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Postprandial lipaemia and its relation to premature atherosclerosis in middle-aged men

thesis
posted on 2024-09-02, 17:59 authored by Susanna Boquist

The present research programme was set up to investigate whether pertubations of the metabolism of postprandial triglyceride-rich lipoproteins (TRLs) are related to premature atherosclerosis and to determine if treatment with a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (atorvastatin) improves deranged alimentary lipaemia in postinfarction patients with combined hyperlipidaemia. The relation between plasma insulin and alimentary lipaemia was investigated as well.

To this purpose healthy middle-aged men and male survivors of a myocardial infarction underwent an oral fat tolerance test of a mixed meal type. TRLs were subfractionated according to particle size by cumulative density gradient ultracentrifugation. The apolipoprotein (apo) B-48 and B-100 concentrations in each fraction of TRLs were determined by analytical sodium dodecyl sulphate polyacrylamide gel electrophoresis as a measure of chylomicron remnant (intestinally derived) and very low-density lipoprotein ((VLDL) liver derived) particle concentrations.

In study I the relation between alimentary lipaemia and common carotid artery intima-media thickness IMT) was investigated in 96 healthy 50-year-old men with an apo E3/E3 genotype. This study demonstrated that the early triglyceride response after the mixed meal is independently associated with common carotid MT. Similarly, in study IV, the postprandial triglyceridaemia was exaggerated in a group of 41 male postinfarction patients compared to healthy controls. The patients had elevated plasma concentrations of all subfractions of TRLs. However, in the postprandial state, this appeared to be a consequence of the plasma concentrations of these particles being elevated already in the fasting state. In the group of healthy 50-year-old men, on the other hand, the large VLDL particles measured at 3 hours after the test meal represented the only subfraction of TRLs that correlated with IMT, and this relation was lost in multivariate analysis.

In study II the relations of fasting plasma insulin concentrations to fasting and postprandial TRLs were determined in 99 healthy 50-year-old men with an apo E3/E3 genotype. The plasma insulin concentration was associated with the postprandial plasma concentrations of triglycerides, large VLDLs and large and small chylomicron remnants. For the large TRL particles this relation reflected an association between plasma insulin and these particles present already in the fasting state. In addition, strong positive correlations were found between the late increases in large TRLs and plasma free fatty acid concentrations at 6 hours.

Study III was performed to investigate the effects of treatment with a P, receptor-blocking agent, metoprolol, on postprandial lipaemia as a preparation for study IV. Sixteen healthy men were randomized to metoprolol 100 mg or placebo once daily. Metoprolol induced modest increases in the postprandial plasma concentrations of triglycerides and VLDL particles, especially larger VLDLs. This seemed to be mainly an effect of increased basal production of large VLDL particles.

In study V, 16 postinfarction patients with combined hyperlipidaemia were randomized to atorvastatin 40 mg or placebo once daily. In the postprandial state, atorvastatin induced profound reductions of the plasma concentrations of all subfractions of TRLs and of plasma triglycerides. The effect on large VLDL particles depended to a large extent on a reduced fasting plasma concentration of this particle species and this was also the case for plasma triglycerides.

Conclusions: Enhanced postprandial lipaemia is implicated in the development of premature atherosclerosis in middle-aged men and seems to be linked to the metabolic syndrome by means of insulin resistance. Furthermore, atorvastatin is effective in reducing postprandial plasma concentrations of triglycerides and all subfractions of TRLs in male postinfarction patients with combined hyperlipidaemia.

List of scientific papers

I. Boquist S, Ruotolo G, Tang R, Björkegren J, Bond MG, de Faire U, Karpe F, Hamsten A (1999). "Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men" Circulation 100(7): 723-728
https://pubmed.ncbi.nlm.nih.gov/99380070

II. Boquist S, Hamsten A, Karpe F, Ruotolo G (2000). "Insulin and non-esterified fatty acid relations to alimentary lipaemia and plasma concentrations of postprandial triglyceride-rich lipoproteins in healthy middle-aged men" Diabetologia 43(2): 185-193
https://pubmed.ncbi.nlm.nih.gov/20214714

III. Boquist S, Ruotolo G, Hellénius ML, Danell-Toverud K, Karpe F, Hamsten A. (1998). "Effects of a cardioselective beta-blocker on postprandial triglyceride-rich lipoproteins, low density lipoprotein particle size and glucose-insulin homeostasis in middle-aged men with modestly increased cardiovascular risk" Atherosclerosis 137(2): 391-400
https://pubmed.ncbi.nlm.nih.gov/98283625

IV. Boquist S, Lundman P, Sannegård A, Ericsson CG, Tornvall P, Hamsten A (2000). "Enhanced postprandial lipaemia in midle-aged postinfarction patiens is primarily a consequence of disturbed basal liopoprotein metabolism" (Manuscript)

V. Boquist S, Karpe F, Danell-Toverud K, Hamsten A (2000). "Effects of atorvastatin on fasting and postprandial plasma lipoproteins in postinfarction patients with combined hyperlipidermia" (Manuscript)

History

Defence date

2000-10-20

Department

  • Department of Medicine, Solna

Publication year

2000

Thesis type

  • Doctoral thesis

ISBN-10

91-628-4324-9

Number of supporting papers

5

Language

  • eng

Original publication date

2000-09-29

Author name in thesis

Boquist, Susanna

Original department name

Department of Medicine

Place of publication

Stockholm

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