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High-density lipoprotein

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High-density lipoprotein (HDL) is one of the five major groups of lipoproteins, which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream. In healthy individuals, about thirty percent of blood cholesterol is carried by HDL.[1]

Blood tests typically report HDL-C level, i.e. the amount of cholesterol contained in HDL particles. It is often contrasted with low-density or LDL cholesterol or LDL-C. HDL particles are able to remove cholesterol from within artery atheroma[citation needed] and transport it back to the liver for excretion or re-utilization, which is the main reason why the cholesterol carried within HDL particles (HDL-C) is sometimes called "good cholesterol" (despite the fact that it is exactly the same as the cholesterol in LDL particles). Those with higher levels of HDL-C seem to have fewer problems with cardiovascular diseases, while those with low HDL-C cholesterol levels (less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease.[2] While higher HDL levels are correlated with cardiovascular health, no incremental increase in HDL has been proven to improve health. In other words, while high HDL levels might correlate with better cardiovascular health, specifically increasing one's HDL might not increase cardiovascular health.[3] Additionally, those few individuals producing an abnormal, apparently more efficient, HDL ApoA1 protein variant called ApoA-1 Milano, have low measured HDL-C levels yet very low rates of cardiovascular events even with high blood cholesterol values.[citation needed]


Structure and function

HDL is the smallest of the lipoprotein particles. They are the densest because they contain the highest proportion of protein to cholesterol. Their most abundant apolipoproteins are apo A-I and apo A-II.[4] The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles. They are capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-binding cassette transporter A1 (ABCA1). A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually making the newly synthesized HDL spherical. They increase in size as they circulate through the bloodstream and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, for example by the interaction with the ABCG1 transporter and the phospholipid transport protein (PLTP).

HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals, ovary, and testes by direct and indirect pathways. HDL is removed by HDL receptors such as scavenger receptor BI (SR-BI), which mediate the selective uptake of cholesterol from HDL. In humans, probably the most relevant pathway is the indirect one, which is mediated by cholesteryl ester transfer protein (CETP). This protein exchanges triglycerides of VLDL against cholesteryl esters of HDL. As the result, VLDLs are processed to LDL, which are removed from the circulation by the LDL receptor pathway. The triglycerides are not stable in HDL, but degraded by hepatic lipase so that finally small HDL particles are left, which restart the uptake of cholesterol from cells.

The cholesterol delivered to the liver is excreted into the bile and, hence, intestine either directly or indirectly after conversion into bile acids. Delivery of HDL cholesterol to adrenals, ovaries, and testes is important for the synthesis of steroid hormones.


Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid-laden macrophages of atherosclerotic arteries, termed foam cells, to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL toward atherosclerosis.

However, HDL carries many lipid and protein species, several of which have very low concentrations but are biologically very active. For example, HDL and their protein and lipid constituents help to inhibit oxidation, inflammation, activation of the endothelium, coagulation, and platelet aggregation. All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known what are the most important.

In the stress response, serum amyloid A, which is one of the acute-phase proteins and an apolipoprotein, is under the stimulation of cytokines (IL-1, IL-6), and cortisol produced in the adrenal cortex and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in the tissues manifests itself as amyloidosis.

It has been postulated that the concentration of large HDL particles more accurately reflects protective action, as opposed to the concentration of total HDL particles.[5] This ratio of large HDL to total HDL particles varies widely and is measured only by more sophisticated lipoprotein assays using either electrophoresis (the original method developed in the 1970s) or newer NMR spectroscopy methods (See also: NMR and spectroscopy), developed in the 1990s.


Men tend to have noticeably lower HDL levels, with smaller size and lower cholesterol content, than women. Men also have an increased incidence of atherosclerotic heart disease. Alcohol consumption tends to raise HDL levels,[6] and moderate alcohol consumption is associated with lower cardiovascular and all-cause mortality.

Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against cardiovascular diseases such as ischemic stroke and myocardial infarction. Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) increase the risk for atherosclerotic diseases.

Data from the landmark Framingham Heart Study showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high.[7][8]

Even people with very low LDL levels are exposed to increased risk if their HDL levels are not high enough.[9]

Estimating HDL via associated cholesterol

Reference ranges for blood tests, comparing HDL cholesterol (in orange at right) to other blood constituents.

Many laboratories used a two-step method: Chemical precipitation of lipoproteins containing apoprotein B, then calculating HDL associated cholesterol as the cholesterol remaining in the supernate,[10] and there are also direct methods. Both methods have long been promoted on the basis of lowest cost, though neither of these measurements directly, or reliably, reflects HDL particle functionality to remove cholesterol from atherosclerotic plaque and can therefore be misleading, especially on an individual patient-by-patient basis[11] Labs use the routine dextran sulfate-Mg2+ precipitation method with ultracentrifugation/dextran sulfate-Mg2+ precipitation as reference method.[12] HPLC can be used.[13]

Subfractions (HDL-2C, HDL-3C) can be measured[14] and have clinical significance.

Recommended ranges

The American Heart Association, NIH and NCEP provides a set of guidelines for fasting HDL levels and risk for heart disease.[15][16][17]

Level mg/dL Level mmol/L Interpretation
<40 for men, <50 for women <1.03 Low HDL cholesterol, heightened risk for heart disease
40–59 1.03–1.55 Medium HDL level
>60 >1.55 High HDL level, optimal condition considered protective against heart disease

Low LDL with low HDL level is also risk factor for cardiovascular disease.

Measuring HDL concentration and sizes

As technology has reduced costs and clinical trial have continued to demonstrate the importance of HDL, methods for directly measuring HDL concentrations, and size (which indicates function) at lower costs have become increasingly available and regarded as more important for assessing individual risk for progressive arterial disease and improve treatment methods.

Chemical measurements

HDL, as discussed above, forms from two large proteins, predominantly apo A-I and apo A-II, positioned, back to back. Charged amino acids on the outer surface attract water, making the particles both water-soluble (so as to carry fats within the blood) and able to associate with HDL receptors on in the surface of cells, e.g. the macrophages of which plaque is predominantly composed, at least in the early stages. Cholesterol is carried within and between the two particles. If the particles pick up more cholesterol, then the particles enlarge and a third or fourth apo A protein joins the grouping, termed large HDL. Chemical measurements can be used to estimate HDL concentrations present in a blood sample, though such measurements may not indicate how well the HDL particles are functioning to reverse transport cholesterol from tissues. HDL-cholesterol is measured by first removing LDL particles by aggregation or precipitation with divalent ions (such as Mg++) and then coupling the products of a cholesterol oxidase reaction to an indicator reaction. The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but is thought to be less accurate.

Electrophoresis measurements

Since the HDL particles have a net negative charge and vary by size, electrophoresis measurements have been utilized since the 1960s to both indicate the number of HDL particles and additionally sort them by size. Larger HDL particles are carrying more cholesterol.

NMR measurements

The newest methodology for measuring HDL particles, available clinically since the late 1990s [1]

uses Nuclear Magnetic Resonance fingerprinting of the particles to measure both concentration and sizes. This methodology has reduced costs relative to ultracentrifugation.

