© 1995 American Heart Association, Inc.
Articles |
Lipoprotein Lipase Mass and Activity in Plasma and Their Increase After Heparin Are Separate Parameters With Different Relations to Plasma Lipoproteins
From the King Gustaf V Research Institute, Karolinska Institute, and Departments of Cardiology (P.T.) and Internal Medicine, (F.K., A.H.), Karolinska Hospital, Stockholm, and the Department of Medical Biochemistry and Biophysics (G.O., T.O.), University of Umeå, Umeå, Sweden.
Correspondence to Dr Per Tornvall, King Gustaf V Research Institute, Karolinska Hospital, Karolinska Institute, S-171 76 Stockholm, Sweden.
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Abstract |
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Abstract Lipoprotein lipase (LPL) activity and mass in plasma and their increase after heparin administration were measured in 61 men who had suffered myocardial infarction before the age of 45 years and in 69 population-based age- and sex-matched control subjects without coronary heart disease to study the relations between these parameters in plasma and their correlations with plasma lipoproteins in subjects with a wide range of lipoprotein and LPL levels. There was a relatively large amount of LPL protein compared with LPL activity in preheparin plasma, indicating that the majority of circulating LPL is catalytically inactive. LPL mass and activity in postheparin plasma (postheparin minus preheparin values) were highly correlated, and the calculated mean specific activity (0.35 mU/ng) was in the range expected for catalytically active LPL. Hence, heparin releases mainly active LPL. The four LPL parameters (mass and activity in plasma and their increase after heparin administration) were not related to each other, except for postheparin plasma LPL mass and activity, and they showed different correlations with plasma lipoprotein lipid concentrations. There was a strong positive correlation between LPL mass in preheparin plasma and the HDL cholesterol level as well as weak negative relations to VLDL triglyceride and cholesterol concentrations in the patients. In contrast, preheparin LPL activity showed no correlation with the HDL cholesterol level but weak positive relations to VLDL triglyceride and cholesterol concentrations in the control subjects. Postheparin plasma LPL activity related positively to the HDL cholesterol level and negatively to the VLDL triglyceride concentration in the control subjects. Case subjects differed from control subjects in that they had higher preheparin plasma LPL activity and a tendency toward lower specific activity of postheparin plasma LPL. The different relations of the measured LPL parameters to plasma lipoproteins and the difference in preheparin plasma LPL activity between patients and control subjects might reflect a disturbance of the LPL system in the patients.
Key Words: lipoprotein lipase • plasma lipoproteins • coronary heart disease
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Introduction |
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LPL catalyzes the bulk reaction in lipoprotein metabolism, unloading plasma triglycerides in peripheral tissues.1 2 Several studies have explored the relation between LPL activity and parameters of lipoprotein metabolism (for discussion, see References 3 and 43 4 ) by measuring LPL activity in plasma after heparin injection, which is assumed to reflect the LPL available at the endothelial surface, or by studies of LPL activity in tissue biopsies. Some of these studies have shown decreased postheparin plasma LPL activity in hypertriglyceridemic subjects5 6 7 8 9 and a weak inverse correlation of LPL activity to plasma or VLDL triglyceride concentrations5 7 9 10 and a stronger positive relation to HDL-C7 9 11 levels in subjects with a wide range of triglyceride levels. High LPL activity has also been linked to a more rapid clearance of triglycerides12 and chylomicrons13 from plasma after oral fat intake. Heterozygotes for LPL deficiency have decreased LPL activity in postheparin plasma and tend to develop hypertriglyceridemia with decreased LDL-C and HDL-C levels after the age of 40 years.14
LPL activity in plasma before and after heparin injection are unrelated.15 16 17 The implication is that LPL in plasma is not in static equilibrium with LPL bound to the endothelium. This is not surprising, since the exchange of LPL between endothelial binding sites and plasma18 19 20 21 and the recycling of the enzyme through endothelial cells22 are under metabolic control, and binding of LPL to endothelial heparan sulfate involves an additional 116-kD protein.23 Furthermore, there is a net flux of LPL from peripheral tissues to the liver, where the enzyme is degraded.24 LPL acts not only as an enzyme but also as a ligand that promotes binding to cell-surface heparan sulfate25 26 27 and to dedicated lipoprotein receptors.28 29 Plasma contains both catalytically active LPL and inactive LPL protein,30 which is associated with lipoproteins.31 32
In the present study we measured four parameters, LPL activity and mass in plasma and the increase in LPL activity and mass in plasma after the administration of heparin. Our principal questions were whether these parameters are related to each other, whether they are correlated with plasma lipoprotein lipid concentrations, and if so, whether the associations are with the same lipoproteins. Young survivors of myocardial infarction, a group with a high prevalence of hypertriglyceridemia,33 were studied together with population-based sex- and age-matched control subjects without CHD. This choice of study groups also allowed us to assess the relations of LPL activity and mass to CHD.
