Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet - the RESOLVE trial

Frédéric Dutheil, Guillaume Walther, Robert Chapier, George Mnatzaganian, Bruno Lesourd, Geraldine Naughton, Julien Verney, Anne Fogli, Vincent Sapin, Martine Duclos, Agnès Vinet, Philippe Obert, Daniel Courteix, Gérard Lac, Frédéric Dutheil, Guillaume Walther, Robert Chapier, George Mnatzaganian, Bruno Lesourd, Geraldine Naughton, Julien Verney, Anne Fogli, Vincent Sapin, Martine Duclos, Agnès Vinet, Philippe Obert, Daniel Courteix, Gérard Lac

Abstract

Background: We aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) - a surrogate indicator of atherogenesis.

Methods: 100 participants (50-70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercise volume (15-20 h/week), restrictive diet (-500 kcal/day), and education. For baseline references, 40 aged-matched healthy controls were recruited. Independent associations between subfractions of lipoproteins and CIMT were evaluated using a generalized estimating equations model accounting for variation in correlations between repeated measures. The lipoprotein subfractions profile was assessed using Lipoprint® electrophoresis allowing to separate: the very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL) C, B and A, the low-density lipoprotein (LDL) with subfractions 1 and 2 as large LDL and subfractions 3 to 7 as small dense LDL (sdLDL), and the high density lipoprotein (HDL) subfractions categorized into large, intermediate, and small HDL. Apolipoproteins A1 and B were also measured.

Results: 78 participants completed the program. At baseline, apolipoproteins B/A1, VLDL, sdLDL and small HDL were higher in MetS than in healthy controls; IDL, LDL size, large and intermediate HDL were lower. Despite time-related regains during the follow-up, lipoprotein subfractions traditionally involved in cardiovascular risk, such as sdLDL, improved immediately after the residential program with values closest to those of healthy controls. CIMT improved throughout the lifestyle intervention. Using a generalized estimating equations model, none of the subfractions of lipoproteins nor apolipoproteins were linked to CIMT.

Conclusions: Lipoprotein subfractions traditionally involved in CVR, decreased after the 3-week residential program. During a 12 month follow-up, the time-related regains remained closer to the values of healthy controls than they were at baseline. CIMT improved throughout the lifestyle intervention. However, we failed to demonstrate a link between some lipoprotein subfractions and the atherogenicity directly measured from the wall thickness of arteries (CIMT). Further investigations are required to explore the atherogenicity of lipoprotein subfractions.

Trial registration: NCT00917917.

Figures

Figure 1
Figure 1
Apolipoprotein B/A1 ratio and other lipoproteins sub-fractions profile using quantimetrix Lipoprint™ system. The very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL), the low-density lipoprotein (LDL) size which can distinguish the large LDL sub-fractions 1–2, non atherogenic, and the small dense LDL (sdLDL) sub-fractions 3–7, atherogenic, and the high-density lipoprotein (HDL) sub-fractions (large, intermediate and small). *: p < .05; **: p < .01; ***: p < .001 between different time of measurements for MetS participants. ‡: p < .05; ‡‡: p < .01; ‡‡‡: p < .001 between MetS participants and controls.
Figure 2
Figure 2
Framingham score and carotid-intima-media thickness in patients with MetS undertaking a lifestyle intervention. *: p < .05; **: p < .01; ***: p < .001 between different time of measurements for MetS participants. ‡‡‡: p < .001 between MetS participants and controls.
Figure 3
Figure 3
Range of lipoproteins sub-fractions on the separating gel (A), with a normal profile (B) and a pathological profile (C), using quantimetrix Lipoprint™ system.

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