Optimal Total and Large HDL concentrations

The HDL particle concentrations are typically categorized by event rate percentiles based on the people participating and being tracked in the MESA [2]

trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute.

Total HDL particle Table

MESA Percentile Total HDL particles μmol/L Interpretation
>75% >34.9 Those with highest (Optimal) total HDL particle concentrations & lowest rates of cardiovascular disease events
50–75% 30.5–34.5 Those with moderately high total HDL particle concentrations & moderate rates of cardiovascular disease events
25–50% 26.7–30.5 Those with lower total HDL particle concentrations & Borderline-High rates of cardiovascular disease
0–25% <26.7 Those with lowest total HDL particle concentrations & Highest rates of cardiovascular disease events

Large (protective) HDL particle Table

MESA Percentile Large HDL particles μmol/L Interpretation
>75% >7.3 Those with highest (Optimal) Large HDL particle concentrations & lowest rates of cardiovascular disease events
50–75% 4.8–7.3 Those with moderately high Large HDL particle concentrations & moderate rates of cardiovascular disease events
25–50% 3.1–4.8 Those with lower Large HDL particle concentrations & Borderline-High rates of cardiovascular disease
0–25% <3.1 Those with lowest Large HDL particle concentrations & Highest rates of cardiovascular disease events

low LDL level with The lowest incidence of atherosclerotic events over time occurs within those with both the highest concentrations of total HDL particles, the top quarter (>75%), and the highest concentrations of large HDL particle concentrations. Multiple other measures, including LDL particle concentrations, small LDL particle concentrations, along with VLDL concentrations, 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.


Fasting serum lipids have been associated with short term verbal memory. In a large sample of middle aged adults, low HDL cholesterol was associated with poor memory and decreasing levels over a five year follow-up period were associated with decline in memory.[18]

Increasing HDL levels

Diet and lifestyle

Certain changes in lifestyle may have a positive impact on raising HDL levels:[19]

Most saturated fats increase HDL cholesterol to varying degrees but also raise total and LDL cholesterol.[32] A high-fat, adequate-protein, low-carbohydrate ketogenic diet may have similar response to taking niacin as described below (lowered LDL and increased HDL) through beta-hydroxybutyrate coupling the Niacin receptor 1.[33]


While higher HDL levels are correlated with cardiovascular health, no increase in HDL has been proven to improve health. In other words, while high HDL levels might correlate with better cardiovascular health, specifically increasing one's HDL might not increase cardiovascular health.[3] Pharmacological therapy to increase the level of HDL cholesterol includes use of fibrates and niacin. Fibrates have not been proven to have an effect on overall deaths from all causes, despite their effects on lipids.[34] Similarly, increased HDL levels from niacin have not been shown to be efficacious in reducing cardiovascular disease in a randomized controlled trial.[3]

Niacin (vitamin B3), increases HDL by selectively inhibiting hepatic Diacylglycerol acyltransferase 2, reducing triglyceride synthesis and VLDL secretion through a receptor HM74[35] otherwise known as Niacin receptor 2 and HM74A / GPR109A,[33] Niacin receptor 1.

Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10–30%,[36] making it the most powerful agent to increase HDL-cholesterol.[37][38] A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events.[39] However, niacin products sold as "no-flush", i.e. not having side-effects such as "niacin flush", do not contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as "sustained-release" may contain free nicotinic acid, but "some brands are hepatotoxic"; therefore the recommended form of niacin for raising HDL is the cheapest, immediate-release preparation.[40] Both fibrates and niacin increase artery toxic homocysteine, an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins[citation needed], however multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates. A 2011 niacin study was halted early because patients showed no increase in heart health, but did experience an increase in the risk of stroke.[41]

In contrast, while the use of statins is effective against high levels of LDL cholesterol, it has little or no effect in raising HDL cholesterol.[37]

Lovaza has been shown to increase HDL-C.[42]

Magnesium supplements raise HDL-C.[43]

Apo-A1 Milano, the most effective proven HDL agent, is in commercial production by a Canadian company, Sembiosys, but as of 2010 may still be several years away from clinical availability.[citation needed]

