- Email: [email protected]
Results of cardiac rehabilitation in patients with diabetes mellitus
Results of Cardiac Rehabilitation in Patients With Diabetes Mellitus John A. Banzer, MD, Thomas E. Maguire, MS, Cheryl M. Kennedy, Carol J. O’Malley, RN, and Gary J. Balady, MD To study the prevalence, risk profile, and outcomes of diabetics in cardiac rehabilitation, data on 952 consecutively enrolled patients were evaluated. Diabetics on entry had poor glycemic control, and compared with nondiabetics, had a greater adverse risk profile (body mass index, waist circumference, hypertension, triglycerides, peripheral vascular disease, and lower fitness levels), and a lower program adherence rate. Although exercise capacity significantly improved, it is clear from the outcomes reported in this study that more effective interventions in weight management, lipid lowering, and glycemic control are needed. This study emphasizes the need to identify diabetic patients in contemporary cardiac rehabilitation programs and target them for an aggressive program of risk factor management, including exercise training. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:81– 84)
iabetes is a major public health problem with associated morbidity and mortality from coroD nary heart disease, hypertension, dyslipidemia, and 1,2
obesity. Coronary artery disease, the leading cause of premature death among patients with diabetes, accounts for nearly 80% of all deaths3 and hospital admissions in patients with diabetes. Patients with diabetes have a 2- to 4-fold higher risk of myocardial infarction, stroke, and death from cardiovascular disease than those without diabetes.2 Remarkably, the significant decrease in coronary heart disease mortality seen in the general population in recent decades has not been observed in diabetics.4 According to the American Diabetes Association, the estimated prevalence of diabetes among United States adults was 7.4% in 1995, and is expected to increase to 9% by 2025. Cardiac rehabilitation has been shown to improve functional capacity in men and women, and to favorably alter risk factor profiles.5 However, there are limited data that specifically address cardiac rehabilitation in diabetic patients, although such programs may be especially important in this group.6 Therefore, this study compares the clinical profiles of diabetic and nondiabetic patients in cardiac rehabilitation and evaluates their outcomes with respect to the effects of From the Section of Cardiology/Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts. Dr. Balady’s address is: Section of Cardiology, Boston Medical Center, 88 East Newton Street, Boston, Massachusetts 02118. E-mail: [email protected]. Manuscript received May 7, 2003; revised manuscript received and accepted September 5, 2003. ©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 January 1, 2004
MS,
exercise training on functional capacity, modification of coronary risk factors, and compliance. •••
Data were collected prospectively on 952 consecutive patients enrolled in the 10-week Cardiovascular Risk Reduction and Rehabilitation Program at Boston University Medical Center between 1993 and 2001. Patients were categorized as diabetic if they gave a history of diabetes mellitus at the time of enrollment into the cardiac rehabilitation program, whether or not they were taking medications for glycemic control. Data collection and program components have been previously described.7 All patients underwent an initial medical history and physical examination, including height, body weight, and waist measurements. Weight was measured to the nearest pound using a balanced floor scale. Waist circumference was measured by a single observer (GJB) using a standard tape measure at the widest level between the lower end of the rib cage and the top of the iliac crest, and was recorded to the nearest quarter inch. All patients underwent exercise testing in a standard manner using symptom-limited individualized ramp treadmill protocols. Peak MET level was estimated from peak exercise workrate as outlined in a previous study from this laboratory.8 Patients used the same treadmill protocol for initial and follow-up exercise testing at completion of the program. The program included several interventions. Supervised exercise training was conducted at an intensity of 45% to 85% of heart rate reserve9 based on the initial exercise tolerance test, and was further modified by perceived exertion. Exercise training was performed for 30 to 40 minutes, 3 times a week using various upper and lower body training modalities, including cycle ergometer, treadmill, rowing machine, and stairclimber apparatus. Nutritional counseling was provided, including individual assessment and counseling sessions by a registered dietician with follow-up as needed. An individualized diet plan was provided to each patient to establish a diet goal consistent with the American Heart Association/American Association of Cardiovascular and Pulmonary Rehabilitation recommendations.10 Specific recommendations were provided to those patients with diabetes, hypertension, and renal failure. Dietary counseling for weight reduction was also targeted toward those patients who were overweight or obese as defined by body mass index (BMI). Weekly group nutritional counseling sessions were provided to review dietary information and behavioral strategies that aimed to support individual patient goals. Pharmacologic treatment of elevated lipids was initiated or modified when indicated to attain the goals 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.09.017
81
TABLE 1 Baseline Patient Characteristics at Program Entry Diabetes Mellitus Entry Data Men Age (yrs) Black Hispanic Angina Coronary revascularization Myocardial infarction BMI (kg/m2) Waist female (in) Waist male (in) Systemic hypertension Current smoker Former smoker Peripheral vascular disease Medications Insulin/oral hypoglycemic agent Lipid-lowering agent Angiotensin-converting enzyme inhibitor  blocker Calcium antagonist Digoxin Diuretics Nitrates Exercise capacity (METs) Total cholesterol (mg/dL) High-density lipoprotein (mg/dl) Low-density lipoprotein (mg/dl) Triglycerides (mg/dL) Glycosylated HA1C
⫹ (n ⫽ 250) 54% 62 ⫾ 39% 12% 18% 53% 38% 34 ⫾ 42 ⫾ 44 ⫾ 67% 18% 27% 14%
10
8 6 7
0 (n ⫽ 702) 64%* 61 ⫾ 11 30%* 6%* 13% 42% 38% 31 ⫾ 6† 39 ⫾ 6 42 ⫾ 6 43%‡ 23% 28% 5%*
53%
0
58% 50%
46%* 38%*
FIGURE 1. Comparison of peak METs attained on exercise tests at entry (white bars) and at completion (black bars) of the program. Both diabetics (DM) and nondiabetics (non-DM) had significant improvements in exercise capacity. *p <0.001 within group.