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Methods |
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Subjects
Sixty-one men with a first myocardial infarction before the age of 45 years were studied consecutively. The patients had initially been admitted between April 1989 and October 1990 to the 10 hospitals in Stockholm County with coronary or intensive care units.33 They were subsequently referred to the Karolinska Hospital for metabolic and cardiological investigations. Metabolic and angiographic studies were performed 4 to 6 months after the acute event, when it was expected that acute-phase reactions due to myocardial damage had subsided. A total of 104 men fulfilled the criteria for participation in the study. Of the 43 patients not investigated, 3 died during the acute stage or the early postinfarction period, and 10 declined participation. Nine patients were excluded because of the presence of concomitant diseases such as manifest diabetes mellitus (n=2), heterozygous familial hypercholesterolemia (n=1), severely impaired renal function (n=4), or large cerebral infarction (n=2). An additional 16 patients were not investigated due to periods with deficient laboratory capacity, and 5 patients were either referred later than 6 months after their infarction or were not available for study by the research team. None of the eligible patients had hypothyroidism.
As control subjects for the present study, the first 69 men who were recruited from a register containing all the inhabitants in Stockholm County were chosen. In all, 164 men born between 1947 and 1956 were invited. Of these, 129 agreed to participate in the program, which included blood sampling and an interview to exclude individuals with a history of prior myocardial infarction, angina pectoris, or any other severe disease.
None of the patients investigated were on lipid-lowering drugs, but all had been informed about a lipid-lowering diet during their first visit to the outpatient clinic 6 weeks after admission to the coronary care unit. The dietician's instructions given to the patients aimed at a diet low in fat, rich in complex carbohydrates, and with a limited intake of alcohol. The percentage composition of the different sources of energy in the recommended diet was 10% to 15% protein and 30% fat, with the remaining energy from carbohydrates. The saturated/monounsaturated/polyunsaturated fat ratio was 1:1:1. None of the control subjects had received any type of dietary instructions by the time of investigation.
Blood Sampling
Blood samples for determination of plasma lipoproteins and LPL
were taken between 8 and 9 AM after 12 hours of fasting,
during which time smokers were asked to refrain from smoking. All
subjects were free from symptoms of infectious disease at the time of
blood sampling. Venous blood was drawn into precooled sterile tubes
(Vacutainer, Becton Dickinson) containing Na2-EDTA (1.4
mg/mL) for lipoprotein and Na-heparin (29 E/mL) for lipase
analyses. The tubes were immediately placed in an ice bath.
After the initial blood sampling, an injection of heparin (100 U/kg
body wt IV) was given, and venous blood for determination of
postheparin plasma LPL activity and protein concentration
was drawn from the other arm 15 minutes after the heparin injection.
Plasma was recovered by low-speed centrifugation
(1400g for 20 minutes) at 1°C and kept at this temperature
throughout the preparation procedure. Aliquots for LPL determinations
were frozen at -80°C within 1 hour of blood sampling. Samples were
shipped on dry ice from Stockholm to Umeå, where the analyses
were performed.
Lipase Preparations
Bovine LPL, used to raise antibodies, was prepared from milk by
chromatography on heparin-Sepharose.34
Human LPL, used as standard for the ELISA, was purified from
postheparin plasma.28 Human HL, used to raise
antibodies, was prepared from postheparin
plasma.35
Antibodies
Female chickens were immunized with bovine LPL.36
Immunoglobulins were isolated from egg yolks by precipitation followed
by chromatography on DEAE-Affi-Gel Blue (Pharmacia LKB
Biotechnology). Antibodies were then purified by affinity
chromatography on a column of bovine LPL
immobilized on agarose. They were eluted with 0.2 mol/L
glycine, pH 2.7, immediately dialyzed against 10 mmol/L Tris-Cl, pH
7.4, and stored in this buffer at a protein concentration of about 0.5
mg/mL. The monoclonal antibody designated 5D2 was a kind gift from Dr
John Brunzell, University of Washington, Seattle. This antibody
recognizes an epitope present in the C-terminal part of both bovine
and human LPL.37 38 For the ELISA the antibody was
conjugated with peroxidase. Antibodies to HL, used for immunoinhibition
during the LPL assay, were raised in a goat. Immunoglobulins were
purified by using protein A–Sepharose (Pharmacia LKB).
