Low-density lipoprotein
[4] The lipids carried include all fat molecules with cholesterol, phospholipids, and triglycerides dominant; amounts of each vary considerably.
Each LDL has a highly hydrophobic core consisting of polyunsaturated fatty acid known as linoleate and hundreds to thousands (about 1500 commonly cited as an average) of esterified and unesterified cholesterol molecules.
This core also carries varying numbers of triglycerides and other fats and is surrounded by a shell of phospholipids and unesterified cholesterol, as well as the single copy of Apo B-100.
[8] LDL particles are formed when triglycerides are removed from VLDL by the lipoprotein lipase enzyme (LPL) and they become smaller and denser (i.e. fewer fat molecules with same protein transport shell), containing a higher proportion of cholesterol esters.
[17] Some evidence suggests the correlation between Pattern B and coronary heart disease is stronger than the correspondence between the LDL number measured in the standard lipid profile test.
[18][19] With continued research, decreasing cost, greater availability and wider acceptance of other lipoprotein subclass analysis assay methods, including NMR spectroscopy, research studies have continued to show a stronger correlation between human clinically obvious cardiovascular events and quantitatively measured particle concentrations.
[22][25] Blood tests commonly report LDL-C: the amount of cholesterol which is estimated to be contained with LDL particles, on average, using a formula, the Friedewald equation.
The problem with this approach is that LDL-C values are commonly discordant with both direct measurements of LDL particles and actual rates of atherosclerosis progression.
In 2008, the ADA and ACC recognized direct LDL particle measurement by NMR as superior for assessing individual risk of cardiovascular events.
It only estimates them using the Friedewald equation[19][27] by subtracting the amount of cholesterol associated with other particles, such as HDL and VLDL, assuming a prolonged fasting state, etc.
[28] If both total cholesterol and triglyceride levels are elevated then a modified formula, with quantities in mg/dL, may be used This formula provides an approximation with fair accuracy for most people, assuming the blood was drawn after fasting for about 14 hours or longer, but does not reveal the actual LDL particle concentration because the percentage of fat molecules within the LDL particles which are cholesterol varies, as much as 8:1 variation.
As of about 2005, these guidelines were:[36][37][38] Over time, with more clinical research, these recommended levels keep being reduced because LDL reduction, including to abnormally low levels, was the most effective strategy for reducing cardiovascular death rates in one large double blind, randomized clinical trial of men with hypercholesterolemia;[39] far more effective than coronary angioplasty/stenting or bypass surgery.
[40] For instance, for people with known atherosclerosis diseases, the 2004 updated American Heart Association, NIH and NCEP recommendations are for LDL levels to be lowered to less than 70 mg/dL.
The evidence is that the NMR methodology (developed, automated & greatly reduced in costs while improving accuracy as pioneered by Jim Otvos and associates) results in a 22-25% reduction in cardiovascular events within one year,[46] contrary to the longstanding claims by many in the medical industry that the superiority over existing methods was weak, even by statements of some proponents.
[citation needed] Direct LDL particle measurement by NMR was mentioned by the ADA and ACC, in a 28 March 2008 joint consensus statement,[48] as having advantages for predicting individual risk of atherosclerosis disease events, but the statement noted that the test is less widely available, is more expensive [about $13.00 US (2015 without insurance coverage) from some labs which use the Vantera Analyzer[49]].
Using NMR, the total LDL particle concentrations, in nmol/L plasma, are typically subdivided by percentiles referenced to the 5,382 men and women, not on any lipid medications, who are participating in the MESA trial.
[51] The LDL particle concentrations are typically categorized by percentiles, <20%, 20–50%, 50th–80th%, 80th–95% and >95% groups of the people participating and being tracked in the MESA trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute.
(Per 2004 United States Government Minimum Guidelines[52][53]) The mevalonate pathway serves as the basis for the biosynthesis of many molecules, including cholesterol.
[65] Saturated fats are found in meat products (including poultry), full-fat dairy, eggs, and refined tropical oils like coconut and palm.
[67] However, trans fat can still be found in red meat and dairy products as it is produced in small amounts by ruminants such as sheep and cows.
[citation needed] In 2021, scientists demonstrated that CRISPR gene editing can decrease blood levels of LDL cholesterol in Macaca fascicularis monkeys for months by 60% via knockout of PCSK9 in the liver.