as outlined per the National Cholesterol Education Program.11,12 Smoking cessation counseling was provided with pharmacologic treatment as indicated for those who were smoking at the time of program entry. Follow-up testing at program completion included an exercise tolerance test, measurement of body weight, and fasting lipid profile. Attendance rates were defined as the number of sessions attended divided by the number of sessions scheduled. Patients were defined as having completed the program if they underwent repeat testing and had an attendance record of ⱖ70%. Data are reported as mean ⫾ SD or 95% confidence intervals (CI). Initial and post-training risk factor and exercise variables were compared within and between groups using paired and nonpaired t tests or chi-square evaluation. A p value ⬍0.05 was considered statistically significant. Patient characteristics are listed in Table 1, grouped according to diabetic or nondiabetic status. Of the 952 patients, 582 were men and 370 were women (mean age 61 ⫾ 10 years). Twenty-six percent (n ⫽ 250) of the patient population had a history of diabetes at program entry, of whom 53% were taking insulin and/or oral hypoglycemic medications. There were more black and Hispanic patients in the diabetic
compared with the nondiabetic group (51% v 36%, respectively; p ⬍0.05). The prevalence of diabetes increased from 22% from 1993 to 1997 to 30% during 1998 to 2001. Diabetics had a greater adverse risk profile, including greater prevalence of hypertension (p ⬍0.0001), obesity (p ⬍0.0001), peripheral vascular disease (p ⬍0.05), and lower exercise capacity (p ⬍0.0001). At entry, the initial glycosylated hemoglobin A1C (HA1C) of the diabetics was 8.4% (95% CI 8.1 to 8.7). Overall, 428 patients (45% of the total group) completed the cardiac rehabilitation program as defined above. Significantly fewer diabetics (38%) completed the program compared with nondiabetics (48%; p ⬍0.05). Of those not completing cardiac rehabilitation, exacerbation of a medical problem (cardiac and noncardiac etiology) was the cause of dropout among 29% of diabetics versus 18% of nondiabetics (p ⬍0.01). Exercise capacity was determined by the peak MET level from the exercise test. Diabetics had a significantly lower exercise capacity at entry than nondiabetics (5.7 vs 7.0 METs, respectively; p ⬍0.0001). Of the 428 patients who completed the program, the peak MET level between the initial and follow-up exercise tolerance test increased significantly and similarly in both groups (26% in the diabetics and 27% in the nondiabetics; p ⬍0.001 pre- vs postexercise training) (Figure 1). Diabetics were significantly more obese upon program entry than nondiabetics (BMI 34.1 vs 30.8, respectively; p ⬍0.0001). Analysis of weight change in overweight patients (BMI ⱖ25) who completed the program was performed by dividing the diabetic and nondiabetic patients each into 2 groups: those with a BMI of ⱖ25.0 to 29.9 and those with a BMI of ⱖ30.0. Among the nondiabetic patients with a BMI of ⱖ30, there was a significant weight loss of 5.4 pounds from program entry to completion (p ⬍0.0001) (see Figure 2). Weight did not change in any other subgroup. No differences in weight change were observed between those diabetic patients who were taking or not taking
82 THE AMERICAN JOURNAL OF CARDIOLOGY姞
JANUARY 1, 2004
68% 44% 10% 36% 32% 5.7 ⫾ 2.3 188 ⫾ 50 43 ⫾ 15
61% 30%* 13% 23% 21% 7.0 ⫾ 2.6† 193 ⫾ 46 44 ⫾ 15
105 ⫾ 39
118 ⫾ 41
195 ⫾ 219 8.4%
161 ⫾ 129* —
Data are shown as mean ⫾ SD or percentages. *p ⬍0.05; †p ⬍0.0001.
