Secondary Logo

Journal Logo

Effects of physical activity and diet on lipoprotein(a)

MACKINNON, LAUREL T.; HUBINGER, LYLE; LEPRE, FRANK

Section Editor(s): von Duvillard, Serge P. Chair

Medicine & Science in Sports & Exercise: November 1997 - Volume 29 - Issue 11 - p 1429-1436
Basic Sciences: Symposium: Exercise, Brain and Behaviour
Free

Lipoprotein(a) [Lp(a)] represents a class of lipoproteins with some structural similarity to low density lipoprotein (LDL), but containing a unique apoprotein, apoprotein(a). First reported in 1963, Lp(a) is now considered to have an independent role in the development of atherosclerotic lesions. The level of Lp(a) in the blood is under strong genetic influence and does not appear to be alterable by lifestyle factors known to influence other lipoproteins. Regular moderate exercise has been shown to favorably alter other lipoproteins, and recent attention has focused on whether Lp(a) level can be influenced by physical activity. Current data from cross-sectional and intervention studies show little effect of moderate exercise on serum Lp(a) concentration. One possible exception may be an elevation of serum Lp(a) concentration in adult endurance and power athletes who exercise intensely on a daily basis. However, not all studies have taken into account possible racial or ethnic differences in Lp(a) concentrations and the skewed distribution observed within most populations. Standard dietary intervention such as a low fat diet recommended for weight loss and control of other blood lipids has little effect on serum Lp(a) level. At present, serum Lp(a) concentration does not appear to be significantly altered by realistic dietary changes and moderate physical activity as recommended for health. The synergistic effect on cardiovascular disease risk when both LDL-cholesterol and Lp(a) are elevated highlight the importance of attending to those risk factors that can be modified by exercise and other lifestyle changes.

Submitted for publication February 1997.

Accepted for publication May 1997.

Address for correspondence: Laurel Mackinnon, Department of Human Movement Studies, The University of Queensland, Queensland, AUSTRALIA 4072. E-mail:laurel@hms.uq.edu.au.

Departments of Human Movement Studies and Medicine, The University of Queensland, Brisbane, Queensland, AUSTRALIA 4072

Lipoprotein (a) [Lp(a)] represents a heterogeneous class of lipoprotein particles with some structural similarity to low density lipoprotein (LDL)(1). First described by Berg in 1963 as a variant of LDL(6), Lp(a) is now recognized as a distinct lipoprotein complex (1). Lp(a) has received renewed interest over the past ten years due to its apparent independent association with cardiovascular diseases (3,9,25,54-56). The serum level of Lp(a) is an inherited genetic trait that remains relatively constant in any given individual (9). Gender, at least before menopause, age and standard dietary manipulation do not appear to influence serum Lp(a) levels (17), but racial differences have been noted (2,25,27,60,64). Since regular exercise is now recognized as one factor influencing plasma lipoprotein profiles (reviewed by 8,21), recent attention has focused on whether serum Lp(a) level can be modified by physical activity.

Structure and function of Lp(a). Lp(a) consists of an LDL-like particle containing apoprotein B-100 (apoB-100), linked via a disulfide bond to apoprotein(a) [apo(a)], a glycoprotein which confers a unique structure and function to the Lp(a) particle. Apo(a) is polymorphic, with at least 16 isoforms identified in humans (2,5). There is wide variation in apo(a) molecular size (range approximately 300-800 kDa) and serum Lp(a) concentrations, both of which are believed to be genetically determined. Serum Lp(a) concentrations may vary from as low as 1 to over 100 mg·dL-1 and appear to be inversely related to molecular size, that is, smaller isoforms are associated with higher serum Lp(a) concentrations (reviewed by2,9,57,64).

Lp(a) is synthesized in the liver, and although the physiological function and metabolic and degradative pathways are not yet fully understood, it is generally accepted that Lp(a) and LDL synthesis occur independently(2,9,57). It was initially believed that, owing to the presence of the LDL-like moiety, serum Lp(a) is cleared by the LDL receptor. However, recent evidence from individuals with familial hypercholesterolemia resulting from LDL receptor defects show that Lp(a) uptake and clearance are not mediated via the LDL receptor(53).

Apo(a) displays striking homology to plasminogen, both of which are part of a protein superfamily encompassing the fibrinolytic and coagulation systems(48,58). The two proteins exhibit about 80% homology, as determined by both amino acid and DNA sequencing(2,44,52). This structural similarity confers apo(a) with the ability to compete with plasminogen for binding to fibrin(5). It has been suggested that the atherogenic effect of Lp(a) occurs via this ability to compete with plasminogen for binding to fibrin, indirectly interfering with the balance of clot formation and dissolution and possibly with regulation of smooth muscle cell proliferation(5). It has been suggested that at low to moderate concentrations, Lp(a) may play a role in the normal repair of the arterial wall (9), and only becomes atherogenic at high concentration (e.g. > 30 mg·dL-1).

