Hypercholesterolemia

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 * Associate Editor(s)-In-Chief: Smit Shrivastava, M.D. [mailto:dr.smit.shrivastava@gmail.com] and Bhaskar Purushottam, M.D. [mailto:bpurushottam@gmail.com]

Keywords and synonyms: cholesterol guidelines, NCEP guidelines, ATP guidelines, high cholesterol, hyperlipidemia

Overview
Hypercholesterolemia (literally: high blood cholesterol) is the presence of high levels of cholesterol in the blood. 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). Familial hypercholesterolemia is a rare genetic disorder that can occur in families, where sufferers cannot properly metabolise cholesterol.

Diagnosis
History and symptoms | Physical examination

Differential Diagnosis of Disorders Associated with Hypercholesterolemia
When measuring cholesterol, it is important to measure its subfractions before drawing a conclusion on 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. As of 1980, the original methods, developed by research work in the mid-1970s cost about $5K, 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.

Screening
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.

Classification
See also hyperlipoproteinemia for biochemical details

Fredrickson classification
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.

Secondary causes
There are a number of secondary causes for high cholesterol:
 * Diabetes mellitus and metabolic syndrome
 * Kidney disease (nephrotic syndrome)
 * Hypothyroidism
 * Anorexia nervosa
 * Zieve's syndrome
 * Family history
 * Diet: Saturated fat raises blood cholesterol levels. Although dietary cholesterol exerts some influence, the regulatory mechanism of the liver upon absorption of cholesterol decreases the effect of dietary cholesterol on total cholesterol levels. Thus it is mainly by limiting the amount of saturated fat in one's diet that helps lower total serum cholesterol.
 * Weight. Being overweight is a definite risk factor for heart disease. It also tends to increase your cholesterol. Losing weight can help lower your LDL and total cholesterol levels, as well as raise your HDL and lower your triglyceride levels.
 * Physical Activity. Lack of physical activity is a risk factor for heart disease. Regular physical activity can also help lower LDL (bad) cholesterol and raise HDL (good) cholesterol levels. It also helps you lose weight.

All three of these activities done together can have a positive effect on one's blood cholesterol level.

Dietary influence
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.

Carbohydrates
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. Thus a low fat diet, which often means a higher carbohydrate intake, may actually be an unhealthy change.

Trans fats
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.

Treatment
The primary target for hypercholesterolemia according to the latest NCEP ATP III guidelines is LDL cholesterol. A target LDL goal is established and treatment options are considered based on that.

Clinical practice guidelines
The NCEP revised their guidelines ; however, their 2004 revisions have been criticized for use of nonrandomized, observational data. Various other clinical practice guidelines have addressed the treatment of hypercholesterolemia. The American College of Physicians has addressed hypercholesterolemia in patients with diabetes. However, most of the management for treatment of high blood cholesterol is based on NCEP guidelines.

Alternative medicine
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 ( 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).