VOL. 93
FIGURE 2. Weight change in patients with BMI of >30 who completed the program (n ⴝ 184). ‡p <0.0001 within group. Abbreviations as in Figure 1.
medications for glycemic control. Lipid-lowering therapy was taken by 58% of diabetics and 46% of nondiabetics at program entry. Lipid-lowering medications were added or modified in 3.2% of diabetics and 3.7% of nondiabetics. However, follow-up lipid levels were obtained in only 36% of patients, limiting this variable in outcome assessment. There was no significant change in mean total cholesterol, low-density lipoprotein, high-density lipoprotein, or triglyceride levels from program entry to program completion in either group. •••
Outcome assessment is integral to the successful evaluation and delivery of services provided in cardiac rehabilitation/secondary prevention programs.13,10 Accordingly, interventions that are found to be successful can be enhanced and promoted, whereas those with little effect can be modified or eliminated. Publication of outcome data are important to increase awareness regarding the needs and issues specific to a given population or subgroup, promote effective interventions, and foster further research in those areas in which better outcomes are clearly needed. This study examined the prevalence, clinical profile, and outcome of diabetic patients among a large number of patients enrolled in a single clinical program, which offered standard, comprehensive cardiac rehabilitation.10 The data reveal that diabetics have a greater prevalence of cardiac risk factors and lower exercise capacity than nondiabetics. Diabetics more frequently have hypertension, obesity, and peripheral vascular disease than nondiabetics. Although no data were available regarding the effect of cardiac rehabilitation on HA1C levels in diabetics, the mean HA1C of 8.4% demonstrates evidence of poor glycemic control on enrollment. Thus, the case for effective cardiac rehabilitation/secondary prevention interventions is compelling. The compliance rate of 45% for all patients in this program is on the low end of the 39% to 86% compliance rate range reported for cardiac rehabilitation programs.14,15 However, diabetics had a remarkable 62% dropout rate, and tended to be less likely than
nondiabetics to complete the program. Diabetic patients withdrew more often because of an exacerbation of a medical problem, although cardiac conditions precluded program completion at a similar rate in both groups (9.8% of diabetics vs 8.5% of nondiabetics). Whether diabetic patients had more severe cardiovascular illness is not known, although they did have a greater number of co-morbidities. Whether the exercise training component of cardiac rehabilitation led to an exacerbation of medical problems in these patients cannot be answered by these data, but poses an important question for further research. For those diabetics who completed the program, significant improvements in functional capacity were demonstrated. Compared with nondiabetics, diabetics had a lower initial exercise capacity, but achieved the same degree of improvement in functional capacity with training in cardiac rehabilitation. The change in functional capacity among diabetic patients was similar to that of nondiabetics from this program,7,16 and others.5,17 Although not evaluated in this study, improvement in peak MET level may yield benefits in activities of daily living, quality of life, and possibly subsequent morbidity and mortality. Weight loss among overweight and obese patients was limited to the group of nondiabetic patients with a BMI of ⱖ30, yet the change in weight was only modest. These weight change data, and those of other reports and programs6,18 –21 call attention to the need for more effective weight management strategies and interventions in cardiac rehabilitation/secondary prevention programs. Although no change in lipid levels in either group was observed, the outcome data for this variable are limited because lipids were measured and treated as clinically indicated. Often, if lipidlowering therapy was initiated or modified mid-program, a follow-up profile might not have been obtained until some time after the patient had completed the program. Despite our best efforts to obtain these data, they remain incomplete. There are a few additional limitations to the present study. Only 45% of the original cohort completed the 10-week program. However, the definition of dropout was stringent in that either the failure to attend ⬎70% of scheduled sessions, or failure to return to the program to complete a follow-up exercise test, lipid profile, or weight measurement (despite attending ⬎70% of scheduled sessions) met criteria. Finally, this observational study lacked a control group of matched patients who were not enrolled in cardiac rehabilitation. The American Heart Association promotes a multifaceted approach to the delivery of preventive efforts in diabetic patients.18 Accordingly, cardiac rehabilitation/secondary prevention programs represent an important venue for the delivery of these interventions to diabetic patients with cardiovascular disease. Data from this study emphasize the need to identify diabetic patients in cardiac rehabilitation programs and target them for an aggressive program of risk factor management. Although exercise capacity significantly improved, risk factor outcomes were disappointing. It is clear that more effective and sustained interventions in BRIEF REPORTS
83
