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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:2550-2555, October 2004

Human Nutrition and Metabolism

Postprandial Lipoprotein(a) Is Affected Differently by Specific Individual Dietary Fatty Acids in Healthy Young Men1

Tine Tholstrup2 and Samir Samman*

Research Department of Human Nutrition and Center for Advanced Food Studies; The Royal Veterinary and Agricultural University, Frederiksberg, Denmark and * Human Nutrition Unit Department of Biochemistry, University of Sydney, New South Wales 2006, Australia

2To whom correspondence should be addressed. E-mail: Tine.Tholstrup{at}fhe.kvl.dk.


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Lipoprotein(a) [Lp(a)] is considered a risk factor for coronary heart disease. Our aim was to investigate the effect of individual fatty acids on postprandial plasma Lp(a) and its association with lipemia and tissue plasminogen activator (t-PA). Five test fats dominated by (approximately 43% g/kg) stearic (S), palmitic (P), oleic, C18:1 trans (T), or linoleic acid were produced by interesterification. Sixteen young healthy men were served the individual test fats incorporated into meals (1g fat/kg body wt) after a 12-h fast in random order on different days, separated by 3-wk washout periods. Blood samples were drawn before and 2, 4, 6, and 8 h after eating. There was a pronounced increase in Lp(a) concentrations after intake of the test meals, and the test fats resulted in a difference in Lp(a) response (P < 0.001; diet x time interaction). However, T fat did not change Lp(a) during the time course studied. T fat resulted in less area under the plasma Lp(a) concentration curve compared to S and P fat (P ≤ 0.003). Test fat with saturated fatty acids resulted in the highest Lp(a) and lowest plasma triacylglycerol (TAG) response, with the reversed situation for T fat. There was no association between Lp(a) and t-PA. In conclusion, intake of meals high in individual dietary fatty acids increased postprandial plasma Lp(a) differently. There seems to be a complex regulatory role of plasma TAG on nonfasting plasma Lp(a) concentrations.

KEY WORDS: • lipoprotein(a) • postprandial lipemia • stearic acid • trans fatty acid • oleic acid

Lipoprotein(a) [Lp(a)]3 is strongly associated with coronary heart disease (CHD) and has been shown to be a predictor for survival in patients with ischemic heart disease (1).

Lp(a) is an LDL that contains a lipid core and an apolipoprotein B subunit. Lp(a) differs from LDL, because it also contains an apolipoprotein(a) subunit, apo(a). This subunit is very similar to plasminogen. The homology between apo(a) and plasminogen (Pg) led to the suggestion that Lp(a) suppresses normal fibrinolytic activity. In vitro studies demonstrated that Lp(a) competes with Pg for various binding sites and inhibits plasmin generation by several Pg activators (2).

The physiological role of Lp(a) is unknown (3,4). Lp(a) concentrations are resistant to most forms of LDL-lowering therapy (5–7). An exception is the antihyperlipidemic drug, niacin, which decreases Lp(a) as well as LDL cholesterol (8). In addition anabolic steroids (9) and alcohol (10) decrease Lp(a). The fact that Lp(a) is not affected by most lipid-lowering drugs suggests that the regulation is different from that of LDL. Although Lp(a) and LDL are rather similar in structure the 2 lipoproteins are metabolized differently. Lp(a) does not have a precursor lipoprotein, because it is secreted in the blood directly from the liver (11). Lp(a) formation is a 2-step process involving an initial noncovalent interaction between apo(a) and apoB 100 that precedes specific disulfide bond formation (12). A possible coupling between the metabolism of triacylglycerol-rich lipoproteins (TRL) and that of Lp(a) was suggested (13,14). An inverse relation between Lp(a) and plasma triacylglycerol (TAG) was reported in hyperlipidemics (15). Although an interaction between TRL and Lp(a) is plausible (16), the mechanism is not fully understood. Degradation of Lp(a) may be mediated through VLDL receptors (16,17) or apo(a) may be cleaved from an Lp(a) particle in the kidney, leaving the lipid and apoB components to be cleared through the LDL receptor (16). The Lp(a) concentration remains rather constant throughout life (18) and is mainly under genetic control (19). Lp(a) was previously not thought to be affected by diet; however, studies by us (20) and others (5,21,22) showed that Lp(a) concentration during a fasting state can be affected by the composition of dietary fatty acids.

