Regular participation in aerobic exercise has been associated with positive modifications in lipid and lipoprotein profiles(12). Decreases in plasma triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), as well as increases in high density lipoprotein cholesterol (HDL-C) have been reported in both cross-sectional(13) and longitudinal studies(40,41). Some of these observed changes have been suggested to be a result of the last exercise session(38). Although many studies exist evaluating the effects of a single session of exercise on blood lipid and lipoprotein concentrations, little information concerning the effects of a single exercise session on lipoprotein(a) (Lp(a)) is available. Lp(a) is a spherical lipid particle found predominantly in the upper LDL molecule density range (1.05-1.21 g·ml-1) (37). The principle apolipoprotein associated with Lp(a) is apolipoprotein(a) (apo(a)). When apo(a) is found in plasma, it is covalently bonded by disulfide linkage to apolipoprotein B-100(the prominent protein associated with the LDL molecule)(2). Originally identified by Berg(4), Lp(a) has been described as a variant of LDL-C and has been positively correlated with increased risk for coronary artery disease(CAD) (14,32). The precise mechanism for this association is not known, but most likely is related to the similarity between apo(a) and plasminogen that results in a competitive inhibition relationship between Lp(a) and plasminogen. Since plasminogen is an essential element in the fibrinolytic process, the presence of Lp(a) in plasma would reduce the effects of plasminogen, thus inhibiting fibrinolysis(14,32). There, however, is another Lp(a) CAD hypothesis. Cardoso et al. (6) have shown that long-distance runners have significantly higher Lp(a) concentrations than do anaerobically trained body builders, while both distance runners and body builders have higher values when compared to a sedentary group. This elevated Lp(a) concentration in highly trained athletes may represent a way of delivering cholesterol to muscles in need of tissue repair(34). Thus, depending on the situation, elevated Lp(a) may be beneficial (skeletal muscle repair), whereas there may be times when elevated Lp(a) is not beneficial and could enhance a pathologic condition(arterial injury promoted by hypercholesterolemia, hypertension, or smoking)(15).
Presently, only two published studies (10,21) have examined the effects of a single session of exercise on Lp(a) levels. Dufaux et al. (10) found significant increases in Lp(a) in moderately trained male subjects 2 d after a 3-h running test. In contrast, Hellsten et al. (21) observed a large decrease (22%) in Lp(a) following 8 d (10 h·d-1) of high intensity cross-country skiing. No corrections for estimated plasma volume changes were reported by either study. Nor were confounding factors such as the influence of cold exposure and limited caloric and fat intake considered. Thus, the role of a single session of exercise in mediating Lp(a) changes remains unclear. The present study was therefore undertaken to examine the effects of a single low volume exercise session of 30 min at two different intensities on Lp(a) concentration.
MATERIALS AND METHODS
Twelve healthy adult male Caucasians, 28-43 yr of age, were recruited. All subjects were nonsmokers, nonobese, currently not taking lipid-altering medications, and had participated in regular structured exercise(approximately 30 min/session) three to five times each week for at least the previous 3 months before entry into the study. Informed consent was obtained in accordance with the policy statement regarding the use of human subjects as published by Medicine and Science in Sports and Exercise.
All subjects completed a graded exercise test to determine maximal oxygen consumption (˙VO2max). Each subject then performed two 30-min submaximal treadmill exercise sessions during two separate visits: one low intensity (LI) exercise session at 50% ˙VO2max and on a second day another high intensity (HI) exercise session at 80% of ˙VO2max. The order of the submaximal exercise sessions was randomized and counterbalanced. Subjects completed both exercise sessions in a fasted state (12 h), were instructed not to engage in physical activity at least 24 h prior to a testing session, and were asked to maintain similar eating habits throughout the study.
Work rates for the exercise sessions were determined using heart rate and oxygen consumption data from the maximal exercise test. To ensure subjects were exercising at appropriate intensities, oxygen consumption was monitored for 5 min during each exercise session. Caloric expenditure was calculated using respiratory exchange ratio (RER) values to determine the caloric equivalent per liter of oxygen consumed.
Percentage body fat was estimated with the equations of Jackson and Pollock(26) using four skinfold sites (abdomen, ilium, tricep, thigh). Height was measured to the nearest centimeter, while weight was assessed to the nearest half kilogram using standard physician scales.