weight management, lipid lowering, and glycemic control are needed. A coordinated program, designed to work closely with primary care providers and consultants specializing in diabetes care, has the potential to deliver the best short- and long-term results. The prevalence of diabetic patients in cardiac rehabilitation programs appears to be increasing, and is likely to continue to do so as the national prevalence of diabetes increases. Such targeted programs need to be designed, implemented and evaluated, and offer a great opportunity for future research, as well as internal quality improvement efforts. 1. Barret-Connor E, Cohn BA, Wingard DL, Edelstein SL. Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study. JAMA 1991;265:627–631. 2. Haffner SM, Lehto S, Ro¨ nnemaa T, Pyo¨ ra¨ la¨ K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior MI. N Engl J Med 1998;339:229 –234. 3. Kannel WB. Lipids, diabetes, and coronary heart disease: insights from the Framingham Study. Am Heart J 1985;110:1100 –1107. 4. Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA 1999;281:1291–1297. 5. Wenger NK, Froelicher ES, Smith LK. Cardiac Rehabilitation. Clinical Practice Guideline No. 17. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agencies for Health Care Policy and Research and the National Heart, Lung and Blood Institute. AHCPR Publication No. 96-0672. October 1995. 6. Milani RV, Lavie CJ. Behavioral differences and effects of cardiac rehabilitation in diabetic patients following cardiac events. Am J Med 1996;100:517–523. 7. Bader DS, Maguire TE, Spahn C, O’Malley CJ, Balady GJ. Clinical profile and outcome of obese patients in cardiac rehabilitation as stratified according to NHLBI criteria. J Cardiopulmonary Rehabil 2001;21:210 –217. 8. McInnis KJ, Bader DS, Maguire T, Balady GJ. Comparison of cardiopulmonary responses in obese women using ramp versus step treadmill protocols. Am J Cardiol 1999;83:289 –291. 9. American College of Sports Medicine. American College of Sports Medicine Position Stand. The recommended quantity and quality of exercise for developing
and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Med Sci Sports Exerc 1998;30:975–979. 10. Balady GJ, Ades PA, Comoss P, Limacher M, Pina I, Southard D, Williams MA, Bazzarre T. AHA/AACVPR core components of cardiac rehabilitation/ secondary prevention programs. Circulation 2000;102:1069 –1073. 11. National Cholesterol Education Program Expert Panel. Second Report of the Expert Panel in detection, evaluation and treatment of high blood cholesterol in adults. Bethesda, MD: National Institutes of Health, National Heart, Lung and Blood Institute. NIH Publication 93-3095, 1993. 12. Cleeman J. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285: 2486 –2496. 13. American Association for Cardiovascular and Pulmonary Rehabilitation. Guidelines for Cardiac Rehabilitation and Secondary Prevention Programs. Champaign, IL: Human Kinetics Publishers, 1999. 14. Oldridge NB, Wicks JR, Hanley G, Sutton JR, Jones NL. Noncompliance in an exercise rehabilitation program for men who have suffered a myocardial infarction. Can Med Assoc J 1978;111:361–364. 15. Bruce EH, Frederick R, Bruce RA, Fisher LD. Comparison of active participants and dropouts in CAPRI cardiopulmonary rehabilitation programs. Am J Cardiol 1976;37:53–60. 16. Cannistra L, Balady GJ, O’Malley CJ, Weiner DA, Ryan TJ. Comparison of the clinical profile and outcome of women and men in cardiac rehabilitation. Am J Cardiol 1992;69:1274 –1279. 17. Balady GJ, Jette D, Scheer J, Downing J. Changes in exercise capacity following cardiac rehabilitation in patients stratified according to age, and gender. Results from the MACVPR Database. J Cardiopulmonary Rehabil 1996;16:38 – 46. 18. Yu C, Li L, Ho H, Lau C. Long-term changes in exercise capacity, quality of life, body anthropometry, and lipid profiles after a cardiac rehabilitation program in obese patients with coronary heart disease. Am J Cardiol 2003;91:321–325. 19. Lavie CJ, Milani RV. Effects of cardiac rehabilitation, exercise training, and weight reduction on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in obese coronary patients. Am J Cardiol 1997;79: 397–401. 20. Gordon NF, English C, Contractor AS, Slamon RD, Leighton R, Franklin BA, Haskell WL. Effectiveness of three models for comprehensive cardiovascular disease risk reduction. Am J Cardiol 2002;89:1263–1268. 21. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC, Sowers JR. Diabetes, and cardiovascular care. A Statement for Healthcare Professionals from the American Heart Association. Circulation 1999;100:1134 –1146.
Effect of Atorvastatin 80 mg on Endothelial Cell Function (Forearm Blood Flow) in Patients With Pretreatment Serum Low-Density Lipoprotein Cholesterol Levels <130 mg/dl Sven Wassmann, MD, Nicole Ribaudo, MS, Anna Faul, MS, Ulrich Laufs, Michael Bo ¨ hm, MD, and Georg Nickenig, MD The effect of 6-week treatment with 80 mg/day atorvastatin on vascular function in the forearm was investigated in 18 patients with mean pretreatment serum low-density lipoprotein cholesterol concentrations of 112 ⴞ 4 mg/dl in a double-blind, placebo-controlled, randomized study. Statin treatFrom the Medizinische Klinik und Poliklinik, Innere Medizin III, Universita¨ tskliniken des Saarlandes, Homburg/Saar, Germany. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) Bonn, and by an unrestricted research grant from Pfizer Germany, Karlsruhe, Germany. Dr. Wassmann’s address is: Medizinische Klinik und Poliklinik, Innere Medizin III, Universita¨ tskliniken des Saarlandes, 66421 Homburg/Saar, Germany. E-mail: [email protected]. de. Manuscript received April 30, 2003; revised manuscript received and accepted September 2, 2003.
