Attenuated Progression of Coronary Artery Disease After 6 Years of Multifactorial Risk Intervention
Role of Physical Exercise
Background It was the aim of this study to assess the long-term effects of physical exercise and low-fat diet on the progression of coronary artery disease. At the beginning of the study, 113 male patients with coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57); 90 patients (80%) could be reevaluated after 6 years.
Methods and Results Patients in the intervention group (n=40) showed a reduction in total serum cholesterol (6.03±1.03 versus 5.67±1.01 mmol/L; P<.03) and triglyceride levels (1.94±0.8 versus 1.6±0.89 mmol/L; P<.005) and maintained their initial body mass index (26±2 versus 27±2 kg/m2; P=NS), but results were not statistically different from the control group (n=50) (total serum cholesterol, 6.05±1.02 versus 5.79±0.88 mmol/L; triglycerides, 2.25±1.28 versus 1.85±0.96 mmol/L [both P=NS]; body mass index, 26±2 versus 28±3 kg/m2 [P<.0001]). In the intervention group, there was a significant 28% increase in physical work capacity (166±59 versus 212±89 W; P<.001), whereas values remained essentially unchanged in the control group (165±51 versus 170±60 W; P=NS; between groups, P<.05). In the intervention group, coronary stenoses progressed at a significantly slower rate than in the control group (P<.0001). Energy expenditure during exercise was assessed in a subgroup; patients with regression of coronary stenoses spent an average of 1784±384 kcal/wk (≈4 hours of moderate aerobic exercise per week). Multivariate regression analysis identified only physical work capacity as independently contributing to angiographic changes.
Conclusions After 6 years of multifactorial risk intervention, there is significant and persistent improvement in lipoprotein levels and physical work capacity, which results in a significant retardation of disease progression. These beneficial effects appear to be largely due to chronic physical exercise.
Moderate to aggressive lipid lowering as well as regular physical exercise have both been shown to slow the progression of and in some cases even lead to regression of coronary artery disease,1-5 as well as to reduce rates of cardiac events,2,5,6 morbidity, and mortality.5,7-9 Although the individual effects have been studied extensively, their combined effects have received less attention. Although two other trials also implemented multifactorial risk intervention programs2,10,11 but concentrated on diet and/or lipid lowering, the emphasis of the present study was on regular physical exercise. In the present report, the long-term (6-year) impact of a multifactorial risk intervention on changes in angiographically documented atherosclerotic lesions and the contributions made by physical exercise will be assessed.
Patients (n=113) were recruited after angiography for suspected coronary artery disease. Inclusion criteria were male sex, stable angina pectoris, coronary artery stenoses documented by angiography, and permanent residence within 25 km of the training facilities at Heidelberg. Exclusion criteria were unstable angina pectoris, left main coronary artery stenosis >25%, left ventricular ejection fraction <35%, valvular heart disease greater than NYHA class I, insulin-dependent diabetes mellitus, primary hypercholesterolemia (type II hyperlipoproteinemia, LDL >210 mg/dL), and any condition precluding regular exercise.
Patients were familiarized with the aims of the study, randomization process, and alternative therapeutic approaches before written informed consent was obtained. Sealed envelopes were used to randomize patients between intervention and control groups. The investigational protocol was approved by the ethics committee for human studies at the University of Heidelberg.
Patients stayed on a metabolic ward during the initial 3 weeks, where they were instructed how to lower the fat and cholesterol content of their regular diet on the basis of the American Heart Association recommendations, phase III (protein 15%, carbohydrates 65%, fat <20 energy%, total cholesterol <200 mg, polyunsaturated/saturated fatty acids ratio >1).12,13
Throughout the study period, patients were asked to exercise daily at home on a cycle ergometer for a minimum of 30 minutes and to participate in at least two of four group training sessions of 60 minutes each per week. Assessment of compliance during home exercise was based on log books. Body weight, metabolic variables, and hemodynamic variables were evaluated at 3-month intervals during the first year and at yearly intervals thereafter.
Patients spent 1 week on a metabolic ward, where they received identical recommendations on physical exercise and on how to lower their dietary fat intake. Adherence to these guidelines was left to their own initiative, and “usual care” was rendered by their private physicians.