Lp(a) and cardiovascular diseases. Although less than 15% of total cholesterol in the blood is carried by Lp(a), high levels of Lp(a) have been associated with cardiovascular disease(3,7,16). Lp(a) is considered pathogenic when levels are greater than 30 mg·dL-1, elevating risk by more than two-fold compared with a serum Lp(a) concentration of less than 5 mg·dL-1(3). About 20% of the Caucasian populations studied to date have levels above 30 mg·dL-1, but this proportion is higher in black Americans (see below;25,34). Although serum LDL-cholesterol (LDL-C) and Lp(a) concentrations appear to be independently regulated, there is an additive risk for cardiovascular disease, up to five-fold, when both are elevated (10). High serum Lp(a) concentrations have been observed in individuals with angiographically-defined coronary arteriosclerosis and in those with family history of coronary artery disease(3,16,24). Elevated serum Lp(a) levels are also associated with increased risk of restenosis of coronary arterial grafts(33) and after angioplasty (18).

Factors that may influence Lp(a) level in the blood. It is now generally accepted that the level of serum Lp(a) is under strong genetic influence (43,57). Lp(a) concentrations in the blood are not normally distributed but are skewed toward the lower end in most populations studied to date(2,16,17,27,34). Racial and ethnic differences have been noted (25,27,34). For example, skewed distributions of Lp(a) concentration were reported in a recent study on more than 2000 young adult white and black Americans(34). However, a much higher proportion of whites exhibited serum Lp(a) levels below 10 mg·dL-1 (60% and 23% in whites and blacks, respectively), with proportionately more blacks exhibiting serum Lp(a) concentrations above 10 mg·dL-1. In another recent population-based study, serum Lp(a) levels were reported to be lower in 316 Mexican Americans compared with 242 non-Hispanic white Americans(27). Moreover, the proportion of each population with serum Lp(a) values above 30 mg·dL-1 was significantly higher in non-Hispanic compared with Mexican-American subjects in this study (18.6 vs 7.6%, respectively). The skewed distribution and racial/ethnic differences must be taken into account in statistical analysis and interpretation of data and may account for some discrepancies among studies.

Other nongenetic factors that appear to influence serum Lp(a) concentrations include liver, kidney, and metabolic diseases which may increase serum Lp(a) levels (28,30,39); both male and female sex hormones which may decrease Lp(a) concentrations(1,14,26,63); pregnancy which is associated with very high serum Lp(a) levels during the second trimester(65); some medications such as HMGCoA reductase inhibitors which may not influence (38) or may increase serum Lp(a) concentrations (42,56); and possibly age and gender, although population studies do not always show such differences (17,56).

Assays to measure Lp(a). A variety of assay techniques have been used to quantify Lp(a). The availability of purified antibodies led to development of methods such as radialimmunodiffusion, electroimmunodiffusion, and immunoelectrophoresis. However, these procedures are laborious, time consuming, and not easily automated; radialimmunodiffusion has the added disadvantage of being influenced by Lp(a) particle size(2). More recent techniques such as immunoturbidimetry and immunonephelometry (13) are less affected by molecular size variation, but are influenced by triglyceride concentration and freezing of samples, and have a low sensitivity (6-7 mg·dL-1)(54). Recently developed commercially-available radioimmunoassays (RIA) and enzyme-linked immunosorbent assays (ELISA)(23) overcome many of these difficulties and have the advantage of improved sensitivity (as low as 1 mg·dL-1) with negligible interference from other lipoproteins or plasminogen. This improved sensitivity is important, given the skewed distribution of Lp(a) toward the low end, with as high as 70% of the Caucasian population having serum Lp(a) levels below 10 mg·dL-1. A number of issues, such as calibration and sample storage, are still not fully resolved and are currently being addressed by an international working party (11).

Rationale and approaches to studying physical activity and Lp(a). Regular physical activity is associated with favorable changes in certain blood lipids and lipoproteins, in particular increased plasma high density lipoprotein cholesterol (HDL-C), and decreased plasma triglyceride concentrations as well as a decrease in the ratio of total cholesterol to HDL-C (reviewed by 8,21). The observation that exercise can favorably modify at least some lipoproteins has led to further study to determine whether serum Lp(a) concentrations are also affected by physical activity.

Four basic experimental approaches have been used to study the relationship between physical activity and serum Lp(a) concentrations: (i) population studies including physical activity or fitness level as one variable; (ii) cross-sectional comparisons between athletes and non-athletes and/or between athletes from different sports (e.g. weight lifting, distance running); (iii) exercise intervention studies lasting several months to a few years; and (iv) acute studies on the effects of a single bout of exercise on Lp(a) level.

The first published report which sparked the interest in this topic suggested that Lp(a) concentration may be decreased by very rigorous exercise(31). Sixteen very fit men participated in an eight day cross-country ski tour in the Swedish mountains. Daily ski trips varied between 12 and 25 km (≈10 h), the subjects carried 25-30 kg back-packs, and temperature ranged between -10 and -25°C. Compared with pretour values, serum Lp(a) concentration declined in 12 of the 16 skiers, and mean serum Lp(a) concentrations decreased significantly by 22%. Because the ski tour involved extremes of exercise, environmental conditions, and changes in dietary intake, it is unclear whether changes in serum Lp(a) levels resulted from the exercise itself, these other factors, or to some combination of factors. Moreover, later re-analysis of the data using median values and nonparametric analysis showed that median Lp(a) did not change significantly after the 8-d ski tour (35). Nevertheless, this study prompted speculation that Lp(a) concentration may be influenced by physical exercise.