See also


  1. ^ "LDL and HDL Cholesterol: What's Bad and What's Good?"
    . American Heart Association. 2 July 2009. Retrieved 8 October 2009.
  2. ^ Toth, Peter (2005). "The "Good Cholesterol" High-Density Lipoprotein"
    . Circulation 111 (5): e89-e91. Retrieved 2 June 2011.
  3. ^ a b c "NIH stops clinical trial on combination cholesterol treatment"
    . National Institute of Health. National Heart, Lung, and Blood Institute (NHLBI). Retrieved 2 June 2011.
  4. ^ Després, Jean-Pierre. "The Atherogenic Triad of New Metabolic Risk Factors: Importance of Waist and Fasting Triglycerides as Screening Tools"
    . Visceral Adipose Tissue and Cardiometabolic Risk: Does It Really Matter? Part 2. Retrieved 8 October 2009.
    [self-published source?]
  5. ^ Kwiterovich Jr, PO (2000). "The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review". The American journal of cardiology 86 (12A): 5L–10L. doi:10.1016/S0002-9149(00)01461-2
    . PMID 11374859
  6. ^ Ruidavets JB, Ducimetière P, Arveiler D, et al. (January 2002). "Types of alcoholic beverages and blood lipids in a French population"
    . J Epidemiol Community Health 56 (1): 24–8. PMC 1732002
    . PMID 11801616
  7. ^ Rahilly, Catherine (2011). "Relation between high-density lipoprotein cholesterol and survival to age 85 years in men (from the VA normative aging study)". Am J Cardiol 107 (8): 1173–7. doi:10.1016/j.amjcard.2010.12.015
    . PMID 21296318
  8. ^ HB, HB (2002). "Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT)". Arch. Intern. Med. 162 (22): 2597–604. PMID 12456232
  9. ^ Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera et al (2007). "HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events". New England Journal of Medicine 357 (13): 1301–10. doi:10.1056/NEJMoa064278
    . PMID 17898099
  10. ^ Lin, Maun-Jan; Hoke, Carolyn; Ettinger, Bruce (1998). "Evaluation of Homogeneous High-Density Lipoprotein Cholesterol Assay on a BM/Hitachi 747-200 Analyzer"
    . Clinical Chemistry 44 (5): 1050–2. PMID 9590383
  11. ^ "Lipid Measurement Fact Sheet"
    . University of Michigan Health System. Retrieved 8 October 2009.
  12. ^ Bairaktari, E; Elisaf, M; Katsaraki, A; Tsimihodimos, V; Tselepis, AD; Siamopoulos, KC; Tsolas, O (1999). "Homogeneous HDL-cholesterol assay versus ultracentrifugation/dextran sulfate-Mg2+ precipitation and dextran sulfate-Mg2+ precipitation in healthy population and in hemodialysis patients". Clinical Biochemistry 32 (5): 339–46. doi:10.1016/S0009-9120(99)00031-4
    . PMID 10480448
  13. ^ Okazaki, Mitsuyo; Sasamoto, Keiko; Muramatsu, Toshio; Hosaki, Seijin (1997). "Evaluation of precipitation and direct methods for HDL-cholesterol assay by HPLC"
    . Clinical Chemistry 43 (10): 1885–90. PMID 9342008
  14. ^ Hirano, Tsutomu; Nohtomi, Kyoko; Koba, Shinji; Muroi, Ayako; Ito, Yasuki (2008). "A simple and precise method for measuring HDL-cholesterol subfractions by a single precipitation followed by homogenous HDL-cholesterol assay". The Journal of Lipid Research 49 (5): 1130–6. doi:10.1194/jlr.D700027-JLR200
    . PMID 18223297
  15. ^ "Cholesterol Levels"
    . American Heart Association. Retrieved 14 November 2009.
  16. ^ "What Do My Cholesterol Levels Mean?"
    (PDF). American Heart Association. September 2007. Retrieved 14 November 2009.
  17. ^ "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"
    . National Heart, Lung, and Blood Institute (NHLBI). National Institutes of Health. May 2001.
  18. ^ Singh-manoux, A; Gimeno, D; Kivimaki, M; Brunner, E; Marmot, MG (2008). "Low HDL cholesterol is a risk factor for deficit and decline in memory in midlife: the Whitehall II study"
    . Arteriosclerosis, thrombosis, and vascular biology 28 (8): 1556–62. doi:10.1161/ATVBAHA.108.163998
    . PMC 2581752
    . PMID 18591462
  19. ^ Fogoros, Richard N. (15 September 2009). "Raising Your HDL Levels"
    . Retrieved 8 October 2009.
  20. ^ Spate-douglas, T; Keyser, RE (1999). "Exercise intensity: its effect on the high-density lipoprotein profile". Archives of physical medicine and rehabilitation 80 (6): 691–5. doi:10.1016/S0003-9993(99)90174-0
    . PMID 10378497
  21. ^ a b c Hausenloy DJ, Yellon DM (June 2008). "Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels". Heart 94 (6): 706–14. doi:10.1136/hrt.2007.125401
    . PMID 18480348
  22. ^ "Trans fat: Avoid this cholesterol double whammy"
    . Mayo Foundation for Medical Education and Research (MFMER). Retrieved 25 June 2010.
  23. ^ Baer, D.; Judd, J.; Clevidence, B.; Muesing, R.; Campbell, W.; Brown, E.; Taylor, P. (2002). "Moderate alcohol consumption lowers risk factors for cardiovascular disease in postmenopausal women fed a controlled diet". The American journal of clinical nutrition 75 (3): 593–599. PMID 11864868
  24. ^ Van Der Gaag, M.; Van Tol, A.; Vermunt, S.; Scheek, L.; Schaafsma, G.; Hendriks, H. (2001). "Alcohol consumption stimulates early steps in reverse cholesterol transport". Journal of lipid research 42 (12): 2077–2083. PMID 11734581
  25. ^ Hendriks, H.; Veenstra, J.; Van Tol, A.; Groener, J.; Schaafsma, G. (1998). "Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition". Alcohol and alcoholism (Oxford, Oxfordshire) 33 (4): 403–410. PMID 9719399
  26. ^ Clevidence, B.; Reichman, M.; Judd, J.; Muesing, R.; Schatzkin, A.; Schaefer, E.; Li, Z.; Jenner, J. et al (1995). "Effects of alcohol consumption on lipoproteins of premenopausal women. A controlled diet study". Arteriosclerosis, thrombosis, and vascular biology 15 (2): 179–184. PMID 7749823
  27. ^ Cuvelier, I.; Steinmetz, J.; Mikstacki, T.; Siest, G. (1985). "Variations in total phospholipids and high-density lipoprotein phospholipids in plasma from a general population: Reference intervals and influence of xenobiotics". Clinical chemistry 31 (5): 763–766. PMID 3987006
  28. ^ Brenn, T. (1986). "The Tromsø heart study: Alcoholic beverages and coronary risk factors"
    . Journal of epidemiology and community health 40 (3): 249–256. PMC 1052533
    . PMID 3772283
  29. ^ Hermansen K, et al. "Effects of soy and other natural products on LDL:HDL ratio and other lipid parameters: a literature review."
    , "National Institutes of Health", 2003 Jan–Feb. Accessed 2011 May 31.
  30. ^ "The Power of Fish"
    . The Cleveland Clinic Heart and Vascular Institute. Retrieved 8 October 2009.
  31. ^ Mensink, Ronald P.; Zock, Peter L.; Kester, Arnold D. M.; Katan, Martijn B. (2003). "Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials"
    . American Journal of Clinical Nutrition 77 (5): 1146–55. PMID 12716665
  32. ^ Thijssen, M.A. and R.P. Mensink. (2005). Fatty Acids and Atherosclerotic Risk
    . In Arnold von Eckardstein (Ed.) Atherosclerosis: Diet and Drugs. Springer. pp. 171–172. ISBN 978-3-540-22569-0.
  33. ^ a b Soudijn, W; Van Wijngaarden, I; Ijzerman, AP (2007). "Nicotinic acid receptor subtypes and their ligands". Medicinal Research Reviews 27 (3): 417–33. doi:10.1002/med.20102
    . PMID 17238156
  34. ^ Benatar, JR; Stewart, RA (2007). "Is it time to stop treating dyslipidaemia with fibrates?"
    . The New Zealand medical journal 120 (1261): U2706. PMID 17853928
  35. ^ Meyers, CD; Kamanna, VS; Kashyap, ML (2004). "Niacin therapy in atherosclerosis". Current opinion in lipidology 15 (6): 659–65. doi:10.1097/00041433-200412000-00006
    . PMID 15529025
  36. ^ Rader, Daniel J. (2004). "Raising HDL in Clinical Practice"
    . Raising HDL in Clinical Practice: Clinical Strategies to Elevate HDL. Retrieved 8 October 2009.
  37. ^ a b Brewer, H. Bryan (27 December 2005). "Raising HDL-Cholesterol and Reducing Cardiovascular Risk: An Expert Interview With H. Bryan Brewer, Jr, MD"
    . Retrieved 8 October 2009.
  38. ^ Chapman, M. John; Assmann, Gerd; Fruchart, Jean-Charles; Shepherd, James; Sirtori, Cesare; European Consensus Panel on HDL-C (2004). "Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid – a position paper developed by the European Consensus Panel on HDL-C". Current medical research and opinion 20 (8): 1253–68. doi:10.1185/030079904125004402
    . PMID 15324528
  39. ^ Drexel, H. (2006). "Reducing risk by raising HDL-cholesterol: the evidence". European Heart Journal Supplements 8: F23. doi:10.1093/eurheartj/sul037
  40. ^ Meyers, C. Daniel; Carr, Molly C.; Park, Sang; Brunzell, John D. (2003). "Varying Cost and Free Nicotinic Acid Content in Over-the-Counter Niacin Preparations for Dyslipidemia"
    . Annals of Internal Medicine 139 (12): 996–1002. PMID 14678919
  41. ^
  42. ^
  43. ^ Rosanoff A, Seelig MS (October 2004). "Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals"
    . J Am Coll Nutr 23 (5): 501S–505S. PMID 15466951
    . "HMG CoA Reductase is an important enzyme in lipid and cholesterol metabolism, but it is not the only one. The statins act by inhibiting, temporarily, the enzyme, in a dose response relationship whereas the magnesium ion (Mg2+) is an important part of a complex control and regulation of this important pathway. Both lower LDL-C, some statins can raise HDL-C and lower triglycerides, but Mg supplements do both quite reliably."

