low-density lipoprotein

 

  • [7] Since LDL particles contain a variable and changing number of fatty acid molecules, there is a distribution of LDL particle mass and size.

  • [23] Atherogenicity of oxidized LDL has been explained by lack of recognition of oxidation-modified LDL structures by the LDL receptors, preventing the normal metabolism of
    LDL particles and leading eventually to development of atherosclerotic plaques.

  • [9][10] Transport into the cell[edit] When a cell requires additional cholesterol (beyond its current internal HMGCoA production pathway), it synthesizes the necessary LDL
    receptors as well as PCSK9, a proprotein convertase that marks the LDL receptor for degradation.

  • [13] LDL size patterns[edit] LDL can be grouped based on its size: large low density LDL particles are described as pattern A, and small high density LDL particles are pattern
    B.

  • [2][3] Lipoproteins are complex particles composed of multiple proteins, typically 80–100 proteins per particle (organized by a single apolipoprotein B for LDL and the larger
    particles).

  • Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water.

  • In the presence of low pH, such as that found in the endosome, LDL receptors undergo a conformation change, releasing LDL.

  • fewer fat molecules with same protein transport shell), containing a higher proportion of cholesterol esters.

  • Besides the oxidative reactions taking place in vascular wall, oxidized lipids in LDL can also be derived from oxidized dietary lipids.

  • [4] The lipids carried include all fat molecules with cholesterol, phospholipids, and triglycerides dominant; amounts of each vary considerably.

  • [24] Acting as a transporter of these injurious molecules is another mechanism by which LDL can increase the risk of atherosclerosis.

  • [5] The common clinical interpretation of blood lipid levels is that high LDL is associated with increased risk of cardiovascular diseases.

  • A single LDL particle is about 220–275 angstroms in diameter, typically transporting 3,000 to 6,000 fat molecules per particle, and varying in size according to the number
    and mix of fat molecules contained within.

  • 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.

  • Specifically, LDL particle number (concentration), and to a lesser extent size, have shown slightly stronger correlations with atherosclerotic progression and cardiovascular
    events than obtained using chemical measures of the amount of cholesterol carried by the LDL particles.

  • [26] Estimation of LDL particles via cholesterol content[edit] Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they
    have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available.

  • Correspondingly, it is possible that LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low.

  • [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.

  • Direct LDL particle measurement by NMR was mentioned by the ADA and ACC, in a 28 March 2008 joint consensus statement,[49] 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[50]].

  • Multiple other measures, including particle sizes, small LDL particle concentrations, large total and HDL particle concentrations, along with estimations of insulin resistance
    pattern and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are also routinely provided.

  • Debate continues that it is “…unclear whether LDL particle size measurements add value to measurement of LDL-particle concentration”, though outcomes have always tracked
    LDL particle, not LDL-C, concentrations.

  • [34] However, the concentration of LDL particles, and to a lesser extent their size, has a stronger and consistent correlation with individual clinical outcome than the amount
    of cholesterol within LDL particles, even if the LDL-C estimation is approximately correct.

  • 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.

  • 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.

  • [48] Since the later 1990s, because of the development of NMR measurements, it has been possible to clinically measure lipoprotein particles at lower cost [under $80 US (including
    shipping) & is decreasing; versus the previous costs of >$400 to >$5,000] and higher accuracy.

  • [35] It is possible that the LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high.

  • [citation needed] A study was conducted measuring the effects of guideline changes on LDL cholesterol reporting and control for diabetes visits in the US from 1995 to 2004.

  • Testing 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.

  • In clinical context, mathematically calculated estimates of LDL-C are commonly used as an estimate of how much low density lipoproteins are driving progression of atherosclerosis.

  • Direct LDL measurements are also available and better reveal individual issues but are less often promoted or done due to slightly higher costs and being available from only
    a couple of laboratories in the United States.

  • [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, unspecified how much lower.

  • It has been estimated from the results of multiple human pharmacologic LDL lowering trials[42] that LDL should be lowered to below 30 to reduce cardiovascular event rates
    to near zero.