84
©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 January 1, 2004
MD,
ment improved hyperemic forearm blood flow and decreased serum markers of oxidative stress and inflammation. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:84 – 88)
he effect of 3-hydroxy-3 methylglutary co-enzyme A reductase inhibitors (statins) on vascular funcT tion in patients with low serum cholesterol levels is unclear. Trials investigating the impact of statins on coronary endothelial dysfunction have included patients with low-density lipoprotein (LDL) cholesterol levels between 140 and 195 mg/dl.1–3 In recent clinical trials, statin treatment prevented cardiovascular events irrespective of baseline cholesterol levels, including patients who had LDL cholesterol levels of 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.09.018
iabetes is a major public health problem with associated morbidity and mortality from coroD nary heart disease, hypertension, dyslipidemia, and 1,2
obesity. Coronary artery disease, the leading cause of premature death among patients with diabetes, accounts for nearly 80% of all deaths3 and hospital admissions in patients with diabetes. Patients with diabetes have a 2- to 4-fold higher risk of myocardial infarction, stroke, and death from cardiovascular disease than those without diabetes.2 Remarkably, the significant decrease in coronary heart disease mortality seen in the general population in recent decades has not been observed in diabetics.4 According to the American Diabetes Association, the estimated prevalence of diabetes among United States adults was 7.4% in 1995, and is expected to increase to 9% by 2025. Cardiac rehabilitation has been shown to improve functional capacity in men and women, and to favorably alter risk factor profiles.5 However, there are limited data that specifically address cardiac rehabilitation in diabetic patients, although such programs may be especially important in this group.6 Therefore, this study compares the clinical profiles of diabetic and nondiabetic patients in cardiac rehabilitation and evaluates their outcomes with respect to the effects of From the Section of Cardiology/Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts. Dr. Balady’s address is: Section of Cardiology, Boston Medical Center, 88 East Newton Street, Boston, Massachusetts 02118. E-mail: [email protected]. Manuscript received May 7, 2003; revised manuscript received and accepted September 5, 2003. ©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 January 1, 2004
MS,
exercise training on functional capacity, modification of coronary risk factors, and compliance. •••
Data were collected prospectively on 952 consecutive patients enrolled in the 10-week Cardiovascular Risk Reduction and Rehabilitation Program at Boston University Medical Center between 1993 and 2001. Patients were categorized as diabetic if they gave a history of diabetes mellitus at the time of enrollment into the cardiac rehabilitation program, whether or not they were taking medications for glycemic control. Data collection and program components have been previously described.7 All patients underwent an initial medical history and physical examination, including height, body weight, and waist measurements. Weight was measured to the nearest pound using a balanced floor scale. Waist circumference was measured by a single observer (GJB) using a standard tape measure at the widest level between the lower end of the rib cage and the top of the iliac crest, and was recorded to the nearest quarter inch. All patients underwent exercise testing in a standard manner using symptom-limited individualized ramp treadmill protocols. Peak MET level was estimated from peak exercise workrate as outlined in a previous study from this laboratory.8 Patients used the same treadmill protocol for initial and follow-up exercise testing at completion of the program. The program included several interventions. Supervised exercise training was conducted at an intensity of 45% to 85% of heart rate reserve9 based on the initial exercise tolerance test, and was further modified by perceived exertion. Exercise training was performed for 30 to 40 minutes, 3 times a week using various upper and lower body training modalities, including cycle ergometer, treadmill, rowing machine, and stairclimber apparatus. Nutritional counseling was provided, including individual assessment and counseling sessions by a registered dietician with follow-up as needed. An individualized diet plan was provided to each patient to establish a diet goal consistent with the American Heart Association/American Association of Cardiovascular and Pulmonary Rehabilitation recommendations.10 Specific recommendations were provided to those patients with diabetes, hypertension, and renal failure. Dietary counseling for weight reduction was also targeted toward those patients who were overweight or obese as defined by body mass index (BMI). Weekly group nutritional counseling sessions were provided to review dietary information and behavioral strategies that aimed to support individual patient goals. Pharmacologic treatment of elevated lipids was initiated or modified when indicated to attain the goals 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.09.017
81
TABLE 1 Baseline Patient Characteristics at Program Entry Diabetes Mellitus Entry Data Men Age (yrs) Black Hispanic Angina Coronary revascularization Myocardial infarction BMI (kg/m2) Waist female (in) Waist male (in) Systemic hypertension Current smoker Former smoker Peripheral vascular disease Medications Insulin/oral hypoglycemic agent Lipid-lowering agent Angiotensin-converting enzyme inhibitor  blocker Calcium antagonist Digoxin Diuretics Nitrates Exercise capacity (METs) Total cholesterol (mg/dL) High-density lipoprotein (mg/dl) Low-density lipoprotein (mg/dl) Triglycerides (mg/dL) Glycosylated HA1C
⫹ (n ⫽ 250) 54% 62 ⫾ 39% 12% 18% 53% 38% 34 ⫾ 42 ⫾ 44 ⫾ 67% 18% 27% 14%
10
8 6 7
0 (n ⫽ 702) 64%* 61 ⫾ 11 30%* 6%* 13% 42% 38% 31 ⫾ 6† 39 ⫾ 6 42 ⫾ 6 43%‡ 23% 28% 5%*
53%
0
58% 50%
46%* 38%*
FIGURE 1. Comparison of peak METs attained on exercise tests at entry (white bars) and at completion (black bars) of the program. Both diabetics (DM) and nondiabetics (non-DM) had significant improvements in exercise capacity. *p <0.001 within group.
