Triglyceride-rich lipoproteins, remnant-cholesterol, and atherosclerotic cardiovascular disease

Abstract

Purpose of reviewDespite indisputable role of LDL-C lowering, a considerable residual risk for atherosclerotic cardiovascular disease (ASCVD) persists. The precise mechanism(s) underlying this phenomenon remain unclear. Triglyceride-rich lipoproteins (TRL) appear to be one of the main mediators, based on the genetic and epidemiologic data. However, whether this is caused by direct effects of Triglycerides or other components of TRL remains uncertain. The cholesterol component of TRL remnants (Rem-C) has been proposed as a more pertinent mediator of the increased risk associated with high triglycerides. Recent findingsSeveral long-term observational studies have shown a significant relationship between Rem-C and ASCVD events, compared with other triglyceride-related parameters. Recent trials have shown that lowering of triglyceride levels by various agents, including fibrates and omega-3 fatty acids, in statin-treated subjects, did not explain the reduction in ASCVD events. In a large clinical trial with pemafibrate, a highly selective PPAR-a agonist, in type 2 diabetes and elevated triglycerides, the reduction in triglycerides was accompanied by a significant increase in LDL-C and Apo-B levels, despite a reduction in Rem-C, and no effect on ASCVD events.

Triglyceride-Rich Lipoprotein Metabolism: Key Regulators of Their Flux

“…Together, these activities produce particles known as remnants, with the primary structural proteins of chylomicron and VLDL remnants, respectively, being retained by apoB48 and apoB100. In the case of VLDL remnants, these consist of a group of particles known as intermediate-density lipoproteins (IDLs), with a density (d) of 1.006–1.019 g/mL and an analytical ultracentrifuge flotation rate (Sf) of 12–20, which has been demonstrated to overlap in distribution with small VLDL particles with d 1.006 g/mL and Sf 20–60 [ 7 , 12 , 37 , 38 , 39 , 69 ].…”

Serum lipoprotein subfractions are associated with the periodontal status: Results from the population‐based cohort SHIP‐TREND

“…In this study, mediation via systemic inflammation seemed plausible, as triglyceride contents of LDL, HDL and the respective particles were associated with higher CRP levels. In agreement, a recent review based on results from the Copenhagen City study reported that triglyceride-rich lipoproteins caused systemic low-grade inflammation (Ganda, 2023). In line with increased chronic inflammation, it has been argued that systemic inflammation alters the microenvironment in the periodontal pocket, favouring a shift to a dysbiotic microbiome (Van Dyke et al, 2020).…”

The chylomicron saga: time to focus on postprandial metabolism

“…The limitation is that it is not possible to separate remnants using DGU alone. Undeniably, remnant particles produced by the lipolysis of newly synthesized postprandial lipoproteins, CM and VLDL, cover nearly the whole spectrum of lipoprotein densities ( 1 , 9 , 149 ).…”