We hypothesized that specific dietary fatty acids may affect Lp(a) metabolism in the postprandial state. In addition we investigated whether the proposed antifibrinolytic function of Lp(a) would occur postprandially in vivo. We reported previously data on the effect of individual fatty acids on postprandial plasma lipoprotein TAG and cholesterol concentrations, plasma free fatty acids, preheparin lipoprotein lipase (LPL), cholesterol ester transfer protein (CETP) activities (23), and tissue plasminogen activator (t-PA) activity (24). Thus in this paper we present the effects of individual dietary fatty acids on nonfasting Lp(a) and the relation among nonfasting lipemia, t-PA activity, LPL, and CETP.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
    Study design. The test meals were provided in random order (16 men were served test fats high in stearic, palmitic, oleic, and linoleic acids and 15 were served test fats high in trans fatty acid C18:1). The test meal was provided in the morning after a 12-h fast and eaten within 15 min. The different intervention periods were separated by at least 3 wk consumption of habitual diet.

    Subjects. Sixteen young men were recruited for the study. Their age ranged from 21 to 28 y (mean ± SD: 23.4 ± 2.4) and their body mass index ranged from 20 to 28.1 kg/m2 (23 ± 2). The lipid profile was normal with fasting plasma cholesterol 3.1–5.1 mmol/L (4.0 ± 0.5) and fasting plasma TAG 0.4–1.3 mmol/L (0.8 ± 0.3 mmol/L). None of the men had any history of atherosclerotic disease; none had hypertension or were taking any medication and they were all apparently healthy as indicated by a medical questionnaire. Most had a moderate physical activity level (training max 1–2 h twice a week and/or daily biking to work) and only 1 volunteer was a smoker (<10 cigarettes/d).

The protocol and the aim of the study were fully explained to the subjects, who gave their written consent. The research protocol was approved by the Scientific Ethics Committee of the municipalities of Copenhagen and Frederiksberg (01274/95).

    Diets. To minimize any effect of the diet eaten prior to the study days standardized food items were delivered to the subjects on the last 2 days before each experimental day. The fatty acid composition of the delivered diet was standardized: 40% (w:w) of total fats as SFA, 41% (w:w) monounsaturated fatty acids (MUFA), and 19% (w:w) PUFA, which resembles the fatty acid composition of the Danish diet (25). The delivered food consisted of margarine, bread, "ready-made" dinner dishes, and cakes. The subjects were instructed: 1) to refrain from high-fat foods, 2) to report all items eaten 2 days before the experimental days in order to repeat the food choice, amount of food, and time for intake of the meals prior to the experimental days, and 3) to standardize and report physical activity in the 3 days before the experimental days.

The test meals were prepared and weighed in individual servings at the experimental kitchen of the department. The meals consisted of mashed potato, in which the test fats were incorporated, and juice. The fat intake from each test meal was fixed at 1 g/kg body wt, which represents ~7 MJ for a 75-kg person. The test meals contained 50.6 E% from fat, 43 E% from carbohydrates, and 6.4 E% from protein.

Five matching synthetic dietary fats dominated by stearic (S), palmitic (P), oleic (O), trans (T), and linoleic (L) acid, respectively, were obtained from Aarhus Olie, Oils and Fats Division. The fats were produced from commercial fats (tristearin and tripalmitin) (Hüls), high oleic sunflower oil (HOSO) (Trisun 80), a fat rich in trans C18:1 (produced by nickel-catalyzed isomerization of HOSO specifically for this study by Aarhus Olie), and high linoleic sunflower oil (a commercial oil by Aarhus Olie), respectively. The interesterification resulted in a random distribution with an equal amount of test fatty acids in the 3 positions of the TAG molecules, as verified by finding the same proportion of fatty acid in the 2 position (2MAG) and total TAG molecules as the 1 of total TAG (Table 1). The melting points of the test fats were in the interval 58–59°C for S, 47–48°C for P, and 31–32°C for T. The melting points for O and L were below 20°C. The specified fatty acid characterizing each test fat comprised 41–47% of total fatty acid (w:w). The purpose of using TAG (tristearin and tripalmitin) was to reduce nonglyceride constituents to a minimum. Furthermore, a single batch of Trisun 80 was used for interesterification to balance the nonglyceride content of the dietary fats. Table 1 presents the fatty acid composition of the test fats.


