Remnant cholesterol

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Remnant cholesterol, also known as remnant lipoprotein and triglyceride-rich lipoprotein cholesterol is an atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) with chylomicron remnants. [1] [2] [3] Elevated remnant cholesterol is associated with increased risk of atherosclerotic cardiovascular disease and stroke. [3] [4]

Contents

Definition

Remnant cholesterol is the cholesterol content of triglyceride-rich lipoproteins, which comprise of very low-density lipoproteins and intermediate-density lipoproteins with chylomicron remnants. [2] [5] Remnant cholesterol is primarily chylomicron and VLDL, and each remnant particle contains about 40 times more cholesterol than LDL. [6]

Remnant cholesterol corresponds to all cholesterol not found in high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C). It is calculated as total cholesterol minus HDL-C and LDL-C. [7]

Health effects

Elevated remnant cholesterol is associated with an increased risk of atherosclerotic cardiovascular disease, chronic inflammation, myocardial infarction and stroke. [4] [5] [8] [9] Remnant cholesterol is especially predictive of coronary artery disease in patients with normal total cholesterol. [10] [11]

High plasma remnant cholesterol is associated with increased plasma triglyceride levels. [12] Hypertriglyceridemia is characteristic of high plasma remnant cholesterol, but persons with high plasma triglycerides without high remnant cholesterol rarely have coronary artery disease. [13]

Remnant cholesterol has about twice the association with ischemic heart disease as LDL cholesterol. [14] Although remnant cholesterol tends to be higher in people who are overweight (high body mass index), normal-weight persons with high remnant cholesterol tend to have a higher risk of myocardial infarction. [15]

Lowering remnant cholesterol

Vupanorsen, an ANGPTL3 inhibitor has been shown to lower remnant cholesterol up to 59%. [16]

See also

Related Research Articles

<span class="mw-page-title-main">Cholesterol</span> Sterol biosynthesized by all animal cells

Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.

High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.

<span class="mw-page-title-main">Low-density lipoprotein</span> One of the five major groups of lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL has been associated with the progression of atherosclerosis.

<span class="mw-page-title-main">Lipoprotein</span> Biochemical assembly whose purpose is to transport hydrophobic lipid molecules

A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.

<span class="mw-page-title-main">Hypercholesterolemia</span> High levels of cholesterol in the blood

Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.

Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases, which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for cardiovascular disease, abnormal levels do not mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia.

Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.

<span class="mw-page-title-main">LDL receptor</span> Mammalian protein found in Homo sapiens

The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants—i.e. intermediate-density lipoprotein (IDL), and LDL particles. The receptor also recognizes apolipoprotein E (ApoE) which is found in chylomicron remnants and IDL. In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19. It belongs to the low density lipoprotein receptor gene family. It is most significantly expressed in bronchial epithelial cells and adrenal gland and cortex tissue.

<span class="mw-page-title-main">Apolipoprotein B</span> Protein-coding gene in the species Homo sapiens

Apolipoprotein B (ApoB) is a protein that in humans is encoded by the APOB gene. Its measurement is commonly used to detect risk of atherosclerotic cardiovascular disease.

<span class="mw-page-title-main">Foam cell</span> Fat-laden M2 macrophages seen in atherosclerosis

Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger myocardial infarction and stroke.

The lipid hypothesis is a medical theory postulating a link between blood cholesterol levels and the occurrence of cardiovascular disease. A summary from 1976 described it as: "measures used to lower the plasma lipids in patients with hyperlipidemia will lead to reductions in new events of coronary heart disease". It states, more concisely, that "decreasing blood cholesterol [...] significantly reduces coronary heart disease".

<span class="mw-page-title-main">Familial hypercholesterolemia</span> Genetic disorder characterized by high cholesterol levels

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.

<span class="mw-page-title-main">Lipoprotein(a)</span> Low-density lipoprotein containing apolipoprotein(a)

Lipoprotein(a) is a low-density lipoprotein variant containing a protein called apolipoprotein(a). Genetic and epidemiological studies have identified lipoprotein(a) as a risk factor for atherosclerosis and related diseases, such as coronary heart disease and stroke.

Blood lipids are lipids in the blood, either free or bound to other molecules. They are mostly transported in a phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its influence on metabolism. Examples of these lipids include cholesterol and triglycerides. The concentration of blood lipids depends on intake and excretion from the intestine, and uptake and secretion from cells. Hyperlipidemia is the presence of elevated or abnormal levels of lipids and/or lipoproteins in the blood, and is a major risk factor for cardiovascular disease.

<span class="mw-page-title-main">Familial dysbetalipoproteinemia</span> Medical condition

Familial dysbetalipoproteinemia or type III hyperlipoproteinemia is a condition characterized by increased total cholesterol and triglyceride levels, and decreased HDL levels.

A lipid profile or lipid panel is a panel of blood tests used to find abnormalities in blood lipid concentrations. The results of this test can identify certain genetic diseases and can determine approximate risks for cardiovascular disease, certain forms of pancreatitis, and other diseases.

<span class="mw-page-title-main">Evacetrapib</span> Chemical compound

Evacetrapib was a drug under development by Eli Lilly and Company that inhibits cholesterylester transfer protein. CETP collects triglycerides from very low-density lipoproteins (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa, but primarily increasing high-density lipoprotein and lowering low-density lipoprotein. It is thought that modifying lipoprotein levels modifies the risk of cardiovascular disease. The first CETP inhibitor, torcetrapib, was unsuccessful because it increased levels of the hormone aldosterone and increased blood pressure, which led to excess cardiac events when it was studied. Evacetrapib does not have the same effect. When studied in a small clinical trial in people with elevated LDL and low HDL, significant improvements were noted in their lipid profile.