  • Specifically, LDL particle number (concentration), and to a lesser extent size, have shown slightly stronger correlations with atherosclerotic progression and cardiovascular
    events than obtained using chemical measures of the amount of cholesterol carried by the LDL particles.

  • [26] Estimation of LDL particles via cholesterol content[edit] Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they
    have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available.

  • Correspondingly, it is possible that LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low.

  • [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.

  • Direct LDL particle measurement by NMR was mentioned by the ADA and ACC, in a 28 March 2008 joint consensus statement,[49] 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[50]].

  • Multiple other measures, including particle sizes, small LDL particle concentrations, large total and HDL particle concentrations, along with estimations of insulin resistance
    pattern and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are also routinely provided.

  • Debate continues that it is “…unclear whether LDL particle size measurements add value to measurement of LDL-particle concentration”, though outcomes have always tracked
    LDL particle, not LDL-C, concentrations.

  • [34] However, the concentration of LDL particles, and to a lesser extent their size, has a stronger and consistent correlation with individual clinical outcome than the amount
    of cholesterol within LDL particles, even if the LDL-C estimation is approximately correct.

  • 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.

  • 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.

  • [48] Since the later 1990s, because of the development of NMR measurements, it has been possible to clinically measure lipoprotein particles at lower cost [under $80 US (including
    shipping) & is decreasing; versus the previous costs of >$400 to >$5,000] and higher accuracy.

  • [35] It is possible that the LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high.

  • [citation needed] A study was conducted measuring the effects of guideline changes on LDL cholesterol reporting and control for diabetes visits in the US from 1995 to 2004.

  • Testing 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.

  • In clinical context, mathematically calculated estimates of LDL-C are commonly used as an estimate of how much low density lipoproteins are driving progression of atherosclerosis.

  • Direct LDL measurements are also available and better reveal individual issues but are less often promoted or done due to slightly higher costs and being available from only
    a couple of laboratories in the United States.

  • [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, unspecified how much lower.

  • It has been estimated from the results of multiple human pharmacologic LDL lowering trials[42] that LDL should be lowered to below 30 to reduce cardiovascular event rates
    to near zero.

 

