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Hypercholesterolemia |
| Hypercholesterolemia Classification and external resources |
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|---|---|
| Cholesterol | |
| ICD-10 | E78.0 |
| ICD-9 | 272.0 |
| DiseasesDB | 6226 |
| eMedicine | med/1073 |
| MeSH | D006937 |
Hypercholesterolemia (literally: high blood cholesterol) is the presence of high levels of cholesterol in the blood 1. It is not a disease but a metabolic derangement that can be secondary to many diseases and can contribute to many forms of disease, most notably cardiovascular disease. It is closely related to the terms "hyperlipidemia" (elevated levels of lipids) and "hyperlipoproteinemia" (elevated levels of lipoproteins).1
Elevated cholesterol in the blood is due to abnormalities in the levels of lipoproteins, the particles that carry cholesterol in the bloodstream. This may be related to diet, genetic factors (such as LDL receptor mutations in familial hypercholesterolemia) and the presence of other diseases such as diabetes and an underactive thyroid. The type of hypercholesterolemia depends on which type of particle (such as low density lipoprotein) is present in excess.1
High cholesterol levels are treated with diets low in cholesterol, medications, and rarely with other treatments including surgery (for particular severe subtypes). This is also increased emphasis on other risk factors for cardiovascular disease, such as high blood pressure.1
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Elevated cholesterol does not lead to specific symptoms unless it has been longstanding. Some types of hypercholesterolemia lead to specific physical findings: xanthoma (deposition of cholesterol in patches on the skin or in tendons), xanthelasma palpabrum (yellowish patches around the eyelids) and arcus senilis (white discoloration of the peripheral cornea).1
Longstanding elevated hypercholesterolemia leads to accelerated atherosclerosis; this can express itself in a number of cardiovascular diseases: coronary artery disease (angina pectoris, heart attacks), stroke and short stroke-like episodes and peripheral vascular disease.123
There is no specific level at which cholesterol levels are abnormal. Cholesterol levels are found in a continuum within a population. Higher cholesterol levels lead to increased risk of specific disease, most notably cardiovascular diseases. Specifically, high LDL cholesterol levels are associated with increased risk. When speaking of hypercholesterolemia, most people are referring to high levels of LDL cholesterol.citation needed
When measuring cholesterol, it is important to measure its subfractions before drawing a conclusion as to the cause of the problem. The subfractions are LDL, HDL and VLDL. In the past, LDL and VLDL levels were rarely measured directly due to cost concerns. VLDL levels are reflected in the levels of triglycerides (generally about 45% of triglycerides is composed of VLDL). LDL was usually estimated as a calculated value from the other fractions (total cholesterol minus HDL and VLDL); this method is called the Friedewald calculation; specifically: LDL ~= Total Cholesterol - HDL - (0.2 x Triglycerides).
Less expensive (and less accurate) laboratory methods and the Friedewald calculation have long been utilized because of the complexity, labor and expense of the electrophoretic methods developed in the 1970s to identify the different lipoprotein particles which transport cholesterol in the blood. In 1980, the original methods, developed by research work in the mid-1970s cost about $5,000, in US 1980 dollars, per blood sample/person.
With time, more advanced laboratory analyses have been developed which do measure LDL and VLDL particle sizes and levels, and at far lower cost. These have partly been developed and become more popular as a result of the increasing clinical trial evidence that intentionally changing cholesterol transport patterns, including to certain abnormal values compared to most adults, often has a dramatic effect on reducing, even partially reversing, the atherosclerotic process. With ongoing research and advances in laboratory methods, the prices for more sophisticated analyses have markedly decreased, to less than $100, US 2004, by some labs, and with simultaneous increases in the accuracy of measurement for some of the methods.
Classically, hypercholesterolemia was categorized by lipoprotein electrophoresis and the Fredrickson classification. Newer methods, such as "lipoprotein subclass analysis" have offered significant improvements in understanding the connection with atherosclerosis progression and clinical consequences.
If the hypercholesterolemia is hereditary (familial hypercholesterolemia), there is more often a family history of premature, earlier onset atherosclerosis, as well as familial occurrence of the signs mentioned above.
There are a number of secondary causes for high cholesterol:
All three of these activities done together can have a positive effect on one's blood cholesterol level.