After an overnight fasting period, body weights were obtained and blood was drawn for measurements of triglycerides, total cholesterol, HDL, LDL, and apolipoprotein (apo) A-I, A-II, and B.13 Samples were processed in the central laboratory of the University of Heidelberg Medical Center. Apolipoproteins were assessed in our research laboratory with the use of anti–h-apolipoprotein sera (Boehringer Mannheim Biochemica) and by measuring the antigen-antibody reaction immunoturbidimetrically (end-point method).14
Assessment of Leisure-Time Physical Activity
In a subgroup of patients (intervention group, n=29; control group, n=33), energy expenditure in leisure-time physical activity was estimated by use of a modified Minnesota leisure-time physical activity questionnaire.15
β-Blockers and antianginal medication were discontinued 48 hours before the test. After an overnight fasting period, symptom-limited treadmill testing was performed with the use of a modified Balke-Ware protocol. Exercise was terminated when patients experienced progressive anginal chest pain or physical exhaustion or when 3-mm horizontal ST-segment depression was reached. Maximal rate-pressure product was calculated from maximal heart rate and maximal systolic blood pressure recorded simultaneously during treadmill testing. Individual target heart rate for home and group exercise sessions was calculated as 75% of the maximal heart rate at which all patients were free of evidence of myocardial ischemia. This was further verified by Holter monitoring during the first group exercise session.16
After 6 years of study, repeat coronary angiograms were available in 66 of 92 patients (2 patients were lost to follow-up, 6 died of cancer, and 18 refused the angiograms). Coronary angiography was performed by the femoral approach according to the Judkins technique. A minimum of six standard projections were supplemented by additional angulations to accomplish optimal visualization of all stenotic segments. During follow-up angiography after 1 and 6 years, identical projections were reproduced. Vasoactive drugs (nitroglycerin, calcium channel blockers) were stopped 24 hours before catheterization and were not used during the procedure. In the per patient analysis, subsequent balloon angioplasty, bypass surgery, and myocardial infarction were considered progression of the disease.
Digital Image Processing
Two technicians who were blinded to the patients’ identity and group assignment analyzed the angiograms in random order using a computer-assisted digital image–processing system (MIPRON, Kontron).13 Relative stenosis diameter was used to compare stenotic segments, and only changes between sequential measurements exceeding 10% (more than twice the interobserver variability of 4.4%)13 were considered relevant. “Progression,” “no change,” and “regression” have been calculated as the average of the changes in all individual lesions. Absolute numbers and changes in minimal stenosis diameter correlated strongly with absolute numbers and changes in relative stenosis diameter (r=−.8871, P<.0001, and r=−.775, P<.0001). To allow for a concise and nonredundant presentation, only results for relative stenosis diameter will be reported.
Collateral filling was analyzed by grading the degree of opacification of the stenotic vessel that was supplied via collaterals.17 The score at baseline was subtracted from that after 6 years, and changes were classified as increase, no change, or decrease in collateral formation.
Nonparametric tests (Wilcoxon signed-rank test for intraindividual comparisons within groups and the Mann-Whitney U test for interindividual changes between groups) and χ2 test (for nominal variables) were used. ANOVA was performed to identify a significant difference among the mean values of a variable measured in more than two groups. When ANOVA was significant, comparisons of the mean values were made by unpaired Student’s t test with Fisher’s exact test correction. Correlation coefficients were calculated by Pearson product-moment correlations. Multivariate analyses were performed for data collected at baseline and 6 years later and for changes during the study period (difference between 6 years and baseline). A stepwise, backward, linear regression model was built to evaluate the independent contribution of body mass index, metabolic variables, and physical work capacity to the prediction of change in angiographically documented relative diameter reduction. Multivariate analysis was also performed in a subgroup of patients in whom leisure-time physical activity was assessed. For all statistical tests, differences were considered statistically significant at P<.05. Results are expressed as mean±1 SD.
Patients were randomly assigned to either an intervention group (n=56) or control group (n=57). Their mean age was 53.5 (range, 35 to 68) years. Severity of coronary artery disease and left ventricular performance were comparable in both groups; 66% of the patients had sustained an acute myocardial infarction before the beginning of the study. At the end of the first year, complete data for 92 patients were available (dropouts [n=12] and clinical events [n=9]).13 After an average study period of 6.1±1.7 years, only 2 more patients were lost to follow-up, thus permitting analysis of 90 patients (intervention group: 40 patients; control group: 50 patients).