˙VO2max was determined by a modified Balke treadmill test that was designed to fatigue subjects within 11-15 min (3). Oxygen consumption was continuously monitored by an automated system (Rayfield Equipment, Waitsfied, VT) using an Applied Electrochemistry S-3A O2 analyzer (Amtek, Pittsburgh, PA), a Beckman LB-2 carbon dioxide analyzer, and a Parkinson-Cowan gasometer. ˙VO2max was defined as the highest˙VO2 observed during any full minute of the exercise test. The criteria used for attaining ˙VO2max included a plateau in˙VO2max after an increase in work rate, a RER ≥ 1.05, and/or a maximum heart rate within five contractions/min of age-predicted maximum. Known concentrations of gases were used for calibration purposes.
Blood Collection and Analysis
All blood samples were collected in a seated position immediately before and after exercise. Before exercise samples were obtained following 10 min of rest, while after exercise samples were collected immediately after exercise. Blood samples (10 ml) were obtained with little or no stasis by venipuncture from an antecubital vein and collected into tubes containing 50 μl of 15% K3-EDTA. Immediately after the collection of blood, hematocrit and hemoglobin were measured. Blood samples were centrifuged at 1000 ×g for 10 min at room temperature. Plasma was separated and stored at-80°C until analyzed. Lp(a) measurements were completed within 1 yr after collection.
Hematocrit was measured using the standard microhematocrit method. The Drabkin and Austin (9) cyanmet-hemoglobin technique was used to determine hemoglobin concentrations. After exercise, percent change in plasma volume was estimated using the Dill and Costill(8) equation. Spectrophotometric analysis using a stable Liebermann-Burchard reagent containing phosphoric acid, acetic acid, acetic anhydride, and sulfuric acid was used to determine total cholesterol(28). Triglyceride concentration was measured enzymatically using a commercialized kit (Sigma Diagnostics, St. Louis, MO, Procedure No. 339-10). Lp(a) concentrations were determined using the Macra Lp(a) (measurements of Lp(a) were completed in triplicate; sensitivity of this measurement is 0.5 mg·dl-1) enzyme immunoassay kit (Strategic Diagnostics, Newark, DE). All samples were analyzed serially and in one setting to reduce interassy variation. Assays of control sera for triglycerides, total cholesterol, and Lp(a) yielded interassay coefficient of variations of 2.7, 2.1, and 4.6%, respectively.
Differences in total cholesterol, triglycerides, and Lp(a) were analyzed with a two (intensity) by two (time) analysis of variance with repeated measures. Since the Lp(a) data were skewed, differences in Lp(a) were assessed by the Wilcoxon signed rank test. Statistical significance was set atP < 0.05.
Subject descriptive characteristics are summarized inTable 1. Subjects' mean ˙VO2max was 51.4± 3.9 ml·kg-1·min-1. The average resting total cholesterol (TC) concentration ranged from approximately the 15 to 25th percentile for men residing in the United States(33).
Results for the two exercise sessions are presented inTable 2. The actual percentage of achieved˙VO2max during the LI exercise protocol was 50% and during the HI exercise protocol 77%. Energy expenditure for the LI protocol was 304 ± 37 kcal, while energy expenditure for the HI protocol was 479 ± 61 kcal. Plasma volume decreased significantly following both the LI and HI exercise sessions (LI 5.5%, HI 11.3%). After correcting for estimated plasma volume shifts, no significant changes in TC, TG, and Lp(a) concentrations following exercise in either the LI or the HI exercise sessions were found. No significant differences were found between the LI and HI exercise sessions for TC, TG, and Lp(a) concentrations. When nonparametric analysis was completed for Lp(a), no differences were found.
This study examined the effect of 30 min of LI and HI exercise on Lp(a) concentrations. Following a single session of exercise, no changes in Lp(a) concentrations were observed for either exercise intensity. This is in contrast to work completed by Dufaux et al. (10) who found a 11.6% increase in Lp(a) in moderately trained men 2 d after a single session of exercise that involved running for 3 h on a treadmill at 75% of lactate threshold. However, since plasma volume shifts were not determined and since plasma volume can change as much as 10% or more during and in the days after a single session of exercise, estimation of these changes is critical. Therefore, the changes reported by Dufaux et al. (10) could have been the result of a plasma volume shift, as opposed to changes resulting from exercise. In contrast, Hellsten et al.(21) found significant reductions in Lp(a) in moderately active men following 8 d of cross-country skiing. The authors attributed these change to a combined decrease intake of fat during the days of exercise and to the high amount of physical activity completed (10 h·d-1). Again, plasma volume changes were not determined, nor were other confounding factors such as weight loss and cold exposure considered.