While part of the circulating cholesterol originates from diet, and restricting cholesterol intake may reduce blood cholesterol levels, there are various other links between the dietary pattern and cholesterol levels. The American Heart Association also compiles a list of the acceptable/unacceptable foods for those who are diagnosed with hypercholesterolemia.
Dietary changes can potentially be very strong: when a group of Tarahumara Indians from Mexico with no obesity and cholesterol problems were exposed to a Western diet, their risk profile worsened significantly, with cholesterol levels rising over thirty percent.4
Evidence is accumulating that eating more carbohydrates - especially simpler, more refined carbohydrates - increases levels of triglycerides in the blood, lowers HDL, and may shift the LDL particle distribution pattern into unhealthy atherogenic patterns.
An increasing number of researchers are suggesting that a major dietary risk factor for cardiovascular diseases is trans fatty acids, and in the US the FDA has revised food labeling requirements to include listing trans fat quantities.5
Any decision to treat elevated risk
Clinical Evidence has summarized treatment for both primary prevention 6 and secondary prevention 7. Two factors to consider when choosing therapy are the patient's risk of coronary disease and their lipoprotein pattern.
Multiple clinical trials, each, by design, examining only one of multiple relevant issues, have increasingly examined the connection between these issues and atherosclerosis clinical consequences. Some of the better recent randomized human outcome trials include ASTEROID, ASCOT-LLA, REVERSAL, PROVE-IT, CARDS, Heart Protection Study, HOPE, PROGRESS, COPERNICUS, and especially a newer research approach utilizing a synthetically produced and IV administered human HDL, the Apo A-I Milano Trialcitation needed.
In strictly controlled surroundings, such as a hospital ward dedicated to metabolism problems, a diet can reduce cholesterol levels by 15%. In practice, dietary advice can provide a modest decrease in cholesterol levels and may be sufficient in the treatment of mildly elevated cholesterol.10
Many primary physicians and heart specialists will initially prescribe medication in combination with diet and exercise. According to various resources, statins are the most commonly used and effective forms of medication for the treatment of high cholesterol. The U.S. Preventive Services Task Force (USPSTF) estimated that after 5 to 7 years of treatment, the relative risk reduction by statins on coronary heart disease events is decreased by approximately 30% 1112 More recently, a meta-analysis reported an almost identical relative risk reduction of 29.2% in low risk patients treated for 4.3 years 13. A relative risk reduction of 19% in coronary mortality was found in a meta-analysis of patients at all levels of risk.14
Various clinical practice guidelines have addressed the treatment of hypercholesterolemia. The American College of Physicians has addressed hypercholesterolemia in patients with diabetes 15. Their recommendations are:
The National Cholesterol Education Program revised their guidelines17; however, their 2004 revisions have been criticized for use of nonrandomized, observational data.18
In the UK, the National Institute for Health and Clinical Excellence (NICE) has made recommendations for the treatment of elevated cholesterol levels, published in 2008.19
A survey released in May 2004 by the National Center for Complementary and Alternative Medicine focused on who used complementary and alternative medicine (CAM), what was used, and why it was used in the United States by adults age 18 years and over during 2002. According to this survey, CAM was used to treat cholesterol by 1.1% of U.S. adults who used CAM during 2002 ([1] table 3 on page 9). Consistent with previous studies, this study found that the majority of individuals (i.e., 54.9%) used CAM in conjunction with conventional medicine (page 6).
Screening for a disease refers to testing for a disease, such as hypercholesterolemia, in patients who have no signs or symptoms of the disease.
In patients without any other risk factors, moderate hypercholesterolemia is often not treated. According to Framingham Heart Study, people with an age greater than 50 years have no increased overall mortality with either high or low serum cholesterol levels. There is, however, a correlation between falling cholesterol levels over the first 14 years and mortality over the following 18 years (11% overall and 14% CVD death rate increase per 1 mg/dL per year drop in cholesterol levels). This, however, does not mean that a decrease in serum levels is dangerous, as there has not yet been a recorded heart attack in the study in a person with a total cholesterol below 150 mg/dL.
The U.S. Preventive Services Task Force (USPSTF) has evaluated screening for hypercholesterolemia 11 12.
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