Population and cross-sectional studies. Few population studies on Lp(a) have included assessment of habitual physical activity or fitness level, especially in adults (19,43,49)(Table 1). In a national study of 109 monozygotic and 113 dizygotic American twins, serum Lp(a) levels were not reported to be associated with weekly energy expended in physical activity(43). In contrast, in 54 healthy overweight adult males, 23-61 yr, serum Lp(a) concentrations were significantly inversely correlated with self-reported physical activity (19). However, in the latter study, the majority of association was accounted for by comparing Lp(a) in those reporting “no activity” with those reporting“any activity” (i.e. at least once per wk). The authors suggested the possibility that the association could be caused by errors in self-reported activity and/or to confounding variables such as body mass, or serum testosterone or serum insulin levels which were each correlated with Lp(a) level.

In a recent cross-sectional study using a two-stage probability sample of 1600 adults over age 16 yr in Northern Ireland, no relationship was found between current or past physical activity level and serum Lp(a) concentrations in men (49). A significant association was reported between serum Lp(a) level and past participation in physical activity in women, but this correlation was no longer significant when adjusted for age. Physical activity was assessed using a detailed interview recording all aspects of physical activity in the preceding 4 wk, including physical activity in the home such as housework, recreational and occupational activity outside the home, and current and past sporting activity (since age 14 yr). Subjects were grouped into activity levels according to estimated energy expenditure and intensity, duration, and frequency of activity. Taken together, these population studies suggest that serum Lp(a) level is not influenced by physical activity in adults.

In a large multicenter prospective study on 2500 Finnish children and young adults (ages 9-24 yr), median serum Lp(a) concentration was inversely correlated with physical activity as assessed by questionnaire(62). Median serum Lp(a) concentration was 45% lower in subjects in the highest 5th percentile compared with the lowest 5th percentile of activity. Moreover, there was a significant dose-response relationship between physical activity and serum Lp(a) levels. Austin et al. (4) also reported a significant inverse relationship between serum Lp(a) concentrations and fitness level, as measured by ˙VO2max, in children and adolescents (28 male, 31 female, ages 9.5-19 yr) with insulin-dependent diabetes mellitus (IDDM) and in healthy children (9 male, 9 female). In these diabetic children, serum Lp(a) levels were not related to glycemic control. In contrast, Suter et al.(61) found no significant relationship between serum Lp(a) concentrations, ˙VO2max, body mass, or diet in healthy children and adolescents (39 boys and 58 girls, 10-15 yr). Differences in assay techniques may account for discrepancies among studies. For example, studies reporting significant relationship between physical activity and serum Lp(a) levels have generally used the more sensitive and recently developed ELISA and RIA (4,62).

Cross-sectional comparisons between athletes and nonathletes or between different types of athletes have generally reported no association between physical activity and serum Lp(a) concentrations, although there are some notable exceptions which have yet to be fully explained(Table 1). In a recent study on 150 Caucasians (100 men, 50 women, mean ages 44 and 35 yr, respectively), serum Lp(a) concentrations were not significantly correlated with any number of factors, including endurance exercise capacity, age, sex, body composition, waist to hip ratio, or other lipoproteins (40). As expected, serum Lp(a) distribution was highly skewed and data were analyzed nonparametrically; multiple ANCOVA controlling for age was also used to compare across fitness quartiles, with no relationship observed between fitness and serum Lp(a) levels.

In another recent cross-sectional comparison, serum Lp(a) concentration was measured in 57 middle-aged endurance runners and 62 sedentary subjects matched for age and body mass index (35). Subjects were male Caucasians of mean age 48 yr, and data were analyzed nonparametrically. Median Lp(a) concentration did not differ significantly between groups (15.0 vs 12.5 mg·dL-1 for runners and sedentary, respectively), although expected differences were found between groups for other lipoproteins and apoproteins (e.g. higher plasma HDL-C levels in runners). The ranges and distribution of serum Lp(a) concentrations were also similar between groups. There was no significant relationship between Lp(a) level and any other measured variable, including training distance, other lipoproteins and apoproteins, body mass and composition, dietary intake, or waist to hip ratio. These two cross-sectional studies suggest that a lifestyle of moderate to intense exercise training does not exert a significant impact on serum Lp(a) concentration in young adult and middle-aged Caucasian adults.

