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Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1106-1113

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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1106-1113.)
© 1997 American Heart Association, Inc.

Articles

Fibrinolytic Activity Is Similar in Physically Active Men With and Without a History of Myocardial Infarction

Bo Fernhall; Linda M. Szymanski; Patrick A. Gorman; James Milani; Donald C. Paup; ; Craig M. Kessler

From the Exercise Science Programs (B.F., J.M., D.C.P.) and the Divisions of Hematology-Oncology (L.M.S., C.M.K.) and Cardiology (P.A.G.), The George Washington University Medical Center, Washington, DC.


*    Abstract
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 *Abstract
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 down arrowResults
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Abstract The purpose of this study was to evaluate fibrinolytic potential at rest and after a fibrinolytic stressor in men with a history of myocardial infarction (MI) compared with an age- and activity-matched group of men without coronary artery disease (CAD). All men were currently enrolled in exercise programs. Tissue-type plasminogen activator (TPA) and plasminogen activator inhibitor 1 (PAI-1) activity and antigen levels were measured at rest and after a maximal exercise test. A 2x2 (groupxtime) ANOVA with repeated measures was used to evaluate fibrinolytic potential. Bivariate regressions were conducted to evaluate relations between fibrinolytic potential and maximal oxygen uptake (O2max). Age was similar between groups (CAD, 57.5±6.6; non-CAD, 58.1±7.3 years); however, O2max was higher in non-CAD subjects (36.2±6.2 vs 27.5±5.9 mL·kg-1·min-1). Mean±SEM resting TPA and PAI-1 activities were similar between CAD and non-CAD subjects (TPA, 2.8±0.2 vs 2.8±0.2 IU/mL; PAI-1, 15.9±3.1 vs 13.1±4.1 AU/mL). Both groups showed similar significant increases in TPA activity with exercise (P<.05), and postexercise TPA activity was also similar (CAD, 9.1±2.0 IU/mL; non-CAD, 11.7±2.6 IU/mL). Both groups also showed similar significant decreases in PAI-1 activity with exercise (P<.05) and no differences in postexercise PAI-1 activity (CAD, 13.2±2.5 AU/mL; non-CAD, 10.4±3.6 AU/mL). Significantly higher resting TPA antigen levels were seen in CAD (14.8 ng/mL) than non-CAD (10.2 ng/mL) subjects (P<.05), but neither group showed significant changes with exercise (CAD, 12.9 ng/mL; non-CAD, 11.8 ng/mL). Resting PAI-1 antigen was similar in the two groups (CAD, 71.4 ng/mL; non-CAD, 74.2 ng/mL) and did not significantly change with exercise (CAD, 77.9 ng/mL; non-CAD, 72.3 ng/mL). O2max was positively correlated with postexercise TPA activity (r=.52, P<.05) and negatively correlated with resting TPA antigen (r=-.43, P<.05). Resting TPA antigen was also directly correlated with body mass index (r=.63, P<.05). The finding that functional fibrinolytic activity was not different in physically active men with and without CAD contrasts with previous reports. This suggests that matching subjects on the bases of age and habitual physical activity status and controlling exercise intensity are important factors to consider when evaluating fibrinolytic potential.


Key Words: plasminogen activator inhibitor • coronary artery disease • tissue-type plasminogen activator


*    Introduction
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 *Introduction
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The fibrinolytic system has been identified as an important contributor to the development and presentation of CAD.1 2 3 4 Because thrombosis has been identified as the immediate cause of most MIs,5 it is often suggested that disturbances in the fibrinolytic system may play an important role in CAD.2 6 TPA, an important fibrinolytic stimulator, and its specific inhibitor PAI-1 are typically measured to assess fibrinolytic potential. Whereas antigen levels refer to the total amount of the circulating proteins (both bound and free), activity levels refer to the functionally active portions of the proteins. Impaired fibrinolytic activity may be a result of reduced release of TPA or elevated levels of PAI-1, resulting in greater inhibition of TPA.2 7 Increased PAI-1 levels have been observed in patients with CAD6 7 8 9 and have been identified as a risk factor for recurrent MI.1 Furthermore, increased TPA antigen levels have also been associated with MI10 and have recently been found to be a long-term risk factor for mortality in CAD patients.2 This is probably because an elevated TPA antigen is often a reflection of high levels of circulating PAI-1, resulting in a large portion of TPA's being bound to PAI-1 and thereby rendering it inactive. In addition, it has been suggested that the ability to increase TPA activity in response to venous occlusion, a fibrinolytic stressor, is lower in patients with CAD.11 12