The clinical outcome was known in 96 patients (intervention group: n=43; control group: n=53; Table 1⇓). Myocardial infarction, balloon angioplasty, bypass surgery of coronary arteries, and death (of all causes) were regarded as clinical events. There were no statistical differences between groups.
Results for patients who sustained clinical events during the study period were compared with those for patients without clinical events. The only differences that became apparent were a less marked improvement in apo A-I (Δapo A-I: 0.23±0.31 versus 0.49±0.59 mmol/L [9±12 versus 19±23 mg/dL]; P<.05), lower levels of physical work capacity (157±47 versus 200±94 W; P<.05), and rate-pressure product (24.62±5 versus 28±6 mm Hg×1000/min; P<.05), as well as a trend toward a reduced amount of energy expenditure during leisure-time physical activity (1121±303 versus 1389±565 kcal/wk; P=.085).
Initially in the intervention group, 78% of the patients were taking β-blockers, 55% were taking calcium channel blockers, and 73% were taking nitrates, and no patient was taking lipid-lowering medication. After 6 years, the respective percentages were 88%, 48%, 80%, and 20% (P=NS). In the control group, 73% of the patients were taking β-blockers at the beginning of the study period, 60% were taking calcium channel blockers, and 69% were taking nitrates, and no patient was taking lipid-lowering drugs. After 6 years, the corresponding percentages were 94%, 56%, 84%, and 41%. There were no statistically significant changes observed within or between groups.
At the beginning of the study, 6 of 56 patients in the intervention group were smokers (11%; mean, 8.1 cigarettes/d; range, 4 to 20 cigarettes/d); after 6 years, 3 of the smokers were still participating in the study, of whom 2 continued smoking (2 [5%] of 40 patients; mean, 10 cigarettes/d; range, 5 to 15 cigarettes/d). In the control group, there were initially 6 smokers among the 57 patients (11%; mean, 10.3 cigarettes/d; range, 1 to 25 cigarettes/d), of whom 3 remained in the study (3 [6%] of 50 patients; mean, 16.6 cigarettes/d; range, 10 to 20 cigarettes/d). There were no significant differences within or between groups.
Quantitative Coronary Angiography
As previously reported,13 after 1 year of study, there was a significant retardation of progression of coronary artery disease in patients in the intervention group compared with the control group (intervention group: progression, 20%; no change, 50%; regression, 30%; control group: progression, 42%; no change, 54%; regression, 4%; P<.001).
After 6 years of study, a total of 204 lesions were documented in 66 patients (mean, 3.1 lesions/patient; range, 1 to 6; intervention group: 98 lesions in 32 patients; mean, 3.2 lesions/patient; range, 1 to 6; control group: 106 lesions in 34 patients; mean, 3.0 lesions/patient; range, 1 to 6). In the intervention group, there were 6 patients with 8 new lesions, 2 patients with recanalization of previously occluded segments, and no new occlusions; in the control group, there were 11 patients with 14 new lesions, 4 patients with recanalization of previously occluded segments, and 2 patients with 1 new occlusion each. Although relative stenosis diameter remained essentially unchanged in the intervention group during the 6-year study course (58.9±27.7% versus 62.0±25.9%; P=NS), there was a significant worsening documented in the control group (54.7±34.7 versus 66.6±30.2%; P<.0005). When both groups were compared on a per lesion basis, relative stenosis diameter indicated a significantly lower rate of narrowing in the intervention group than in the control group (intervention group: 3.1±24.6%; control group: 11.9±28.2%; P<.05). Because each lesion probably cannot be considered statistically independent in patients with multiple lesions, analysis was also performed on a per patient basis. In the intervention group, 59% (n=19) of the patients showed progression, 22% (n=7) showed no change, and 19% (n=6) had regression of coronary lesions (Fig 1⇓). In the control group, 74% (n=25) of the patients had progression and 26% (n=9) had no change, while regression of coronary lesions was not observed. When both groups were compared, patients in the intervention group showed a significant retardation of lesion progression (P<.0001).
Body Mass Index and Metabolic Variables
After 6 years, patients in the intervention group showed improved levels of triglycerides, total serum cholesterol, HDL, total serum cholesterol/HDL, VLDL, apo A-I, apo A-I/B, and apo A-II and displayed a trend toward reduction in LDL (P=.058) while maintaining their initial body mass index (P=NS) (Table 2⇓). In the control group, there was also significant improvement in patients’ levels of HDL, total serum cholesterol/HDL, VLDL, apo A-I, apo A-I/B, and apo A-II, while their body mass index significantly worsened. There were no significant differences between groups.