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  		TABLE 1 Major fatty acids in test fat TAG and 2MAG in young healthy men 4 h after consumption of a single fatty meal dominated by specific fatty acids in a postprandial randomized controlled, crossover study

 
    Blood sampling and analysis. Blood samples were taken in the morning of each test day after at least 12 h of fasting and 20 min of supine rest. Subjects refrained from alcohol intake and heavy physical activity for at least 36 h before sampling. Postprandial samplings were collected 2, 4, 6, and 8 h after the beginning of the meal. Between blood drawings, the subjects pursued their usual study activities or walked around in a restricted area of the department. Blood for lipid and lipoprotein analyses was collected in tubes containing EDTA, which were immediately placed on ice and centrifuged at 3000 x g for 15 min at 4°C. Plasma for apolipoprotein and fatty acid analysis was stored at –80°C. Plasma for lipoprotein analysis was stored at 4°C and analyzed within 48 h. Chylomicrons were separated as described (30). The top fraction (d < 1.006 kg/L) containing VLDL and chylomicron remnants was separated from the bottom fraction containing LDL + HDL by ultracentrifugal flotation of fresh plasma [170,000 x g, 16 h 4°C at a density of 1.006 kg/L in a 50-Ti rotor (Beckmann)]. Cholesterol and TAG concentrations were assessed in plasma and lipoprotein fractions by enzymatic procedures (Boehringer Mannheim GmbH) on a Cobas Mira analyzer (Roche). HDL concentration was measured enzymatically after precipitation with polyethylene glycol (Quantolip, Immuno AG) (26). LDL cholesterol was calculated as the difference of cholesterol in the infranatant and HDL cholesterol.

Plasma Lp(a) was determined by a quantitative immunoturbidimetric assay (Unimate 3, Roche). According to the manufacturer the kit detects Lp(a) in samples with TAG > 3.42 mmol/L. To adjust for TAG interference samples were diluted if plasma TAG > 1.5 mmol/L. Precision of Lp(a) measurement was determined by analysis of control (LPA T control Roche), which gave a CV% of 2.6.

Preheparin (i.e., without prior heparin injection) LPL and CETP activities were measured as previously described (23).

The plasma concentration of C-reactive protein was assessed to rule out infectious diseases of the subjects at the time of blood collection. Values were in the normal range (<5 mg/L).

    Statistical analysis. Two-factor R-MANCOVA was used to compare the effect of the 5 test meals, using the baseline value as covariate. Differences were detected for the effects of test diets (diet x time interaction). A significant interaction means that the mean difference between the fats varies with time. Pairwise comparisons were carried out by area under the curve (AUC) and peak analysis (at 4 h postprandially) using a two-factor ANCOVA with baseline value as covariate. A P value < 0.05 was considered significant. However, Tukey’s post hoc test was applied, in the case of multiple comparisons, to reduce the risk of a type 1 error. Associations between Lp(a) and TAG at baseline and after 4 h were analyzed using a general linear model procedure, with a factor for subject and a factor for diet applied when all test fats were included in the analysis. Differences between S and T fat (after 4 h) were tested using simple correlation analysis. Unless otherwise stated, we report our results as means ± SEM. We used SAS (Version 8.0; SAS Institute, Inc.) for statistical analyses.


   RESULTS
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
Fasting and postprandial values for plasma Lp(a) are shown in Figure 1a. Graphs for plasma TAG (Fig. 1b) are included for comparison and have been published (23). There was an overall increase in plasma Lp(a) concentration with a maximum 4 h postprandially (Fig. 1a) and an overall diet x time interaction (P < 0.001). P values for pairwise comparisons are given in Table 2. Intake of T did not change Lp(a) during the time course studied. T resulted in a lower Lp(a) AUC than did S and P (P ≤ 0.003; AUC) and a lower peak response at 4 h postprandially (P ≤ 0.02), (Fig. 1a and Table 2).



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  		FIGURE 1 Entry plasma concentrations of (a) Lp(a) and (b) TAG before high fat load (1 g fat/kg body wt) and changes in 15 healthy young men after consuming individual test fats, S, P, O, T, and L fat in a postprandial randomized controlled, crossover study. (a) Samplings at hours 0 are fasting values; other values are postprandial. Values are means ± SEM; n = 16, for S, P, O, and L fat; n = 15 for T fat. For details of fatty acid composition of the test fats, see Table 1. There was a diet x time interaction (P < 0.05, unadjusted) for the following pairwise comparisons: T vs. S (P = 0.004), T vs. O (P = 0.015), T vs. L (P = 0.026); L vs. P (P = 0.003), L vs. S (P = 0.009); O vs. P (P = 0.032); P vs. S (P = 0.032). (b) Values are given for comparison.