as outlined per the National Cholesterol Education Program.11,12 Smoking cessation counseling was provided with pharmacologic treatment as indicated for those who were smoking at the time of program entry. Follow-up testing at program completion included an exercise tolerance test, measurement of body weight, and fasting lipid profile. Attendance rates were defined as the number of sessions attended divided by the number of sessions scheduled. Patients were defined as having completed the program if they underwent repeat testing and had an attendance record of ⱖ70%. Data are reported as mean ⫾ SD or 95% confidence intervals (CI). Initial and post-training risk factor and exercise variables were compared within and between groups using paired and nonpaired t tests or chi-square evaluation. A p value ⬍0.05 was considered statistically significant. Patient characteristics are listed in Table 1, grouped according to diabetic or nondiabetic status. Of the 952 patients, 582 were men and 370 were women (mean age 61 ⫾ 10 years). Twenty-six percent (n ⫽ 250) of the patient population had a history of diabetes at program entry, of whom 53% were taking insulin and/or oral hypoglycemic medications. There were more black and Hispanic patients in the diabetic
compared with the nondiabetic group (51% v 36%, respectively; p ⬍0.05). The prevalence of diabetes increased from 22% from 1993 to 1997 to 30% during 1998 to 2001. Diabetics had a greater adverse risk profile, including greater prevalence of hypertension (p ⬍0.0001), obesity (p ⬍0.0001), peripheral vascular disease (p ⬍0.05), and lower exercise capacity (p ⬍0.0001). At entry, the initial glycosylated hemoglobin A1C (HA1C) of the diabetics was 8.4% (95% CI 8.1 to 8.7). Overall, 428 patients (45% of the total group) completed the cardiac rehabilitation program as defined above. Significantly fewer diabetics (38%) completed the program compared with nondiabetics (48%; p ⬍0.05). Of those not completing cardiac rehabilitation, exacerbation of a medical problem (cardiac and noncardiac etiology) was the cause of dropout among 29% of diabetics versus 18% of nondiabetics (p ⬍0.01). Exercise capacity was determined by the peak MET level from the exercise test. Diabetics had a significantly lower exercise capacity at entry than nondiabetics (5.7 vs 7.0 METs, respectively; p ⬍0.0001). Of the 428 patients who completed the program, the peak MET level between the initial and follow-up exercise tolerance test increased significantly and similarly in both groups (26% in the diabetics and 27% in the nondiabetics; p ⬍0.001 pre- vs postexercise training) (Figure 1). Diabetics were significantly more obese upon program entry than nondiabetics (BMI 34.1 vs 30.8, respectively; p ⬍0.0001). Analysis of weight change in overweight patients (BMI ⱖ25) who completed the program was performed by dividing the diabetic and nondiabetic patients each into 2 groups: those with a BMI of ⱖ25.0 to 29.9 and those with a BMI of ⱖ30.0. Among the nondiabetic patients with a BMI of ⱖ30, there was a significant weight loss of 5.4 pounds from program entry to completion (p ⬍0.0001) (see Figure 2). Weight did not change in any other subgroup. No differences in weight change were observed between those diabetic patients who were taking or not taking
82 THE AMERICAN JOURNAL OF CARDIOLOGY姞
JANUARY 1, 2004
68% 44% 10% 36% 32% 5.7 ⫾ 2.3 188 ⫾ 50 43 ⫾ 15
61% 30%* 13% 23% 21% 7.0 ⫾ 2.6† 193 ⫾ 46 44 ⫾ 15
105 ⫾ 39
118 ⫾ 41
195 ⫾ 219 8.4%
161 ⫾ 129* —
Data are shown as mean ⫾ SD or percentages. *p ⬍0.05; †p ⬍0.0001.
VOL. 93
FIGURE 2. Weight change in patients with BMI of >30 who completed the program (n ⴝ 184). ‡p <0.0001 within group. Abbreviations as in Figure 1.