Works Cited

[‘1. “LDL and HDL: Bad and Good Cholesterol”. Centers for Disease Control and Prevention. CDC. Retrieved 11 September 2017.
2. ^ Dashti M, Kulik W, Hoek F, Veerman EC, Peppelenbosch MP, Rezaee F (2011). “A phospholipidomic analysis of all defined
human plasma lipoproteins”. Sci. Rep. 1 (139): 139. Bibcode:2011NatSR…1E.139D. doi:10.1038/srep00139. PMC 3216620. PMID 22355656.
3. ^ Dashty M, Motazacker MM, Levels J, de Vries M, Mahmoudi M, Peppelenbosch MP, Rezaee F (2014). “Proteome of human
plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism”. Thromb. Haemost. 111 (3): 518–530. doi:10.1160/TH13-02-0178. PMID 24500811. S2CID 20566238.
4. ^ Jump up to:a b Segrest JP, Jones
MK, De Loof H, Dashti N (September 2001). “Structure of apolipoprotein B-100 in low density lipoproteins”. Journal of Lipid Research. 42 (9): 1346–67. doi:10.1016/S0022-2275(20)30267-4. PMID 11518754.
5. ^ Sira, Elevina E. Pérez (2021-10-05). Foods
for Special Dietary Regimens. Bentham Science Publishers. ISBN 978-981-4998-07-9.
6. ^ Carson, Jo Ann S.; Lichtenstein, Alice H.; Anderson, Cheryl A.M.; Appel, Lawrence J.; Kris-Etherton, Penny M.; Meyer, Katie A.; Petersen, Kristina; Polonsky,
Tamar; Van Horn, Linda (2020-01-21). “Dietary cholesterol and cardiovascular risk: A science advisory from the American Heart Association”. Circulation. 141 (3): e39–e53. doi:10.1161/cir.0000000000000743. ISSN 0009-7322. PMID 31838890.
7. ^ Campos,
Hannia (1992). “LDL Particle Size Distribution”. Arteriosclerosis, Thrombosis, and Vascular Biology. 12 (12): 1410–1419. doi:10.1161/01.ATV.12.12.1410. PMID 1450174.
8. ^ Kumar V, Butcher SJ, Katrina O, Engelhardt P, Heikkonen J, Kaski K, Ala-Korpela
M, Kovanen PT (May 2011). “Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16Å Resolution at Physiological Body Temperature”. PLOS ONE. 6 (5): e18841. Bibcode:2011PLoSO…618841K. doi:10.1371/journal.pone.0018841. PMC 3090388. PMID
21573056.
9. ^ Pirahanchi, Yasaman; Sinawe, Hadeer; Dimri, Manjari (2022), “Biochemistry, LDL Cholesterol”, StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30137845, retrieved 2022-12-26
10. ^ Sun, Hung-Yu; Lin, Chun-Chieh; Lee,
Jin-Ching; Wang, Shainn-Wei; Cheng, Pin-Nan; Wu, I.-Chin; Chang, Ting-Tsung; Lai, Ming-Derg; Shieh, Dar-Bin; Young, Kung-Chia (July 3, 2013). “Very low-density lipoprotein/lipo-viro particles reverse lipoprotein lipase-mediated inhibition of hepatitis
C virus infection via apolipoprotein C-III”. Gut. 62 (8): 1193–1203. doi:10.1136/gutjnl-2011-301798. ISSN 1468-3288. PMID 22689516. S2CID 326884.
11. ^ Zhang, Da-Wei; Garuti, Rita; Tang, Wan-Jin; Cohen, Jonathan C.; Hobbs, Helen H. (2008-09-02).
“Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor”. Proceedings of the National Academy of Sciences of the United States of America. 105 (35): 13045–13050. Bibcode:2008PNAS..10513045Z. doi:10.1073/pnas.0806312105.
ISSN 0027-8424. PMC 2526098. PMID 18753623.
12. ^ Santulli G, Jankauskas SS, Gambardella J (May 2021). “Inclisiran: a new milestone on the PCSK9 road to tackle cardiovascular risk”. Eur Heart J Cardiovasc Pharmacother. 7 (3): e11–e12. doi:10.1093/ehjcvp/pvab014.
PMID 33655296.
13. ^ Peterson MM, Mack JL, Hall PR, et al. (December 2008). “Apolipoprotein B Is an innate barrier against invasive Staphylococcus aureus infection”. Cell Host & Microbe. 4 (6): 555–66. doi:10.1016/j.chom.2008.10.001. PMC 2639768.
PMID 19064256.
