Dr Jess says: We may have been told that having high cholesterol is bad, but not really understand why or if it is bad, and what cholesterol actually is. As part of our series on cholesterol, this article explains exactly what cholesterol is and its different component parts, so if you have been diagnosed with high cholesterol, you can better understand where the problem is, so that you can then discuss it with your medical provider and address it in the right way.
what is cholesterol?
Cholesterol – as is evident from its name, is a sterol, a fatty type of substance that is present in the blood and in most cell membranes. Our bodies need cholesterol to function correctly as it helps to regulate our hormones, bile salts and keeps our cell membranes lubricated and fluid. As a fat, cholesterol won’t dissolve in water and so it is attached to a protein carrier and called a lipoprotein.
There are two main cholesterol-carrying lipoproteins in our body, LDL (low-density lipoprotein) and HDL(high-density lipoprotein). HDL and LDL are measured as part of a standard blood test to measure cholesterol.
what is LDL (low-density lipoprotein)?
LDL has historically been called ‘bad cholesterol,’ although it is in itself not always harmful. However, certain types of LDL can be used to build plaque in the blood vessel walls that can lead to heart disease or a stroke. LDL only forms into plaques with other factors present, including inflammation and oxidative stress.1
If your cholesterol test suggests that your LDL is raised, it doesn’t always mean that you are at greater risk of heart disease. As part of a cholesterol test, the concentration of LDL is measured, when in fact a more useful measure would be the number of LDL particles (called an LDL-P).2 This is shown to be much better at assessing your individual risk of a heart attack or stroke. You may have a raised LDL and a normal LDL-P (making you low risk) or more worryingly have a normal LDL cholesterol and a high LDL-P. If you have a raised LDL, checking your LDL-P levels is very important, to assess your actual cholesterol risk.
LDL is made up of lots of different sizes of particles. Think of it as a big bundle of basketballs, footballs, tennis and golf balls. Most of the larger particles (the footballs) aren’t actually problematic and are likely beneficial.3,4 Only the small particles (the tennis balls and golf balls) are likely to be dangerous. These smaller particles are not routinely measured in a cholesterol test.3,4 These smaller, denser particles are small enough to fit through the gaps in the lining of the blood vessel (endothelium), where they can become oxidised and contribute to the formation of plaques and atherosclerosis, increasing the risk of heart attacks and strokes.
A standard LDL test measures the overall amount of LDL, not the proportions of the different size particles.
If you have high LDL cholesterol, you can measure whether you are pattern A, which means you have a high LDL, mostly made up of the larger, non-damaging particles (footballs), or pattern B, which means your LDL is mainly made up of smaller particles (tennis balls) that are associated with a higher risk of cardiovascular disease. Pattern B can be more likely with certain genetic tendencies, but is also increased by high sugar and high carbohydrate diets.5
An LDL subfractions test is the only way to truly understand the type and size of particles of LDL cholesterol. If you have raised LDL cholesterol, it is definitely worth considering taking the test.6
LDL can be modified to become more dangerous:
The other issue with LDL is that it can be altered by oxidation (from toxins and damage) and glycation (changed by raised blood sugar). These make it much more harmful. Oxidised LDL can be measured in a blood test and if it is raised, it is a strong risk factor for heart disease7 and can trigger more inflammation in the body.8
Powerful antioxidants like green tea extracts,9,10 diet and lifestyle modification11 are all great steps to take if your oxidised LDL is raised. If your blood sugar is raised because you have pre-diabetes or diabetes, this makes glycation (the use of sugar to change your LDL) more likely and significantly increases your risk of heart disease.12
do you have raised Lp(a)?
The final type of LDL that can be dangerous is a particle called Lipoprotein a (Lp(a). Lp(a) seems to have a strong genetic component, and if your Lp(a) is raised, then it is a risk factor on its own, even if all your other cholesterol levels are normal.