medications for glycemic control. Lipid-lowering therapy was taken by 58% of diabetics and 46% of nondiabetics at program entry. Lipid-lowering medications were added or modified in 3.2% of diabetics and 3.7% of nondiabetics. However, follow-up lipid levels were obtained in only 36% of patients, limiting this variable in outcome assessment. There was no significant change in mean total cholesterol, low-density lipoprotein, high-density lipoprotein, or triglyceride levels from program entry to program completion in either group. •••
Outcome assessment is integral to the successful evaluation and delivery of services provided in cardiac rehabilitation/secondary prevention programs.13,10 Accordingly, interventions that are found to be successful can be enhanced and promoted, whereas those with little effect can be modified or eliminated. Publication of outcome data are important to increase awareness regarding the needs and issues specific to a given population or subgroup, promote effective interventions, and foster further research in those areas in which better outcomes are clearly needed. This study examined the prevalence, clinical profile, and outcome of diabetic patients among a large number of patients enrolled in a single clinical program, which offered standard, comprehensive cardiac rehabilitation.10 The data reveal that diabetics have a greater prevalence of cardiac risk factors and lower exercise capacity than nondiabetics. Diabetics more frequently have hypertension, obesity, and peripheral vascular disease than nondiabetics. Although no data were available regarding the effect of cardiac rehabilitation on HA1C levels in diabetics, the mean HA1C of 8.4% demonstrates evidence of poor glycemic control on enrollment. Thus, the case for effective cardiac rehabilitation/secondary prevention interventions is compelling. The compliance rate of 45% for all patients in this program is on the low end of the 39% to 86% compliance rate range reported for cardiac rehabilitation programs.14,15 However, diabetics had a remarkable 62% dropout rate, and tended to be less likely than
nondiabetics to complete the program. Diabetic patients withdrew more often because of an exacerbation of a medical problem, although cardiac conditions precluded program completion at a similar rate in both groups (9.8% of diabetics vs 8.5% of nondiabetics). Whether diabetic patients had more severe cardiovascular illness is not known, although they did have a greater number of co-morbidities. Whether the exercise training component of cardiac rehabilitation led to an exacerbation of medical problems in these patients cannot be answered by these data, but poses an important question for further research. For those diabetics who completed the program, significant improvements in functional capacity were demonstrated. Compared with nondiabetics, diabetics had a lower initial exercise capacity, but achieved the same degree of improvement in functional capacity with training in cardiac rehabilitation. The change in functional capacity among diabetic patients was similar to that of nondiabetics from this program,7,16 and others.5,17 Although not evaluated in this study, improvement in peak MET level may yield benefits in activities of daily living, quality of life, and possibly subsequent morbidity and mortality. Weight loss among overweight and obese patients was limited to the group of nondiabetic patients with a BMI of ⱖ30, yet the change in weight was only modest. These weight change data, and those of other reports and programs6,18 –21 call attention to the need for more effective weight management strategies and interventions in cardiac rehabilitation/secondary prevention programs. Although no change in lipid levels in either group was observed, the outcome data for this variable are limited because lipids were measured and treated as clinically indicated. Often, if lipidlowering therapy was initiated or modified mid-program, a follow-up profile might not have been obtained until some time after the patient had completed the program. Despite our best efforts to obtain these data, they remain incomplete. There are a few additional limitations to the present study. Only 45% of the original cohort completed the 10-week program. However, the definition of dropout was stringent in that either the failure to attend ⬎70% of scheduled sessions, or failure to return to the program to complete a follow-up exercise test, lipid profile, or weight measurement (despite attending ⬎70% of scheduled sessions) met criteria. Finally, this observational study lacked a control group of matched patients who were not enrolled in cardiac rehabilitation. The American Heart Association promotes a multifaceted approach to the delivery of preventive efforts in diabetic patients.18 Accordingly, cardiac rehabilitation/secondary prevention programs represent an important venue for the delivery of these interventions to diabetic patients with cardiovascular disease. Data from this study emphasize the need to identify diabetic patients in cardiac rehabilitation programs and target them for an aggressive program of risk factor management. Although exercise capacity significantly improved, risk factor outcomes were disappointing. It is clear that more effective and sustained interventions in BRIEF REPORTS
