Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk

Abstract

Randomized clinical trials with statins and other lipid-lowering drugs have shown the presence of a “residual cardiovascular risk” in those treated to “target” for LDL-cholesterol. This risk is mainly associated to lipid components other than LDL and in particular to remnant cholesterol (RC) and to lipoproteins rich in triglycerides in fasting and non-fasting conditions. During fasting, RCs correspond to the cholesterol content of the VLDL and their partially depleted triglyceride remnant containing apoB-100. Conversely, in non-fasting conditions, RCs include also cholesterol present in chylomicrons containing apoB-48. Therefore, RCs refer to total plasma cholesterol minus HDL-cholesterol and LDL-cholesterol, that is, all the cholesterol present in the VLDL, chylomicrons and in their remnants. A large body of experimental and clinical data suggests a major role of RCs in the development of atherosclerosis. In fact, RCs easily pass the arterial wall and bind to the connective matrix stimulating the progression of smooth muscle cells and the proliferation of resident macrophages. RCs are a causal risk factor for cardiovascular events. Fasting and non-fasting RCs are equivalent for predicting vascular events. Further studies on drugs effect on RC levels and clinical trials to evaluate the efficacy of RC reduction on cardiovascular events are needed.

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 ].…”

“…Chylomicron and very low-density lipoprotein (VLDL) intravascular catabolism results in a variety of remnant particles that have undergone partial lipolysis. Lipases, lipid transfer proteins, and the number of exchangeable lipoproteins all have an impact on the amounts and characteristics of these molecules in plasma [ 27 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Remnants may develop pathologic characteristics that aid in the progression of ASCVD, such as elevated cholesterol levels and the transport of thrombogenic and inflammatory mediators, during their plasma transit [ 7 ].…”

The Combination of Remnant Cholesterol and Waist Circumference Offers Predictive Value for Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study from a Medical Examination Center

“…This study was thus formulated to evaluate the predictive value of a non-invasive and clinically accessible index when used to gauge NAFLD risk in the general population. RC levels are closely tied to atherosclerosis, hypertension, cardiovascular disease, and diabetes, 12 and there have been prior research efforts documenting the relationship between RC and NAFLD in healthy non-diabetic populations or younger individuals. 17 , 18 Here, higher RC levels were significantly associated with greater NAFLD risk under both adjusted and unadjusted models.…”

“… 11 RC has been identified as a risk factor for cardiovascular events and atherosclerosis. 12 There have been few reports, however, systematically evaluating whether RC can predict the incidence of NAFLD in the general population or whether this predictive performance can be improved by combining RC levels and WC values. The present study was thus designed with the goal of constructing a single, noninvasive, inexpensive index suitable for use in general screening and the early treatment of NAFLD.…”

The chylomicron saga: time to focus on postprandial metabolism

“…In combination, lipolysis by LPL and other lipases results in remnants, which are particles with primary structural proteins that are maintained ( 23 , 25 , 103 ). As already indicated, these proteins are apoB48 (CM) and apoB100 (VLDL).…”