External links

HAD : TRIGLYCERIDE = 1:<2 is optimal
HDL has two kinds of particles: Small and large and floppy
Believe it or not I have somewhat elevated blood cholesterol numbers and I just received the latest data from my doctor. But being the typical numbers geek, I want to analyze the numbers to death just for the sheer joy of it. First, off there does not seem to be a good working "find the missing value" calculator for cholesterol numbers on the internet when the math is so incredibly easy.

Enter any three of the following numbers and the calculator will find the fourth missing value, and then it will tell you the ratios and how good they are. You can read the article from the American Heart Association on desired levels here.. The articles on the Total Cholesterol/HDL and HDL/LDL ratios from eMedTV can be found here and here, and the article on triglycerides over HDL ratio is here.


Total Cholesterol mg/dL
HDL (High density lipoprotein) mg/dL
LDL (Low density lipoprotein) mg/dL
Triglycerides mg/dL


When comparing "good cholesterol" (HDL) to "bad cholesterol" (LDL), there is a ratio that may be used. When using it, the goal is to keep the ratio of HDL/LDL above 0.3, with the ideal being above 0.4. The medical community is divided on the effectiveness of using the ratio to predict the chances of developing heart disease. At this time, it is generally believed that the absolute cholesterol numbers are more useful when planning treatment than using the ratio.


  • Accurate - The accuracy of VAP measurements
    are verified by beta quantification, a standard procedure for lipoprotein analysis based
    on centrifugation.

  • Affordable - The VAP Test is reimbursed by
    most insurance carriers and Medicare/Medicaid.
    You can find out more information
    by contacting Atherotech.

  • Accessible - Obtaining a VAP Test is easy.
    Contact your local clinical lab, or obtain a VAP
    Test directly by contacting Atherotech.

Download Accuracy Data
  • Easy – Because we are directly measuring LDL-C, fasting is not required.

  • Effective – By reporting 22 different components of cholesterol, the VAP Test identifies
    risks you can't see with a standard lipid panel.

More Comprehensive Test
The VAP Test uses an advanced technology that provides a more accurate, individualized picture of your heart disease and diabetes risk so you and your doctor can take steps to prevent a future heart attack. For example, the VAP Expanded Lipid Profile measures not only the basic information provided by the routine cholesterol test, but also identifies hidden cholesterol problems that can increase your risk of developing heart disease or diabetes—even if your routine cholesterol test results are "normal." As a result, the VAP Test was named one of "Ten Ways to Live Longer" by and was selected as one of "Five Tests Worth Paying For" by The Wall Street Journal.

Why the Need for a VAP Test
Heart disease is the leading killer of both men and women in the United States—causing the deaths of more than 500,000 people each year. Unfortunately, getting "normal" results back from a routine cholesterol test doesn't mean one is safe from heart disease. That's because routine cholesterol tests fail to identify half of those at risk—robbing many people of the opportunity to take preventive steps that might save their lives.

The VAP Test provides valuable information that can identify hidden heart disease risks. It breaks down cholesterol beyond HDL (high-density lipoprotein, the "good" cholesterol), LDL (low-density lipoprotein, the "bad" cholesterol), and triglycerides—providing new information that can help your doctor better assess and manage your heart disease risk. VAP Tests also help identify the metabolic syndrome-which leads to diabetes and heart disease, and affects a staggering 55 million Americans.

Clinical Need
The role of cholesterol testing in clinical practice is to stratify a patient's risk for cardiovascular disease and to direct therapy to reduce that risk. Accuracy and comprehensiveness in cholesterol testing are critical, especially in light of lower LDL goals, as well as the need to measure and treat a variety of cholesterol subclasses and components. As a result, the heart disease and diabetes risk factors reported by the the VAP Test technology are the best choice for patients at risk for cardiometabolic disorders.

Apolipoprotein B100 (apoB100)
Several studies have shown that apolipoprotein B (apoB) is a better risk predictor for coronary heart disease (CHD) than several other risk factors, including LDL cholesterol.[1],[2] Since each atherogenic lipoprotein (Lp(a), LDL, IDL, and VLDL) contains one molecule of apoB, apoB concentration therefore represents the total number of atherogenic particles. Atherotech has developed a novel procedure to report apoB utilizing non-HDL-cholesterol along with lipoprotein density distribution using the patented VAP ultracentrifugation method. Atherotech has thoroughly validated this new procedure by comparing the VAP apoB with measured apoB using serum from 1,797 patients. This comparison has yielded an excellent correlation coefficient (r = 0.97) with bias of only 0.8%.
      1. AMORIS Study, Lancet, 2001; 358: 2026-33.
      2. Health Professionals Follow-Up Study, Circulation, 2005; 112: 3375-83.

Direct-Measured LDL
One of the key benefits of the VAP technology is a direct-measured LDL. The routine cholesterol panel, which estimates LDL using the Friedewald formula, provides only a 40% predictive value for coronary heart disease. In contrast, the VAP Test, which directly measures LDL, identifies a far greater number of patients at risk for heart disease.

Because of the concerns regarding the reliability of estimated LDL, the NCEP ATP III guidelines recommend that direct LDL measurement methods be used as they are unaffected by triglycerides and patient fasting. In fact, estimated LDL cholesterol levels become significantly inaccurate in patients with heart disease or the equivalent (LDL goal <70-100 mg/dL). Estimated LDL cholesterol levels often fail to accurately classify risk for those patients with triglycerides >200 mg/dL.

How to get a VAP Test
Obtaining a VAP Test is easy. Your physician can
refer you to a local clinical lab to handle the test,
which requires just a small blood sample. The
VAP Test is reimbursed by most insurance carriers
and Medicare/Medicaid. You can also obtain a VAP
Test directly by contacting Atherotech.

VAP Report
View a sample

NCEP ATP III Secondary Targets of Therapy and Emerging Risk Factors
In addition to the LDL cholesterol level, the VAP technology also reports the NCEP ATP III secondary targets of therapy and emerging risk factors, which play a role in raising a patient's level of risk. Measuring these risk factors is the key to managing atherogenic dyslipidemia, setting more aggressive LDL goals, and providing expanded indications for therapy.

