Cardiovascular disease is the main cause of morbidity and mortality in individuals with metabolic syndrome (MetS). Cardiovascular disease risk factors (CVR) include an excess of body fat, promoting dyslipidemia, with reduced high-density lipoprotein cholesterol (HDL) and increased low-density lipoprotein cholesterol (LDL). A low level of HDL is regarded as a sensitive discriminator of atherogenicity and is one among the five criteria selected by the International Diabetes Federation (IDF) to characterize MetS. More specifically, lipoproteins can be differentiated into subfractions using electrophoresis. LDL was categorized into subfractions 1 to 7, relative to decreasing size and increasing density. Among them, the small dense subfractions 3 to 7 (sdLDL), not routinely assessed in clinical practice, are presumed to be more atherogenic than larger LDL particles[4, 5]. The notion of HDL functionality was more recently introduced, with an increased CVR associated with a decreased HDL size[6–8]. Relationships also emerged between atherogenesis and other lipoproteins classes, very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). Moreover, apolipoproteins (Apo) are the structural protein constituting the lipoproteins. The atherogenicity of MetS is possibly mediated by elevated ApoB, with the proatherogenic/antiatherogenic ratio ApoB/ApoA1 being strongly linked to CVR. The relationship between lipoprotein profiles and atherogenesis has a strong clinical focus. Early detection of CVR may prevent a later diagnosis of cardiovascular disease by using strategies such as lifestyle interventions[13, 14]. The Framingham score, although commonly used to estimate the CVR, may not permit the early risk detection available from profiling the lipoprotein subfractions.
However, 1) previous studies that assessed the relationship between CVR and some subfractions of lipoproteins were mainly cross-sectional[16–20], 2) the role of each subfractions is debated. Even for the more robust theory on atherogenicity of sdLDL, a predominance of very large rather than sdLDL has been reported with increased CVR, 3) The few studies reporting longitudinal changes of lipoprotein subfractions following a lifestyle intervention (diet, physical activity) describe relatively acute or short term responses[13, 24–26], 4) lack direct measures of atherogenicity inside the walls or arteries[13, 23–26], 5) provide limited selections of lipoprotein subfractions[13, 23–26], and 6) are not reported in populations with MetS[13, 23–26].
Therefore, we aimed to describe long-term changes in the profile of the lipoprotein subfractions among metabolic syndrome volunteers from the RESOLVE trial who participated in a lifestyle intervention (diet and physical activity). A secondary aim was to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) – a surrogate indicator of atherogenesis.