In contrast to the two studies described above, another recent cross-sectinal comparison noted significant differences in serum Lp(a) concentrations between power and endurance athletes and nonathletes(12). Three groups of 20 adult males, ages 22-33 yr, residents of Mexico City were compared: distance runners, body builders and sedentary individuals. Data were analyzed nonparametrically and with cluster analysis. Serum Lp(a) concentrations differed significantly among all groups. Both mean and median serum Lp(a) concentrations were significantly higher in runners compared with the other groups, and serum Lp(a) levels were more than twice as high in runners compared with sedentary subjects (mean 52 and 24 mg·dL-1, respectively). Serum Lp(a) concentrations were intermediate in body builders (40 mg·dL-1), significantly higher than in the sedentary, but lower than in the runners groups. Serum Lp(a) concentrations were significantly correlated with ˙VO2max. Moreover, the ranges of serum Lp(a) concentrations differed considerably between groups, with far more athletes exhibiting serum Lp(a) levels above 30 mg·dL-1. Cluster analysis revealed a group of runners with exceptionally high serum Lp(a) levels, above 60 mg·dL-1; in contrast, values were below 30 mg·dL-1 in all sedentary subjects. These data contrast with other studies, suggesting no relationship between serum Lp(a) concentrations and physical activity levels in adults, and are unique in showing higher Lp(a) levels in exercise-trained individuals. In the study by Cardoso (12), both the runners and body builders trained extensively over several years: 25-30 km·d-1 at greater than 70% age-predicted maximal heart rate in runners, and 2-3 h daily weight lifting at greater than 70% one repetition maximum in body builders. It was suggested that in these athletes elevated serum Lp(a) values may reflect a normal metabolic response to chronic tissue injury resulting from high volume intensive exercise over many years.

In contrast to these data, another recent report found no differences in the range and distribution of serum Lp(a) levels between German endurance and power athletes and nonathletes (100 subjects in each group)(8). In addition, the distribution of serum Lp(a) concentrations was within expected population values, that is, below 10 mg·dL-1 in more than 70% of subjects regardless of group, and no more than 10% of each group exhibited serum Lp(a) concentration above 25 mg·dL-1). The racial origins of the subjects in the study by Cardoso et al. (12), in Mexico City, were not specified, and it is unclear whether these contrasting data reflect different racial/ethnic groups studied or the amount of exercise training or some combination of factors.

Androgenic hormones have been associated with a lowering of serum Lp(a) concentrations (2). A recent cross-sectional study on body builders suggests that synthetic anabolic steroid use may lower serum Lp(a) levels (14). Median serum Lp(a) concentration was 23% lower in 10 South African body builders who self-administered anabolic steroids compared with eight body builders who were nonusers. Moreover, the proportion of subjects with serum Lp(a) levels above 30 mg·dL-1 was higher in nonusers compared with users (7 of 8 nonusers vs 3 of 10 users). However, the subject number was small for a cross-sectional comparison, the subjects' races were not specified, and serum Lp(a) concentrations were high, over 30 mg·dL-1 in 12 of 18 subjects. These high values are consistent with data from Cardoso et al. (12) suggesting high serum Lp(a) concentrations in body builders. Alternatively, these data from a small subject pool may not be representative of the general population or may relate specifically to the populations in South Africa from which this subject sample was drawn.

In summary, population and cross-sectional studies are consistent in showing a lack of relationship between regular moderate exercise and serum Lp(a) concentrations in adults. Recent data, however, suggest the possibility that several hours of daily intensive exercise training over many years (at least distance running and body building) may increase serum Lp(a) concentrations. In contrast, in children and young adults, high level physical activity has been associated with lower serum Lp(a) levels in one epidemiological study. Certainly, further work is needed to clearly identify whether, and in which direction, high level exercise training influences serum Lp(a) levels.

Exercise intervention studies. In general, intervention studies using moderate exercise as recommended for prevention of cardiovascular and other diseases have not reported any change in serum Lp(a) levels(Table 2). For example, in a 12-wk exercise intervention study, 17 previously sedentary middle-aged Caucasian males were assigned to a supervised moderate exercise program consisting of 30 min walking/jogging at 60-85% age-predicted maximum heart rate three times per wk(36). Eleven sedentary control subjects matched for age and body mass index did not participate in the exercise program. Median serum Lp(a) concentrations did not differ significantly between groups and did not change significantly in either group after the 12 wk despite a significant increase in ˙VO2max in the exercisers. Ranges and distribution of serum Lp(a) concentrations were also similar between groups. Moreover, there was no significant correlation between serum Lp(a) levels and any other measured variable before or after training, including other lipoproteins and apoproteins, body mass or composition, dietary intake, or waist to hip ratio.

Serum Lp(a) levels also appear to be unchanged by longer periods of moderate exercise training in older individuals and patients with coronary artery disease. In 57 (28 men and 29 women) previously sedentary, obese individuals, aged 60-72 yr, 9-12 months of moderate exercise training did not alter serum Lp(a) concentrations despite marked improvements in aerobic power, body composition, and other blood lipids and lipoproteins(59). Supervised exercise consisted of 45-60 min walking, jogging, or cycle ergometry at 60-85% age-predicted maximal heart rate three to five times per wk; weekly energy expenditure averaged about 1200 kcal for women and 1800 kcal for men. In another study on postmenopausal middle-aged women, serum Lp(a) concentrations were unaffected by 6 months moderate exercise training with or without hormone replacement therapy, despite favorable changes in other lipoproteins (47). The supervised exercise program consisted of 30 min walking/cycling at 70-80% age-predicted maximal heart rate three to four times per wk; parametric analysis used log transformed data.

