High density lipoprotein
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High-density lipoproteins (HDL) form a class of lipoproteins, varying somewhat in their size (8–11 nm in diameter), that carry cholesterol from the body's tissues to the liver. About one-third to a quarter of blood cholesterol is carried by HDL. [1]
It is hypothesised that HDL can remove cholesterol from atheroma within arteries, and transport it back to the liver for excretion or re-utilization; the main reason why HDL-bound cholesterol is sometimes called "good cholesterol", or HDL-C. A high level of HDL-C seems to protect against cardiovascular diseases, and low HDL cholesterol levels [less than 40 mg/dL] increase the risk for heart disease. [2] When measuring cholesterol, any contained in HDL particles is considered as protection to the body's cardiovascular health, in contrast to "bad" LDL cholesterol.
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[edit] Structure and function
HDL are the smallest of the lipoproteins. They are the densest because they contain the highest proportion of protein. They contain the A class of apolipoproteins.[3] 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 they interact with. 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 molecules into their structure. Thus it is the concentration of large HDL particles which more accurately reflects protective action, as opposed to the concentration of total HDL particles.[4] This ratio of large HDL to total HDL particles varies widely and is only measured by more sophisticated lipoprotein assays using either electrophoresis, the original method developed in the 1970s or newer NMR spectroscopy methods, developed in the 1990s.
HDL particles are not to inherently protective. It is only the HDL particles which become the largest, i.e. are actually picking up and carrying cholesterol, which are protective. There is no reliable relationship between total HDL and large HDL, and more sophisticated analyses which actually measure large HDL, not just total, correlate much better with clinical outcomes.
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 liver 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.
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.
[edit] Epidemiology
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) are a positive risk factor for these atherosclerotic diseases.
Data from the famous Framingham Heart Study showed that for a given level of LDL, the risk of heart disease varies 10-fold as the HDL varies from high to low. Conversely, for a fixed level of HDL, the risk varies 3-fold as LDL varies from low to high. So, for example, for a fixed LDL level of 220 mg/dl, the risk of coronary heart disease is 3-times normal if the HDL is low (25 mg/dl) but just one-third of normal if the HDL is high (85 mg/dl). On the other hand, for a fixed HDL level of 85 mg/dl, the risk of coronary heart disease is one-tenth normal if the LDL is low (100 mg/dl) and still only three-tenths of normal if the LDL is high (220 mg/dl). Phrased differently, this data implies that HDL is a more potent risk factor than LDL. Indeed, for a high HDL level (85 mg/dl), the risk of coronary disease remains lower than average even when the LDL level is high. Lowering LDL levels in such people, while of some benefit, merely converts a low risk situation to a very low risk situation.
[edit] Recommended range
The American Heart Association, NIH and NCEP provides a set of guidelines for male fasting HDL levels and risk for heart disease.
| Level mg/dL | Level mmol/L | Interpretation |
| <40 | <1.03 | Low HDL cholesterol, heightened risk for heart disease, <50 is the value for women |
| 40–59 | 1.03–1.52 | Medium HDL level |
| >60 | >1.55 | High HDL level, optimal condition considered protective against heart disease |
More sophisticated laboratory methods measure not just the total HDL but also the range of HDL particles, e.g. "lipoprotein subclass analysis", typically divided into several groups by size, instead of just the total HDL concentration as listed above. The largest groups (most functional) of HDL particles have the most protective effects. The groups of smallest particles reflect HDL particles which are not actively transporting cholesterol, thus not protective.
[edit] Raising HDL
Given this data, one could ask why more attention is not paid to raising HDL levels rather than lowering LDL levels. The answer to this question is multifaceted. In part, the reason is that LDL cholesterol drew early researchers' attention more than did HDL. Hence, much of the thrust of cholesterol research (including clinical trials) was directed at the effects of lowering LDL. Likewise, pharmaceutical company research enjoyed early success at developing medicines to lower LDL. Taken together, these factors tended to thrust LDL into the "limelight". On the other hand, although epidemiologically more important than LDL, efforts to emphasize the benefit of raised HDL came later. In large part this was due to the absence of effective, safe, and well-tolerated medicines with which to increase HDL. Although the use of niacin and fibrates will often lead to increased HDL levels, the former is poorly tolerated, and both have a number of other effects on cholesterol and triglyceride levels (meaning that no conclusions could be drawn on the basis of their ability to raise HDL, but, instead, would have to be based on their total spectrum of effects on blood lipids). Finally, at this point (2007), both physicians and the lay public have been instructed and educated for years with respect to the "whys" and the "how-to's" of LDL lowering. To change the paradigm at this stage would take a huge (and expensive) effort.
As of 2006, randomized clinical trials have demonstrated significant reduction of atherosclerosis progression and cardiovascular events with treatments that increase HDL-cholesterol (nicotinic acid or a fibrate). [5]
Pharmacological therapy to increase the level of HDL cholesterol includes use of fibrates and niacin. Consumption of niacin, an immediate release crystallin form of Vitamin B3, can increase HDL levels by 15–30%, and is the most powerful agent currently available to increase HDL-cholesterol. [6] [7] The use of statins is effective against high levels of LDL cholesterol, but it has little or no effect in raising HDL-cholesterol.[8] The use of antioxidants in combination with statin and niacin therapy reduces the effectiveness of Niacin by 33%. (NIH HATS).
Torceptrapib, a promising new drug developed by Pfizer to raise HDL by inhibition of cholesteryl ester transfer protein (CETP), was terminated after a greater percentage of patients treated with torcetrapib died compared with patients treated with placebo.
Certain changes in lifestyle can have a positive impact on raising HDL levels:[9]
- Aerobic exercise
- Weight loss
- Smoking cessation
- Supplements like Omega 3 Fish Oil
- Removing trans fatty acids from the diet
- Adding monounsaturated and polyunsaturated fats to the diet
- Drinking 1–2 servings of alcoholic beverages per day
- Adding soluble fiber to diet
- Limiting intake of dietary fat to 30–35% of total calories
[edit] Citations
- ^ http://www.americanheart.org/presenter.jhtml?identifier=180
- ^ http://www.americanheart.org/presenter.jhtml?identifier=180
- ^ Baylor College of Medicine, Lipids Online (January 29, 2001). Heterogeneity of HDL. Retrieved on February 20, 2006.
- ^ Kwiterovich PO. The Metabolic Pathways of High-Density Lipoprotein, Low-Density Lipoprotein, and Triglycerides: A Current Review. Am J Cardiol 2000;86(suppl):5L.
- ^ Reducing risk by raising HDL-cholesterol: the evidence. # European Heart Journal Supplements Vol 8 Suppl F p. F23-F29 http://eurheartjsupp.oxfordjournals.org/cgi/content/abstract/8/suppl_F/F23
- ^ Reducing risk by raising HDL-cholesterol: the evidence. # European Heart Journal Supplements Vol 8 Suppl F p. F23-F29 http://eurheartjsupp.oxfordjournals.org/cgi/content/abstract/8/suppl_F/F23
- ^ Raising HDL-Cholesterol and Reducing Cardiovascular Risk. Medscape Cardiology http://www.medscape.com/viewarticle/520393
- ^ Raising HDL-Cholesterol and Reducing Cardiovascular Risk. Medscape Cardiology http://www.medscape.com/viewarticle/520393
- ^ Richard N. Fogoros, M.D.. Raising Your HDL Levels. Retrieved on July 29, 2006.