Determination of Plasma Lipase Activities
Assay conditions for LPL activity (sonicated emulsion of
[3H]oleic acid–labeled triolein in 20% Intralipid
[Kabi Nutrition]) were the same as those described.39 In
the LPL assay, samples were preincubated for 2 hours on ice with 0.5
vol goat antibodies to HL to suppress HL activity. All determinations
were done in triplicate. The reliability of the lipase activity assay
has been described.17 Lipase activities are expressed in
milliunits, which correspond to 1 nanomole of fatty acid released
per minute.
ELISA for LPL Mass
Wells of microtiter plate were coated with 100 µL purified
chicken anti-LPL (10 µg/mL in phosphate-buffered saline [PBS] [10
mmol/L sodium phosphate and 150 mmol/L NaCl, pH 7.4]) for 4 hours at
room temperature. After three washes with PBS/0.05% Tween 20
(vol/vol), 100 µL sample or human LPL standard (0 to 300 ng/mL)
diluted in PBS/0.05% Tween 20, 1 mg heparin/mL, and 4 mg bovine serum
albumin/mL were incubated for 12 to 16 hours at 4°C. Wells
were then rinsed three times with PBS/0.05% Tween 20. After this the
peroxidase-conjugated 5D2 antibody (diluted 1:5000 in PBS/0.05% Tween
20) was added, and the plates were incubated for 4 hours at room
temperature. After four rinses with PBS/0.05% Tween 20, development
was carried out with 0.4 mg/mL o-phenylenediamine substrate
(DAKO). Three dilutions were used for each sample, and the values that
fell on the linear portion of the standard curve were used. The
variations within the assays were 1.8% and 2.1% and between the
assays, 14.5% and 13.1% (pre- and postheparin plasma,
respectively, for both).
Major Plasma Lipoproteins
The major plasma lipoproteins (VLDL, LDL, and HDL) were
determined by a combination of preparative
ultracentrifugation and precipitation of
apoB-containing lipoproteins followed by lipid
analyses.40 Cholesterol41
and triglyceride42 levels were determined in
triplicate after extraction with dichloromethane and
methanol.43 The cutoff limits for lipoprotein phenotyping
were set at the 90th percentiles of VLDL triglyceride (1.79
mmol/L) and LDL-C values (4.83 mmol/L) for all 129 control subjects
except for 3 individuals on ß-blockers and 2 individuals with known
diabetes mellitus.
Oral Glucose Tolerance Test
An oral glucose tolerance test was performed in patients and
control subjects on a separate occasion 1 to 2 weeks after blood
sampling, including postheparin plasma. Glucose was
ingested in a dose of 1.75 g/kg body wt in 150 to 200 mL of water
flavored with lemon extract. Venous blood samples were collected before
and 15, 30, 45, 60, and 120 minutes after glucose intake for blood
glucose determination according to the glucose oxidation
method.44 Oral glucose tolerance was assessed according to
criteria adapted from Reaven et al.45 Repeated fasting
blood glucose values above 7.0 mmol/L were used as the criterion for
manifest type II diabetes.
Statistical Methods
Conventional methods were used for calculating medians, means,
and SDs. Coefficients of skewness and kurtosis were calculated to test
deviations from a normal distribution. Logarithmic transformation of
VLDL triglyceride and cholesterol levels was
performed on the individual values, and a normal distribution was
confirmed before statistical computations and significance testing were
performed. Differences in continuous variables were tested by
repeated Student's t tests and covariance
analysis. Relations between lipases and lipoprotein
variables were analyzed by computation of Pearson
correlation coefficients. Values are expressed as mean±SD unless
otherwise stated.
Ethical Considerations
The study protocol was approved by the local ethics committee at
the Karolinska Hospital, and all subjects gave their informed consent
to participate in the study.