 

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  		TABLE 2 P values from statistical comparison between postprandial Lp(a) response in 15 healthy young men after consuming individual test fats in a postprandial randomized controlled, crossover study1

 
There was a linear association between baseline fasting TAG and fasting Lp(a) (P = 0.0001; R2 = 0.94), meaning that 94% of the variability in Lp(a) was explained by TAG and subject (P < 0.0001) at baseline (Fig. 2a). The association remained significant 4 h postprandial (P < 0.0001; R2 = 0.85), with 85% of the variability in Lp(a) explained by TAG, subject (P = 0.002), and diet (P < 0.0001) (Fig. 2b). The correlation was strong after S, r = 0.99, P < 0.001 (Fig. 2c), whereas there was no significant association after T fat (Fig. 2d).



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  		FIGURE 2 Scattergrams showing (a) the relation between baseline fasting TAG and fasting Lp(a) (R2 = 0.94, P = 0.0001), adjusting for the factors subject (P < 0.0001) and diet (P = 0.79), (b) postprandial total plasma TAG 4 h after intake of the fatty meals (R2 = 0.85, P < 0.0001) adjusting for the factors subject (P = 0.002) and diet (P < 0.0001), (c) postprandial Lp(a) and Lp(a) 4 h after intake of S (r = 0.99, P < 0.0001, n = 16), and (d) postprandial Lp(a) and Lp(a) 4 h after intake of T (r = 0.321, P = 0.299, n = 13) in 15 healthy young men in a postprandial randomized controlled, crossover study. For details of fatty acid composition of the test fats, see Table 1.

 
There was a negative correlation between CETP and Lp(a) 4 h (r = –0.547, P = 0.053) and after 6 h (r = –0.574, P = 0.025) after intake of T, whereas no associations were found after S and when all 5 test fats were included. There were no associations between lipoprotein lipase (LPL) and Lp(a) either in regard to single test fats or when data for all test fats were included.

The univariate linear regression coefficient of difference between S and T diets showed positive associations between plasma changes in total TAG, chylomicron TAG, VLDL TAG, and the change in Lp(a) (P < 0.001). There were no associations between changes in LDL cholesterol, LDL TAG, LPL, CETP, t-PA, and the change in Lp(a) measured 4 h postprandially (Table 3). Concentrations of total TAG, chylomicron TAG, VLDL TAG, LDL TAG, LDL cholesterol, LPL, and CETP were previously reported (23) as were values for t-PA (24).


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  		TABLE 3 Univariate regression coefficients, SE of ß, and P values of difference in Lp(a) in 15 healthy young men 4 h after consuming individual test fats (S and T diets) in a postprandial randomized controlled, crossover study

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
In this study we found considerable variation in the postprandial response of Lp(a) after intake of specific fatty acids in young normolipidemic men. The test meal, which was predominantly C18:0 (S), resulted in the highest Lp(a) and lowest plasma TAG response with the reversed situation for trans fat, suggesting a regulatory role for dietary fatty acids on Lp(a) metabolism. An in vivo antifibrinolytic effect of Lp(a) in the postprandial state could not be confirmed in our study.

The postprandial increase in Lp(a) concentration after the majority of test fats agrees with observations by others (27). Fat feeding in healthy humans induced lipoproteins of d < 1.006 kg/L that are enriched in Lp(a) (3,28), mainly due to a redistribution of Lp(a) from lipoprotein in the d > 1.006 kg/L fraction (28). This last finding agrees with results from 2 other studies, which showed no net effect of fatty meals on Lp(a) (29,30). The lack of consistency in reported postprandial Lp(a) response between studies may be due to differences in response between healthy individuals as shown in this study (Fig. 2b) and previously by us (20) and others (31).