Raised levels of Lp(a) increase your risk of heart attacks, blood vessel disease, DVT and strokes by up to three times.13 This is because Lp(a) makes you more likely to develop blood clots on any atherosclerotic plaques, causing a sudden heart attack or stroke. Lp(a) is very difficult to lower. Statins may in fact increase, not decrease Lp(a).14 This is something that Dr Jess has, and she has helped not only herself but several patients using resveratrol, niacin, coenzyme Q10, curcumin (turmeric) supplements and high doses of krill oil.15
what is HDL (high-density lipoprotein)?
HDL (high-density lipoprotein) is often what is known as ‘good cholesterol’. It has a higher proportion and different types of protein to LDL. While LDL transports cholesterol from the liver to the rest of our body and to our tissues, HDL transports cholesterol from the blood back to the liver. It’s a bit like a rubbish truck clearing out the rubbish (excess cholesterol) and taking it away. The more rubbish trucks you have, the more you are able to clear. If you don’t have enough HDL, the rubbish builds up.
HDL is considered ‘good’ because higher levels (1-1.5mmol/L) have been shown to have a protective effect against cardiovascular disease and also has antioxidant and anti-inflammatory properties, as well as reducing the risk of blood clots16.
the number of HDL particles and their size matters
While a standard cholesterol test measures the proportion of HDL, a more accurate measure is the number of HDL particles; the HDL-P.24 HDL comes in different sizes of particles: larger HDL particles are more protective, while smaller particles can increase the risk of heart disease.17
Having low levels of HDL is high risk and yet high levels of HDL are not without risks either. High levels of HDL (2.3mmol/L or more) can sometimes show that you have damaged HDL which is not working properly.18 This altered HDL has been shown to increase the risk severity of atrial fibrillation (a heart arrhythmia)19 and increase your risk of heart attack, stroke and death.20
So how do you know if your HDL is healthy and protective? You can test for myeloperoxidase. Myeloperoxidase is an inflammatory enzyme that can be measured by a blood test. Myeloperoxidase is produced by white blood cells, and levels rise when there is inflammation in your blood vessels. It can cause changes in the HDL (oxidising it), to make it less healthy. If your HDL is raised and your myeloperoxidase is also raised it would suggest that your HDL is not protective.21
High myeloperoxidase levels can also oxidise LDL and can damage atherosclerotic plaques, making them more likely to rupture and cause a heart attack or stroke.22 If myeloperoxidase is raised, your risk of a heart attack is twice that of a normal reading.23
Triglycerides are another type of fat-like cholesterol. High levels are strongly and independently linked to an increased risk of heart disease, stroke and also high blood sugar and fatty liver disease. They are shown to contribute to the creation of plaques in your arteries (atherosclerosis).24 Triglycerides are increased by a diet high in sugar and decreased by a diet low in carbohydrates (like our Refresh programme).25,26 If you have a high triglyceride level on your blood test, even if everything else is normal, it is important to address your diet and lifestyle.
VLDL – the lesser-known dangerous cholesterol
The third type of lipoprotein is VLDL (Very Low-density Lipoprotein). VLDL contains more triglycerides than cholesterol and can significantly increase the risk of heart attack and stroke.
VLDL is created by the liver to carry triglycerides, so higher VLDL levels will also reflect higher levels of triglycerides. Whilst the body uses some triglycerides for energy, if we eat too many carbohydrates then it is inevitable that we will have higher levels of both triglycerides and VLDL. VLDL levels can be checked on a blood test and improve with weight loss and positive diet changes.27
Some laboratories are moving away from testing LDL levels as part of a standard cholesterol panel and instead use non-HDL levels, which is basically the total cholesterol level minus the HDL cholesterol.
What is left includes LDL and other remnants and lipoproteins and serves as a general marker of ‘bad cholesterol’. Non-HDL testing seems to be a more accurate measure of ‘bad’ cholesterol than tests that check for LDL. However, the gold standard for testing remains the LDL-P test. 28
other articles in this series:
- Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL. Oxidative Stress in Atherosclerosis. Curr Atheroscler Rep. 2017 Sep 18;19(11):42. doi: 10.1007/s11883-017-0678-6. PMID: 28921056.