  • Increased remnant lipids (intermediate-density lipoprotein and small very low-density lipoprotein) are candidates for intervention, and can heighten heart disease risk substantially beyond that predicted by LDL alone.
  • The presence of the "lipid triad" (small LDL, low HDL and elevated triglycerides) of the metabolic syndrome is considered, as a whole, a risk factor.
  • LDL Pattern B is an indication of atherogenic dyslipidemia and the metabolic syndrome.
  • Elevated levels of lipoprotein(a) are an independent risk factor for heart disease.

Patients with abnormal screening profiles or positive family history also benefit from identification of secondary and emerging risk factors. These may be used along with clinical judgment to raise a patient's risk classification, lower their target LDL goal, and/or modify their treatment plan.

Atherotech offers a comprehensive education program designed to increase physician understanding and use of advanced lipid testing in clinical practice. Included are presentations, articles, and other educational materials. Contact Atherotech for more information.



The VAP (vertical auto profile) test is a cholesterol, lipid and lipoprotein test. The name "VAP test" was coined by the privately held cardio-diagnostic company Atherotech[1] to identify their direct-measurement method which categorizes not just total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL), but all lipids and subclasses, with an LDL measurement accuracy unaffected by triglycerides.[citation needed]

Atherotech claims their VAP test has a unique ability to identify far more areas of risk to patients than the standard lipid panel, specifically because it reports 15 separate components versus four in the standard cholesterol test. The more comprehensive test was shown[citation needed] to identify more than twice the number of patients with lipid abnormalities than the standard lipid panel (cholesterol and triglyceride test).

Unlike the standard lipid panel, the VAP test directly measures LDL. The test is also the only commercially available test that meets the new American Diabetes Association and American College of Cardiology (ADA-ACC) cholesterol guidelines for people at high risk of heart attack and stroke (including people with Type 2 diabetes). The ADA-ACC consensus statement establishes measurement and treatment guidelines for apoB in addition to LDL and non-HDL in high-risk patients. The VAP test is the first cholesterol profile to comply with updated National Cholesterol Education Program ATP III recommendations for LDL measurement and the only commercially available advanced lipid profile that routinely reports all three lipoprotein parameters considered necessary by the American Diabetes Association and American College of Cardiology expert consensus guidelines.

People with a family history or an existing condition of diabetes, high blood pressure or heart disease—or who are already taking cholesterol lowering medication—are candidates for the comprehensive VAP (vertical auto profile) test. In addition, those who don't score within the desirable ranges of the standard cholesterol test can opt for the more detailed test to assist in improved diagnosis by their physician.

  1. ^


'Great Cholesterol Con': The Most Compelling Health Book Nobody's Ever Heard Of

Anthony Colpo's magnum opus will stand the test of time

Every genius of his day has that one masterpiece from his life's work that has endured throughout the generations as the defining moment in his career when greatness befalls upon him and his name will live forever in infamy.

For Albert Einstein, it was his theory of relativity.

For Leonardo da Vinci it was his painting "Mona Lisa."

For Francis Crick and James Watson, it was discovering DNA.

But even these men of great infamy were not given the immediate critical acclaim and accolades from their peers that such displays of cerebral excellence deserved in their own time. It wasn't until years later in the context of historical significance that each of these discoveries and works of art became known as the brilliant showpieces they are today.

Now we have another candidate that fulfills the litmus test for genius and yet his work is not being heralded by the people of his generation as it deserves to be. I suppose he should feel proud to be placed in the same company as an Einstein, da Vinci, or Crick and Watson because his discoveries about cholesterol are no less spectacular than what they found.

Remember the name: Anthony Colpo. His book is called The Great Cholesterol Con. If ever there was a more compelling health book in my lifetime that has the potential to directly influence the decisions of so many doctors, patients, and researchers on the subject of cholesterol, then I haven't seen it. And yet, how many people have even heard of Colpo and his prodigious independent research?

Not many...yet! But I expect that to change rather quickly as word about this 368-page dissertation about the biggest health scam of the 21st Century spreads from those of us who have had the privilege of experiencing this great work by Colpo.

It literally took me weeks to get through and absorb all of the information contained within the pages of this amazing book, but it was defintely NOT a boring, laborious book of scientific annotations that will go completely over your heard. Colpo writes in a meticulous style that leaves no stone unturned while also captivating your attention with head-on language he dares you to ignore. The time and energy it must have taken him to write his very first and probably best book of his career is clearly evident in page turn after every glorious page turn.

Colpo is a brave fighter who is unafraid to expose the medical and research community for perpetrating an outright fraud on a public who is either too ignorant or uneducated to question their conclusions regarding health. That's why statin drugs have become one of the top moneymakers for drug companies today because of this false illusion that everyone "needs" to artificially lower their cholesterol for the sake of their heart health. LIAR!

The big secret that Colpo exposes is the FACT that the rate of heart disease has not decreased one iota since the introduction of statins, such as Lipitor and Crestor, and yet you never hear anybody ever talking about this. Why?

Furthermore, the suspicious side effects of taking these expensive medications, including intense joint and muscle pain, are swept under the rug as a necessary part of treating cholesterol. What a big fat joke this "great cholesterol con" has become!

As someone who has been fooled into taking these drugs all "for the sake of my health," it angered me that I could be so duped by the very doctors that I trust to provide me with the best medical care possible. Thankfully for me I was able to come off of the cholesterol-lowering drugs after losing 180 pounds on the low-carb lifestyle. But not everyone is able to figure this out on their own, which is why Colpo's book has been so sorely needed for far too long.

Colpo really does deserve a medal for putting himself out there as the direct target of the drug manufacturers, pharmaceutical reps, and doctors who have been making BILLIONS of dollars in profit off of this scheme for far too long. If you aren't outraged about this as much as Colpo is, then you REALLY need to read his book as soon as possible. It will open your eyes to an underground world of corruption and deceit that is jeopardizing the very health of the world's population.

Does this sound like a conspiracy of some sort? I suppose it has those markings. But Colpo is DEAD serious and provides all the references you need to see for yourself how this "great cholesterol con" has been allowed to exist. This book should be a warning to everyone who thinks taking that cholesterol-lowering drug will protect them against a heart attack or heart disease. It's time to stop letting others think for you and to start thinking for yourself by arming yourself with the facts.

In addition to cholesterol, Colpo also gets into such issues as how saturated fat and low-carb diets have been unfairly maligned as health threats while behind-the-scenes they are being proven by new scientific evidence to be a lot healthier and safe for weight and health management than the failed low-fat diets ever will be. My weight loss experience is living proof of that!

An eyeopener for sure, The Great Cholesterol Con will one day become required reading for medical students wanting to find out the truth about cholesterol, diet and heart disease. It is Colpo's genius that we should be celebrating for coming along at this point in time in the history of the world to be the beacon of truth for all the world to see.

Will you remain blinded by the lies you've been told or will you become enlightened by the invaluable information Colpo has provided as his gift to the world? That's a decision YOU and you alone must make which can impact your life more than you even realize regardless of what you choose to do.