Our study showed that the long-chain saturated fatty acids and S and P acids resulted in the highest increase in Lp(a), whereas trans C18:1 (T) intake did not cause change from baseline Lp(a). Only a few studies compared the effect of fatty acid quality on postprandial Lp(a). A modest effect of (n-3) compared with SFA on postprandial Lp(a) was reported (32), whereas oleic acid and its trans isomer did not affect Lp(a) differently (27). The observed positive association between fasting and postprandial lipemia and Lp(a) in healthy men in this study was demonstrated by others (27), whereas several studies showed a clear inverse relation between fasting plasma TAG and plasma Lp(a) (15,16,33). When Lp(a) concentrations in all subjects were plotted against total plasma TAG in the fasting phase (Fig. 2a) and 4 h postprandially, there were significant positive relations after 4 h (Fig. 2b). Our results also showed that the stearic acid test fat, which increased plasma TAG response less than trans fat (23), resulted in higher plasma Lp(a) and vice versa. This is unlikely to be an artifact because a similar phenomenon was observed in the fasting state in hyperlipidemics (15,16). Although neither the role of Lp(a) nor the mechanism by which it is regulated is fully understood, it is generally thought that the liver is responsible for production and secretion of TAG-rich particles containing apoB 100-apo(a) in response to a fat meal and that Lp(a) is not generated from a TAG-rich precursor (34). It may be that a noncovalent interaction between TRL-apoB and the kringle-like domains of apo(a) in Lp(a) is most likely responsible for the presence of Lp(a) in TRL isolated from human plasma (34). The extent of accumulation of these particles in plasma may depend on the degree of hepatic secretion of TAG (32,14). This process may be coupled to an early phase degradation of Lp(a) (32). Thus a high plasma TAG may enhance clearance of Lp(a) by increased clearance of TAG-rich Lp(a) (16,15). This hypothesis is consistent with the association between Lp(a) and lipemia (13,33) induced by the specific test fats in our study. The rate at which Lp(a) concentrations decreased agrees with results from a recent study showing acute effects of insulin-like growth factor-1 and growth hormone on Lp(a) levels in baboons (35). However, to address the question of whether a postprandial Lp(a) increase is associated with an increase in "classical Lp(a)" or Lp(a) associated with TAG-rich lipoproteins (36) the distribution of Lp(a) postprandially in lipoproteins should be investigated. Thus a recent study on postprandial effect of trans fatty acids on Lp(a) resulted in a higher content of Lp(a) in triacylglycerol-rich lipoproteins after trans fatty acid compared to oleic acid, whereas plasma total Lp(a) concentration remained constant (27).

The lack of effect of trans fatty acid on postprandial Lp(a) response is inconsistent with the effect of feeding these diets over longer time, where trans fatty acids increased fasting Lp(a) (5,21,37). However, the lack of effect on Lp(a) of trans fatty acid in the postprandial state is in accordance with the fact that there is no association between preprandial Lp(a) and the postprandial rise in Lp(a) (32). The increase in postprandial Lp(a) after intake of high stearic acid is in line with our previous findings that showed an Lp(a) increasing effect in the fasting state after 3 wk intervention with dietary fats high in stearic acid compared to fats high in palmitic acid (20). We did not observe any relation between CETP activity and Lp(a) 4 or 6 h after intake of the fatty meals when data for all test fats were included. When specific test fats were examined, trans test fat showed an inverse relation between CETP and Lp(a) 4 and 6 h after intake. Because CETP activity is affected by plasma TAG concentration (23,38,39), we speculate that the finding is related to the presumed affiliation between plasma TAG and Lp(a).

Due to the striking structural homology between apo(a) and plasminogen, it has been suggested that Lp(a) inhibits fibrinolysis and thus is a risk factor for thrombosis (2,40). A competition for binding of plasminogen for either fibrinogen or fibrin was shown in vitro (41) and Lp(a) reduced the generation of t-PA from vascular endothelial cells (42). In apo(a) transgenic mice t-PA–mediated thrombolysis was inhibited by the presence of Lp(a) (43). Although there is evidence that Lp(a) could attenuate fibrinolysis in vivo (42,44–46), studies in humans have not been able to provide evidence for the possible inhibition of fibrinolysis by Lp(a). This is consistent with the results in this (Table 3) and a previous study by us (20) that did not show any correlation between changes in Lp(a) activity and t-PA activity. Thus the lack of correlation between change in Lp(a) and t-PA activity does not support an in vivo antifibrinolytic effect of Lp(a) in the nonfasting state, although it cannot be ruled out. More research is needed to determine whether or how Lp(a) may act thrombogenically by interfering with the clotting system in vivo. Besides a possible thrombogenic effect, Lp(a) is suggested to be a risk factor for atherosclerosis. Thus postprandially increased Lp(a) may cause development of CHD, because the presence of apo(a) in TAG may enhance uptake of macrophages into the vessel wall (36).

In conclusion, intake of meals high in individual dietary fatty acids increased postprandial plasma Lp(a) differently. The long-chain saturated fatty acids, specifically stearic acid, elicited the highest increase, whereas trans C18:1 did not seem to increase Lp(a). Test fat with T resulted in the lowest plasma Lp(a) and highest plasma TAG response, with the opposite situation for S fat. No association between Lp(a) and t-PA was observed. Our results suggest a complex regulatory role of plasma triacylglycerol on nonfasting plasma Lp(a) levels, probably coupled to an early phase degradation of Lp(a). To elucidate the mechanism further future research should address the distribution of Lp(a) postprandially in TAG- and cholesterol-rich lipoproteins.