Habitual physical activity and high physical fitness levels have a protective effect on the development of CAD.13 14 It has been argued that at least part of this cardioprotective effect may be mediated through alterations in the fibrinolytic system.15 16 It has been well documented that short, intense bouts of physical exercise produce increases in global fibrinolytic and TPA activity and decreases in PAI-1 activity.16 17 18 19 The magnitude of these changes in fibrinolytic activity with short-term, intense exercise appears to differ according to habitual physical activity and physical fitness levels. Healthy, physically active individuals exhibit greater increases in both global fibrinolytic and TPA activity after short-term, intense exercise than do their sedentary counterparts.16 18 19 Resting PAI-1 activity has also been observed to be lower in physically active than inactive individuals.16 20 Furthermore, exercise training may increase resting fibrinolytic activity in older individuals15 ; however, longitudinal data are limited.

There are only a few investigations on the effect of short-term, intense exercise on the fibrinolytic system in patients with CAD. As in healthy subjects, fibrinolytic activity has been shown to increase after exercise in patients with CAD; however, this increase appears to be blunted when compared with that in subjects without CAD.7 21 22 23 Although the data suggest that patients with CAD may have impaired fibrinolysis both at rest and in response to exercise, methodological differences among studies make it difficult to draw any general conclusions. In earlier studies, the intensity of exercise was either only estimated or not well quantified.7 21 22 23 This may have an impact the findings, because exercise intensity is a major determinant of both TPA and PAI-1 activity responses.24 25 In addition, the physical activity level of the subjects has typically not been controlled. Because active subjects have a lower resting PAI-1 level and a greater fibrinolytic response to exercise than do inactive subjects,16 18 this may also influence the results. Finally, when responses to short-term, intense exercise are evaluated, it is also important to account for plasma volume shifts,26 which has not been done consistently in previous investigations.

The purpose of this study was to evaluate the fibrinolytic response to a short-term, intense, maximal exercise bout in men with a history of MI compared with an age- and activity-matched control group without a history of CAD by using TPA and PAI-1 activity and antigen levels as measures of fibrinolytic potential.


*    Methods
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Subjects
Subjects included men with (n=14) and without (n=11) CAD. Power analysis of published data7 11 12 16 21 22 indicated that this sample size was adequate to detect significant poststressor (exercise or venous occlusion) differences in TPA and PAI-1 activity levels between physically active and inactive groups or between patients with and without CAD (power=.80). The CAD subjects were recruited from local cardiac rehabilitation programs and were included if they fulfilled the following criteria: (1) history of uncomplicated MI (as documented from hospital records based on ECG and enzyme criteria); (2) current enrollment in an organized physical fitness or cardiac rehabilitation program; and (3) clinically stable, no evidence of exercise-induced ischemia, an estimated exercise capacity of >=7 metabolic equivalents on their last graded exercise test, and no evidence of high-grade ventricular arrhythmias. Subjects were excluded if they had experienced >1 MI or a recent MI (<3 months), were >70 years old, had an electronic pacemaker or implantable cardioverter defibrillator, regularly used tobacco or nicotine products, had diabetes mellitus, or exhibited neuromuscular or musculoskeletal disorders. The CAD subjects were not asked to discontinue taking their medications, as we wanted to evaluate the fibrinolytic response in their normal functional state. Six CAD subjects used ß-blockers, and 3 used either an angiotensin-converting enzyme inhibitor, a calcium channel blocker, or a diuretic. Eleven of 14 subjects were also taking daily aspirin.

The non-CAD (control) subjects were recruited from local fitness facilities. They were included if (1) their age and activity levels matched those of the CAD subjects, (2) they exhibited no evidence of cardiopulmonary or metabolic disease, and (3) they had no significant risk factors for CAD. Control subjects who did not match CAD subjects for age and activity levels were excluded, as were those who exhibited any evidence of the exclusion criteria listed for the CAD subjects. None of the control subjects was taking any medication. The CAD and control subjects participated in regular physical activity for 30 to 45 minutes per session, 3 to 5 sessions per week, and had been actively participating for >=3 months before the study. All subjects volunteered to participate in the study, and after they were screened for inclusion, gave their written, informed consent. The study protocol was approved by the University Medical Center Institutional Review Board.