- Folse HJ, Goswami D, Rengarajan B, Budoff M, Kahn R. Clinical- and cost-effectiveness of LDL particle-guided statin therapy: a simulation study. Atherosclerosis. 2014 Sep;236(1):154-61. doi: 10.1016/j.atherosclerosis.2014.06.027. Epub 2014 Jul 7. PMID: 25050538.
- Halle M, Berg A, Baumstark MW, Keul J. LDL-Subfraktionen und koronare Herzerkrankung–Eine Ubersicht [LDL subfractions and coronary heart disease–an overview]. Z Kardiol. 1998 May;87(5):317-30. German. doi: 10.1007/s003920050187. PMID: 9658546.
- Žitňanová I, Šiarnik P, Füllöp M, Oravec S, Penesová A, Ďuračková Z, Vaská E, Turčáni P, Kollár B. Gender differences in LDL- and HDL-cholesterol subfractions in patients after the acute ischemic stroke and their association with oxidative stress markers. J Clin Biochem Nutr. 2018 Sep;63(2):144-148. doi: 10.3164/jcbn.17-105. Epub 2018 Mar 30. PMID: 30279626; PMCID: PMC6160728.
- Noakes TD, Windt J. Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review. Br J Sports Med. 2017 Jan;51(2):133-139. doi: 10.1136/bjsports-2016-096491. PMID: 28053201.
- Shiffman D, Louie JZ, Caulfield MP, Nilsson PM, Devlin JJ, Melander O. LDL subfractions are associated with incident cardiovascular disease in the Malmö Prevention Project Study. Atherosclerosis. 2017 Aug;263:287-292. doi: 10.1016/j.atherosclerosis.2017.07.003. Epub 2017 Jul 5. PMID: 28728064.
- Kuklinska AM, Mroczko B, Musial WJ, Usowicz-Szarynska M, Sawicki R, Borowska H, Knapp M, Szmitkowski M. Diagnostic biomarkers of essential arterial hypertension: the value of prostacyclin, nitric oxide, oxidized-LDL, and peroxide measurements. Int Heart J. 2009 May;50(3):341-51. doi: 10.1536/ihj.50.341. PMID: 19506338.
- Rhoads JP, Major AS. How Oxidized Low-Density Lipoprotein Activates Inflammatory Responses. Crit Rev Immunol. 2018;38(4):333-342. doi: 10.1615/CritRevImmunol.2018026483. PMID: 30806246; PMCID: PMC6527110.
- Tinahones FJ, Rubio MA, Garrido-Sánchez L, Ruiz C, Gordillo E, Cabrerizo L, Cardona F. Green tea reduces LDL oxidability and improves vascular function. J Am Coll Nutr. 2008 Apr;27(2):209-13. doi: 10.1080/07315724.2008.10719692. PMID: 18689551.
- Suzuki-Sugihara N, Kishimoto Y, Saita E, Taguchi C, Kobayashi M, Ichitani M, Ukawa Y, Sagesaka YM, Suzuki E, Kondo K. Green tea catechins prevent low-density lipoprotein oxidation via their accumulation in low-density lipoprotein particles in humans. Nutr Res. 2016 Jan;36(1):16-23. doi: 10.1016/j.nutres.2015.10.012. Epub 2015 Nov 3. PMID: 26773777.
- Amarowicz R, Pegg RB. The Potential Protective Effects of Phenolic Compounds against Low-density Lipoprotein Oxidation. Curr Pharm Des. 2017;23(19):2754-2766. doi: 10.2174/1381612823666170329142936. PMID: 28356039.
- Soran H, Durrington PN. Susceptibility of LDL and its subfractions to glycation. Curr Opin Lipidol. 2011 Aug;22(4):254-61. doi: 10.1097/MOL.0b013e328348a43f. PMID: 21734572.
- Berman AN, Blankstein R. Current and future role of lipoprotein(a) in preventive cardiology. Curr Opin Cardiol. 2019 Sep;34(5):514-518. doi: 10.1097/HCO.0000000000000661. PMID: 31261178.
- Tsimikas S. A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. J Am Coll Cardiol. 2017 Feb 14;69(6):692-711. doi: 10.1016/j.jacc.2016.11.042. PMID: 28183512.