   ACKNOWLEDGMENTS
 
We thank our colleagues Anette Bysted and Gunhild Hølmer, from The Department of Biochemistry and Nutrition, Technical University of Denmark, Lyngby, for analyses and melting points determinations of the test fats and our technicians, Karen Rasmussen and Hanne Lydal Petersen, for their contribution. We thank dietitian Hanne Jensen, Berit Christensen, and the other staff of the metabolic kitchen. Research assistant Robin Christensen is thanked for reviewing the statistics.


   FOOTNOTES
 
1 Supported by the Danish Research and Development Program for Food Technology through the LMC Center for Advanced Food Studies. Back

3 Abbreviations used: AUC, area under the curve; CETP, cholesterol ester transfer protein; CHD, coronary heart disease; CRP, C-reactive protein; HOSO, high oleic sunflower oil; L, test fat containing linoleic; Lp(a), lipoprotein(a); LPL, lipoprotein lipase; O, test fat containing oleic acid; MUFA, monounsaturated fatty acid; P, test fat containing palmitic acid; Pg, plasminogen; t-PA, plasminogen activator; S, test fat containing stearic acid; T, C18:1 trans, test fat containing trans fatty acids; TAG, triacylglycerol; TRL, triacylglycerol-rich lipoproteins; 2MAG, 2-monoacylglycerol. Back

Manuscript received 4 June 2004. Initial review completed 24 June 2004. Revision accepted 15 July 2004.


   LITERATURE CITED
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 

1. Glader, C. A., Birgander, L. S., Stenlund, H. & Dahlen, G. H. (2002) Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden. J. Intern. Med. 252:27-35.[Medline]

2. Edelberg, J. & Pizzo, S. V. (1992) Why is lipoprotein(a) relevant to thrombosis?. Am. J. Clin. Nutr. 56:791S-792S.[Free Full Text]

3. Bersot, T. P., Innerarity, T. L., Pitas, R. E., Rall, S. C., Weisgraber, K. H. & Mahley, R. W. (1986) Fat feeding in humans induces lipoproteins of density less than 1.006 that are enriched in apolipoprotein (a) and that cause lipid accumulation in macrophages. J. Clin. Invest. 77:622-630.

4. Marcoux, C., Lussier-Cacan, S., Davignon, J. & Cohn, J. S. (1997) Association of Lp(a) rather than integrally-bound apo(a) with triglyceride-rich lipoproteins of human subjects. Biochim. Biophys. Acta 1346:261-274.[Medline]

5. Nestel, P., Noakes, M., Belling, B., McArthur, R., Clifton, P., Janus, E. & Abbey, M. (1992) Plasma lipoprotein lipid and Lp[a] changes with substitution of elaidic acid for oleic acid in the diet. J. Lipid. Res. 33:1029-1036.[Abstract]

6. Wiklund, O., Angelin, B., Olofsson, S.-O., Eriksson, M., Fager, G., Berglund, L. & Bondjers, G. (1990) Apolipoprotein(a) and ischaemic heart disease in familial hypercholesterolaemia. Lancet 335:1360-1363.[Medline]

7. Thiery, J., Armstron, V. W., Schleef, J., Creutzfeldt, C., Creutzfeldt, W. & Seidel, D. (1988) Serum lipoprotein Lp(a) concentrations are not influenced by an HMG CoA reductase inhibitor. Klin. Wochenschr. 66:462-463.[Medline]

8. Brown, S. A., Morrisett, J., Patsch, J. R., Reeves, R., Gotto, A. M., Jr & Patsch, W. (1991) Influence of short term dietary cholesterol and fat on human plasma Lp[a] and LDL levels. J. Lipid. Res. 32:1281-1289.[Abstract]

9. Albers, J. J., Taggart, H. M., Applebaum-Bowden, D., Haffner, S., Chesnut, C. H., III & Hazzard, W. R. (1984) Reduction of lecithin-cholesterol acyltransferase, apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid stanozolol. Biochim. Biophys. Acta 795:293-296.[Medline]

10. Kostner, G., Klein, G. & Krempler, F. (1984) Can serum Lp(a) concentrations be lowered by drugs and/or diet?. Carlson, L. A. Olsson, A. G. eds. Treatment of Hyperlipoproteinemia 1984:151-156 Raven Press New York, NY. .