Design
Subjects reported to the laboratory between 7 and 10 am (to avoid the influence of diurnal variation) after a 12-hour fast and took their medications as usual. The subjects were asked not to exercise 24 hours before testing, and subject eligibility was reverified before testing. Height and weight were measured for all subjects by using a standard physician's scale, and BMI was calculated as weight (in kilograms) divided by the square of height (in meters squared). All subjects completed a maximal exercise test.

Blood Collection
A polytetrafluoroethylene catheter was placed in an antecubital vein and kept patent with a 5% dextrose drip. To limit exaggerated elbow flexion during the exercise test, the catheterized arm was placed in a lightweight splint. Resting blood samples were obtained after 10 minutes of seated rest and postexercise samples were obtained immediately after cessation of exercise. The first 3 mL of blood was discarded and 5 mL was collected for analysis. The blood was immediately transferred to a 5-mL vial containing 0.05 mL of 15% EDTA. To stabilize TPA activity, 1 mL of anticoagulated blood was combined with 0.5 mL of 0.5 mol/L sodium acetate (pH 4.2) within 60 seconds of collection.27 Blood was then centrifuged at 1000g for 15 minutes and plasma was separated and stored at -80°C until analyzed.

Maximal Exercise Test
A modified Bruce treadmill protocol was used to evaluate O2. A 12-lead ECG was recorded at rest, during each exercise stage, at peak exercise, and during recovery. HRs were recorded from the ECG every minute. Blood pressure was obtained through standard sphygmomanometry at rest, in the middle of each exercise stage, at peak exercise, and during recovery. Expired gases were collected continuously throughout exercise and analyzed for volume and percent O2 and CO2, and O2 was calculated and expressed as 1-minute averages by using a Quinton Q-Plex metabolic system. Criteria for maximal effort included (1) inability of the subject to keep up with the treadmill speed, (2) a plateau in O2 with an increase in workload, (3) a failure of HR to increase with an increase in workload, and (4) a respiratory exchange ratio >1.1. The test was considered maximal effort if two of the aforementioned criteria were met. O2max was expressed as the highest O2 observed during exercise.

Blood Analyses
Hematocrit was measured in duplicate by the standard microhematocrit technique. Hemoglobin was measured in duplicate by the cyanmethemoglobin method.28 Plasma volume changes were estimated from hemoglobin and hematocrit data.26

TPA activity was determined by measuring the amidolytic activity of plasmin on a chromogenic substrate (S-2251) with the use of commercially available kits (Coatest t-PA, Chromogenix, Helena Laboratories). Values were corrected for acetate buffer dilution and plasma volume shifts and are expressed in international units per milliliter. PAI-1 activity was determined by measuring the amidolytic activity of plasmin on a chromogenic substrate (S-2403) performed in the presence of excess TPA with the use of commercially available kits (Coatest PAI, Chromogenix, Helena Laboratories). This measure of residual TPA activity is inversely proportional to the PAI-1 activity in the sample. Values, corrected for plasma volume shifts, are expressed in arbitrary units per milliliter, where 1 AU is defined as that amount of PAI-1 that inhibits 1 IU of TPA under specified conditions. TPA and PAI-1 antigen levels were determined by using commercially available enzyme-linked immunoassay kits (IMUBIND Total tPA, IMUBIND PAI-1; American Diagnostica Inc). All samples from each subject were analyzed in the same assay run to control for interassay variations.

Statistical Analyses
t tests were used to compare descriptive variables between groups. A 2x2 (groupxtime [rest and exercise]) ANOVA with repeated measures was used to evaluate TPA and PAI-1 activities and antigen levels before and after exercise. Bivariate regressions were conducted to evaluate the relation between TPA and PAI-1 activities and antigen levels and O2max and BMI. The significance level was set at P<.05.


*    Results
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The descriptive characteristics and physiological responses to maximal exercise are described in the TableDown. Age, height, and weight were similar between groups, but control subjects had a lower BMI than did CAD subjects (P<.05). The non-CAD subjects also attained a significantly higher O2max, maximal HR, and ventilation (P<.05). None of the subjects exhibited any evidence of exercise-induced ischemia; ie, none had any significant ST-segment depression (defined as a depression >1 mm) or any exercise-induced angina.