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weight management, lipid lowering, and glycemic control are needed. A coordinated program, designed to work closely with primary care providers and consultants specializing in diabetes care, has the potential to deliver the best short- and long-term results. The prevalence of diabetic patients in cardiac rehabilitation programs appears to be increasing, and is likely to continue to do so as the national prevalence of diabetes increases. Such targeted programs need to be designed, implemented and evaluated, and offer a great opportunity for future research, as well as internal quality improvement efforts. 1. Barret-Connor E, Cohn BA, Wingard DL, Edelstein SL. Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study. JAMA 1991;265:627–631. 2. Haffner SM, Lehto S, Ro¨ nnemaa T, Pyo¨ ra¨ la¨ K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior MI. N Engl J Med 1998;339:229 –234. 3. Kannel WB. Lipids, diabetes, and coronary heart disease: insights from the Framingham Study. Am Heart J 1985;110:1100 –1107. 4. Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA 1999;281:1291–1297. 5. Wenger NK, Froelicher ES, Smith LK. Cardiac Rehabilitation. Clinical Practice Guideline No. 17. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agencies for Health Care Policy and Research and the National Heart, Lung and Blood Institute. AHCPR Publication No. 96-0672. October 1995. 6. Milani RV, Lavie CJ. Behavioral differences and effects of cardiac rehabilitation in diabetic patients following cardiac events. Am J Med 1996;100:517–523. 7. Bader DS, Maguire TE, Spahn C, O’Malley CJ, Balady GJ. Clinical profile and outcome of obese patients in cardiac rehabilitation as stratified according to NHLBI criteria. J Cardiopulmonary Rehabil 2001;21:210 –217. 8. McInnis KJ, Bader DS, Maguire T, Balady GJ. Comparison of cardiopulmonary responses in obese women using ramp versus step treadmill protocols. Am J Cardiol 1999;83:289 –291. 9. American College of Sports Medicine. American College of Sports Medicine Position Stand. The recommended quantity and quality of exercise for developing
and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Med Sci Sports Exerc 1998;30:975–979. 10. Balady GJ, Ades PA, Comoss P, Limacher M, Pina I, Southard D, Williams MA, Bazzarre T. AHA/AACVPR core components of cardiac rehabilitation/ secondary prevention programs. Circulation 2000;102:1069 –1073. 11. National Cholesterol Education Program Expert Panel. Second Report of the Expert Panel in detection, evaluation and treatment of high blood cholesterol in adults. Bethesda, MD: National Institutes of Health, National Heart, Lung and Blood Institute. NIH Publication 93-3095, 1993. 12. Cleeman J. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285: 2486 –2496. 13. American Association for Cardiovascular and Pulmonary Rehabilitation. Guidelines for Cardiac Rehabilitation and Secondary Prevention Programs. Champaign, IL: Human Kinetics Publishers, 1999. 14. Oldridge NB, Wicks JR, Hanley G, Sutton JR, Jones NL. Noncompliance in an exercise rehabilitation program for men who have suffered a myocardial infarction. Can Med Assoc J 1978;111:361–364. 15. Bruce EH, Frederick R, Bruce RA, Fisher LD. Comparison of active participants and dropouts in CAPRI cardiopulmonary rehabilitation programs. Am J Cardiol 1976;37:53–60. 16. Cannistra L, Balady GJ, O’Malley CJ, Weiner DA, Ryan TJ. Comparison of the clinical profile and outcome of women and men in cardiac rehabilitation. Am J Cardiol 1992;69:1274 –1279. 17. Balady GJ, Jette D, Scheer J, Downing J. Changes in exercise capacity following cardiac rehabilitation in patients stratified according to age, and gender. Results from the MACVPR Database. J Cardiopulmonary Rehabil 1996;16:38 – 46. 18. Yu C, Li L, Ho H, Lau C. Long-term changes in exercise capacity, quality of life, body anthropometry, and lipid profiles after a cardiac rehabilitation program in obese patients with coronary heart disease. Am J Cardiol 2003;91:321–325. 19. Lavie CJ, Milani RV. Effects of cardiac rehabilitation, exercise training, and weight reduction on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in obese coronary patients. Am J Cardiol 1997;79: 397–401. 20. Gordon NF, English C, Contractor AS, Slamon RD, Leighton R, Franklin BA, Haskell WL. Effectiveness of three models for comprehensive cardiovascular disease risk reduction. Am J Cardiol 2002;89:1263–1268. 21. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC, Sowers JR. Diabetes, and cardiovascular care. A Statement for Healthcare Professionals from the American Heart Association. Circulation 1999;100:1134 –1146.
Effect of Atorvastatin 80 mg on Endothelial Cell Function (Forearm Blood Flow) in Patients With Pretreatment Serum Low-Density Lipoprotein Cholesterol Levels <130 mg/dl Sven Wassmann, MD, Nicole Ribaudo, MS, Anna Faul, MS, Ulrich Laufs, Michael Bo ¨ hm, MD, and Georg Nickenig, MD The effect of 6-week treatment with 80 mg/day atorvastatin on vascular function in the forearm was investigated in 18 patients with mean pretreatment serum low-density lipoprotein cholesterol concentrations of 112 ⴞ 4 mg/dl in a double-blind, placebo-controlled, randomized study. Statin treatFrom the Medizinische Klinik und Poliklinik, Innere Medizin III, Universita¨ tskliniken des Saarlandes, Homburg/Saar, Germany. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) Bonn, and by an unrestricted research grant from Pfizer Germany, Karlsruhe, Germany. Dr. Wassmann’s address is: Medizinische Klinik und Poliklinik, Innere Medizin III, Universita¨ tskliniken des Saarlandes, 66421 Homburg/Saar, Germany. E-mail: [email protected]. de. Manuscript received April 30, 2003; revised manuscript received and accepted September 2, 2003.
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©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 January 1, 2004
MD,
ment improved hyperemic forearm blood flow and decreased serum markers of oxidative stress and inflammation. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:84 – 88)
he effect of 3-hydroxy-3 methylglutary co-enzyme A reductase inhibitors (statins) on vascular funcT tion in patients with low serum cholesterol levels is unclear. Trials investigating the impact of statins on coronary endothelial dysfunction have included patients with low-density lipoprotein (LDL) cholesterol levels between 140 and 195 mg/dl.1–3 In recent clinical trials, statin treatment prevented cardiovascular events irrespective of baseline cholesterol levels, including patients who had LDL cholesterol levels of 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.09.018