11. Krempler, F., Kostner, G., Bolzano, K. & Sandhofer, F. (1979) Lipoprotein (a) is not a metabolic product of other lipoproteins containing apolipoprotein B. Biochim. Biophys. Acta 575:63-70.[Medline]

12. Gabel, B. R., May, L. F., Marcovina, S. M. & Koschinsky, M. L. (1996) Lipoprotein(a) assembly. Quantitative assessment of the role of Apo(a) kringle IV types 2–10 in particle formation. Arterioscler. Thromb. Vasc. Biol. 16:1559-1567.[Abstract/Free Full Text]

13. Vessby, B.O.H. (1996) Diet and lipoprotein(a). Nutr. Metab. Cardiovasc. Dis. 6:239-244.

14. Nassir, F., Bonen, D. K. & Davidson, N. O. (1998) Apolipoprotein(a) synthesis and secretion from hepatoma cells is coupled to triglyceride synthesis and secretion. J. Biol. Chem. 273:17793-17800.[Abstract/Free Full Text]

15. Werba, J. P., Safa, O., Gianfranceschi, G., Michelagnoli, S., Sirtori, C. R. & Franceschini, G. (1993) Plasma triglycerides and lipoprotein(a): inverse relationship in a hyperlipidemic Italian population. Atherosclerosis 101:203-211.[Medline]

16. McConathy, W. J., Trieu, V. N., Koren, E., Wang, C.-S. & Corder, C. C. (1994) Triglyceride-rich lipoprotein interactions with Lp(a). Chem. Phys. Lipids 67/68:105-113.

17. Argraves, K. M., Kozarsky, K. F., Fallon, J. T., Harpel, P. C. & Strickland, D. K. (1997) The atherogenic lipoprotein Lp(a) is internalized and degraded in a process mediated by the VLDL receptor. J. Clin. Invest. 100:2170-2181.[Medline]

18. Sandkamp, M., Funke, H., Schulte, H., Köhler, E. & Assmann, G. (1990) Lipoprotein(a) is an independent risk factor for myocardial infarction at a young age. Clin. Chem. 36:20-23.[Abstract/Free Full Text]

19. Schriewer, H., Assmann, G. & Sandkamp, M. (1984) The relationship of lipoprotein (a) (Lp(a)) to risk factors of coronary heart disease: Initial results of the prospective epidemiological study on company employees in Westfalia. J. Clin. Chem. Clin. Biochem. 22:591-596.[Medline]

20. Tholstrup, T., Marckmann, P., Vessby, B. & Sandström, B. (1995) Effect of fats high in individual saturated fatty acids on plasma lipoprotein[a] levels in young healthy men. J. Lipid. Res. 36:1447-1452.[Abstract]

21. Mensink, R. P., Zock, P. L., Katan, M. B. & Hornstra, G. (1992) Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans. J. Lipid. Res. 33:1493-1501.[Abstract]

22. Hornstra, G., Houwelingen, A.C.v., Kester, A.D.M. & Sundram, K. (1991) A palm oil-enriched diet lowers serum lipoprotein(a) in normocholesterolemic volunteers. Atherosclerosis 90:91-93.[Medline]

23. Tholstrup, T., Sandström, B., Bysted, A. & Hølmer, G. (2001) Effect of six dietary fatty acids on postpandial lipid profile, plasma free fatty acids, lipoprotein lipase and cholesterol ester transfer activities in healthy young men. Am. J. Clin. Nutr. 73:198-208.[Abstract/Free Full Text]

24. Tholstrup, T., Miller, G. J., Bysted, A. & Sandstrom, B. (2003) Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men. Am. J. Clin. Nutr. 77:1125-1132.[Abstract/Free Full Text]

25. Haraldsdóttir, J., Holm, L., Jensen, J. H. & Møller, A. (1986) Dietary habits in Denmark 1985. 1. Main results. Natl. Food Agency Publ. 136:1-152.

26. Kostner, G. M., Molinari, E. & Pichler, P. (1985) Evaluation of a new HDL2/HDL3 quantitation method based on precipitation with polyethylene glycol. Clin. Chim. Acta 148:139-147.[Medline]

27. Gatto, L. M., Sullivan, D. R. & Samman, S. (2003) Postprandial effects of dietary trans fatty acids on apolipoprotein(a) and cholesteryl ester transfer. Am. J. Clin. Nutr. 77:1119-1124.[Abstract/Free Full Text]

28. Cohn, J. S., Lam, C.W.K., Sullivan, D. R. & Hensley, W. J. (1991) Plasma lipoprotein distribution of apolipoprotein(a) in the fed and fasted states. Atherosclerosis 90:59-66.[Medline]

29. Pfaffinger, D., Schuelke, J., Kim, C., Fless, G. M. & Scanu, A. M. (1991) Relationship between apo[a] isoforms and Lp[a] density in subjects with different apo[a] phenotype: a study before and after a fatty meal. J. Lipid Res. 32:679-683.[Abstract]

30. Hoppichler, F., Kraft, H. G., Sandholzer, C., Lechleitner, M., Patsch, J. R. & Utermann, G. (1996) Lipoprotein(a) is increased in triglyceride-rich lipoproteins in men with coronary heart disease, but does not change acutely following oral fat ingestion. Atherosclerosis 122:127-134.[Medline]

31. Rader, D. J., Cain, W., Zech, L. A., Usher, D. & Brewer, H. B., Jr (1993) Variation in lipoprotein(a) concentrations among individuals with the same apolipoprotein (a) isoform is determined by the rate of lipoprotein(a) production. J. Clin. Invest. 91:443-447.