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  		Table 1. Descriptive Characteristics and Physiological Responses to Maximal Exercise

Results of the mean (±SEM) TPA activity and antigen levels are presented in Fig 1Down, and individual responses are shown in Fig 2Down. TPA activity was not different between groups (P=.43) at rest (CAD, 2.8±0.2 IU/mL; non-CAD, 2.8±0.2 IU/mL). Both groups had a significantly (P<.05) increased TPA activity from rest to maximal exercise (CAD, 9.1±2.0 IU/mL; non-CAD, 11.7±2.6 IU/mL) but showed similar increases with exercise. Resting TPA antigen level was significantly (P<.05) higher in CAD subjects (14.8 ng/mL) than non-CAD subjects (10.2 ng/mL). Neither group showed significant changes in antigen levels with maximal exercise (CAD, 12.9 ng/mL; non-CAD, 11.8 ng/mL). Individual responses for both TPA activity and antigen appear to be similar between the two groups.




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  		Figure 1. TPA activity (top) and antigen (bottom) at rest and after maximal exercise in men with and without CAD. Values are mean±SEM. *Significantly different (P<.05) from resting value; **significantly different (P<.05) between groups.




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  		Figure 2. Individual responses of TPA activity (2 left panels) and antigen (2 right panels) to maximal exercise in men with (CAD) and without (non-CAD) CAD.

Results of the mean (±SEM) PAI-1 activity and antigen level are presented in Fig 3Down, and individual responses are shown in Fig 4Down. PAI-1 activity was not significantly different (P=.54) between groups at rest (CAD, 15.9±3.1 AU/mL; non-CAD, 13.1±4.1 AU/mL). Both groups had a significantly (P<.05) decreased PAI-1 activity from rest to maximal exercise, but there was no difference between groups in postexercise values (CAD, 13.2±2.5 AU/mL; non-CAD, 10.4±3.6 AU/mL). Resting PAI-1 antigen levels were similar in both groups (CAD, 71.4 ng/mL; non-CAD, 74.2 ng/mL) and did not change significantly with exercise (CAD, 77.9 ng/mL; non-CAD, 72.3 ng/mL). Similar to the TPA results, with the exception of 2 non-CAD subjects who exhibited large decreases in PAI-1 antigen with exercise, individual responses for both PAI-1 activity and antigen appeared similar between groups.




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  		Figure 3. PAI-1 activity (top) and antigen (bottom) at rest and after maximal exercise in men with and without CAD. Values are mean±SEM. *Significantly different (P<.05) from resting value.




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  		Figure 4. Individual responses of PAI-1 activity (2 left panels) and antigen (2 right panels) to maximal exercise in men with (CAD) and without (non-CAD) CAD.

A significant positive correlation was found between O2max and postexercise TPA activity (r=.52, P<.05) and a significant negative correlation with TPA antigen (r=-.43, P<.05). BMI was positively related to resting PAI-1 activity (r=.43, P<.05) and resting TPA antigen (r=.63, P<.05). Resting PAI-1 antigen was directly correlated with PAI-1 activity at rest (r=.58, P<.05) and after exercise (r=.63, P<.05) and was negatively correlated with postexercise TPA activity (r=-.46, P<.05).


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowReferences
 
One of the major findings of this study was that functional fibrinolytic activity, as assessed by TPA and PAI-1 activity, was similar in physically active men with and without a history of MI. Neither resting values of TPA and PAI-1 activity nor the response to exercise was different between the groups. However, both groups significantly increased their TPA activity and decreased their PAI-1 activity from rest to maximal exercise. The similarity between groups is also evident when individual responses to exercise are examined, as shown in Figs 2Up and 4Up. These findings are important because TPA and PAI-1 activity are functional measures of the fibrinolytic system29 and may have important implications regarding fibrinolytic function and the risk of thrombosis.

Resting TPA antigen levels were significantly higher in CAD subjects than non-CAD subjects, a finding that agrees with previous results.30 Neither TPA nor PAI-1 antigen levels changed significantly with exercise in either group. Because functional TPA was similar in both groups, it would indicate that non-CAD subjects have a greater percentage of TPA in the active form, particularly at rest.

Cross-sectional studies of resting levels of fibrinolytic activity have typically shown that subjects with CAD have lower fibrinolytic activity than do control subjects,6 9 11 12 although some studies have found no difference.31 Longitudinal studies have also shown that elevated PAI-1 and decreased TPA activities are independently related to reinfarction within 3 years.1 12 Increased PAI-1 activity and TPA antigen levels have also been related to an increased risk of thrombotic events and sudden death.32 33 Thus, it appears that fibrinolytic potential is impaired in CAD patients, even though they often have normal or above-normal TPA antigen concentrations.30 However, it is thought that this elevation in TPA antigen is a reflection of elevated PAI-1, because TPA antigen assays do not distinguish free TPA from TPA that is complexed with PAI-1. Because patients with CAD are often characterized by elevated resting PAI-1 levels and activity (which binds most of the available TPA in a TPA/PAI-1 complex), TPA antigen may be high, but TPA activity is low.