14. ^ “When it comes to LDL, size matters”. HLTH Code. 2022-07-18. Retrieved 2022-08-04.
15. ^ Jump up to:a b Ivanova EA, Myasoedova VA, Melnichenko AA, Grechko AV, Orekhov AN (2017). “Small Dense Low-Density Lipoprotein as Biomarker
for Atherosclerotic Diseases”. Oxidative Medicine and Cellular Longevity. 2017 (10): 1273042. doi:10.1155/2017/1273042. PMC 5441126. PMID 28572872.
16. ^ Bhalodkar, Narendra C.; Blum, Steve; Rana, Thakor; Kitchappa, Radha; Bhalodkar, Ami N.; Enas,
Enas A. (1 May 2005). “Comparison of high-density and low-density lipoprotein cholesterol subclasses and sizes in Asian Indian women with Caucasian women from the framingham offspring study”. Clin Cardiol. 28 (5): 247–251. doi:10.1002/clc.4960280510.
PMC 6654695. PMID 15971461.
17. ^ “No association between ‘bad cholesterol’ and elderly deaths: Systematic review of studies of over 68,000 elderly people also raises questions about the benefits of statin drug treatments”. sciencedaily.com.
18. ^
Superko HR, Nejedly M, Garrett B (2002). “Small LDL and its clinical importance as a new CAD risk factor: a female case study”. Progress in Cardiovascular Nursing. 17 (4): 167–73. doi:10.1111/j.0889-7204.2002.01453.x. PMID 12417832.
19. ^ Jump up
to:a b Warnick GR, Knopp RH, Fitzpatrick V, Branson L (January 1990). “Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints”. Clinical Chemistry.
36 (1): 15–9. doi:10.1093/clinchem/36.1.15. PMID 2297909. Archived from the original on 2019-09-12. Retrieved 2009-11-02.
20. ^ Otvos J (June 1999). “Measurement of triglyceride-rich lipoproteins by nuclear magnetic resonance spectroscopy”. Clin
Cardiol. 22 (6 Suppl): II21–7. doi:10.1002/clc.4960221405. PMC 6655988. PMID 10376193.
21. ^ Staprans, I.; Rapp, J. H.; Pan, X. M.; Feingold, K. R. (1996). “Oxidized lipids in the diet are incorporated by the liver into very low density lipoprotein
in rats”. Journal of Lipid Research. 37 (2): 420–30. doi:10.1016/S0022-2275(20)37628-8. PMID 9026539.
22. ^ Jump up to:a b Ahotupa, Markku (2017). “Oxidized lipoprotein lipids and atherosclerosis”. Free Radical Research. 51 (4): 439–447. doi:10.1080/10715762.2017.1319944.
PMID 28412863. S2CID 3397099.
23. ^ Jump up to:a b Stocker, Roland; Keaney, John F. (2004). “Role of Oxidative Modifications in Atherosclerosis”. Physiological Reviews. 84 (4): 1381–1478. doi:10.1152/physrev.00047.2003. PMID 15383655.
24. ^ Birukov,
K. G. (2006). “Oxidized lipids: The two faces of vascular inflammation”. Current Atherosclerosis Reports. 8 (3): 223–31. doi:10.1007/s11883-006-0077-x. PMID 16640959. S2CID 7852910.
25. ^ Shao, Baohai; Heinecke, Jay W. (2009). “HDL, lipid peroxidation,
and atherosclerosis”. Journal of Lipid Research. 50 (4): 599–601. doi:10.1194/jlr.E900001-JLR200. PMC 2656652. PMID 19141435.
26. ^ John D. Brunzell, MD, FACP, Michael Davidson, MD, FACC, Curt D. Furberg, MD, PhD, Ronald B. Goldberg, MD, Barbara
V. Howard, PhD, James H. Stein, MD, FACC, FACP and Joseph L. Witztum, MD Lipoprotein Management in Patients With Cardiometabolic Risk, J Am Coll Cardiol, 2008; 51:1512-1524. [1] Archived 2012-02-27 at the Wayback Machine
27. ^ Friedewald WT, Levy
RI, Fredrickson DS (June 1972). “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge”. Clinical Chemistry. 18 (6): 499–502. doi:10.1093/clinchem/18.6.499. PMID 4337382. Archived
from the original on 2019-09-12. Retrieved 2008-05-05.