A long term intervention study investigated the effects of an intensive multifactor risk reduction program, including exercise, in more than 300 men and women with angiographically defined coronary atherosclerosis (mean age 56 yr) (29). Subjects were randomly assigned to either the risk reduction group or to a group receiving usual care. Risk reduction included medication, dietary modification and weight loss, exercise, and other lifestyle changes designed to alter the plasma lipoprotein profile. Patients were prescribed individual exercise programs based on results of fitness testing. Frequent contact was maintained with patients over a 4-yr period to ensure subject compliance. Intensive risk reduction resulted in significant changes in various risk factors, including other plasma lipoproteins, body mass, exercise capacity and diet, as well as less progression of disease. Despite these other changes, however, serum Lp(a) levels did not change significantly, nor were there differences between intervention and usual care groups at any time. These data indicate that even long-term changes in physical activity, diet, and other lifestyle factors do not influence serum Lp(a) levels.

Exercise intervention studies are often difficult owing to the extended period of time (generally > 6 months) needed to induce changes in blood lipids and fall-off in subject compliance with time. Moreover, it is often difficult to intensely train previously sedentary subjects to study the effects of high level exercise. An alternative approach is to study the opposite effect, that is, of detraining to see whether the effects of exercise are reversible with cessation of training. In eight male distance runners who refrained from training for 14-22 d, ˙VO2max and plasma HDL-C levels decreased suggesting loss of fitness and beneficial effects of training(51). There was a nearly significant (P = 0.076) increase in mean serum Lp(a) concentration from before to after the detraining period. However, subsequent nonparametric statistical analysis showed no significant change in median serum Lp(a) level in these runners(36). Thus, Lp(a) concentration does not appear to change with cessation of intensive exercise training, at least over the short term.

In summary, moderate exercise intervention studies for up to 4 yr have failed to influence serum Lp(a) concentrations in middle-aged and older individuals, despite favorable changes in diet, lipoprotein profile, and body mass or composition. These data indicate that the type of physical activity recommended for prevention of cardiovascular and other lifestyle-related diseases is ineffective in altering serum Lp(a) concentration.

Acute exercise studies. Interest has also focused on the acute response of serum Lp(a) concentrations to a single exercise session(22,37), based on the suggestion that Lp(a) behaves as an acute phase reactant in certain conditions (37). For example, serum Lp(a) levels have been reported to increase dramatically in the days following myocardial infarction when other acute phase reactants also appear in the blood (50). Exercise can also induce an acute phase response; for example, the concentration of some acute phase reactants such as C-reactive protein increase in plasma for up to 7 d after prolonged (2-3 h) running (20,46).

In a recent study, serum Lp(a) concentrations were reported to remain unchanged after various durations of distance running(37). Eight middle-aged male distance runners ran for 2 h at 80% age-predicted maximal heart rate on a flat treadmill, with blood sampled immediately before and after exercise, and then at the same time of day on days 1, 3, 5, and 7 postexercise. At no time point was median serum Lp(a) concentration significantly different from preexercise levels. These runners were preselected for their relatively high serum Lp(a) levels (median values > 35 mg·dL-1), since it was reasoned that exercise-induced changes in serum Lp(a) concentrations would be more apparent in those with high values.

In a related study, in eight young adult active but untrained males (17-19 yr), serum Lp(a) concentrations were unchanged for up to 7 d after 60 min treadmill running at 80% age-predicted maximal heart rate(37). Thirty minutes of moderate exercise at two intensities (50 and 80% ˙VO2max) did not induce significant changes in serum Lp(a) levels in 12 active adult males (22). In addition, serum Lp(a) concentrations were not significantly changed for up to 7 d after downhill running in six active but untrained young adult males and females (3 male, 3 female, 21 yr) (37). In the latter study, exercise with an eccentric bias was chosen to induce muscle soreness suggestive of muscle inflammation and cellular damage, and an acute phase response. Subjects ran downhill at 75-80% age-predicted maximal heart rate for 40 min total in three intervals (15, 15, and 10 min) each separated by 5 min of passive rest. Subjects reported extreme muscle soreness for up to 7 d and serum creatine kinase activity in blood increased, suggestive of cellular damage. These data suggest that Lp(a) is not released acutely after a single session of exercise that induces muscle damage and that Lp(a) may not always act as an acute phase reactant.

Diet and Lp(a). It is beyond the scope of this paper to fully describe the literature relating to diet and Lp(a). Population studies and those using dietary intervention generally show no relationship between diet and serum Lp(a) concentration. Moreover, serum Lp(a) levels do not appear to be altered by the standard dietary intervention recommended for prevention of coronary artery disease, nor are serum Lp(a) concentrations influenced by changes in body mass or composition known to alter other plasma lipoprotein concentrations (15,24,41). For example, in eight women and seven men, 44-78 yr, with elevated plasma LDL-C levels, serum Lp(a) concentration remained unchanged after 32 d on a low fat diet (30% of daily energy from fat), despite favorable changes in plasma total cholesterol, LDL-C, and apoB concentrations (45). Moreover, serum Lp(a) levels were unaffected by including 20% of daily energy intake as polyunsaturated or monounsaturated fats.

In one study, 4 wk of daily fish oil supplements (8 mg·d-1) combined with moderate exercise (swimming) training was effective in lowering serum Lp(a) concentrations in 22 of 32 (67%) overweight men with angina or ischemic heart disease (32). However, peanut oil supplementation and exercise were ineffective in altering serum Lp(a) levels, suggesting that any changes in serum Lp(a) concentrations may have resulted from some combination of dietary and exercise intervention. These data suggest that realistic dietary intervention likely to ensure continued compliance as recommended for good health and prevention of cardiovascular disease and obesity is ineffective in altering serum Lp(a) concentrations.