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Results |
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Basic Characteristics of the Study Groups
The majority of patients had hyperlipoproteinemia of hypertriglyceridemic phenotypes, mainly type IV hyperlipidemia; control subjects were generally normolipidemic. The patients also had a higher BMI and increased prevalences of hypertension and decreased oral glucose tolerance. About one third of both patients and control subjects were smokers at the time of the metabolic investigation. ß-Blockers were taken by nearly all patients according to the current treatment policy for postinfarction patients (Table 1
).
The plasma concentrations of cholesterol and
triglycerides, VLDL cholesterol and
triglycerides, LDL-C, LDL triglycerides, and
HDL triglycerides were higher in patients than control
subjects, whereas the HDL-C level was considerably lower (Table 2).
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LPL in Preheparin and Postheparin Plasma
In preheparin plasma, LPL activity and mass were 1.7±1.1 mU/mL
and 92.1±38.6 ng/mL, respectively, when patients and control subjects
were analyzed together (Table 3). There were no
correlations between LPL mass and activity (r=-.03,
r=-.13, and r=.12 in all subjects, patients, and
control subjects, respectively, NS; Fig 1). The
calculated specific activity ranged between 0.002 and 0.116 mU/ng, and
the mean specific activity was 0.022±0.018 mU/ng considering patients
and control subjects together. The specific activity of purified human
LPL has been reported as 0.40,46 1.55,47 and
0.5148 mU/ng. Thus, preheparin plasma appears to contain
only a small amount of active LPL, and the major portion of LPL protein
was catalytically inactive. Mean LPL activity increased about 170-fold,
whereas mean LPL mass increased only about ninefold after heparin
injection (Table 3). A significant correlation between pre- and
postheparin values for activity was found in the patient
group (r=.07 [NS], r=.32 [P<.05],
and r=-.07 [NS] in all subjects, patients, and control
subjects, respectively), whereas no significant relations were obtained
between pre- and postheparin mass (r=.06,
r=.03, and r=.09 in all subjects, patients, and
control subjects, respectively, NS). LPL activity and mass in
postheparin plasma were highly correlated, whether measured
as absolute values in postheparin plasma (r=.77,
r=.75, and r=.80 in all subjects, patients, and
control subjects, respectively, P<.001) or as values
obtained after subtraction of preheparin values (r=.78,
r=.78, and r=.81 in all subjects, patients, and
control subjects, respectively, P<.001; Fig 2). Stimulated LPL parameters are from now
on presented as postheparin minus preheparin
values. The calculated mean specific activity of
postheparin LPL was 0.35±0.08 mU/ng (Table 3), which is in
the range expected for bovine LPL activity under these assay
conditions.45 46 47 Hence, heparin releases mainly active
LPL. A corollary is that there are at least three relatively
independent variables to consider: a small amount of active LPL in
preheparin plasma, a larger amount of inactive LPL protein in
preheparin plasma, and the amount of active LPL released by
heparin.
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indicates control subjects (n=69); 
, patients (n=61).
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Differences Between Patients and Control Subjects and Their
Respective Subgroups
LPL activity in preheparin plasma was increased in patients
compared with control subjects (P<.01). In contrast, no
group differences were seen for LPL mass in pre- and
postheparin plasma or for LPL activity in
postheparin plasma (Table 3
). Patients had higher BMI and
larger area under the curve of glucose levels during the oral glucose
tolerance test than did control subjects. Covariance
analysis of the influence of these factors could not explain
the difference between patients and control subjects in LPL activity in
preheparin plasma. Since some of the control subjects were
hypertriglyceridemic, group
analysis was also performed to compare patients to
normolipidemic control subjects. In this comparison, the difference in
preheparin plasma LPL activity (higher in patients) was strengthened
(P<.005), and the difference in postheparin
plasma activity (lower in patients) became larger but remained
insignificant (P=.06). The difference in
postheparin plasma LPL activity between patients and
control subjects became significant only when
normotriglyceridemic individuals were considered
(P<.05) as a separate subgroup. The only difference found
in LPL parameters between
normotriglyceridemic and
hypertriglyceridemic patients was for
postheparin LPL activity, which was higher in the
hypertriglyceridemic patients. Patients had
higher specific activity of LPL in preheparin plasma, reflecting the
higher absolute activity but similar protein concentrations, whereas
the specific LPL activity in postheparin plasma was
slightly lower in patients than in control subjects (Table 3). The
difference between patients and control subjects in specific
postheparin LPL activity became insignificant when BMI was
introduced as a covariate. The distribution of patients and control
subjects was skewed, with more patients falling in the lowest quartile
of the distribution for specific LPL activity in
postheparin plasma (Fig 3).