The complete data of 78 patients could be analyzed (Figs 1⇑ and 2⇓). In the intervention group (n=34), patients significantly increased their maximal, symptom-limited physical work capacity (166±59 versus 212±89 W; P<.001) while performing an increased workload with an essentially unchanged maximal rate-pressure product (27±5 versus 27±7 mm Hg · 1000/min; P=NS). In the control group (n=44), there were no statistically significant changes observed (physical work capacity: 165±51 versus 170±60 W; rate-pressure product: 28±6 versus 26±4 mm Hg · 1000/min; P=NS). There was a significant difference in maximal physical work capacity between groups (P<.05).
Metabolic and Hemodynamic Variables: Both Groups Combined
Patients in both groups were combined and then divided into three groups according to angiographic changes (progression, no change, or regression) to evaluate the relation between changes in metabolic and exercise-related variables and their effect on angiographic results. With regard to metabolic variables, only absolute values as well as changes in levels of LDL were significantly greater in patients with regression than in patients with no change or progression (absolute levels: regression, 3.25±0.85; no change, 4.40±0.52; progression, 4.06±0.85 mmol/L; P<.05; changes in levels: regression, −0.78±1.09; no change, 0.13±0.52; progression, 0.08±0.75 mmol/L; P<.05).
For exercise-related variables, there was a significant correlation detected between physical work capacity and relative stenosis diameter (r=.319; P<.01). Patients with regression significantly increased their physical work capacity (86±53 W) compared with patients with no change (2±42 W) and those with progression (14±56 W; P<.005) (Fig 2⇑). In addition, absolute values of physical work capacity were significantly higher in patients with regression (281±117 W) than in patients with no change (179±71 W) and those with progression (171±69 W; P<.01). Similarly, patients with regression expended significantly more energy during leisure-time physical activity (1784±384 kcal) than patients with no change (1239±607 kcal) or those with progression (1260±425 kcal; regression versus no change/progression, P<.05).
In the intervention group, collaterals were documented in 18 (58%) of 31 patients, in whom 29 collaterals supplied 20 stenotic segments (right artery, 40%; left circumflex artery, 40%; left anterior descending artery, 20%). There was only one new collateral detected in a patient with otherwise unchanged angiographic results, whereas 1 collateral was recanalized in another patient who also had an unchanged angiogram. In the control group, collaterals were documented in 27 (77%) of 35 patients, in whom 28 stenotic segments (right artery, 58%; left circumflex artery, 25%; left anterior descending artery, 17%) were supplied by 44 collaterals. Two new collaterals were detected in 2 patients who both showed progression, whereas 1 collateral recanalized during the study course. There were no significant changes within or between groups with respect to the total number of coronary collaterals or the degree of opacification (P=NS).
Groups were combined to evaluate the effects of body mass index, metabolic variables, and hemodynamic variables on formation of epicardial collaterals, but no significant differences were detected. In an additional analysis, angiographic changes (progression, no change, or regression) were compared with changes in collateral formation (increase, no change, or decrease) (Fig 3⇓). It was revealed that progression was associated with an increase and regression with a decrease in collateral formation (P<.0001).
Compliance for attending group exercise sessions (2×1 h/wk=100%) was highest during the first year (68%; range, 39% to 92%) and averaged 33% (range, 3% to 89%) during the next 5 years. Attendance during group exercise sessions was inversely correlated with absolute levels of total cholesterol (r=−0.476; P<.05) and correlated directly with changes in physical work capacity (r=.604; P<.001), absolute values of physical work capacity (r=.499; P<.05), absolute values of leisure-time physical activity (r=.713; P<.002), and changes in relative stenosis diameter (r=.417; P<.05). Patients with regression attended exercise sessions significantly more often (54±24%) than patients with no change (20±24%; P<.05) and those with progression (31±20%; P<.05).
A stepwise linear multivariate regression model was built to assess the independent contributions of the following variables on changes in relative stenosis diameter (listed in order of removal): HDL, body mass index, LDL, rate-pressure product, total cholesterol/HDL, total cholesterol, triglycerides, VLDL, and physical work capacity. Only physical work capacity (r=.357; P<.01) contributed independently to changes in relative diameter reduction. In keeping with findings reported after 1 year of study, the inclusion of apolipoproteins into the regression model did not add to the prediction of changes in relative stenosis diameter.14
This study demonstrates that a multifactorial risk intervention program is capable of inducing retardation of the progression of coronary artery disease even later than 6 years after initiation of therapy. Furthermore, to the best of our knowledge, this is the first intervention trial that provides evidence of an independent beneficial effect of regular physical exercise on atherosclerotic luminal narrowing.
