This article may rely excessively on sources too closely associated with the subject , potentially preventing the article from being verifiable and neutral.(August 2023) |
James D. Otvos [1] [2] [3] [4] [5] [6] [7] [8] [9] is an academician/researcher/entrepreneur in nuclear magnetic resonance spectroscopy who has pioneered and published, since the later 1970s, extensive research [10] on the roles of the various lipoproteins in cardiovascular disease and led the company, LipoScience, which developed the Vantera Analyzer. [11]
From 1950 (when the first research was published identifying lipoproteins as the primary driver of the atherosclerosis process [12] ) through the 1990s, the basic science work which led to sub-fractionation of lipoprotein particles: chylomicrons (AKA ULDL), VLDL, IDL, LDL & HDL had long remained too expensive for routine use in clinical medicine. This issue was (and is) complicated by the multiple sub-distinctions within these groupings.
While this work was a giant breakthrough in understanding how fat molecules (needed and manipulated by all cells in the body) are carried within the water-based blood and intracellular transport systems, work which led to a Nobel prize in Medicine in 1985 for identification of the LDL receptor protein via which cells ingest (termed endocytosis) LDL particles, cost (about $5,000 USD per blood sample in the 1970s for the ultracentrifugation and gradient-gel electrophoresis methods which had been developed and utilized in earlier research) remained a major barrier to clinical use of this valuable information.
In the early 1990s, given increasing evidence and understanding of the role which the many different lipoproteins (not cholesterol per-se) played in the usual progression of atherosclerotic disease, Otvos began novel research work in using NMR spectroscopy to quantify the lipoproteins in first primate and then human plasma. This in turn led to giant decreases in cost while improving accuracy.
His work has led to several rewards [1] for both accuracy and, even more importantly, for great reductions in the cost to patients of having quantitative lipoprotein fractionation; it is no longer just an expensive research tool but has become low enough in cost for most physicians and patients to use the methodology to greatly improve treatment strategies and greatly reducing cardiovascular event rates without resorting to only arterial bypass surgery or angioplasty/stents to treat the symptoms of advanced disease, often after the individual has become permanently disabled.
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.
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 is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which arteries are affected.
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.
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.
Apolipoproteins are proteins that bind lipids to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph.
Hyperlipidemia is abnormally elevated 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.
Apolipoprotein B (ApoB) is a protein that in humans is encoded by the APOB gene. It is commonly used to detect risk of atherosclerotic cardiovascular disease.
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 heart attacks 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".
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.
Lecithin cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism. The disease has two forms: Familial LCAT deficiency, in which there is complete LCAT deficiency, and Fish-eye disease, in which there is a partial deficiency.
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.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (orthologs) are found across many species. As with many proteins, PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.
A lipid profile or lipid panel is a panel of blood tests used to find abnormalities in lipids, such as cholesterol and triglycerides. 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.
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.
Remnant cholesterol, also known as remnant lipoprotein, is a very atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). Stated another way, remnant cholesterol is all plasma cholesterol that is not LDL cholesterol or HDL cholesterol, which are triglyceride-poor lipoproteins. However, remnant cholesterol is primarily chylomicron and VLDL, and each remnant particle contains about 40 times more cholesterol than LDL.
Dr. Robert S. Rosenson is a Professor of Medicine and also lending his services as the Director of cardio metabolic disorders at the Icahn School of Medicine at Mount Sinai.