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The prevalence of hypertension was higher in patients than in control subjects, but no differences in any LPL parameters were seen between individuals with or without hypertension when considering patients and control subjects together or only patients. Testing for the influence of hypertension in the control group was not possible because of the small number of hypertensive subjects. The percentage of smokers was similar among patients and control subjects. No differences were found for any LPL parameter when individuals who were present smokers were compared with nonsmokers, considering patients and control subjects together. Similar results were obtained in both study groups.
Relations Between LPL and Lipoproteins
Preheparin LPL mass showed a positive correlation with the HDL-C
level (Fig 4) and negative relations to VLDL lipid
concentrations (Table 4). In contrast, preheparin LPL
activity showed no correlation with the HDL-C concentration but was
related to the levels of cholesterol and
triglycerides in VLDL. The relations to preheparin LPL
activity were seen in control subjects, whereas the relations to
preheparin LPL mass were confined to patients (Table 4). This
reinforces the conclusion that preheparin LPL mass and activity should
be considered as separate parameters.
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For the increase of LPL activity after heparin there was a positive
relation to the HDL-C level when all subjects were considered. This was
due to a strong correlation in control subjects; the corresponding
association in case subjects was absent. There was also a significant
but weak negative relation between postheparin plasma LPL
activity and the VLDL triglyceride concentration in the
control group. Relations of the increase of LPL mass in
postheparin plasma to plasma lipoproteins were
qualitatively the same as for LPL activity (Table 4). When only
normotriglyceridemic control subjects were
considered, the negative relation between postheparin
plasma LPL activity and VLDL cholesterol concentration
became significant (r=-.30, P<.05), and the
corresponding correlation with the VLDL triglyceride level
was strengthened (r=-.38, P<.01). In addition,
a negative relation between postheparin plasma LPL protein
and VLDL triglyceride concentration was noted
(r=-.28, P<.05).
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Discussion |
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This study shows that LPL mass and activity in preheparin plasma and the increase of LPL after the administration of heparin are separate parameters. All four showed significant correlations with plasma lipoprotein lipid concentrations, but the relations were different for the four parameters. This is in line with available evidence from molecular biology, biochemistry, and cell biology that suggests that the LPL mass and activity in preheparin and postheparin plasma reflect different aspects of the function, turnover, and transport of LPL.2
The classical parameter is LPL activity in postheparin plasma, which is assumed to reflect the pool of functional LPL at endothelial surfaces.1 In the present study as well as others5 7 9 10 postheparin LPL activity showed a fairly strong positive relation to the HDL-C level and weak negative correlations with VLDL lipid concentrations. This accords with the idea that postheparin LPL activity would be expected to be related to the efficiency of lipolysis of triglyceride-rich lipoproteins. Further support for this has come from studies showing that the magnitude of the response of triglyceride-rich lipoproteins to an oral fat load is inversely related to postheparin LPL activity. These relations have been seen mainly in healthy individuals12 13 rather than patients with CHD.49 50 51 In our study, the relations of plasma lipoprotein lipids to postheparin LPL were confined to the control group. The implication is that other factors override postheparin LPL activity as determinants of plasma triglycerides in the patient group.52 53
Further evidence that measurements of postheparin plasma LPL activity provide a poor reflection of mechanisms relating to hypertriglyceridemia was the absence of a significant difference in postheparin plasma LPL activity between patients, who had a high prevalence of hypertriglyceridemia, and control subjects. This finding is in contrast to studies that show reduced postheparin plasma LPL activity in hypertriglyceridemic patients.5 6 7 8 9 Most of these studies have used selected normolipidemic control subjects, whereas we used population-based age- and sex-matched control subjects for the comparison. When we omitted control subjects with hypertriglyceridemia from the analysis, our patients tended to have lower postheparin plasma LPL activity than the control subjects.
Potential patient-associated confounding factors in the case-control comparison were the frequent use of ß-blockers, the elevated BMI, the high prevalence of decreased oral glucose tolerance, and a potential difference in dietary habits. However, the lack of large differences between patients and control subjects in any of the measurements of LPL, except for LPL activity in preheparin plasma, argues against an important effect of ß-blockers. Nevertheless, an effect of ß-blockers on triglyceride levels that is mediated by factors other than LPL cannot be ruled out. No significant effects of BMI or postload glycemia were found on any of the LPL parameters in covariance analysis, whereas a confounding influence of any differences in dietary habits could not be disentangled due to a lack of detailed information on diet composition.
