Hyperlipidemias and Atherosclerotic Cardiovascular Disease ________________________________________
The ratio of total cholesterol (TC) to HDL (TC:HDL) and the ratio of LDL to HDL (LDL:HDL) are clinically relevant predictors of coronary heart disease (CHD) risk. The lower the ratio value, the better the predicted outcome [66; 67; 68; 69]. The Apo B:Apo A-I lipoprotein ratio has also been used as a predictor for CHD. However, comparative studies have concluded that Apo B:Apo A-I ratio for prediction of CHD “does not provide incremental value for CHD risk prediction over established traditional lipid ratios” [66]. However, the ratio may be useful for evaluating the severity of CHD [70]. A cross-sectional study enrolled 792 patients with angiographically defined CHD following hospital admission. The patients were placed into three groups based on the degree of angiographic atherosclerosis or the number of stenotic coronary branches. Demographic and biochemical data were collected, and lipoprotein ratios were calculated. According to the results, the ratios of LDL:HDL and Apo B:Apo A-I increased with increasing degree of angiographic atherosclerosis, and the ratios of triglyceride:HDL, TC:HDL, LDL:HDL and Apo B:Apo A-I increased with the number of stenotic coronary branches. The ratios of TC:HDL, LDL:HDL, and Apo B:Apo A-I were positively associated with both the degree of atherosclerosis and the number of stenotic vessels, and the ratio of triglyceride:HDL was positively associated with the number of stenotic vessels. The Apo B:Apo A-I ratio was also shown to be a direct mediator between the risk factors of age, BMI, HDL, LDL, and severity of CHD [70].
Chylomicrons secreted by intestinal cells are known as “incomplete” chylomicrons because they only express Apo B-48. After entering the lymph and later reaching the bloodstream, chylomicrons interact with circulating HDL, from which they receive Apo C-II and Apo E and then referred to as “complete” chylomicrons. In the capillaries of muscle and adipose tissue, chylomicrons are transformed by the enzyme lipoprotein lipase, a process that requires Apo C-II as a cofactor. As a result of this process, 90% of the triglycerides are hydrolyzed to free fatty acids and glycerol that will be used either as a source of energy in the muscle or stored in the adipose tissue. Individual chylomicrons have a short half-life of 15 to 20 minutes [71]. After interaction with lipoprotein lipase, these cholesterol-rich chylomicron remnants deliver cholesterol and triglycerides to the liver. This process of endocytosis is mediated by a protein, the LDL receptor, expressed on the surface of hepatocytes and requires Apo E and Apo B as cofactors [72]. The concentration of chylomicrons can only be lowered by reducing dietary fat consumption or by drugs that inhibit the intestinal absorption of cholesterol. However, drugs specifically targeting the step of chylomicron secretion have not yet been developed [14]. Although rare, individuals with a genetic deficiency that results in low lipoprotein lipase activity may present with abnormally high concentrations of circulating triglycerides (1,000–5,000 mg/dL) [31]. Very-Low-Density Lipoproteins VLDLs are smaller than chylomicrons (80 nm in diameter) and have a very high triglyceride and cholesterol content—five times more triglycerides by weight than cholesterol. As noted, VLDL makes up 15% to 20% of the total blood cholesterol and most of the circulating triglycerides [73]. In the muscle and adipose tissue capillaries, lipoprotein lipase interacts with circulating VLDL, from which it removes triglycerides in a process that requires Apo C-II as a cofactor, as described for chylomicrons. VLDL also expresses Apo E and Apo B-100. Apo B-100 plays a fundamental role in the regulation of circulating cholesterol. From a metabolic viewpoint, both chylomicrons and VLDL deliver triglycerides to muscle and adipose tissue [30]. Dietary triglycerides absorbed via the intestinal lymphatics are transported in chylomicrons, whereas endogenous triglycerides and cholesterol esters synthesized in the liver are transported in VLDL. From a clinical perspective, it is particularly relevant to point out that the hepatic synthesis of VLDL is increased when the concentration of free fatty acids in the liver is increased (e.g., in high-fat diets) as well as when adipose tissue releases high amounts of free fatty acids in the circulation (e.g., as a result of obesity or diabetes) [46]. Genetic deficiencies that result in either total (abetalipoproteinemia) or partial liver failure to produce Apo B-100 (familial hypobetalipoproteinemia) inhibit the release of VLDL by hepatocytes and result in fatty liver [74].
In adults who are 20 years of age or older and not on lipid-lowering therapy, the ACC/AHA assert measurement of either a fasting or a nonfasting plasma lipid profile is effective in estimating ASCVD risk and documenting baseline LDL. If an individual
has ingested an extremely high-fat meal in the preceding eight hours, it may be prudent to assess lipids on another day after counseling the patient to avoid such meals. (http://www.onlinejacc.org/content/73/24/ e285?_ga=2.118995977.141815126.1563751668- 1264536891.1558548868. Last accessed July 24, 2025.) Level of Evidence : Expert Opinion/Consensus Statement Chylomicrons Chylomicrons are large lipoproteins 75–1,200 nm in diameter that are very rich in lipids (98% content), mainly triglycerides (83%) and cholesterol (8%), and have the lowest protein content (2%) of all lipoproteins. Chylomicrons are only synthesized in the intestine and are produced in large amounts during fat ingestion [53]. In normolipidemic individuals they are present in the plasma for 3 to 6 hours after fat ingestion and are absent after 10 to 12 hours fasting [14].
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MDNE1526
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