32. Scanu, A. M., Edelstein, C., Fless, G. M., Eisenbart, J., Sitrin, M., Kasawa, B. & Hinman, J. (1992) Postprandial lipoprotein(a) response to a single meal containing either saturated or w-3 polyunsaturated fatty acids in subjects with hypoalphalipoproteinemia. Metabolism 41:1361-1366.[Medline]

33. Randall, O. S., Feseha, H. B., Illoh, K., Xu, S., Ketete, M., Kwagyan, J., Tilghman, C. & Wrenn, M. (2004) Response of lipoprotein(a) levels to therapeutic life-style change in obese African-Americans. Atherosclerosis 172:155-160.[Medline]

34. Sandholzer, C., Feussner, G., Brunzell, J. & Utermann, G. (1992) Distribution of apolipoprotein(a) in the plasma from patients with lipoprotein lipase deficiency ad with type III hyperlipoproteinemia. J. Clin. Invest. 90:1958-1965.

35. Wang, X. L., Wang, J. & Rainwater, D. L. (2002) Acute effects of insulin-like growth factor-1 and recombinant growth hormone on liporotein(a) levels in baboons. Metabolism 51:508-513.[Medline]

36. Gaubatz, J. W., Hoogeveen, R. C., Hoffman, A. S., Ghazzaly, K. G., Pownall, H. J., Guevara, J., Jr, Koschinsky, M. L. & Morrisett, J. D. (2001) Isolation, quantitation, and characterization of a stable complex formed by Lp[a] binding to triglyceride-rich lipoproteins. J. Lipid Res. 42:2058-2068.[Abstract/Free Full Text]

37. Almendingen, K., Jordal, O., Kierulf, P., Sandstad, B. & Pedersen, J. I. (1995) Effects of partially hydrogenated fish oil, partially hydrogenated soybean oil, and butter on serum lipoproteins and Lp(a) in men. J. Lipid Res. 36:1370-1384.[Abstract]

38. Tall, A., Sammett, D. & Granot, E. (1986) Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apolipoprotein B-containing lipoproteins during alimentary lipemia. J. Clin. Invest. 77:1163-1172.

39. Dullaart, R.P.F., Groener, J.E.M., Wijk, H. V., Sluiter, W. J. & Erkelens, D. W. (1989) Alimentary lipemia-induced redistribution of cholesteryl ester between lipoproteins. Arteriosclerosis 9:614-622.[Abstract/Free Full Text]

40. Miles, L. A., Fless, G. M., Levin, E. G., Scanu, A. M. & Plow, E. F. (1989) A potential basis for the thrombotic risks associated with lipoprotein(a). Nature 339:301-303.[Medline]

41. White, A. L. & Lanford, R. E. (1995) Biosynthesis and metabolism of lipoprotein (a). Curr. Opin. Lipidol. 6:75-80.[Medline]

42. Shen, G. X. (2003) Impact and mechanism for oxidized and glycated lipoproteins on generation of fibrinolytic regulators from vascular endothelial cells. Mol. Cell Biochem. 246:69-74.[Medline]

43. Palabrica, T. M., Liu, A. C., Aronovitz, M. J., Furie, B., Lawn, R. M. & Furie, B. C. (1995) Antifibrinolytic activity of apolipoprotein(a) in vivo: Human apolipoprotein(a) ransgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis. Nat. Med. 1:256-259.[Medline]

44. Brändström, A., Dahlén, G. H. & Rånby, M. (1988) Lipoprotein(a): in vitro effects on tPA mediated fibrinolysis. Fibrinol Suppl. 2:140.

45. Wolf, K., Rath, M., Niendorf, A., Beisiegel, U. & Dietel, M. (1989) Thrombosis: cellular elements of the vasculature. Circulation 80(Suppl. II):II-522.

46. Loscalzo, J., Weinfeld, M., Fless, G. M. & Scanu, A. M. (1990) Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis 10:240-245.[Abstract/Free Full Text]





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