Back to Top | Article Outline

CONCLUSION

Although not yet conclusive, the evidence to date suggests that physical activity does not influence Lp(a) concentration in the blood. Both cross-sectional and intervention studies in adults indicate that serum Lp(a) level is not influenced by regular moderate exercise. These data support the notion that serum Lp(a) concentration is regulated independently of body mass, other blood lipids, and lifestyle factors such as physical activity. Possible exceptions are highly active children who may exhibit lower serum Lp(a) levels compared with their sedentary peers and experienced adult athletes training intensely on a daily basis over many years who may exhibit higher serum Lp(a) concentrations. The mechanisms and implications of such changes owing to high level exercise, if confirmed, are not known. Serum Lp(a) level does not appear to change acutely in response to endurance exercise lasting up to 2 h, although the possible effects of more prolonged exercise have not yet been studied. Realistic dietary intervention recommended for prevention of cardiovascular disease does not appear to influence serum Lp(a) level.

The lack of effect of moderate exercise on serum Lp(a) concentration points to the importance of attending to other factors that can be influenced by physical activity and other lifestyle modifications, especially when serum Lp(a) concentration is elevated and with low molecular weight isoforms associated with increased risk of cardiovascular disease. The synergistic effect on disease risk when both serum LDL-C and Lp(a) concentrations are elevated suggests that concerted effort should be directed to ways of decreasing LDL-C (e.g., via diet) and increasing HDL-C (e.g., via exercise) in the blood. It is possible that, by modifying other blood lipids and risk factors for cardiovascular disease, regular moderate physical activity may lessen the risk of developing disease.