28. ^ Sniderman AD, Blank D, Zakarian R, Bergeron J, Frohlich J (October 2003). “Triglycerides and small dense LDL: the twin Achilles heels of the Friedewald formula”. Clinical Biochemistry.
36 (7): 499–504. doi:10.1016/S0009-9120(03)00117-6. PMID 14563441.
29. ^ Anandaraja, S.; Narang, R.; Godeswar, R.; Laksmy, R.; Talwar, K.K. (June 2005). “Low-density lipoprotein cholesterol estimation by a new formula in Indian population”. International
Journal of Cardiology. 102 (1): 117–120. doi:10.1016/j.ijcard.2004.05.009. PMID 15939107.
30. ^ de Cordova, Caio Mauricio Mendes; de Cordova, Mauricio Mendes (January 2013). “A new accurate, simple formula for LDL-cholesterol estimation based on
directly measured blood lipids from a large cohort”. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine. 50 (1): 13–19. doi:10.1258/acb.2012.011259. ISSN 0004-5632. PMID 23108766. S2CID 207193749.
31. ^ Chen, Yunqin; Zhang,
Xiaojin; Pan, Baishen; Jin, Xuejuan; Yao, Haili; Chen, Bin; Zou, Yunzeng; Ge, Junbo; Chen, Haozhu (2010). “A modified formula for calculating low-density lipoprotein cholesterol values”. Lipids in Health and Disease. 9 (1): 52. doi:10.1186/1476-511X-9-52.
ISSN 1476-511X. PMC 2890624. PMID 20487572. S2CID 414939.
32. ^ Martin, Seth S.; Blaha, Michael J.; Elshazly, Mohamed B.; Toth, Peter P.; Kwiterovich, Peter O.; Blumenthal, Roger S.; Jones, Steven R. (2013-11-20). “Comparison of a novel method vs
the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile”. JAMA. 310 (19): 2061–2068. doi:10.1001/jama.2013.280532. ISSN 1538-3598. PMC 4226221. PMID 24240933.
33. ^ Sampson, Maureen; Ling,
Clarence; Sun, Qian; Harb, Roa; Ashmaig, Mohmed; Warnick, Russell; Sethi, Amar; Fleming, James K.; Otvos, James D.; Meeusen, Jeff W.; Delaney, Sarah R.; Jaffe, Allan S.; Shamburek, Robert; Amar, Marcelo; Remaley, Alan T. (2020-05-01). “A New Equation
for Calculation of Low-Density Lipoprotein Cholesterol in Patients With Normolipidemia and/or Hypertriglyceridemia”. JAMA Cardiology. 5 (5): 540–548. doi:10.1001/jamacardio.2020.0013. ISSN 2380-6591. PMC 7240357. PMID 32101259.
34. ^ Jump up to:a
b Ramasamy, Jagadish; Job, Victoria; Mani, Thenmozhi; Jacob, Molly (2021-05-06). “Calculated values of serum LDL-cholesterol (LDL-C) – for better or worse?”. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD. 31 (5): 1486–1493. doi:10.1016/j.numecd.2021.01.016.
ISSN 1590-3729. PMID 33744036. S2CID 232309411.
35. ^ http://www.liposcience.com/userfiles/content/files/weightofevidence.pdf[permanent dead link]
36. ^ “Cholesterol Levels”. American Heart Association. Retrieved 2009-11-14.
37. ^ “What Do My
Cholesterol Levels Mean?” (PDF). American Heart Association. September 2007. Retrieved 2009-11-14.
38. ^ “Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol
in Adults (Adult Treatment Panel III) Executive Summary” (PDF). National Heart, Lung, and Blood Institute (NHLBI). National Institutes of Health. May 2001.
39. ^ Shepherd J, Cobbe SM, Ford I, et al. (November 1995). “Prevention of coronary heart
disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group”. The New England Journal of Medicine. 333 (20): 1301–7. doi:10.1056/NEJM199511163332001. PMID 7566020.
40. ^ William E. Boden; et al. (April
2007). “Optimal Medical Therapy with or without PCI for Stable Coronary Disease”. The New England Journal of Medicine. 356 (15): 1503–1516. doi:10.1056/NEJMoa070829. PMID 17387127.
41. ^ Hayward, Rodney A. (3 October 2006). “Narrative Review: Lack
