(Circulation. 1997;96:2534-2541.)
© 1997 American Heart Association, Inc.
Articles |
Attenuated Progression of Coronary Artery Disease After 6 Years of Multifactorial Risk Intervention
Role of Physical Exercise
From Medizinische Universitätsklinik Heidelberg, Abteilung Innere Medizin III–Kardiologie (J.N., T.V., K.H., C.M., B.K., C.W., G. Schlierf, R.Z., W.K.), Heidelberg, Germany; Herzzentrum der Universität Leipzig (R.H., G. Schuler), Abteilung Innere Medizin–Kardiologie, Leipzig, Germany; and Herzzentrum Lahr (E. von H.), Abteilung Kardiologie, Lahr, Germany.
Correspondence to Josef Niebauer, MD, Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, London SW3 6LY, UK. E-mail j.niebauer{at}ic.ac.uk
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Abstract |
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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.
Key Words: prevention • exercise • angiography • diet • atherosclerosis
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Introduction |
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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.
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Methods |
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Patient Selection
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.
Intervention Group
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.
Control Group
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.
Metabolic Variables
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
Exercise Testing
ß-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
Cardiac Catheterization
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.
Statistical Analyses
Nonparametric tests (Wilcoxon signed-rank
test for intraindividual comparisons within groups and the Mann-Whitney
U test for interindividual changes between groups) and
2 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.
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Results |
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Patient Population
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).
Clinical Events
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.
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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 (
apo 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 Hgx1000/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).
Medical Treatment
Initially in the intervention group, 78% of the patients were
taking ß-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 ß-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.
Nicotine Consumption
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).
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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.
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Hemodynamic Variables
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).
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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).
Collaterals
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).
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Compliance for attending group exercise sessions (2x1 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
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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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.
Metabolic Variables
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.
Hemodynamic Variables
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.
Angiographic Changes
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.
Collateral Formation
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.
Clinical Events
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.
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Acknowledgments |
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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.
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