Back to Top | Article Outline

REFERENCES

1. Albers, J. J., H. M. Taggart, D. Applebaum-Bowden, S. Haffner, C. H. Chestnut III and W. R. Hazzard. Reduction of lecithin-cholesterol acyltransferase apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid stanozolol. Biochem. Biophys. Acta 795:293-296, 1984.
2. Albers, J. J., S. M. Marcovina, and M. S. Lodge. The unique lipoprotein(a): properties and immunochemical measurement. Clin. Chem. 36:2019-2026, 1990.
3. Armstrong, V. W., P. Cremer, E. Eberle, et al The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Atherosclerosis 62:249-257, 1986.
4. Austin, A., J. Janosky, V. Warty, and S. Arslanian. The relationship of physical fitness to lipid and lipoprotein(a) levels in adolescents with IDDM. Diabetes Care 16:421-425, 1993.
5. Bartens, W. and C. Wanner. Lipoprotein(a): new insights into an atherogenic lipoprotein. Clin. Invest. 72:558-567, 1994.
6. Berg, K. A new serum type system in man-the Lp system.Acta Pathol. Microbiol. Scand. 59:(Suppl.):369, 1963.
7. Berg, K., G. Dahlen, and A. L. Borreson. Lp(a) phenotypes, other lipoprotein parameters, and a family history of coronary heart disease in middle-aged males. Clin. Genet. 16:347-352, 1979.
8. Berg, K., I. Frey, M. W. Baumstark, M. Halle, and J. Keul. Physical activity and lipoprotein lipid disorders. Sports Med. 17:6-21, 1994.
9. Berg, K. Lipoprotein(a): an overview. Chem. Physics Lipids 67/68:9-16, 1994.
10. Brown, M. S. and J. L. Goldstein. Plasma lipoproteins: teaching old dogmas new tricks. Nature 330:113-114, 1987.
11. Cambell, B., J. Tate, F. Lepre, and P. Hickman. Lipoprotein(a): biology, clinical utility and measurement. Clin. Biochem. Rev. 13:55-59, 1992.
12. Cardoso, G. C., C. Posadas, O. O. Orvananos, et al Long distance runners and body-builders exhibit elevated plasma levels of lipoprotein(a). Chem. Physics Lipids 67/68:207-221, 1994.
13. Cazzalato, G., G. Prahasch, S. Green, and G. M. Kostner. The determination of Lp(a) by rate end-point nephelometry. Clin. Chim. Acta 135:203-208, 1983.
14. Cohen, L. I. C. G. Hartford, and G. G. Rogers. Lipoprotein(a) and cholesterol in body builders using anabolic androgenic steroids. Med. Sci. Sports Exerc. 28:176-179, 1996.
15. Corsetti, J. P., J. A. Sterry, J. D. Sparks, C. E. Sparks, and M. Weintraub. Effect of weight loss on serum lipoprotein(a) concentrations in an obese population. Clin. Chem. 37:1191-1195, 1991.
16. Dahlen, G. H., J. R. Guyton, M. Attar, J. A. Farmer, J. A. Kautz, and A. M. Gotto. Association of levels of lipoprotein(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 74:758-765, 1986.
17. Dahlen, G. H. Incidence of Lp(a) lipoprotein among populations. In Lipoprotein(a). A.M. Scanu (Ed.). San Diego: Academic Press, 1990, pp. 151-176.
18. Desmaris, R., I. J. Sarembock, C. R. Ayers, S. M. Vernon, E. R. Powers, and L. W. Gimple. Elevated serum lipoprotein(a) is a risk factor for clinical recurrence after coronary balloon angioplasty.Circulation 91:1403-1409, 1995.
19. Duell, P. B., F. Hagemenas, and W. E. Connor. The relationship between serum lipoprotein(a) and insulinemia in healthy nondiabetic adult men. Diabetes Care 17:1135-1140, 1994.
20. Dufaux, B., U. Order, H. Geyer, and W. Hollmann. C-reactive protein serum concentration in well-trained athletes. Int. J. Sports Med. 5:102-106, 1984.
21. Durstine, L. J. and W. L. Haskell. Effects of exercise training on plasma lipids and lipoproteins. Ex. Sport Sci. Rev. 22:477-521, 1994.
22. Ferguson, M. A., L. M. Szymansi, P. G. Davis, et al. Effect of a single session of exercise on lipoprotein(a) [Lp(a)]. Med. Sci. Sports Exerc. 27(Suppl.):S69, 1995.
23. Fless, G. M., M. L. Snyder, and A. M. Scanu. Enzyme-linked immunoassay for Lp(a). J. Lipid Res. 30:651-662, 1989.
24. Genest, J. J. L. Jenner, J. R. McNamara, et al Prevalence of lipoprotein(a) [Lp(a)] excess in coronary artery disease.Am. J. Cardiol. 67:1039-1045, 1991.
25. Guyton, J. R., G. H. Dahlen, W. Patsch, J. A. Kautz, and A. Gotto. Relationship of plasma lipoprotein(a) levels to race and apoprotein B. Arteriosclerosis 5:265-272, 1985.
26. Haenggi. W. W. Riesen, and M. H. Birkhaeuser. Postmenopausal hormone replacement therapy with tobolone decreases serum lipoprotein(a). Eur. J. Clin. Chem. Clin. Biochem. 31:645-650, 1993.
27. Haffner, S. M., K. K. Gruber, P. A. Morales, et al Lipoprotein(a) concentration in Mexican Americans and non-Hispanic whites: the San Antonio heart study. Am. J. Epidemiol. 136:1060-1068, 1992.
28. Haffner, S. M. Lipoprotein(a) and diabetes: an update.Diabetes Care 16:819-823, 1993.
29. Haskell, W. L. E. L. Alderman, J. M. Fair, et al. Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. Circulation 89:975-990, 1994.
30. Heller, F. R., J. Jamart, P. Honore, et al. Serum lipoprotein(a) in patients with diabetes mellitus. Diabetes Care 16:819-823, 1993.
31. Hellsten, G., K. Boman, G. Hallmans, and G. Dahlen. Lipids and endurance physical activity. Atherosclerosis 75:93-94, 1989.
32. Hermann, W., J. Biermann, H. G. Lindhofer, and G. Kostner. Modification of the atherogenic risk factor Lp(a) by supplementary fish oil administration in patients with moderate physical training.Med. Klin. 84:429-433, 1989.
33. Hoff, H. F. G. J. Beck, M. S. Skibinski, et al Serum Lp(a) level as a predictor of vein graft stenosis after coronary artery bypass surgery in patients. Circulation 77:1238-1244, 1988.
34. Howard, B. V., N.-A. Le, J. D. Belcher, et al. Concentrations of Lp(a) in black and white young adults: relations to risk factors for cardiovascular disease. Ann. Epidemiol. 4:341-350, 1994.