Patients recruited for this study had only moderately elevated cholesterol levels, as do the majority of patients with coronary artery disease. Compared with other multifactorial intervention trials, beneficial changes in body weight and total serum cholesterol were less than those reported after 4 years in the Stanford Coronary Risk Intervention Project (SCRIP)2 and after 5 years in the Lifestyle Heart Trial.10,11 However, in the Lifestyle Heart Trial, a carbohydrate-rich vegetarian diet not only led to beneficial lipoprotein modulation but also produced an unfavorable 8% increase in triglycerides and a 13% decrease in HDL levels. Although this can commonly be seen with carbohydrate-rich diets alone, physical exercise would have been expected to lead to a decrease in triglyceride and an increase in HDL levels, as shown in this as well as in other studies.18 This suggests that either the vegetarian diet was too rich in carbohydrates and/or the chosen exercise intensity was not high enough to compensate for this unfavorable dietary effect.
Apolipoproteins have been investigated as quantitative risk factors for coronary artery disease, and conflicting results have been reported regarding their predictive value for the incidence and severity of coronary artery disease.14,19-22 In keeping with data reported after 1 year, apolipoprotein levels did not add significantly to the predictability of angiographic changes, again calling into question their potential to add to the predictive value of currently used metabolic markers, eg, total cholesterol/HDL and LDL. LDL was the only metabolic variable that was significantly improved in patients with regression compared with those with no change or progression. This is consistent with current literature that shows an association between LDL lowering and reduced progression,1-3,5,19 cardiac events,2,5,6 and mortality.5 Thus, it appears that although total cholesterol/HDL and LDL have their limitations as predictors of disease progression, they are still superior to apolipoprotein levels.
Although improvement in lipoprotein levels and body weight was greater in the SCRIP2 and Lifestyle Heart Trials,10,11 physical work capacity increased to a lesser extent than in the present study. This is not unexpected, because compared with the present study, both intervention trials focused on lipid lowering. Whereas SCRIP promoted a combination of a low-fat diet and lipid-lowering drugs but gave only recommendations regarding exercise training, the Lifestyle Heart Trial provided vegetarian take-home meals and offered classes of mild to moderate exercise intensity. Patients in the present study were also regularly instructed on how to improve their diets, but emphasis was placed on physical exercise. Patients were encouraged to participate in supervised group exercise sessions and to train on bicycle ergometers that were provided for home-based exercise free of charge. In addition, patients were asked to increase their leisure-time physical activity not only by increasing the amount of exercise but also by including walking, stair climbing, gardening, and similar activities in their daily routine. To provide a safe environment for high-intensity group exercise, a physical education specialist certified in designing group exercise sessions for patients with coronary artery disease conducted each session, during which a nurse and at least one of the physician coauthors was present at all times.
Assessment of physical work capacity was performed during maximal, symptom-limited treadmill testing before which patients were asked to discontinue their cardiac medication. In the intervention group, patients significantly increased their physical work capacity, and levels achieved were well above both those reached at baseline and those seen in patients receiving usual care. Despite an increase in physical work capacity of 28%, myocardial oxygen consumption (estimated by rate-pressure product) remained essentially unchanged, which constitutes a beneficial adaptation to chronic physical exercise.
Compelling evidence is accumulating that not only high but also moderate amounts of exercise exert beneficial effects on coronary artery disease.9 Indeed, data reported in this intervention trial are also supportive of this effect. During the first year of study, an average of 1500 kcal/wk was spent by patients in whom angiographically documented stenoses did not progress further, and 2200 kcal/wk was expended by patients with regression.15 During the next 5 years, lower levels of energy expenditure appeared to produce similar effects. After 6 years of study, patients with progression or no change spent on average 1250 kcal/wk, whereas patients with regression spent an average of 1800 kcal/wk (ie, ≈4 hours of moderate aerobic exercise per week), less than patients during the first year of study. This finding suggests that although high amounts of physical exercise are necessary to halt progression or even achieve regression within a short period of time (ie, 1 year), smaller amounts of exercise may be sufficient if exerted regularly over a longer period of time.
