Remnant lipoproteins: are they equal to or more atherogenic than LDL?

Abstract

Purpose of review To critically appraise new insights into the biology of remnant lipoproteins and their putative role in the pathophysiology of atherosclerotic cardiovascular disease, and to compare the atherogenicity of remnant particles with that of LDL. Recent findings New in vivo stable isotope tracer studies of the kinetics of apoB48-and apoB100-containing lipoproteins in postprandial conditions have revealed that apoB48-containing VLDL accumulated markedly in hypertriglyceridemic subjects. These intestinally-derived particles were cleared slowly, and represented up to 25% of circulating VLDL; as part of the remnant particle population, they may increase cardiovascular risk. Importantly, the PCSK9 inhibitor, evolocumab, was shown to reduce remnant levels (-29%) during the postprandial period in diabetic subjects on statin therapy, an effect which may be additive to that of LDL cholesterol reduction in conferring cardiovascular benefit. In recent Mendelian randomization studies, the effect of lowering triglyceride-rich lipoproteins or LDL cholesterol translated to similar clinical benefit per unit of apoB. Finally, in randomized trials involving statin-treated patients with ASCVD, remnant cholesterol levels were associated with coronary atheroma progression independently of LDL cholesterol. Summary Overall, data from observational studies in large cohorts, Mendelian randomization studies, metaregression analyses and post-hoc analyses of randomized trials are consistent with the contention that remnants are highly atherogenic particles and contribute to the atherosclerotic burden in an equivalent manner to that of LDL.

Remnant cholesterol is a risk factor for metabolic syndrome and cardiovascular disease: a cross-sectional study

“…Furthermore, our study found that MetS mediated the association between RC and new-onset CVD. In recent years, RC had attracted a lot of attention as a residual cardiovascular risk factor in many large cohort studies, and was highly instrumental due to its great atherogenic capacity [41,42]. Unlike LDL-C, RC is free to enter the intima and become trapped in the connective tissue matrix, and could also be taken up by macrophages without modi cation.…”

Associations between remnant lipoprotein cholesterol and central systolic blood pressure in a Chinese community-based population: a cross-sectional study

“…RLP-C is defined as the cholesterol content in TG-rich lipoproteins (TRLs), namely intermediate-density lipoprotein (IDL), very low-density lipoprotein (VLDL), and chylomicron remnants [ 47 – 49 ]. As TG contents are gradually degraded by lipoprotein lipase in the bloodstream, the cholesterol in RLP-C could also be involved in atherosclerosis plaque formation and subsequent cardiovascular events, and it has been recognized as more atherogenic and proinflammatory than the cholesterol in LDL-C [ 48 – 52 ]. A recent study indicated associations of plasma TGs and relatively small-sized LDL particles with the carotid-femoral PWV, despite no significant associations between VLDL/large IDL subclasses (the main carriers of TG in the blood) and the carotid-femoral PWV [ 53 ].…”

Triglyceride and Triglyceride-Rich Lipoproteins in Atherosclerosis

“…Cholesterol carried by TGRLs and their remnants is a causal factor of ASCVD except for LDL-C. The structural characteristics of TGRLs and their remnants, such as lipid content, apolipoprotein components, particle size, and retention time in circulation, determine the burden of atherosclerosis ( Aguilar Salinas and John Chapman, 2020 ; Packard et al, 2020 ; Duran and Pradhan, 2021 ). Although there are several available methods for quantification of TGRLs and their remnants, more specific methods are needed to accurately determine and quantify the subclasses of these particles that are derived from different metabolic pathways.…”