It has been suggested that assessing fibrinolytic response to a stressor, such as venous occlusion or physical exercise, can give valuable information on fibrinolytic potential and capacity.34 35 Consistent with this view, patients with CAD have been observed to have a reduced response to venous occlusion.11 12 The increase in TPA activity after venous occlusion is reduced by 50% in patients with CAD compared with control subjects.11 12 However, Szymanski et al16 found that maximal exercise triggered much greater increases in TPA activity than did a 5-minute venous occlusion, suggesting that exercise might be a better stressor for evaluation of fibrinolytic potential, especially when considering subject discomfort during venous occlusion for >5 minutes.

Although most patients with CAD show an increased TPA activity after a short-term, intense exercise bout, it has been suggested that the magnitude of the increase may not be as large as that observed in subjects without CAD. Aznar et al21 found that patients with a history of angina and prior MI exhibited significantly lower TPA activity at rest and a smaller increase (86%) in TPA activity after exercise than non-CAD control subjects (298%). In contrast, our data show similar increases for both CAD and non-CAD groups (327% versus 422%). In the study by Aznar et al,21 PAI-1 activity was also higher in patients with CAD than in the control group (>700%) both at rest and after the exercise bout, although both groups showed a slight decrease in PAI-1 with exercise. Our results showed smaller differences in PAI-1 activity between CAD and non-CAD groups (22%). Rydzewski et al7 reported that TPA activity increased and PAI-1 activity decreased significantly more in the subjects without CAD. Estelles et al22 found that resting TPA activity was lower in MI patients than in control subjects and that a greater percentage of MI patients failed to significantly increase their TPA activity during exercise. These findings were similar to those of Hamouratidis et al,23 who also showed a decrease in fibrinolytic response to exercise, as evaluated by euglobulin lysis time, in patients with CAD. Thus, these studies suggest that patients with CAD have reduced fibrinolytic activity at rest and possibly a blunted response with exercise.

Our findings do not agree with most of the aforementioned investigations, since we found no difference in resting or exercise-induced functional fibrinolytic activity between subjects with and without CAD, even though the CAD subjects has higher TPA antigen levels. It is possible that our findings were partially influenced by subject selection. If one considers that our patients were classified as low risk and none had exercise-induced ischemia, it is possible that our group may not resemble subjects with CAD from other studies, which may have influenced our findings. For instance, Rydzewski et al7 found that a subset of patients with CAD but without exercise-induced ischemia exhibited TPA and PAI-1 activity responses similar to those of control subjects. However, Hamouratidis et al23 still found a reduced fibrinolytic response to exercise in CAD patients without exercise-induced ischemia when compared with a non-CAD control group. Similarly, Speiser et al20 reported higher PAI-1 levels in physically active post-MI subjects than in age-matched physically active men without CAD. They also reported similar TPA antigen responses with exercise in the men with and without CAD.

It is also possible that the habitual physical activity level of our subjects influenced our results. Szymanski et al16 found that physically active men exhibited an increase in TPA activity (from rest to after maximal exercise) of 261% to 292% compared with 119% for inactive men, even though there was no difference between these groups at rest. All groups showed a significant decrease in PAI-1 activity after exercise, but the inactive men still had triple the PAI-1 activity of active men. Because habitual physical activity level was not controlled for in previous studies of subjects with CAD, it is possible that at least part of the difference between subjects with and without CAD may be explained by habitual physical activity status. Our patients with and without CAD were matched for physical activity levels, and similar fibrinolytic responses were observed in both groups.

It is interesting to note that fitness level (O2max) was positively related to postexercise TPA activity and negatively related to TPA antigen. Other research36 has recently reported that O2max was correlated with post-exercise TPA activity in healthy men with different habitual physical activity levels (r=.67). These data and the data herein suggest that physical fitness, in addition to physical activity, influences exercise-related increases in TPA activity. This relation is consistent with the notion that the protective effect of physical fitness on CAD mortality may be partially modulated by the fibrinolytic system.