The increases of LPL activity and mass after the administration of heparin were closely correlated in the present study, as previously reported by Peterson at al.38 Patients had slightly lower specific activity of LPL released by heparin and were more and less frequently represented in the lowest and highest quartiles, respectively, of the distribution of values for LPL specific activity for all subjects. There could be several possible reasons for this. For instance, metabolic parameters could influence the stability of the dimeric, active form of the enzyme. Some of the subjects could be heterozygous for a mutation that produces an unstable variant of LPL.38 54 Others could be heterozygous for the common premature stop variant,55 which, according to Kobayashi et al,56 has lower than normal LPL activity.
The LPL activity in preheparin plasma was low (<1% of the activity in postheparin plasma). As in previous studies, preheparin plasma LPL activity was not correlated with postheparin plasma LPL activity.15 16 17 Weak but significant positive correlations with VLDL triglyceride and cholesterol levels and LDL-C concentrations were confined to the control subjects. Glaser et al16 also found a positive relation of preheparin plasma LPL activity to the LDL-C level, mainly in normolipidemic individuals, but they report no relations to other lipoprotein lipid levels. In our study preheparin plasma LPL activity in patients differed from that in control subjects in two ways. The activity was higher and the relations to plasma lipoprotein lipid concentrations seen in control subjects were weaker or nonexistent in the patient group. This may point to a derangement of the LPL system in the patients, but such a conjecture is not easy to put into a mechanistic framework. The mean plasma activity, 1.7 mU/mL, corresponds to hydrolysis of about 0.05 µmol triglycerides · mL plasma-1 · h-1, or less than 5% of all plasma triglycerides per hour. In view of the much higher LPL activity present at endothelial surfaces, it is unlikely that the activity in plasma would significantly affect the hydrolysis of triglyceride-rich lipoproteins. One possibility is that the increased preheparin plasma LPL activity in the patients reflects changes of the vascular endothelium21 22 23 or changes in tissue fatty-acid metabolism, resulting in impeded binding of LPL and release of LPL with a higher specific activity.17 18 19 20
There was a relatively large amount of LPL protein in preheparin plasma, much more than would correspond to the LPL activity. In addition, mass and activity were not related to each other. Most of the LPL protein in preheparin plasma elutes as an early peak from heparin-Sepharose, corresponding to the position for inactive monomeric LPL. This protein is a full-length LPL and is bound to plasma lipoproteins.32 The functional significance of this inactive LPL is unclear. It may act as a ligand targeting lipoproteins for binding to cell surfaces25 26 27 and receptors.27 28 29 Preheparin LPL mass did not correlate with any of the lipoprotein lipids in the control subjects. In contrast, there were weak negative correlations with the VLDL lipid concentrations and a strong positive relation to the HDL-C level in the patient group. Furthermore, these lipoprotein lipid concentrations correlated with the postheparin plasma LPL activity in the control group. This is a suggestive pattern, but more information on the dynamics and functional role of preheparin LPL mass is needed before mechanistic interpretations can be made.
In summary, the results of this study might reflect a derangement of the LPL system in the patients. In the control subjects there were a number of correlations between LPL activity in pre- and postheparin plasma and lipoprotein lipid concentrations. All these correlations disappeared in the patients, who instead showed correlations with inactive LPL mass, relations that did not exist in the control subjects. It is noteworthy that the strongest correlation observed in this study was between the new parameter, preheparin LPL mass, and the HDL-C level (patients, r=.53, P<.001; control subjects, r=.09, P=NS). In agreement with previous studies, our data show that measurement of postheparin plasma LPL activity in CHD patients is not very informative. On the other hand, all relations between the LPL parameters and lipoprotein lipids showed different patterns in patients and control subjects. This takes the problem one step further and demonstrates that we need to arrive at an integrated view of the LPL system to unravel the derangement that clearly exists among CHD patients.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This work was supported in part by grants from the Swedish Medical Research Council (727 and 8691), the Swedish Heart-Lung Foundation, the Marianne and Marcus Wallenberg Foundation, the King Gustaf V 80th Birthday Fund, the Torsten and Ragnar Söderberg Foundation, the Swedish Margarine Industry Fund for Research on Nutrition, and the Karolinska Institute.
Received December 1, 1994; accepted May 3, 1995.
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References |
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