Several physiological, pharmacological, and environmental factors that affect other lipoprotein concentrations have been ineffective in lowering Lp(a) concentration (1). Though Lp(a) is thought to be genetically determined with greater than 90% of its variability in the population owing to the activity of the apo(a) gene (5), the process for synthesis and removal of Lp(a) from the circulation remains unclear. Current evidence suggests that the liver is the major and perhaps the only site of Lp(a) synthesis (39), whereas some studies have shown modest removal of Lp(a) from circulation by LDL receptors(20,30). In addition, once apo(a) is removed from Lp(a), the resulting particles are most likely removed by the LDL receptor pathway (20,30). Furthermore, present information suggests that additional avenues for Lp(a) uptake and degradation do exist and include: 1) uptake by scavenger receptor pathways in macrophages after interaction with glycosaminglycans (18) or modification by malondialdehyde (29), 2) specific receptors for Lp(a) uptake, and 3) nonreceptor-mediated pathways that are possibly controlled by the glycosylation of apo(a) (36). Presently, the effect of an exercise session on the synthesis and the removal of Lp(a) by these pathways is not known.
We have shown that subjects with moderate levels of aerobic fitness do not have immediate Lp(a) concentration changes in response to 30 min of LI or HI exercise. The possibility does exist that inactive subjects (subjects that do not regularly participate in physical activity) may have a different response to a single session of exercise. However, some cross-sectional reports evaluating physical inactive and active subjects have found no differences in Lp(a) concentrations. Data reported by Israel et al.(25) found no association between Balke treadmill time and Lp(a) concentrations. Hubinger et al. (24) found that regular physical activity was not associated with Lp(a) concentrations. MacAuley et al. (31) found no change in Lp(a) concentrations with physical activity except with past participation among women, which was not significant after age adjustment.
Recent longitudinal studies do not agree regarding the effects of exercise training on Lp(a) concentration. Hubinger et al. (23) found no changes in Lp(a) following 12 wk of endurance training in middle-aged men. However, work by Holme et al. (22) found increases in Lp(a) following a 1-yr intervention program. Presently, added information is needed to enhance our knowledge concerning the effects of regular participation in physical activity on Lp(a). However, our results suggest that a single session of exercise with a duration of 30 min is most likely not a factor in immediately altering Lp(a) concentrations. In addition, some studies have reported delayed changes in lipid and lipoprotein concentrations 24-72 h after a single exercise session (16,27). Since we did not make measurements at these time points, it is not possible to address this issue. Nonetheless, data from this study indicate that exercise of short duration with a low energy expenditure at different intensities may not provide an adequate stimulus to immediately modify plasma Lp(a) concentrations.
On the other hand, exercise sessions designed to induce significant muscle damage might increase Lp(a) concentration. Hamburg et al.(19) reported elevated Lp(a) in patients with elevated creatine kinase activity 2 d following myocardial infarction. Cardoso et al.(6) compared Lp(a) concentrations of marathoners, body builders, and inactive control subjects. The marathoners had Lp(a) levels significantly higher than those of the body builders, while the body builders had significantly higher Lp(a) levels than those of the control subjects. If the most recent session of exercise for these subjects involved a high amount of eccentric contractions, or was long in duration, significant muscle damage and elevated creatine kinase activity may have been present when blood was sampled and would provide additional support regarding the beneficial affect of elevated Lp(a) levels.
We observed no changes in TC concentrations following either exercise session. This finding is consistent with other studies of short duration(7,17). Nor did TG concentrations differ following either exercise session. These results are also similar to other reports that also used short duration exercise(7,11,16). In the present study, 304 kcal of energy were expended during the LI session, while 479 kcal were expended during the HI session. Altered TG concentrations following an exercise session of longer durations have been reported. In these cases the change was related to increased lipoprotein lipase activity(27,35).
In conclusion, plasma Lp(a) concentrations in moderately trained male subjects were unchanged following 30 min of low and high intensity exercise. Since Lp(a) may be associated with increased risk of CAD and since some exercise studies using greater expenditure of energy have found changes in some lipids and lipoproteins in the days following exercise, future studies should emphasize greater caloric expenditure during the exercise session and expand the follow-up time to include evaluation during the 24-48-h period after the exercise session. Furthermore, information regarding the role of a single session of exercise in modifying Lp(a) concentrations in subjects with elevated Lp(a) levels is not available and should be considered.
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LIPOPROTEIN(a); EXERCISE INTENSITY; LIPIDS; CORONARY ARTERY DISEASE