Then, if you decide to have your eyes opened, do you keep it to yourself or will you also share it with your friends and family? This is the kind of book that every living man, woman, and child should have to read just once.

If you decide to reject what is contained within the book, then at least you'll be armed with the facts.

But if instead you decide to embrace what you've read and be moved to action, then the legend of Colpo will rise beyond this mundane world of ours to metamorphose into a greater understanding of what healthy living is really all about.

When that happens, the genius of Colpo will FINALLY be recognized and he will take his rightful place in history behind those great names of the past for what he has contributed to the world.

Remember the name: Anthony Colpo.

Labels: , , , ,


Blogger Science4u1959 said...

A Magnum Opus it is indeed. And sorely needed: nobody ever made the effort! The evidence is there: in the literal mountains of scientific evidence. What Colpo has done is simply fantastic - now everybody can learn the truth, thanks to Colpo taking upon himself the gruelling task of reading thousands of hard-to-digest research papers and publications, and compiling it into a extremely valuable, very readable tome.

Anthony Colpo's book has a special place on my bookshelf, and the person of Colpo has a special place in my heart.

If only we had more people like him, this world would be a much better place.

7/20/2006 10:09 PM
Blogger Robert Angel said...

Great book. Highly recommended

3/23/2007 1:37 AM
Blogger Mousetrapper said...

Interesting book, toning down the cholesterol hype. I think every single-minded explanation of things has to be questioned. Cholesterol makes no exception. I am impressed about your weight loss, Jimmy. Did you achieve it with diet only? Or did you exercise in addition?

4/02/2007 5:08 PM
Blogger Jimmy Moore said...

Hey Mousetrapper! When I started at 410, I was following the Atkins diet alone. But after I lost 30 pounds in the first month, I started a rigorous daily cardio exercise routine. In fact, one entire chapter of my book is called "Exercise Is Not A Dirty Word." :D

4/02/2007 5:16 PM

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Clinics. 2008 August; 63(4): 427–432.
PMCID: PMC2664115

High Ratio of Triglycerides to HDL-Cholesterol Predicts Extensive Coronary Disease


An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c) indicates an atherogenic lipid profile and a risk for the development of coronary disease.


To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease.


High-risk patients (n = 374) submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index.


The subjects consisted of 220 males and 154 females, age 57.2 ± 11.1 years, with total cholesterol of 210± 50.3 mg/dL, triglycerides of 173.8 ± 169.8 mg/dL, HDL-cholesterol (HDL-c) of 40.1 ± 12.8 mg/dL, LDL-cholesterol (LDL-c) of 137.3 ± 46.2 mg/dL, TG/HDL-c of 5.1 ± 5.3, and a Friesinger index of 6.6 ± 4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal) was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31–3.1; p = 0.0018); HDL-c, odds ratio of 2.21 (1.42–3.43; p = 0.0005); and TG/HDL-c, odds ratio of 2.01(1.30–3.09; p = 0.0018). However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82–1.91; p = 0.33)] or LDL-c [1.47 (0.96–2.25; p = 0.0842)]. The chi-square for linear trends for Friesinger > 4 and lipid quartiles was statistically significant for triglycerides (p = 0.0017), HDL-c (p = 0.0001), and TG/HDL-c (p = 0.0018), but not for total cholesterol (p = 0.393) or LDL-c (p = 0.0568). The multivariate analysis by logistic regression OR gave 1.3 ± 0.79 (p = .0001) for TG/HDL-c, 0.779 ± 0.074 (p = .0001) for HDL-c, and 1.234 ± 0.097 (p = 0.03) for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease.


Although some lipid variables were associated with the extent of coronary disease, the ratio of triglycerides to HDL-cholesterol showed the strongest association with extent.

Keywords: Lipids, Triglycerides, HDL, Cholesterol, Coronary disease


Lipid abnormalities have long been suspected to contribute to atherosclerosis; several epidemiological and cohort studies have established a strong association between total cholesterol, LDL-cholesterol (LDL-c), or low HDL-cholesterol (HDL-c) and the incidence of atherosclerosis-related diseases, such as ischemic heart disease, stroke, and peripheral vascular disease.

Recently, lipid particle subfractions have also been implicated in the atherogenic process. Small dense LDL particles are more atherogenic than larger buoyant ones, and different HDL subfractions play different roles in atherogenesis. The larger and less dense HDL2 particles are considered protective, while the small dense HDL3 particles are atherogenic., The former correlate inversely with serum triglycerides and small dense LDL. The ratio of triglycerides to HDL-cholesterol ratio (TG/HDL-c) correlates inversely with the plasma level of small, dense LDL particles. A TG/HDL-c ratio of 3.8 divides the distribution of LDL phenotypes, with 79% of phenotype B greater than this value, and 81% of phenotype A lower than this value. We recently analyzed the relationship between plasma lipids and development of coronary artery disease (CAD) as manifested by angina, positive ischemic tests, or significant obstructive lesions in the coronary angiogram. We found that an TG/HDL-c ratio >4 is the most powerful independent predictor of CAD development. Thus, this ratio shows promise as an attractive surrogate index of the atherogenicity of the plasma lipid profile. However, little data exist on the association between TG/HDL-c ratio and the extent or severity of lesions in coronary disease.


To evaluate the correlation between lipid variables, especially the TG/HDL-c ratio, and the extent of coronary disease in patients investigated for suspected CAD.

Study design

Eligible patients were outpatients who underwent diagnostic coronary angiography for suspected coronary disease.

The presence of risk factors were defined as follows: hypercholesterolemia (total cholesterol >200 mg/dL), hypertriglyceridemia (>150 mg/dL), high LDL-cholesterolemia (LDL-c) (>130 mg/dL), low HDL-cholesterolemia (HDL-c) (<40 mg/dL for male and <50 mg/dL for female), elevated TG/HDL-c ratio (>4), diabetes mellitus (fasting glucose ≥ 126 mg/dL, casual or GTT over 200 mg/dL, or current use of oral hypoglycemiant or insulin), hypertension (cutoff points were 140/90 mm Hg), and status as a current smoker.

Laboratory tests for total cholesterol and fractions, triglycerides, and glycemia were performed using standard techniques.

Coronary lesion extent was evaluated using the Friesinger index. This classification uses the following categories: 0, no arteriographic abnormalities; 1, trivial irregularities (lesions from 1–29%); 2, lesions from 30–68%; 3, multiple narrowing in the same vessel, and the segment has either one lesion with a morphology defined as multiple, diffuse or tubular, or two segments with stenosis of 30–68%; 4, at least one lesion of 69–100%, except in the proximal segment where it should be less than 100%; and 5, occlusion of a proximal segment of a vessel. Left main lesions were counted as proximal lesions of both left descending and circumflex arteries. Coronary lesions were scored by experts blinded to patient lipid profiles.


Statistics were calculated by univariate analysis with chi-square and non-parametric ANOVA (Kruskal-Wallis), followed by multivariate analysis using stepwise forward logistic regression to assess the independent influence of lipid variables on extent of coronary disease extension, dichotomized by a Friesinger index of 5.