It has also been demonstrated that exercise intensity affects the fibrinolytic response. Szymanski and Pate25 reported that exercise in healthy men at 80% of maximal capacity more than doubled their TPA activity compared with exercise at 50% of maximal capacity. These responses were not time related, as exercising for 30 minutes at 80% or 50% of maximal capacity did not increase TPA activity any more than did 18 minutes. Molz et al24 also found that high-intensity activity (maximal or near maximal) tripled TPA activity compared with low-intensity activity (at an HR of 120 beats per minute) in young men. Although physically active men show greater responses at all intensity levels,16 19 both active and inactive men showed greater increases during more intense exercise. Prior studies on patients with CAD were not tightly controlled for exercise intensity. Thus, it is possible that our data may differ from previous findings because we ensured that all patients exercised to a defined maximum.

Because we measured the patients in their "functional state" and did not ask them to discontinue any of their medications, it is possible that the patients' drug regimens influenced our findings. Most of our patients were taking daily aspirin; however, most evidence indicates that daily aspirin does not affect resting levels of fibrinolytic activity.37 38 39 Aspirin ingestion does appear to blunt the fibrinolytic response to venous occlusion,37 39 although not all studies agree.38 However, aspirin ingestion does not appear to alter the fibrinolytic response to physical exercise.39 Furthermore, Speiser et al9 found no difference in fibrinolytic activity in patients with CAD who were or were not taking aspirin. Also, 6 of our patients were taking ß-blockers, which may influence fibrinolytic activity. Propranolol has been found to decrease fibrinolytic activity in hypertensive subjects40 at rest and in healthy, physically active volunteers after maximal exercise.41 However, others have found no effect of ß-blockade on TPA activity in healthy volunteers42 43 or in patients with CAD.44

Although it is not possible to separate the effects of medications from other factors in our study, it is unlikely that the medications were responsible for the difference between our findings and those of previous studies of patients with CAD. The major effect of both ß-blockade and aspirin ingestion appears to be either a blunting of the fibrinolytic response or no effect. Thus, if medications had influenced our results, we would have expected to see a blunted response in our CAD patients. Because no such effect was observed, it is more likely that the matching of physical activity and controlling for exercise intensity in our study were responsible for the similarity in responses between men with and without CAD. It is possible that regular physical activity may protect subjects with CAD from a decrease in fibrinolytic activity. More research is needed to investigate this possibility.

In the present study, BMI was positively correlated with PAI-1 activity and TPA antigen. Previous investigations have also reported associations between fibrinolytic activity and a number of body composition measures. Similar to the present study, other investigators have found positive relations between BMI and PAI-1 activity.45 46 Additional evidence linking fibrinolytic activity to body composition includes observations of a positive correlation between waist-hip ratio34 and percent body fat36 45 with PAI-1 activity. Furthermore, weight reduction appears to decrease PAI-1 activity and antigen levels.47 Consequently, these findings suggest that impaired fibrinolytic activity may be an important mechanism mediating the increased CAD risk observed in obese individuals.

Finally, it is also possible that subject grouping could have influenced our findings. Because we did not have catheterization data for our subjects, it is possible that some of our CAD subjects may not have truly suffered an MI. However, hospitalization records showed that each subject was diagnosed with an MI. It is also possible that some subjects in the control group may have had asymptomatic CAD, thus causing the groups to overlap. However, when one considers that the control subjects had no history of CAD, no symptoms suggestive of CAD, no significant controllable CAD risk factors, and a negative exercise test, it is unlikely that there would be much group overlap.

In summary, we found that physically active men with and without CAD exhibited similar TPA and PAI-1 activity levels at rest and in response to maximal exercise. These results contrast with earlier findings in patients with CAD, suggesting that matching subjects on the bases of age and participation in regular physical activity, and controlling the exercise intensity during testing are important factors when the fibrinolytic responses of subjects with and without CAD are compared. Additionally, significant relations between O2max and fibrinolytic variables emphasizes the important influence that physical fitness may have on fibrinolytic activity.


*    Selected Abbreviations and Acronyms
 
BMI = body mass index
CAD = coronary artery disease
ECG = electrocardiogram
HR = heart rate
MI = myocardial infarction
PAI-1 = plasminogen activator inhibitor 1
TPA = tissue-type plasminogen activator
O2(max) = (maximal) oxygen uptake


*    Footnotes
 
Reprint requests to Bo Fernhall, PhD, The George Washington University, Exercise Science Programs, School of Medicine and Health Sciences, 817 23rd St NW, Washington, DC 20052.

Received June 24, 1996; accepted January 23, 1997.


*    References
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 up arrowAbstract
 up arrowIntroduction
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 up arrowDiscussion
 *References
 

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