In the present study, quantitative coronary angiography revealed a significantly lower rate of progression for relative stenosis diameter in patients in the intervention group than for those in the control group. Similar results have been reported in the Lifestyle Heart Trial and SCRIP.2,10,11 As opposed to these two studies that concentrated on lipid lowering and consequently achieved their greatest changes in metabolic variables, the current study focused on the role of physical exercise. When results of patients with regression were compared with those of patients with no change and progression, it became apparent that patients with regression had the highest scores for attendance of group exercise sessions as well as leisure-time physical activity and physical work capacity. Furthermore, multivariate analyses identified physical work capacity to be the only independent contributor to changes in relative stenosis diameter. According to these findings, beneficial angiographic changes of coronary stenoses represent an effect of exercise rather than diet.
Indeed, there is strong evidence that exercise-induced increases in blood flow have direct effects on vascular function and structure.23 During physical exercise, intracoronary blood flow increases, which results in an endothelium-dependent vasodilation of the epicardial coronary arteries.24,25 Chronic exercise in dogs has been shown to increase mRNA expression of nitric oxide (NO) synthase, which augments NO activity and subsequently leads to an improvement in vascular reactivity in coronary arteries.25 NO and prostacyclin both inhibit multiple processes involved in atherogenesis and restenosis (including generation of superoxide anion, adherence of monocytes, aggregation of platelets, and proliferation of vascular smooth muscle).26-29 In hypercholesterolemic rabbits, oral l-arginine consistently inhibited atherogenesis30 and induced regression of preexisting intimal lesions.31 Furthermore, flow modulates the expression of numerous paracrine substances, including endothelial growth factors, matrix modulators, adhesion molecules, chemokines, and regulators of blood fluidity, all of which may participate in the beneficial effects of exercise-induced vascular remodeling and reactivity.32,33 Taken together, it appears likely that retardation if not regression of atherosclerotic lesions can be achieved by increased coronary flow due to regular physical exercise.
There are conflicting reports from animal and human studies regarding the potential of physical exercise to induce enlargement and/or formation of epicardial collaterals.17,34-37 Results reported herein after 6 years mirror those previously communicated after 1 year.17 Collateral formation was only documented in patients with progression of coronary artery disease, and decreases were reported in patients with regression. Although the underlying cause remains elusive, it appears plausible that regression of existing stenoses decreases the necessity for additional blood supply to the myocardium distal of the stenoses, which will thus lead to reduced collateral opacification.
Although regular physical exercise is a safe and effective component of both primary and secondary prevention of cardiovascular events,9,38 it has also been shown to be a precipitating factor for myocardial infarction incurred by individuals who otherwise lead a sedentary existence.39,40 In keeping with these reports, there were two exercise-related cardiac deaths in the present study and one in the Lifestyle Heart Trial during the first year of study but a lower rate of cardiac deaths in the SCRIP study as well as the present study during the subsequent 3 and 5 years, respectively.2 It could be speculated that an abrupt increase in coronary flow in patients unaccustomed to exercise might trigger the rupture of vulnerable plaques, whereas regular physical exercise could have a plaque-stabilizing effect by the mechanisms eluded to above. In fact, Brown et al,4 in their Familial Atherosclerotic Treatment Study (FATS), observed a surprisingly great reduction in cardiovascular events despite modest angiographic improvement of proximal stenoses. The authors speculated that lipid lowering reduced the number of lipid-laden intimal macrophages and depleted cholesterol from the core lipid pool, thus stabilizing the plaque, reducing the likelihood of fissuring and rupture as well as increasing the luminal diameter.
In conclusion, the data provided herein are in keeping with results from other long-term multifactorial intervention trials, which all show a significant association between improvement in coronary risk factor profile and beneficial changes in angiographically documented coronary artery stenoses. In addition to the well-known effects of lipid lowering on the retardation of coronary artery disease, the present study further indicates that regular physical exercise contributes independently to the beneficial changes in risk factor profile as well as to retardation of progressive coronary lesions. Therefore, in addition to adhering to a low-fat diet, patients with coronary artery disease should be motivated to include physical exercise in their daily routine.
This study was supported by a grant from Bundesministerium für Forschung und Technologie, Bonn, Germany.
- Received March 14, 1997.
- Revision received May 19, 1997.
- Accepted May 22, 1997.
- Copyright © 1997 by American Heart Association
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