The subjects included 374 patients, 165 (60.2%) men and 109 (39.8%) women, with a mean age of 57 ± 11.5 years. Total cholesterol was 214 ± 50.2 mg/dL; triglycerides, 167.9±91.7 mg/dL; HDL-c, 38.5 ± 11.9 mg/dL; LDL-c, 142.9 ± 45 mg/dL; TG/HDL-c, 5.1 ± 4.0; and Friesinger index, 6.9 ± 4.4. Hypertensive and dyslipidemic subjects were predominantly male. Table 1 shows demographics of the patient sample, as well as the distribution of coronary lesions.

Table 1

Table 1

Demographic characteristics of patient sample and Friesinger index frequency

Extensive coronary disease, by univariate analysis, presented a direct relationship with the quartiles of total triglycerides, and TG/HDL-c, and an inverse relationship with HDL-c quartiles (Table 2).

Table 2

Table 2

Frequency of extensive coronary disease (Friesinger index ≥5) by lipid quartile

The odds ratios for the extent of coronary disease between the fourth and first quartiles were as follows: total cholesterol, 1.08, 95%CI (0.57–2.03), p = 0.87; LDL-c, 1.62, 95%CI (0.86–3.06), p = 0.15; triglycerides, 1.7, 95%CI (0.94–3.08), p = 0.986; HDL-c, 0.25, 95%CI (0.13–0.46), p = 0.0001; and TG/HDL-c, 3.31, 95%CI (1.78–6.14), p = 0.0002 (Figure 1). This analysis showed that only HDL-c and TG/HDL-c show statistically significant frequency differences between the fourth and first quartiles, and that the difference was larger for TG/HDL-c. The non-parametric ANOVA (Kruskal-Wallis) demonstrated a significant association between extensive coronary disease and the lipid variable quartiles. However, only HDL-c and TG/HDL-c--primarily the latter--showed statistically significant differences in median Friesinger index between abnormal values and normal ones. Total cholesterol and LDL-c showed a similar distribution and Figure 2 therefore presents only the Friesinger distribution for the quartiles of total cholesterol, triglycerides, HDL-c, and TG/HDL-c.

Figure 1

Figure 1

Odds ratios between fourth and first quartiles of lipid variables for extensive coronary disease (Friesinger index >4)
Figure 2

Figure 2

Boxplot distribution of Friesinger index by quartiles of total cholesterol, triglycerides, HDL-cholesterol, and TG/HDL-cholesterol

The multivariate analysis by logistic regression included these lipid variables, and it showed that the TG/HDL-c ratio showed the strongest correlation [association] with extent of coronary disease. Increasing the HDL-c quartile led to a 22% decrease in extent, while increasing the LDL-c or TG/HDL-c quartiles led to a 23% and 30% increase in disease extent, respectively (Table 3).

Table 3

Table 3

Results of multivariate analysis

Of the 246 subjects with low HDL-c, 171 (69.5%) had extensive coronary disease, and of the 170 subjects with high TG/HDL-c, 122 (72%) had extensive coronary disease. This may be due to the fact that HDL-c and Triglycerides levels were discordant in 35 (25%) of subjects with low extents of disease and in 75 (32%) of subjects with extensive coronary disease. Thus, taking both variables into account by using the Triglycerides to HDL-c ratio increased the accuracy of detecting extensive coronary disease.

Analysis of the ROC curves showed the following areas under the curves: 0.35 for HDL-c (p = 0.0001), 0.55 for LDL-c (p = 0.131), and 0.63 for TG/HDL-c (p = 0.0001).


We found a relationship between the extent of coronary disease and lipid variables using univariate analysis. In a multivariate model that included these variables, the ratio of triglycerides to HDL-cholesterol was found to be a powerful independent indicator of extensive coronary disease.

Despite the fact that small, dense LDL particles are an established risk factor for cardiovascular disease, the assessment of their subfractions by current methods have been too technically demanding to be applicable in a routine clinical laboratory. The usual techniques include density gradient ultracentrifugation, non-denaturing gradient gel electrophoresis (NDGGE), and nuclear magnetic resonance (NMR) spectroscopy, which have the disadvantages of being labor-intensive, technically demanding, expensive, or slow to produce results. As a result, these precise and accurate techniques are not widely used in clinical settings. Thus, developing surrogate markers of lipid particle profiles are of great clinical and economic importance.

Several studies have attempted to determine the risk levels for CAD using lipid indexes or formulas. The goal of this work is to manage patients better in order to prevent cardiac events. Of particular interest are ratios that have atherogenic particles in the numerator and HDL-c or its constituents in the denominator. The ratio of total cholesterol to HDL-c, and, to a lesser extent, the ratio of LDL-c to HDL-c have been shown to be better predictors of CAD than lipid alone. More recently, in the INTERHEART case-control study, the apoB/apoA1 ratio was shown to be the strongest risk factor associated with myocardial infarction. This ratio had already been proposed as an accurate predictor of risk for major coronary events in the AFCAPS/TexCAPS and AMORIS studies.

The ratio TG/HDL-c, initially proposed by Gaziano et al, is an atherogenic index that has proven to be a highly significant independent predictor of myocardial infarction, even stronger than TC/HDL-c and LDL-c/HDL-c. The Copenhagen Male Study showed triglycerides on their own to be another strong risk factor, but it found that stratifying triglyceride levels by HDL-c levels led to more accurate detection of increased risk of coronary disease.

The atherogenic link between high triglycerides and HDL-c is due to the higher plasma concentration of triglyceride-rich, very low-density lipoprotein that generates small, dense LDL during lipid exchange and lipolysis. These LDL particles accumulate in the circulation and form small, dense HDL particles, which undergo accelerated catabolism, thus closing the atherogenic circle.,

The present study indicates that TG/HDL-c, which we previously showed to be an indicator of development of coronary heart disease development, is also related to the severity of vessel compromise. Thus this ratio is an easy, non-invasive means of predicting the presence and extent of coronary atherosclerosis.

Study limitations

We studied a high-risk subset of patients, who showed a higher prevalence of coronary disease than the general population. We compared only lipid variables, and did not take into account the current use of medication or the inflammatory state of the patients. Since the commonly used statin and angiotensin enzyme inhibitors and angiotensin II receptor blockers may alter the inflammatory state, they may weaken the relationship between total cholesterol and LDL-cholesterol and the extent of coronary disease. This is because they act more on LDL-cholesterol and less on HDL-cholesterol and triglycerides.


Nearly all routinely assessed lipid variables were associated with the extent of coronary disease, but only the ratio of triglycerides to HDL-cholesterol or to HDL-c were robustly associated with disease extent. Elevation in the ratio of TG to HDL-c was the single most powerful predictor of extensive coronary heart disease among all the lipid variables examined.