<span class="mw-page-title-main">Lipidology</span>

Lipidology is the scientific study of lipids. Lipids are a group of biological macromolecules that have a multitude of functions in the body. Clinical studies on lipid metabolism in the body have led to developments in therapeutic lipidology for disorders such as cardiovascular disease.

The vertical auto profile (VAP) test is a cholesterol, lipid and lipoprotein test.

Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes was a randomized control trial designed to assess the efficacy of niacin (extended-release) added to statin therapy in reducing cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD). These patients had well-controlled low-density lipoprotein (LDL) cholesterol but persistently low high-density lipoprotein (HDL) cholesterol and elevated triglycerides. 3,414 patients with established ASCVD were enrolled. The mean follow-up period was three years. The trial was stopped early due to a lack of efficacy and a trend towards an increase in the incidence of ischemic stroke.

References

  1. ↑ Jørgensen AB, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG, Tybjærg-Hansen A (2013). "Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction". European Heart Journal . 34 (24): 1826–1833. doi: 10.1093/eurheartj/ehs431 . PMID   23248205.
  2. 1 2 Davidson, Michael H. (2018). "Triglyceride-rich lipoprotein cholesterol (TRL-C): the ugly stepsister of LDL-C". European Heart Journal. 39 (7): 620–622. doi:10.1093/eurheartj/ehx741.
  3. 1 2 Davidson, Michael H. (2020). Therapeutic Lipidology. Springer. pp. 139–158. ISBN   978-3-030-56513-8.
  4. 1 2 Yang XH, Zhang BL, Cheng Y, Fu SK, Jin HM. (2023). "Association of remnant cholesterol with risk of cardiovascular disease events, stroke, and mortality: A systemic review and meta-analysis". Atherosclerosis. 371: 21–31. doi:10.1016/j.atherosclerosis.2023.03.012. PMID   36966562.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. 1 2 Nordestgaard BG (2016). "Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology". Circulation Research . 118 (4): 547–563. doi: 10.1161/CIRCRESAHA.115.306249 . PMID   26892957.
  6. ↑ Dallinga-Thie GM, Kroon J, Borén J, Chapman MJ (2016). "Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?". Current Cardiology Reports. 18 (7): 67. doi:10.1007/s11886-016-0745-6. PMC   4877422 . PMID   27216847.
  7. ↑ Stürzebecher, Paulina E; Katzmann, Julius L; Laufs, Ulrich (2023). "What is 'remnant cholesterol'?". European Heart Journal. 44 (16): 1446–1448. doi:10.1093/eurheartj/ehac783.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Varbo A, Nordestgaard BG (2014). "Remnant cholesterol and ischemic heart disease". Current Opinion in Lipidology. 25 (4): 266–273. doi:10.1097/MOL.0000000000000093. PMID   24977981.
  9. ↑ Goliasch G, Wiesbauer F, Blessberger H, Demyanets S, Wojta J, Huber K, Maurer G, Schillinger M, Speidl WS (2015). "Premature myocardial infarction is strongly associated with increased levels of remnant cholesterol". Journal of Clinical Lipidology. 9 (6): 801–6.e1. doi:10.1016/j.jacl.2015.08.009. PMID   26687701.
  10. ↑ Masuoka H, Kamei S, Wagayama H, Ozaki M, Kawasaki A, Tanaka T, Kitamura M, Katoh S, Shintani U, Misaki M, Sugawa M, Ito M, Nakano T (2000). "Association of remnant-like particle cholesterol with coronary artery disease in patients with normal total cholesterol levels". American Heart Journal . 139 ((2 Pt 1)): 305–310. doi:10.1016/j.atherosclerosis.2008.05.024. PMID   10650304.
  11. ↑ Nakamura T, Kugiyama K (2006). "Triglycerides and remnant particles as risk factors for coronary artery disease". Current Atherosclerosis Reports . 8 (2): 107–110. doi:10.1007/s11883-006-0047-3. PMID   16510044.
  12. ↑ Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Nordestgaard BG, Ray KK, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A, Watts GF, European Atherosclerosis Society Consensus Panel (2011). "Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management". European Heart Journal . 32 (11): 1345–1361. doi:10.1093/eurheartj/ehr112. PMC   3105250 . PMID   21531743.
  13. ↑ Fujioka Y, Ishikawa Y (2009). "Remnant lipoproteins as strong key particles to atherogenesis". Journal of Atherosclerosis and Thrombosis. 16 (3): 145–154. doi: 10.5551/jat.E598 . PMID   19556722.
  14. ↑ Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG (2013). "Remnant cholesterol as a causal risk factor for ischemic heart disease". Journal of the American College of Cardiology . 61 (4): 427–436. doi: 10.1016/j.jacc.2012.08.1026 . PMID   23265341.
  15. ↑ Varbo A, Freiberg JJ, Nordestgaard BG (2018). "Remnant Cholesterol and Myocardial Infarction in Normal Weight, Overweight, and Obese Individuals from the Copenhagen General Population Study". Clinical Chemistry . 64 (1): 219–230. doi: 10.1373/clinchem.2017.279463 . PMID   29021326.
  16. ↑ Zimerman A, Wiviott SD, Park JG, Murphy SA, Ran X, Bramson CR, Curto M, Ramos V, Jevne A, Kuder JF, Verma S, Wojakowski W, Terra SG, Sabatine MS, Bergmark BA, Marston NA. (2024). "Reductions in remnant cholesterol and VLDL cholesterol through inhibition of ANGPTL3 protein synthesis: an analysis from the TRANSLATE-TIMI 70 trial". European Journal of Preventive Cardiology. 31 (10): 1216–1223. doi: 10.1093/eurjpc/zwae090 .{{cite journal}}: CS1 maint: multiple names: authors list (link)
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