Signs and symptoms

Elevated cholesterol does not lead to specific symptoms unless it has been longstanding. Some types of hypercholesterolaemia lead to specific physical findings: xanthoma (thickening of tendons due to accumulation of cholesterol), xanthelasma palpabrum (yellowish patches around the eyelids) and arcus senilis (white discoloration of the iris).

Longstanding elevated hypercholesterolemia leads to accelerated atherosclerosis; this can express itself in a number of cardiovascular diseases:

• Angina pectoris, leading to PTCA or CABG
• Myocardial infarction
• Transient ischemic attacks (TIA's)
• Cerebrovascular accidents/Strokes
• Peripheral artery disease (PAOD)

Diagnosis

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. LDL and VLDL levels are 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 is 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 which 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.

There is a number of secondary causes for high cholesterol:

• Diabetes mellitus and syndrome X
• Kidney disease (nephrotic syndrome)
• Hypothyroidism

Classification

Classically, hypercholesterolemia is categorised by its appearance on lipoprotein electrophoresis by the Fredrickson classification.

• Type I: high chylomicrons
• Type II:
  • Type IIa: high LDL
  • Type IIb: high LDL and VLDL
• Type III: high chylomicrons and IDL (intermediate density lipoprotein)
• Type IV: high triglycerides
• Type V: very similar to Type I, but with high VLDL
• Non-classified forms are:
  • Hypo-alpha lipoproteinemia
  • Hypo-beta lipoproteinemia

Apart from Type II and Type IV, these disorders are very rare. Some have hereditary as well as acquired forms. If the hypercholesterolemia is hereditary (familial hypercholesterolemia), there is often a family history of premature atherosclerosis, as well as familial occurrence of the signs mentioned above.

Treatment

The treatment depends on the type of hypercholesterolemia. Types IIa and IIb can be treated with diet, statins, fibrates, nicotinic acid, bile acid sequestrants, LDL apheresis and liver transplantation.

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).

On the other hand, and though less dramatic than the many cardiovascular procedures, some people, especially with newer and more sophisticated information, are changing their eating and especially food supplement patterns, many of the supplements still being prescription agents. Though generally not aware of the internal changes in their cholesterol transport patterns, recent trials have demonstrated increasing success with some of these strategies; see the LDL, HDL and IVUS sections.

In other words, clinical trails, starting in the 1970s, have repeatedly and increasingly found that normal cholesterol values do not necessarily reflect healthy cholesterol values. This has increasingly lead to the newer concept of dyslipidemia, despite normo-cholesterolemia. Though each, by design, examine only a single of multiple relevant issues, some of the better recent randomized human outcome trials include 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 Trial

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, even though not elevated, into unhealthy blood transport, atheroma-stimulating patterns. Thus a low fat diet, which often means a higher carbohydrate intake, may be a very unhealthy change. This is consistent with the low fat diet promotion in the US over the last 15-20 years with simultaneous increases in obesity and Diabetes Mellitus rates. However, as with all observational studies, association does not prove cause and effect connection.

Trans fats

An increasing number of researchers are suggesting that a major dietary risk factor for cardiovascular diseases is trans fatty acids, not saturated fats, as had been suggested by the Framingham Heart Study and the FDA plans revised food labeling to include listing trans fat quantities, by 2007. Meanwhile, amount of trans fat can be calculated from the food label by substracting the various reported fats from the total fat: trans fat = ( total fats - saturated fats - monounsaturates - polyunsaturates).

Cholesterol questioners

Some doctors, known as "the dissidents of the lipid hypothesis", claim that cholesterol itself is a healthy nutrient and that the whole "lipid hypothesis", which links cholesterol with heart disease and atherosclerosis, is incorrect. Some information can be found at the Weston A. Prince foundation (http://www.westonaprice.org), The International Network of Cholesterol Skeptics (http://www.thincs.org) and The Cholesterol Myths (http://www.ravnskov.nu/cholesterol.htm).

Cholesterol and alternative medicine

A survey released in May 2004 (http://nccam.nih.gov/news/2004/052704.htm) 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] (http://nccam.nih.gov/news/report.pdf) 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).