: o Complete the post-test. o Complete the program evaluation form. o Enclose a check for $25 payable to: Regents of the University of California or o Submit Visa/MasterCard information. PROGRAM EVALUATION 1. Did the material presented in this educational activity meet the stated learning objectives? o Yes o No 2. Please rate the contents of this activity using the following scale: 1=Poor; 2=Fair; 3=Good; 4=Very Good; 5=Excellent (circle the response for each question) Poor Excellent Timely and up-to-date? Practical? Relevant to your practice? Are there any other topics you would like to have seen addressed in this activity? o Yes (please specify): o No o Mail or fax your completed answer sheet and check to: Continuing Medical Education, UC Davis Health System, 3560 Business Drive, Suite 130, Sacramento, CA 95820; fax: In order to receive CME credit, the answer sheet must be received by January 2008 Thank you 4. Please describe any changes you plan to make in your clinical practice based on the information presented in this program. 5. Did you detect any commercial bias in this activity? o Yes o No If yes, please describe: 6. Any other comments/suggestions for future educational activities relating to preventive cardiology? POST-TEST RESPONSES (Please check the single BEST answer) 1. A B C D 2. A B C D 3. A B C D Please type or print clearly: Re: Franklin BA. Fitness: the ultimate marker for risk stratification and health outcomes? Prev Cardiol. 2007;10: Name: First Last Specialty Degree Street address City State Zip code Office phone with area code Social Security # (for transcript purposes only) Signature Date Please check your payment method: o Check payable to: Regents of the University of California o Visa o MasterCard Account number Expiration date Authorized signature