35. Hubinger, L. M., L. T. Mackinnon, and F. Lepre. Lipoprotein(a) [Lp(a)] levels in middle-aged male runners and sedentary controls. Med. Sci. Sports Exerc. 27:490-496, 1995.
36. Hubinger, L. M. and L. T. Mackinnon. The effect of endurance training on lipoprotein(a) [Lp(a)] levels in middle-aged males.Med. Sci. Sports Exerc. 28:757-764, 1996.
37. Hubinger, L. M., L. T. Mackinnon, L. Barber, J. McCosker, A. Howard, and F. Lepre. The acute effects of treadmill running on lipoprotein(a) levels in males and females. Med. Sci. Sports Exerc. 29:436-442, 1997.
38. Hunninghake, D. B., E. A. Stein, and M. J. Mellies. Effects of one year treatment with pravastatin, an HMG-CoA reductase inhibitor, on lipoprotein(a). J. Clin. Pharmacol. 33:574-580, 1993.
39. Irish, A. B., L. A. Simons, and J. Simons. Lipoprotein(a) concentration in diabetes; relationship to proteinuria and diabetes control. Aust. N. Z. J. Med. 22:329-333, 1992.
40. Israel, R. G., M. J. Sullivan, R. H. L. Marks, R. S. Cayton, and T. C. Chenier. Relationship between cardiorespiratory fitness and lipoprotein(a) in men and women. Med. Sci. Sports Exerc. 26:425-431, 1994.
41. Jenner, J. L. J. M. Ordovas, S. Lamon-Fava, et al Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels: The Framingham offspring study. Circulation 87:1135-1141, 1993.
42. Klausen, I. C., L. U. Gerdes, H. Meinertz, F. A. Hansen, and O. Faerman. Apoprotein(a) polymorphism predicts the increase of Lp(a) by pravastatin in patients with faimilial hypercholeterolemia treated with bile acid sequestration. Eur. J. Clin. Invest. 23:240-245, 1993.
43. Lamon-Fava, S. D. Jimenez, J. C. Christian, et al. The NHLBI twin study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).Atherosclerosis 91:97-106, 1991.
44. Lawn, R. M., J. E. Tomlinson, J. W. McLean, and D. L. Eaton. Molecular biology of apolipoprotein(a). In Lipoprotein(a). A.M. Scanu (Ed.). San Diego: Academic Press, 1990, pp. 25-40.
45. Lichtenstein, A. H., L. M. Ausman, W. Carrasco, et al. Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a national cholesterol education program step 2 diet. Arterioscler. Thromb. 13:1533-1542, 1993.
46. Liesen, H., B. Dufaux, and W. Hollmann. Modifications of serum glycoproteins the days following a prolonged physical exercise and the influence of physical training. Eur. J. Appl. Physiol. Occup. Physiol. 37:243-254, 1977.
47. Lobo, R. A., M. Notelovitz, L. Bernstein, F. Y. Khan, R. K. Ross, and W. L. Paul. Lp(a) lipoprotein: relationship to cardiovascular disease risk factors, exercise, and estrogen. Am. J. Obstet. Gynecol. 166:1182-1190, 1992.
48. Loscalzo, J. Lipoprotein(a) a unique risk factor for atherothrombotic disease. Arteriosclerosis 10:672-679, 1990.
49. MacAuley, D., E. E. McCrum, G. Stott, et al. Physical activity, lipids, apolipoproteins, and Lp(a) in the Northern Ireland health and activity survey. Med. Sci. Sports Exerc. 28:720-736, 1996.
50. Maeda, S., A. Abe, M. Seishima, K. Makino, A. Noma, and M. Kawade. Transient changes of serum lipoprotein(a) as an acute phase protein. Atherosclerosis 78:145-150, 1989.
51. Mankowitz, K., R. Seip, C. F. Semenkovich, A. Daugherty, and G. Schonfeld. Short-term interruption of training affects both fasting and post-prandial lipoproteins. Atherosclerosis 95:181-189, 1992.
52. McLean, J. W., J. E. Tomlinson, W.-J. Kuang, et al cDNA sequence of human apolipoprotein(a) is homologous to plasminogen.Nature 300:132-137, 1987.
53. Rader, D. J., W. A. Mann, W. Cain, et al The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans.J. Clin. Invest. 95:1403-1408, 1995.
54. Ranby, M. Lp(a): strong hypervariable risk factor for atherosclerosis and cardiovascular disease. Clin. Hemostas. Rev. 5:9-10, 1991.
55. Rhoads, G. G., G. Dahlen, K. Berg, N. E. Morton, and A. L. Dannenberg. Lp(a) lipoprotein as a risk factor for myocardial infarction.JAMA 256:2540-2544, 1986.
56. Scanu, A. M. Update of lipoprotein(a). Curr. Opin. Lipidol. 2:253-258, 1991.
57. Scanu, A. M. Lipoprotein(a): a genetic risk factor for premature coronary heart disease. JAMA 267:3326-3329, 1992.
58. Scott, J. Thrombogenesis liked to atherogenesis at last?Nature 341:22-23, 1989.
59. Seip, R. L. P. Moulin, T. Cocke, et al. Exercise training decreases plasma cholesteryl ester transfer protein.Arterioscler. Thromb. 13:1359-1367, 1993.
60. Sorrentino, M. J. C. Vielhauer, J. D. Eisenbart, et al. Plasma lipoprotein(a) concentration and coronary artery disease in black patients compared with white patients. Am. J. Med. 93:658-662, 1992.
61. Suter, E. and M. R. Hawes. Relationship of physical activity, body fat, diet, and blood lipid profile in youths 10-15 yr.Med. Sci. Sports Exerc. 25:748-754, 1993.
62. Taimela, A., J. S. A. Viikari, K. V. K. Porkka, and G. H. Dahlen. Lipoprotein(a) levels in children and young adults: the influence of physical activity: The cardiovascular risk in young Finns study.Acta Paediatr. 83:1258-1263, 1994.
63. Tonstad, S. L. Ose, C. Gorbitz, O. Djoseland, J. M. Bard, and J. C. Fruchart. Efficacy of sequential hormone replacement therapy in the treatment of hypercholesterolaemia among postmenopausal women.J. Intern. Med. 238:39-47, 1995.
64. Utermann, G. The mysteries of lipoprotein(a).Science 246:904-910, 1989.
65. Zechner, R., G. Dosoye, M. O. Schweditsch, K. P. Pfeiffer, and G. M. Kostner. Fluctuation of plasma lipoprotein(a) concentrations during pregnancy and postpartum. Metabolism 35:33-336, 1986.
Keywords:

EXERCISE; APOPROTEIN(a); CARDIOVASCULAR DISEASE RISK FACTORS; BLOOD LIPIDS

©1997The American College of Sports Medicine