Triglyceride-Rich Lipoprotein Remnants and Cardiovascular Disease

Abstract

Background Triglycerides, cholesterol, and their metabolism are linked due to shared packaging and transport within circulating lipoprotein particles. While a case for a causal role of cholesterol-carrying low-density lipoproteins (LDLs) in atherosclerosis is well made, the body of scientific evidence for a causal role of triglyceride-rich lipoproteins (TRLs) is rapidly growing, with multiple lines of evidence (old and new) providing robust support. Content This review will discuss current perspectives and accumulated evidence that an overabundance of remnant lipoproteins stemming from intravascular remodeling of nascent TRLs—chylomicrons and very low-density lipoproteins (VLDL)—results in a proatherogenic milieu that augments cardiovascular risk. Basic mechanisms of TRL metabolism and clearance will be summarized, assay methods reviewed, and pivotal clinical studies highlighted. Summary Remnant lipoproteins are rendered highly atherogenic by their high cholesterol content, altered apolipoprotein composition, and physicochemical properties. The aggregate findings from multiple lines of evidence suggest that TRL remnants play a central role in residual cardiovascular risk.

Prognostic Role of Fasting Remnant Cholesterol with In-Stent Restenosis After Drug-Eluting Stent Implantation

“…Dyslipidemia is a major pathogenic risk factor for atherosclerosis, and numerous studies 6 , 9–12 , 17 have confirmed that dyslipidemia is not only an independent risk factor for CHD but also closely related to ISR. For the postoperative lipid management of PCI patients, lipid-lowering therapy is recommended for the secondary prevention of PCI patients according to the guidelines for PCI.…”

“…An increasing number of studies have shown that dyslipidemia and ISR are indissolubly linked. 6 To the best of our knowledge, the majority of the previous related literature 7 , 8 has concentrated on investigating the impact of low-density lipoprotein cholesterol (LDL-C) levels on ISR. However, a growing number of studies have demonstrated that patients are still at considerable risk of developing cardiovascular disease even after lowering LDL-C to recommended concentrations and controlling other risk factors (eg, hypertension and diabetes).…”

Sex hormones drive changes in lipoprotein metabolism

“…We found that HDL subsets were increased in young trans-women treated with estradiol (on puberty blockers) and were lost in young trans-men treated with testosterone (on puberty blockers) where an increase in VLDL and LDL was detected. It is well reported that TG-rich VLDL particles are responsible for residual cardiovascular risk ( Duran and Pradhan, 2021 ). Of interest, no difference in VLDL or LDL subsets were seen in young trans-women, suggesting HDL levels and cellular lipid efflux to HDL may be more sensitive to estradiol fluctuations.…”

Triglyceride-Rich Lipoproteins: Their Role in Atherosclerosis

“…The chylomicron end products are known as remnants; the intermediate-density lipoproteins (IDL) are the corresponding ones for VLDLs. Some (remnants, IDLs, and the denser VLDLs) but not all TRLs are involved in the development of atherosclerotic cardiovascular disease [1][2][3] . As a result, clinicians should be able to discern in which cases TRLs should be considered as treatment targets (besides low-density lipoprotein [LDL]-cholesterol).…”