of Evidence for Recommended Low-Density Lipoprotein Treatment Targets: A Solvable Problem”. Ann Intern Med. 145 (7): 520–30. doi:10.7326/0003-4819-145-7-200610030-00010. PMID 17015870. S2CID 29849069.
42. ^ “The straight dope on cholesterol – Part
VI – The Eating Academy – Peter Attia, M.D.” 30 May 2012. Archived from the original on 6 May 2016. Retrieved 24 April 2016.
43. ^ Cybulska, Barbara; Kłosiewicz-Latoszek, Longina; Penson, Peter E.; Nabavi, Seyed Mohammad; Lavie, Carl J.; Banach,
Maciej; International Lipid Expert Panel (ILEP) (2021). “How much should LDL cholesterol be lowered in secondary prevention? Clinical efficacy and safety in the era of PCSK9 inhibitors”. Progress in Cardiovascular Diseases. 67: 65–74. doi:10.1016/j.pcad.2020.12.008.
ISSN 1873-1740. PMID 33383060. S2CID 229942314.
44. ^ Wolska, Anna; Remaley, Alan T. (2020). “Measuring LDL-cholesterol: what is the best way to do it?”. Current Opinion in Cardiology. 35 (4): 405–411. doi:10.1097/HCO.0000000000000740. ISSN 1531-7080.
PMC 7360339. PMID 32412961.
45. ^ Howard, B. V.; Robbins, D. C.; Sievers, M. L.; Lee, E. T.; Rhoades, D.; Devereux, R. B.; Cowan, L. D.; Gray, R. S.; Welty, T. K.; Go, O. T.; Howard, W. J. (2000-03-01). “LDL cholesterol as a strong predictor of
coronary heart disease in diabetic individuals with insulin resistance and low LDL: The Strong Heart Study”. Arteriosclerosis, Thrombosis, and Vascular Biology. 20 (3): 830–835. doi:10.1161/01.atv.20.3.830. ISSN 1079-5642. PMID 10712410.
46. ^ Wang,
Y Richard; G Caleb Alexander; David O Meltzer (December 2005). “Lack of Effect of Guideline Changes on LDL Cholesterol Reporting and Control for Diabetes Visits in the U.S., 1995–2004”. Diabetes Care. 28 (12): 2942–2944. doi:10.2337/diacare.28.12.2942.
PMID 16306559.
47. ^ Peter P. Toth; Michael Grabner; Rajeshwari S. Punekar; Ralph A. Quimbo; Mark J. Cziraky; Terry A. Jacobson (August 2014). “Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets”.
Atherosclerosis. 235 (2): 585–591. doi:10.1016/j.atherosclerosis.2014.05.914. PMID 24956532.
48. ^ Krauss RM (August 2010). “Lipoprotein subfractions and cardiovascular disease risk”. Current Opinion in Lipidology. 21 (4): 305–11. doi:10.1097/MOL.0b013e32833b7756.
PMID 20531184. S2CID 1775446.
49. ^ Brunzell, John D.; Davidson, Michael; Furberg, Curt D.; Goldberg, Ronald B.; Howard, Barbara V.; Stein, James H.; Witztum, Joseph L. (15 April 2008). “Lipoprotein Management in Patients With Cardiometabolic Risk”.
J Am Coll Cardiol. 51 (15): 1512–1524. doi:10.1016/j.jacc.2008.02.034. PMID 18402913.
50. ^ “Google”. www.google.com.
51. ^ “MESA – Multi-Ethnic Study of Atherosclerosis”. www.mesa-nhlbi.org.
52. ^ “Management of Blood Cholesterol in Adults:
Systematic Evidence Review from the Cholesterol Expert Panel | National Heart, Lung, and Blood Institute (NHLBI)”. Archived from the original on 2014-11-25. Retrieved 2014-11-16.
53. ^ “Archived copy” (PDF). Archived from the original (PDF) on 2016-03-03.
Retrieved 2014-11-16.
54. ^ Jump up to:a b c d e f g h Consumer Reports; Drug Effectiveness Review Project (March 2013), “Evaluating statin drugs to treat High Cholesterol and Heart Disease: Comparing Effectiveness, Safety, and Price” (PDF), Best
Buy Drugs, Consumer Reports, p. 9, retrieved 27 March 2013, which cites
 United States Department of Health and Human Services; National Heart, Lung, and Blood Institute; National Institutes of Health (June 2005). “NHLBI, High Blood Cholesterol:
What You Need to Know”. nhlbi.nih.gov. Archived from the original on 2013-04-01. Retrieved 27 March 2013.
55. ^ Research, Center for Drug Evaluation and. “Drug Safety Information for Healthcare Professionals – Follow-up to the January 25, 2008 Early
Communication about an Ongoing Data Review for Ezetimibe/Simvastatin (marketed as Vytorin), Ezetimibe (marketed as Zetia), and Simvastatin (marketed as Zocor)”. Food and Drug Administration.
56. ^ Meyers CD, Kamanna VS, Kashyap ML (December 2004).
“Niacin therapy in atherosclerosis”. Current Opinion in Lipidology. 15 (6): 659–65. doi:10.1097/00041433-200412000-00006. PMID 15529025.
57. ^ Soudijn W, van Wijngaarden I, Ijzerman AP (May 2007). “Nicotinic acid receptor subtypes and their ligands”.
Medicinal Research Reviews. 27 (3): 417–33. doi:10.1002/med.20102. PMID 17238156. S2CID 20876888.
58. ^ “WHO cooperative trial on primary prevention of ischemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up.
Report of the Committee of Principal Investigators”. Lancet. 2 (8403): 600–4. September 1984. doi:10.1016/s0140-6736(84)90595-6. PMID 6147641. S2CID 2473318.
59. ^ http://www.rxabbott.com/pdf/trilipix_pi.pdf [bare URL PDF]
60. ^ Song, B.L.; DeBose-Boyd,
R.A. (2006). “Insig-Dependent Ubiquitination and Degradation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Stimulated by Delta- and Gamma-Tocotrienols”. J. Biol. Chem. 281 (35): 25054–25601. doi:10.1074/jbc.M605575200. PMID 16831864.
61. ^
European Food Safety Authority, Journal (2010). “Scientific opinion on the substantiation of health claims related to plant sterols and plant stanols and maintenance of normal blood cholesterol concentrations”.
62. ^ Trautwein, Elke; Vermeer, Mario;
Hiemstra, Harry; Ras, Rouyanne (7 September 2018). “LDL-Cholesterol Lowering of Plant Sterols and Stanols—Which Factors Influence Their Efficacy?”. Nutrients. 10 (9). MDPI AG: 1262. doi:10.3390/nu10091262. ISSN 2072-6643. PMC 6163911. PMID 30205492.
63. ^
Cabral, Carlos Eduardo; Klein, Márcia Regina Simas Torres (2017). “Phytosterols in the Treatment of Hypercholesterolemia and Prevention of Cardiovascular Diseases”. Arquivos Brasileiros de Cardiologia. 109 (5). Sociedade Brasileira de Cardiologia:
475–482. doi:10.5935/abc.20170158. ISSN 0066-782X. PMC 5729784. PMID 29267628.
64. ^ Demonty, I.; Ras, R.T.; van der Knaap, H.C.; Duchateau, G.S.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A. (Feb 2009). “Continuous dose-response relationship
of the LDL-cholesterol-lowering effect of phytosterol intake”. The Journal of Nutrition. 139 (2): 271–84. doi:10.3945/jn.108.095125. PMID 19091798.
65. ^ “Scientists Gene-Hacked Monkeys to Fix Their Cholesterol”. Futurism. Retrieved 13 June 2021.
66. ^
Musunuru, Kiran; et al. (May 2021). “In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates”. Nature. 593 (7859): 429–434. Bibcode:2021Natur.593..429M. doi:10.1038/s41586-021-03534-y. ISSN 1476-4687. PMID 34012082. S2CID 234790939.
Retrieved 13 June 2021.
67. ^ Jump up to:a b “Cholesterol Diet: How Nutrition & Foods Impact Levels”. Cleveland Clinic. Retrieved 2024-02-16.
68. ^ “Saturated Fat”. www.heart.org. Retrieved 2024-02-16.
69. ^ Nutrition, Center for Food Safety
and Applied (2023-08-30). “Trans Fat”. FDA.
70. ^ “Trans Fatty Acid – an overview | ScienceDirect Topics”. www.sciencedirect.com. Retrieved 2024-02-16.
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