1. Miller NE. Associations of high-density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis. Am Heart J. 1987;113:589–97. [PubMed]
2. Robinson D, Ferns GA, Bevan EA, Stocks J, Williams PT, Galton DJ. High density lipoprotein subfractions and coronary risk factors in normal men. Arteriosclerosis. 1987;7:341–6. [PubMed]
3. Williams PT, Krauss RM, Vranizan KM, Stefanick ML, Wood PDS, Lindgren FT. Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women. Arterioscler Thromb. 1992;12:332–40. [PubMed]
4. Hanak V, Munoz J, Teaque J, Stanley A, Jr, Bittner V. Accuracy of the triglyceride to high-density lipoprotein cholesterol ratio for prediction of the low-density lipoprotein phenotype B. Am J Cardiol. 2004;94:219–22. [PubMed]
5. Da luz PL, Cesena FH, Favarato D, Cerqueira ES. Comparison of serum lipid values in patients with coronary artery disease at <50, 50 to 59, 60 to 69, and >70 years of age. Am J Cardiol. 2005;96:1640–3. [PubMed]
6. Rinqqvist I, Fisher LD, Mock M, Davis KB, Wedel H, Chaitman BR, et al. The Coronary Artery Surgery Study. Prognostic Value of Angiographic Indices of Coronary Artery Disease from the Coronary Artery Surgery Study (CASS) J Clin Invest. 1983;71:1854–66. [PMC free article] [PubMed]
7. Krauss RM, Burke DJ. Identification of multiple subclasses of plasma low density lipoprotein in normal humans. J Lipid Res. 1982;23:97–104. [PubMed]
8. Scheffer PG, Bakker SJL, Heine RJ, Teerlink T. Measurement of LDL particle size in whole plasma and serum by high performance gel-filtration chromatography using a fluorescent lipid probe. Clin Chem. 1998;44:2148–51. [PubMed]
9. Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, et al. Nuclear Magnetic Resonance Spectroscopy of Lipoproteins and Risk of Coronary Heart Disease in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol. 2002;22:1175–80. [PubMed]
10. Ballantyne CM, Hoogeveen RC. Role of lipid and lipotrotein profiles in risk assessment and therapy. Am Heart J. 2003;146:227–33. [PubMed]
11. Hong MK, Romm PA, Reagan K, Green CE, Rackley CE. Usefulness of the total cholesterol to high density lipoprotein cholesterol ratio in predicting angiographic coronary disease in women. Am J Cardiol. 1991;68:1646–50. [PubMed]
12. Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease. The Framingham Study. Ann Epidemiol. 1992;2:23–8. [PubMed]
13. Manninen V, Tenkanen L, Koshinen P, Huttunen JK, Manttari M, Heinonen PO, et al. Join effects of serum triglycerides and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Sudy. Implications for treatment. Circulation. 1992;85:37–45. [PubMed]
14. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;363:937–52. [PubMed]
15. Gotto AM, Jr, Whitney E, Stein EA, Shapiro DR, Clearfield, Weis S, et al. Relation between baseline and on-treatment lipid parameters and first acute major coronary event in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/Tex CAPS) Circulation. 2000;101:477–84. [PubMed]
16. Walldius G, Jungner I, Holme I, Astveit AH, Kolar W, Steiner E. High apoliprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS Study): a prospective study. Lancet. 2001;358:2026–33. [PubMed]
17. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE. Fasting triglycerides, high density lipoprotein, and risk of myocardial infarction. Circulation. 1997;96:2520–5. [PubMed]
18. Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Triglycerides concentration and ischemic heart disease: an eight-year follow-up in the Copenhagen Male Study. Circulation. 1998;97:1029–36. [PubMed]
19. Packard CJ, Shepherd J. Lipoprotein heterogenity and apolipoprotein B metabolism. Arterioscler Thromb Vasc Biol. 1999;19:2456–64. [PubMed]
20. Brinton EA, Eeisenberg S, Breslow JL. Increased apo A-I and apo-AII fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia. J Clin Invest. 1991;87:536–44. [PMC free article] [PubMed]

Articles from Clinics are provided here courtesy of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

Triglyceride to HDL Ratio

May 16, 2011 | By Kathryn Gilhuly

High levels of triglycerides in your bloodstream put you at risk for heart attacks and strokes. Diet and lifestyle affect the amount of triglycerides stored in your fat cells. High-density lipoprotein, also known as the "good" cholesterol, helps your body eliminate triglycerides. Improve your heart health by maintaining a healthy balance--ratio--between triglycerides and HDL cholesterol.

Healthy Triglyceride and HDL Levels

You want to keep your triglycerides low and your HDL cholesterol high. Triglyceride levels below 150mg/dl--milligrams per deciliter of blood--and HDL cholesterol above 60 mg/dl rank as healthy. Aim to keep your triglycerides below 100mg/dl for optimal heart health, according to the American Heart Association. Triglycerides that measure more than 200mg/dl put you at high risk of heart attack and levels above 500mg/dl put you at very high risk. Women face additional cardiovascular health risks if their HDL cholesterol falls below 50mg/dl, men if below 40mg/dl.

Triglyceride-HDL Cholesterol Ratio

Strive for a triglyceride-HDL ratio of less than 2:l. This means that your triglycerides should not total more than twice your HDL cholesterol. If your triglycerides measure 100mg/dl and your HDL cholesterol is 50mg/dl, this would give you a 2:1 ratio--100 divided by 50 equals 2. Higher ratios signal potential for heart problems. A 4:1 ratio is high and a 6:1 is very high. If your triglycerides measure 200mg/dl and your HDL cholesterol is 50mg/dl, this would give you a 4:1 ratio. Triglyceride levels of 300mg/dl and an HDL of 50md/dl provides a 6:1 ratio.

Importance of Balance

Your HDL cholesterol scavenges your bloodstream for triglycerides and low-density lipoprotein, LDL or "bad" cholesterol. It removes as many triglyceride and LDL cholesterol deposits as it can and ships them to your liver for disposal. But your HDL cholesterol can't function properly when the ratio of triglycerides to HDL moves beyond 2:1. When your HDL cholesterol becomes greatly outnumbered by triglycerides, your risk of developing cardiovascular disease increases. Diet and exercise can help you achieve a healthy balance.

American Heart Association Guidelines

The American Heart Association recommends a triglyceride-lowering diet that limits consumption of saturated fat to 16g a day and trans fat to 2g daily. The AHA diet also restricts calories obtained from foods with added sugar to 100 per day for women and 150 per day for men. Adding exercise can help lower your triglycerides and boost your HDL cholesterol. Aim to include 150 minutes of moderate exercise in your weekly routine. Brisk walking counts as moderate exercise.


Article reviewed by Lisa Michael Last updated on: May 16, 2011


Read more:

Cardiovascular Disease

Ratio of Triglycerides to HDL Predicts Cardiac Events at 10 Years

By: CAROLINE HELWICK, Internal Medicine News Digital Network

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”


Cardiovascular Disease

Ratio of Triglycerides to HDL Predicts Cardiac Events at 10 Years

By: CAROLINE HELWICK, Internal Medicine News Digital Network

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.