- Momtazi-Borojeni AA, Katsiki N, Pirro M, Banach M, Rasadi KA, Sahebkar A. Dietary natural products as emerging lipoprotein(a)-lowering agents. J Cell Physiol. 2019 Aug;234(8):12581-12594. doi: 10.1002/jcp.28134. Epub 2019 Jan 13. PMID: 30637725.
- Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res. 2004 Oct 15;95(8):764-72. doi: 10.1161/01.RES.0000146094.59640.13. PMID: 15486323.
- Kontush A. HDL particle number and size as predictors of cardiovascular disease. Front Pharmacol. 2015 Oct 5;6:218. doi: 10.3389/fphar.2015.00218. PMID: 26500551; PMCID: PMC4593254.
- Riggs KA, Rohatgi A. HDL and Reverse Cholesterol Transport Biomarkers. Methodist Debakey Cardiovasc J. 2019 Jan-Mar;15(1):39-46. doi: 10.14797/mdcj-15-1-39. PMID: 31049148; PMCID: PMC6489608.
- Trieb M, Kornej J, Knuplez E, Hindricks G, Thiele H, Sommer P, Scharnagl H, Dagres N, Dinov B, Bollmann A, Husser D, Marsche G, Buettner P. Atrial fibrillation is associated with alterations in HDL function, metabolism, and particle number. Basic Res Cardiol. 2019 May 8;114(4):27. doi: 10.1007/s00395-019-0735-0. PMID: 31069509.
- März W, Kleber ME, Scharnagl H, Speer T, Zewinger S, Ritsch A, Parhofer KG, von Eckardstein A, Landmesser U, Laufs U. HDL cholesterol: reappraisal of its clinical relevance. Clin Res Cardiol. 2017 Sep;106(9):663-675. doi: 10.1007/s00392-017-1106-1. Epub 2017 Mar 24. PMID: 28342064; PMCID: PMC5565659.
- Tietge UJF. The impact of myeloperoxidase on HDL function in myocardial infarction. Curr Opin Endocrinol Diabetes Obes. 2018 Apr;25(2):137-142. doi: 10.1097/MED.0000000000000394. PMID: 29356689.
- Ramachandra CJA, Ja KPMM, Chua J, Cong S, Shim W, Hausenloy DJ. Myeloperoxidase As a Multifaceted Target for Cardiovascular Protection. Antioxid Redox Signal. 2020 May 20;32(15):1135-1149. doi: 10.1089/ars.2019.7971. Epub 2020 Mar 6. PMID: 31847538.
- Heslop CL, Frohlich JJ, Hill JS. Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography. J Am Coll Cardiol. 2010 Mar 16;55(11):1102-9. doi: 10.1016/j.jacc.2009.11.050. PMID: 20223364.
- Abdel-Maksoud MF, Hokanson JE. The complex role of triglycerides in cardiovascular disease. Semin Vasc Med. 2002 Aug;2(3):325-33. doi: 10.1055/s-2002-35403. PMID: 16222622.
- Fechner E, Smeets ETHC, Schrauwen P, Mensink RP. The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans-A Systematic Review and Meta-Analysis. Nutrients. 2020 Apr 2;12(4):991. doi: 10.3390/nu12040991. PMID: 32252374; PMCID: PMC7230871.
- Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, Szapary PO, Rader DJ, Edman JS, Klein S. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003 May 22;348(21):2082-90. doi: 10.1056/NEJMoa022207. PMID: 12761365.
- Repas T. Obesity and dyslipidemia. S D Med. 2011 Jul;64(7):241-3, 245, 247 passim. PMID: 21848021.
- Carr SS, Hooper AJ, Sullivan DR, Burnett JR. Non-HDL-cholesterol and apolipoprotein B compared with LDL-cholesterol in atherosclerotic cardiovascular disease risk assessment. Pathology. 2019 Feb;51(2):148-154. doi: 10.1016/j.pathol.2018.11.006. Epub 2018 Dec 27. PMID: 30595507.